# Biophysical Basis of Functional Connectivity by MRI

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2024 · $608,775

## Abstract

SUMMARY / ABSTRACT
 The overall goals of the research proposed are to verify whether inter-regional correlations in resting state
fluctuations of MRI signals (rsfMRI) reliably measure functional connectivity (FC) between brain regions, to
quantify factors that modulate rsFC derived from MRI, and to validate the neurobiological and behavioral
relevance of changes in rsFC following specific interventions. We aim to continue our studies of the functional
architecture of the sensorimotor system in non-human primates (NHPs) using multi-modal measurements of
neural activity before and after perturbations of neural circuits. We will establish how fMRI data correlate with
other metrics of connectivity obtained using optogenetic and electrophysiological techniques, and quantify
changes in neural circuits that result from specific, targeted interventions, along with their functional
consequences. These studies are important for the interpretation of fMRI studies in humans that are in
widespread use but which have not previously been properly validated. Such studies can be performed using
only invasive techniques in animals whose brain architecture resembles humans. We will use high resolution
(sub-millimeter) fMRI at 9.4T to assess mesoscopic scale networks within a well defined functional region of
somatosensory cortex in monkeys, where we can measure spatial patterns of resting state correlations in
cortical layers and validate their interpretation with electrophysiological signals and anatomic tracers. We will:
(1) Quantify laminar-resolved patterns of rsFC in sub-regions of S1, S2, thalamus and inter-hemispheric
regions, and compare networks engaged by vibrotactile and layer-specific microelectrode stimulation with rsFC
data. Cerebral cortex exhibits a laminar structure, but the laminar distribution of rsFC is poorly understood. We
will confirm that CBV provides more faithful metrics of fine-scale connectivity than BOLD: (2) Quantify effects of
selective deafferentation of inputs from (i) spinal cord (ii) thalamus, and (iii) area 3b of S1, on the patterns and
strengths of rsFC and behavior. We will show how disruption of driver inputs alters rsfMRI correlations between
regions in a layer-specific and functionally-relevant manner: (3) Identify and compare networks engaged by
optogenetic stimulation of different cell populations with rsFC data. By comparing optogenetic vs fMRI
responses for different transfection viruses we can assess the relative contributions to rsFC of selective
activation of excitatory pyramidal or inhibitory interneurons, or inhibition of excitatory neurons, locally at the S2
site and at the network level at interconnected brain regions. For each set of experiments we will acquire
rsfMRI and invasive multi-electrode measurements in the same animals to quantitatively compare different
metrics of neural activity and anatomical connections. We will also measure animal behaviors in skilled hand
use to identify specific effects of change...

## Key facts

- **NIH application ID:** 10869971
- **Project number:** 5R01NS078680-13
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Li Min Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $608,775
- **Award type:** 5
- **Project period:** 2012-09-28 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10869971

## Citation

> US National Institutes of Health, RePORTER application 10869971, Biophysical Basis of Functional Connectivity by MRI (5R01NS078680-13). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10869971. Licensed CC0.

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