# Uncovering the neurophysiology of motivation in Parkinson™s disease with implanted adaptive brain stimulation

> **NIH NIH K23** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $200,478

## Abstract

TITLE: UNCOVERING THE NEUROPHYSIOLOGY OF MOTIVATION IN PARKINSON’S DISEASE WITH
IMPLANTED ADAPTIVE BRAIN STIMULATION
PROJECT SUMMARY
Behavioral symptoms such as apathy and impulsivity represent a prevalent, highly-disabling feature of
Parkinson’s disease (PD) and many other neurological conditions, for which treatments are currently very
limited. The long-term goal of this award is to understand the neurocircuitry of motivation in order to develop
precise and personalized therapies for motor and non-motor symptoms in neurological disorders. The overall
objective is to establish the neural structures and signals that underpin motivation in PD. My central hypothesis
is that the human motivation system comprises two functionally distinct frontal cortex - basal ganglia (FC-
BG) circuits that drive behavior: 1) the prefrontal - basal ganglia circuit evaluates rewards and operates in the
theta (3-7Hz) frequency range and 2) the premotor - basal ganglia circuit evaluates action costs, and is
mediated by beta (13-30Hz) frequency signals, with both modulated by dopamine. Therefore, the rationale of
the project is that understanding the neural structures and signals of the FC-BG reward circuit is critical for the
development of effective stimulation therapies for behavioral symptoms in PD. The central hypothesis will be
tested by pursuing two Specific Aims: Aim 1) Identify the neurophysiological signatures of reward cost-benefit
evaluation in PD. Patients with chronically implanted, sensing-enabled brain stimulators will perform reward
cost-benefit evaluation tasks with simultaneous FC-BG recordings, on and off dopamine medication.
Additionally, patients will trigger recordings of neural signals at home, with paired self-reports of apathy and
impulsivity. Aim 2) Evaluate the causal relationship of frontal cortex-basal ganglia structures & signals to
behavior. Spatio-temporally targeted brain stimulation will be delivered to the FC-BG network during reward
cost-benefit evaluation to test the causal role of these structures and signals to motivated behavior. The
research is innovative because it uses a) chronic invasive brain recordings, in patients, during behavioral
tasks that index motivation, b) recordings at home to determine within-subject reproducibility and link to
naturalistic motivational states and c) causal interventions to demonstrate mechanistic relationships. It is
significant because determining an accurate understanding of the neurocircuitry of reward will enable the
future development of precise, spatio-temporally targeted adaptive brain stimulation for apathy and impulsivity
in PD, a major unmet need. As such, Dr. Little has assembled a multidisciplinary mentoring group led by Prof.
Philip Starr and supported by advisors Profs. Edward Chang, Wendy Mendes and Joshua Berke to develop a
comprehensive structured training plan involving 1) cognitive-affective neuroscience 2) electrocorticography 3)
machine learning and 4) trial design and stati...

## Key facts

- **NIH application ID:** 10106490
- **Project number:** 1K23NS120037-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Simon Little
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $200,478
- **Award type:** 1
- **Project period:** 2021-03-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10106490

## Citation

> US National Institutes of Health, RePORTER application 10106490, Uncovering the neurophysiology of motivation in Parkinson™s disease with implanted adaptive brain stimulation (1K23NS120037-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10106490. Licensed CC0.

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