All Publications

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


    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 DOI 10.1016/j.neuroimage.2018.05.055

    View details for PubMedID 29803959

  • 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


    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 DOI 10.3758/s13415-017-0545-5

    View details for Web of Science ID 000416835000013

    View details for PubMedID 29063520

    View details for PubMedCentralID PMC5709503

  • Effects of Sensitivity to Life Stress on Uncinate Fasciculus Segments in Early Adolescence. Social cognitive and affective neuroscience Ho, T. C., King, L. S., Leong, J. K., Colich, N. L., Humphreys, K. L., Ordaz, S. J., Gotlib, I. H. 2017


    Previous research suggests that exposure to early life stress (ELS) affects the structural integrity of the uncinate fasciculus (UF), a frontolimbic white matter tract that undergoes protracted development throughout adolescence. Adolescence is an important transitional period characterized by the emergence of internalizing psychopathology such as anxiety, particularly in individuals with high levels of stress sensitivity. We examined the relations among sensitivity to ELS, structural integrity of the UF, and anxiety symptoms in 104 early adolescents. We conducted structured interviews to assess exposure to ELS and obtained subjective and objective ratings of stress severity, from which we derived an index of ELS sensitivity. We also acquired diffusion MRI and conducted deterministic tractography to visualize UF trajectories and to compute measures of structural integrity from three distinct segments of the UF: frontal, insular, temporal. We found that higher sensitivity to ELS predicted both reduced fractional anisotropy in right frontal UF and higher levels of anxiety symptoms. These findings suggest that fibers in frontal UF, which are still developing throughout adolescence, are most vulnerable to the effects of heightened sensitivity to ELS, and that reduced structural integrity of frontal UF may underlie the relation between early stress and subsequent internalizing psychopathology.

    View details for DOI 10.1093/scan/nsx065

    View details for PubMedID 28460088

  • Age-dependent effects of APOE epsilon 4 in preclinical Alzheimer's disease ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY Bonham, L. W., Geier, E. G., Fan, C. C., Leong, J. K., Besser, L., Kukull, W. A., Kornak, J., Andreassen, O. A., Schellenberg, G. D., Rosen, H. J., Dillon, W. P., Hess, C. P., Miller, B. L., Dale, A. M., Desikan, R. S., Yokoyama, J. S. 2016; 3 (9): 668-677


    The ε4 allele of apolipoprotein E (APOE) is the strongest known common genetic risk factor for Alzheimer's disease (AD) and alters age of onset in retrospective studies. Here, we longitudinally test the effects of APOE ε4 genotype and age during progression from normal cognition to AD.Using data from 5381 cognitively normal older individuals and Cox proportional hazards models, we longitudinally tested the effects of APOE genotype on progression from normal cognition to mild cognitive impairment (MCI) or AD in four age strata (<60, 60-70, 70-80, 80 + ) and with a sliding window approach between ages 60 and 85.We found that APOE ε4 carrier status and dosage significantly influenced progression to MCI or AD in all four age groups and that APOE ε4-associated progression risk peaked between ages 70 and 75. We confirmed APOE ε4-associated progression risk in a subset of the cohort with pathologically proven diagnoses.Our findings indicate that in clinically normal individuals, APOE ε4 status significantly predicts progression to MCI or AD across older adulthood and that this risk varies with age. This information will be useful as therapeutic interventions become available and clinical decisions can be individually tailored based on age and genetic data.

    View details for DOI 10.1002/acn3.333

    View details for Web of Science ID 000384124200001

    View details for PubMedID 27648456

    View details for PubMedCentralID PMC5018579

  • 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


    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