Brian Knutson

All Publications

• News source bias and sentiment on social media. PloS one Knutson, B., Hsu, T. W., Ko, M., Tsai, J. L. 2024; 19 (10): e0305148

  Abstract

  As social media becomes a key channel for news consumption and sharing, proliferating partisan and mainstream news sources must increasingly compete for users' attention. While affective qualities of news content may promote engagement, it is not clear whether news source bias influences affective content production or virality, or whether any differences have changed over time. We analyzed the sentiment of ~30 million posts (on twitter.com) from 182 U.S. news sources that ranged from extreme left to right bias over the course of a decade (2011-2020). Biased news sources (on both left and right) produced more high arousal negative affective content than balanced sources. High arousal negative content also increased reposting for biased versus balanced sources. The combination of increased prevalence and virality for high arousal negative affective content was not evident for other types of affective content. Over a decade, the virality of high arousal negative affective content also increased, particularly in balanced news sources, and in posts about politics. Together, these findings reveal that high arousal negative affective content may promote the spread of news from biased sources, and conversely imply that sentiment analysis tools might help social media users to counteract these trends.

  View details for DOI 10.1371/journal.pone.0305148

  View details for PubMedID 39441772

  View details for PubMedCentralID PMC11498708

• Multi-dimensional predictors of first drinking initiation and regular drinking onset in adolescence: A prospective longitudinal study. Developmental cognitive neuroscience Nguyen-Louie, T. T., Thompson, W. K., Sullivan, E. V., Pfefferbaum, A., Gonzalez, C., Eberson-Shumate, S. C., Wade, N. E., Clark, D. B., Nagel, B. J., Baker, F. C., Luna, B., Nooner, K. B., de Zambotti, M., Goldston, D. B., Knutson, B., Pohl, K. M., Tapert, S. F. 2024; 69: 101424

  Abstract

  Early adolescent drinking onset is linked to myriad negative consequences. Using the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) baseline to year 8 data, this study (1) leveraged best subsets selection and Cox Proportional Hazards regressions to identify the most robust predictors of adolescent first and regular drinking onset, and (2) examined the clinical utility of drinking onset in forecasting later binge drinking and withdrawal effects. Baseline predictors included youth psychodevelopmental characteristics, cognition, brain structure, family, peer, and neighborhood domains. Participants (N=538) were alcohol-naïve at baseline. The strongest predictors of first and regular drinking onset were positive alcohol expectancies (Hazard Ratios [HRs]=1.67-1.87), easy home alcohol access (HRs=1.62-1.67), more parental solicitation (e.g., inquiring about activities; HRs=1.72-1.76), and less parental control and knowledge (HRs=.72-.73). Robust linear regressions showed earlier first and regular drinking onset predicted earlier transition into binge and regular binge drinking (βs=0.57-0.95). Zero-inflated Poisson regressions revealed that delayed first and regular drinking increased the likelihood (Incidence Rate Ratios [IRR]=1.62 and IRR=1.29, respectively) of never experiencing withdrawal. Findings identified behavioral and environmental factors predicting temporal paths to youthful drinking, dissociated first from regular drinking initiation, and revealed adverse sequelae of younger drinking initiation, supporting efforts to delay drinking onset.

  View details for DOI 10.1016/j.dcn.2024.101424

  View details for PubMedID 39089172

• A pilot, randomized clinical trial: Left dorsolateral prefrontal cortex intermittent theta burst stimulation improves treatment outcomes in veterans with alcohol use disorder. Alcohol, clinical & experimental research Padula, C. B., McCalley, D. M., Tenekedjieva, L., MacNiven, K., Rauch, A., Morales, J. M., Knutson, B., Humphreys, K., Williams, L. M., Durazzo, T. C. 2024; 48 (1): 164-177

  Abstract

  BACKGROUND: Transcranial magnetic stimulation (TMS) offers a promising treatment avenue to modulate brain function in alcohol use disorder (AUD). To the best of our knowledge, this pilot study is the first randomized, double-blind, sham-controlled trial to deliver intermittent theta burst stimulation to the left dorsolateral prefrontal cortex (DLPFC) among US veterans with AUD. We hypothesized that 20 sessions of real TMS are tolerable and feasible. As a secondary line of inquiry, we hypothesized that, relative to sham TMS, individuals receiving real TMS would experience greater reductions in 6-month relapse rates, anhedonia, and alcohol cue-reactivity.METHODS: Veterans (n=17, one woman) were enrolled in a double-blind, sham-controlled trial (2-3 sessions/day; 7-10days; 600 pulses/session; 20 sessions). Pre- and posttreatment assessments included responses to self-report questionnaires and functional magnetic resonance imaging measures of alcohol cue-reactivity. Alcohol consumption was assessed for 6months. Linear mixed-effects models were constructed to predict posttreatment craving, mood, and cue-reactivity.RESULTS: Individuals who received active iTBS (n=8) were less likely to relapse within 3months after treatment than the sham-treated group (n=9) (OR=12.0). Greater reductions in anhedonia were observed following active iTBS (Cohen's d=-0.59), relative to sham (d=-0.25). Alcohol cue-reactivity was reduced following active iTBS and increased following sham within the left insula (d=-0.19 vs. 0.51), left thalamus (d=-0.28 vs. 0.77), right insula (d=0.18 vs. 0.52), and right thalamus (d=-0.06 vs. 0.62).CONCLUSIONS: Relative to sham, we demonstrate that 20 sessions of real left DLPFC iTBS reduced the likelihood of relapse for at least 3months. The potential utility of this approach is underscored by observed decreases in anhedonia and alcohol cue-reactivity-strong predictors of relapse among veterans. These initial data offer a valuable set of effect sizes to inform future clinical trials in this patient population.

  View details for DOI 10.1111/acer.15224

  View details for PubMedID 38197808

• Commentaries on "Reconsidering the path for neural and physiological methods in consumer psychology" JOURNAL OF CONSUMER PSYCHOLOGY Hutchinson, J., Reimann, M., Knutson, B., Huber, J. 2023

  View details for DOI 10.1002/jcpy.1398

  View details for Web of Science ID 001123606700001

• Left Dorsolateral Prefrontal Cortex Intermittent Theta Burst Stimulation Improves Treatment Outcomes in Veterans With Alcohol Use Disorder: A Randomized, Sham-Controlled Clinical Pilot Trial McCalley, D., Tenekedjieva, L., MacNiven, K., Rauch, A., Morales, J., Knutson, B., Humphreys, K., Williams, L., Durazzo, T., Padula, C. SPRINGERNATURE. 2023: 449

  View details for Web of Science ID 001126640300420

• Leveraging neuroscience for climate change research NATURE CLIMATE CHANGE Doell, K. C., Berman, M. G., Bratman, G. N., Knutson, B., Kuhn, S., Lamm, C., Pahl, S., Sawe, N., Van Bavel, J. J., White, M. P., Brosch, T. 2023

  View details for DOI 10.1038/s41558-023-01857-4

  View details for Web of Science ID 001101579200001

• Cultural variation in neural responses to social but not monetary reward outcomes. Social cognitive and affective neuroscience Blevins, E., Ko, M., Park, B., Qu, Y., Knutson, B., Tsai, J. L. 2023

  Abstract

  European Americans view high intensity, open-mouthed "excited" smiles more positively than Chinese because they value excitement and other high arousal positive states more (Tsai et al. 2018). This difference is supported by reward-related neural activity, with European Americans showing greater Nucleus Accumbens (NAcc) activity to excited (vs. calm) smiles than Chinese (Park et al., 2018). But do these cultural differences generalize to all rewards, and are they related to real-world social behavior? European American (N = 26) and Chinese (N = 27) participants completed social and monetary incentive delay tasks that distinguished between the anticipation and receipt (outcome) of social and monetary rewards while undergoing Functional Magnetic Resonance Imaging (FMRI). The groups did not differ in NAcc activity when anticipating social or monetary rewards. However, as predicted, European Americans showed greater NAcc activity than Chinese when viewing excited smiles during outcome (the receipt of social reward). No cultural differences emerged when participants received monetary outcomes. Individuals who showed increased NAcc activity to excited smiles during outcome had friends with more intense smiles on social media. These findings suggest that culture plays a specific role in modulating reward-related neural responses to excited smiles during outcome, which are associated with real-world relationships.

  View details for DOI 10.1093/scan/nsad068

  View details for PubMedID 37952225

• Ketamine's acute effects on negative brain states are mediated through distinct altered states of consciousness in humans. Nature communications Hack, L. M., Zhang, X., Heifets, B. D., Suppes, T., van Roessel, P. J., Yesavage, J. A., Gray, N. J., Hilton, R., Bertrand, C., Rodriguez, C. I., Deisseroth, K., Knutson, B., Williams, L. M. 2023; 14 (1): 6631

  Abstract

  Ketamine commonly and rapidly induces dissociative and other altered states of consciousness (ASCs) in humans. However, the neural mechanisms that contribute to these experiences remain unknown. We used functional neuroimaging to engage key regions of the brain's affective circuits during acute ketamine-induced ASCs within a randomized, multi-modal, placebo-controlled design examining placebo, 0.05 mg/kg ketamine, and 0.5 mg/kg ketamine in nonclinical adult participants (NCT03475277). Licensed clinicians monitored infusions for safety. Linear mixed effects models, analysis of variance, t-tests, and mediation models were used for statistical analyses. Our design enabled us to test our pre-specified primary and secondary endpoints, which were met: effects of ketamine across dose conditions on (1) emotional task-evoked brain activity, and (2) sub-components of dissociation and other ASCs. With this design, we also could disentangle which ketamine-induced affective brain states are dependent upon specific aspects of ASCs. Differently valenced ketamine-induced ASCs mediated opposing effects on right anterior insula activity. Participants experiencing relatively higher depersonalization induced by 0.5 mg/kg of ketamine showed relief from negative brain states (reduced task-evoked right anterior insula activity, 0.39 SD). In contrast, participants experiencing dissociative amnesia showed an exacerbation of insula activity (0.32 SD). These results in nonclinical participants may shed light on the mechanisms by which specific dissociative states predict response to ketamine in depressed individuals.

  View details for DOI 10.1038/s41467-023-42141-5

  View details for PubMedID 37857620

  View details for PubMedCentralID 5126726

• Blunted Neurobehavioral Loss Anticipation Predicts Relapse to Stimulant Drug Use Biological Psychiatry Mortazavi*, L., MacNiven*, K. H., Knutson, B. 2023

  Abstract

  Stimulant Use Disorder (SUD) patients suffer from high rates of relapse. While neurobehavioral mechanisms involved in initiating drug use have been extensively studied, less research has focused on relapse.To assess motivational processes involved in relapse and diagnosis, we acquired Functional Magnetic Resonance Imaging (FMRI) responses to nondrug (monetary) gains and losses in detoxified SUD patients (n=68) and community controls (n=42). In a prospective multi-modal design, we combined imaging of brain function, brain structure, and behavior to longitudinally track subsequent risk for relapse. At the six-month follow-up assessment, 27 patients remained abstinent, but 33 had relapsed.Patients with blunted Anterior Insula (AIns) activity during loss anticipation were more likely to relapse, an association which remained robust after controlling for potential confounds (i.e., craving, negative mood, years of use, age, and gender). Lower AIns activity during loss anticipation was associated with lower self-reported negative arousal to loss cues and slower behavioral responses to avoid losses, which independently also predicted relapses. AIns activity during loss anticipation was further associated with structural coherence of a tract connecting the AIns and Nucleus Accumbens (NAcc), as was functional connectivity between the AIns and NAcc during loss processing. These neurobehavioral responses did not, however, differ between patients and controls.Together, neurobehavioral markers predicted relapse above and beyond conventional self-report measures with a cross-validated accuracy of 72.7%. These findings offer convergent multi-modal evidence implicating blunted avoidance motivation in relapse to stimulant use, and so may guide interventions targeting those most vulnerable to relapse.

  View details for DOI 10.1016/j.biopsych.2023.07.020

• Blunted neurobehavioral loss anticipation predicts relapse to stimulant drug use. Biological psychiatry MacNiven, K. H., Mortazavi, L., Knutson, B. 2023

  Abstract

  Stimulant Use Disorder (SUD) patients suffer from high rates of relapse. While neurobehavioral mechanisms involved in initiating drug use have been extensively studied, less research has focused on relapse.To assess motivational processes involved in relapse and diagnosis, we acquired Functional Magnetic Resonance Imaging (FMRI) responses to nondrug (monetary) gains and losses in detoxified SUD patients (n=68) and community controls (n=42). In a prospective multi-modal design, we combined imaging of brain function, brain structure, and behavior to longitudinally track subsequent risk for relapse. At the six-month follow-up assessment, 27 patients remained abstinent, but 33 had relapsed.Patients with blunted Anterior Insula (AIns) activity during loss anticipation were more likely to relapse, an association which remained robust after controlling for potential confounds (i.e., craving, negative mood, years of use, age, and gender). Lower AIns activity during loss anticipation was associated with lower self-reported negative arousal to loss cues and slower behavioral responses to avoid losses, which independently also predicted relapses. AIns activity during loss anticipation was further associated with structural coherence of a tract connecting the AIns and Nucleus Accumbens (NAcc), as was functional connectivity between the AIns and NAcc during loss processing. These neurobehavioral responses did not, however, differ between patients and controls.Together, neurobehavioral markers predicted relapse above and beyond conventional self-report measures with a cross-validated accuracy of 72.7%. These findings offer convergent multi-modal evidence implicating blunted avoidance motivation in relapse to stimulant use, and so may guide interventions targeting those most vulnerable to relapse.

  View details for DOI 10.1016/j.biopsych.2023.07.020

  View details for PubMedID 37567334

• Acute Effects of MDMA on Intrinsic Functional Connectomes Associated With Altered States of Consciousness and Defensiveness Zhang, X., Hack, L., Heifets, B., Suppes, T., van Roessel, P., Yesavage, J., Gray, N., Hilton, R., Rodriguez, C., Deisseroth, K., Knutson, B., Williams, L. ELSEVIER SCIENCE INC. 2023: S87-S88

  View details for Web of Science ID 000993018500208

• Ketamine's Acute Effects on Negative Brain States are Mediated Through Distinct Altered States in Humans Zhang, X., Hack, L., Heifets, B., Suppes, T., Van Roessel, P., Yesavage, J., Gray, N., Hilton, R., Rodriguez, C., Deisseroth, K., Knutson, B., Williams, L. ELSEVIER SCIENCE INC. 2023: S312

  View details for Web of Science ID 000993018500757

• Acute Effects of MDMA on Negative Affective Brain Circuit Function: A Randomized Controlled Mechanistic Trial Hack, L., Zhang, X., Heifets, B., Suppes, T., van Roessel, P., Yesavage, J., Gray, N., Hilton, R., Rodriguez, C., Deisseroth, K., Knutson, B., Williams, L. ELSEVIER SCIENCE INC. 2023: S88

  View details for Web of Science ID 000993018500209

• Replication of neural responses to monetary incentives and exploration of reward-influenced network connectivity in fibromyalgia. Neuroimage. Reports Park, S. H., Deng, E. Z., Baker, A. K., MacNiven, K. H., Knutson, B., Martucci, K. T. 2022; 2 (4)

  Abstract

  Neuroimaging research has begun to implicate alterations of brain reward systems in chronic pain. Previously, using functional magnetic resonance imaging (fMRI) and a monetary incentive delay (MID) task, Martucci et al. (2018) showed that neural responses to reward anticipation and outcome are altered in fibromyalgia. In the present study, we aimed to test the replicability of these altered neural responses to reward in a separate fibromyalgia cohort. In addition, the present study was conducted at a distinct U.S. location but involved a similar study design. For the present study, 20 patients with fibromyalgia and 20 healthy controls participated in MID task fMRI scan procedures and completed clinical/psychological questionnaires. fMRI analyses comparing patient and control groups revealed a consistent trend of main results which were largely similar to the prior reported results. Specifically, in the replication fibromyalgia cohort, medial prefrontal cortex (MPFC) response was reduced during gain anticipation and was increased during no-loss (non-punishment) outcome compared to controls. Also consistent with previous findings, the nucleus accumbens response to gain anticipation did not differ in patients vs. controls. Further, results from similarly-designed behavioral, correlational, and exploratory analyses were complementary to previous findings. Finally, a novel network-based functional connectivity analysis of the MID task fMRI data across patients vs. controls implied enhanced connectivity within the default mode network in participants with fibromyalgia. Together, based on replicating prior univariate results and new network-based functional connectivity analyses of MID task fMRI data, we provide further evidence of altered brain reward responses, particularly in the MPFC response to reward outcomes, in patients with fibromyalgia.

  View details for DOI 10.1016/j.ynirp.2022.100147

  View details for PubMedID 36618964

  View details for PubMedCentralID PMC9815752

• Disentangling the Skeins of Brain. Journal of cognitive neuroscience Knutson, B., Srirangarajan, T. 2022: 1-5

  Abstract

  Some have argued that the brain is so complex that it cannot be understood using current reductive approaches. Drawing on examples from decision neuroscience, we instead contend that combining new neuroscientific techniques with reductive approaches that consider central brain components in time and space has generated significant progress over the past 2 decades. This progress has allowed researchers to advance from the scientific goals of description and explanation to prediction and control. Resulting knowledge promises to improve human health and well-being. As an alternative to the extremes of reductive versus emergent approaches, however, we propose a middle way of "expansion." This expansionist approach promises to leverage the specific spatial localization, temporal precision, and directed connectivity of central neural components to ultimately link levels of analysis.

  View details for DOI 10.1162/jocn_a_01952

  View details for PubMedID 36473099

• Neural responses clarify how ecolabels promote sustainable purchases. NeuroImage Sawe, N., Srirangarajan, T., Sahoo, A., Tang, G. S., Knutson, B. 2022: 119668

  Abstract

  While behavioral and policy interventions such as ecolabels (e.g., the Energy Star label) promote sustainable purchases, the reason for their influence remains unclear. We combined incentive-compatible purchasing experiments, neuroimaging assessments, and a national stated choice survey to examine how the Energy Star label might influence choices of light bulbs within individuals, across individuals (n=36), and out-of-sample in a national survey (n=1,550). Presence of the Energy Star label increased activity in neural regions associated with positive affective responses that predicted purchasing (e.g., the Nucleus Accumbens or NAcc), particularly in more impulsive individuals. Group-averaged NAcc activity could also account for consumer demand for similar sustainable product combinations in a national survey. These findings suggest that ecolabels may leverage affective responses in individuals as well as markets to promote sustainable purchases, which might inform the promotion of sustainable products.

  View details for DOI 10.1016/j.neuroimage.2022.119668

  View details for PubMedID 36206938

• Brain tract structure predicts relapse to stimulant drug use. Proceedings of the National Academy of Sciences of the United States of America Tisdall, L., MacNiven, K. H., Padula, C. B., Leong, J. K., Knutson, B. 2022; 119 (26): e2116703119

  Abstract

  Diffusion tractography allows identification and measurement of structural tracts in the human brain previously associated with motivated behavior in animal models. Recent findings indicate that the structural properties of a tract connecting the midbrain to nucleus accumbens (NAcc) are associated with a diagnosis of stimulant use disorder (SUD), but not relapse. In this preregistered study, we used diffusion tractography in a sample of patients treated for SUD (n = 60) to determine whether qualities of tracts projecting from medial prefrontal, anterior insular, and amygdalar cortices to NAcc might instead foreshadow relapse. As predicted, reduced diffusion metrics of a tract projecting from the right anterior insula to the NAcc were associated with subsequent relapse to stimulant use, but not with previous diagnosis. These findings highlight a structural target for predicting relapse to stimulant use and further suggest that distinct connections to the NAcc may confer risk for relapse versus diagnosis.

  View details for DOI 10.1073/pnas.2116703119

  View details for PubMedID 35727973

• Deconstructing Ketamine-Induced Changes in Cortisol and Dissociative and Affective States in a Controlled Mechanistic Study Hack, L. M., Zhang, X., Brawer, J., Gray, N., Heifets, B., Suppes, T., van Roessel, P., Rodriguez, C., Knutson, B., Williams, L. ELSEVIER SCIENCE INC. 2022: S178-S179

  View details for Web of Science ID 000789022200436

• Acute Ketamine Modulates Cognitive Control Network Activity During Cognitive Inhibition: Evidence From a Mechanistic Trial Zhang, X., Hack, L., Brawer, J., Gray, N., Heifets, B., Suppes, T., van Roessel, P., Rodriguez, C., Knutson, B., Williams, L. ELSEVIER SCIENCE INC. 2022: S225

  View details for Web of Science ID 000789022200552

• Longitudinal tracking of human plasma oxytocin suggests complex responses to moral elevation. Comprehensive psychoneuroendocrinology Parkitny, L., Carter, C. S., Peckins, M. K., Hon, D. A., Saturn, S., Nazarloo, H. P., Hurlbut, W., Knutson, B., Crane, S., Harris, X., Younger, J. 2022; 9: 100105

  Abstract

  Positive social experiences may induce oxytocin release. However, previous studies of moral elevation have generally utilized cross-sectional and simple modeling approaches to establish the relationship between oxytocin and emotional stimuli. Utilizing a cohort of 30 non-lactating women (aged 23.6 ± 5.7 years), we tested whether exposure to a video identified as capable of eliciting moral elevation could change plasma oxytocin levels. Uniquely, we utilized a high-frequency longitudinal sampling approach and multilevel growth curve modeling with landmark registration to test physiological responses. The moral elevation stimulus, versus a control video, elicited significantly greater reports of being "touched/inspired" and "happy/joyful". However, the measured plasma oxytocin response was found to be markedly heterogeneous. While the moral elevation stimulus elicited increased plasma oxytocin as expected, this increase was only modestly larger than that seen following the control video. This increase was also only present in some individuals. We found no relationship between plasma oxytocin and self-report responses to the stimulus. From these data, we argue that future studies of the relationship between oxytocin and emotion need to anticipate heterogeneous responses and thus incorporate comprehensive individual psychological data; these should include evidence-based variables known to be associated with oxytocin such as a history of trauma, and the individual's psychological and emotional state at the time of testing. Given the complexity of physiological oxytocin release, such studies also need to incorporate frequent biological sampling to properly examine the dynamics of hormonal release and response.

