tDCS for Inhibitory Control Deficits: A Test in OCD
Phase: NA
Conditions: Obsessive-Compulsive Disorder
Sponsor: Butler Hospital

 
Date most recently revised (02/16/18) 
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tDCS for Inhibitory Control Deficits: A Test in OCD. Alternate title (Consent Form): 
Transcranial Direct Current Stimulation Augmented Exposure and Response Prevention 
 for Obsessive-Compulsive Disorder 
 
NCT02329587 
 

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II.  DESCRIPTION OF STUDY 
A.  Specific Aims   
The long-term goal of this research program is to leverage a well-developed body of literature 
on the neural basis of response control to develop more effective treatment approaches for patients 
with deficits in behavioral inhibition. The overall objective of this project, which is the first step 
toward this long-term goal, is to evaluate feasibility, acceptability, and preliminary efficacy of 
transcranial direct current stimulation (tDCS) over right inferior frontal gyrus (rIFG) as an adjunct to 
exposure and response prevention (ERP) for obsessive-compulsive disorder (OCD) patients. The 
rationale for this proposal is that effectively enhancing inhibitory control in OCD patients may allow 
them to better engage in ERP, resulting in improved treatment outcomes. The objectives will be 
achieved by pursuing these specific aims:  
Aim 1: Establish feasibility and acceptability of research procedures and clinical 
intervention.  
Hypothesis: Patients with OCD will tolerate this combined ERP + tDCS treatment and will find it 
acceptable, as determined by rates of retention, treatment completion, and patient report.  
Aim 2: Gather evidence on preliminary efficacy of tDCS over rIFG as an adjunct to ERP for 
OCD.  
Hypothesis: Patients in the group receiving ERP + active tDCS will show greater reduction in 
symptom severity over 10 sessions of the combined treatment than those receiving ERP + sham tDCS.  
Aim 3: Characterize the relationship between measures of inhibitory control and outcome 
of the combined intervention.  
Hypotheses: a) Response inhibition, as measured by the stop signal task (SST), will improve more 
after ERP plus active vs sham tDCS; b) Improvement in OCD severity will correspond to improved 
inhibitory control on the SST; and c) Patients receiving ERP plus active tDCS will report less difficulty 
inhibiting compulsions during ERP exercises than those receiving ERP plus sham tDCS. 
 
B.  Background  
Deficient inhibitory control is a hallmark of many types of psychopathology, including 
attention deficit hyperactivity disorder, substance abuse and dependence, and obsessive-compulsive 
and related disorders. As of yet, there are no established interventions broadly targeting deficits in 
inhibitory control. Addressing inhibitory control deficits is now a tractable problem. The 
neurocircuitry underlying behavioral inhibition is becoming increasingly well understood while, 
simultaneously, non-invasive methods of modulating brain functioning, such as transcranial direct 
current stimulation (tDCS) are seeing a resurgence in both clinical and research settings. The time is 
right to begin leveraging findings in neuroscience to develop a neurocircuit-based method to address 
disorders of inhibitory control.  
Obsessive-compulsive disorder (OCD) patients are one group with well-established deficits in 
behavioral inhibition. The ritualistic compulsions which characterize this disorder clearly indicate 
difficulty with inhibitory control. In inhibition paradigms, OCD patients consistently perform worse 
than healthy individuals on tasks requiring inhibition of a prepotent response (e.g., stop-signal task, 
go/no-go task). A recent study by Gillan et al. also found that patients with OCD continue responding 
in a way they have learned will avoid punishment despite explicit knowledge that punishment is no 
longer possible.  

