My research focuses on discovering the cognitive and neural mechanisms that make human behavior flexible and intelligent.
Brain network mechanisms of flexible cognitive control Flexible control – a capacity supporting adaptive, goal-directed behavior important in daily life – is affected in a variety of mental illnesses, markedly reducing quality of life. See Cole & Schneider (2007) for evidence that flexible control is implemented by a set of integrated brain regions sometimes referred to as the cognitive control network. See Cole, Pathak, et al. (2010) and Cole, Yarkoni, et al. (2012) for evidence that this network implements control via its high connectivity throughout the brain, as indexed by global brain connectivity (GBC). See Cole, Anticevic, et al. (2011) for a recent demonstration of how a breakdown in the GBC of a core node of this network may contribute to the profound cognitive control deficits associated with schizophrenia.
Rapid instructed task learning (RITL; "rittle")
A key aspect of flexible control is our ability to rapidly reconfigure our minds to perform a nearly infinite variety of possible tasks. For instance, you utilized RITL the first time you used a cell phone – transfering what you knew about 'land line' phones while expanding what was possible with such a device. Comprehensive understanding of this ability would have important implications for research in education, aging, and a variety of mental illnesses. See Cole, Bagic, et al. (2010) for a novel cognitive paradigm for investigating RITL, as well as evidence that RITL involves a specific shift in dynamics within prefrontal cortex. See Cole, Etzel, et al. (2011) for evidence that RITL is possible due to rapid transfer of practiced task rule representations within prefrontal cortex to novel contexts. See Cole, Laurent, & Stocco (2013) for a review of RITL findings and an integrative theory of how prefrontal cortex may implement RITL abilities and cognitive flexibility generally.
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On the Web:
Neurevolution – A blog dedicated to communicating cognitive neuroscience to a broad audience
Meiran N., Cole M.W., and Braver T.S. (In Press). "When Planning Results in Loss of Control: Intention-Based Reflexivity and Proactive Control". Book chapter in: Seebass, G., Schmitz, M., & Gollwitzer, P. M. Acting intentionally and its limits: Individuals, groups, institutions. Berlin: De Gruyter.
Anticevic A., Brumbaugh M.S., Winkler A.M., Lombardo L.E., Barrett J., Corlett P.R., Kober H., Gruber J., Repovs G., Cole M.W., Krystal J.H., Pearlson G.D., & Glahn D.C. (In Press). "Global prefrontal and fronto-amygdala dysconnectivity in bipolar I disorder with psychosis history." Biological Psychiatry.
The human ability to flexibly adapt to novel circumstances is extraordinary. Perhaps the most illustrative, yet underappreciated, form of this cognitive flexibility is rapid instructed task learning (RITL) – the ability to rapidly reconfigure our minds to perform new tasks from instructions. This ability is important for everyday life (e.g., learning to use new technologies) and is used to instruct participants in nearly every study of human cognition. We review the development of RITL as a circumscribed domain of cognitive neuroscience investigation, culminating in recent demonstrations that RITL is implemented via brain circuits centered on lateral prefrontal cortex. We then build on this and the recent discovery of compositional representations within lateral prefrontal cortex to develop an integrative theory of cognitive flexibility and cognitive control that identifies mechanisms that may enable RITL within the human brain. The insights gained from this new theoretical account have important implications for further developments and applications of RITL research.
Etzel, J.A., Cole M.W., Braver T.S. (2012). "Looking Outside the Searchlight". In G. Langs, I. Rish, M. Grosse-Wentrup, & B. Murphy (Eds.), Machine Learning and Interpretation in Neuroimaging. Lecture Notes in Computer Science. (vol. 7263, pp. 26–33). Springer Berlin / Heidelberg. doi:10.1007/978-3-642-34713-9_4
Anticevic A., Cole M.W., Murray J., Corlett P.R., Wang X., & Krystal J.H. (2012). "The role of default network deactivation in cognition and disease". Trends in Cognitive Sciences. 16(12): 584–592; doi: 10.1016/j.tics.2012.10.008.
