Honors & Awards

  • Banting Fellowship, Canadian Institutes of Health Research (2017-2019)

Professional Education

  • Postdoctoral Fellowship, Harvard Medical School (2016)
  • Doctor of Philosophy, University of Toronto (2014)
  • Bachelor of Science, York University (2009)

Stanford Advisors

Current Research and Scholarly Interests

Intracranial electrophysiology of the human default mode network

All Publications

  • Large-scale network interactions involved in dividing attention between the external environment and internal thoughts to pursue two distinct goals. NeuroImage Maillet, D., Beaty, R. E., Kucyi, A., Schacter, D. L. 2019


    Previous research suggests that default-mode network (DMN) and dorsal attention network (DAN) are involved in internally- and externally-directed attention, respectively, through interactions with salience network (SN) and frontoparietal network (FPCN). Performing a task requiring external attention is often accompanied by a down-regulation of attention to internal thoughts, and vice-versa. In contrast, we often divide our attention between the external environment and internal thoughts to pursue distinct goals, yet virtually no prior research has examined how brain networks support this functionally critical neurocognitive process. In the current study, participants planned their responses for an upcoming alternate uses divergent thinking task (AUT-Condition), indicated whether arrows were pointing left or right (Arrows-Condition) or performed both tasks simultaneously (Dual-Task condition). Behaviorally, the Dual-Task condition was associated with equivalent generation of alternate uses but increased RT variability compared to the single-task conditions. Static connectivity analyses indicated that FPCN and SN increased their connectivity to DMN and reduced their connectivity to DAN during the Dual-Task condition and the AUT-Condition compared to the Arrows-Condition. Furthermore, DAN-SN connectivity was highest during the Arrows-Condition, intermediate during the Dual-Task condition and lowest during the AUT-Condition. Finally, time-varying connectivity analyses indicated that individuals who reported spending less time thinking of alternate uses during the Dual-Task condition spent more time in a state associated with performing the Arrows-Condition. Overall, our results suggest that interactions between DMN, FPCN, SN and DAN allow internal-external dual-tasking, and that time-varying functional connectivity between these networks is sensitive to attentional fluctuations between tasks during dual-tasking.

    View details for PubMedID 31018153

  • Just a thought: How mind-wandering is represented in dynamic brain connectivity. NeuroImage Kucyi, A. 2018; 180 (Pt B): 505–14


    The neuroscience of mind-wandering has begun to flourish, with roles of brain regions and networks being defined for various components of spontaneous thought. However, most of brain activity does not represent immediately occurring thoughts. Instead, spontaneous, organized network activity largely reflects "intrinsic" functions that are unrelated to the current experience. There remains no consensus on how brain networks represent mind-wandering in parallel to functioning in other ongoing, predominantly unconscious processes. Commonly, in network analysis of functional neuroimaging data, functional connectivity (FC; correlated time series) between remote brain regions is considered over several minutes or longer. In contrast, dynamic functional connectivity (dFC) is a new, promising approach to characterizing spontaneous changes in neural network communication on the faster time-scale at which intra-individual fluctuations in thought contents may occur. Here I describe how a potential relationship between mind-wandering and FC has traditionally been considered in the literature, and I review methods and results pertaining to the study of the dFC-mind-wandering relationship. While acknowledging challenges to the dFC approach and to behaviorally capturing fluctuations in inner experiences, I describe a framework for describing spontaneous thoughts in terms of brain-network activity patterns that are comprised of connections weighted by time-varying relevance to conscious and unconscious processing. This perspective suggests preferential roles of certain anatomical communication avenues (e.g., via the default mode network) in mind-wandering, while also implying that a region's connectivity fluctuates over time in its immediate degree of relevance to conscious contents, ultimately allowing novelty and diversity of thought.