  View details for DOI 10.1016/j.cpnec.2021.100105

  View details for PubMedID 35755919

  View details for PubMedCentralID PMC9216598

• Targeting the Salience Network: A Mini-Review on a Novel Neuromodulation Approach for Treating Alcohol Use Disorder. Frontiers in psychiatry Padula, C. B., Tenekedjieva, L., McCalley, D. M., Al-Dasouqi, H., Hanlon, C. A., Williams, L. M., Kozel, F. A., Knutson, B., Durazzo, T. C., Yesavage, J. A., Madore, M. R. 2022; 13: 893833

  Abstract

  Alcohol use disorder (AUD) continues to be challenging to treat despite the best available interventions, with two-thirds of individuals going on to relapse by 1 year after treatment. Recent advances in the brain-based conceptual framework of addiction have allowed the field to pivot into a neuromodulation approach to intervention for these devastative disorders. Small trials of repetitive transcranial magnetic stimulation (rTMS) have used protocols developed for other psychiatric conditions and applied them to those with addiction with modest efficacy. Recent evidence suggests that a TMS approach focused on modulating the salience network (SN), a circuit at the crossroads of large-scale networks associated with AUD, may be a fruitful therapeutic strategy. The anterior insula or dorsal anterior cingulate cortex may be particularly effective stimulation sites given emerging evidence of their roles in processes associated with relapse.

  View details for DOI 10.3389/fpsyt.2022.893833

  View details for PubMedID 35656355

• Taking gambles at face value: Effects of emotional expressions on risky decisions. Frontiers in psychology Winkielman, P., Trujillo, J. L., Bornemann, B., Knutson, B., Paulus, M. P. 2022; 13: 958918

  Abstract

  Emotional facial expressions are ubiquitous and potent social stimuli that can signal favorable and unfavorable conditions. Previous research demonstrates that emotional expressions influence preference judgments, basic approach-avoidance behaviors, and reward learning. We examined whether emotional expressions can influence decisions such as choices between gambles. Based on theories of affective cue processing, we predicted greater risk taking after positive than negative expressions. This hypothesis was tested in four experiments across tasks that varied in implementation of risks, payoffs, probabilities, and temporal decision requirements. Facial expressions were presented unobtrusively and were uninformative about the choice. In all experiments, the likelihood of a risky choice was greater after exposure to positive versus neutral or negative expressions. Similar effects on risky choice occurred after presentation of different negative expressions (e.g., anger, fear, sadness, and disgust), suggesting involvement of general positive and negative affect systems. These results suggest that incidental emotional cues exert a valence-specific influence of on decisions, which could shape risk-taking behavior in social situations.

  View details for DOI 10.3389/fpsyg.2022.958918

  View details for PubMedID 36312095

• Multi-band FMRI compromises detection of mesolimbic reward responses. NeuroImage Srirangarajan, T., Mortazavi, L., Bortolini, T., Moll, J., Knutson, B. 2021: 118617

  Abstract

  Recent innovations in Functional Magnetic Resonance Imaging (FMRI) have sped data collection by enabling simultaneous scans of neural activity in multiple brain locations, but have these innovations come at a cost? In a meta-analysis and preregistered direct comparison of original data, we examined whether acquiring FMRI data with multi-band versus single-band scanning protocols might compromise detection of mesolimbic activity during reward processing. Meta-analytic results (N=44 studies; cumulative n=5005 subjects) indicated that relative to single-band scans, multi-band scans showed significantly decreased effect sizes for reward anticipation in the Nucleus Accumbens (NAcc) by more than half. Direct within-subject comparison of single-band versus multi-band scanning data (multi-band factors=4 and 8; n=12 subjects) acquired during repeated administration of the Monetary Incentive Delay task indicated that reductions in temporal signal-to-noise ratio could account for compromised detection of task-related responses in mesolimbic regions (i.e., the NAcc). Together, these findings imply that researchers should opt for single-band over multi-band scanning protocols when probing mesolimbic responses with FMRI. The findings also have implications for inferring mesolimbic activity during related tasks and rest, for summarizing historical results, and for using neuroimaging data to track individual differences in reward-related brain activity.

  View details for DOI 10.1016/j.neuroimage.2021.118617

  View details for PubMedID 34600102

• Social media users produce more affect that supports cultural values, but are more influenced by affect that violates cultural values. Journal of personality and social psychology Hsu, T. W., Niiya, Y., Thelwall, M., Ko, M., Knutson, B., Tsai, J. L. 2021

  Abstract

  Although social media plays an increasingly important role in communication around the world, social media research has primarily focused on Western users. Thus, little is known about how cultural values shape social media behavior. To examine how cultural affective values might influence social media use, we developed a new sentiment analysis tool that allowed us to compare the affective content of Twitter posts in the United States (55,867 tweets, 1,888 users) and Japan (63,863 tweets, 1,825 users). Consistent with their respective cultural affective values, U.S. users primarily produced positive (vs. negative) posts, whereas Japanese users primarily produced low (vs. high) arousal posts. Contrary to cultural affective values, however, U.S. users were more influenced by changes in others' high arousal negative (e.g., angry) posts, whereas Japanese were more influenced by changes in others' high arousal positive (e.g., excited) posts. These patterns held after controlling for differences in baseline exposure to affective content, and across different topics. Together, these results suggest that across cultures, while social media users primarily produce content that supports their affective values, they are more influenced by content that violates those values. These findings have implications for theories about which affective content spreads on social media, and for applications related to the optimal design and use of social media platforms around the world. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

  View details for DOI 10.1037/pspa0000282

  View details for PubMedID 34491077

• Striatal and septo-hypothalamic responses to anticipation and outcome of affiliative rewards. NeuroImage Bortolini, T., Melo, B., Basilio, R., Fischer, R., Zahn, R., de Oliveira-Souza, R., Knutson, B., Moll, J. 2021: 118474

  Abstract

  Humans are intrinsically motivated to bond with others. The ability to experience affiliative emotions (such as affection/tenderness, sexual attraction, and admiration/awe) may incentivize and promote these affiliative bonds. Here, we interrogate the role of the critical reward circuitry, especially the Nucleus Accumbens (NAcc) and the septo-hypothalamic region, in the anticipation of and response to affiliative rewards using a novel incentive delay task. During Functional Magnetic Resonance Imaging (FMRI), participants (n=23 healthy humans; 14 female) anticipated and watched videos involving affiliative (tenderness, erotic desire, and awe) and nonaffiliative (i.e., food) rewards, as well as neutral scenes. On the one hand, anticipation of both affiliative and nonaffiliative rewards increased activity in the NAcc, anterior insula, and supplementary motor cortex, but activity in the amygdala and the ventromedial prefrontal cortex (vmPFC) increased in response to reward outcomes. On the other hand, affiliative rewards more specifically increased activity in the septo-hypothalamic area. Moreover, NAcc activity during anticipation correlated with positive arousal for all rewards, whereas septo-hypothalamic activity during the outcome correlated with positive arousal and motivation for subsequent re-exposure only for affiliative rewards. Together, these findings implicate a general appetitive response in the NAcc to different types of rewards but suggests a more specific response in the septo-hypothalamic region in response to affiliative rewards outcomes. This work also presents a new task for distinguishing between neural responses to affiliative and non-affiliative rewards.

  View details for DOI 10.1016/j.neuroimage.2021.118474

  View details for PubMedID 34407439

• The rise of affectivism. Nature human behaviour Dukes, D., Abrams, K., Adolphs, R., Ahmed, M. E., Beatty, A., Berridge, K. C., Broomhall, S., Brosch, T., Campos, J. J., Clay, Z., Clement, F., Cunningham, W. A., Damasio, A., Damasio, H., D'Arms, J., Davidson, J. W., de Gelder, B., Deonna, J., de Sousa, R., Ekman, P., Ellsworth, P. C., Fehr, E., Fischer, A., Foolen, A., Frevert, U., Grandjean, D., Gratch, J., Greenberg, L., Greenspan, P., Gross, J. J., Halperin, E., Kappas, A., Keltner, D., Knutson, B., Konstan, D., Kret, M. E., LeDoux, J. E., Lerner, J. S., Levenson, R. W., Loewenstein, G., Manstead, A. S., Maroney, T. A., Moors, A., Niedenthal, P., Parkinson, B., Pavlidis, I., Pelachaud, C., Pollak, S. D., Pourtois, G., Roettger-Roessler, B., Russell, J. A., Sauter, D., Scarantino, A., Scherer, K. R., Stearns, P., Stets, J. E., Tappolet, C., Teroni, F., Tsai, J., Turner, J., Reekum, C. V., Vuilleumier, P., Wharton, T., Sander, D. 2021

  View details for DOI 10.1038/s41562-021-01130-8

  View details for PubMedID 34112980

• Brain activity foreshadows stock price dynamics. The Journal of neuroscience : the official journal of the Society for Neuroscience Stallen, M., Borg, N., Knutson, B. 2021

  Abstract

  Successful investing is challenging, since stock prices are difficult to consistently forecast. Recent neuroimaging evidence suggests, however, that activity in brain regions associated with anticipatory affect may not only predict individual choice, but also forecast aggregate behavior out-of-sample. Thus, in two experiments, we specifically tested whether anticipatory affective brain activity in healthy humans could forecast aggregate changes in stock prices. Using Functional Magnetic Resonance Imaging (FMRI), we found in a first experiment (n=34, 6 females; 140 trials per subject) that Nucleus Accumbens (NAcc) activity forecast stock price direction, whereas Anterior Insula (AIns) activity forecast stock price inflections. In a second preregistered replication experiment (n=39, 7 females) that included different subjects and stocks, AIns activity still forecast stock price inflections. Importantly, AIns activity forecast stock price movement even when choice behavior and conventional stock indicators did not (e.g., previous stock price movements), and classifier analysis indicated that forecasts based on brain activity should generalize to other markets. By demonstrating that AIns activity might serve as a leading indicator of stock price inflections, these findings imply that neural activity associated with anticipatory affect may extend to forecasting aggregate choice in dynamic and competitive environments such as stock markets.SIGNIFICANCE STATEMENTMany try but fail to consistently forecast changes in stock prices. New evidence, however, suggests not only that anticipatory affective brain activity may not only predict individual choice, but also may forecast aggregate choice. Assuming that stock prices index collective choice, we tested whether brain activity sampled during assessment of stock prices could forecast subsequent changes in the prices of those stocks. In two neuroimaging experiments, a combination of previous stock price movements and brain activity in a region implicated in processing uncertainty and arousal forecast next-day stock price changes - even when behavior did not. These findings challenge traditional assumptions of market efficiency by implying that neuroimaging data might reveal "hidden information" capable of foreshadowing stock price dynamics.

  View details for DOI 10.1523/JNEUROSCI.1727-20.2021

  View details for PubMedID 33685944

• White-matter tract connecting anterior insula to nucleus accumbens predicts greater future motivation in adolescents. Developmental cognitive neuroscience Leong, J. K., Ho, T. C., Colich, N. L., Sisk, L., Knutson, B., Gotlib, I. H. 2020; 47: 100881

  Abstract

  The motivation to approach or avoid incentives can change during adolescence. Advances in neuroimaging allow researchers to characterize specific brain circuits that underlie these developmental changes. Whereas activity in the nucleus accumbens (NAcc) can predict approach toward incentive gain, activity in anterior insula (AIns) is associated with avoidance of incentive loss. Recent research characterized the structural white-matter tract connecting the two brain regions, but the tract has neither been characterized in adolescence nor linked to functional activity during incentive anticipation. In this study, we collected diffusion MRI and characterized the tract connecting the AIns to the NAcc for the first time in early adolescents. We then measured NAcc functional activity during a monetary incentive delay task and found that structural coherence of the AIns-NAcc tract is correlated with decreased functional activity at the NAcc terminal of the tract during anticipation of no incentives. In adolescents who completed an assessment 2 years later, we found that AIns-NAcc tract coherence could predict greater future self-reported motivation, and that NAcc functional activity could statistically mediate this association. Together, the findings establish links from brain structure to function to future motivation and provide targets to study the reciprocal development of brain structure and function.

  View details for DOI 10.1016/j.dcn.2020.100881

  View details for PubMedID 33373886

• Medial forebrain bundle structure is linked to human impulsivity. Science advances MacNiven, K. H., Leong, J. K., Knutson, B. 2020; 6 (38)

  Abstract

  Comparative research indicates that projections from midbrain dopamine nuclei [including the ventral tegmental area (VTA)] to the ventral striatum [including the nucleus accumbens (NAcc)] critically support motivated behavior. Using diffusion-weighted imaging and probabilistic tractography in humans, we characterized the trajectory and structure of two tracts connecting the VTA and NAcc, as well as others connecting the substantia nigra and dorsal striatum. Decreased structural coherence of an inferior VTA-NAcc tract was primarily and replicably associated with increased trait impulsivity and also distinguished individuals with a stimulant use disorder from healthy controls. These findings suggest that decreased coherence of the inferior VTA-NAcc tract is associated with increased impulsivity in humans and identify a previously uncharacterized structural target for diagnosing disorders marked by impulsivity.

  View details for DOI 10.1126/sciadv.aba4788

  View details for PubMedID 32938676

• Brain activity forecasts video engagement in an internet attention market. Proceedings of the National Academy of Sciences of the United States of America Tong, L. C., Acikalin, M. Y., Genevsky, A., Shiv, B., Knutson, B. 2020

  Abstract

  The growth of the internet has spawned new "attention markets," in which people devote increasing amounts of time to consuming online content, but the neurobehavioral mechanisms that drive engagement in these markets have yet to be elucidated. We used functional MRI (FMRI) to examine whether individuals' neural responses to videos could predict their choices to start and stop watching videos as well as whether group brain activity could forecast aggregate video view frequency and duration out of sample on the internet (i.e., on youtube.com). Brain activity during video onset predicted individual choice in several regions (i.e., increased activity in the nucleus accumbens [NAcc] and medial prefrontal cortex [MPFC] as well as decreased activity in the anterior insula [AIns]). Group activity during video onset in only a subset of these regions, however, forecasted both aggregate view frequency and duration (i.e., increased NAcc and decreased AIns)-and did so above and beyond conventional measures. These findings extend neuroforecasting theory and tools by revealing that activity in brain regions implicated in anticipatory affect at the onset of video viewing (but not initial choice) can forecast time allocation out of sample in an internet attention market.

  View details for DOI 10.1073/pnas.1905178117

  View details for PubMedID 32152105

• Brain-Responsive Neurostimulation for Loss of Control Eating: Early Feasibility Study. Neurosurgery Wu, H. n., Adler, S. n., Azagury, D. E., Bohon, C. n., Safer, D. L., Barbosa, D. A., Bhati, M. T., Williams, N. R., Dunn, L. B., Tass, P. A., Knutson, B. D., Yutsis, M. n., Fraser, A. n., Cunningham, T. n., Richardson, K. n., Skarpaas, T. L., Tcheng, T. K., Morrell, M. J., Roberts, L. W., Malenka, R. C., Lock, J. D., Halpern, C. H. 2020

  Abstract

  Loss of control (LOC) is a pervasive feature of binge eating, which contributes significantly to the growing epidemic of obesity; approximately 80 million US adults are obese. Brain-responsive neurostimulation guided by the delta band was previously found to block binge-eating behavior in mice. Following novel preclinical work and a human case study demonstrating an association between the delta band and reward anticipation, the US Food and Drug Administration approved an Investigational Device Exemption for a first-in-human study.To assess feasibility, safety, and nonfutility of brain-responsive neurostimulation for LOC eating in treatment-refractory obesity.This is a single-site, early feasibility study with a randomized, single-blinded, staggered-onset design. Six subjects will undergo bilateral brain-responsive neurostimulation of the nucleus accumbens for LOC eating using the RNS® System (NeuroPace Inc). Eligible participants must have treatment-refractory obesity with body mass index ≥ 45 kg/m2. Electrophysiological signals of LOC will be characterized using real-time recording capabilities coupled with synchronized video monitoring. Effects on other eating disorder pathology, mood, neuropsychological profile, metabolic syndrome, and nutrition will also be assessed.Safety/feasibility of brain-responsive neurostimulation of the nucleus accumbens will be examined. The primary success criterion is a decrease of ≥1 LOC eating episode/week based on a 28-d average in ≥50% of subjects after 6 mo of responsive neurostimulation.This study is the first to use brain-responsive neurostimulation for obesity; this approach represents a paradigm shift for intractable mental health disorders.

  View details for DOI 10.1093/neuros/nyaa300

  View details for PubMedID 32717033

• Culturally valued facial expressions enhance loan request success. Emotion (Washington, D.C.) Park, B., Genevsky, A., Knutson, B., Tsai, J. 2019

  Abstract

  Why do people share resources with some strangers, but not others? This question becomes increasingly relevant as online platforms that promote lending world-wide proliferate (e.g., www.kiva.org). We predicted that lenders from nations that value excitement and other high-arousal positive states (HAP; e.g., United States) would loan more to borrowers who show excitement in their profile photos because the lenders perceive them to be more affiliative (e.g., trustworthy). As predicted, using naturally occurring Kiva data, lenders from the United States and Canada were more likely to lend money to borrowers (N = 13,500) who showed greater positive arousal (e.g., excitement) than were lenders from East Asian nations (e.g., Taiwan), above and beyond loan features (amount, repayment term; Study 1). In a randomly selected sample of Kiva lenders from 11 nations (N = 658), lenders from nations that valued HAP more were more likely to lend money to borrowers who showed open "excited" versus closed "calm" smiles, above and beyond other socioeconomic and cultural factors (Study 2). Finally, we examined whether cultural differences in lending were related to judgments of affiliation in an experimental study (Study 3, N = 103). Compared with Koreans, European Americans lent more to excited borrowers because they viewed them as more affiliative, regardless of borrowers' race (White, Asian) or sex (male, female). These findings suggest that people use their culture's affective values to decide with whom to share resources, and lend less to borrowers whose emotional expressions do not match those values, regardless of their race or sex. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

  View details for DOI 10.1037/emo0000642

  View details for PubMedID 31380663

• Apparent Effects of Opioid Use on Neural Responses to Reward in Chronic Pain. Scientific reports Martucci, K. T., MacNiven, K. H., Borg, N. n., Knutson, B. n., Mackey, S. C. 2019; 9 (1): 9633

  Abstract

  Neural responses to incentives are altered in chronic pain and by opioid use. To understand how opioid use modulates the neural response to reward/value in chronic pain, we compared brain functional magnetic resonance imaging (fMRI) responses to a monetary incentive delay (MID) task in patients with fibromyalgia taking opioids (N = 17), patients with fibromyalgia not taking opioids (N = 17), and healthy controls (N = 15). Both groups of patients with fibromyalgia taking and not taking opioids had similar levels of pain, psychological measures, and clinical symptoms. Neural responses in the nucleus accumbens to anticipated reward and non-loss outcomes did not differ from healthy controls in either fibromyalgia group. However, neural responses in the medial prefrontal cortex differed, such that patients with fibromyalgia not taking opioids demonstrated significantly altered responses to anticipated rewards and non-loss outcomes compared to healthy controls, but patients with fibromyalgia taking opioids did not. Despite limitations including the use of additional non-opioid medications by fibromyalgia patients taking opioids, these preliminary findings suggest relatively "normalized" neural responses to monetary incentives in chronic pain patients who take opioids versus those who do not.

  View details for DOI 10.1038/s41598-019-45961-y

  View details for PubMedID 31270360

• Neural responses to monetary incentives in bipolar disorder. NeuroImage. Clinical Johnson, S. L., Mehta, H. n., Ketter, T. A., Gotlib, I. H., Knutson, B. n. 2019; 24: 102018

  Abstract

  Although behavioral sensitivity to reward predicts the onset and course of mania in bipolar disorder, the evidence for neural abnormalities in reward processing in bipolar disorder is mixed. To probe neural responsiveness to anticipated and received rewards in the context of bipolar disorder, we scanned individuals with remitted bipolar I disorder (n = 24) and well-matched controls (n = 24; matched for age and gender) using Functional Magnetic Resonance Imaging (FMRI) during a Monetary Incentive Delay (MID) task. Relative to controls, the bipolar group showed reduced NAcc activity during anticipation of gains. Across groups, this blunting correlated with individual differences in impulsive responses to positive emotions (Positive Urgency), which statistically accounted for the association of blunted NAcc activity with bipolar diagnosis. These results suggest that blunted NAcc responses during gain anticipation in the context of bipolar disorder may reflect individual differences in Positive Urgency. These findings may help resolve discrepancies in the literature on neural responses to reward in bipolar disorder, and clarify the relationship between brain activity and the propensity to experience manic episodes.

  View details for DOI 10.1016/j.nicl.2019.102018

  View details for PubMedID 31670069

• Toward a Deep Science of Affect and Motivation Knutson, B., Srirangarajan, T., Neta, M., Haas, I. J. SPRINGER INTERNATIONAL PUBLISHING AG. 2019: 193–220

  View details for DOI 10.1007/978-3-030-27473-3_7

  View details for Web of Science ID 000537307300007

• Association of Neural Responses to Drug Cues With Subsequent Relapse to Stimulant Use. JAMA network open MacNiven, K. H., Jensen, E. L., Borg, N., Padula, C. B., Humphreys, K., Knutson, B. 2018; 1 (8): e186466

  Abstract

  Although chronic relapse is a characteristic of addiction to stimulants, conventional measures (eg, clinical, demographic, and self-report) do not robustly identify which individuals are most vulnerable to relapse.To test whether drug cues are associated with increased mesolimbic neural activity in patients undergoing treatment for stimulant use disorder and whether this activity is associated with risk for subsequent relapse.This prospective cohort study of 76 participants included a control group for baseline group comparisons. Veteran patients (n = 36) with stimulant use disorders were recruited from a 28-day residential treatment program at the Veterans Affairs Palo Alto Health Care System. Healthy controls (n = 40) were recruited from the surrounding community. Baseline data were collected between September 21, 2015, and January 26, 2018, from patients and healthy controls using functional magnetic resonance imaging during a performance of a reward cue task. Patients' stimulant use was subsequently assessed after treatment discharge (at approximately 1, 3, and 6 months) to assess relapse outcomes.Primary measures included neural responses to drug and food cues in estimated mesolimbic volumes of interest, including the medial prefrontal cortex, nucleus accumbens (NAcc), and ventral tegmental area. The primary outcome variable was relapse (defined as any stimulant use), assessed both dichotomously (3 months after discharge) and continuously (days to relapse). Brain activity measures were contrasted between groups to validate neural measures of drug cue reactivity, which were then used to estimate relapse outcomes of patients.Relative to controls (n = 40; 16 women and 24 men; mean [SD] age, 32.0 [11.6] years), patients (n = 36; 2 women and 34 men; mean [SD] age, 43.4 [13.3] years) showed increased mesolimbic activity in response to drug cues (medial prefrontal cortex, t74 = 2.90, P = .005, Cohen d = 0.66; NAcc, t74 = 2.39, P = .02, Cohen d = 0.54; and ventral tegmental area, t74 = 4.04, P < .001, Cohen d = 0.92). In patients, increased drug cue response in the NAcc (but not other volumes of interest) was associated with time to relapse months later (Cox proportional hazards regression hazard ratio, 2.30; 95% CI, 1.40-3.79). After controlling for age, NAcc response to drug cues classified relapsers (12 patients; 1 woman and 11 men; mean [SD] age, 49.3 [14.1] years) and abstainers (21 patients; 1 woman and 20 men; mean [SD] age, 39.3 [12.3] years) at 3 months with 75.8% classification accuracy. Model comparison further indicated that NAcc responses to drug cues were associated with relapse above and beyond estimations of relapse according to conventional measures.Responses in the NAcc to stimulant cues appear to be associated with relapse in humans. Identification of neural markers may eventually help target interventions to the most vulnerable individuals.

