Cortical Stimulation to Treat Mood and Behavioral Symptoms in Parkinson's
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Parkinson's Disease
- Sponsor
- Simon J. Little, MBBS, PhD
- Enrollment
- 5
- Locations
- 1
- Primary Endpoint
- Association Between Basal Ganglia Beta Power and Effort Level (Beta Coefficient)
- Status
- Completed
- Last Updated
- 5 months ago
Overview
Brief Summary
This study will investigate cortical stimulation to treat mood and behavioral symptoms in Parkinson's disease patients.
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.
Investigators
Simon J. Little, MBBS, PhD
Assistant Professor, Clinical Neurology
University of California, San Francisco
Eligibility Criteria
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:
- •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
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
Outcomes
Primary Outcomes
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.
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.
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.
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.
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.
Secondary Outcomes
- 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.)