# Mapping a Causal Prefrontal Pathway for Amygdala Modulation Utilizing Invasive and Noninvasive Brain Stimulation and Recording Methods in Humans

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2024 · $604,724

## Abstract

PROJECT SUMMARY
While the amygdala is a key focus in psychiatric treatments and invasive modulation of amygdala activity has
shown promise in treating certain refractory cases, its widespread use among millions of treatment-resistant
patients is impractical and entails inherent neurosurgery-related risks. The development of transcranial
magnetic stimulation (TMS) provides a potential noninvasive alternative. However, the effective modulation
of the amygdala with TMS
is hindered by
the lack of knowledge in pinpointing a TMS-accessible cortical site
that can reliably target and modulate the amygdala. The dorsolateral prefrontal cortex (DLPFC) emerges as
a promising candidate for stimulation based on findings from extensive preliminary data, published work, and
large human connectome datasets. The overall objective in this proposal to determine whether and how
DLPFC repetitive stimulation modulates the amygdala activity with an unparalleled combination of
invasive and noninvasive stimulation and recording methods in humans. The central hypothesis is that
both invasive and noninvasive stimulation of DLPFC modulate the amygdala activity through their functional
connectivity mechanism. This central hypothesis will be tested by pursuing three specific aims: determine
invasive modulatory effects of intracranial stimulation of DLPFC on the amygdala recorded with intracranial
EEG (iEEG) in epilepsy patients (Aim 1), translate stimulation with noninvasive TMS of DLPFC while tracking
modulatory effects on the amygdala with iEEG in epilepsy patients (Aim 2a) and with functional MRI in healthy
individuals (Aim 2b), and evaluate the role of DLPFC-amygdala functional connectivity in predicting
modulatory effects of DLPFC stimulation on the amygdala (Aim 3). The proposed research is innovative,
because it can determine a unique causal prefrontal pathway for noninvasive amygdala modulation in
humans. It also represents the first attempt of any group worldwide to creatively combine multimodal cutting-
edge brain stimulation and recordings to comprehensively evaluate modulatory effects of DLPFC stimulation
on the human amygdala. The proposed research is significant because it is expected to provide compelling
and conclusive causal evidence of amygdala modulation by DLPFC stimulation and inform a novel circuit-
based strategy that can efficiently pinpoint a stimulation site within the DLPFC for noninvasive amygdala
modulation. Ultimately, such knowledge will facilitate the rational design of personalized, circuit-guided
noninvasive neuromodulatory therapies aimed at modulating the amygdala for psychiatric disorders.

## Key facts

- **NIH application ID:** 10857564
- **Project number:** 1R01MH136197-01
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Jing Jiang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $604,724
- **Award type:** 1
- **Project period:** 2024-04-19 → 2029-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10857564

## Citation

> US National Institutes of Health, RePORTER application 10857564, Mapping a Causal Prefrontal Pathway for Amygdala Modulation Utilizing Invasive and Noninvasive Brain Stimulation and Recording Methods in Humans (1R01MH136197-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10857564. Licensed CC0.

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