    View details for PubMedID 28684334

  • Direct Cortical Recordings Suggest Temporal Order of Task Evoked Responses in Human Dorsal Attention and Default Networks. The Journal of neuroscience : the official journal of the Society for Neuroscience Raccah, O., Daitch, A. L., Kucyi, A., Parvizi, J. 2018


    The past decade has seen a large number of neuroimaging studies focused on the anti-correlated functional relationship between the default mode network (DMN) and the dorsal attention network (DAN). Due principally to the low-temporal resolution of functional neuroimaging modalities, the fast-neuronal dynamics across these networks remains poorly understood. Here we report novel human intracranial electrophysiology data from six neurosurgical patients (four males) with simultaneous coverage of well-characterized nodes of the DMN and DAN. Subjects performed an arithmetic processing task, shown previously to evoke reliable deactivations (below baseline) in the DMN and activations in the DAN. In this cohort, we show that DMN deactivations lag DAN activations by over 200 milliseconds. Our findings suggest a clear temporal order of processing across the two networks during the current task and place the DMN further than the DAN in a plausible information-processing hierarchy.Significance Statement: The human brain contains an intrinsic and strictly organized network architecture. Our understanding of the interplay across association networks has relied primarily on the slow fluctuations of the hemodynamic response, and as such it has lacked critical evidence regarding the temporal dynamics of activity across these networks. The current study presents evidence from high spatiotemporal methods showing that well-studied areas of the default mode network (DMN) display delayed task-induced activity relative to divergent responses in dorsal attention network (DAN) nodes. This finding provides direct and critical evidence regarding the temporal chronology of neuronal events across opposing brain networks.

    View details for PubMedID 30315126

  • Multivariate machine learning distinguishes cross-network dynamic functional connectivity patterns in state and trait neuropathic pain PAIN Cheng, J. C., Rogachov, A., Hemington, K. S., Kucyi, A., Bosma, R. L., Lindquist, M. A., Inman, R. D., Davis, K. D. 2018; 159 (9): 1764–76


    Communication within the brain is dynamic. Chronic pain can also be dynamic, with varying intensities experienced over time. Little is known of how brain dynamics are disrupted in chronic pain, or relates to patients' pain assessed at various timescales (eg, short-term state vs long-term trait). Patients experience pain "traits" indicative of their general condition, but also pain "states" that vary day to day. Here, we used network-based multivariate machine learning to determine how patterns in dynamic and static brain communication are related to different characteristics and timescales of chronic pain. Our models were based on resting-state dynamic functional connectivity (dFC) and static functional connectivity in patients with chronic neuropathic pain (NP) or non-NP. The most prominent networks in the models were the default mode, salience, and executive control networks. We also found that cross-network measures of dFC rather than static functional connectivity were better associated with patients' pain, but only in those with NP features. These associations were also more highly and widely associated with measures of trait rather than state pain. Furthermore, greater dynamic connectivity with executive control networks was associated with milder NP, but greater dynamic connectivity with limbic networks was associated with greater NP. Compared with healthy individuals, the dFC features most highly related to trait NP were also more abnormal in patients with greater pain. Our findings indicate that dFC reflects patients' overall pain condition (ie, trait pain), not just their current state, and is impacted by complexities in pain features beyond intensity.

    View details for PubMedID 29708944

  • Intracranial Electrophysiology Reveals Reproducible Intrinsic Functional Connectivity within Human Brain Networks JOURNAL OF NEUROSCIENCE Kucyi, A., Schrouff, J., Bickel, S., Foster, B. L., Shine, J. M., Parvizi, J. 2018; 38 (17): 4230–42


