# Reliability of Repetitive TMS-induced Modulation of Cortical Excitability

> **NIH NIH R01** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2021 · $536,814

## Abstract

ABSTRACT
Repetitive Transcranial Magnetic Stimulation (rTMS) is a noninvasive brain stimulation technique capable of
modulating activity in the targeted brain region and its connected brain circuits beyond the duration of the
stimulation itself. rTMS is utilized in neuroscience research to investigate brain function during human cognition
and behavior, and to understand brain pathophysiology in neuropsychiatric diseases. Clinically, rTMS protocols
have diagnostic and therapeutic utility across a wide spectrum of disease states, and four rTMS devices are
cleared by the Food and Drug Administration (FDA) for treatment of medication-resistant depression.
However, the variability of the neuromodulatory effects of rTMS and its sources are ill-defined. This knowledge
gap represents a fundamental limitation for both, the interpretation of rTMS results and the design of studies.
For example, it is challenging to calculate or assess the sample size for a study, and one cannot optimize
rTMS parameters for an individual without knowing whether individual differences in rTMS response are
reproducible. In addition, one cannot assume that rTMS protocols tested in motor cortex will produce similar
neuromodulatory effects when administered to other brain regions.
In this proposal we will use MRI-guided rTMS in combination with EMG, EEG and behavioral measures to
characterize the variability of rTMS effects in primary motor cortex (M1) and in dorsolateral prefrontal cortex
(DLPFC). In a cohort of 60 subjects, we will evaluate the inter-subject and intra-subject test-retest reliability of
the modulatory effects of the most widely used rTMS protocols applied to M1. We will compare the impact of
different rTMS protocols on corticospinal excitability (measured via motor-evoked potentials), cortical
excitability (measured via simultaneous TMS-EEG), and motor performance (using a sequential finger tapping
task). Each subject will undergo a total of 10 TMS-EMG-EEG-behavior sessions, evaluating repeated
sessions of excitatory and inhibitory protocols. In a separate cohort of 60 subjects, we will evaluate the transfer
of rTMS effects across brain regions by applying 10 Hz rTMS and iTBS to both M1 and DLPFC. Each subject
will undergo a total of 10 TMS-EEG-behavior sessions contrasting stimulation protocols across regions (M1
versus DLPFC). All subjects will undergo extensive baseline assessment, including detailed exam,
neuropsychological measures, structural and resting-state functional-connectivity MRI, computational
modeling, laboratory and genetic testing, and EEG to identify predictors of inter-subject variability in response
to rTMS. All data will be placed in a secure repository and made publicly accessible to other investigators.
This study will define the reproducibility of the neuromodulatory effects of rTMS, quantifying the intrinsic
variability of the method within and across individuals, across levels of analysis (neurophysiologic and
behavioral) and brain reg...

## Key facts

- **NIH application ID:** 10112309
- **Project number:** 5R01MH115949-04
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Mouhsin Shafi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $536,814
- **Award type:** 5
- **Project period:** 2018-06-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10112309

## Citation

> US National Institutes of Health, RePORTER application 10112309, Reliability of Repetitive TMS-induced Modulation of Cortical Excitability (5R01MH115949-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10112309. Licensed CC0.

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