  View details for DOI 10.1001/jamanetworkopen.2018.6466

  View details for PubMedID 30646331

  View details for PubMedCentralID PMC6324538

• Striatal dopamine deficits predict reductions in striatal functional connectivity in major depression: a concurrent 11C-raclopride positron emission tomography and functional magnetic resonance imaging investigation. Translational psychiatry Hamilton, J. P., Sacchet, M. D., Hjornevik, T., Chin, F. T., Shen, B., Kampe, R., Park, J. H., Knutson, B. D., Williams, L. M., Borg, N., Zaharchuk, G., Camacho, M. C., Mackey, S., Heilig, M., Drevets, W. C., Glover, G. H., Gambhir, S. S., Gotlib, I. H. 2018; 8 (1): 264

  Abstract

  Major depressive disorder (MDD) is characterized by the altered integration of reward histories and reduced responding of the striatum. We have posited that this reduced striatal activation in MDD is due to tonically decreased stimulation of striatal dopamine synapses which results in decremented propagation of information along the cortico-striatal-pallido-thalamic (CSPT) spiral. In the present investigation, we tested predictions of this formulation by conducting concurrent functional magnetic resonance imaging (fMRI) and 11C-raclopride positron emission tomography (PET) in depressed and control (CTL) participants. We scanned 16 depressed and 14 CTL participants with simultaneous fMRI and 11C-raclopride PET. We estimated raclopride binding potential (BPND), voxel-wise, and compared MDD and CTL samples with respect to BPND in the striatum. Using striatal regions that showed significant between-group BPND differences as seeds, we conducted whole-brain functional connectivity analysis using the fMRI data and identified brain regions in each group in which connectivity with striatal seed regions scaled linearly with BPND from these regions. We observed increased BPND in the ventral striatum, bilaterally, and in the right dorsal striatum in the depressed participants. Further, we found that as BPND increased in both the left ventral striatum and right dorsal striatum in MDD, connectivity with the cortical targets of these regions (default-mode network and salience network, respectively) decreased. Deficits in stimulation of striatal dopamine receptors in MDD could account in part for the failure of transfer of information up the CSPT circuit in the pathophysiology of this disorder.

  View details for PubMedID 30504860

• Neural sensitivity to personal and vicarious reward differentially relates to prosociality and well-being SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE Morelli, S. A., Knutson, B., Zaki, J. 2018; 13 (8): 831–39

  Abstract

  Individuals stably vary in their responses to rewards, but researchers have not yet determined whether sensitivity to rewarding outcomes translates across social and non-social contexts or whether different forms of reward sensitivity relate to distinct behavioral tendencies. We tested for responsiveness to different types of rewards by assessing individuals' neural sensitivity to personal vs. vicarious monetary reward outcomes and explored how responses to each related to prosociality and well-being. Forty-six participants underwent functional magnetic resonance imaging (fMRI) scanning while winning money for themselves and observing a friend and stranger win money. All types of reward outcomes engaged the ventral striatum, but neural sensitivity to rewards for the self and for others were uncorrelated across individuals. Further, while sensitivity to rewards for the self or a close friend correlated with individuals' psychological well-being, only sensitivity to a friend's rewards correlated with individuals' prosociality. These findings highlight the value of independently assessing responsiveness to different types of reward and illuminate affective mechanisms that may promote prosocial behavior and well-being.

  View details for PubMedID 30016481

  View details for PubMedCentralID PMC6123524

• Distinct neural circuits support incentivized inhibition. NeuroImage Leong, J. K., MacNiven, K. H., Samanez-Larkin, G. R., Knutson, B. 2018; 178: 435–44

  Abstract

  The ability to inhibit responses under high stakes, or "incentivized inhibition," is critical for adaptive impulse control. While previous research indicates that right ventrolateral prefrontal cortical (VLPFC) activity plays a key role in response inhibition, less research has addressed how incentives might influence this circuit. By combining a novel behavioral task, functional magnetic resonance imaging (FMRI), and diffusion-weighted imaging (DWI), we targeted and characterized specific neural circuits that support incentivized inhibition. Behaviorally, large incentives enhanced responses to obtain money, but also reduced response inhibition. Functionally, activity in both right VLPFC and right anterior insula (AIns) predicted successful inhibition for high incentives. Structurally, characterization of a novel white-matter tract connecting the right AIns and VLPFC revealed an association of tract coherence with incentivized inhibition performance. Finally, individual differences in right VLPFC activity statistically mediated the association of right AIns-VLPFC tract coherence with incentivized inhibition performance. These multimodal findings bridge brain structure, brain function, and behavior to clarify how individuals can inhibit impulses, even in the face of high stakes.

  View details for PubMedID 29803959

• Altered prefrontal correlates of monetary anticipation and outcome in chronic pain. Pain Martucci, K. T., Borg, N., MacNiven, K. H., Knutson, B., Mackey, S. C. 2018

  Abstract

  Chronic pain may alter both affect- and value-related behaviors, which represents a potentially treatable aspect of chronic pain experience. Current understanding of how chronic pain influences the function of brain reward systems, however, is limited. Using a monetary incentive delay task and functional magnetic resonance imaging (fMRI), we measured neural correlates of reward anticipation and outcomes in female participants with the chronic pain condition of fibromyalgia (N = 17) and age-matched, pain-free, female controls (N = 15). We hypothesized that patients would demonstrate lower positive arousal, as well as altered reward anticipation and outcome activity within corticostriatal circuits implicated in reward processing. Patients demonstrated lower arousal ratings as compared with controls, but no group differences were observed for valence, positive arousal, or negative arousal ratings. Group fMRI analyses were conducted to determine predetermined region of interest, nucleus accumbens (NAcc) and medial prefrontal cortex (mPFC), responses to potential gains, potential losses, reward outcomes, and punishment outcomes. Compared with controls, patients demonstrated similar, although slightly reduced, NAcc activity during gain anticipation. Conversely, patients demonstrated dramatically reduced mPFC activity during gain anticipation-possibly related to lower estimated reward probabilities. Further, patients demonstrated normal mPFC activity to reward outcomes, but dramatically heightened mPFC activity to no-loss (nonpunishment) outcomes. In parallel to NAcc and mPFC responses, patients demonstrated slightly reduced activity during reward anticipation in other brain regions, which included the ventral tegmental area, anterior cingulate cortex, and anterior insular cortex. Together, these results implicate altered corticostriatal processing of monetary rewards in chronic pain.

  View details for PubMedID 29790868

• Neuroforecasting Aggregate Choice CURRENT DIRECTIONS IN PSYCHOLOGICAL SCIENCE Knutson, B., Genevsky, A. 2018; 27 (2): 110–15

  Abstract

  Advances in brain-imaging design and analysis have allowed investigators to use neural activity to predict individual choice, while emerging Internet markets have opened up new opportunities for forecasting aggregate choice. Here, we review emerging research that bridges these levels of analysis by attempting to use group neural activity to forecast aggregate choice. A survey of initial findings suggests that components of group neural activity might forecast aggregate choice, in some cases even beyond traditional behavioral measures. In addition to demonstrating the plausibility of neuroforecasting, these findings raise the possibility that not all neural processes that predict individual choice forecast aggregate choice to the same degree. We propose that although integrative choice components may confer more consistency within individuals, affective choice components may generalize more broadly across individuals to forecast aggregate choice.

  View details for PubMedID 29706726

  View details for PubMedCentralID PMC5892847

• Reward and loss anticipation in panic disorder: An fMRI study PSYCHIATRY RESEARCH-NEUROIMAGING Held-Poschardt, D., Sterzer, P., Schlagenhauf, F., Pehrs, C., Wittmann, A., Stoy, M., Haegele, C., Knutson, B., Heinz, A., Stroehle, A. 2018; 271: 111–17

  Abstract

  Anticipatory anxiety and harm avoidance are essential features of panic disorder (PD) and may involve deficits in the reward system of the brain, in particular in the ventral striatum. While neuroimaging studies on PD have focused on fearful and negative affective stimulus processing, no investigations have directly addressed deficits in reward and loss anticipation. To determine whether the ventral striatum shows abnormal neural activity in PD patients during anticipation of loss or gain, an event-related functional magnetic resonance imaging experiment using a monetary incentive delay task was employed in 10 patients with PD and 10 healthy controls. A repeated-measures ANOVA to identify effects of group (PD vs. Control) and condition (anticipation of loss vs. gain vs. neutral outcome) revealed that patients with PD showed significantly reduced bilateral ventral striatal activation during reward anticipation but increased activity during loss anticipation. Within the patient group, the degree of activation in the ventral striatum during loss-anticipation was positively correlated with harm avoidance and negatively correlated with novelty seeking. These findings suggest that behavioural impairments in panic disorder may be related to abnormal neural processing of motivational cues.

  View details for PubMedID 29169660

• Closing the loop on impulsivity via nucleus accumbens delta-band activity in mice and man. Proceedings of the National Academy of Sciences of the United States of America Wu, H. n., Miller, K. J., Blumenfeld, Z. n., Williams, N. R., Ravikumar, V. K., Lee, K. E., Kakusa, B. n., Sacchet, M. D., Wintermark, M. n., Christoffel, D. J., Rutt, B. K., Bronte-Stewart, H. n., Knutson, B. n., Malenka, R. C., Halpern, C. H. 2018; 115 (1): 192–97

  Abstract

  Reward hypersensitization is a common feature of neuropsychiatric disorders, manifesting as impulsivity for anticipated incentives. Temporally specific changes in activity within the nucleus accumbens (NAc), which occur during anticipatory periods preceding consummatory behavior, represent a critical opportunity for intervention. However, no available therapy is capable of automatically sensing and therapeutically responding to this vulnerable moment in time when anticipation-related neural signals may be present. To identify translatable biomarkers for an off-the-shelf responsive neurostimulation system, we record local field potentials from the NAc of mice and a human anticipating conventional rewards. We find increased power in 1- to 4-Hz oscillations predominate during reward anticipation, which can effectively trigger neurostimulation that reduces consummatory behavior in mice sensitized to highly palatable food. Similar oscillations are present in human NAc during reward anticipation, highlighting the translational potential of our findings in the development of a treatment for a major unmet need.

  View details for PubMedID 29255043

• Association of Neural Responses to Drug Cues With Subsequent Relapse to Stimulant Use JAMA Netw Open MacNiven, K. H., Jensen, E. L., Borg, N., Padula, C. B., Humphreys, K., Knutson, B. 2018

  View details for DOI 10.1001/jamanetworkopen.2018.6466

• Individual differences in skewed financial risk-taking across the adult life span COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE Seaman, K. L., Leong, J. K., Wu, C. C., Knutson, B., Samanez-Larkin, G. R. 2017; 17 (6): 1232–41

  Abstract

  Older adults are disproportionately targeted by fraud schemes that advertise unlikely but large returns (positively skewed risks). We examined adult age differences in choice and neural activity as individuals considered risky gambles. Gambles were symmetric (50% chance of modest win or loss), positively skewed (25% chance of large gain), or negatively skewed (25% chance of large loss). The willingness to accept positively skewed relative to symmetric gambles increased with age, and this effect replicated in an independent behavioral study. Whole-brain functional magnetic resonance imaging analyses comparing positively (vs. negatively) skewed trials revealed that relative to younger adults, older adults showed increased anticipatory activity for negatively skewed gambles but reduced activity for positively skewed gambles in the anterior cingulate and lateral prefrontal regions. Individuals who were more biased toward positively skewed gambles showed increased activity in a network of regions including the nucleus accumbens. These results reveal age biases toward positively skewed gambles and age differences in corticostriatal regions during skewed risk-taking, and have implications for identifying financial decision biases across adulthood.

  View details for PubMedID 29063520

  View details for PubMedCentralID PMC5709503

• When Brain Beats Behavior: Neuroforecasting Crowdfunding Outcomes. The Journal of neuroscience : the official journal of the Society for Neuroscience Genevsky, A., Yoon, C., Knutson, B. 2017; 37 (36): 8625-8634

  Abstract

  Although traditional economic and psychological theories imply that individual choice best scales to aggregate choice, primary components of choice reflected in neural activity may support even more generalizable forecasts. Crowdfunding represents a significant and growing platform for funding new and unique projects, causes, and products. To test whether neural activity could forecast market-level crowdfunding outcomes weeks later, 30 human subjects (14 female) decided whether to fund proposed projects described on an Internet crowdfunding website while undergoing scanning with functional magnetic resonance imaging. Although activity in both the nucleus accumbens (NAcc) and medial prefrontal cortex predicted individual choices to fund on a trial-to-trial basis in the neuroimaging sample, only NAcc activity generalized to forecast market funding outcomes weeks later on the Internet. Behavioral measures from the neuroimaging sample, however, did not forecast market funding outcomes. This pattern of associations was replicated in a second study. These findings demonstrate that a subset of the neural predictors of individual choice can generalize to forecast market-level crowdfunding outcomes-even better than choice itself.SIGNIFICANCE STATEMENT Forecasting aggregate behavior with individual neural data has proven elusive; even when successful, neural forecasts have not historically supplanted behavioral forecasts. In the current research, we find that neural responses can forecast market-level choice and outperform behavioral measures in a novel Internet crowdfunding context. Targeted as well as model-free analyses convergently indicated that nucleus accumbens activity can support aggregate forecasts. Beyond providing initial evidence for neuropsychological processes implicated in crowdfunding choices, these findings highlight the ability of neural features to forecast aggregate choice, which could inform applications relevant to business and policy.

  View details for DOI 10.1523/JNEUROSCI.1633-16.2017

  View details for PubMedID 28821681

  View details for PubMedCentralID PMC5588458

• Neurocultural Evidence That Ideal Affect Match Promotes Giving. Social cognitive and affective neuroscience Park, B., Blevins, E., Knutson, B., Tsai, J. L. 2017

  Abstract

  Why do people give to strangers? We propose that people trust and give more to those whose emotional expressions match how they ideally want to feel ("ideal affect match"). European Americans and Koreans played multiple trials of the Dictator Game with recipients who varied in emotional expression (excited, calm), race (White, Asian), and sex (male, female). Consistent with their culture's valued affect, European Americans trusted and gave more to excited than calm recipients, whereas Koreans trusted and gave more to calm than excited recipients. These findings held regardless of recipient race and sex. We then used fMRI to probe potential affective and mentalizing mechanisms. Increased activity in the nucleus accumbens (NAcc; associated with reward anticipation) predicted giving, as did decreased activity in the right temporo-parietal junction (rTPJ; associated with reduced belief prediction error). Ideal affect match decreased rTPJ activity, suggesting that people may trust and give more to strangers whom they perceive to share their affective values.

  View details for DOI 10.1093/scan/nsx047

  View details for PubMedID 28379542

• Blunted ventral striatal responses to anticipated rewards foreshadow problematic drug use in novelty-seeking adolescents. Nature communications Büchel, C., Peters, J., Banaschewski, T., Bokde, A. L., Bromberg, U., Conrod, P. J., Flor, H., Papadopoulos, D., Garavan, H., Gowland, P., Heinz, A., Walter, H., Ittermann, B., Mann, K., Martinot, J., Paillère-Martinot, M., Nees, F., Paus, T., Pausova, Z., Poustka, L., Rietschel, M., Robbins, T. W., Smolka, M. N., Gallinat, J., Schumann, G., Knutson, B. 2017; 8: 14140-?

  Abstract

  Novelty-seeking tendencies in adolescents may promote innovation as well as problematic impulsive behaviour, including drug abuse. Previous research has not clarified whether neural hyper- or hypo-responsiveness to anticipated rewards promotes vulnerability in these individuals. Here we use a longitudinal design to track 144 novelty-seeking adolescents at age 14 and 16 to determine whether neural activity in response to anticipated rewards predicts problematic drug use. We find that diminished BOLD activity in mesolimbic (ventral striatal and midbrain) and prefrontal cortical (dorsolateral prefrontal cortex) regions during reward anticipation at age 14 predicts problematic drug use at age 16. Lower psychometric conscientiousness and steeper discounting of future rewards at age 14 also predicts problematic drug use at age 16, but the neural responses independently predict more variance than psychometric measures. Together, these findings suggest that diminished neural responses to anticipated rewards in novelty-seeking adolescents may increase vulnerability to future problematic drug use.

  View details for DOI 10.1038/ncomms14140

  View details for PubMedID 28221370

  View details for PubMedCentralID PMC5321762

• Blunted ventral striatal responses to anticipated rewards foreshadow problematic drug use in novelty-seeking adolescents NATURE COMMUNICATIONS Buechel, C., Peters, J., Banaschewski, T., Bokde, A. L., Bromberg, U., Conrod, P. J., Flor, H., Papadopoulos, D., Garavan, H., Gowland, P., Heinz, A., Walter, H., Ittermann, B., Mann, K., Martinot, J., Paillere-Martinot, M., Nees, F., Paus, T., Pausova, Z., Poustka, L., Rietschel, M., Robbins, T., Smolka, M. N., Gallinat, J., Schumann, G., Knutson, B. 2017; 8

  Abstract

  Novelty-seeking tendencies in adolescents may promote innovation as well as problematic impulsive behaviour, including drug abuse. Previous research has not clarified whether neural hyper- or hypo-responsiveness to anticipated rewards promotes vulnerability in these individuals. Here we use a longitudinal design to track 144 novelty-seeking adolescents at age 14 and 16 to determine whether neural activity in response to anticipated rewards predicts problematic drug use. We find that diminished BOLD activity in mesolimbic (ventral striatal and midbrain) and prefrontal cortical (dorsolateral prefrontal cortex) regions during reward anticipation at age 14 predicts problematic drug use at age 16. Lower psychometric conscientiousness and steeper discounting of future rewards at age 14 also predicts problematic drug use at age 16, but the neural responses independently predict more variance than psychometric measures. Together, these findings suggest that diminished neural responses to anticipated rewards in novelty-seeking adolescents may increase vulnerability to future problematic drug use.

  View details for DOI 10.1038/ncomms14140

  View details for Web of Science ID 000394498300001

  View details for PubMedCentralID PMC5321762

• Brains, environments, and policy responses to addiction. Science (New York, N.Y.) Humphreys, K. n., Malenka, R. C., Knutson, B. n., MacCoun, R. J. 2017; 356 (6344): 1237–38

  View details for PubMedID 28642399

• A Genetic Polymorphism of the Human Dopamine Transporter Determines the Impact of Sleep Deprivation on Brain Responses to Rewards and Punishments JOURNAL OF COGNITIVE NEUROSCIENCE Greer, S. M., Goldstein, A. N., Knutson, B., Walker, M. P. 2016; 28 (6): 803-810

  Abstract

  Despite an emerging link between alterations in motivated behavior and a lack of sleep, the impact of sleep deprivation on human brain mechanisms of reward and punishment remain largely unknown, as does the role of trait dopamine activity in modulating such effects in the mesolimbic system. Combining fMRI with an established incentive paradigm and individual genotyping, here, we test the hypothesis that trait differences in the human dopamine transporter (DAT) gene-associated with altered synaptic dopamine signalling-govern the impact of sleep deprivation on neural sensitivity to impending monetary gains and losses. Consistent with this framework, markedly different striatal reward responses were observed following sleep loss depending on the DAT functional polymorphisms. Only participants carrying a copy of the nine-repeat DAT allele-linked to higher phasic dopamine activity-expressed amplified striatal response during anticipation of monetary gain following sleep deprivation. Moreover, participants homozygous for the ten-repeat DAT allele-linked to lower phasic dopamine activity-selectively demonstrated an increase in sensitivity to monetary loss within anterior insula following sleep loss. Together, these data reveal a mechanistic dependency on human of trait dopaminergic function in determining the interaction between sleep deprivation and neural processing of rewards and punishments. Such findings have clinical implications in disorders where the DAT genetic polymorphism presents a known risk factor with comorbid sleep disruption, including attention hyperactive deficit disorder and substance abuse.

  View details for DOI 10.1162/jocn_a_00939

  View details for Web of Science ID 000375780300003

  View details for PubMedID 26918589

• Nucleus accumbens D2R cells signal prior outcomes and control risky decision-making. Nature Zalocusky, K. A., Ramakrishnan, C., Lerner, T. N., Davidson, T. J., Knutson, B., Deisseroth, K. 2016; 531 (7596): 642-646

  Abstract

  A marked bias towards risk aversion has been observed in nearly every species tested. A minority of individuals, however, instead seem to prefer risk (repeatedly choosing uncertain large rewards over certain but smaller rewards), and even risk-averse individuals sometimes opt for riskier alternatives. It is not known how neural activity underlies such important shifts in decision-making-either as a stable trait across individuals or at the level of variability within individuals. Here we describe a model of risk-preference in rats, in which stable individual differences, trial-by-trial choices, and responses to pharmacological agents all parallel human behaviour. By combining new genetic targeting strategies with optical recording of neural activity during behaviour in this model, we identify relevant temporally specific signals from a genetically and anatomically defined population of neurons. This activity occurred within dopamine receptor type-2 (D2R)-expressing cells in the nucleus accumbens (NAc), signalled unfavourable outcomes from the recent past at a time appropriate for influencing subsequent decisions, and also predicted subsequent choices made. Having uncovered this naturally occurring neural correlate of risk selection, we then mimicked the temporally specific signal with optogenetic control during decision-making and demonstrated its causal effect in driving risk-preference. Specifically, risk-preferring rats could be instantaneously converted to risk-averse rats with precisely timed phasic stimulation of NAc D2R cells. These findings suggest that individual differences in risk-preference, as well as real-time risky decision-making, can be largely explained by the encoding in D2R-expressing NAc cells of prior unfavourable outcomes during decision-making.

