Neurobiology and Cognitive Role of Slow Brain Network Fluctuations

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CENTER ABSTRACT: Patterns of ongoing thought vary over time, and experiences like “mind-wandering” show that cognition is often decoupled from an ongoing task. A traditional assumption is that states of off-task cognition reflects a cognitive error. An emerging alternative view is that switching between “off-task” and on- task states is a fundamental feature of human cognition, facilitating long term goals and mental health. Experimental findings over the past several decades show that off-task cognition is accompanied by slow, correlated fluctuations in neural/autonomic signals and behavior, and that these are strongly linked to slow quasiperiodic shifts in large scale brain network activations. This Conte Center explores the cost/benefits of off- task cognition while testing the overarching hypothesis that related slow fluctuations of neural activity extending below 1 Hz, down to at least 0.01 Hz (timescales of seconds to 10’s of seconds) are critical determinants of affect, cognition and behavior. We pose a set of linking hypotheses (Overview, b.2.a.), two of which relate to features of slow neural fluctuations may represent organizing principles for brain operation. First, local slow neural fluctuations link to larger scale slow brain network fluctuations (SBNFs) that significantly impact cognitive processes like attention, behavioral indices like reaction times and autonomic measures like cardiac variability and pupil diameter. Second, there is causal hierarchical coupling of neural activity across frequencies extending from infraslow up to action potential frequency ranges; i.e., the phase of lower frequency controls the amplitude of activity in higher frequencies. This “phase-amplitude coupling” (PAC) provides a likely mechanism for network orchestration of excitability states in distributed ensembles of neurons, that by definition, integrates across time scales. On one hand, the SBNF may be a tool the brain can use to deploy and shift/re-deploy PAC and other resources according to momentary needs or task demands. On the other hand, when endogenously-triggered SBNFs may provide the brain with a means of avoiding entrapment of its resources by the demands of an immediate task or context. Despite our increasingly nuanced understanding of individual brain network states and their transitions, the precise cognitive/behavioral functions and the underlying physiological mechanisms of SBNFs remain largely open questions. We address these two broad questions with an integrative program of research combining: 1) fMRI/EEG and intracranial (i)EEG in humans, with fMRI/EEG and field potential/unit recordings in nonhuman primates (NHPs), and with autonomic measures in all cases, 2) local cell circuit and network biophysical modeling, 3) experimental conditions ranging from structured tasks to completely unscripted sessions and 4) approaches aimed at identifying causal elements in network dynamics. The Center’s discoveries will contribute to the integrated mechanistic understanding of the brain and to improved treatment of neuropsychiatric disorders.