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Paradoxically (given these deficits), successful inhibitory control is also an essential 
component of the first-line psychosocial treatment for OCD – exposure and response prevention 
(ERP). During ERP, patients face situations which trigger irrational fear or discomfort (i.e., exposure), 
while simultaneously inhibiting their compulsions (i.e., response prevention). ERP is effective at 
reducing symptom severity for many patients who complete a full course of the treatment; however, 
few patients are “cured” of their symptoms following ERP and many patients are unwilling or unable 
to complete a full course of this challenging treatment. Although this is the best known treatment, it 
is, unfortunately, far from perfect in its outcomes.  
Enhancing inhibitory control via non-invasive neurostimulation may improve the efficacy and 
efficiency of ERP for OCD. The right inferior frontal gyrus (rIFG) is a particularly promising target for 
such an approach. This region is a key node in neurocircuitry underlying inhibition of a prepotent 
response. The location of rIFG makes it easily accessible to tDCS, a type of non-invasive 
neurostimulation delivering a weak electrical current (1-2 mA) via two electrodes placed on the scalp. 
Neurostimulation via tDCS modulates neuronal excitability by changing membrane potentials and 
can enhance behavioral plasticity. In healthy individuals, tDCS over rIFG improves inhibitory control 
of a prepotent response during the SST, a well-established response inhibition paradigm. Such effects 
have been seen after a single tDCS session, and when stimulation over rIFG was delivered during a 
course of inhibition training sessions over four days. We propose to extend this approach by coupling 
tDCS and behavioral training, i.e., ERP, to inhibit compulsive behaviors in OCD.  
 
C.  Experimental Method 
 
1.  Brief Description of Subjects 
For the TIES (Therapy Integrating Exposure and Stimulation) study we will recruit 32 patients with a 
primary diagnosis of OCD, aged 18-65, with clinically significant OCD symptoms (Y-BOCS total score 
of ≥16). Participants will be naïve to tDCS and will never have completed a minimally adequate trial 
of ERP (see human subjects section below for additional inclusion/exclusion criteria). 
 
 
2.  Study Design 
For this study we will recruit 32 patients with a primary diagnosis of OCD. Each participant will 
undergo an assessment which will include a structured clinical interview, brief assessments of 
depression, anxiety, OCD symptoms, and medication and treatment history. Participants will be 
randomized to one of two combination interventions: Exposure and response prevention (ERP) plus 
active transcranial direct current stimulation (tDCS) over right inferior frontal gyrus (rIFG) or ERP 
plus sham tDCS over rIFG. Each group will complete 1 session of psychoeducation and treatment 
planning, followed by 10 90-minute sessions of their assigned combination intervention. Participants 
will also complete a post-treatment and one month follow-up assessment. 
 
3.  Specific Procedures or Treatments 
Screening. Interested individuals will be screened via brief telephone interviews and those meeting 
entry criteria will be invited to participate. After providing informed consent to trained study 
personnel, patients will complete a thorough screening interview which will include the following 
measures: the Structured Clinical Interview for DSM-IV (SCID-IV) will be used to verify a DSM-IV 
diagnosis of OCD, as well as to assess for comorbid Axis I diagnoses which constitute exclusion from 
the study (see “Participants”). We will supplement the SCID by asking  a few additional questions as 
part of the semi-structured interview to assess new specifiers added to the DSM-5 OCD diagnosis 
(e.g., tic-related OCD and absent insight) ; a modified version of the OCD Database,41 a semi-

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structured clinical interview, will be used to gather information about demographic and clinical 
features of OCD and assess medication and treatment history; the Hoarding Rating Scale will be used 
to assess any hoarding symptoms endorsed on the Y-BOCS-SC; the Yale-Brown Obsessive 
Compulsive Scale -- Symptom Checklist (Y-BOCS-SC), a 58-item checklist, will be used to assess 
presence/absence of specific current and past OCD symptoms43, 44; the Yale-Brown Obsessive 
Compulsive Scale (Y-BOCS) will be used to assess OCD symptom severity43, 44; the Beck Depression 
Inventory-II (BDI-II)45 will be used to assess depressive symptoms, including suicidality; the 
Cognitive-Behavioral Treatment History Form (Abramowitz, 2006) , will be used to assess whether a 
patient has had an adequate course of CBT for OCD.  
 
