# Identifying the neural mechanisms of goal-directed decision-making in Parkinson's disease using closed-loop deep brain stimulation

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $74,500

## Abstract

TITLE: IDENTIFYING THE NEURAL MECHANISMS OF GOAL-DIRECTED DECISION-MAKING IN
PARKINSON’S DISEASE USING CLOSED-LOOP DEEP BRAIN STIMULATION
PROJECT SUMMARY
People with Parkinson’s disease commonly suffer from non-motor symptoms, including motivation deficits, that
impact quality of life more than classical motor symptoms and are exacerbated by current treatments like
dopaminergic drugs and deep brain stimulation. The long-term goal of this research is to understand the neural
basis of motivated decision-making to develop new therapies that can re-tune reward networks and address
this therapy gap. The overall objective of this proposal is to identify the neural signals that implement top-down,
goal-directed control of choices and their causal role in decision-making. My central hypothesis is that theta
frequency activity in the basal ganglia is required for implementing top-down control over decisions, and that
inhibiting the basal ganglia with closed-loop neurostimulation based on theta activity will reduce goal-directed
decision-making. Therefore, the rationale of the project is that identifying the neural signals underlying goal-
directed decision-making and causally manipulating them in a reward learning paradigm will reveal biomarkers
that can be used to re-tune these circuits and treat behavioral disorders. The central hypothesis will be tested
by pursuing two Specific Aims: Aim 1) Identify spatially and spectrally specific neural network signals for goal-
directed decision-making. We will record chronic frontal cortical and basal ganglia activity using
electrocorticography and sensing-enabled deep brain stimulation devices implanted in patients with
Parkinson’s disease while they perform a reward learning task. We will quantify choice strategies using
reinforcement learning models and relate goal-directed decision-making to neural signals, both ON and OFF
dopaminergic medications. Aim 2) Test the causal role of theta in goal-directed decision-making using closed-
loop brain stimulation. We will trigger inhibitory deep brain stimulation in the basal ganglia when theta power is
high to disrupt goal-directed decisions, thereby establishing the causal role of theta in top-down control of
decision-making. The research is innovative because it will be the first to use chronic, multi-site, invasive
electrophysiology and closed-loop brain stimulation to establish causal relationships between specific neural
signals and goal-directed decision-making in humans. It is significant because it will lead to biomarkers to
guide diagnosis and treatment of motivation deficits in patients with Parkinson’s disease and other
neuropsychiatric conditions. Dr. Hoy has assembled an interdisciplinary team of mentors led by Dr. Simon
Little and supported by Drs. Philip Starr, Wouter Kool, and Winston Chiong. Together, they have designed a
comprehensive training plan involving (1) closed-loop deep brain stimulation and subcortical neurophysiology,
(2) reinforcement lear...

## Key facts

- **NIH application ID:** 10805391
- **Project number:** 5F32MH132174-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Colin Hoy
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $74,500
- **Award type:** 5
- **Project period:** 2023-03-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10805391

## Citation

> US National Institutes of Health, RePORTER application 10805391, Identifying the neural mechanisms of goal-directed decision-making in Parkinson's disease using closed-loop deep brain stimulation (5F32MH132174-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10805391. Licensed CC0.

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