A considerable body of evidence has accumulated over recent years on the functions of the default-mode network (DMN) – a set of brain regions whose activity is high when the mind is not engaged in specific behavioral tasks and low during focused attention on the external environment. In this review, we focus on DMN suppression and its functional role in health and disease, summarizing evidence that spans several disciplines, including cognitive neuroscience, pharmacological neuroimaging, clinical neuroscience, and theoretical neuroscience. Collectively, this research highlights the functional relevance of DMN suppression for goal-directed cognition, possibly by reducing goal-irrelevant functions supported by the DMN (e.g., mind-wandering), and illustrates the functional significance of DMN suppression deficits in severe mental illness.
Control of thought and behavior is fundamental to human intelligence. Evidence suggests a frontoparietal brain network implements such cognitive control across diverse contexts. We identify a mechanism — global connectivity — by which components of this network might coordinate control of other networks. A lateral prefrontal cortex (LPFC) region’s activity was found to predict performance in a high control demand working memory task and also to exhibit high global connectivity. Critically, global connectivity in this LPFC region, involving connections both within and outside the frontoparietal network, showed a highly selective relationship with individual differences in fluid intelligence. These findings suggest LPFC is a global hub with a brainwide influence that facilitates the ability to implement control processes central to human intelligence.
In this review, the authors discuss the seemingly paradoxical loss of control associated with states of high readiness to execute a plan, termed “intention-based reflexivity.” The review suggests that the neuro-cognitive systems involved in the preparation of novel plans are different than those involved in preparation of practiced plans (i.e., those that have been executed beforehand). When the plans are practiced, intention-based reflexivity depends on the prior availability of response codes in long-term memory (LTM). When the plans are novel, reflexivity is observed when the plan is pending and the goal has not yet been achieved. Intention-based reflexivity also depends on the availability of working-memory (WM) limited resources and the motivation to prepare. Reflexivity is probably related to the fact that, unlike reactive control (once a plan is prepared), proactive control tends to be relatively rigid.
Flexible, adaptive behavior is thought to rely on abstract rule representations within lateral prefrontal cortex (LPFC), yet it remains unclear how these representations provide such flexibility. We recently demonstrated that humans can learn complex novel tasks in seconds. Here we hypothesized that this impressive mental flexibility may be possible due to rapid transfer of practiced rule representations within LPFC to novel task contexts. We tested this hypothesis using functional MRI and multivariate pattern analysis, classifying LPFC activity patterns across 64 tasks. Classifiers trained to identify abstract rules based on practiced task activity patterns successfully generalized to novel tasks. This suggests humans can transfer practiced rule representations within LPFC to rapidly learn new tasks, facilitating cognitive performance in novel circumstances.
A fundamental challenge for understanding neuropsychiatric disease is identifying sources of individual differences in psychopathology, especially when there is substantial heterogeneity of symptom expression such as is found in schizophrenia. We hypothesized that such heterogeneity may arise in part from consistently widespread yet variably patterned alterations in the connectivity of focal brain regions. Methods
We used resting state functional MRI to identify variable global dysconnectivity in 23 patients with DSM-IV schizophrenia relative to 22 age, gender, and parental socioeconomic status matched controls using a novel global brain connectivity (GBC) functional MRI method that is robust to high variability across individuals. We examined cognitive functioning using a modified Sternberg task and subtests from the Wechsler Adult Intelligence Scale - Third Edition. We measured symptom severity using the Scale for Assessment of Positive and Negative Symptoms. Results
We identified a dorsolateral prefrontal cortex (DLPFC) region with global and highly variable dysconnectivity involving within-PFC under-connectivity and non-PFC over-connectivity in patients. Variability in this ‘under/over’ pattern of dysconnectivity strongly predicted the severity of cognitive deficits (matrix reasoning IQ, verbal IQ, and working memory performance) as well as individual differences in every cardinal symptom domain of schizophrenia (poverty, reality distortion, and disorganization). Conclusion
These results suggest that global dysconnectivity underlies DLPFC involvement in the neuropathology of schizophrenia. Further, these results demonstrate the possibility that specific patterns of dysconnectivity with a given network hub region may explain individual differences in symptom presentation in schizophrenia. Critically, such findings may extend to other neuropathologies with diverse presentation.
