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

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, 3) Develop closed-loop stimulation paradigms and 4) 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 Activa
PC+S pulse generator (Medtronic), an investigational device 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. 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.

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 QUIP-A (Questionnaire
for Impulsive-Compulsive disorders in Parkinson's Disease) 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.