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Cole, M. W.

Publications and source records attributed to Cole, M. W..

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A whole-brain and cross-diagnostic perspective on functional brain network dysfunction

A wide variety of mental disorders have been associated with resting-state functional network alterations, which are thought to contribute to the cognitive changes underlying mental illness. These observations have seemed to support various theories postulating large-scale disruptions of brain systems in mental illness. However, existing approaches isolate differences in network organization without putting those differences in broad, whole-brain perspective. Using a graph distance measure - connectome-wide correlation - we found that whole-brain resting-state functional network organization in humans is highly similar across a variety of mental diseases and healthy controls. This similarity was observed across autism spectrum disorder, attention-deficit hyperactivity disorder, and schizophrenia. Nonetheless, subtle differences in network graph distance were predictive of diagnosis, suggesting that while functional connectomes differ little across health and disease those differences are informative. Such small network alterations may reflect the fact that most psychiatric patients maintain overall cognitive abilities similar to those of healthy individuals (relative to, e.g., the most severe schizophrenia cases), such that whole-brain functional network organization is expected to differ only subtly even for mental diseases with devastating effects on everyday life. These results suggest a need to reevaluate neurocognitive theories of mental illness, with a role for subtle functional brain network changes in the production of an array of mental diseases.

neuroscience

Task activations produce spurious but systematic inflation of task functional connectivity estimates

Most neuroscientific studies have focused on task-evoked activations (activity amplitudes at specific brain locations), providing limited insight into the functional relationships between separate brain locations. Task-state functional connectivity (FC) - statistical association between brain activity time series during task performance moves beyond task-evoked activations by quantifying functional interactions during tasks. However, many task-state FC studies do not remove the first-order effect of taskevoked activations prior to estimating task-state FC. It has been argued that this results in the ambiguous inference \"likely active or interacting during the task\", rather than the intended inference \"likely interacting during the task\". Utilizing a neural mass computational model, we verified that task-evoked activations substantially and inappropriately inflate task-state FC estimates, especially in functional MRI (fMRI) data. Various methods attempting to address this problem have been developed, yet the efficacies of these approaches have not been systematically assessed. We found that most standard approaches for fitting and removing mean task-evoked activations were unable to correct these inflated correlations. In contrast, methods that flexibly fit mean task-evoked response shapes effectively corrected the inflated correlations without reducing effects of interest. Results with empirical fMRI data confirmed the models predictions, revealing activation-induced task-state FC inflation for both Pearson correlation and psychophysiological interaction (PPI) approaches. These results demonstrate that removal of mean task-evoked activations using an approach that flexibly models task-evoked response shape is an important preprocessing step for valid estimation of task-state FC.\n\nHighlightsO_LIComputational model shows task inflation of functional connectivity estimates\nC_LIO_LIHemodynamic responses cause task activations to further inflate estimates\nC_LIO_LIStandard approaches to remove task activations leave many false positives\nC_LIO_LIMethods that flexibly fit hemodynamic response shape effectively correct inflation\nC_LIO_LICorrection of functional connectivity inflation verified with empirical fMRI data\nC_LI

neuroscience

Network dimensionality underlies flexible representation of cognitive information

Many studies have identified the role of localized and distributed cognitive functionality by mapping either local task-related activity or distributed functional connectivity (FC). However, few studies have directly explored the relationship between a brain regions localized task activity and its distributed task FC. Here we systematically evaluated the differential contributions of task-related activity and FC changes to identify a relationship between localized and distributed processes across the cortical hierarchy. We found that across multiple tasks, the magnitude of regional task-evoked activity was high in unimodal areas, but low in transmodal areas. In contrast, we found that task-state FC was significantly reduced in unimodal areas relative to transmodal areas. This revealed a strong negative relationship between localized task activity and distributed FC across cortical regions that was associated with the previously reported principal gradient of macroscale organization. Moreover, this dissociation corresponded to hierarchical cortical differences in the intrinsic timescale estimated from resting-state fMRI and region myelin content estimated from structural MRI. Together, our results contribute to a growing literature illustrating the differential contributions of a hierarchical cortical gradient representing localized and distributed cognitive processes. HighlightsO_LITask activations and functional connectivity changes are negatively correlated across cortex C_LIO_LITask activation and connectivity dissociations reflect differences in localized and distributed processes in cortex C_LIO_LIDifferences in localized and distributed processes are associated with differences in intrinsic timescale organization C_LIO_LIDifferences in localized and distributed processes are associated with differences in cortical myelin content C_LIO_LICortical heterogeneity in localized and distributed processes revealed by activity flow mapping prediction error C_LI