  View details for DOI 10.1038/nature17400

  View details for PubMedID 27007845

• Neural evidence for cultural differences in the valuation of positive facial expressions. Social cognitive and affective neuroscience Park, B., Tsai, J. L., Chim, L., Blevins, E., Knutson, B. 2016; 11 (2): 243-252

  Abstract

  European Americans value excitement more and calm less than Chinese. Within cultures, European Americans value excited and calm states similarly, whereas Chinese value calm more than excited states. To examine how these cultural differences influence people's immediate responses to excited vs calm facial expressions, we combined a facial rating task with functional magnetic resonance imaging. During scanning, European American (n = 19) and Chinese (n = 19) females viewed and rated faces that varied by expression (excited, calm), ethnicity (White, Asian) and gender (male, female). As predicted, European Americans showed greater activity in circuits associated with affect and reward (bilateral ventral striatum, left caudate) while viewing excited vs calm expressions than did Chinese. Within cultures, European Americans responded to excited vs calm expressions similarly, whereas Chinese showed greater activity in these circuits in response to calm vs excited expressions regardless of targets' ethnicity or gender. Across cultural groups, greater ventral striatal activity while viewing excited vs. calm expressions predicted greater preference for excited vs calm expressions months later. These findings provide neural evidence that people find viewing the specific positive facial expressions valued by their cultures to be rewarding and relevant.

  View details for DOI 10.1093/scan/nsv113

  View details for PubMedID 26342220

  View details for PubMedCentralID PMC4733341

• White-Matter Tract Connecting Anterior Insula to Nucleus Accumbens Correlates with Reduced Preference for Positively Skewed Gambles NEURON Leong, J. K., Pestilli, F., Wu, C. C., Samanez-Larkin, G. R., Knutson, B. 2016; 89 (1): 63-69

  Abstract

  Individuals sometimes show inconsistent risk preferences, including excessive attraction to gambles featuring small chances of winning large amounts (called "positively skewed" gambles). While functional neuroimaging research indicates that nucleus accumbens (NAcc) and anterior insula (AIns) activity inversely predict risky choice, structural connections between these regions have not been described in humans. By combining diffusion-weighted MRI with tractography, we identified the anatomical trajectory of white-matter tracts projecting from the AIns to the NAcc and statistically validated these tracts using Linear Fascicle Evaluation (LiFE) and virtual lesions. Coherence of the right AIns-NAcc tract correlated with reduced preferences for positively skewed gambles. Further, diminished NAcc activity during gamble presentation mediated the association between tract structure and choice. These results identify an unreported tract connecting the AIns to the NAcc in humans and support the notion that structural connections can alter behavior by influencing brain activity as individuals weigh uncertain gains against uncertain losses.

  View details for DOI 10.1016/j.neuron.2015.12.015

  View details for Web of Science ID 000373564300008

  View details for PubMedID 26748088

  View details for PubMedCentralID PMC4720154

• Prefrontal cortical regulation of brainwide circuit dynamics and reward-related behavior. Science Ferenczi, E. A., Zalocusky, K. A., Liston, C., Grosenick, L., Warden, M. R., Amatya, D., Katovich, K., Mehta, H., Patenaude, B., Ramakrishnan, C., Kalanithi, P., Etkin, A., Knutson, B., Glover, G. H., Deisseroth, K. 2016; 351 (6268)

  Abstract

  Motivation for reward drives adaptive behaviors, whereas impairment of reward perception and experience (anhedonia) can contribute to psychiatric diseases, including depression and schizophrenia. We sought to test the hypothesis that the medial prefrontal cortex (mPFC) controls interactions among specific subcortical regions that govern hedonic responses. By using optogenetic functional magnetic resonance imaging to locally manipulate but globally visualize neural activity in rats, we found that dopamine neuron stimulation drives striatal activity, whereas locally increased mPFC excitability reduces this striatal response and inhibits the behavioral drive for dopaminergic stimulation. This chronic mPFC overactivity also stably suppresses natural reward-motivated behaviors and induces specific new brainwide functional interactions, which predict the degree of anhedonia in individuals. These findings describe a mechanism by which mPFC modulates expression of reward-seeking behavior, by regulating the dynamical interactions between specific distant subcortical regions.

  View details for DOI 10.1126/science.aac9698

  View details for PubMedID 26722001

• Neural valuation of environmental resources. NeuroImage Sawe, N., Knutson, B. 2015; 122: 87-95

  Abstract

  How do people value environmental resources? To estimate public valuation of natural resources, researchers often conduct surveys that ask people how much they would be willing to pay to preserve or restore threatened natural resources. However, these survey responses often elicit complex affective responses, including negative reactions toward proposed destructive land uses of those resources. To better characterize processes that underlie the valuation of environmental resources, we conducted behavioral and neuroimaging experiments in which subjects chose whether or not to donate money to protect natural park lands (iconic versus non-iconic) from proposed land uses (destructive versus non-destructive). In both studies, land use destructiveness motivated subjects' donations more powerfully than did the iconic qualities of the parks themselves. Consistent with an anticipatory affect account, nucleus accumbens (NAcc) activity increased in response to more iconic parks, while anterior insula activity increased in response to more destructive uses, and the interaction of these considerations altered activity in the medial prefrontal cortex (MPFC). Further, anterior insula activity predicted increased donations to preserve parks threatened by destructive uses, but MPFC activity predicted reduced donations. Finally, individuals with stronger pro-environmental attitudes showed greater anterior insula activity in response to proposed destructive uses. These results imply that negative responses to destructive land uses may play a prominent role in environmental valuation, potentially overshadowing positive responses to the environmental resources themselves. The findings also suggest that neuroimaging methods might eventually complement traditional survey methods by allowing researchers to disentangle distinct affective responses that influence environmental valuation.

  View details for DOI 10.1016/j.neuroimage.2015.08.010

  View details for PubMedID 26265156

• Neural Affective Mechanisms Predict Market-Level Microlending. Psychological science Genevsky, A., Knutson, B. 2015; 26 (9): 1411-1422

  Abstract

  Humans sometimes share with others whom they may never meet or know, in violation of the dictates of pure self-interest. Research has not established which neuropsychological mechanisms support lending decisions, nor whether their influence extends to markets involving significant financial incentives. In two studies, we found that neural affective mechanisms influence the success of requests for microloans. In a large Internet database of microloan requests (N = 13,500), we found that positive affective features of photographs promoted the success of those requests. We then established that neural activity (i.e., in the nucleus accumbens) and self-reported positive arousal in a neuroimaging sample (N = 28) predicted the success of loan requests on the Internet, above and beyond the effects of the neuroimaging sample's own choices (i.e., to lend or not). These findings suggest that elicitation of positive arousal can promote the success of loan requests, both in the laboratory and on the Internet. They also highlight affective neuroscience's potential to probe neuropsychological mechanisms that drive microlending, enhance the effectiveness of loan requests, and forecast market-level behavior.

  View details for DOI 10.1177/0956797615588467

  View details for PubMedID 26187248

  View details for PubMedCentralID PMC4570982

• Cost Conscious? The Neural and Behavioral Impact of Price Primacy on Decision Making JOURNAL OF MARKETING RESEARCH Karmarkar, U. R., Shiv, B., Knutson, B. 2015; 52 (4): 467-481

  View details for DOI 10.1509/jmr.13.0488

  View details for Web of Science ID 000359178800005

• Decision making in the ageing brain: changes in affective and motivational circuits NATURE REVIEWS NEUROSCIENCE Samanez-Larkin, G. R., Knutson, B. 2015; 16 (5): 278-289

  Abstract

  As the global population ages, older decision makers will be required to take greater responsibility for their own physical, psychological and financial well-being. With this in mind, researchers have begun to examine the effects of ageing on decision making and associated neural circuits. A new 'affect-integration-motivation' (AIM) framework may help to clarify how affective and motivational circuits support decision making. Recent research has shed light on whether and how ageing influences these circuits, providing an interdisciplinary account of how ageing can alter decision making.

  View details for DOI 10.1038/nrn3917

  View details for Web of Science ID 000353229800007

  View details for PubMedID 25873038

• Probing psychiatric symptoms with the monetary incentive delay task. Biological psychiatry Knutson, B., Heinz, A. 2015; 77 (5): 418-420

  View details for DOI 10.1016/j.biopsych.2014.12.022

  View details for PubMedID 25645271

• Advancing consumer neuroscience MARKETING LETTERS Smidts, A., Hsu, M., Sanfey, A. G., Boksem, M. A., Ebstein, R. B., Huettel, S. A., Kable, J. W., Karmarkar, U. R., Kitayama, S., Knutson, B., Liberzon, I., Lohrenz, T., Stallen, M., Yoon, C. 2014; 25 (3): 257-267

  View details for DOI 10.1007/s11002-014-9306-1

  View details for Web of Science ID 000340452000002

• Control of nucleus accumbens activity with neurofeedback NEUROIMAGE Greer, S. M., Trujillo, A. J., Glover, G. H., Knutson, B. 2014; 96: 237-244

  Abstract

  The nucleus accumbens (NAcc) plays critical roles in healthy motivation and learning, as well as in psychiatric disorders (including schizophrenia and attention deficit hyperactivity disorder). Thus, techniques that confer control of NAcc activity might inspire new therapeutic interventions. By providing second-to-second temporal resolution of activity in small subcortical regions, functional magnetic resonance imaging (fMRI) can resolve online changes in NAcc activity, which can then be presented as "neurofeedback." In an fMRI-based neurofeedback experiment designed to elicit NAcc activity, we found that subjects could increase their own NAcc activity, and that display of neurofeedback significantly enhanced their ability to do so. Subjects were not as capable of decreasing their NAcc activity, however, and enhanced control did not persist after subsequent removal of neurofeedback. Further analyses suggested that individuals who recruited positive aroused affect were better able to increase NAcc activity in response to neurofeedback, and that NAcc neurofeedback also elicited functionally correlated activity in the medial prefrontal cortex. Together, these findings suggest that humans can modulate their own NAcc activity and that fMRI-based neurofeedback may augment their efforts. The observed association between positive arousal and effective NAcc control further supports an anticipatory affect account of NAcc function.

  View details for DOI 10.1016/j.neuroimage.2014.03.073

  View details for Web of Science ID 000338809200022

  View details for PubMedID 24705203

  View details for PubMedCentralID PMC4181613

• Inferring affect from fMRI data TRENDS IN COGNITIVE SCIENCES Knutson, B., Katovich, K., Suri, G. 2014; 18 (8): 422-428

  Abstract

  Neuroimaging findings are often interpreted in terms of affective experience, but researchers disagree about the advisability or even possibility of such inferences, and few frameworks explicitly link these levels of analysis. Here, we suggest that the spatial and temporal resolution of functional magnetic resonance imaging (fMRI) data could support inferences about affective states. Specifically, we propose that fMRI nucleus accumbens (NAcc) activity is associated with positive arousal, whereas a combination of anterior insula activity and NAcc activity is associated with negative arousal. This framework implies quantifiable and testable inferences about affect from fMRI data, which may ultimately inform predictions about approach and avoidance behavior. We consider potential limits on neurally inferred affect before highlighting theoretical and practical benefits.

  View details for DOI 10.1016/j.tics.2014.04.006

  View details for Web of Science ID 000340325000009

  View details for PubMedID 24835467

• Adult age differences in frontostriatal representation of prediction error but not reward outcome COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE Samanez-Larkin, G. R., Worthy, D. A., Mata, R., McClure, S. M., Knutson, B. 2014; 14 (2): 672-682

  View details for DOI 10.3758/s13415-014-0297-4

  View details for Web of Science ID 000338516800015

• Adult age differences in frontostriatal representation of prediction error but not reward outcome. Cognitive, affective & behavioral neuroscience Samanez-Larkin, G. R., Worthy, D. A., Mata, R., McClure, S. M., Knutson, B. 2014; 14 (2): 672-682

  Abstract

  Emerging evidence from decision neuroscience suggests that although younger and older adults show similar frontostriatal representations of reward magnitude, older adults often show deficits in feedback-driven reinforcement learning. In the present study, healthy adults completed reward-based tasks that did or did not depend on probabilistic learning, while undergoing functional neuroimaging. We observed reductions in the frontostriatal representation of prediction errors during probabilistic learning in older adults. In contrast, we found evidence for stability across adulthood in the representation of reward outcome in a task that did not require learning. Together, the results identify changes across adulthood in the dynamic coding of relational representations of feedback, in spite of preserved reward sensitivity in old age. Overall, the results suggest that the neural representation of prediction error, but not reward outcome, is reduced in old age. These findings reveal a potential dissociation between cognition and motivation with age and identify a potential mechanism for explaining changes in learning-dependent decision making in old adulthood.

  View details for DOI 10.3758/s13415-014-0297-4

  View details for PubMedID 24853269

• Dissociating Motivation from Reward in Human Striatal Activity JOURNAL OF COGNITIVE NEUROSCIENCE Miller, E. M., Shankar, M. U., Knutson, B., McClure, S. M. 2014; 26 (5): 1075-1084

  Abstract

  Neural activity in the striatum has consistently been shown to scale with the value of anticipated rewards. As a result, it is common across a number of neuroscientific subdiscliplines to associate activation in the striatum with anticipation of a rewarding outcome or a positive emotional state. However, most studies have failed to dissociate expected value from the motivation associated with seeking a reward. Although motivation generally scales positively with increases in potential reward, there are circumstances in which this linkage does not apply. The current study dissociates value-related activation from that induced by motivation alone by employing a task in which motivation increased as anticipated reward decreased. This design reverses the typical relationship between motivation and reward, allowing us to differentially investigate fMRI BOLD responses that scale with each. We report that activity scaled differently with value and motivation across the striatum. Specifically, responses in the caudate and putamen increased with motivation, whereas nucleus accumbens activity increased with expected reward. Consistent with this, self-report ratings indicated a positive association between caudate and putamen activity and arousal, whereas activity in the nucleus accumbens was more associated with liking. We conclude that there exist regional limits on inferring reward expectation from striatal activation.

  View details for DOI 10.1162/jocn_a_00535

  View details for Web of Science ID 000333627800012

  View details for PubMedID 24345173

• Affective traits link to reliable neural markers of incentive anticipation. NeuroImage Wu, C. C., Samanez-Larkin, G. R., Katovich, K., Knutson, B. 2014; 84: 279-289

  Abstract

  While theorists have speculated that different affective traits are linked to reliable brain activity during anticipation of gains and losses, few have directly tested this prediction. We examined these associations in a community sample of healthy human adults (n=52) as they played a Monetary Incentive Delay task while undergoing functional magnetic resonance imaging (FMRI). Factor analysis of personality measures revealed that subjects independently varied in trait Positive Arousal and trait Negative Arousal. In a subsample (n=14) retested over 2.5years later, left nucleus accumbens (NAcc) activity during anticipation of large gains (+$5.00) and right anterior insula activity during anticipation of large losses (-$5.00) showed significant test-retest reliability (intraclass correlations>0.50, p's<0.01). In the full sample (n=52), trait Positive Arousal correlated with individual differences in left NAcc activity during anticipation of large gains, while trait Negative Arousal correlated with individual differences in right anterior insula activity during anticipation of large losses. Associations of affective traits with neural activity were not attributable to the influence of other potential confounds (including sex, age, wealth, and motion). Together, these results demonstrate selective links between distinct affective traits and reliably-elicited activity in neural circuits associated with anticipation of gain versus loss. The findings thus reveal neural markers for affective dimensions of healthy personality, and potentially for related psychiatric symptoms.

  View details for DOI 10.1016/j.neuroimage.2013.08.055

  View details for PubMedID 24001457

  View details for PubMedCentralID PMC3849140

• Neural Underpinnings of the Identifiable Victim Effect: Affect Shifts Preferences for Giving JOURNAL OF NEUROSCIENCE Genevsky, A., Vastfjall, D., Slovic, P., Knutson, B. 2013; 33 (43): 17188-17196

  Abstract

  The "identifiable victim effect" refers to peoples' tendency to preferentially give to identified versus anonymous victims of misfortune, and has been proposed to partly depend on affect. By soliciting charitable donations from human subjects during behavioral and neural (i.e., functional magnetic resonance imaging) experiments, we sought to determine whether and how affect might promote the identifiable victim effect. Behaviorally, subjects gave more to orphans depicted by photographs versus silhouettes, and their shift in preferences was mediated by photograph-induced feelings of positive arousal, but not negative arousal. Neurally, while photographs versus silhouettes elicited activity in widespread circuits associated with facial and affective processing, only nucleus accumbens activity predicted and could statistically account for increased donations. Together, these findings suggest that presenting evaluable identifiable information can recruit positive arousal, which then promotes giving. We propose that affect elicited by identifiable stimuli can compel people to give more to strangers, even despite costs to the self.

  View details for DOI 10.1523/JNEUROSCI.2348-13.2013

  View details for Web of Science ID 000326088500032

  View details for PubMedID 24155323

  View details for PubMedCentralID PMC3807035

• Interpretable whole-brain prediction analysis with GraphNet NEUROIMAGE Grosenick, L., Klingenberg, B., Katovich, K., Knutson, B., Taylor, J. E. 2013; 72: 304-321

  Abstract

  Multivariate machine learning methods are increasingly used to analyze neuroimaging data, often replacing more traditional "mass univariate" techniques that fit data one voxel at a time. In the functional magnetic resonance imaging (fMRI) literature, this has led to broad application of "off-the-shelf" classification and regression methods. These generic approaches allow investigators to use ready-made algorithms to accurately decode perceptual, cognitive, or behavioral states from distributed patterns of neural activity. However, when applied to correlated whole-brain fMRI data these methods suffer from coefficient instability, are sensitive to outliers, and yield dense solutions that are hard to interpret without arbitrary thresholding. Here, we develop variants of the Graph-constrained Elastic-Net (GraphNet), a fast, whole-brain regression and classification method developed for spatially and temporally correlated data that automatically yields interpretable coefficient maps (Grosenick et al., 2009b). GraphNet methods yield sparse but structured solutions by combining structured graph constraints (based on knowledge about coefficient smoothness or connectivity) with a global sparsity-inducing prior that automatically selects important variables. Because GraphNet methods can efficiently fit regression or classification models to whole-brain, multiple time-point data sets and enhance classification accuracy relative to volume-of-interest (VOI) approaches, they eliminate the need for inherently biased VOI analyses and allow whole-brain fitting without the multiple comparison problems that plague mass univariate and roaming VOI ("searchlight") methods. As fMRI data are unlikely to be normally distributed, we (1) extend GraphNet to include robust loss functions that confer insensitivity to outliers, (2) equip them with "adaptive" penalties that asymptotically guarantee correct variable selection, and (3) develop a novel sparse structured Support Vector GraphNet classifier (SVGN). When applied to previously published data (Knutson et al., 2007), these efficient whole-brain methods significantly improved classification accuracy over previously reported VOI-based analyses on the same data (Grosenick et al., 2008; Knutson et al., 2007) while discovering task-related regions not documented in the original VOI approach. Critically, GraphNet estimates fit to the Knutson et al. (2007) data generalize well to out-of-sample data collected more than three years later on the same task but with different subjects and stimuli (Karmarkar et al., submitted for publication). By enabling robust and efficient selection of important voxels from whole-brain data taken over multiple time points (>100,000 "features"), these methods enable data-driven selection of brain areas that accurately predict single-trial behavior within and across individuals.

  View details for DOI 10.1016/j.neuroimage.2012.12.062

  View details for Web of Science ID 000317166800030

  View details for PubMedID 23298747

• Neural Sensitivity to Absolute and Relative Anticipated Reward in Adolescents PLOS ONE Vaidya, J. G., Knutson, B., O'Leary, D. S., Block, R. I., Magnotta, V. 2013; 8 (3)

  Abstract

  Adolescence is associated with a dramatic increase in risky and impulsive behaviors that have been attributed to developmental differences in neural processing of rewards. In the present study, we sought to identify age differences in anticipation of absolute and relative rewards. To do so, we modified a commonly used monetary incentive delay (MID) task in order to examine brain activity to relative anticipated reward value (neural sensitivity to the value of a reward as a function of other available rewards). This design also made it possible to examine developmental differences in brain activation to absolute anticipated reward magnitude (the degree to which neural activity increases with increasing reward magnitude). While undergoing fMRI, 18 adolescents and 18 adult participants were presented with cues associated with different reward magnitudes. After the cue, participants responded to a target to win money on that trial. Presentation of cues was blocked such that two reward cues associated with $.20, $1.00, or $5.00 were in play on a given block. Thus, the relative value of the $1.00 reward varied depending on whether it was paired with a smaller or larger reward. Reflecting age differences in neural responses to relative anticipated reward (i.e., reference dependent processing), adults, but not adolescents, demonstrated greater activity to a $1 reward when it was the larger of the two available rewards. Adults also demonstrated a more linear increase in ventral striatal activity as a function of increasing absolute reward magnitude compared to adolescents. Additionally, reduced ventral striatal sensitivity to absolute anticipated reward (i.e., the difference in activity to medium versus small rewards) correlated with higher levels of trait Impulsivity. Thus, ventral striatal activity in anticipation of absolute and relative rewards develops with age. Absolute reward processing is also linked to individual differences in Impulsivity.

  View details for DOI 10.1371/journal.pone.0058708

  View details for Web of Science ID 000317480700009

  View details for PubMedID 23544046

  View details for PubMedCentralID PMC3609767

• Spatial smoothing systematically biases the localization of reward-related brain activity NEUROIMAGE Sacchet, M. D., Knutson, B. 2013; 66: 270-277

  View details for DOI 10.1016/j.neuroimage.2012.10.056

  View details for Web of Science ID 000322355800029

• Serotonergic Genotypes, Neuroticism, and Financial Choices PLOS ONE Kuhnen, C. M., Samanez-Larkin, G. R., Knutson, B. 2013; 8 (1)

  Abstract

  Life financial outcomes carry a significant heritable component, but the mechanisms by which genes influence financial choices remain unclear. Focusing on a polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR), we found that individuals possessing the short allele of this gene invested less in equities, were less engaged in actively making investment decisions, and had fewer credit lines. Short allele carriers also showed higher levels of the personality trait neuroticism, despite not differing from others with respect to cognitive skills, education, or wealth. Mediation analysis suggested that the presence of the 5-HTTLPR short allele decreased real life measures of financial risk taking through its influence on neuroticism. These findings show that 5-HTTLPR short allele carriers avoid risky and complex financial choices due to negative emotional reactions, and have implications for understanding and managing individual differences in financial choice.