    Evidence for intrinsic functional connectivity (FC) within the human brain is largely from neuroimaging studies of hemodynamic activity. Data are lacking from anatomically precise electrophysiological recordings in the most widely studied nodes of human brain networks. Here we used a combination of fMRI and electrocorticography (ECoG) in five human neurosurgical patients with electrodes in the canonical "default" (medial prefrontal and posteromedial cortex), "dorsal attention" (frontal eye fields and superior parietal lobule), and "frontoparietal control" (inferior parietal lobule and dorsolateral prefrontal cortex) networks. In this unique cohort, simultaneous intracranial recordings within these networks were anatomically matched across different individuals. Within each network and for each individual, we found a positive, and reproducible, spatial correlation for FC measures obtained from resting-state fMRI and separately recorded ECoG in the same brains. This relationship was reliably identified for electrophysiological FC based on slow (<1 Hz) fluctuations of high-frequency broadband (70-170 Hz) power, both during wakeful rest and sleep. A similar FC organization was often recovered when using lower-frequency (1-70 Hz) power, but anatomical specificity and consistency were greatest for the high-frequency broadband range. An interfrequency comparison of fluctuations in FC revealed that high and low-frequency ranges often temporally diverged from one another, suggesting that multiple neurophysiological sources may underlie variations in FC. Together, our work offers a generalizable electrophysiological basis for intrinsic FC and its dynamics across individuals, brain networks, and behavioral states.SIGNIFICANCE STATEMENT The study of human brain networks during wakeful "rest", largely with fMRI, is now a major focus in both cognitive and clinical neuroscience. However, little is known about the neurophysiology of these networks and their dynamics. We studied neural activity during wakeful rest and sleep within neurosurgical patients with directly implanted electrodes. We found that network activity patterns showed striking similarities between fMRI and direct recordings in the same brains. With improved resolution of direct recordings, we also found that networks were best characterized with specific activity frequencies and that different frequencies show different profiles of within-network activity over time. Our work clarifies how networks spontaneously organize themselves across individuals, brain networks, and behavioral states.

    View details for PubMedID 29626167

  • Intracranial Electrophysiology of the Human Default Network TRENDS IN COGNITIVE SCIENCES Fox, K. R., Foster, B. L., Kucyi, A., Daitch, A. L., Parvizi, J. 2018; 22 (4): 307–24


    The human default network (DN) plays a critical role in internally directed cognition, behavior, and neuropsychiatric disease. Despite much progress with functional neuroimaging, persistent questions still linger concerning the electrophysiological underpinnings, fast temporal dynamics, and causal importance of the DN. Here, we review how direct intracranial recording and stimulation of the DN provides a unique combination of high spatiotemporal resolution and causal information that speaks directly to many of these outstanding questions. Our synthesis highlights the electrophysiological basis of activation, suppression, and connectivity of the DN, each key areas of debate in the literature. Integrating these unique electrophysiological data with extant neuroimaging findings will help lay the foundation for a mechanistic account of DN function in human behavior and cognition.

    View details for PubMedID 29525387

    View details for PubMedCentralID PMC5957519

  • Spontaneous cognitive processes and the behavioral validation of time-varying brain connectivity. Network neuroscience (Cambridge, Mass.) Kucyi, A., Tambini, A., Sadaghiani, S., Keilholz, S., Cohen, J. R. 2018; 2 (4): 397–417


    In cognitive neuroscience, focus is commonly placed on associating brain function with changes in objectively measured external stimuli or with actively generated cognitive processes. In everyday life, however, many forms of cognitive processes are initiated spontaneously, without an individual's active effort and without explicit manipulation of behavioral state. Recently, there has been increased emphasis, especially in functional neuroimaging research, on spontaneous correlated activity among spatially segregated brain regions (intrinsic functional connectivity) and, more specifically, on intraindividual fluctuations of such correlated activity on various time scales (time-varying functional connectivity). In this Perspective, we propose that certain subtypes of spontaneous cognitive processes are detectable in time-varying functional connectivity measurements. We define these subtypes of spontaneous cognitive processes and review evidence of their representations in time-varying functional connectivity from studies of attentional fluctuations, memory reactivation, and effects of baseline states on subsequent perception. Moreover, we describe how these studies are critical to validating the use of neuroimaging tools (e.g., fMRI) for assessing ongoing brain network dynamics. We conclude that continued investigation of the behavioral relevance of time-varying functional connectivity will be beneficial both in the development of comprehensive neural models of cognition, and in informing on best practices for studying brain network dynamics.

