ON/OFF Stimulation and Reward Motivation in Patients With Deep Brain Stimulators

DBS Patients:

The study will take place at a clinical office in the Charlestown Navy Yard (CNY), and will consist of one 8 hour visit with an optional second 8 hour visit, for a potential total of 16 hours. Study staff will schedule a convenient time for patients to arrive, or the research visit may be paired with a regularly scheduled DBS programming visit. A member of the Division of Neurotherapeutics authorized to manipulate DBS programming will turn the device on and off during the study. The subject's therapeutic parameters of the DBS system will not be changed. The subject will be asked to complete several questionnaires Beck Depression Inventory-II, Quick Inventory of Depressive Symptomatology, Snaith Hamilton Pleasure Scale, Mood and Anxiety Symptoms Questionnaire, and the Cognitive-Behavioral Avoidance Scale.

Following these questionnaires, a member of the study staff will teach the subjects to perform a modified version of the Approach-Avoidance task (adapted from Aupperle et al., in press and Amemori & Graybiel, 2012). Participants will be given a choice between a monetary reward (approach condition) plus an aversive stimulus (mild electric current further described below) or no monetary reward plus no aversive stimulus (avoid condition). Two partially filled rectangles (one red and one blue) will indicate the relative amount of potential punishment and reward. Subjects will use a joystick to direct a circle from a center fixation point to select either a plus sign associated with the approach condition or a square associated with the avoid condition. Subjects therefore control the outcome of each trial and whether or not they receive any aversive stimuli. After the task, participants will complete the AAC Task: Post-Questionnaire (adapted from Aupperle et al.)

The aversive stimulus is delivered in the form of a mild half second stimulation to the ankle at a level of their choice that is uncomfortable but not painful. This electrical current is produced by the Digitimer DS8R Constant Current Stimulator (Digitimer North America, LLC. Ft. Lauderdale, FL). Its previous model DS71 has been safely implemented in studies with previously MGH-approved IRB's (Milad et al., 2013). Patients will complete the task with DBS ON and DBS OFF. Because we are not changing the therapeutic parameters of stimulation, subjects should not experience any changes during the ON condition. Should any discomfort arise in the OFF condition, the subject will be able to terminate the study and return to the ON condition immediately.

Electroencephalography recordings (EEG) will be collected at 1450 Hz throughout the task in the ON and OFF conditions, using a Brain Research Products 96-channel active EEG system. Before each task run, we will also collect eyes-open and eyes-closed resting data, aiming for at least 1 min of data free from any eyeblink, muscle, or other artifact. All recordings will take place in a sound-isolated room, with careful scalp and electrode preparation to keep impedances under 5 kΏ. Ground/references will be in the midline to minimize hemispheric effects, and simultaneous EOG will permit blink/eyeroll artifact correction. The EEG system includes a camera, tracking devices, and software optimized for registration. All electrode positions will be digitized and referenced to subjects' pre-operative MRIs, enabling source-localized analysis.