  View details for DOI 10.1371/journal.pone.0054632

  View details for Web of Science ID 000315563800059

  View details for PubMedID 23382929

• SPATIAL SMOOTHING AND THE FUNCTIONAL LOCALIZATION OF NUCLEUS ACCUMBENS ACTIVITY 20th Annual Meeting of the Cognitive-Neuroscience-Society Sacchet, M., Knutson, B. MIT PRESS. 2013: 231–232

  View details for Web of Science ID 000317030501278

• BRAIN TO BANK: NEURAL PREDICTORS OF FINANCIAL RISK TAKING 20th Annual Meeting of the Cognitive-Neuroscience-Society Wu, C., Knutson, B. MIT PRESS. 2013: 265–265

  View details for Web of Science ID 000317030501439

• Spatial smoothing systematically biases the localization of reward-related brain activity. NeuroImage Sacchet, M. D., Knutson, B. 2012; 66C: 270-277

  Abstract

  Neuroimaging methods with enhanced spatial resolution such as functional magnetic resonance imaging (FMRI) suggest that the subcortical striatum plays a critical role in human reward processing. Analysis of FMRI data requires several preprocessing steps, some of which entail tradeoffs. For instance, while spatial smoothing can enhance statistical power, it may also bias localization towards regions that contain more gray than white matter. In a meta-analysis and reanalysis of an existing dataset, we sought to determine whether spatial smoothing could systematically bias the spatial localization of foci related to reward anticipation in the nucleus accumbens (NAcc). An activation likelihood estimate (ALE) meta-analysis revealed that peak ventral striatal ALE foci for studies that used smaller spatial smoothing kernels (i.e. <6mm FWHM) were more anterior than those identified for studies that used larger kernels (i.e. >7mm FWHM). Additionally, subtraction analysis of findings for studies that used smaller versus larger smoothing kernels revealed a significant cluster of differential activity in the left relatively anterior NAcc (Talairach coordinates: -10, 9, -1). A second meta-analysis revealed that larger smoothing kernels were correlated with more posterior localizations of NAcc activation foci (p<0.015), but revealed no significant associations with other potentially relevant parameters (including voxel volume, magnet strength, and publication date). Finally, repeated analysis of a representative dataset processed at different smoothing kernels (i.e., 0-12mm) also indicated that smoothing systematically yielded more posterior activation foci in the NAcc (p<0.005). Taken together, these findings indicate that spatial smoothing can systematically bias the spatial localization of striatal activity. These findings have implications both for historical interpretation of past findings related to reward processing and for the analysis of future studies.

  View details for DOI 10.1016/j.neuroimage.2012.10.056

  View details for PubMedID 23110886

  View details for PubMedCentralID PMC3618861

• Hyporeactivity of ventral striatum towards incentive stimuli in unmedicated depressed patients normalizes after treatment with escitalopram JOURNAL OF PSYCHOPHARMACOLOGY Stoy, M., Schlagenhauf, F., Sterzer, P., Bermpohl, F., Haegele, C., Suchotzki, K., Schmack, K., Wrase, J., Ricken, R., Knutson, B., Adli, M., Bauer, M., Heinz, A., Stroehle, A. 2012; 26 (5): 677-688

  Abstract

  Major Depressive Disorder (MDD) involves deficits in the reward system. While neuroimaging studies have focused on affective stimulus processing, few investigations have directly addressed deficits in the anticipation of incentives. We examined neural responses during gain and loss anticipation in patients with MDD before and after treatment with a selective serotonin reuptake inhibitor (SSRI). Fifteen adults with MDD and 15 healthy participants, matched for age, verbal IQ and smoking habits, were investigated in a functional magnetic resonance imaging (fMRI) study using a monetary incentive delay task. Patients were scanned drug-free and after 6 weeks of open-label treatment with escitalopram; controls were scanned twice at corresponding time points. We compared the blood oxygenation level dependent (BOLD) response during the anticipation of gain and loss with a neutral condition. A repeated measures ANOVA was calculated to identify effects of group (MDD vs. controls), time (first vs. second scan) and group-by-time interaction. Severity of depression was measured with the Hamilton Rating Scale of Depression and the Beck Depression Inventory. MDD patients showed significantly less ventral striatal activation during anticipation of gain and loss compared with controls before, but not after, treatment. There was a significant group-by-time interaction during anticipation of loss in the left ventral striatum due to a signal increase in patients after treatment. Ventral striatal hyporesponsiveness was associated with the severity of depression and in particular anhedonic symptoms. These findings suggest that MDD patients show ventral striatal hyporesponsiveness during incentive cue processing, which normalizes after successful treatment.

  View details for DOI 10.1177/0269881111416686

  View details for Web of Science ID 000304662500010

  View details for PubMedID 21926423

• Frontostriatal White Matter Integrity Mediates Adult Age Differences in Probabilistic Reward Learning JOURNAL OF NEUROSCIENCE Samanez-Larkin, G. R., Levens, S. M., Perry, L. M., Dougherty, R. F., Knutson, B. 2012; 32 (15): 5333-5337

  Abstract

  Frontostriatal circuits have been implicated in reward learning, and emerging findings suggest that frontal white matter structural integrity and probabilistic reward learning are reduced in older age. This cross-sectional study examined whether age differences in frontostriatal white matter integrity could account for age differences in reward learning in a community life span sample of human adults. By combining diffusion tensor imaging with a probabilistic reward learning task, we found that older age was associated with decreased reward learning and decreased white matter integrity in specific pathways running from the thalamus to the medial prefrontal cortex and from the medial prefrontal cortex to the ventral striatum. Further, white matter integrity in these thalamocorticostriatal paths could statistically account for age differences in learning. These findings suggest that the integrity of frontostriatal white matter pathways critically supports reward learning. The findings also raise the possibility that interventions that bolster frontostriatal integrity might improve reward learning and decision making.

  View details for DOI 10.1523/JNEUROSCI.5756-11.2012

  View details for Web of Science ID 000302793500031

  View details for PubMedID 22496578

  View details for PubMedCentralID PMC3744863

• Interactivity and Reward-Related Neural Activation during a Serious Videogame PLOS ONE Cole, S. W., Yoo, D. J., Knutson, B. 2012; 7 (3)

  Abstract

  This study sought to determine whether playing a "serious" interactive digital game (IDG)--the Re-Mission videogame for cancer patients--activates mesolimbic neural circuits associated with incentive motivation, and if so, whether such effects stem from the participatory aspects of interactive gameplay, or from the complex sensory/perceptual engagement generated by its dynamic event-stream. Healthy undergraduates were randomized to groups in which they were scanned with functional magnetic resonance imaging (FMRI) as they either actively played Re-Mission or as they passively observed a gameplay audio-visual stream generated by a yoked active group subject. Onset of interactive game play robustly activated mesolimbic projection regions including the caudate nucleus and nucleus accumbens, as well as a subregion of the parahippocampal gyrus. During interactive gameplay, subjects showed extended activation of the thalamus, anterior insula, putamen, and motor-related regions, accompanied by decreased activation in parietal and medial prefrontal cortex. Offset of interactive gameplay activated the anterior insula and anterior cingulate. Between-group comparisons of within-subject contrasts confirmed that mesolimbic activation was significantly more pronounced in the active playgroup than in the passive exposure control group. Individual difference analyses also found the magnitude of parahippocampal activation following gameplay onset to correlate with positive attitudes toward chemotherapy assessed both at the end of the scanning session and at an unannounced one-month follow-up. These findings suggest that IDG-induced activation of reward-related mesolimbic neural circuits stems primarily from participatory engagement in gameplay (interactivity), rather than from the effects of vivid and dynamic sensory stimulation.

  View details for DOI 10.1371/journal.pone.0033909

  View details for Web of Science ID 000303836500074

  View details for PubMedID 22442733

• Toward an affective neuroscience account of financial risk taking. Frontiers in neuroscience Wu, C. C., Sacchet, M. D., Knutson, B. 2012; 6: 159-?

  Abstract

  To explain human financial risk taking, economic, and finance theories typically refer to the mathematical properties of financial options, whereas psychological theories have emphasized the influence of emotion and cognition on choice. From a neuroscience perspective, choice emanates from a dynamic multicomponential process. Recent technological advances in neuroimaging have made it possible for researchers to separately visualize perceptual input, intermediate processing, and motor output. An affective neuroscience account of financial risk taking thus might illuminate affective mediators that bridge the gap between statistical input and choice output. To test this hypothesis, we conducted a quantitative meta-analysis (via activation likelihood estimate or ALE) of functional magnetic resonance imaging experiments that focused on neural responses to financial options with varying statistical moments (i.e., mean, variance, skewness). Results suggested that different statistical moments elicit both common and distinct patterns of neural activity. Across studies, high versus low mean had the highest probability of increasing ventral striatal activity, but high versus low variance had the highest probability of increasing anterior insula activity. Further, high versus low skewness had the highest probability of increasing ventral striatal activity. Since ventral striatal activity has been associated with positive aroused affect (e.g., excitement), whereas anterior insular activity has been associated with negative aroused affect (e.g., anxiety) or general arousal, these findings are consistent with the notion that statistical input influences choice output by eliciting anticipatory affect. The findings also imply that neural activity can be used to predict financial risk taking - both when it conforms to and violates traditional models of choice.

  View details for DOI 10.3389/fnins.2012.00159

  View details for PubMedID 23129993

  View details for PubMedCentralID PMC3487049

• Ventral striatal activation during reward processing in subjects with ultra-high risk for schizophrenia. Neuropsychobiology Juckel, G., Friedel, E., Koslowski, M., Witthaus, H., Ozgürdal, S., Gudlowski, Y., Knutson, B., Wrase, J., Brüne, M., Heinz, A., Schlagenhauf, F. 2012; 66 (1): 50-56

  Abstract

  Early dysfunction of the brain reward system in schizophrenia might be already recognized in the prodromal phase of this illness. We used functional magnetic resonance imaging to assess the blood oxygen level-dependent response in the ventral striatum (VS) of subjects with ultra-high risk for psychosis during the presentation of reward-indicating and loss-indicating stimuli.Thirteen prodromal patients (mean age: 25.5 ± 4.6 years) and 13 age-matched healthy volunteers participated in an incentive monetary delay task, in which visual cues predicted that a rapid response to a subsequent target stimulus will gain money, avoid losing money or have no consequence.Compared with the neutral condition, anticipation of reward loss-avoidance elicited significant activation of the VS in both healthy subjects and subjects with ultra-high risk for psychosis, but there was only a statistical tendency for less activation during loss-avoidance anticipation in prodromal compared to healthy subjects.This study provides a first weak hint, as revealed by functional magnetic resonance imaging, for impaired activation of a central area of the mesolimbic dopaminergic brain reward system, the VS, already in subjects with ultra-high risk for psychosis, which is in line with results of patients with full-blown schizophrenic psychosis. This pilot study has, however, strong limitations, and its results need to be replicated first before they can be used e.g. for early recognition of patients in the schizophrenic prodrome.

  View details for DOI 10.1159/000337130

  View details for PubMedID 22797277

• Ventral Striatal Activation during Reward Processing in Subjects with Ultra-High Risk for Schizophrenia NEUROPSYCHOBIOLOGY Juckel, G., Friedel, E., Koslowski, M., Witthaus, H., Oezguerdal, S., Gudlowski, Y., Knutson, B., Wrase, J., Bruene, M., Heinz, A., Schlagenhauf, F. 2012; 66 (1): 50-56

  View details for DOI 10.1159/000337130

  View details for Web of Science ID 000306403500007

• Toward an affective neuroscience account of financial risk taking FRONTIERS IN NEUROSCIENCE Wu, C. C., Sacchet, M. D., Knutson, B. 2012; 6

  View details for DOI 10.3389/fnins.2012.00159

  View details for Web of Science ID 000209165300165

• Gain and Loss Learning Differentially Contribute to Life Financial Outcomes PLOS ONE Knutson, B., Samanez-Larkin, G. R., Kuhnen, C. M. 2011; 6 (9)

  Abstract

  Emerging findings imply that distinct neurobehavioral systems process gains and losses. This study investigated whether individual differences in gain learning and loss learning might contribute to different life financial outcomes (i.e., assets versus debt). In a community sample of healthy adults (n = 75), rapid learners had smaller debt-to-asset ratios overall. More specific analyses, however, revealed that those who learned rapidly about gains had more assets, while those who learned rapidly about losses had less debt. These distinct associations remained strong even after controlling for potential cognitive (e.g., intelligence, memory, and risk preferences) and socioeconomic (e.g., age, sex, ethnicity, income, education) confounds. Self-reported measures of assets and debt were additionally validated with credit report data in a subset of subjects. These findings support the notion that different gain and loss learning systems may exert a cumulative influence on distinct life financial outcomes.

  View details for DOI 10.1371/journal.pone.0024390

  View details for Web of Science ID 000294689200041

  View details for PubMedID 21915320

  View details for PubMedCentralID PMC3167846

• The Influence of Affect on Beliefs, Preferences, and Financial Decisions JOURNAL OF FINANCIAL AND QUANTITATIVE ANALYSIS Kuhnen, C. M., Knutson, B. 2011; 46 (3): 605-626

  View details for DOI 10.1017/S0022109011000123

  View details for Web of Science ID 000292793200001

• Reward processing in male adults with childhood ADHD-a comparison between drug-naive and methylphenidate-treated subjects PSYCHOPHARMACOLOGY Stoy, M., Schlagenhauf, F., Schlochtermeier, L., Wrase, J., Knutson, B., Lehmkuhl, U., Huss, M., Heinz, A., Stroehle, A. 2011; 215 (3): 467-481

  Abstract

  Dysfunctional reward processing has been proposed as a main deficit in attention-deficit/hyperactivity disorder (ADHD), which could be modulated by treatment with methylphenidate (MPH).We examined differences in reward processing in adulthood (independent of actual ADHD) depending on MPH treatment during childhood.Eleven males with childhood ADHD treated with MPH, 12 drug-naïve males with childhood ADHD, and 12 controls matched by age, handedness, and smoking behavior were studied drug-free using functional magnetic resonance imaging. BOLD-responses were compared during a monetary incentive delay task using an ANOVA design focusing on the ventral striatum during anticipation and the orbitofrontal cortex during outcome.Controls, drug-naïve, and treated subjects did not differ significantly in their activations in the ventral striatum and orbitofrontal cortex. Explorative analyses revealed decreased insula activation during outcome of loss avoidance in drug-naïve subjects in comparison to both groups, while treated subjects did not differ from controls. Insula activation correlated significantly positive with harm avoidance in the treated group. Furthermore, comparing subjects with actual ADHD symptoms, remitters and controls we observed decreased putamen activition in ADHD persisters.Basal ganglia reward processing seemed to be unrelated to MPH pretreatment, but was related to remission. On the other hand, the revealed differences between treated and drug-naïve subjects with childhood ADHD, i.e., in the insula, give evidence for more pronounced abnormal activation in reward-associated brain regions in untreated subjects with childhood ADHD and underpin the need of prospective studies on long-term effects of psychostimulant treatment.

  View details for DOI 10.1007/s00213-011-2166-y

  View details for Web of Science ID 000290448300006

  View details for PubMedID 21298512

• Expected value information improves financial risk taking across the adult life span SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE Samanez-Larkin, G. R., Wagner, A. D., Knutson, B. 2011; 6 (2): 207-217

  Abstract

  When making decisions, individuals must often compensate for cognitive limitations, particularly in the face of advanced age. Recent findings suggest that age-related variability in striatal activity may increase financial risk-taking mistakes in older adults. In two studies, we sought to further characterize neural contributions to optimal financial risk taking and to determine whether decision aids could improve financial risk taking. In Study 1, neuroimaging analyses revealed that individuals whose mesolimbic activation correlated with the expected value estimates of a rational actor made more optimal financial decisions. In Study 2, presentation of expected value information improved decision making in both younger and older adults, but the addition of a distracting secondary task had little impact on decision quality. Remarkably, provision of expected value information improved the performance of older adults to match that of younger adults at baseline. These findings are consistent with the notion that mesolimbic circuits play a critical role in optimal choice, and imply that providing simplified information about expected value may improve financial risk taking across the adult life span.

  View details for DOI 10.1093/scan/nsq043

  View details for Web of Science ID 000291543100006

  View details for PubMedID 20501485

  View details for PubMedCentralID PMC3073388

• The Affective Impact of Financial Skewness on Neural Activity and Choice PLOS ONE Wu, C. C., Bossaerts, P., Knutson, B. 2011; 6 (2)

  Abstract

  Few finance theories consider the influence of "skewness" (or large and asymmetric but unlikely outcomes) on financial choice. We investigated the impact of skewed gambles on subjects' neural activity, self-reported affective responses, and subsequent preferences using functional magnetic resonance imaging (FMRI). Neurally, skewed gambles elicited more anterior insula activation than symmetric gambles equated for expected value and variance, and positively skewed gambles also specifically elicited more nucleus accumbens (NAcc) activation than negatively skewed gambles. Affectively, positively skewed gambles elicited more positive arousal and negatively skewed gambles elicited more negative arousal than symmetric gambles equated for expected value and variance. Subjects also preferred positively skewed gambles more, but negatively skewed gambles less than symmetric gambles of equal expected value. Individual differences in both NAcc activity and positive arousal predicted preferences for positively skewed gambles. These findings support an anticipatory affect account in which statistical properties of gambles--including skewness--can influence neural activity, affective responses, and ultimately, choice.

  View details for DOI 10.1371/journal.pone.0016838

  View details for Web of Science ID 000287369200010

  View details for PubMedID 21347239

  View details for PubMedCentralID PMC3039661

• REINFORCEMENT LEARNING AND AGE-RELATED CHANGES IN RELATIVE CODING IN MESOLIMBIC BRAIN REGIONS Samanez-Larkin, G. R., Worthy, D. A., McClure, S. M., Knutson, B. OXFORD UNIV PRESS INC. 2010: 10–10

  View details for Web of Science ID 000286006701049

• When Giving Is Good: Ventromedial Prefrontal Cortex Activation for Others' Intentions NEURON Cooper, J. C., Kreps, T. A., Wiebe, T., Pirkl, T., Knutson, B. 2010; 67 (3): 511-521

  Abstract

  In social decision-making, people care both about others' outcomes and their intentions to help or harm. How the brain integrates representations of others' intentions with their outcomes, however, is unknown. In this study, participants inferred others' decisions in an economic game during functional magnetic resonance imaging. When the game was described in terms of donations, ventromedial prefrontal cortex (VMPFC) activation increased for inferring generous play and decreased for inferring selfish play. When the game was described in terms of individual savings, however, VMPFC activation did not distinguish between strategies. Distinct medial prefrontal regions also encoded consistency with situational norms. A separate network, including right temporoparietal junction and parahippocampal gyrus, was more activated for inferential errors in the donation than in the savings condition. These results demonstrate that neural responses to others' generosity or selfishness depend not only on their actions but also on their perceived intentions.

  View details for DOI 10.1016/j.neuron.2010.06.030

  View details for Web of Science ID 000280942900017

  View details for PubMedID 20696386

  View details for PubMedCentralID PMC2919841

• Variability in Nucleus Accumbens Activity Mediates Age-Related Suboptimal Financial Risk Taking JOURNAL OF NEUROSCIENCE Samanez-Larkin, G. R., Kuhnen, C. M., Yoo, D. J., Knutson, B. 2010; 30 (4): 1426-1434

  Abstract

  As human life expectancy continues to rise, financial decisions of aging investors may have an increasing impact on the global economy. In this study, we examined age differences in financial decisions across the adult life span by combining functional neuroimaging with a dynamic financial investment task. During the task, older adults made more suboptimal choices than younger adults when choosing risky assets. This age-related effect was mediated by a neural measure of temporal variability in nucleus accumbens activity. These findings reveal a novel neural mechanism by which aging may disrupt rational financial choice.

  View details for DOI 10.1523/JNEUROSCI.4902-09.2010

  View details for Web of Science ID 000274050000024

  View details for PubMedID 20107069

  View details for PubMedCentralID PMC2821055

• The Reward Circuit: Linking Primate Anatomy and Human Imaging NEUROPSYCHOPHARMACOLOGY Haber, S. N., Knutson, B. 2010; 35 (1): 4-26

  Abstract

  Although cells in many brain regions respond to reward, the cortical-basal ganglia circuit is at the heart of the reward system. The key structures in this network are the anterior cingulate cortex, the orbital prefrontal cortex, the ventral striatum, the ventral pallidum, and the midbrain dopamine neurons. In addition, other structures, including the dorsal prefrontal cortex, amygdala, hippocampus, thalamus, and lateral habenular nucleus, and specific brainstem structures such as the pedunculopontine nucleus, and the raphe nucleus, are key components in regulating the reward circuit. Connectivity between these areas forms a complex neural network that mediates different aspects of reward processing. Advances in neuroimaging techniques allow better spatial and temporal resolution. These studies now demonstrate that human functional and structural imaging results map increasingly close to primate anatomy.

  View details for DOI 10.1038/npp.2009.129

  View details for Web of Science ID 000272784600002

  View details for PubMedID 19812543

• Available alternative incentives modulate anticipatory nucleus accumbens activation SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE Cooper, J. C., Hollon, N. G., Wimmer, G. E., Knutson, B. 2009; 4 (4): 409-416

  Abstract

  A reward or punishment can seem better or worse depending on what else might have happened. Little is known, however, about how neural representations of an anticipated incentive might be influenced by the available alternatives. We used event-related FMRI to investigate the activation in the nucleus accumbens (NAcc), while we varied the available alternative incentives in a monetary incentive delay task. Some task blocks included only uncertain gains and losses; others included the same uncertain gains and losses intermixed with certain gains and losses. The availability of certain gains and losses increased NAcc activation for uncertain losses and decreased the difference between uncertain gains and losses. We suggest that this pattern of activation can result from reference point changes across blocks, and that the worst available loss may serve as an important anchor for NAcc activation. These findings imply that NAcc activation represents anticipated incentive value relative to the current context of available alternative gains and losses.

  View details for DOI 10.1093/scan/nsp031

  View details for Web of Science ID 000273231000010

  View details for PubMedID 19843618

  View details for PubMedCentralID PMC2799954

• Ventral Striatal Activation During Reward Anticipation Correlates with Impulsivity in Alcoholics BIOLOGICAL PSYCHIATRY Beck, A., Schlagenhauf, F., Wuestenberg, T., Hein, J., Kienast, T., Kahnt, T., Schmack, K., Haegele, C., Knutson, B., Heinz, A., Wrase, J. 2009; 66 (8): 734-742

  Abstract

  Alcohol dependence is often associated with impulsivity, which may be correlated with dysfunction of the brain reward system. We explored whether functional brain activation during anticipation of incentive stimuli is associated with impulsiveness in detoxified alcoholics and healthy control subjects.Nineteen detoxified male alcoholics and 19 age-matched healthy men participated in a functional magnetic resonance imaging (fMRI) study using a monetary incentive delay (MID) task, in which visual cues predicted that a rapid response to a subsequent target stimulus would either result in monetary gain, avoidance of monetary loss, or no consequence. Impulsivity was assessed with the Barratt Impulsiveness Scale-Version 10 (BIS-10).Detoxified alcoholics showed reduced activation of the ventral striatum during anticipation of monetary gain relative to healthy control subjects. Low activation of the ventral striatum and anterior cingulate during gain anticipation was correlated with high impulsivity only in alcoholics, not in control subjects.This study suggests that reduced ventral striatal recruitment during anticipation of conventional rewards in alcoholics may be related to their increased impulsivity and indicate possibilities for enhanced treatment approaches in alcohol dependence.

