# Neurobiology and Cognitive Role of Slow Brain Network Fluctuations

> **NIH NIH P50** · NATHAN S. KLINE INSTITUTE FOR PSYCH RES · 2024 · $3,166,995

## Abstract

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 integrat...

## Key facts

- **NIH application ID:** 10834832
- **Project number:** 5P50MH109429-07
- **Recipient organization:** NATHAN S. KLINE INSTITUTE FOR PSYCH RES
- **Principal Investigator:** Michael Peter Milham
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $3,166,995
- **Award type:** 5
- **Project period:** 2017-04-15 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10834832

## Citation

> US National Institutes of Health, RePORTER application 10834832, Neurobiology and Cognitive Role of Slow Brain Network Fluctuations (5P50MH109429-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10834832. Licensed CC0.

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