# Stopping behavior and interrupting cognition via subthalamic nucleus

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $445,871

## Abstract

PROJECT SUMMARY
Research in several species shows that rapidly stopping action activates the subthalamic nucleus (STN) of the
basal ganglia (BG) – and that the STN may be recruited via a hyperdirect pathway (HDP) from prefrontal
cortical stopping nodes. Human research also shows that unexpected events (such as a surprising tones) also
recruit the stopping system (including the STN), and interrupt working memory (WM). At the core of this
proposal is the idea that WM is maintained via a recurrent cortico-BG loop, and that this can be interrupted via
HDP recruitment of the STN. The interruption is induced via stop signals and unexpected events, and could
function to `clear cognition'. This is a radical new theory: that a fronto-BG circuit for stopping underlies cognitive
interruptions. Validating this theory has broad implications for understanding the BG, for mechanisms of
cognitive interruptions, and for potential cognitive under-and-over flexibility in Parkinson's disease (PD) and
ADHD. Here we propose to systematically test this theory using parallel human-mouse studies, based on
extensive preliminary data and using several novel approaches, including event-related Deep Brain Stimulation
(eDBS). Aim 1 (motor stop) will use STN eDBS in humans and optogenetic stimulation in mice to test whether
the STN is causally important for stopping action. Aim 2 (cognitive stop) will use eDBS and functional MRI in
humans and optogenetics in mice to test whether the STN is causally important for decrementing WM. Aim 3
(HDP) will use combinatorial optogenetics in mice and novel combinations of transcranial magnetic stimulation
with concurrent local field recordings in human STN to test whether motor and cognitive Stops are
implemented via HDP inputs to STN from frontal cortex. Throughout the proposal we focus on designing
complementary experiments across species, so that what is learned in mice can directly inform our
understanding of human neural circuit function and behavior.

## Key facts

- **NIH application ID:** 10145085
- **Project number:** 5R01NS106822-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Adam Robert Aron
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $445,871
- **Award type:** 5
- **Project period:** 2018-05-15 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10145085

## Citation

> US National Institutes of Health, RePORTER application 10145085, Stopping behavior and interrupting cognition via subthalamic nucleus (5R01NS106822-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10145085. Licensed CC0.

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