The ability to rapidly reconfigure our minds to perform novel tasks is important for adapting to an ever-changing world, yet little is understood about its basis in the brain. Further, it is unclear how this kind of task preparation changes with practice. Previous research suggests that prefrontal cortex (PFC) is essential when preparing to perform either novel or practiced tasks. Building upon recent evidence that PFC is organized in an anterior-to-posterior hierarchy, we postulated that novel and practiced task preparation would differentiate hierarchically distinct regions within PFC across time. Specifically, we hypothesized and confirmed using functional MRI and magnetoencephalography with humans that novel task preparation is a bottom-up process that involves lower-level rule representations in dorsolateral PFC (DLPFC) prior to a higher-level rule-integrating task representation in anterior PFC (aPFC). In contrast, we identified a complete reversal of this activity pattern during practiced task preparation. Specifically, we found that practiced task preparation is a top-down process that involves a higher-level rule-integrating task representation (recalled from long-term memory) in aPFC prior to lower-level rule representations in DLPFC. These findings reveal two distinct yet highly inter-related mechanisms for task preparation, one involving task set formation from instructions during rapid instructed task learning and the other involving task set retrieval from long-term memory to facilitate familiar task performance. These two mechanisms demonstrate the exceptional flexibility of human PFC as it rapidly reconfigures cognitive brain networks to implement a wide variety of possible tasks.
Investigations of individual differences have become increasingly important in the cognitive neuroscience of executive control. For instance, individual variation in lateral prefrontal cortex function (and that of associated regions) has recently been used to identify contributions of executive control processes to a number of domains, including working memory capacity, anxiety, reward/motivation, and emotion regulation. However, the origins of such individual differences remain poorly understood. Recent progress toward identifying the genetic and environmental sources of variation in neural traits, in combination with progress in identifying the causal relationships between neural and cognitive processes, will be essential for developing a mechanistic understanding of executive control.
Recent advances in brain connectivity methods have made it possible to identify hubs – the brain’s most globally connected regions. Such regions are essential for coordinating brain functions due to their connectivity with numerous regions with a variety of specializations. Current structural and functional connectivity methods generally agree that default mode network (DMN) regions have among the highest global brain connectivity (GBC). We developed two novel statistical approaches using resting state functional connectivity MRI – weighted and unweighted GBC (wGBC and uGBC) – to test the hypothesis that the highest global connectivity also occurs in the cognitive control network (CCN), a network anti-correlated with the DMN across a variety of tasks. High global connectivity was found in both CCN and DMN. The newly developed wGBC approach improves upon existing methods by quantifying inter-subject consistency, quantifying the highest GBC values by percentage, and avoiding arbitrary connection strength thresholding. The uGBC approach is based on graph theory and includes many of these improvements, but still requires an arbitrary connection threshold. We found high GBC in several subcortical regions (e.g., hippocampus, basal ganglia) only with wGBC despite the regions’ extensive anatomical connectivity. These results demonstrate the complementary utility of wGBC and uGBC analyses for the characterization of the most highly connected, and thus most functionally important, regions of the brain. Additionally, the high connectivity of both the CCN and the DMN demonstrates that brain regions outside primary sensory-motor networks are highly involved in coordinating information throughout the brain.
Cognitive neuroscience research relies, in part, on homologies between the brains of human and non-human primates. A quandary therefore arises when presumed anatomical homologues exhibit different functional properties. Such a situation has recently arisen in the case of the anterior cingulate cortex (ACC). In humans, numerous studies suggest a role for ACC in detecting conflicts in information processing. Studies of macaque monkey ACC, in contrast, have failed to find conflict-related responses. We consider several interpretations of this discrepancy, including differences in research methodology and cross-species differences in functional neuroanatomy. New directions for future research are outlined, emphasizing the importance of distinguishing illusory cross-species differences from the true evolutionary differences that make our species unique.
