# Examining the Effects of Suppression of Slow Rhythms on Resting State fMRI

> **NIH NIH R21** · EMORY UNIVERSITY · 2021 · $430,375

## Abstract

PROJECT SUMMARY/ABSTRACT
Blood oxygenation level dependent (BOLD) resting state fMRI (rsfMRI) has become the preeminent tool for
exploring brain function and pathology. However, the neurophysiological basis of rsfMRI signals is not fully
understood, impeding comprehensive interpretations of these studies. Recently, brain slow rhythms have been
put forth as possible sources of rsfMRI signal. RsfMRI signals are characterized by presence of transient
quasiperiodic patterns (QPPs), which are often not specific any canonical brain function networks (e.g., those
that subserve cognition). QPPs confound the estimation of accurate brain functional connectivity (FC) in
canonical brain function networks. These transient signals share a number of properties with cortical slow
rhythms. They exist in the absence of stimulation, propagate across the cortex, and are strongly modulated by
vigilance, similar to slow waves. It is possible that only these components QPPs, and not rsfMRI signal specific
to FC in canonical brain function networks are driven by slow rhythms. One mechanism for expression and
maintenance of cortical slow rhythms in the brain is through a thalamocortical network of coupled oscillators
driven by burst firing induced by low-threshold T-type calcium (Ca2+) channels. Systemic administration of the
selective T-type Ca2+ channel blocker (TTCCB) TTA-P2 suppresses slow brain rhythms (i.e., decrease the
number of slow waves observed in a given time window) by up to 60% in rats. In this study, we will examine
the effects of suppression of slow waves on rsfMRI signals. We hypothesize that suppression of slow rhythms
will reduce the strength of QPPs. And this reduction in expression of QPPs will enhance the specificity of FC in
canonical brain function network.
We will acquire simultaneous rsfMRI and EEG data from a group of 25 rats 90 min before and 90 minutes after
subcutaneous injection of the drug TTA-P2 at an optimal dose to be determined on a separate cohort of 20
rats. Another group of 15 rats will receive the vehicle as control. The strength and frequency of expression of
QPPs will be estimated under pre- (Baseline) and post-TTA-P2 (or Vehicle) conditions. We will estimate FC in
different canonical brain function networks through seed-based cross-correlation analysis with a priori regions
of interest specific to each network examined. Differences in QPP metrics, and FC in brain function networks
between different conditions will be examined with appropriate hypotheses tests. We expect QPP metrics to be
significantly reduced from Baseline after slow wave suppression post-TTA-P2. FC in canonical brain function
networks will increase, and non-specific correlations between unconnected brain regions will decrease from
baseline post-TTA-P2, thereby increasing the specificity of FC in canonical brain function networks. No
significant differences in rsfMRI signal metrics will be observed between Baseline and Vehicle conditions.
Successful completion ...

## Key facts

- **NIH application ID:** 10373750
- **Project number:** 1R21NS122013-01A1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Kaundinya Srinivasan Gopinath
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $430,375
- **Award type:** 1
- **Project period:** 2021-09-29 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10373750

## Citation

> US National Institutes of Health, RePORTER application 10373750, Examining the Effects of Suppression of Slow Rhythms on Resting State fMRI (1R21NS122013-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10373750. Licensed CC0.

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