# Using phasic stimulation to explore the subthalamic nucleus - cortical decision-making network in Parkinson's disease

> **NIH NIH K23** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $201,960

## Abstract

Project Summary / Abstract
 Parkinson’s disease (PD) affects 10 million people worldwide, and roughly half of the disease-
related morbidity from PD arises not from the motor symptoms, but rather from debilitating neuropsychiatric
symptoms that respond inadequately to current modes of treatment. Whereas deep brain stimulation (DBS)
of the subthalamic nucleus (STN) relieves many motor symptoms in moderate to severe PD, it can worsen
cognitive and psychiatric function. A deeper understanding of how STN stimulation alters cognitive network
function is required to understand these cognitive symptoms and, ultimately, to support development of new
approaches to DBS that could treat neuropsychiatric symptoms.
 Working with patients treated with DBS for Parkinson’s disease, this project utilizes a novel form of
phasic DBS to deliver brief bursts of stimulation to the STN while subjects engage in a computerized
gambling task that assesses risk-taking behavior. Our preliminary results show that phasic STN stimulation
biased subjects to bet more conservatively, but only when precisely-timed after subjects had information
about their likelihood of winning. Single-neuron recordings from the STN obtained intraoperatively showed
that STN neurons exhibited greater activity prior to low-risk than high-risk wagers and suggested an optimal
time for STN stimulation shortly before the subject’s decision. This proposal tests this hypothesis directly
and studies the effect of phasic STN stimulation on the medial prefrontal – ventral STN circuit that we
hypothesize mediates mediates the behavioral effect of stimulation.
 Dr. Todd Herrington is a movement disorders neurologist at Harvard Medical School and
Massachusetts General Hospital. His clinical specialization is in the treatment of patients with DBS and use
of intraoperative neurophysiology to assist placement of DBS electrodes. Dr. Herrington’s career goal is to
be an independently-funded scientist using novel forms of brain stimulation and invasive and non-invasive
neurophysiology to study human brain function, with the ultimate goal of developing new approaches to
neuromodulation to treat human neurologic and psychiatric illness. This career development plan provides a
critical education in human subjects study design, translational research, and training in advances methods
of non-invasive neurophysiology through high-density, high-sampling rate EEG recordings.
 Dr. Emad Eskandar, the mentor on this project, is an internationally recognized expert in deep brain
stimulation, the development of novel approaches to brain stimulation in animal models and translational
research in human subjects. Dr. Sydney Cash, the co-mentor on this project, is an expert in studying
cortical neurophysiology in human subjects using EEG. Dr. Thilo Deckersbach, is a neuropsychologist and
cognitive neuroscientist with expertise in neuropsychiatric pathology. All of these mentors are successful
physician scientists committed to Dr. Her...

## Key facts

- **NIH application ID:** 9976599
- **Project number:** 5K23NS099380-04
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Todd Herrington
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $201,960
- **Award type:** 5
- **Project period:** 2017-09-15 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9976599

## Citation

> US National Institutes of Health, RePORTER application 9976599, Using phasic stimulation to explore the subthalamic nucleus - cortical decision-making network in Parkinson's disease (5K23NS099380-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9976599. Licensed CC0.

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