Monitoring Assessments. 
To monitor for symptom 
change, short 
assessments will be 
given at baseline, and 
approximate weekly (see 
Table 1) during  
treatment (for clinical 
symptoms monitoring), 
post-treatment, and 1-
month after treatment, 
using the Y-BOCS43, 44; 
BDI-II45 (see “Screening,” 
above); and the Beck 
Anxiety Inventory 
(BAI),46 to assess general 
anxiety symptoms. The 
Patient Ex/RP Adherence Scale (PEAS)47 will be used at each ERP session to assess adherence to ERP 
homework, since adherence relates to treatment outcome.48 Patients will also complete the 8-item 
Client Satisfaction Questionnaire (CSQ-8)49 at post-treatment and 1-month follow-up to assess 
satisfaction with the intervention. A modified version of the Systematic Assessment for Treatment 
Emergent Events-Specific Inquiry (SAFTEE-SI) will be administered assess for emergent side-effects. 
This is a self-report measure which inquires about the presence and severity of 55 of the most 
commonly reported side effects in clinical trials, as well as how much reported side effects bother 
patients or interfere with daily activities. The SAFTEE-SI will be administered at baseline, at sessions 
1, 3, 5, 7, and 9, at post-treatment, and at 1 month follow-up. At each administration, the evaluator or 
therapist will note items rated more bothersome than during the previous administration. The 
therapist or evaluator will inquire further about each such item, including asking for a description of 
the side effect, when it occurs, how much it interfered, and what the participant attributes the 
symptom to. The therapist or evaluator will also inquire in an open-ended fashion about any other 
adverse effects experienced which are not listed on the SAFTEE-SI and will document the nature and 
tolerability of any additional side-effects reported. For any item rated "severe," or if the participant 
reports that side effects are interfering with daily activities "markedly," the therapist or evaluator will 
notify Dr. [Name] MD (PI) (or covering physician) immediately and Dr. [Name] (or covering 
physician) will provide further evaluation as medically necessary. Any item rated as "moderate" or 
Table 1. Schedule of Assessments 
Assessment 
Scr BL Psychoed/
Planning 
Sn1 Sn2 Sn3 Sn4 Sn5 Sn6 Sn7 Sn8 Sn9 Sn10 PT 1M 
SCID-IV 
X X 
 
 
 
 
 
 
 
 
 
 
 
 
 
OCD Database 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Med. History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hoarding Rating Scale X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Y-BOCS-SC 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Y-BOCS 
X X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X X 
BDI 
X X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X X 
BAI 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X X 
PEAS 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
SST 
 
X 
 
 
 
 
 
 
 
 
 
 
 
X X 
CSQ-8 
 
 
 
 
 
 
 
 
 
 
 
 
 
X X 
Inhibition VAS 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
SAFTEE-SI 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X X 
FMPS 
 
X 
 
 
 
 
 
 
 
 
 
 
 
X X 
POPS 
 
X 
 
 
 
 
 
 
 
 
 
 
 
X X 
OBQ 
 
X 
 
 
 
 
 
 
 
 
 
 
 
X X 
IUS 
 
X 
 
 
 
 
 
 
 
 
 
 
 
X X 
OC-TCDQ 
 
X 
 
 
 
 
 
 
 
 
 
 
 
X X 
Scr=screen, BL= baseline, Sn=Session, PT=Post-treatment, 1M=1month follow-up 

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"moderately" interfering will be reported to Dr. [Name] by the therapist or evaluator within 24 hours. 
All other reported side-effects endorsed on the SAFTEE-SI will be discussed with Dr. [Name] during 
weekly meetings of study staff. Additionally, the following self-report measures will be given at 
baseline, post-treatment, and 1-month follow-up: the Frost Multidimensional Perfectionism Scale 
(FMPS), to assess dimensions of perfectionism; the Pathological Obsessive-Compulsive Personality 
Scale (POPS), to assess current Obsessive Compulsive Personality Disorder; the Obsessional Beliefs 
Questionnaire (OBQ), to assess dysfunctional beliefs typical of OCD patients; the Intolerance of 
Uncertainty Scale (IUS), to assess reactions to uncertainty, ambiguous situations, and the future; and 
the Obsessive-Compulsive Trait Core Dimensions Questionnaire (OC-TCDQ), a measure of harm 
avoidance and incompleteness. Finally, at the post-treatment assessment, we will use a questionnaire 
to probe the integrity of the blind. 
 
