# Circuit Specific Electrical Brain Stimulation

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2020 · $469,842

## Abstract

ABSTRACT
Over the past decade, a revolution in genetic tools has allowed neuroscientists to probe the function of well-
defined brain circuits and specific cell types within those circuits. Those studies have revealed likely
underpinnings of mental illness, in the form of specific circuits that can be modulated to dramatically change
emotion-related behaviors in laboratory animals. The challenge is that those circuit insights do not readily
translate into psychiatric treatments. Laboratory tools such as optogenetics are far from being validated in
humans, particularly for the 40+ years that a human lives with a mental illness. Electrical/magnetic brain
stimulation, on the other hand, is a known, safe, and long-term-sustainable technology that already in clinical
use. Unfortunately, electrical stimulation has its own challenge: although it can limit its intervention to a focused
anatomical area, the stimulating field activates many cell types and affects neurons projecting to many brain
regions. In other words, although electrical methods are anatomically specific, they are not functionally- or circuit-
specific.
We propose to overcome these challenges by developing electrical stimulation methods that limit their effects to
defined circuits and physiologic signatures within those circuits. Specifically, local field potential (LFP) oscillations
and their synchrony (coherence) between brain regions are increasingly implicated as a mechanism by which
circuits organize and communicate. Controlling coherence within defined circuits and frequencies might thus be
a way to limit electrical stimulation's effects to a specific target/function. My lab recently showed that by precisely
controlling the timing of stimulation pulses, we can dramatically increase inter-area coherence. We can limit the
effect to a narrow frequency band, and in some cases, the stimulation leads to persistent synaptic change. We
propose to continue our rodent investigations and test four key properties of these new methods: behavioral
efficacy, directionality, specificity, and generalizability. We expect to show that controlling coherence through our
methods can modulate animals' behavior, that we can both enhance and inhibit a desired behavior, that we can
limit our effects to a specific anatomic projection, and that these methods work on multiple circuits and LFP
frequencies. These studies also provide a causal test of the hypothesis that LFP coherence is a mechanism of
circuit function, by showing whether behavior directly tracks coherence. If successful, we will have developed a
new set of tools that are clinically safe and capable of controlling specific brain circuits. The PI is a brain
stimulation psychiatrist with extensive experience in human and animal experiments, positioning us to then take
the next step into human pilots. These methods could become a "translational bridge" that lets clinical psychiatry
more efficiently leverage the growing scientific knowledge base.

## Key facts

- **NIH application ID:** 9901632
- **Project number:** 5R01MH119384-02
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Alik S. Widge
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $469,842
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9901632

## Citation

> US National Institutes of Health, RePORTER application 9901632, Circuit Specific Electrical Brain Stimulation (5R01MH119384-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9901632. Licensed CC0.

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