    View details for PubMedID 30465033

    View details for PubMedCentralID PMC6195165

  • Spontaneous cognitive processes and the behavioral validation of time-varying brain connectivity NETWORK NEUROSCIENCE Kucyi, A., Tambini, A., Sadaghiani, S., Keilholz, S., Cohen, J. R. 2018; 2 (4): 397–417
  • Distinct Patterns of Temporal and Directional Connectivity among Intrinsic Networks in the Human Brain JOURNAL OF NEUROSCIENCE Shine, J. M., Kucyi, A., Foster, B. L., Bickel, S., Wang, D., Liu, H., Poldrack, R. A., Hsieh, L., Hsiang, J., Parvizi, J. 2017; 37 (40): 9667–74


    To determine the spatiotemporal relationships among intrinsic networks of the human brain, we recruited seven neurosurgical patients (four males and three females) who were implanted with intracranial depth electrodes. We first identified canonical resting-state networks at the individual subject level using an iterative matching procedure on each subject's resting-state fMRI data. We then introduced single electrical pulses to fMRI pre-identified nodes of the default network (DN), frontoparietal network (FPN), and salience network (SN) while recording evoked responses in other recording sites within the same networks. We found bidirectional signal flow across the three networks, albeit with distinct patterns of evoked responses within different time windows. We used a data-driven clustering approach to show that stimulation of the FPN and SN evoked a rapid (<70 ms) response that was predominantly higher within the SN sites, whereas stimulation of the DN led to sustained responses in later time windows (85-200 ms). Stimulations in the medial temporal lobe components of the DN evoked relatively late effects (>130 ms) in other nodes of the DN, as well as FPN and SN. Our results provide temporal information about the patterns of signal flow between intrinsic networks that provide insights into the spatiotemporal dynamics that are likely to constrain the architecture of the brain networks supporting human cognition and behavior.SIGNIFICANCE STATEMENT Despite great progress in the functional neuroimaging of the human brain, we still do not know the precise set of rules that define the patterns of temporal organization between large-scale networks of the brain. In this study, we stimulated and then recorded electrical evoked potentials within and between three large-scale networks of the brain, the default network (DN), frontoparietal network (FPN), and salience network (SN), in seven subjects undergoing invasive neurosurgery. Using a data-driven clustering approach, we observed distinct temporal and directional patterns between the three networks, with FPN and SN activity predominant in early windows and DN stimulation affecting the network in later windows. These results provide important temporal information about the interactions between brain networks supporting human cognition and behavior.

    View details for PubMedID 28893929

  • Modulation of cognitive cerebello-cerebral functional connectivity by lateral cerebellar continuous theta burst stimulation NEUROIMAGE Rastogi, A., Cash, R., Dunlop, K., Vesia, M., Kucyi, A., Ghahremani, A., Downar, J., Chen, J., Chen, R. 2017; 158: 48–57


    Network connectivity measured with resting state functional magnetic resonance imaging (rsfMRI) has revealed the contribution of distinct cerebellar lobules to an array of brain wide networks sub-serving motor and cognitive processes. As distinct cerebellar lobules form relatively accessible nodes of different brain networks, this raises the possibility for site-specific modulation of network connectivity using non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS). Continuous theta burst transcranial magnetic stimulation (cTBS) induces long-lasting inhibition of cortical areas. Although previous studies have shown that cTBS of the lateral cerebellum modulates motor cortical excitability and improves symptoms in several movement disorders, the effect on cognitive domains has not been examined. We explored the immediate effects of cTBS in a sham-controlled study on the strength of intrinsic functional connectivity between cerebellar and cortical motor and cognitive regions in 12 participants. Lateral cerebellar cTBS significantly decreased functional connectivity with frontal and parietal cognitive regions, while connectivity with motor regions remained unaltered. Sham stimulation had no effect on either motor or cognitive connectivity. These results show that inhibitory cerebellar stimulation reduces intrinsic functional connectivity between different cortical areas, in keeping with the known connectivity pattern of the cerebellum. The results highlight the plasticity of cerebello-cerebral networks and indicate for the first time that this functional connectivity can be downregulated using an inhibitory neurostimulation paradigm. This may shed light on the pathophysiology of network dysfunction and is a potential treatment for cognitive and movement disorders.

