ON/OFF Stimulation and Reward Motivation in Patients With Deep Brain Stimulators
ON/OFF Stimulation and Reward Motivation in Patients With Deep Brain Stimulators
We propose to study approach/avoidance behavior as measured by the Approach Avoidance task in
 20 epilepsy patients undergoing implementation of depth electrodes for seizure monitoring in
 the Epilepsy Monitoring Unit at MGH. We will also study the effects of VC/VS electrical
 stimulation on approach-avoidance conflict in 20 adult patients who have undergone DBS
 implantation for severe MDD and/or OCD. There are 100-200 patients in the world with DBS
 electrodes in the VC/VS, and our research team cares for more than any other institution.
 Both participant groups will be assessed with respect to reward-aversion decision conflict
 using the task. The task will be performed with concurrent EEG recordings in DBS patients,
 and with continuous recording through our invasive neurophysiology rig in EMU subjects.
DBS Patients:

 The study will take place at a clinical office in the Charlestown Navy Yard (CNY), and will
 consist of one 4 hour visit. 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.

 Epilepsy Patients:

 We will administer the same Ap-Av task in 20 epilepsy patients undergoing implantation of
 depth electrodes for seizure monitoring in the Epilepsy Monitoring Unit at MGH. Epilepsy unit
 experiments will involve both recording and stimulation. Recordings with the Ap-Av task will
 be collected throughout the clinical stay. At the end of the stay, there are 1-2 days when
 the patient resumes anti-seizure medications and the risk of a stimulation induced seizure is
 low. On those days, we will attempt to modify task behavior through stimulation. Based on our
 prior experience, we expect to test 1-2 stimulation targets per patient. In the first 10
 patients, we will seek to replicate results that pregenual ACC stimulation leads to increased
 avoidance. On a randomly selected 50% of trials (interleaved so that patients are blind to
 stimulation), we will bilaterally stimulate the pregenual ACC (single bipolar pair per
 hemisphere) at 130 Hz and 2 mA, for 600 ms during cue presentation. In the subsequent 10
 patients, we will attempt to extend the result that dACC theta power predicts approach
 behavior. When theta power rises above a set threshold (determined during the recording-only
 days), we will again stimulate the pACC.

 For patients who have been implanted with clinical intracranial electrodes (whether or not
 they have also been implanted with research electrodes), additional scalp electrodes may be
 used. Usually, some electrodes are placed on the scalp for clinical purposes (as decided on
 by the clinical team). Patients receiving depth electrodes, for example, usually receive a
 standard set of scalp electrodes as well. However, if the clinical team decides that only a
 very small number of electrodes are needed for their purposes we may supplement this further
 with less than 10 additional electrodes. For this purpose, routinely-used clinical scalp
 electrodes (including EOG and EMG) will be employed. The exact number and placement will be
 constrained by clinical parameters. Specifically, regions close to any wound will be avoided
 to minimize the risk of infection. Also, as the clinical recording systems have limited
 numbers of channels, additional recording electrodes will be limited to what channels are
 available. In cases where a full set of scalp electrodes are used, the amount of time they
 are on the patient's head will be limited to approximately one day to decrease the risk of
 infection. This additional recording will be done one day before the scheduled date for
 removal of the intracranial electrodes.
DBS Patients:

 Inclusion Criteria:

 • Deep brain stimulator implantation performed at least three months prior to study

 Exclusion Criteria:

 -  Subjects unable to visualize stimulus objects with correction

 -  Dementia or other known cognitive deficit

 Psychiatric Patients:

 Inclusion Criteria:

 -  Right-handed (as determined by the Handedness Inventory; Oldfield,1971)

 -  Normal or corrected-to normal vision and hearing

 -  Current diagnosis of MDD or OCD

 Exclusion Criteria for Patients:

 -  Clinical history of bipolar disorder

 -  Current or past psychotic disorder

 -  Gross structural brain damage

 -  Cognitive impairment that would affect a participant's ability to give informed
 consent

 -  Current substance abuse, or abuse within the past 3 months

 -  Clinical history of severe personality disorder

 -  Imminent risk of suicide or an inability to control suicide attempts

 -  Evidence of dementia or other significant cognitive impairment on neuropsychological
 evaluation