Measures of Inhibitory Control. Stop-signal task (SST). We will evaluate the impact of active vs sham 
tDCS plus ERP on a laboratory measure of inhibitory control (Aim 3). Participants will be tested using 
the SST50 at baseline, post-treatment, and 1 month post-treatment. During the SST, participants will 
see images of either a right- or left-pointing arrow on a computer screen. They develop a prepotent 
response (based on instruction) to press a button with their right or left index finger, congruent with 
the direction of the arrow. On a small percent of trials, participants will hear a beep, indicating they 
should try to stop themselves from pressing the button. The primary outcome variable used to assess 
inhibitory control is stop-signal reaction time (SSRT), which is the estimated time it takes to inhibit the 
prepotent response. Visual Analog Scale (VAS). To evaluate the impact of active vs sham tDCS plus 
ERP on participants’ clinical state, we will use a self-report, asking them to rate their ability to resist 
engaging compulsive behavior during the ERP exercises. Immediately after each ERP exercise, they 
will rate their experience on a standard VAS, a face-valid assessment of inhibitory control in the 
clinical context. 
 
tDCS procedures. tDCS delivers brain stimulation noninvasively. While cellular and molecular 
mechanisms of tDCS are still under investigation, it is known to modulate the excitability of 
underlying cortex.53, 54 During tDCS, the low amplitude current (typically 1-2 mA) is delivered via two 
scalp electrodes.54 This low-level current passes from the positive electrode, or anode, to the negative 
electrode, or cathode. When current passes from anode to cathode, it simultaneously enhances 
excitability of the cortex by the anode and decreases excitability near the cathode53, 54 If tDCS is 
delivered for a sufficient duration (e.g., >10 min,) these excitability changes have been found to persist 
for up to 1 hour.55, 56 There is strong indication that long-lasting changes in excitability can be induced 
with repeated stimulation, giving tDCS the potential for use as a therapeutic tool.57 The tDCS device is 
battery-powered and is adjustable in both intensity and duration of stimulation delivered.  
While tDCS was first used more than a century ago, it has recently seen a marked resurgence 
of interest in basic and systems neuroscience,54 and in neurotherapeutics research.58 A recent review of 
clinical research with tDCS40 noted that “tDCS has been tested in thousands of subjects world-wide 
with no evidence of toxic effects to date.” The most common side effects include mild local sensations 
at the electrode sites, including tingling or itching, and moderate fatigue, and headache.40, 59 In 
general, these effects have paralleled those of sham stimulation. In research experience totaling 567 
tDCS sessions, no participants requested tDCS be stopped or required any medical intervention 

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during or after stimulation.59 Notably, adverse effects did not differ between healthy individuals and 
patients.59 Additional safety information is detailed in Human Subjects.  
 
 
In the present study, each participant will undergo 10 separate 20-minute sessions of either 
active or sham tDCS in a between-subjects design. Each session of tDCS will be immediately followed 
by a behavioral intervention (see “Behavioral Intervention” section below). Active tDCS intensity will 
be 1.5 mA. The anode and cathode are each contained in a 5x5cm rectangular sponge (25 cm2). 
Electrode placements will follow Jacobson et al.19: the anode will be over rIFG, defined as the 
intersection between T4-Fz and F8-Cz in the EEG 10-20 system and the cathode over the left eyebrow 
(over lOFC). Small marks may be placed on the scalp with a washable, non-toxic marker to aid in the 
correct placement of the electrodes.  tDCS will be delivered via two saline-soaked surface sponge 
electrodes and a battery-driven, constant current stimulator (NeuroConn DC-Stimulator Plus). For 
those randomized to sham tDCS, electrodes will be placed in the same locations as for active tDCS. To 
simulate the sensation of active tDCS, stimulation will be ramped up and back down over a 30-second 
period at the beginning of sham tDCS. This “ramp up/ramp down” sham approach has been found to 
be an effective sham condition in previous studies using tDCS at 1-2mA.60-62 Immediately following 
the 20-minute tDCS period participants will undergo the following behavioral intervention: 
 
