The functional connectome reflects the endogenous pattern of information exchange among brain regions. However, the role of this fundamental network organization in mental disorders remains elusive, in part because its function in healthy cognition is largely unknown. The urgent need and translational importance of closing this knowledge gap is reflected in the NIMH?s strategic objective 1.3 to ?map the connectomes for mental illnesses?. The functional connectome is traditionally observed using functional Magnetic Resonance Imaging (fMRI), since this method provides a means of investigating neural connections across the whole brain with high spatial resolution. As observed with fMRI, functional connectivity is not static, instead shifting between various network configurations. While this connectome flexibility is well-documented, its relation to moment-to-moment cognition is unknown. To better understand this relationship, novel experimental paradigms must be developed to characterize the contribution of connectome reconfigurations to trial-by-trial behavioral variability. Additionally, since fMRI is an indirect measure of neural activity and prone to artifacts, the fidelity of connectome dynamics should be established using a more direct measure of neural activity (Electroencephalography, EEG) concurrently with fMRI. The current project uses simultaneous fMRI and EEG to characterize intrinsic connectome states and relate them to concurrent cognitive processes. In the current study we look to address three aims: 1) to identify cognitively significant connectome states by their impact on behavior, 2) to identify such states in the resting brain and quantify their temporal flexibility, and 3) to link this connectome flexibility to cognitive flexibility, the ability to shift among tasks and mental sets. We expect to find distinct and behaviorally relevant connectome states differing in two measures: level of global integration among networks and involvement of the default mode network (DMN). Further, we posit that connectome flexibility, the spontaneous iterations among the identified connectome states, predicts individual differences in cognitive flexibility. Cognitive flexibility is a trait implicated in numerous psychopathologies. A link between this function and connectome flexibility would have a broad clinical impact, establishing which dynamic connectome features are most promising for future biomarkers and treatment targets.

Public Health Relevance

Communication between regions of the brain is directed by a functional network structure. The role of this organization, however, is unknown in both healthy cognition and mental disorders. Elucidating how this functional connectivity structure and its various reconfigurations contribute to flexible cognition is critical for understanding the healthy brain, as well as the neurobiology of mental disorders and the development of future treatments.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Cognition and Perception Study Section (CP)
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Rossi, Andrew
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University of Illinois Urbana-Champaign
Schools of Arts and Sciences
United States
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