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.
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.