Behavioral Intervention: Exposure and Response Prevention (ERP) is a specific type of CBT that has 
been shown to be effective at reducing symptom severity in OCD. ERP involves individuals placing 
themselves in anxiety-provoking situations (exposure) and inhibiting their compulsions (response 
prevention). Compulsive behaviors usually serve as an attempt to reduce distress. By refraining from 
compulsions, participants gain corrective information that the feared situation is not dangerous. ERP 
typically proceeds in a graded manner, as it will here, beginning with exposure to more manageable 
situations and progressing to more difficult situations as treatment continues. The behavioral 
intervention here includes 11 sessions in total: one 90-minute session including psychoeducation and 
treatment planning followed by 10 ERP sessions lasting approximately 90-min each. These 11 sessions 
will be delivered twice-weekly over a 5.5 week period. All intervention sessions must be completed 
within a maximum of seven weeks. Between sessions, self-directed ERP will be assigned as 
homework. During each of the 10 ERP sessions, tDCS will be delivered for 20 min immediately prior 
to the ERP exercise. We selected a 10-session ERP intervention (plus 1 session of psychoeducation and 
treatment planning) in an attempt to balance feasibility with allowing sufficient sessions to evaluate 
treatment effects. While 10 sessions is shorter than most manualized ERP protocols, ERP interventions 
of similar length, session frequency, session content, and design have often been used to evaluate the 
efficacy of augmentation of ERP with pharmacotherapy including D-cycloserine (Kushner et al., 2007; 
Storch et al., 2010; Wilhelm et al., 2008). All sessions will be audio recorded using digital voice 
recorders in order to assess for treatment fidelity. As stated below, 15% of sessions will be reviewed to 
ensure adherence to the treatment protocol. In order to obtain an unbiased assessment of therapist 
fidelity to the intervention, participants will not be allowed to opt out of session recording. (Handling 
of digital audio recordings to protect against loss of confidentiality and privacy is outlined below 
under III. Human Subjects.) 
 
Assessment Training and Monitoring of Treatment Integrity. Assessments will be completed by a 
trained, supervised, advanced (i.e., BA or higher) evaluator who will be kept blind to participant’s 
group assignment. The evaluator will initially be trained to an inter-rater reliability of ≥ 0.80. 
Assessments will be audio recorded and will be checked periodically to minimize rater drift. To 

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ensure fidelity to the intervention and consistency between therapists, study therapists will undergo 
training in this approach including directed readings and regular supervision of on-going cases. 
Treatment sessions will be audio recorded and a randomly selected 15% of sessions will be reviewed 
to ensure adherence to the treatment protocol.  
 
Participant Withdrawal. Participants may be withdrawn from the study for any of the following 
reasons: 1) A significantly deteriorating clinical course, such as the emergence of active suicidal 
ideation or a need for hospitalization, 2) Significant adverse reaction to tDCS, assessed using a 
modified version of the Systematic Assessment for Treatment Emergent Events (SAFTEE), 3) Serious 
physical illness, 4) Missing two consecutive study visits, 5) Initiation or reinstitution of other 
treatment (psychosocial treatment with proven efficacy, psychotropic medication changes) during the 
acute treatment phase, 6) Investigators’ decision that withdrawal from the study is in the participant’s 
best interest, 7) Participant’s decision to withdraw. Reasons for withdrawal will be documented, 
participants will be referred for appropriate treatment, and we will make every attempt to conduct 
scheduled follow-ups with those who withdraw. The current study will employ several measures to 
minimize attrition, including frequent contact with participants for the duration of the study and 
compensation for participants’ time for post-treatment and follow-up assessment visits. 
 
 
 
4.  Data Analysis  
Original Data Analysis Plan: 
Preliminary and Primary Data Analyses. As the proposed study is a small-sample pilot study, our 
primary focus will be on examining feasibility, acceptability, and direction of effects. Additionally, all 
randomized participants will be used in an intent-to-treat analysis. We will use chi-square and t-tests 
to evaluate any differences between the two conditions at baseline on demographic and other relevant 
variables, such as initial symptom severity, comorbid depression, or patient adherence to ERP 
homework. If significant differences exist, we will covary for these variables in our analyses (though 
we do not anticipate significant group differences at baseline, as urn randomization tends to result in 
balanced samples.)  
 