Consensus across hundreds of published studies indicates that the same regions are involved in many forms of cognitive control. Using functional magnetic resonance imaging (fMRI), we found that these coactive regions form a functionally connected cognitive control network (CCN). Network status was identified by convergent methods, including: high interregional correlations during rest and task performance, consistently higher correlations within the CCN than the rest of cortex, co-activation in a visual search task, and mutual sensitivity to decision difficulty. Regions within the CCN include anterior cingulate cortex / pre-supplementary motor area (ACC/pSMA), dorsolateral prefrontal cortex (DLPFC), inferior frontal junction (IFJ), anterior insular cortex (AIC), dorsal pre-motor cortex (dPMC), and posterior parietal cortex (PPC). We used a novel visual line search task which included periods when the probe stimuli were occluded but subjects had to maintain and update working memory in preparation for the sudden appearance of a probe stimulus. The six CCN regions operated as a tightly coupled network during the ‘non-occluded’ portions of this task, with all regions responding to probe events. In contrast, the network was differentiated during occluded search. DLPFC, not ACC/pSMA, was involved in target memory maintenance when probes were absent, while both regions became active in preparation for difficult probes at the end of each occluded period. This approach illustrates one way in which a neuronal network can be identified, its high functional connectivity established, and its components dissociated in order to better understand the interactive and specialized internal mechanisms of that network.
The ability to select an appropriate response among competing alternatives is a fundamental requirement for successful performance of a variety of everyday tasks. Recent research suggests that a frontal–parietal network of brain regions (including dorsal prefrontal, dorsal premotor and superior parietal cortices) mediate response selection for spatial material. Most of this research has used blocked experimental designs. Thus, the frontal–parietal activity reported may be due either to tonic activity across a block or to processing occurring at the trial level. Our current event-related fMRI study investigated response selection at the level of the trial in order to identify possible response selection sub-processes. In the study, participants responded to a visually presented stimulus with either a spatially compatible or incompatible manual response. On some trials, several seconds prior to stimulus onset, a cue indicated which task was to be performed. In this way we could identify separate brain regions for task preparation and task performance, if they exist. Our results showed that the frontal–parietal network for spatial response selection activated both during task preparation as well as during task performance. We found no evidence for preparation specific brain mechanisms in this task. These data suggest that spatial response selection and response preparation processes rely on the same neurocognitive mechanisms.
Recent functional imaging studies of working memory (WM) have suggested a relationship between the requirement for response selection and activity in dorsolateral prefrontal (DLPFC) and parietal regions. Although a number of WM operations are likely to occur during response selection, the current study was particularly interested in the contribution of this neural network to WM-based response selection when compared to the selection of an item from a list being maintained in memory, during a verbal learning task. The design manipulated stimulus–response mappings so that selecting an item from memory was not always accompanied with selecting a motor response. Functional activation during selection supported previous findings of fronto-parietal involvement, although in contrast to previous findings left, rather than right, DLPFC activity was significantly more active for selecting a memory-guided motor response, when compared to selecting an item currently maintained in memory or executing a memory-guided response. Our results contribute to the debate over the role of fronto-parietal activity during WM tasks, suggesting that this activity appears particularly related to response selection, potentially supporting the hypothesized role of prefrontal activity in biasing attention toward task-relevant material in more posterior regions.
We investigated the voluntary control of motor behavior by studying the process of deciding whether or not to execute a movement. We imaged the human dorsal cortex while subjects performed a countermanding task that allowed us to manipulate the probability that subjects would be able to cancel a planned saccade in response to an imperative stop signal. We modeled the behavioral data as a race between gaze-shifting mechanisms and gaze-holding mechanisms towards a finish line where a saccade is generated or canceled, and estimated that saccade cancelation took ∼160 ms. The frontal eye fields showed greater activation on stop signal trials regardless of successful cancelation, suggesting coactivation of saccade and fixation mechanisms. The supplementary eye fields, however, distinguished between successful and unsuccessful cancelation, suggesting a role in monitoring performance. These oculomotor regions play distinct roles in the decision processes mediating saccadic choice.
