# Investigating Network Plasticity Effects of Repetitive Brain Stimulation Following Invasive and Noninvasive Methods in Humans

> **NIH NIH K23** · UNIVERSITY OF IOWA · 2021 · $186,840

## Abstract

Project Summary
The goal of this Mentored Patient-Oriented Research Career Development Award (K23) application is to
support the additional training, mentorship and experience needed to develop a new methodology for
analyzing the effects of repetitive brain stimulation using intracranial electroencephalography (iEEG) in
humans. One form of repetitive brain stimulation is transcranial magnetic stimulation (TMS). TMS has
revolutionized the field of therapeutics for neuropsychiatric disorders – it is a novel, noninvasive treatment
option used most commonly for medication-refractory major depressive disorder. Despite this, remission rates
from its use are suboptimal and ideal stimulation parameters are unknown.
Suboptimal outcomes are due in large part to our poor understanding of TMS neurophysiology and
antidepressant effects. TMS is thought to work by altering brain excitability within a network of targeted brain
structures; for depression, this target is an emotional network including the dorsolateral prefrontal cortex. The
ability of the brain to change excitability in response to repeated stimuli is referred to as plasticity. Noninvasive
methods of measuring plasticity, such as scalp EEG and magnetic resonance imaging (MRI), are often
imprecise and unreliable. This project proposes a novel method to invasively characterize brain plasticity
induced by intracranial stimulation (Aim 1) or TMS (Aim 2) with exquisite spatiotemporal resolution. The
method involves using iEEG single-pulse evoked potentials to probe and quantify excitability change (a
correlate of plasticity) after repetitive stimulation in epilepsy patients. Network connectivity profiles will be
analyzed with both iEEG and resting state MRI (Aim 3) to provide a unique bridge between invasive and
noninvasive physiology measures. This project tests the hypothesis that repetitive brain stimulation
(delivered via TMS and intracranial stimulation) will alter brain excitability in a parameter-dependent
manner, and these effects will be most pronounced within the nodes of the stimulated brain network.
A better understanding of how repetitive stimulation propagates through brain networks and alters brain
excitability will revitalize the to-date fruitless search for reproducible biomarkers of target engagement and
treatment response with these new technologies. Novel aspects of this study include the use of TMS in human
subjects with iEEG, and the unique combination of both invasive and noninvasive connectivity measures (iEEG
and MRI) to deeply characterize network effects of stimulation. Future directions will be 1) using this method to
evaluate and refine novel brain stimulation protocols to optimize plasticity and therapeutic efficacy, and 2)
applying learned principles about network effects of repetitive stimulation to inform clinical trial design and
therapeutic use in other brain disorders, such as depression. The University of Iowa and this mentor team
provide a rich research environment...

## Key facts

- **NIH application ID:** 10104024
- **Project number:** 1K23MH125145-01
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Nicholas Thomas Trapp
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $186,840
- **Award type:** 1
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10104024

## Citation

> US National Institutes of Health, RePORTER application 10104024, Investigating Network Plasticity Effects of Repetitive Brain Stimulation Following Invasive and Noninvasive Methods in Humans (1K23MH125145-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10104024. Licensed CC0.

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