Aim 1: Establish feasibility and acceptability of research procedures and clinical intervention. 
Hypothesis: Patients with OCD will tolerate this combined ERP + tDCS treatment and will find it 
acceptable, as determined by rates of retention, treatment completion, and patient report. For Aim 1, 
we will chi-square or t-test to compare treatment conditions on rates of retention, session attendance, 
homework and treatment completion, and patient satisfaction on the CSQ-8.  
 
Aim 2: Gather evidence on preliminary efficacy of tDCS over rIFG as an adjunct to ERP for OCD. 
Hypothesis: Patients in the group receiving ERP + active tDCS will show greater reduction in 
symptom severity over 10 sessions of the combined treatment than those receiving ERP + sham tDCS.  
For Aim 2, we will use repeated-measures ANOVA with a between-group factor (condition) to 
evaluate differences in Y-BOCS severity between groups across assessment timepoints. Since this is a 
small pilot study (N=32), we will also examine group means and direction of effects across all 
timepoints, not relying solely on statistical approaches which may be underpowered to detect a 
significant effect.  
 

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Aim 3: Characterize the relationship between measures of inhibitory control and outcome of the 
combined intervention. Hypotheses: a) Response inhibition, as measured by the SST, will improve 
more after ERP plus active vs sham tDCS; b) Improvement in OCD severity will correspond to 
improved inhibitory control on the SST; and c) Patients receiving ERP plus active tDCS will report 
less difficulty inhibiting compulsions during ERP exercises than those receiving ERP plus sham tDCS.  
To test our hypotheses for Aim 3, we will: a) use independent measures t-tests to compare change in 
SSRT from pre- to post-treatment between conditions, and from pre-treatment to follow-up; b) 
compute a correlation between percent change in Y-BOCS score and percent change in SSRT from 
baseline to post-treatment, and from baseline to 1-month follow-up, c) use an independent measures 
t-test to compare self-reported mean difficulty inhibiting compulsions (VAS) during ERP across 
stimulation conditions.  
 
Revised Data Analysis Plan: 
Preliminary and Primary Data Analyses. Given that this study resulted in a smaller than 
anticipated final sample size, we created a revised analysis plan, appropriate for the smaller 
sample. Consistent with the original plan for this pilot study, our primary focus will be on examining 
feasibility, acceptability, and direction of effects. Additionally, all randomized participants will be 
used in an intent-to-treat analysis. Analyses will focus on descriptive statistics (e.g., means or 
proportions) with between-group effect sizes calculated, as appropriate.  
 
Aim 1: Establish feasibility and acceptability of research procedures and clinical intervention. 
Hypothesis: Patients with OCD will tolerate this combined ERP + tDCS treatment and will find it 
acceptable, as determined by rates of retention, treatment completion, and patient report. Our 
primary feasibility outcome of interest is rates of session completion. Our primary acceptability 
outcome is patient-reported client satisfaction.  
 
Aim 2: Gather evidence on preliminary efficacy of tDCS over rIFG as an adjunct to ERP for OCD. 
Hypothesis: Patients in the group receiving ERP + active tDCS will show greater reduction in 
symptom severity over 10 sessions of the combined treatment than those receiving ERP + sham tDCS.  
For Aim 2, we will examine group means on the Y-BOCS and direction of effects at post-treatment, 
and 1-month follow-up , not relying on statistical approaches which will be underpowered to detect 
an effect. The Y-BOCS is our primary clinical outcome. 
 
Aim 3: Characterize the relationship between measures of inhibitory control and outcome of the 
combined intervention. Hypotheses: a) Response inhibition, as measured by the SST, will improve 
more after ERP plus active vs sham tDCS; b) Improvement in OCD severity will correspond to 
improved inhibitory control on the SST; and c) Patients receiving ERP plus active tDCS will report 
less difficulty inhibiting compulsions during ERP exercises than those receiving ERP plus sham tDCS. 
We regard aim 3 and related hypotheses to be largely exploratory. To investigate our hypotheses for 
Aim 3, we will:  a) calculate mean change in SSRT from pre- to post-treatment, and from pre-
treatment to follow-up for both conditions, and between groups effect size; b) compute a correlation 
between percent change in Y-BOCS score and percent change in SSRT from baseline to post-
treatment, and from baseline to 1-month follow-up, c) calculate self-reported mean difficulty 
inhibiting compulsions (VAS) during ERP and direction of effects across stimulation conditions.  
 

