# Leveraging behavioral state to enhance specificity of non-invasive brain stimulation on motor circuits

> **NIH NIH R21** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $429,000

## Abstract

Project Summary
The last two decades have seen an exponential growth in the use of noninvasive brain stimulation techniques,
including repetitive transcranial magnetic stimulation (rTMS), in both basic neuroscience and clinical practice.
rTMS holds promise for the study and treatment of neurological disorders. Yet, there is a limited understanding
of the effects of rTMS on brain and behavior. We will examine a particular type of rTMS, known as theta burst
stimulation (TBS), which induces longer lasting effects than other forms of rTMS, making TBS an important tool
for therapeutic applications. While TBS provides relatively focal stimulation, effects on the brain occur through
interconnected networks in ways that are poorly understood. Moreover, stimulation is highly state-dependent,
and the use of rTMS in most therapeutic settings, such as the treatment of motor disorders, leaves the
behavioral state uncontrolled. Augmenting rTMS by pairing it with behavioral interventions is an attractive idea
for improving therapeutic rTMS, but its efficacy and mechanisms remain unknown. To address this critical gap,
this exploratory R21 proposal will examine the effects of TBS and behavioral state on brain and behavior. Our
overall objectives in the proposed work are to (i) elucidate the neural mechanism by which TBS paired with a
motor task leads to improvements in hand function and (ii) develop more targeted network-modulatory rTMS
interventions to enhance motor function. We will focus on the posterior parietal cortex (PPC), and associated
parietal-motor circuits, which subserve skilled grasp control, an ability known to be impaired in stroke,
traumatic brain injury, cerebral palsy, and other motor disorders. We will collect functional magnetic resonance
imaging (fMRI), electrophysiological measures with TMS, and behavioral measures in the same subjects. Five
consecutive daily TBS sessions will be applied to 65 healthy subjects assigned to one of three groups, each
followed by two assessments to evaluate the effects of stimulation. In Aim 1, we will demonstrate improvement
in action performance by manipulating the behavioral state during PPC stimulation. In Aim 2, we will
demonstrate modulation of neurophysiological aftereffects of PPC stimulation by manipulating behavioral state.
In Aim 3, we will assess the relationship between brain connectivity, neural plasticity and behavior in response
to the behavioral state during brain stimulation. Impact: The methods reported here potentially can be modified
to more incisively treat motor disorders after stroke by targeting residual higher motor areas to improve
impaired cortical pathways. Results will lay a mechanistic foundation for future studies to show how controlling
behavioral state during rTMS can improve therapeutic efficacy after stroke.

## Key facts

- **NIH application ID:** 10217389
- **Project number:** 1R21NS118055-01A1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Michael Vesia
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $429,000
- **Award type:** 1
- **Project period:** 2021-04-01 → 2024-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10217389

## Citation

> US National Institutes of Health, RePORTER application 10217389, Leveraging behavioral state to enhance specificity of non-invasive brain stimulation on motor circuits (1R21NS118055-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10217389. Licensed CC0.

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