  View details for DOI 10.1016/j.biopsych.2009.04.035

  View details for Web of Science ID 000270498500005

  View details for PubMedID 19560123

• Correction. "Affect dynamics, affective forecasting, and aging". Emotion Nielsen, L., Knutson, B., Carstensen, L. L. 2009; 9 (5): ii-?

  Abstract

  Reports an error in "Affect dynamics, affective forecasting, and aging" by Lisbeth Nielsen, Brian Knutson and Laura L. Carstensen (Emotion, 2008[Jun], Vol 8[3], 318-330). The first author of the article was listed as being affiliated with both the National Institute on Aging and the Department of Psychology, Stanford University. Dr. Nielsen would like to clarify that the research for this article was conducted while she was a postdoctoral fellow at Stanford University; her current affiliation is only with the National Institute on Aging. The copyright notice should also have been listed as "In the Public Domain." (The following abstract of the original article appeared in record 2008-06717-002.) [Correction Notice: The same erratum for this article was reported in Vol 8(5) of Emotion (see record 2008-13989-013).] Affective forecasting, experienced affect, and recalled affect were compared in younger and older adults during a task in which participants worked to win and avoid losing small monetary sums. Dynamic changes in affect were measured along valence and arousal dimensions, with probes during both anticipatory and consummatory task phases. Older and younger adults displayed distinct patterns of affect dynamics. Younger adults reported increased negative arousal during loss anticipation and positive arousal during gain anticipation. In contrast, older adults reported increased positive arousal during gain anticipation but showed no increase in negative arousal on trials involving loss anticipation. Additionally, younger adults reported large increases in valence after avoiding an anticipated loss, but older adults did not. Younger, but not older, adults exhibited forecasting errors on the arousal dimension, underestimating increases in arousal during anticipation of gains and losses and overestimating increases in arousal in response to gain outcomes. Overall, the findings are consistent with a growing literature suggesting that older people experience less negative emotion than their younger counterparts and further suggest that they may better predict dynamic changes in affect.

  View details for DOI 10.1037/a0015739

  View details for PubMedID 19803581

• Reward Processing After Catecholamine Depletion in Unmedicated, Remitted Subjects with Major Depressive Disorder BIOLOGICAL PSYCHIATRY Hasler, G., Luckenbaugh, D. A., Snow, J., Meyers, N., Waldeck, T., Geraci, M., Roiser, J., Knutson, B., Charney, D. S., Drevets, W. C. 2009; 66 (3): 201-205

  Abstract

  We investigated whether performance on a reward processing task differs between fully remitted patients with major depressive disorder (MDD) and healthy control subjects after catecholamine depletion.Seventeen unmedicated subjects with remitted MDD (RMDD) and 13 healthy control subjects underwent catecholamine depletion with oral alpha-methyl-para-tyrosine (AMPT) in a randomized, placebo-controlled, double-blind crossover study. The main outcome measure was the reaction time on the monetary incentive delay (MID) task.A diagnosis x drug interaction was evident (p = .001), which was attributable to an increase in reaction time across all incentive levels after AMPT in RMDD subjects (p = .001) but no significant AMPT effect on reaction time in control subjects (p = .17). There was no drug x diagnosis interaction on control tasks involving working memory or attention. In the RMDD sample the AMPT-induced depressive symptoms correlated with AMPT-induced changes in reaction time at all incentive levels of the MID task (r values = .58-.82, p < .002).Under catecholamine depletion the RMDD subjects were robustly differentiated from control subjects by development of performance deficits on a reward processing task. These performance deficits correlated directly with the return of depressive symptoms after AMPT administration. The sensitivity of central reward processing systems to reductions in brain catecholamine levels thus seems to represent a trait-like marker in MDD.

  View details for DOI 10.1016/j.biopsych.2009.02.029

  View details for Web of Science ID 000267961600002

  View details for PubMedID 19393989

• Don't stop thinking about tomorrow: Individual differences in future self-continuity account for saving JUDGMENT AND DECISION MAKING Ersner-Hershfield, H., Garton, M. T., Ballard, K., Samanez-Larkin, G. R., Knutson, B. 2009; 4 (4): 280-286

  Abstract

  Some people find it more difficult to delay rewards than others. In three experiments, we tested a "future self-continuity" hypothesis that individual differences in the perception of one's present self as continuous with a future self would be associated with measures of saving in the laboratory and everyday life. Higher future self-continuity (assessed by a novel index) predicted reduced discounting of future rewards in a laboratory task, more matches in adjectival descriptions of present and future selves, and greater lifetime accumulation of financial assets (even after controlling for age and education). In addition to demonstrating the reliability and validity of the future self-continuity index, these findings are consistent with the notion that increased future self-continuity might promote saving for the future.

  View details for Web of Science ID 000267218800003

  View details for PubMedCentralID PMC2747683

• Don't stop thinking about tomorrow: Individual differences in future self-continuity account for saving. Judgment and decision making Ersner-Hershfield, H., Garton, M. T., Ballard, K., Samanez-Larkin, G. R., Knutson, B. 2009; 4 (4): 280-286

  Abstract

  Some people find it more difficult to delay rewards than others. In three experiments, we tested a "future self-continuity" hypothesis that individual differences in the perception of one's present self as continuous with a future self would be associated with measures of saving in the laboratory and everyday life. Higher future self-continuity (assessed by a novel index) predicted reduced discounting of future rewards in a laboratory task, more matches in adjectival descriptions of present and future selves, and greater lifetime accumulation of financial assets (even after controlling for age and education). In addition to demonstrating the reliability and validity of the future self-continuity index, these findings are consistent with the notion that increased future self-continuity might promote saving for the future.

  View details for PubMedID 19774230

  View details for PubMedCentralID PMC2747683

• Dissociable neural representations of future reward magnitude and delay during temporal discounting NEUROIMAGE Ballard, K., Knutson, B. 2009; 45 (1): 143-150

  Abstract

  In temporal discounting, individuals often prefer smaller immediate rewards to larger delayed rewards, implying a trade off between the magnitude and delay of future rewards. While recent functional magnetic resonance imaging (fMRI) investigations of temporal discounting have generated conflicting findings, no studies have focused on whether distinct neural substrates respond to the magnitude and delay of future rewards. Combining a novel, temporally distributed discounting task with event-related fMRI, we found that while nucleus accumbens (NAcc), mesial prefrontal cortical (MPFC), and posterior cingulate cortical (PCC) activation positively correlated with future reward magnitude, dorsolateral prefrontal cortical (DLPFC) and posterior parietal cortical (PPC) activation negatively correlated with future reward delay. Further, more impulsive individuals showed diminished NAcc activation to the magnitude of future rewards and greater deactivations to delays of future rewards in the MPFC, DLPFC, and PPC. These findings suggest that while mesolimbic dopamine projection regions show greater sensitivity to the magnitude of future rewards, lateral cortical regions show greater (negative) sensitivity to the delay of future rewards, potentially reconciling different neural accounts of temporal discounting.

  View details for DOI 10.1016/j.neuroimage.2008.11.004

  View details for Web of Science ID 000263862900017

  View details for PubMedID 19071223

  View details for PubMedCentralID PMC2685201

• Saving for the future self: Neural measures of future self-continuity predict temporal discounting SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE Ersner-Hershfield, H., Wimmer, G. E., Knutson, B. 2009; 4 (1): 85-92

  Abstract

  Despite increases in the human life span, people have not increased their rate of saving. In a phenomenon known as 'temporal discounting', people value immediate gains over future gains. According to a future self-continuity hypothesis, individuals perceive and treat the future self differently from the present self, and so might fail to save for their future. Neuroimaging offers a novel means of testing this hypothesis, since previous research indicates that self- vs other-judgments elicit activation in the rostral anterior cingulate (rACC). Using event-related functional magnetic resonance imaging, we predicted and found not only individual differences in rACC activation while rating the current vs future self, but also that individual differences in current vs future self activation predicted temporal discounting assessed behaviorally a week after scanning. In addition to supporting the future self-continuity hypothesis, these findings hold implications for significant financial decisions, such as choosing whether to save for the future or spend in the present.

  View details for DOI 10.1093/scan/nsn042

  View details for Web of Science ID 000264398000009

  View details for PubMedID 19047075

  View details for PubMedCentralID PMC2656877

• Anticipatory affect: neural correlates and consequences for choice PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES Knutson, B., Greer, S. M. 2008; 363 (1511): 3771-3786

  Abstract

  'Anticipatory affect' refers to emotional states that people experience while anticipating significant outcomes. Historically, technical limitations have made it difficult to determine whether anticipatory affect influences subsequent choice. Recent advances in the spatio-temporal resolution of functional magnetic resonance imaging, however, now allow researchers to visualize changes in neural activity seconds before choice occurs. We review evidence that activation in specific brain circuits changes during anticipation of monetary incentives, that this activation correlates with affective experience and that activity in these circuits may influence subsequent choice. Specifically, an activation likelihood estimate meta-analysis of cued response studies indicates that nucleus accumbens (NAcc) activation increases during gain anticipation relative to loss anticipation, while anterior insula activation increases during both loss and gain anticipation. Additionally, anticipatory NAcc activation correlates with self-reported positive arousal, whereas anterior insula activation correlates with both self-reported negative and positive arousal. Finally, NAcc activation precedes the purchase of desirable products and choice of high-risk gambles, whereas anterior insula activation precedes the rejection of overpriced products and choice of low-risk gambles. Together, these findings support a neurally plausible framework for understanding how anticipatory affect can influence choice.

  View details for DOI 10.1098/rstb.2008.0155

  View details for Web of Science ID 000260864600002

  View details for PubMedID 18829428

  View details for PubMedCentralID PMC2607363

• Interpretable Classifiers for fMRI Improve Prediction of Purchases IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING Grosenick, L., Greer, S., Knutson, B. 2008; 16 (6): 539-548

  Abstract

  Despite growing interest in applying machine learning to neuroimaging analyses, few studies have gone beyond classifying sensory input to directly predicting behavioral output. With spatial resolution on the order of millimeters and temporal resolution on the order of seconds, functional magnetic resonance imaging (fMRI) is a promising technology for such applications. However, fMRI data's low signal-to-noise ratio, high dimensionality, and extensive spatiotemporal correlations present formidable analytic challenges. Here, we apply different machine-learning algorithms to previously acquired data to examine the ability of fMRI activation in three regions-the nucleus accumbens (NAcc), medial prefrontal cortex (MPFC), and insula-to predict purchasing. Our goal was to improve spatiotemporal interpretability as well as classification accuracy. To this end, sparse penalized discriminant analysis (SPDA) enabled automatic selection of correlated variables, yielding interpretable models that generalized well to new data. Relative to logistic regression, linear discriminant analysis, and linear support vector machines, SPDA not only increased interpretability but also improved classification accuracy. SPDA promises to allow more precise inferences about when specific brain regions contribute to purchasing decisions. More broadly, this approach provides a general framework for using neuroimaging data to build interpretable models, including those that predict choice.

  View details for DOI 10.1109/TNSRE.2008.926701

  View details for Web of Science ID 000262557000004

  View details for PubMedID 19144586

• Incentive-elicited striatal activation in adolescent children of alcoholics ADDICTION Bjork, J. M., Knutson, B., Hommer, D. W. 2008; 103 (8): 1308-1319

  Abstract

  Deficient recruitment of motivational circuitry by non-drug rewards has been postulated as a pre-morbid risk factor for substance dependence (SD). We tested whether parental alcoholism, which confers risk of SD, is correlated with altered recruitment of ventral striatum (VS) by non-drug rewards in adolescence.During functional magnetic resonance imaging, adolescent children of alcoholics (COA; age 12-16 years) with no psychiatric disorders (including substance abuse) and similarly aged children with no risk factors responded to targets to win or avoid losing $0, $0.20, $1, $5 or a variable amount (ranging from $0.20 to $5).In general, brain activation by either reward anticipation or outcome notification did not differ between COA and age/gender-matched controls. Cue-elicited reward anticipation activated portions of VS in both COA and controls. In nucleus accumbens (NAcc), signal change increased with anticipated reward magnitude (with intermediate recruitment by variable incentives) but not with loss magnitudes. Reward deliveries activated the NAcc and mesofrontal cortex in both COA and controls. Losses activated anterior insula bilaterally in both groups, with more extensive right anterior insula activation by losses in controls. NAcc signal change during anticipation of maximum rewards (relative to non-reward) correlated positively with both Brief Sensation-Seeking Scale scores and with self-reported excitement in response to maximum reward cues (relative to cues for non-reward).Among adolescents with no psychiatric disorders, incentive-elicited VS activation may relate more to individual differences in sensation-seeking personality than to presence of parental alcoholism alone. Future research could focus on adolescents with behavior disorders or additional risk factors.

  View details for DOI 10.1111/j.1360-0443.2008.02250.x

  View details for Web of Science ID 000257692800010

  View details for PubMedID 18851716

• Neural antecedents of the endowment effect NEURON Knutson, B., Wimmer, G. E., Rick, S., Hollon, N. G., Prelec, D., Loewenstein, G. 2008; 58 (5): 814-822

  Abstract

  The "endowment effect" refers to the tendency to place greater value on items that one owns-an anomaly that violates the reference-independence assumption of rational choice theories. We investigated neural antecedents of the endowment effect in an event-related functional magnetic resonance imaging (fMRI) study. During scanning, 24 subjects considered six products paired with 18 different prices under buying, choosing, or selling conditions. Subjects showed greater nucleus accumbens (NAcc) activation for preferred products across buy and sell conditions combined, but greater mesial prefrontal cortex (MPFC) activation in response to low prices when buying versus selling. During selling, right insular activation for preferred products predicted individual differences in susceptibility to the endowment effect. These findings are consistent with a reference-dependent account in which ownership increases value by enhancing the salience of the possible loss of preferred products.

  View details for DOI 10.1016/j.neuron.2008.05.018

  View details for Web of Science ID 000256870800017

  View details for PubMedID 18549791

• Affect dynamics, affective forecasting, and aging EMOTION Nielsen, L., Knutson, B., Carstensen, L. L. 2008; 8 (3): 318-330

  Abstract

  Affective forecasting, experienced affect, and recalled affect were compared in younger and older adults during a task in which participants worked to win and avoid losing small monetary sums. Dynamic changes in affect were measured along valence and arousal dimensions, with probes during both anticipatory and consummatory task phases. Older and younger adults displayed distinct patterns of affect dynamics. Younger adults reported increased negative arousal during loss anticipation and positive arousal during gain anticipation. In contrast, older adults reported increased positive arousal during gain anticipation but showed no increase in negative arousal on trials involving loss anticipation. Additionally, younger adults reported large increases in valence after avoiding an anticipated loss, but older adults did not. Younger, but not older, adults exhibited forecasting errors on the arousal dimension, underestimating increases in arousal during anticipation of gains and losses and overestimating increases in arousal in response to gain outcomes. Overall, the findings are consistent with a growing literature suggesting that older people experience less negative emotion than their younger counterparts and further suggest that they may better predict dynamic changes in affect.

  View details for DOI 10.1037/1528-3542.8.3.318

  View details for Web of Science ID 000256512900002

  View details for PubMedID 18540748

  View details for PubMedCentralID PMC2652507

• Individual differences in insular sensitivity during loss anticipation predict avoidance learning PSYCHOLOGICAL SCIENCE Samanez-Larkin, G. R., Hollon, N. G., Carstensen, L. L., Knutson, B. 2008; 19 (4): 320-323

  Abstract

  The anterior insula has been implicated in both the experience and the anticipation of negative outcomes. Although individual differences in insular sensitivity have been associated with self-report measures of chronic anxiety, previous research has not examined whether individual differences in insular sensitivity predict learning to avoid aversive stimuli. In the present study, insular sensitivity was assessed as participants anticipated monetary losses while undergoing functional magnetic resonance imaging. We found that insular responsiveness to anticipated losses predicted participants' ability to learn to avoid losses (but not to approach gains) in a behavioral test several months later. These findings suggest that in addition to correlating with self-reported anxiety, heightened insular sensitivity may promote learning to avoid loss.

  View details for Web of Science ID 000254792000003

  View details for PubMedID 18399882

• Neural responses to monetary incentives in major depression BIOLOGICAL PSYCHIATRY Knutson, B., Bhanji, J. P., Cooney, R. E., Atlas, L. Y., Gotlib, I. H. 2008; 63 (7): 686-692

  Abstract

  Reduced responsiveness to positive incentives is a central feature of Major Depressive Disorder (MDD). In the present study, we compared neural correlates of monetary incentive processing in unmedicated depressed participants and never-depressed control subjects.Fourteen currently depressed and 12 never-depressed participants underwent functional magnetic resonance imaging while participating in a monetary incentive delay task. During the task, participants were cued to anticipate and respond to a rapidly presented target to gain or avoid losing varying amounts of money.Depressed and never-depressed participants did not differ in nucleus accumbens (NAcc) activation or in affective or behavioral responses during gain anticipation. Depressed participants did, however, exhibit increasing anterior cingulate activation during anticipation of increasing gains, whereas never-depressed participants showed increasing anterior cingulate activation during anticipation of increasing loss. Depressed participants also showed reduced discrimination of gain versus nongain outcomes.The present findings indicate that although unmedicated depressed individuals have the capacity to experience positive arousal and recruit NAcc activation during gain anticipation, they also exhibit increased anterior cingulate cortex activation, suggestive of increased conflict during anticipation of gains, in addition to showing reduced discrimination of gain versus nongain outcomes.

  View details for DOI 10.1016/j.biopsych.2007.07.023

  View details for Web of Science ID 000254107100008

  View details for PubMedID 17916330

  View details for PubMedCentralID PMC2290738

• Nucleus accumbens activation mediates the influence of reward cues on financial risk taking NEUROREPORT Knutson, B., Wimmer, G. E., Kuhnen, C. M., Winkielman, P. 2008; 19 (5): 509-513

  Abstract

  In functional magnetic resonance imaging research, nucleus accumbens (NAcc) activation spontaneously increases before financial risk taking. As anticipation of diverse rewards can increase NAcc activation, even incidental reward cues may influence financial risk taking. Using event-related functional magnetic resonance imaging, we predicted and found that anticipation of viewing rewarding stimuli (erotic pictures for 15 heterosexual men) increased financial risk taking, and that this effect was partially mediated by increases in NAcc activation. These results are consistent with the notion that incidental reward cues influence financial risk taking by altering anticipatory affect, and so identify a neuropsychological mechanism that may underlie effective emotional appeals in financial, marketing, and political domains.

  View details for Web of Science ID 000254372100001

  View details for PubMedID 18388729

• Reward system activation in schizophrenic patients switched from typical neuroleptics to olanzapine PSYCHOPHARMACOLOGY Schlagenhauf, F., Juckel, G., Koslowski, M., Kahnt, T., Knutson, B., Dembler, T., Kienast, T., Gallinat, J., Wrase, J., Heinz, A. 2008; 196 (4): 673-684

  Abstract

  High blockade of dopamine D2 receptors in the ventral striatum including the nucleus accumbens may interfere with reward anticipation and cause secondary negative symptoms such as apathy or anhedonia. This may not be the case with newer neuroleptics such as olanzapine, which show less dopamine D2 receptor blockade and a faster off-rate from the receptor.We used functional magnetic resonance imaging to assess the blood oxygenation level dependent response in the ventral striatum of schizophrenics medicated with typical neuroleptics (T1) and after switching them to olanzapine (T2) and of healthy control subjects at corresponding time points during reward anticipation.Ten schizophrenics, while medicated with typical neuroleptics (T1) and after having been switched to olanzapine (T2), and ten matched healthy volunteers participated in a monetary incentive delay task, in which visual cues predicted that a rapid response to a subsequent target stimulus would either result in monetary gain or have no consequence.During reward anticipation, healthy volunteers showed significantly higher ventral striatal activation compared to schizophrenic patients treated with typical neuroleptics but not olanzapine, which was reflected in a significant interaction between group and session. In patients treated with typical neuroleptics, but not with olanzapine, decreased left ventral striatal activation was correlated with negative symptoms.Failure to activate the ventral striatum during reward anticipation was pharmacologically state-dependent and observed only in patients treated with typical neuroleptics but not with olanzapine, which may indicate that this drug did not induce secondary negative symptoms via interference with reward anticipation.

  View details for DOI 10.1007/s00213-007-1016-4

  View details for Web of Science ID 000253202300018

  View details for PubMedID 18097655

• Reward anticipation and outcomes in adult males with attention-deficit/hyperactivity disorder NEUROIMAGE Stroehle, A., Stoy, M., Wrase, J., Schwarzer, S., Schlagenhauf, F., Huss, M., Hein, J., Nedderhut, A., Neumann, B., Gregor, A., Juckel, G., Knutson, B., Lehmkuhl, U., Bauer, M., Heinz, A. 2008; 39 (3): 966-972

  Abstract

  Attention-deficit/hyperactivity disorder (ADHD) has been suggested to involve deficits in reward processing. We used functional magnetic resonance imaging (fMRI) to compare the neural responses to reward anticipation and outcomes in 10 adults with ADHD and 10 controls as they played a monetary incentive delay task. Adults with ADHD were unmedicated, and groups were matched for age, verbal IQ and smoking habits. Adults with ADHD showed decreased activation in the ventral striatum during the anticipation of gain, but increased activation of the orbitofrontal cortex in response to gain outcomes. Ventral striatal activation in adults with ADHD during gain anticipation was negatively correlated with self-rated symptoms of hyperactivity and impulsivity. These findings suggest that male adults with ADHD show neural signs of abnormal reward processing. Future studies will have to investigate whether these dysfunctional patterns might be normalized by treatment.

  View details for DOI 10.1016/j.neuroimage.2007.09.044

  View details for Web of Science ID 000252691800006

  View details for PubMedID 17996464

• Valence and salience contribute to nucleus accumbens activation NEUROIMAGE Cooper, J. C., Knutson, B. 2008; 39 (1): 538-547

  Abstract

  Different accounts of nucleus accumbens (NAcc) function have emphasized its role in representing either valence or salience during incentive anticipation. In an event-related FMRI experiment, we independently manipulated valence and salience by cuing participants to anticipate certain and uncertain monetary gains and losses. NAcc activation correlated with both valence and salience. On trials with certain outcomes, NAcc activation increased for anticipated gains and decreased for anticipated losses. On trials with uncertain outcomes, NAcc activation increased for both anticipated gains and losses but did not differ between them. These findings suggest that NAcc activation separately represents both valence and salience, consistent with its hypothesized role in appetitive motivation.