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D.  Material Inducements 
Compensation for participation in assessments will be offered as part of this study. No compensation 
will be offered for participation in ERP sessions. Participants will receive a payment of $25 for 
completing the screening assessment. Participants will participate in a total of 8 additional 
assessments during the study (baseline, sessions 1, 3, 5, 7, 9, post-treatment, and 1 month follow-up); 
they will received payment for completion of each of these assessments ($30 for the baseline 
assessment, $10 for each mid-treatment assessments, $40 for the baseline assessment, and $40 for the 
post-treatment assessment) for maximum compensation of $185 for completing the screening and all 
assessments. Participants will have the option to receive payment by check in the mail or Stop & Shop 
gift card after each assessment. 
 
E.   Training of Research Personnel 
All research personnel will be trained to properly administer the study instruments by the Co-PIs. All 
research staff will have completed research ethics training—including data management and 
procedures for maintaining data confidentiality and safety—before being allowed to work on the 
project. Postdoctoral therapists training in ERP will include assigned readings, listening to training 
sessions, role play, and weekly supervision. Therapists will also be trained in tDCS prior to 
administering stimulation in this protocol. A physician with advanced training in neuromodulation 
techniques (Dr. [Name] or another qualified research physician) will oversee all tDCS administration 
and will be immediately available for management of emergent events. Prior to administering tDCS 
in this protocol, all research clinicians will be required to undergo training and demonstrate 
competence in the safe delivery of tDCS. There are multiple components of training for a research 
clinician to be qualified for administering tDCS:  
 
(1) The PI [Initials] will provide initial didactic training to introduce concepts critical to tDCS. 
Reading materials and lecture format will be used to teach the basic electrophysiology principles that 
underlie the mechanism of tDCS for modulating neuronal activity. Visual aids will be used to convey 
anatomical guidelines used for identifying targets for electrode placement. Theoretical considerations 
for choice of stimulation targets, electrode size and montage, and stimulation parameters will be 
reviewed (though these factors will not vary in the current study). Training will include methods for 
identifying and managing potential side effects from the tDCS procedure, and review of procedures 
for managing a patient found to have significant clinical deterioration that could put him or others at 
risk for harm.  
 
(2) Research staff will observe each of the following activities with a minimum of 3 participants: a) 
administration of a safety screening questionnaire and interviewing prospective study participants to 
assess possible contraindications to the method; b) administration of tDCS following standard 
methods; c) “debriefing” of participants immediately following the tDCS and evaluation of any 
treatment-emergent adverse effects.  
 
(3) Research staff will have ample opportunity to practice the various steps of setting 
up/administering tDCS and conducting pre/post treatment clinical evaluations, on non-patient 
volunteers. Practice will include role play session for administering the modified SAFTEE instrument 

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as part of routine safety assessment, role-play of scenarios in which the PI or another physician 
should be summoned to further address adverse events related to the study protocol.  
 
(4) Research staff will demonstrate competency in all aspects of relevant subject assessment and in 
administration of the entire tDCS procedure on a minimum of 2 participants, under direct observation 
by the PI [Initials]. Competence in specific aspects of the procedure comprising best practice 
standards for tDCS will be documented in line with [Name] Hospital policy.  
 
(5) Subject feedback will be solicited to further aid training and refine the skills of research staff 
delivering tDCS in this protocol. 
 