National Science Foundation Graduate Research Fellowship
Honors and Awards:
Fellow at the Summer Institute in Cognitive Neuroscience, 2011, Santa Barbara, CA
NeuroImage Editor’s Choice Award(2010), Methods and Modeling Section
For Cole et al. 2010, “Identifying the brain’s most globally connected regions”
Awarded by the editors of NeuroImage in acknowledgement of a study’s importance and high impact
National Science Foundation Graduate Research Fellow, 2005-2008 A three-year grant awarded to graduate students whose plans for research have “intellectual merit and beneficial implications for society”
National Science Foundation Integrative Graduate Education and Research Traineeship (IGERT) Fellow, 2007 Awarded to science graduate students “who will pursue careers in research and education, with the interdisciplinary backgrounds, deep knowledge in chosen disciplines, and technical, professional, and personal skills to become, in their own careers, leaders and creative agents for change.”
Graduated with Highest Honors in Cognitive Science from UC Berkeley Awarded highest honors based on significant contribution to a research project and high quality honors thesis as judged by professors Mark D’Esposito, M.D. and Robert Knight, M.D.
President of the Department of Neuroscience Graduate Student Organization (University of Pittsburgh, Fall 2006 – Fall 2007)
Cognitive Science Student Association of UC Berkeley (officer from Spring 2001 to Fall 2003)
Published Abstracts and Presentations:
Cole M.W. (April, 2013). Brain Network Mechanisms of Flexible Cognitive Control in Health and Disease. Invited talk presented at the Department of Psychiatry, Yale, New Haven, CT.
Cole M.W. (January, 2013). Brain Network Mechanisms of Flexible Cognitive Control. Invited talk presented at the McGovern Institute for Brain Research, MIT, Cambridge, MA.
Cole M.W. (December, 2012). A role for the brain network mechanisms of flexible cognitive control in human intelligence. Invited talk presented at the International Society for Intelligence Research, San Antonio, TX.
Cole M.W. (November, 2012). Global Brain Connectivity and Other Graph Theoretical Approaches: Methods and Findings. Invited talk presented at The Ohio State University, Columbus, OH.
Cole M.W. (November, 2012). Brain network mechanisms of flexible cognitive control. Invited talk presented at the Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, NJ.
Cole M.W., Etzel J., and Braver T.S. (April, 2012). Identifying Flexible Hubs:
A Novel Mechanism for Flexible Cognitive Control. Talk presented at Cognitive Neuroscience Society, Chicago, IL.
Cole M.W., Yarkoni T., Repovs G., and Braver T.S. (November, 2011). Flexible hubs: Global brain connectivity correlates of human intelligence. Talk presented at Society for Neuroscience, Washington, D.C.
Repovs, G., Anticevic, A., Cole, M.W., & Barch, D.M. (May, 2011). Simulated comparisons of slow and rapid event-related task-based functional connectivity. Poster presented at Society for Biological Psychiatry, San Francisco, CA.
Cole M.W., Yarkoni T., Repovs G., Braver T.S. (April, 2011). Flexible hubs: Global brain connectivity correlates of human intelligence. Poster presented at Cognitive Neuroscience Society, San Francisco, CA.
Cole M.W., Etzel J.A., Zacks J.M., Braver T.S. (November, 2010). Independent and distributed coding of
task-set decision rules within prefrontal cortex. Poster presented at Society for Neuroscience, San Diego, CA.
Cole M.W., Anticevic A., Repovs G., Barch D. (August, 2010). Locus of dysconnectivity: Dorsolateral prefrontal connectivity correlates with the cardinal symptoms of schizophrenia. Poster presented at the Gordan Research Conference: Neurobiology of Cognition, Waterville Valley, NH.
Cole M.W., Bagic A., Kass R., Schneider W. (October, 2009). Rapid Task Learning as a Window into the Neural Basis of Executive Control. Poster presented at Society for Neuroscience, Chicago, IL.
Cole M.W., Schneider W. (June, 2009). From Symbols to Rules to Complex Behaviors: The Neural Basis of Rapid Instructed Task Learning. Poster presented at Human Brain Mapping, San Francisco, CA.
Cole M.W., Pathak S., Schneider W. (June, 2009). Identifying the Brain’s Most Globally Interactive Regions. Poster presented at Human Brain Mapping, San Francisco, CA.