neuroscience

Mapping the human brain’s cortical-subcortical functional network organization

Highlights O_LILarge-scale functional network map of the entire human brain\nC_LIO_LICortical networks based on multiband fMRI, recently-identified regions\nC_LIO_LISubcortical extension of networks covering all subcortical structures\nC_LIO_LIMultiple quality assessments demonstrate robustness of functional networks\nC_LIO_LINetwork atlas released as public resource, providing framework for future studies\nC_LI\n\nABSTRACTUnderstanding complex systems such as the human brain requires characterization of the systems architecture across multiple levels of organization - from neurons, to local circuits, to brain regions, and ultimately large-scale brain networks. Here we focus on characterizing the human brains large-scale network organization, as it provides an overall framework for the organization of all other levels. We developed a highly principled approach to identify cortical network communities at the level of functional systems, calibrating our community detection algorithm using extremely well-established sensory and motor systems as guides. Building on previous network partitions, we replicated and expanded upon well-known and recently identified networks, including several higher-order cognitive networks such as a left-lateralized language network. We expanded these cortical networks to subcortex, revealing 358 highly organized subcortical parcels that take part in forming whole-brain functional networks. Notably, the identified subcortical parcels are similar in number to a recent estimate of the number of cortical parcels (360). This whole-brain network atlas - released as an open resource for the neuroscience community - places all brain structures across both cortex and subcortex into a single large-scale functional framework, with the potential to facilitate a variety of studies investigating large-scale functional networks in health and disease.

neuroscience

Global connectivity of the frontoparietal cognitive control network is related to depression symptoms in undiagnosed individuals

We all vary in our mental health, even among healthy (undiagnosed) individuals. Understanding this variability may reveal factors driving the onset of mental illness, as well as factors driving sub-clinical mental health problems that can still influence quality of life. To better understand the large-scale brain network mechanisms underlying this variability in mental health we examined the relationship between mental health symptoms and resting-state functional connectivity patterns in cognitive control systems. The frontoparietal cognitive control network (FPN) consists of flexible hubs that can regulate distributed systems depending on current goals, and dysfunction in the FPN has been identified in a variety of psychiatric disorders. Alterations in FPN connectivity may influence mental health by disrupting the ability to regulate symptoms in a goal-directed manner. This suggests that the FPN may play an important role in the promotion and maintenance of mental health generally. Here we test the hypothesis that disruptions in FPN connectivity are related to mental health (depression) symptoms even among healthy individuals. This hypothesis is consistent with a general role of FPN in the regulation of mental health symptoms. We found that depression symptoms were negatively correlated with between-network global connectivity (BGC) of the FPN as well as the default mode network (DMN). This suggests that decreased connectivity between the FPN (and, separately, DMN) and the rest of the brain is related to increased depression symptoms among undiagnosed individuals. These findings complement previous clinical studies to support the hypothesis that global FPN connectivity contributes to the regulation of mental health symptoms across both mentally healthy and unhealthy individuals.

neuroscience

Cognitive task information is transferred between brain regions via resting-state network topology

Resting-state network connectivity has been associated with a variety of cognitive abilities, yet it remains unclear how these connectivity properties might contribute to the neurocognitive computations underlying these abilities. We developed a new approach - information transfer mapping - to test the hypothesis that resting-state functional network topology describes the computational mappings between brain regions that carry cognitive task information. Here we report that the transfer of diverse, task-rule information in distributed brain regions can be predicted based on estimated activity flow through resting-state network connections. Further, we find that these task-rule information transfers are coordinated by global hub regions within cognitive control networks. Activity flow over resting-state connections thus provides a large-scale network mechanism for cognitive task information transfer and global information coordination in the human brain, demonstrating the cognitive relevance of resting-state network topology.

neuroscience