Cortical Stimulation to Treat Mood and Behavioral Symptoms in Parkinson's Disease Patients

NCT03131817 | Completed Results FDA Device

• 1 other identifier: 16-20284
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This study will investigate cortical stimulation to treat mood and behavioral symptoms in Parkinson's disease patients.

Conditions

Parkinson's Disease

Outcome Measures

Primary Outcomes (5)

• Association Between Basal Ganglia Beta Power and Effort Level (Beta Coefficient)

  Mean beta-band (12-20 Hz) oscillatory power in the basal ganglia (BG) during the decision period, analyzed as a function of the current trial effort level during the reward-effort decision-making task.

  Single recording session per participant (approximately 90 minutes total; 3 blocks of 25 trials each), with outcome assessed at each trial and data aggregated across all trials for all participants.

• Prefrontal Cortex Theta Power Relative to Previous Trial Reward (Beta Coefficient)

  Mean theta-band (4-7 Hz) oscillatory power in the prefrontal cortex (PFC) was assessed during the decision period of each trial. Theta power was modeled as a function of the reward received in the previous trial using linear mixed-effects models. The analysis included trials from structured decision-making task sessions.

  Single recording session per participant (approximately 90 minutes total; 3 blocks of 25 trials each), with outcome assessed at each trial and data aggregated across all trials for all participants.

• Effect of Reward Magnitude and Effort Cost on Offer Acceptance Probability

  This outcome measures the effect of reward magnitude and effort cost on the probability of participants accepting offers during a decision-making task. Effects were assessed using generalized linear mixed models (LMMs) to estimate the relationship between reward, effort, and choice behavior.

  Single recording session per participant (approximately 90 minutes total; 3 blocks of 25 trials each), with outcome assessed at each trial and data aggregated across all trials for all participants.

• Association Between Prefrontal Cortex Beta Band Spectral Power and Mood Symptoms

  This outcome measures the association between prefrontal cortex (PFC) beta band spectral power recorded via chronic subdural ECoG and self-reported symptoms of depression and anxiety assessed using standardized scales. Associations were evaluated using Spearman correlation coefficients calculated for each participant. The Beck Depression Inventory (BDI) ranges from 0 to 63, with higher scores indicating more severe depressive symptoms. The Beck Anxiety Inventory (BAI) ranges from 0 to 63, with higher scores indicating more severe anxiety symptoms.

  Daily paired assessments of neural recordings and IMS scores over 3-5 months for each participant.

• Effect of Chronic Orbitofrontal Cortex (OFC) Stimulation on Depression, Anxiety, and Energy Ratings

  This outcome measures self-reported symptoms of depression, anxiety, and energy levels in participants undergoing chronic orbitofrontal cortex (OFC) stimulation at home. Participants received blinded OFC stimulation for 14 days, with alternating sham and active stimulation days. Symptoms were assessed daily using visual analogue scales (VAS) for depression, anxiety, and energy, as well as the Hamilton Depression Rating Scale (HAM-D). The VAS ranges from 0 to 100. For the depression and anxiety VAS, higher scores indicate worse symptoms, whereas for the energy VAS, higher scores indicate greater energy. The HAM-D ranges from 0 to 52, with higher scores indicating more severe depressive symptoms.

  Daily paired assessments of neural recordings and IMS scores over 14 days for each participant.

Secondary Outcomes (1)

• Effect of Prefrontal Cortex Stimulation on Acceptance Rate of Work Offers During Effort-Based Decision-Making Task

  Six recording blocks (three with stimulation On and three with stimulation Off), each approximately 15 minutes in duration (total ~90 minutes), with outcome assessed on each trial and data aggregated across both conditions for the participant.

Study Arms (2)

Chronic Neural Recording with Prefrontal Cortex ECoG in Parkinson's Disease

EXPERIMENTAL

Participants with Parkinson's disease underwent deep brain stimulation (DBS) lead implantation targeting either the subthalamic nucleus or globus pallidus internus for motor symptom management. A permanent 4-contact subdural electrocorticography (ECoG) strip was also placed over the right prefrontal cortex and connected to a Medtronic Activa PC+S neurostimulator. This setup enabled chronic recording of local field potentials from the prefrontal cortex during daily life and structured experimental tasks. Neural and behavioral data were collected through decision-making tasks and longitudinal self-report of mood and symptoms using a tablet-based tool. Clinical DBS and medication adjustments were performed solely as part of standard care and were not influenced by participation in the study.

Device: Medtronic Activa PC+S System with Chronic Neural Recording; Behavioral: Effort-Reward Decision-Making Task; Behavioral: Tablet-Based Mood Tracking (Immediate Mood Scaler)

Prefrontal Cortex ECoG Stimulation in Parkinson's Disease

EXPERIMENTAL

A subset of participants in the recording cohort also received experimental stimulation through the implanted prefrontal ECoG strip. One participant underwent blinded, block-wise prefrontal cortex stimulation during a behavioral task to assess its causal effects on motivation and decision-making. Additionally, two participants received blinded, chronic prefrontal stimulation at home over a 14-day period, in conjunction with their ongoing subcortical motor DBS. These participants completed daily self-reports of mood and anxiety symptoms during the stimulation period. All stimulation protocols were experimental and distinct from routine motor DBS programming. Clinical DBS and medication adjustments were made exclusively as part of routine care and were not affected by the study procedures.