    View details for PubMedID 28669908

  • Slow-5 dynamic functional connectivity reflects the capacity to sustain cognitive performance during pain. NeuroImage Cheng, J. C., Bosma, R. L., Hemington, K. S., Kucyi, A., Lindquist, M. A., Davis, K. D. 2017


    Some individuals are more distracted by pain during a cognitive task than others, representing poor pain coping. We have characterized individuals as A-type (attention dominates) or P-type (pain dominates) based on how pain interferes with task speed. The ability to optimize behavior during pain may relate to the flexibility in communication at rest between the dorsolateral prefrontal cortex (DLPFC) of the executive control network, and the anterior mid-cingulate cortex (aMCC) of the salience network (SN) - regions involved in cognitive-interference. The aMCC and aIns (SN hub) also signify pain salience; flexible communication at rest between them possibly allowing prioritizing task performance during pain. We tested the hypotheses that pain-induced changes in task performance are related to resting-state dynamic functional connectivity (dFC) between these region pairs (DLPFC-aMCC; aMCC-aIns). We found that 1) pain reduces task consistency/speed in P-type individuals, but enhances performance in A-type individuals, 2) task consistency is related to the FC dynamics within DLPFC-aMCC and aMCC-aIns pairs, 3) brain-behavior relationships are driven by dFC within the slow-5 (0.01-0.027Hz) frequency band, and 4) dFC across the brain decreases at higher frequencies. Our findings point to neural communication dynamics at rest as being associated with prioritizing task performance over pain.

    View details for DOI 10.1016/j.neuroimage.2017.06.005

    View details for PubMedID 28583880

  • Reply to Csifcsák and Mittner: Fitting data to neural models of mind-wandering. Proceedings of the National Academy of Sciences of the United States of America Kucyi, A., Esterman, M., Valera, E. M. 2017; 114 (30): E6033

    View details for PubMedID 28705871

    View details for PubMedCentralID PMC5544335

  • Pharmacological Modulation of Noradrenergic Arousal Circuitry Disrupts Functional Connectivity of the Locus Ceruleus in Humans. The Journal of neuroscience : the official journal of the Society for Neuroscience Song, A. H., Kucyi, A., Napadow, V., Brown, E. N., Loggia, M. L., Akeju, O. 2017; 37 (29): 6938–45


    State-dependent activity of locus ceruleus (LC) neurons has long suggested a role for noradrenergic modulation of arousal. However, in vivo insights into noradrenergic arousal circuitry have been constrained by the fundamental inaccessibility of the human brain for invasive studies. Functional magnetic resonance imaging (fMRI) studies performed during site-specific pharmacological manipulations of arousal levels may be used to study brain arousal circuitry. Dexmedetomidine is an anesthetic that alters the level of arousal by selectively targeting α2 adrenergic receptors on LC neurons, resulting in reduced firing rate and norepinephrine release. Thus, we hypothesized that dexmedetomidine-induced altered arousal would manifest with reduced functional connectivity between the LC and key brain regions involved in the regulation of arousal. To test this hypothesis, we acquired resting-state fMRI data in right-handed healthy volunteers 18-36 years of age (n = 15, 6 males) at baseline, during dexmedetomidine-induced altered arousal, and recovery states. As previously reported, seed-based resting-state fMRI analyses revealed that the LC was functionally connected to a broad network of regions including the reticular formation, basal ganglia, thalamus, posterior cingulate cortex (PCC), precuneus, and cerebellum. Functional connectivity of the LC to only a subset of these regions (PCC, thalamus, and caudate nucleus) covaried with the level of arousal. Functional connectivity of the PCC to the ventral tegmental area/pontine reticular formation and thalamus, in addition to the LC, also covaried with the level of arousal. We propose a framework in which the LC, PCC, thalamus, and basal ganglia comprise a functional arousal circuitry.SIGNIFICANCE STATEMENT Electrophysiological studies of locus ceruleus (LC) neurons have long suggested a role for noradrenergic mechanisms in mediating arousal. However, the fundamental inaccessibility of the human brain for invasive studies has limited a precise understanding of putative brain regions that integrate with the LC to regulate arousal. Our results suggest that the PCC, thalamus, and basal ganglia are key components of a LC-noradrenergic arousal circuit.

