Intraoperative Analysis of Reward and Impulsivity in the Basal Ganglia

This project studies the impulsive side effects of common treatments for Parkinson's Disease. By learning how parts of the brain involved in Parkinson's encode information related to reward and motivation, the investigators will better understand the reasons why Parkinson's patients often suffer from compulsive gambling, hypersexuality, and repetitive tinkering ("punding"). These results may lead to the design of better methods of deep brain stimulation (DBS) that minimize the behavioral side effects of Parkinson's treatment.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease

Detailed Description

While the typical treatments for Parkinson's disease (PD), dopaminergic drugs and deep brain stimulation (DBS), are proven to be effective in mitigating the motor deficits associated with the disease, these same methods also give rise to behavioral side effects including compulsive gambling, hypersexuality, and complex, purposeless stereotyped behavior ("punding"). And while much work has investigated the underlying patterns of neural activity giving rise to tremor, rigidity, and other motor effects of D, little is known about the neural genesis of impulsive side effects in humans. The investigators propose to characterize the patterns of neural activity underlying these failures of impulse control in an actual PD patient population undergoing surgery for the implantation of DBS electrodes. Such procedures offer a unique opportunity to collect data at the single neuron level in humans, since surgeons rely on intraoperative electrophysiology to identify the anatomical boundaries of the subthalamic nucleus (STN), the typical target of DBS in PD. Using multi-channel Ad-Tech microwire arrays, the investigators will simultaneously record multiple channels of single unit activity (both spikes and field potentials ) in STN and nearby structures while subjects perform cognitive tasks with validated links to impulsivity in human populations. In the balloon analogue risk task (BART) participants must balance risk and reward as they decide when to stop inflating a computerized balloon whose point value and risk of popping both grow with size. In the stop signal reaction task (SSRT), participants must respond as quickly as possible when a "go" cue appears, but countermand this response when a "stop" tone is played. At the neural level, the BART allows us to elucidate correlates of risk, outcome (both rewarding and aversive), and anticipation, while the SSRT, a well-studied model of impulsivity in both animal models and humans with strong links to computational models, will allow us to determine not only single unit but network-level patterns of activity underlying failures in impulse control. Through these experiments, as well as computational modeling, the investigators will characterize neural correlates of impulsivity in PD patients that will allow for the design of DBS protocols that mitigate impulsive side effects. The R21 mechanism will be used to further develop and streamline the process of multichannel recording and cognitive testing in the intraoperative setting and validate the hypothesized link between single neuron activity and models of behavior in the stop signal task.

• Study Type: Observational
• Enrollment (Actual): 36

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Participants are patients scheduled to be implanted with Deep Brain Stimulation devices for treatment of Parkinson's Disease or Essential Tremor.

Description

Inclusion Criteria:

• scheduled for implantation of deep brain stimulation device
• appropriate for awake surgery
• interest in participation

Exclusion Criteria:

• none

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain activity data	Extracellular voltage measurements (microelectrode recording) from single and multi-neuron activity in the basal ganglia. Local field potentials from the same recording sites.	during treatment
Behavioral data	Interactions of patients with a video game task, including joystick button responses, points earned, and response times.	during treatment

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Actual): February 27, 2017
• Study Completion (Actual): February 27, 2017

Study Registration Dates

• First Submitted: December 15, 2014
• First Submitted That Met QC Criteria: December 17, 2014
• First Posted (Estimate): December 18, 2014

Study Record Updates

• Last Update Posted (Actual): June 1, 2018
• Last Update Submitted That Met QC Criteria: May 31, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Behavior; Brain; Deep Brain Stimulation; Cognitive; Data; Behavioral; Basal Ganglia; Disease; Cues; Computer Simulation
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Cysts; Connective Tissue Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Mucinoses; Parkinson Disease; Ganglion Cysts; Impulsive Behavior
• Other Study ID Numbers: Pro00045557; R21NS084176 (U.S. NIH Grant/Contract)