Device: Medtronic Activa PC+S System with Chronic Neural Recording; Behavioral: Effort-Reward Decision-Making Task; Other: Prefrontal Cortex Stimulation; Behavioral: Tablet-Based Mood Tracking (Immediate Mood Scaler)

Interventions

Medtronic Activa PC+S System with Chronic Neural Recording DEVICE

Participants received a Medtronic Activa PC+S system incorporating standard-of-care DBS leads implanted in the basal ganglia (subthalamic nucleus or globus pallidus internus) for management of Parkinson's disease motor symptoms. Additionally, a permanent 4-contact subdural electrocorticography (ECoG) strip was implanted over the prefrontal cortex (e.g., dorsolateral, orbitofrontal, or frontopolar regions) to enable chronic recording of local field potentials. The system allowed for long-term, wireless neural recordings in naturalistic or task-based conditions.

Chronic Neural Recording with Prefrontal Cortex ECoG in Parkinson's Disease; Prefrontal Cortex ECoG Stimulation in Parkinson's Disease

Effort-Reward Decision-Making Task BEHAVIORAL

Participants performed a structured task involving repeated choices to accept or reject offers requiring different levels of physical effort in exchange for variable rewards. The task was used to assess motivation and effort-based valuation processes.

Chronic Neural Recording with Prefrontal Cortex ECoG in Parkinson's Disease; Prefrontal Cortex ECoG Stimulation in Parkinson's Disease

Prefrontal Cortex Stimulation OTHER

In one participant, high-frequency stimulation was delivered to the prefrontal cortex via the ECoG strip during a behavioral paradigm. Stimulation was alternated On and Off in a blinded block-wise fashion during the behavioral task to assess causal effects on motivated behavior. In two patients, orbitofrontal cortex (OFC) stimulation was also assessed chronically at home in a within subject, repeated design.

Also known as: Electrical Stimulation

Prefrontal Cortex ECoG Stimulation in Parkinson's Disease

Tablet-Based Mood Tracking (Immediate Mood Scaler) BEHAVIORAL

Participants used a tablet-based Immediate Mood Scaler (IMS) to self-report symptoms related to depression and anxiety in real-time, naturalistic settings. These repeated, in-the-moment assessments were temporally paired with prefrontal cortical recordings to study physio markers of mood fluctuations over several months. No stimulation was delivered through the prefrontal cortex electrode.

Chronic Neural Recording with Prefrontal Cortex ECoG in Parkinson's Disease; Prefrontal Cortex ECoG Stimulation in Parkinson's Disease

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to give informed consent for the study
• Age 30-75
• Diagnosis of Parkinson's disease by a movement disorders specialist
• Movement disorder symptoms that are sufficiently severe, in the setting of best medical therapy, to warrant surgical implantation of deep brain stimulators according to standard clinical criteria
• UPDRS-III score off medication between 20 and 80 and an improvement of at least 30% in the baseline UPDRS-III on medication score, compared to the baseline off-medication score.
• OR Patients with tremor-dominant PD (a tremor score of at least 2 on a UPDRS-III sub-score for tremor), treatment resistant, with significant functional disability despite maximal medical management OR Patients intolerant to medication causing significant functional disability
• Have one or several mild to moderate mood or impulsive behavior as defined by:
• depression (BDI\>=13)
• anxiety (BAI \>=7)
• impulsive behavior as indicated by a positive score on the Questionnaire for Impulsive-Compulsive disorders in Parkinson's Disease (QUIP-A) or as determined by clinical interview or informant report
• Mood or behavior symptom fluctuations corresponding to minimum 30% improvement in non-motor symptoms when comparing visual analogue scales (VAS) scores in the on versus off medication state
• Stable doses of anti-Parkinsonian medications for at least 30 days prior to their baseline assessment.

You may not qualify if:

• Pregnancy or breast feeding
• MRI showing cortical atrophy out of proportion to age
• MRI showing focal brain lesions that could indicate a disorder other than idiopathic PD
• Major comorbidity increasing the risk of surgery (prior stroke, severe hypertension, severe diabetes, or need for chronic anticoagulation other than aspirin)
• Any prior intracranial surgery except DBS surgery
• Significant cognitive impairment (MoCA\<20).
• History of seizures
• Immunocompromised
• Has an active infection
• Requires diathermy, electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS) to treat a chronic condition
• Inability to comply with study follow-up visits
• Any personality or mood symptoms that study personnel believe will interfere with study requirements.

Sponsors & Collaborators

• Simon J. Little, MBBS, PhD: lead

Study Sites (1)

UCSF Surgical Movement Disorders Center

San Francisco, California, 94115, United States

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

Electric Stimulation

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Physical Stimulation; Investigative Techniques

Limitations and Caveats

The study was limited by a small sample size (n=5) and the absence of a control group. PFC stimulation was tested in only one (in laboratory testing) or two (at-home testing) participants per paradigm due to participant preference and availability. Stimulation was restricted to the right PFC, and recordings were localized to specific basal ganglia and PFC regions. Larger, controlled studies with more diverse samples are needed to address these limitations.

Results Point of Contact

• Title: Dr. Simon Little
• Organization: University of California, San Francisco

simon.little@ucsf.edu

4152995650

Study Officials

• Simon Little, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor, Clinical Neurology

Study Record Dates

• First Submitted: September 28, 2016
• First Posted: April 27, 2017
• Study Start: December 16, 2016
• Primary Completion: June 18, 2024
• Study Completion: June 18, 2024
• Last Updated: November 21, 2025
• Results First Posted: November 21, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)