    View details for PubMedID 28626012

    View details for PubMedCentralID PMC5518422

  • Spontaneous default network activity reflects behavioral variability independent of mind-wandering PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Kucyi, A., Esterman, M., Riley, C. S., Valera, E. M. 2016; 113 (48): 13899-13904


    The brain's default mode network (DMN) is highly active during wakeful rest when people are not overtly engaged with a sensory stimulus or externally oriented task. In multiple contexts, increased spontaneous DMN activity has been associated with self-reported episodes of mind-wandering, or thoughts that are unrelated to the present sensory environment. Mind-wandering characterizes much of waking life and is often associated with error-prone, variable behavior. However, increased spontaneous DMN activity has also been reliably associated with stable, rather than variable, behavior. We aimed to address this seeming contradiction and to test the hypothesis that single measures of attentional states, either based on self-report or on behavior, are alone insufficient to account for DMN activity fluctuations. Thus, we simultaneously measured varying levels of self-reported mind-wandering, behavioral variability, and brain activity with fMRI during a unique continuous performance task optimized for detecting attentional fluctuations. We found that even though mind-wandering co-occurred with increased behavioral variability, highest DMN signal levels were best explained by intense mind-wandering combined with stable behavior simultaneously, compared with considering either single factor alone. These brain-behavior-experience relationships were highly consistent within known DMN subsystems and across DMN subregions. In contrast, such relationships were absent or in the opposite direction for other attention-relevant networks (salience, dorsal attention, and frontoparietal control networks). Our results suggest that the cognitive processes that spontaneous DMN activity specifically reflects are only partially related to mind-wandering and include also attentional state fluctuations that are not captured by self-report.

    View details for DOI 10.1073/pnas.1611743113

    View details for Web of Science ID 000388835700092

    View details for PubMedID 27856733

    View details for PubMedCentralID PMC5137714

  • Cortico-Cortical Connections of Primary Sensory Areas and Associated Symptoms in Migraine. eNeuro Hodkinson, D. J., Veggeberg, R., Kucyi, A., Van Dijk, K. R., Wilcox, S. L., Scrivani, S. J., Burstein, R., Becerra, L., Borsook, D. 2016; 3 (6)


    Migraine is a recurring, episodic neurological disorder characterized by headache, nausea, vomiting, and sensory disturbances. These events are thought to arise from the activation and sensitization of neurons along the trigemino-vascular pathway. From animal studies, it is known that thalamocortical projections play an important role in the transmission of nociceptive signals from the meninges to the cortex. However, little is currently known about the potential involvement of cortico-cortical feedback projections from higher-order multisensory areas and/or feedforward projections from principle primary sensory areas or subcortical structures. In a large cohort of human migraine patients (N = 40) and matched healthy control subjects (N = 40), we used resting-state intrinsic functional connectivity to examine the cortical networks associated with the three main sensory perceptual modalities of vision, audition, and somatosensation. Specifically, we sought to explore the complexity of the sensory networks as they converge and become functionally coupled in multimodal systems. We also compared self-reported retrospective migraine symptoms in the same patients, examining the prevalence of sensory symptoms across the different phases of the migraine cycle. Our results show widespread and persistent disturbances in the perceptions of multiple sensory modalities. Consistent with this observation, we discovered that primary sensory areas maintain local functional connectivity but express impaired long-range connections to higher-order association areas (including regions of the default mode and salience network). We speculate that cortico-cortical interactions are necessary for the integration of information within and across the sensory modalities and, thus, could play an important role in the initiation of migraine and/or the development of its associated symptoms.

    View details for DOI 10.1523/ENEURO.0163-16.2016

    View details for PubMedID 28101529

    View details for PubMedCentralID PMC5239993

  • The Neural Code for Pain: From Single-Cell Electrophysiology to the Dynamic Pain Connectome. Neuroscientist Kucyi, A., Davis, K. D. 2016


    Pain occurs in time. In naturalistic settings, pain perception is sometimes stable but often varies in intensity and quality over the course of seconds, minutes, and days. A principal aim in classic electrophysiology studies of pain was to uncover a neural code based on the temporal patterns of single neuron firing. In contrast, modern neuroimaging studies have placed emphasis on uncovering the spatial pattern of brain activity (or "map") that may reflect the pain experience. However, in the emerging field of connectomics, communication within and among brain networks is characterized as intrinsically dynamic on multiple time scales. In this review, we revisit the single-cell electrophysiological evidence for a nociceptive neural code and consider how those findings relate to recent advances in understanding systems-level dynamic processes that suggest the existence of a "dynamic pain connectome" as a spatiotemporal physiological signature of pain. We explore how spontaneous activity fluctuations in this dynamic system shape, and are shaped by, acute and chronic pain experiences and individual differences in those experiences. Highlighting the temporal dimension of pain, we aim to move pain theory beyond the concept of a static neurosignature and toward an ethologically relevant account of naturalistic dynamics.

