Locating Biomarkers in OCD Through Behavioral Tasks

This is a research study in which BCM is collaborating with Brown University/Butler Hospital
and University of Pittsburgh. BCM and Butler Hospital will be enrolling sites. Brown
University and University of Pittsburgh will be analyzing the assessment, EEG and facial
recognition data.

Subjects will participate in a clinical interview (Day 1), and cognitive tasks with EEG (Day
2).

Neural data (through EEG) will be collected from OCD subjects when their symptoms are
provoked, so we can look for biomarkers of that change. The subjects will be monitored
through EEG and video recording for facial recognition. After initial video and EEG setup
subjects will complete the Beads task followed by the Provocation task.

Day 1:

Demographics Questionnaire. Assesses psychiatric and medical treatment history.

SCID-5: Structured Clinical Interview for the DSM 5 (SCID): The SCID will be used to
determine comorbid diagnoses at baseline.

Yale-Brown Obsessive-Compulsive Scale (Y-BOCS): The YBOCS is a 10-item inventory that
assesses severity of OCD symptoms

Y-BOCS Symptom Checklist: The YBOCS symptom checklist assesses OCD symptom subtypes.

Trait Core Dimensions Questionnaire (TCDQ): The TCDQ measures prevalence of harm avoidant or
incompleteness traits related to OCD.

Beck Anxiety Inventory (BAI). The BAI is a 21-question self-report inventory that is used for
measuring the severity of anxiety. The questions used in this measure ask about common
symptoms of anxiety that the participant has had during the past week.

Beck Depression Inventory (BDI): The BDI is a 21-question self-report inventory designed to
measure depression severity.

Beads Task:

Participants will be asked to make a series of categorical decisions that involve combining
information about the value and probability of potential rewards. Subjects will sit in front
of a computer monitor and place their hand over a box with orange and blue button that they
will be asked to press based on their idea of which one will be the majority in a jar full of
orange and blue beads. This task is designed to dissociate information value and quantity as
the guesses are made based on information shown to the subject. Combining asymmetric rewards
beads task with neuroimaging could dissociate neural signals related to information value
from those related to information quantity. That is the goal here as we track neural activity
through EEG measurements and facial recognition through video acquisition. This task should
take 15-20 minutes to complete, not including EEG setup.

Provocation of OC symptoms (PROVOC):

PROVOC will be used to evoke manageable levels of OCD related distress. Three tasks will be
developed collaboratively with the participant and independent evaluator that involve the
participant being exposed in vivo to triggers that are considered by him/her impossible to
confront without ritualizing. Each of the 3 tasks will be broken up into 7 steps, which
provoke increasing levels of distress when encountered. Each step will be uniform in duration
(i.e., one minute exposure) with the potential of 7 one-minute tasks with ~30 seconds break
between steps, to provide brief rest for the patient and introduction of the next task.
Participants will systematically confront triggers without ritualizing starting with easier
items, and will continue until they feel their distress or need to ritualize is intolerable.
This task will involve researchers and subjects deciding upon a few different triggering
items (bloody (fake) napkin, used tissue, etc) that will be moved closer and closer to the
subject as they wear the EEG measuring system. Each step should take one minute or less, and
the subject will always have the option of stopping if the task becomes too distressing.
There will also be a similar process involving objects that should not cause any distress to
be used as a control. Consistent with prior research, 5 scores are calculated including
percentage of steps completed, subjective units of distress (SUDS) across steps, avoidance,
ritual engagement, and composite provocation score, which will be associated with changes in
biosignature from brain recordings. We will pilot the provocation protocol, and start
addressing problems that come up (e.g. EEG movement artifacts). Sessions will be videotaped
with AFAR system concurrent to recording of LFPs from VS and scalp EEG.

High-density EEG System:

The g.BCIsys64USB EEG system, manufactured by g.tec GmBH, uses wide-range DC-coupled
amplifier technology with 24-bit sampling, which results in an input voltage resolution of <
30 nV. Very efficient analog-to-digital converters (2.5 MHz per channel) result in very high
signal to noise ratio, critical for recording subtle changes in EEG measures. The system
combines four bio-amplifiers (16-channels each) that can either be stacked to provide a
higher density (32/48/64 channels) system, or can simultaneously be used on different study
participants. The EEG system makes use of 'active' electrode technology that employs an
additional ultra-low noise pre-amplifier located inside each electrode to maximize the
signal-to-noise ratio. The active electrodes work in a frequency range from 0 - 10 kHz (DC)
or 0.1 - 10 kHz (AC). The EEG system is also equipped with innovative data acquisition and
data analysis software that allows sophisticated signal processing and data analysis
capabilities. The system includes a 3D scalp digitizer that maps the scalp in the
stereotactic space for EEG source localization. Other capabilities of the system include
eye-tracking and acquisition of physiological data (SpO2, pulse and skin conductance).

Automated Facial Affect Recognition (AFAR) will be used to measure facial expression of
positive and negative valence. AFAR is a computer-vision based approach that can objectively
measure the occurrence, intensity, laterality, and timing of facial action units, head pose,
and gaze at video frame rate (30 to 60 frames per second). Participants will be videotaped.
Action units are anatomically based actions that individually or in combination can describe
nearly all-possible facial expressions. AFAR has strong concurrent validity with manual
measurement of facial action units, holistic expressions, depression severity, and
psychological distress; and with ground truth measures of head pose and gaze. Previous
research has identified action units associated with positive (e.g., enjoyment) and negative
(e.g., fear, anger, disgust, and anxiety) emotion; and used them to represent scales for
positive and negative valence and pain. Because gaze and head orientation also are strongly
related to emotion and valence, we include them in positive and negative valence scales.
Videotaped data will be shared with the University of Pittsburgh.

Local data and safety monitoring will be conducted by the PI who will meet regularly with the
study team to review new information from clinical ratings, assessments, and medical records
for each subject. Study-related adverse events or threats to subject confidentiality will be
monitored, and any needed safety changes will be addressed. Assessment of adverse events,
including grading of severity and attribution to research, will be conducted at each visit
and noted on the rating coversheet. The PI will report all unanticipated problems within 5
working days from becoming aware of the event. The PI will evaluate all adverse events and
determine whether the event affects the Risk/Benefit ratio of the study, and whether
modifications to the protocol or consent form are required.

Inclusion Criteria:

- Diagnosis of OCD

- Non-pregnant if female

- Minimum score of 16 on Y-BOCS

- Ability to provide informed consent

Exclusion Criteria:

- Those not meeting inclusion criteria listed above

- Lifetime diagnosis of psychotic disorders such as schizophrenia

- Alcohol or substance abuse/dependence within 6 months, excluding nicotine

- Deemed at high risk of suicidal behavior or impulsivity

- Pregnant or plans to become pregnant in the next 24 months