  View details for DOI 10.1016/j.neuroimage.2007.08.009

  View details for Web of Science ID 000251406000048

  View details for PubMedID 17904386

• Neural antecedents of financial decisions JOURNAL OF NEUROSCIENCE Knutson, B., Bossaerts, P. 2007; 27 (31): 8174-8177

  Abstract

  To explain investing decisions, financial theorists invoke two opposing metrics: expected reward and risk. Recent advances in the spatial and temporal resolution of brain imaging techniques enable investigators to visualize changes in neural activation before financial decisions. Research using these methods indicates that although the ventral striatum plays a role in representation of expected reward, the insula may play a more prominent role in the representation of expected risk. Accumulating evidence also suggests that antecedent neural activation in these regions can be used to predict upcoming financial decisions. These findings have implications for predicting choices and for building a physiologically constrained theory of decision-making.

  View details for DOI 10.1523/JNEUROSCI.1564-07.2007

  View details for Web of Science ID 000248502200006

  View details for PubMedID 17670962

• Different neural systems adjust motor behavior in response to reward and punishment NEUROIMAGE Wrase, J., Kahnt, T., Schiagenhauf, F., Beck, A., Cohen, M. X., Knutson, B., Heinz, A. 2007; 36 (4): 1253-1262

  Abstract

  Individuals use the outcomes of their actions to adjust future behavior. However, it remains unclear whether the same neural circuits are used to adjust behavior due to rewarding and punishing outcomes. Here we used functional magnetic resonance imaging (fMRI) and a reward-providing reaction time task to investigate the adaptation of a simple motor response following four different outcomes (delivery versus omission and monetary gain versus loss). We found that activation in the thalamus and insula predicted adjustments of motor responses due to outcomes that were cued and delivered, whereas activation in the ventral striatum predicted such adjustments when outcomes were cued but omitted. Further, activation of OFC predicted improvement after all punishing outcomes, independent of whether they were omitted rewards or delivered punishments. Finally, we found that activity in anterior cingulate predicted adjustment after delivered punishments and activity in dorsal striatum predicted adaptation after delivered rewards. Our results provide evidence that different but somewhat overlapping circuits mediate the same behavioral adaptation when it is driven by different incentive outcomes.

  View details for DOI 10.1016/j.neuroimage.2007.04.001

  View details for Web of Science ID 000248152400019

  View details for PubMedID 17521924

• Anticipation of monetary gain but not loss in healthy older adults NATURE NEUROSCIENCE Samanez-Larkin, G. R., Gibbs, S. E., Khanna, K., Nielsen, L., Carstensen, L. L., Knutson, B. 2007; 10 (6): 787-791

  Abstract

  Although global declines in structure have been documented in the aging human brain, little is known about the functional integrity of the striatum and prefrontal cortex in older adults during incentive processing. We used event-related functional magnetic resonance imaging to determine whether younger and older adults differed in both self-reported and neural responsiveness to anticipated monetary gains and losses. The present study provides evidence for intact striatal and insular activation during gain anticipation with age, but shows a relative reduction in activation during loss anticipation. These findings suggest that there is an asymmetry in the processing of gains and losses in older adults that may have implications for decision-making.

  View details for DOI 10.1038/nn1894

  View details for Web of Science ID 000246799800022

  View details for PubMedID 17468751

  View details for PubMedCentralID PMC2268869

• Affective influence on judgments and decisions: Moving towards core mechanisms REVIEW OF GENERAL PSYCHOLOGY Winkielman, P., Knutson, B., Paulus, M., Trujillo, J. L. 2007; 11 (2): 179-192

  View details for DOI 10.1037/1089-2680.11.2.179

  View details for Web of Science ID 000247512200008

• Linking nucleus accumbens dopamine and blood oxygenation PSYCHOPHARMACOLOGY Knutson, B., Gibbs, S. E. 2007; 191 (3): 813-822

  Abstract

  Animal research suggests that anticipation of reward can elicit dopamine release in the nucleus accumbens (NAcc). Human functional magnetic resonance imaging (FMRI) research further suggests that reward anticipation can increase local blood oxygen level dependent (BOLD) signal in the NAcc. However, the physiological relationship between dopamine release and BOLD signal increases in the NAcc has not yet been established.This review considers pharmacological MRI (phMRI) evidence for a directional relationship between NAcc dopamine release and BOLD signal, as well as implications for human psychopathological symptoms.Accumulating phMRI evidence supports a simple model in which NAcc dopamine release activates postsynaptic D1 receptors, which changes postsynaptic membrane potential, eventually increasing local BOLD signal. This continuing influence can change on a second-to-second basis.Dopamine release in the NAcc appears to increase local BOLD signal via agonism of postsynaptic D1 receptors. Such a physiological mechanism implies that FMRI may be used to track symptoms related to NAcc dopaminergic dysregulation in psychiatric disorders including schizophrenia and attention deficit/hyperactivity disorder.

  View details for DOI 10.1007/s00213-006-0686-7

  View details for Web of Science ID 000244691500032

  View details for PubMedID 17279377

• Dysfunction of reward processing correlates with alcohol craving in detoxified alcoholics NEUROIMAGE Wrase, J., Schlagenhauf, F., Kienast, T., Wuestenberg, T., Bermpohl, F., Kahnt, T., Beek, A., Stroehle, A., Juckel, G., Knutson, B., Heinz, A. 2007; 35 (2): 787-794

  Abstract

  Alcohol dependence may be associated with dysfunction of mesolimbic circuitry, such that anticipation of nonalcoholic reward fails to activate the ventral striatum, while alcohol-associated cues continue to activate this region. This may lead alcoholics to crave the pharmacological effects of alcohol to a greater extent than other conventional rewards. The present study investigated neural mechanisms underlying these phenomena.16 detoxified male alcoholics and 16 age-matched healthy volunteers participated in two fMRI paradigms. In the first paradigm, alcohol-associated and affectively neutral pictures were presented, whereas in the second paradigm, a monetary incentive delay task (MID) was performed, in which brain activation during anticipation of monetary gain and loss was examined. For both paradigms, we assessed the association of alcohol craving with neural activation to incentive cues.Detoxified alcoholics showed reduced activation of the ventral striatum during anticipation of monetary gain relative to healthy controls, despite similar performance. However, alcoholics showed increased ventral striatal activation in response to alcohol-associated cues. Reduced activation in the ventral striatum during expectation of monetary reward, and increased activation during presentation of alcohol cues were correlated with alcohol craving in alcoholics, but not healthy controls.These results suggest that mesolimbic activation in alcoholics is biased towards processing of alcohol cues. This might explain why alcoholics find it particularly difficult to focus on conventional reward cues and engage in alternative rewarding activities.

  View details for DOI 10.1016/j.neuroimage.2006.11.043

  View details for Web of Science ID 000245293100031

  View details for PubMedID 17291784

• Ventral striatal hyporesponsiveness during reward anticipation in attention-deficit/hyperactivity disorder BIOLOGICAL PSYCHIATRY Scheres, A., Milham, M. P., Knutson, B., Castellanos, F. X. 2007; 61 (5): 720-724

  Abstract

  Although abnormalities in reward processing have been proposed to underlie attention-deficit/hyperactivity disorder (ADHD), this link has not been tested explicitly with neural probes.This hypothesis was tested by using fMRI to compare neural activity within the striatum in individuals with ADHD and healthy controls during a reward-anticipation task that has been shown previously to produce reliable increases in ventral striatum activity in healthy adults and healthy adolescents. Eleven adolescents with ADHD (5 off medication and 6 medication-naïve) and 11 healthy controls (ages 12-17 y) were included. Groups were matched for age, gender, and intelligence quotient.We found reduced ventral striatal activation in adolescents with ADHD during reward anticipation, relative to healthy controls. Moreover, ventral striatal activation was negatively correlated with parent-rated hyperactive/impulsive symptoms across the entire sample.These findings provide neural evidence that symptoms of ADHD, and impulsivity or hyperactivity in particular, may involve diminished reward anticipation, in addition to commonly observed executive dysfunction.

  View details for DOI 10.1016/j.biopsych.2006.04.042

  View details for Web of Science ID 000244476800019

  View details for PubMedID 16950228

• Neural predictors of purchases NEURON Knutson, B., Rick, S., Wirnmer, G. E., Prelec, D., Loewenstein, G. 2007; 53 (1): 147-156

  Abstract

  Microeconomic theory maintains that purchases are driven by a combination of consumer preference and price. Using event-related fMRI, we investigated how people weigh these factors to make purchasing decisions. Consistent with neuroimaging evidence suggesting that distinct circuits anticipate gain and loss, product preference activated the nucleus accumbens (NAcc), while excessive prices activated the insula and deactivated the mesial prefrontal cortex (MPFC) prior to the purchase decision. Activity from each of these regions independently predicted immediately subsequent purchases above and beyond self-report variables. These findings suggest that activation of distinct neural circuits related to anticipatory affect precedes and supports consumers' purchasing decisions.

  View details for DOI 10.1016/j.neuron.2006.11.010

  View details for Web of Science ID 000245126500015

  View details for PubMedID 17196537

  View details for PubMedCentralID PMC1876732

• Splitting the difference - How does the brain code reward episodes? Conference on Reward and Decision-Making in Corticobasal Ganglia Networks Knutson, B., Wimmer, G. E. BLACKWELL PUBLISHING. 2007: 54–69

  Abstract

  Animal research and human brain imaging findings suggest that reward processing involves distinct anticipation and outcome phases. Error terms in popular models of reward learning (such as the temporal difference [TD] model) do not distinguish between the updating of expectations in response to reward cues and outcomes. Thus, correlating a single error term with neural activation assumes recruitment of similar neural substrates at each update. Here, we split the error term to separately model reward prediction and prediction errors, and compare the fit of single versus split error terms to functional magnetic resonance imaging (FMRI) data acquired during a monetary incentive delay task. We speculate and find that while the nucleus accumbens computes gain prediction in response to cues, the mesial prefrontal cortex (MPFC) computes gain prediction errors in response to outcomes. In addition to offering a more comprehensive and anatomically situated view of reward processing, split error terms generate novel predictions about psychiatric symptoms and lesion-induced deficits.

  View details for Web of Science ID 000248194800005

  View details for PubMedID 17416922

• The lure of the unknown NEURON Knutson, B., Cooper, J. C. 2006; 51 (3): 280-282

  Abstract

  Using event-related fMRI, Bunzeck and Düzel show that midbrain regions putatively housing dopamine cell bodies activate more for novel pictures than for negative pictures, pictures requiring a motor response, or repeated pictures. These findings indicate that midbrain regions preferentially respond to novelty and suggest that novelty can serve as its own reward.

  View details for DOI 10.1016/j.neuron.2006.07.017

  View details for Web of Science ID 000239908800003

  View details for PubMedID 16880122

• Dysfunction of ventral striatal reward prediction in schizophrenic patients treated with typical, not atypical, neuroleptics PSYCHOPHARMACOLOGY Juckel, G., Schlagenhauf, F., Koslowski, M., Filonov, D., Wuestenberg, T., Villringer, A., Knutson, B., Kienast, T., Gallinat, J., Wrase, J., Heinz, A. 2006; 187 (2): 222-228

  Abstract

  Clinical studies in patients with schizophrenia suggest that atypical neuroleptics are more effective than typical neuroleptics in reducing negative symptoms including apathy and anhedonia. Dysfunction of the dopaminergic reward system may contribute to negative symptoms in schizophrenia.We used functional magnetic resonance imaging to assess the blood oxygen level dependency response in the ventral striatum of medicated schizophrenics and healthy control subjects during reward anticipation.Twenty schizophrenics [ten medicated with typical (e.g., haloperidol) and ten with atypical (e.g., olanzapine and risperidone) neuroleptics] and ten age-matched healthy volunteers participated in an incentive monetary delay task in which visual cues predicted that a rapid response to a subsequent target stimulus would result either in monetary gain or no consequence.Healthy volunteers and schizophrenics treated with atypical neuroleptics showed ventral striatal activation in response to reward-indicating cues, but schizophrenics treated with typical neuroleptics did not. In patients treated with typical neuroleptics, decrease in activation of the left ventral striatum was correlated with the severity of negative symptoms.Failure to activate the ventral striatum during reward anticipation was previously associated with the severity of negative symptoms in schizophrenia and was also found in schizophrenics treated with typical neuroleptics in this study. Significant blunting of ventral striatal activation was not observed in patients treated with atypical neuroleptics, which may reflect the improved efficacy of these drugs in treating negative symptoms.

  View details for DOI 10.1007/s00213-006-0405-4

  View details for Web of Science ID 000238999000010

  View details for PubMedID 16721614

• Reward-motivated learning: Mesolimbic activation precedes memory formation NEURON Adcock, R. A., Thangavel, A., Whitfield-Gabrieli, S., Knutson, B., Gabrieli, J. D. 2006; 50 (3): 507-517

  Abstract

  We examined anticipatory mechanisms of reward-motivated memory formation using event-related FMRI. In a monetary incentive encoding task, cues signaled high- or low-value reward for memorizing an upcoming scene. When tested 24 hr postscan, subjects were significantly more likely to remember scenes that followed cues for high-value rather than low-value reward. A monetary incentive delay task independently localized regions responsive to reward anticipation. In the encoding task, high-reward cues preceding remembered but not forgotten scenes activated the ventral tegmental area, nucleus accumbens, and hippocampus. Across subjects, greater activation in these regions predicted superior memory performance. Within subject, increased correlation between the hippocampus and ventral tegmental area was associated with enhanced long-term memory for the subsequent scene. These findings demonstrate that brain activation preceding stimulus encoding can predict declarative memory formation. The findings are consistent with the hypothesis that reward motivation promotes memory formation via dopamine release in the hippocampus prior to learning.

  View details for DOI 10.1016/j.neuron.2006.03.036

  View details for Web of Science ID 000237726800018

  View details for PubMedID 16675403

• Cultural variation in affect valuation JOURNAL OF PERSONALITY AND SOCIAL PSYCHOLOGY Tsai, J. L., Knutson, B., Fung, H. H. 2006; 90 (2): 288-307

  Abstract

  The authors propose that how people want to feel ("ideal affect") differs from how they actually feel ("actual affect") and that cultural factors influence ideal more than actual affect. In 2 studies, controlling for actual affect, the authors found that European American (EA) and Asian American (AA) individuals value high-arousal positive affect (e.g., excitement) more than do Hong Kong Chinese (CH). On the other hand, CH and AA individuals value low-arousal positive affect (e.g., calm) more than do EA individuals. For all groups, the discrepancy between ideal and actual affect correlates with depression. These findings illustrate the distinctiveness of ideal and actual affect, show that culture influences ideal affect more than actual affect, and indicate that both play a role in mental health.

  View details for DOI 10.1037/0022-3514.90.2.288

  View details for Web of Science ID 000236445600007

  View details for PubMedID 16536652

• Dysfunction of ventral striatal reward prediction in schizophrenia NEUROIMAGE Juckel, G., Schlagenhauf, F., Koslowski, M., Wustenberg, T., Villringer, A., Knutson, B., Wrase, J., Heinz, A. 2006; 29 (2): 409-416

  Abstract

  Negative symptoms may be associated with dysfunction of the brain reward system in schizophrenia. We used functional magnetic resonance imaging (fMRI) to assess the BOLD response in the ventral striatum of unmedicated schizophrenics during presentation of reward-indicating and loss-indicating stimuli.A total of 10 schizophrenic men (7 never medicated, 3 unmedicated for at least 2 years) and 10 age-matched healthy male volunteers participated in an incentive monetary delay task, in which visual cues predicted that a rapid response to a subsequent target stimulus would result either in monetary gain or loss or would have no consequence.Compared to healthy controls, unmedicated schizophrenics showed reduced ventral striatal activation during the presentation of reward-indicating cues. Decreased activation of the left ventral striatum was inversely correlated with the severity of negative (and trendwise positive) symptoms.Reduced activation in one of the central areas of the brain reward system, the ventral striatum, was correlated with the severity of negative symptoms in medication-free schizophrenics. In unmedicated schizophrenic patients, a high striatal dopamine turnover may increase the "noise" in the reward system, thus interfering with the neuronal processing of reward-predicting cues by phasic dopamine release. This, in turn, may contribute to negative symptoms as such as anhedonia, apathy, and loss of drive and motivation.

  View details for DOI 10.1016/j.neuroimage.2005.07.051

  View details for Web of Science ID 000234841200006

  View details for PubMedID 16139525

• The neural basis of financial risk taking NEURON Kuhnen, C. M., Knutson, B. 2005; 47 (5): 763-770

  Abstract

  Investors systematically deviate from rationality when making financial decisions, yet the mechanisms responsible for these deviations have not been identified. Using event-related fMRI, we examined whether anticipatory neural activity would predict optimal and suboptimal choices in a financial decision-making task. We characterized two types of deviations from the optimal investment strategy of a rational risk-neutral agent as risk-seeking mistakes and risk-aversion mistakes. Nucleus accumbens activation preceded risky choices as well as risk-seeking mistakes, while anterior insula activation preceded riskless choices as well as risk-aversion mistakes. These findings suggest that distinct neural circuits linked to anticipatory affect promote different types of financial choices and indicate that excessive activation of these circuits may lead to investing mistakes. Thus, consideration of anticipatory neural mechanisms may add predictive power to the rational actor model of economic decision making.

  View details for DOI 10.1016/j.neuron.2005.08.008

  View details for Web of Science ID 000231782700016

  View details for PubMedID 16129404

• Functional magnetic resonance imaging of reward prediction CURRENT OPINION IN NEUROLOGY Knutson, B., Cooper, J. C. 2005; 18 (4): 411-417

  Abstract

  Technical and conceptual advances in functional magnetic resonance imaging now allow visualization of real-time changes in oxygenation of deep subcortical regions, leading to rapid advances in scientific characterization of the neural substrates that underlie reward prediction in humans.Neuroimaging research over the past year has focused on determining the necessary neural substrates for reward prediction.While the orbitofrontal cortex has long been implicated in modality-specific reward representation, the ventral striatum (particularly the nucleus accumbens) may play a role in modality-independent representations of predicted reward. On the other hand, the mesial prefrontal cortex appears to play a role in representing reward prediction error and the dorsal caudate in linking reward to behavior. Theoretically, future studies will need to establish the specificity of these responses to reward versus punishment and anticipation versus outcome. Clinically, current findings suggest that patients can predict reward without a prefrontal cortex, but should experience difficulty correcting their behavior when reward predictions are violated.

  View details for Web of Science ID 000231075100009

  View details for PubMedID 16003117

• Neurally reconstructing expected utility GAMES AND ECONOMIC BEHAVIOR Knutson, B., Peterson, R. 2005; 52 (2): 305-315

  View details for DOI 10.1016/j.geb.2005.01.002

  View details for Web of Science ID 000231182200005

• Distributed neural representation of expected value JOURNAL OF NEUROSCIENCE Knutson, B., Taylor, J., Kaufman, M., Peterson, R., Glover, G. 2005; 25 (19): 4806-4812

  Abstract

  Anticipated reward magnitude and probability comprise dual components of expected value (EV), a cornerstone of economic and psychological theory. However, the neural mechanisms that compute EV have not been characterized. Using event-related functional magnetic resonance imaging, we examined neural activation as subjects anticipated monetary gains and losses that varied in magnitude and probability. Group analyses indicated that, although the subcortical nucleus accumbens (NAcc) activated proportional to anticipated gain magnitude, the cortical mesial prefrontal cortex (MPFC) additionally activated according to anticipated gain probability. Individual difference analyses indicated that, although NAcc activation correlated with self-reported positive arousal, MPFC activation correlated with probability estimates. These findings suggest that mesolimbic brain regions support the computation of EV in an ascending and distributed manner: whereas subcortical regions represent an affective component, cortical regions also represent a probabilistic component, and, furthermore, may integrate the two.

  View details for DOI 10.1523/JNEUROSCI.0642-05.2005

  View details for Web of Science ID 000229038300014

  View details for PubMedID 15888656

• Remembrance of rewards past NEURON Knutson, B., Adcock, R. A. 2005; 45 (3): 331-332

  Abstract

  Using event-related fMRI, Wittmann and colleagues report in this issue of Neuron that reward value enhances cue memory and that this process is associated with midbrain modulation of hippocampal consolidation. We propose that their findings introduce a novel mechanism by which positive arousal induced by reward anticipation may promote memory.

  View details for DOI 10.1016/j.neuron.2005.01.020

  View details for Web of Science ID 000226787700004

  View details for PubMedID 15694318

• Sweet revenge? SCIENCE Knutson, B. 2004; 305 (5688): 1246-1247

  View details for Web of Science ID 000223624600027

  View details for PubMedID 15333827

• Amphetamine modulates human incentive processing NEURON Knutson, B., Bjork, J. M., Fong, G. W., Hommer, D., Mattay, V. S., Weinberger, D. R. 2004; 43 (2): 261-269

  Abstract

  Research suggests that psychostimulants can physiologically alter dopamine kinetics in the ventral striatum (VS) and psychologically enhance mood and attention. Using event-related functional magnetic resonance imaging (fMRI), we conducted a within-subject, double-blind, placebo (PLAC)-controlled study of the effects of oral dextroamphetamine (AMPH, 0.25 mg/kg) treatment on brain activity and affect during incentive processing. In two counterbalanced scanning sessions 60-180 min after ingesting AMPH or PLAC, 8 healthy volunteers played a game involving anticipation and receipt of monetary gains and losses. Group and volume of interest analyses suggested that by enhancing tonic over phasic activation, AMPH treatment "equalized" levels of VS activity and positive arousal during anticipation of both gain and loss. These findings suggest that therapeutic effects of amphetamine on incentive processing may involve reducing the difference between anticipation of gains and losses.