    View details for PubMedID 27660241

  • Dynamic Brain Network Correlates of Spontaneous Fluctuations in Attention. Cerebral cortex Kucyi, A., Hove, M. J., Esterman, M., Hutchison, R. M., Valera, E. M. 2016


    Human attention is intrinsically dynamic, with focus continuously shifting between elements of the external world and internal, self-generated thoughts. Communication within and between large-scale brain networks also fluctuates spontaneously from moment to moment. However, the behavioral relevance of dynamic functional connectivity and possible link with attentional state shifts is unknown. We used a unique approach to examine whether brain network dynamics reflect spontaneous fluctuations in moment-to-moment behavioral variability, a sensitive marker of attentional state. Nineteen healthy adults were instructed to tap their finger every 600 ms while undergoing fMRI. This novel, but simple, approach allowed us to isolate moment-to-moment fluctuations in behavioral variability related to attention, independent of common confounds in cognitive tasks (e.g., stimulus changes, response inhibition). Spontaneously increasing tap variance ("out-of-the-zone" attention) was associated with increasing activation in dorsal-attention and salience network regions, whereas decreasing tap variance ("in-the-zone" attention) was marked by increasing activation of default mode network (DMN) regions. Independent of activation, tap variance representing out-of-the-zone attention was also time-locked to connectivity both within DMN and between DMN and salience network regions. These results provide novel mechanistic data on the understudied neural dynamics of everyday, moment-to-moment attentional fluctuations, elucidating the behavioral importance of spontaneous, transient coupling within and between attention-relevant networks.

    View details for PubMedID 26874182

  • The dynamic pain connectome TRENDS IN NEUROSCIENCES Kucyi, A., Davis, K. D. 2015; 38 (2): 86-95


    Traditionally, studies of how pain and attention modulate one another involved explicit cognitive-state manipulations. However, emerging evidence suggests that spontaneous brain-wide network communication is intrinsically dynamic on multiple timescales, and attentional states are in constant fluctuation. Here, in light of studies on neural mechanisms of spontaneous attentional fluctuations and pain variability, we introduce the concept of a dynamic 'pain connectome' in the brain. We describe how recent progress in our understanding of individual differences in intrinsic attention to pain and neural network dynamics in chronic pain can facilitate development of personalized pain therapies. Furthermore, we emphasize that the dynamics of pain-attention interactions must be accounted for in the contemporary search for a 'neural signature' of the pain connectome.

    View details for DOI 10.1016/j.tins.2014.11.006

    View details for Web of Science ID 000349724300004

    View details for PubMedID 25541287

  • Dynamic functional connectivity of the default mode network tracks daydreaming NEUROIMAGE Kucyi, A., Davis, K. D. 2014; 100: 471-480


    Humans spend much of their time engaged in stimulus-independent thoughts, colloquially known as "daydreaming" or "mind-wandering." A fundamental question concerns how awake, spontaneous brain activity represents the ongoing cognition of daydreaming versus unconscious processes characterized as "intrinsic." Since daydreaming involves brief cognitive events that spontaneously fluctuate, we tested the hypothesis that the dynamics of brain network functional connectivity (FC) are linked with daydreaming. We determined the general tendency to daydream in healthy adults based on a daydreaming frequency scale (DDF). Subjects then underwent both resting state functional magnetic resonance imaging (rs-fMRI) and fMRI during sensory stimulation with intermittent thought probes to determine the occurrences of mind-wandering events. Brain regions within the default mode network (DMN), purported to be involved in daydreaming, were assessed for 1) static FC across the entire fMRI scans, and 2) dynamic FC based on FC variability (FCV) across 30s progressively sliding windows of 2s increments within each scan. We found that during both resting and sensory stimulation states, individual differences in DDF were negatively correlated with static FC between the posterior cingulate cortex and a ventral DMN subsystem involved in future-oriented thought. Dynamic FC analysis revealed that DDF was positively correlated with FCV within the same DMN subsystem in the resting state but not during stimulation. However, dynamic but not static FC, in this subsystem, was positively correlated with an individual's degree of self-reported mind-wandering during sensory stimulation. These findings identify temporal aspects of spontaneous DMN activity that reflect conscious and unconscious processes.