Cole M.W., Kunkel A., Martins B., Schneider W. (November, 2008). The Neural Basis of Rapid Instructed Task Learning. Poster presented at Society for Neuroscience, Washington, DC.
Pathak S.*, Cole M.W.*, Schneider W. (November, 2008). Identifying the Brain's Most Globally Interactive Regions. Poster presented at Society for Neuroscience, Washington, DC. *First two authors contributed equally
Cole M.W., Martins B., Schneider W. (April, 2008). The Neural Basis of Rapid Instructed Task Learning. Poster presented at Cognitive Neuroscience Society, San Francisco, CA.
Pathak S., Martins B., Cole M.W., Schneider W. (April, 2008). Anatomical and Functional Segmentation of the Cognitive Control Network: Supporting a preliminary cognitive control network connectome. Poster presented at Cognitive Neuroscience Society, San Francisco, CA.
Cole M.W., Pathak S., Schneider W. (April, 2008). Medial Frontal Cortex Directs Attention along Multiple Pathways
to Resolve Perceptual Decision Difficulty. Poster presented at Cognitive Neuroscience Society, San Francisco, CA.
Cole M.W., Schneider W. (June, 2007). Perceptual Decision Making Is Mediated by the Cognitive Control Network via ACC/pre-SMA to DLPFC Connectivity. Poster presented at Human Brain Mapping, Chicago, IL.
Cole M.W., Schneider W. (May, 2007). Causal Connectivity Within a Cognitive Control Network During Perceptual Decision Making. Poster presented at Cognitive Neuroscience Society, New York, NY.
Cole M.W., Schneider W. (June, 2006). Dissociation of anterior cingulate, dorsolateral prefrontal, and premotor cortex during a visual search task reveals specialized roles within a commonly activated fronto-parietal network. Poster presented at Human Brain Mapping, Florence, Italy.
Schneider W., Siegle G., McHugo M., Gemmer L., Jones D., Fissell K., Koerbel L., Suzuki I., Jung K., Goldberg R., Wheeler M., Cole M.W., Hill N. (June, 2006). 2006 Pittsburgh Brain Activity Interpretation Competition: Inferring Experience Based Cognition from fMRI Data. Poster presented at Human Brain Mapping, Florence, Italy.
Cole M.W., Schneider W. (April, 2006). Dissociation of anterior cingulate, dorsolateral prefrontal, and fronto-polar cortex during a visual search task reveals specialized roles within a commonly activated fronto-parietal network. Poster presented at Cognitive Neuroscience Society, San Francisco, CA.
Cole M.W., Schneider W. (November, 2005). Less Working Memory, More Control: Greater BOLD Response to Overcoming Prepotency in Prefrontal and Parietal Cortices. Talk presented at Society for Neuroscience, Washington, D.C.
Schumacher E.H., Cole M.W., Singer A., D’Esposito M. (October, 2004). Distinguishing Response Selection Sub-processes with Functional Magnetic Resonance Imaging. Poster presented at Society for Neuroscience, San Diego, CA.
Schumacher E.H., Cole M.W., Singer A., D’Esposito M. (April, 2004). Distinguishing Response Selection Sub-processes with Functional Magnetic Resonance Imaging. Poster presented at Cognitive Neuroscience Society, San Francisco, CA.
Curtis C.E., Cole M.W., Rao V., Ollinger J., D’Esposito M. (April, 2004). Canceling planned action: An fMRI study of countermanding saccades. Poster presented at Cognitive Neuroscience Society, San Francisco, CA.
Curtis C.E., Cole M.W., Rao V., Ollinger J., D’Esposito M. (October, 2003). Canceling planned action: An fMRI study of countermanding saccades. Poster presented at Society for Neuroscience, New Orleans, LA.
Statistical tools: R - A free software environment for statistical computing and graphics MATLAB - A commercial software environment for statistical computing and graphics
Functional neuroimaging analysis tools: NITRC - A comprehensive list of neuroimaging tools AFNI - Analysis of fMRI and PET (free) MRIcron - Simple tool for visualizing structural and functional MRI data MNE - Analysis of EEG and MEG FieldTrip - Analysis of EEG and MEG in MATLAB