  View details for Web of Science ID 000222905400014

  View details for PubMedID 15260961

• Voxel-based homogeneity probability maps of grapy matter in groups: assessing the reliability of functional effects NEUROIMAGE Momenan, R., Rawlings, R., Fong, G., Knutson, B., Hommer, D. 2004; 21 (3): 965-972

  Abstract

  A subject of increasing importance in magnetic resonance imaging (MRI) is the analysis of intersubject structural differences, particularly when comparing groups of subjects with different conditions or diagnoses. On the other hand, determining structural homogeneity across subjects using voxel-based morphological (VBM) methods has become even more important to investigators who test for group brain activation using functional magnetic resonance images (fMRI) or positron emission tomography (PET). In the absence of methods that evaluate structural differences, one does not know how much reliability to assign to the functional differences. Here, we describe a voxel-based method for quantitatively assessing the homogeneity of tissues from structural magnetic resonance images of groups. Specifically, this method determines the homogeneity of gray matter for a group of subjects. Homogeneity probability maps (HPMs) of a given tissue type (e.g., gray matter) are generated by using a confidence interval based on binomial distribution. These maps indicate for each voxel the probability that the tissue type is gray for the population being studied. Therefore, HPMs can accompany functional analyses to indicate the confidence one can assign to functional difference at any given voxel. In this paper, examples of HPMs generated for a group of control subjects are shown and discussed. The application of this method to functional analysis is demonstrated.

  View details for DOI 10.1016/j.neuroimage.2003.10.038

  View details for Web of Science ID 000220148900017

  View details for PubMedID 15006663

• Incentive-elicited brain activation in adolescents: Similarities and differences from young adults JOURNAL OF NEUROSCIENCE Bjork, J. M., Knutson, B., Fong, G. W., Caggiano, D. M., Bennett, S. M., Hommer, D. W. 2004; 24 (8): 1793-1802

  Abstract

  Brain motivational circuitry in human adolescence is poorly characterized. One theory holds that risky behavior in adolescence results in part from a relatively overactive ventral striatal (VS) motivational circuit that readily energizes approach toward salient appetitive cues. However, other evidence fosters a theory that this circuit is developmentally underactive, in which adolescents approach more robust incentives (such as risk taking or drug experimentation) to recruit this circuitry. To help resolve this, we compared brain activation in 12 adolescents (12-17 years of age) and 12 young adults (22-28 years of age) while they anticipated the opportunity to respond to obtain monetary gains as well as to avoid monetary losses. In both age groups, anticipation of potential gain activated portions of the VS, right insula, dorsal thalamus, and dorsal midbrain, where the magnitude of VS activation was sensitive to gain amount. Notification of gain outcomes (in contrast with missed gains) activated the mesial frontal cortex (mFC). Across all subjects, signal increase in the right nucleus accumbens during anticipation of responding for large gains independently correlated with both age and self-rated excitement about the high gain cue. In direct comparison, adolescents evidenced less recruitment of the right VS and right-extended amygdala while anticipating responding for gains (in contrast with anticipation of nongains) compared with young adults. However, brain activation after gain outcomes did not appreciably differ between age groups. These results suggest that adolescents selectively show reduced recruitment of motivational but not consummatory components of reward-directed behavior.

  View details for DOI 10.1523/JNEUROSCI.4862-03.2004

  View details for Web of Science ID 000189210300001

  View details for PubMedID 14985419

• Facial EMG discriminates gain and loss anticipation and outcome in a monetary incentive delay task 44th Annual Meeting of the Society-for-Psychophysiological-Research NIELSEN, L., Knutson, B., Kaufman, M., Weinstein, L., Carstensen, L. L. WILEY-BLACKWELL. 2004: S80–S80

  View details for Web of Science ID 000223558200310

• A region of mesial prefrontal cortex tracks monetarily rewarding outcomes: characterization with rapid event-related fMRI NEUROIMAGE Knutson, B., Fong, G. W., Bennett, S. M., Adams, C. M., Homme, D. 2003; 18 (2): 263-272

  Abstract

  The function of the mesial prefrontal cortex (MPFC: including Brodman areas 10/12/32) remains an enigma. Current theories suggest a role in representing internal information, including emotional introspection, autonomic control, and a "default state" of semantic processing. Recent evidence also suggests that parts of this region may also play a role in processing reward outcomes. In this study, we investigated the possibility that a region of the MPFC would be preferentially recruited by monetary reward outcomes using a parametric monetary incentive delay (MID) task. Twelve healthy volunteers participated in functional magnetic resonance scans while playing the MID task. Group analyses indicated that while the ventral striatum was recruited by anticipation of monetary reward, a region of the MPFC instead responded to rewarding monetary outcomes. Specifically, volume-of-interest analyses indicated that when volunteers received $5.00 after anticipating a $5.00 win, MPFC activity increased, whereas when volunteers did not receive $5.00 after anticipating a $5.00 win, MPFC activity decreased, relative to outcomes with no incentive value. These findings suggest that in the context of processing monetary rewards, a region of the MPFC preferentially tracks rewarding outcomes.

  View details for DOI 10.1016/S1053-8119(02)00057-5

  View details for Web of Science ID 000181182500007

  View details for PubMedID 12595181

• Amygdalar recruitment during anticipation of monetary rewards - An event-related fMRI study Conference on the Amygdala in Brain Function Hommer, D. W., Knutson, B., Fong, G. W., Bennett, S., Adams, C. M., Varner, J. L. NEW YORK ACAD SCIENCES. 2003: 476–478

  View details for Web of Science ID 000182918800037

  View details for PubMedID 12724180

• Ultrasonic Vocalizations as indices of affective states in rats PSYCHOLOGICAL BULLETIN Knutson, B., Burgdorf, J., Panksepp, J. 2002; 128 (6): 961-977

  Abstract

  Adult rats spontaneously vocalize in ultrasonic frequencies. Although these ultrasonic vocalizations (USVs) have been described as by-products of locomotor activity or social signals, accumulating evidence suggests that they may also index anticipatory affective states. Converging ethological, pharmacological, and brain stimulation research indicates that whereas long low-frequency (> 0.3-s, approximately 22-kHz) USVs occur during anticipation of punishment or avoidance behavior, short, high-frequency (< 0.3-s, approximately 50-kHz) USVs typically occur during anticipation of reward or approach behavior. Thus, long 22-kHz USVs may index a state of negative activation, whereas short, 50-kHz USVs may instead index a state of positive activation. This hypothesis has theoretical implications for understanding the brain circuitry underlying mammalian affective states and clinical applicability for modeling hedonic properties of different psychotropic compounds.

  View details for DOI 10.1037//0033-2909.128.6.961

  View details for Web of Science ID 000178726100005

  View details for PubMedID 12405139

• Volition to action - An event-related fMRI study NEUROIMAGE Winterer, G., Adams, C. M., Jones, D. W., Knutson, B. 2002; 17 (2): 851-858

  Abstract

  Current concepts of the anterior cingulate cortex (ACC) increasingly emphasize its role as an interface between limbic and neocortical functions. It has been pointed out that ACC activation reflects the intentional amount of effort (volition) that a subject uses in a task. In previous electrophysiological source localization investigations during a choice reaction task, we described a strong early activation in the ACC region approximately 120-150 ms after stimulus presentation. The degree of midline ACC activation correlated negatively with reaction time. This observation together with the finding that ACC activation precedes information processing in cortical association areas provided preliminary support to the notion that the extent of ACC activation is related to a subject's task engagement. However, due to the inverse problem and the relatively low spatial resolution of the electrophysiological measurements, we were not able to make inferences about the validity and the exact localization of the observed midline activation maximum. We addressed this question and performed an event-related fMRI study in six healthy volunteers during a visual choice reaction task. Two checkerboard stimuli were presented either in the left or right visual hemifield in randomized order and with an interstimulus interval requiring an appropriate motor response (left-right button press). A bilateral BOLD maximum was observed in the region of the supplementary motor area confluent with the neighboring motor area of the dorsal ACC. The degree of ACC activation correlated significantly with reaction time. These results are in line with our previous electrophysiological findings and provide further evidence that early ACC activation during a choice reaction task reflects the intentional effort of a subject to carry out a task.

  View details for DOI 10.1006/nimg.2002.1232

  View details for Web of Science ID 000178642000029

  View details for PubMedID 12377159

• The role of brain emotional systems in addictions: a neuro-evolutionary perspective and new 'self-report' animal model ADDICTION Panksepp, J., Knutson, B., Burgdorf, J. 2002; 97 (4): 459-469

  Abstract

  The evolutionary significance of neurochemical events in the brain has received minimal attention in the field of addiction research. Likewise, the general failure of neuroscientists to postulate how basic brain circuits might mediate emotional urges has retarded the development of scientific perspectives that could inform new inquiries into the underlying dynamics and treatment of addictions. In this paper, we revisit the argument that prototypically abused substances activate or alter specific emotional brain systems that were evolutionarily designed to signal potential increments or decrements in fitness. We then discuss two distinct emotional systems (reward seeking and separation distress) which may track different types of potential changes in fitness. Based on this evolutionarily inspired approach, we illustrate how a mammalian model of emotion (i.e. rodent ultrasonic vocalizations) may enable scientists to predict drug-related phenomena such as abuse potential, anatomical location of mediating neural substrates, and the psychological impact of withdrawal. We conclude by discussing some therapeutic and social implications of examining drug addiction processes with multiple emotional brain systems in mind.

  View details for Web of Science ID 000174850900009

  View details for PubMedID 11964061

• Dissociation of reward anticipation and outcome with event-related fMRI NEUROREPORT Knutson, B., Fong, G. W., Adams, C. M., Varner, J. L., Hommer, D. 2001; 12 (17): 3683-3687

  Abstract

  Reward processing involves both appetitive and consummatory phases. We sought to examine whether reward anticipation vs outcomes would recruit different regions of ventral forebrain circuitry using event-related fMRI. Nine healthy volunteers participated in a monetary incentive delays task in which they either responded to a cued target for monetary reward, responded to a cued target for no reward, or did not respond to a cued target during scanning. Multiple regression analyses indicated that while anticipation of reward vs non-reward activated foci in the ventral striatum, reward vs non-reward outcomes activated foci in the ventromedial frontal cortex. These findings suggest that reward anticipation and outcomes may differentially recruit distinct regions that lie along the trajectory of ascending dopamine projections.

  View details for Web of Science ID 000172397000012

  View details for PubMedID 11726774

• Negative association of neuroticism with brain volume ratio in healthy humans BIOLOGICAL PSYCHIATRY Knutson, B., Momenan, R., RAWLINGS, R. R., Fong, G. W., Hommer, D. 2001; 50 (9): 685-690

  Abstract

  Brain volume decreases with normal aging. We sought to determine whether, in addition to age, individual differences in stress reactivity (i.e., neuroticism) would also predict reductions in brain volume.Brain volume ratios were calculated for a sample of 86 healthy volunteers, based on segmented brain volumes taken from T(1)-weighted magnetic resonance imaging and corrected for intracranial volume. Standardized self-reported measures of dispositional neuroticism were concurrently obtained by administering the Revised NEO Personality Inventory.After statistically controlling for age and sex, neuroticism showed a significant negative association with the ratio of brain to the remainder of the intracranial volume, but was not related to intracranial volume itself. In particular, subfactors of neuroticism related to the chronic experience of arousing negative emotions were associated with reduced brain ratio.These results suggest that individual differences in stress reactivity contribute to reductions in brain volume observed during adulthood.

  View details for Web of Science ID 000172035100005

  View details for PubMedID 11704075

• Anticipation of increasing monetary reward selectively recruits nucleus accumbens JOURNAL OF NEUROSCIENCE Knutson, B., Adams, C. M., Fong, G. W., Hommer, D. 2001; 21 (16)

  Abstract

  Comparative studies have implicated the nucleus accumbens (NAcc) in the anticipation of incentives, but the relative responsiveness of this neural substrate during anticipation of rewards versus punishments remains unclear. Using event-related functional magnetic resonance imaging, we investigated whether the anticipation of increasing monetary rewards and punishments would increase NAcc blood oxygen level-dependent contrast (hereafter, "activation") in eight healthy volunteers. Whereas anticipation of increasing rewards elicited both increasing self-reported happiness and NAcc activation, anticipation of increasing punishment elicited neither. However, anticipation of both rewards and punishments activated a different striatal region (the medial caudate). At the highest reward level ($5.00), NAcc activation was correlated with individual differences in self-reported happiness elicited by the reward cues. These findings suggest that whereas other striatal areas may code for expected incentive magnitude, a region in the NAcc codes for expected positive incentive value.

  View details for Web of Science ID 000170318200001

  View details for PubMedID 11459880

• Nucleus accumbens amphetamine microinjections unconditionally elicit 50-kHz ultrasonic vocalizations in rats BEHAVIORAL NEUROSCIENCE Burgdorf, J., Knutson, B., Panksepp, J., Ikemoto, S. 2001; 115 (4): 940-944

  Abstract

  The authors have hypothesized that, in adult rats, 50-kHz ultrasonic vocalizations (USVs) index a state characterized by high arousal and expectations of reward. This study was conducted to investigate whether dopamine agonism of the nucleus accumbens (NAcc) could evoke such an appetitive state, by examining the effects of NAcc amphetamine (AMPH) microinjections on USVs. Intra-NAcc AMPH injections (0.3, 1.0, 3.0, 10.0 microg unilaterally) produced robust, dose-dependent increases in 50-kHz USVs, which could not be accounted for by concomitant increases in locomotor activity (LA). However, AMPH injections into dorsal control caudate putamen sites produced a modest, dose-dependent increase in LA without significant increases in 50-kHz USVs. These findings indicate that NAcc AMPH microinjections selectively evoke 50-kHz USVs in rats, supporting the notion that dopamine elevations in the NAcc may unconditionally elicit a state of reward anticipation.

  View details for Web of Science ID 000170911600020

  View details for PubMedID 11508733

• Evaluation of rat ultrasonic vocalizations as predictors of the conditioned aversive effects of drugs PSYCHOPHARMACOLOGY Burgdorf, J., Knutson, B., Panksepp, J., Shippenberg, T. S. 2001; 155 (1): 35-42

  Abstract

  Since cues that predict aversive outcomes can elicit both avoidance and 20 kHz ultrasonic vocalizations (USVs) in adult rats, 20 kHz USVs may also index the conditioned aversive effects of drugs.We evaluated whether exposure to compartments associated with drugs with aversive effects would selectively increase 20 but not 50 kHz USVs in rats.Rats were injected with naloxone (NAL) or lithium chloride (LiCl) and placed in one compartment or with saline (VEH) and placed in another compartment for three 50-min conditioning sessions. 20 kHz USVs, 50 kHz USVs, and time spent in each chamber were recorded during subsequent 15-min testing sessions during which rats had access to both compartments (expt 1) or were confined to the drug- or VEH-paired compartment (expt 2).In expt 1, animals conditioned either with NAL (0.3 and 3.0 mg/kg) or LiCl (10 and 30 mg/kg) emitted increased 20 kHz USVs in the drug-paired compartment, relative to VEH-conditioned controls. Conditioning with high doses of both drugs also increased conditioned place aversion and decreased emission of 50 kHz USVs. In expt 2, restriction of animals to the compartment paired with high doses of NAL and LiCl also increased emission of 20 kHz USVs and decreased 50 kHz USVs, relative to VEH-conditioned controls.In rats, cues associated with drugs with aversive effects increase 20 kHz USVs and decrease 50 kHz USVs, suggesting that USVs may provide a useful model for predicting the conditioned aversive effects of drugs.

  View details for Web of Science ID 000168522200005

  View details for PubMedID 11374334

• FMRI visualization of brain activity during a monetary incentive delay task NEUROIMAGE Knutson, B., Westdorp, A., Kaiser, E., Hommer, D. 2000; 12 (1): 20-27

  Abstract

  Comparative studies have implicated striatal and mesial forebrain circuitry in the generation of autonomic, endocrine, and behavioral responses for incentives. Using blood oxygen level-dependent functional magnetic resonance imaging, we sought to visualize functional activation of these regions in 12 normal volunteers as they anticipated and responded for monetary incentives. Both individual and group analyses of time-series data revealed significant activation of striatal and mesial forebrain structures (including insula, caudate, putamen, and mesial prefrontal cortex) during trials involving both monetary rewards and punishments. In addition to these areas, during trials involving punishment, group analysis revealed activation foci in the anterior cingulate and thalamus. These results corroborate comparative studies which implicate striatal and mesial forebrain circuitry in the elaboration of incentive-driven behavior. This report also introduces a new paradigm for probing the functional integrity of this circuitry in humans.

  View details for Web of Science ID 000088317700003

  View details for PubMedID 10875899

• Anticipation of rewarding electrical brain stimulation evokes ultrasonic vocalization in rats BEHAVIORAL NEUROSCIENCE Burgdorf, J., Knutson, B., Panksepp, J. 2000; 114 (2): 320-327

  Abstract

  Adult rats emit increased rates of 50-kHz ultrasonic vocalizations (USVs) before receiving social and pharmacological rewards. This study sought to determine whether anticipation of rewarding electrical stimulation of the brain (ESB) would also elicit these vocalizations. In Experiments 1 and 2, rats showed increased 50-kHz USVs before receiving experimenter-delivered ventral tegmental area (VTA) and lateral hypothalamic (LH) ESB on a fixed time 20-s schedule. In Experiments 3 and 4, rats increased their rate of 50-kHz USVs in response to cues that predicted the opportunity to self-stimulate the VTA or LH. Interestingly, unexpected termination of either type of ESB evoked 20-kHz, rather than 50-kHz, USVs. In Experiment 5, a cue that predicted daily 1-hr feeding sessions increased 50-kHz USVs, whereas a cue that predicted footshock decreased 50-kHz USVs. These effects could not be explained simply by changes in locomotor activity or general arousal. Together, these findings support the hypothesis that short 50-kHz USVs may selectively index a state of reward anticipation in rats.

  View details for DOI 10.1037//0735-7044.114.2.320

  View details for Web of Science ID 000087492200010

  View details for PubMedID 10832793

• High-frequency ultrasonic vocalizations index conditioned pharmacological reward in rats PHYSIOLOGY & BEHAVIOR Knutson, B., Burgdorf, J., Panksepp, J. 1999; 66 (4): 639-643

  Abstract

  We have proposed that short (<0.5 s), high-frequency (approximately 50 kHz) ultrasonic vocalizations ("50-kHz USVs") index a positive affective state in adult rats, because they occur prior to rewarding social interactions (i.e., rough-and-tumble play, sex). To evaluate this hypothesis in the case of nonsocial stimuli, we examined whether rats would make increased 50-kHz USVs in places associated with the administration of rewarding pharmacological compounds [i.e., amphetamine (AMPH) and morphine (MORPH)]. In Experiment 1, rats made a greater percentage of 50-kHz USVs on the AMPH-paired side of a two-compartment chamber than on the vehicle-paired side, even after statistical correction for place preference. In Experiment 2, rats made a higher percentage of 50-kHz USVs on the MORPH-paired side than on the vehicle-paired side, despite nonsignificant place preference. These findings support the hypothesis that 50-kHz USVs mark a positive affective state in rats and introduce a novel and rapid marker of pharmacological reward.

  View details for Web of Science ID 000080685000013

  View details for PubMedID 10386908

• Anticipation of play elicits high-frequency ultrasonic vocalizations in young rats JOURNAL OF COMPARATIVE PSYCHOLOGY Knutson, B., Burgdorf, J., Panksepp, J. 1998; 112 (1): 65-73

  Abstract

  The authors provide initial documentation that juvenile rats emit short, high-frequency ultrasonic vocalizations (high USVs, approximately 55 kHz) during rough-and-tumble play. In an observational study, they further observe that these vocalizations both correlate with and predict appetitive components of the play behavioral repertoire. Additional experiments characterized eliciting conditions for high USVs. Without prior play exposure, rats separated by a screen vocalized less than playing rats, but after only 1 play session, separated rats vocalized more than playing rats. This findings suggested that high USVs were linked to a motivational state rather than specific play behaviors or general activity. Furthermore, individual rats vocalized more in a chamber associated with play than in a habituated control chamber. Finally, congruent and incongruent motivational manipulations modulated vocalization expression. Although play deprivation enhanced high USVs, an arousing but aversive stimulus (bright light) reduced them. Taken together, these findings suggest that high USVs may index an appetitive motivation to play in juvenile rats.

  View details for Web of Science ID 000072487600007

  View details for PubMedID 9528115

• Selective alteration of personality and social behavior by serotonergic intervention 149th Annual Meeting of the American-Psychiatric-Association Knutson, B., Wolkowitz, O. M., Cole, S. W., Chan, T., Moore, E. A., Johnson, R. C., Terpstra, J., Turner, R. A., Reus, V. I. AMER PSYCHIATRIC PUBLISHING, INC. 1998: 373–79

  Abstract

  The authors sought to test the causal hypothesis that serotonergic function modulates aspects of the normal spectrum of individual differences in affective experience and social behavior in humans.A selective serotonin reuptake inhibitor (SSRI), paroxetine, 20 mg/day (N = 26), or placebo (N = 25) was administered to normal volunteers in a double-blind manner for 4 weeks, and personality variables and social behavior were assessed at baseline and at weeks 1 and 4 of treatment.Relative to placebo, SSRI administration reduced focal indices of hostility through a more general decrease in negative affect, yet did not alter indices of positive affect. In addition, SSRI administration increased a behavioral index of social affiliation. Changes in both negative affect and affiliative behavior were significantly related to volunteers' plasma SSRI levels at the end of the experiment.Central serotonergic function may modulate a dimension of normal personality characterized by reduced negative affective experience and increased affiliative behavior. SSRI administration has significant and detectable effects on these measures even in the absence of baseline clinical depression or other psychopathology.

  View details for Web of Science ID 000072290600010

  View details for PubMedID 9501748

• Effects of serotonin depletion on the play of juvenile rats Conference of the New-York-Academy-of-Sciences on the Integrative Neurobiology of Affiliation Knutson, B., Panksepp, J. NEW YORK ACAD SCIENCES. 1997: 475–477

  View details for Web of Science ID A1997BJ17S00033

  View details for PubMedID 9071373

• Serotonergic intervention increases affiliative behavior in humans Conference of the New-York-Academy-of-Sciences on the Integrative Neurobiology of Affiliation Knutson, B., Cole, S., Wolkowitz, O., Reus, V., Chan, T., Moore, E. NEW YORK ACAD SCIENCES. 1997: 492–493

  View details for Web of Science ID A1997BJ17S00039

  View details for PubMedID 9071379

• Facial expressions of emotion influence interpersonal trait inferences JOURNAL OF NONVERBAL BEHAVIOR Knutson, B. 1996; 20 (3): 165-182

  View details for Web of Science ID A1996VJ74700002

• Effects of fluoxetine on play dominance in juvenile rats AGGRESSIVE BEHAVIOR Knutson, B., Panksepp, J., Pruitt, D. 1996; 22 (4): 297-307

  View details for Web of Science ID A1996UZ97900005

• ON THE BRAIN AND PERSONALITY SUBSTRATES OF PSYCHOPATHY BEHAVIORAL AND BRAIN SCIENCES Panksepp, J., Knutson, B., Bird, L. 1995; 18 (3): 568-570

  View details for Web of Science ID A1995TJ30000076