Sensory Filtering in the Human Basal Ganglia as a Mechanism of Parkinson's Disease

The purpose of this study is to investigate the functional role of the human basal ganglia in the sensorimotor system. In particular, the investigators are interested in the possibility that the basal ganglia participate in "filtering out" sensory stimuli that are irrelevant to the current behavioral goal. Additionally, the investigators are interested in how this type of sensorimotor processing in these brain areas is related to the severity of movement disorders such as Parkinson's disease and essential tremor.

To do this, the investigators will study both healthy individuals and Parkinson's disease patients undergoing routine deep brain stimulation (DBS) surgery. During the surgery, investigators will place the DBS electrode as routinely performed and additionally place an extra, temporary "strip" electrode along the surface of the brain. Participants will then perform a short behavioral task testing sensorimotor function while investigators record the neural signals from these electrodes. The task will involve the delivery of sensory stimuli (visual, vibrotactile, electrical, and/or proprioceptive), to which the participant will be asked to perform a certain motor response. In order to fully measure the variables of interest, investigators will also attach small stickers (electrodes) to the skin of areas involved in movements for measuring muscle activity (such as the face and limbs), and may attach small, noninvasive devices around the wrist, finger, or arm (e.g., accelerometers) that measure position. The investigators may also apply EEG electrodes to the scalp to measure global brain activity or place a microphone in front of the subject to record speech.

In addition to recording this baseline brain activity, the investigators will evaluate whether deep brain stimulation and dopaminergic medication alters the recorded activity and task performance. Typical deep brain stimulation involves administering specific parameters of high-frequency electrical pulses to achieve clinical benefit. Routine operations involve testing these parameters in the OR in awake patients. For this study, investigators will administer either this high-frequency stimulation or various other patterns of stimulation (e.g., low-frequency, burst stimulation) and measure the changes in behavior and brain activity. As a method of validation, the investigators will also deliver paired pulses of stimulation that enable analysis of stimulation-evoked activity.

Finally, the investigators will correlate recorded brain activity with measures of participants' individual disease severity.

Inclusion criteria

(PD participants):

• Age >18 years
• Clinically definite, advanced idiopathic PD based on consensus criteria.
• Normal, or essentially normal, preoperative brain MRI.
• Patient is available for follow-up visits over the length of the study
• Patient has elected to undergo DBS surgery as part of routine care, and subthalamic nucleus (STN) is determined as the appropriate surgical target

Inclusion criteria

(control participants):

• Age >18 years.
• No diagnosis of PD, other movement disorder, or other significant neurological disease.

Exclusion criteria

(PD participants):

• Age <18 years.
• Medical contraindications such as current uncontrolled hypertension, heart disease, coagulopathy, or other conditions that might increase the risk of surgery
• Diagnosis or suspicion of atypical Parkinsonism (PSP, MSA, CBD) or drug-induced Parkinsonism, or significant neurological disease other than PD.
• Diagnosis of psychogenic movement disorder based on consensus criteria
• Prior DBS surgery or ablation
• Clinical dementia and/or Dementia Rating Scale (DRS) score of <5th percentile adjusted for age and education level, based upon routine pre-op NP testing.
• Unable to withhold dopaminergic medications for at least 12 hours prior to scheduled visit

Exclusion criteria

(control participants):

• Age <18 years.
• Previous diagnosis of PD, other movement disorder, or other significant neurological disease.