Cortical Stimulation to Treat Mood and Behavioral Symptoms in Parkinson's Disease Patients (PC+S_PFC)

November 11, 2025 updated by: Simon J. Little, MBBS, PhD

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

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Depression, anxiety and impulse control disorders are among the most prominent neuropsychiatric symptoms in Parkinson's disease (PD) that greatly impact patients' and caregivers' quality of life. However, the neural correlate underlying these symptoms is still largely unknown preventing the development of comprehensive treatment for these symptoms.

The aims of this study are to 1) Determine the neural correlates of non-motor symptoms, 2) Determine how cortical stimulation can reduce these symptoms and normalize the abnormal brain signals, and 3) Teach patients how to voluntarily modulate the abnormal brain signals.

Ten PD patients undergoing deep brain surgery (DBS) implantation and diagnosed with mild to moderate mood disorder and/or impulsive behavior will be enrolled in this study. In addition to the standard therapeutic DBS electrode used to treat motor symptoms, a flexible electrode will be placed over the prefrontal cortex. Both electrodes will be attached to the Medtronic Activa PC+S pulse generator (and Medtronic Summit RC+S pulse generator as replacements), investigational devices that allows therapeutic stimulation and chronic brain recordings. At multiple time points, up to 2 years post-implantation, in our clinic or patient's home, brain signals will be recorded while patients are resting or performing emotion/cognition tasks. Symptoms will be assessed using validated questionnaires and tasks to allow identification of neurophysiological correlates of non-motor symptoms. There is also an optional sleep study included for better understanding of the brain's physiology. The investigators will then investigate the effect of cortical stimulation on both symptoms severity and brain signals that may be related to symptom expression. These signals will then be used to implement closed-loop controlled cortical stimulation and neuro-feedback controlled strategies.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
5

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94115
        • UCSF Surgical Movement Disorders Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

30 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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:

    1. depression (BDI>=13)
    2. anxiety (BAI >=7)
    3. 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
    4. 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.

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Chronic Neural Recording with Prefrontal Cortex ECoG in Parkinson's Disease

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
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.
Behavioral: Effort-Reward Decision-Making Task
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.
Behavioral: Tablet-Based Mood Tracking (Immediate Mood Scaler)
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.
Experimental: Prefrontal Cortex ECoG Stimulation in Parkinson's Disease

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
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.
Behavioral: Effort-Reward Decision-Making Task
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.
Behavioral: Tablet-Based Mood Tracking (Immediate Mood Scaler)
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.
Other: Prefrontal Cortex Stimulation
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.
Other Names:
  • Electrical Stimulation

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Association Between Basal Ganglia Beta Power and Effort Level (Beta Coefficient)
Time Frame: 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.
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)
Time Frame: 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.
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
Time Frame: 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.
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
Time Frame: Daily paired assessments of neural recordings and IMS scores over 3-5 months for each participant.
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
Time Frame: Daily paired assessments of neural recordings and IMS scores over 14 days for each participant.
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Effect of Prefrontal Cortex Stimulation on Acceptance Rate of Work Offers During Effort-Based Decision-Making Task
Time Frame: 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.
Measured the effect of high-frequency prefrontal cortex (PFC) stimulation on the acceptance rate of work offers during an effort-based decision-making task in one participant (PD5). Stimulation was delivered in a single-blinded, randomized, counterbalanced block-wise design at an amplitude below detectability threshold and without motor effects. Acceptance rate was modeled using a linear mixed model with stimulation condition (On vs Off) as a fixed effect.
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.

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Computational behavioral paradigms of reward processing
Time Frame: 48 months
Reward decision making and learning paradigms with paired neural recordings
48 months
Neurofeedback testing using cortical and subcortical signals
Time Frame: 48 months
Up and down regulation of cortical and subcortical signals with computational paradigms
48 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Simon J. Little, MBBS, PhD

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Simon Little, PhD, University of California, San Francisco

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 16, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 18, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 18, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 28, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 24, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 27, 2017

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 21, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 11, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 16-20284

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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