# Multiscale physiology and causal mechanisms of slow network fluctuations

> **NIH NIH P50** · NATHAN S. KLINE INSTITUTE FOR PSYCH RES · 2024 · $687,339

## Abstract

ABSTRACT: The overarching goal of Project (P) 3 is subsumed under Center Aim 3: Advance the
physiological interpretation of macroscale findings using meso- and microscale measures in humans and
NHPs. To do so, P3 will rely on NHPs as an animal model system to inform the interpretation of human
macroscale neuroimaging (P1) and mesoscale intracranial recording studies (P2) and the biophysical modeling
(P4). NHP work will provide, 1) simultaneous scalp EEG/fMRI, behavioral-cognitive and autonomic data under
three common tasks and conditions: intermodal attention, movie watching and rest, 2) brush and laminar array
recordings to define the microscopic cell circuits and physiological processes, and 3) targets for chemogenetic
manipulation. Aim 1 will link the macroscale measures of P1 meso- and microscale physiology of slow brain
network fluctuations (SBNFs), by defining SBNFs across distributed brain areas, including both the
interoceptive system and a classic exteroceptive system, the thalamocortical auditory system. Proposed
studies will include simultaneous recordings from multiple sites within and across task positive and task
negative networks. This will allow testing the hypothesis that SBNFs entail opposing unit and LFP activation
levels in task positive and task negative networks, with the anterior insular cortex a key site associated with
SBNF network switching from ‘restive’ to more task engaged activation patterns. Aim 2 will define processes
and structures triggering and modulating SBNF dynamics. Here, we will first pharmacologically increase
arousal via Methylphenidate as a direct link to human studies in P1. We will also electrically stimulate the
Vagus Nerve which impacts on neural networks including cholinergic and dopaminergic system and the
interoceptive system. Finally, after initial range-finding studies using electrical µ-stimulation, we will conduct
reversible chemogenetic inactivation of anterior insular cortex (AIC) projections to the anterior cingulate cortex
(ACC) and nucleus basalis (NB) to test hypotheses on the roles of these pathways in control of SBNF
dynamics. P3 will provide crucial information from neurophysiological neuronal recordings to EEG and fMRI
informing the detailed cell-circuit and network modeling in P4 and the human studies in P1 and P2.

## Key facts

- **NIH application ID:** 10834836
- **Project number:** 5P50MH109429-07
- **Recipient organization:** NATHAN S. KLINE INSTITUTE FOR PSYCH RES
- **Principal Investigator:** CHARLES E SCHROEDER
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $687,339
- **Award type:** 5
- **Project period:** 2017-04-15 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10834836

## Citation

> US National Institutes of Health, RePORTER application 10834836, Multiscale physiology and causal mechanisms of slow network fluctuations (5P50MH109429-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10834836. Licensed CC0.

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