    View details for DOI 10.1016/j.neuroimage.2014.06.044

    View details for Web of Science ID 000344235800042

    View details for PubMedID 24973603

  • Enhanced Medial Prefrontal-Default Mode Network Functional Connectivity in Chronic Pain and Its Association with Pain Rumination JOURNAL OF NEUROSCIENCE Kucyi, A., Moayedi, M., Weissman-Fogel, I., Goldberg, M. B., Freeman, B. V., Tenenbaum, H. C., Davis, K. D. 2014; 34 (11): 3969-3975


    Rumination is a form of thought characterized by repetitive focus on discomforting emotions or stimuli. In chronic pain disorders, rumination can impede treatment efficacy. The brain mechanisms underlying rumination about chronic pain are not understood. Interestingly, a link between rumination and functional connectivity (FC) of the brain's default mode network (DMN) has been identified within the context of mood disorders. We, and others, have also found DMN dysfunction in chronic pain populations. The medial prefrontal cortex (mPFC) is a key node of the DMN that is anatomically connected with the descending pain modulatory system. Therefore, we tested the hypothesis that in patients with chronic pain, the mPFC exhibits abnormal FC related to the patient's degree of rumination about their pain. Seventeen patients with idiopathic temporomandibular disorder (TMD) and 17 age- and sex-matched healthy controls underwent resting state functional MRI, and rumination about pain was assessed through the rumination subscale of the Pain Catastrophizing Scale. Compared with healthy controls, we found that TMD patients exhibited enhanced mPFC FC with other DMN regions, including the posterior cingulate cortex (PCC)/precuneus (PCu) and retrosplenial cortex. We also found that individual differences in pain rumination in the chronic pain patients (but not in healthy controls) were positively correlated to mPFC FC with the PCC/PCu, retrosplenial cortex, medial thalamus, and periaqueductal/periventricular gray. These data implicate communication within the DMN and of the DMN with the descending modulatory system as a mechanism underlying the degree to which patients ruminate about their chronic pain.

    View details for DOI 10.1523/JNEUROSCI.5055-13.2014

    View details for Web of Science ID 000332879500016

    View details for PubMedID 24623774

  • Mind wandering away from pain dynamically engages antinociceptive and default mode brain networks PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Kucyi, A., Salomons, T. V., Davis, K. D. 2013; 110 (46): 18692-18697


    Human minds often wander away from their immediate sensory environment. It remains unknown whether such mind wandering is unsystematic or whether it lawfully relates to an individual's tendency to attend to salient stimuli such as pain and their associated brain structure/function. Studies of pain-cognition interactions typically examine explicit manipulation of attention rather than spontaneous mind wandering. Here we sought to better represent natural fluctuations in pain in daily life, so we assessed behavioral and neural aspects of spontaneous disengagement of attention from pain. We found that an individual's tendency to attend to pain related to the disruptive effect of pain on his or her cognitive task performance. Next, we linked behavioral findings to neural networks with strikingly convergent evidence from functional magnetic resonance imaging during pain coupled with thought probes of mind wandering, dynamic resting state activity fluctuations, and diffusion MRI. We found that (i) pain-induced default mode network (DMN) deactivations were attenuated during mind wandering away from pain; (ii) functional connectivity fluctuations between the DMN and periaqueductal gray (PAG) dynamically tracked spontaneous attention away from pain; and (iii) across individuals, stronger PAG-DMN structural connectivity and more dynamic resting state PAG-DMN functional connectivity were associated with the tendency to mind wander away from pain. These data demonstrate that individual tendencies to mind wander away from pain, in the absence of explicit manipulation, are subserved by functional and structural connectivity within and between default mode and antinociceptive descending modulation networks.

    View details for DOI 10.1073/pnas.1312902110

    View details for Web of Science ID 000326830900083

    View details for PubMedID 24167282