III.  HUMAN SUBJECTS  
 
A.  Subject Population (include number; gender; age; diagnosis; inpatient vs. outpatient; 
 
physical health; inclusion/exclusion criteria; rationale for use of special groups)  
For this study we will recruit 32 outpatients with a primary diagnosis of OCD: Inclusion criteria are as 
follows: (1) current DSM-5 OCD diagnosis and current Y-BOCS total score of ≥16, (2) 18-65 years of 
age; (3) ability to speak, read, write, and understand English sufficiently well to complete study 
procedures and provide informed consent; (4) no use of psychiatric medications  or stable psychiatric 
medication use for a minimum of 6 week prior to study entry. Psychiatric medications will be limited 
to the following: serotonin reuptake inhibitors (SRI; including clomipramine) , combination 
antidepressants (including bupropion and SNRIs), buspirone, benzodiazepines, stimulants and/or 
antipsychotics (with the exception of aripiprazole) ; (5) naive to tDCS; Exclusion criteria include: (1) 
active substance use disorder; (2) lifetime diagnosis of psychotic or bipolar mood disorder; (3) 
previous minimally adequate trial of ERP (at least 16 sessions including both therapist and self-
directed exposure and response prevention), (4)  therapy outside the study protocol which has 
evidence for efficacy with OCD during the study intervention period, (5) active suicidal or homicidal 
ideation; (6) organic brain disease or injury; (7) any health problems that would interfere with study 
participation, including contraindications to tDCS (e.g., skin condition, mental implant in skull), (8) 
Women who are pregnant or breastfeeding.  All women participants of child-bearing age are required 
to have a negative pregnancy test prior to treatment, and must use medically acceptable birth control 
during study participation. Medically acceptable birth control includes: established oral, injected, 
implanted, or vaginal ring hormonal contraception, an intrauterine device (IUD), two barrier 
contraception methods (condom or occlusive cap with spermicidal foam/gel/film/cream/suppository), 
or having a vasectomized partner, (10) use of anticonvulsant medications (including depakote, 
gabapentin, tegretol, dilantin, lamictal) and/or glutamate-acting agents (including n-acetylcysteine, 
riluzole, amantadine, memantine). 
 
B.  Recruitment and Consent Procedures  
Participants will be primarily recruited from the [Name] Hospital OCD Clinic which serves over 300 
active patients and has averaged 120 new OCD patient evaluations annually for 20 years. Past study 
recruitment efforts through this clinic have been very successful. Any recruitment materials 
developed for the web, or other advertisements for potential participants, will be submitted to the IRB 
for approval prior to postings.  

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Participants who appear to meet criteria for participation will be approached by study staff, provided 
with a brief verbal description of the study, and invited to participate. An initial assessment session 
will be scheduled. During the initial session, potential participants will again be provided with a 
description of the study and if they remain interested, study staff will obtain written informed 
consent. Participants will be given the opportunity to ask any questions they may have, and they will 
receive a copy of the informed consent document including contact information, should any questions 
or concerns arise at a later time.  
 
C.  Potential Risks   
There are relatively few risks involved in the proposed study. Potential risks to all subjects include: 
(1) Coercion. Subjects may feel coerced to participate, (2) Breach of confidentiality or loss of privacy. 
In the course of this study we will collect sensitive information which, if released, may cause shame, 
embarrassment, or distress; (3) Distress due to assessment procedures. During the assessments we 
will ask participants about their thoughts, feelings, behaviors, and symptoms. It is possible that 
asking participants about this information may increase distress or discomfort. (4) Risks due to tDCS. 
There is some inherent risk with tDCS, mainly risk of skin irritation and, as in a small number of case 
reports, local skin burns where the electrodes are attached. Such cases have typically been seen only 
after repeated daily stimulation to the same region (Palm, 2008), or after unintentional abrasion of the 
skin with alcohol swabs prior to stimulation (Loo, 2011). Though a possible risk, skin burns are rare. 
In a recent review of clinical research with tDCS, Brunoni and colleagues (2011) noted that “tDCS has 
been tested in thousands of subjects world-wide with no evidence of toxic effects to date.” In 
addition, we are aware of reports of a small percentage of patients developing temporary hypomania 
during the course of a daily tDCS protocol for depression targeting the dorsolateral prefrontal cortex. 
It is unclear whether this is a risk for tDCS targeting rIFG or with the electrode montage used in this 
study. The most common side effects include mild local sensations at the electrode sites, including 
tingling or itching, and moderate fatigue, and headache (Brunoni, 2011; Poreisz, 2007). In general, 
these effects have paralleled those of sham stimulation. In research experience totaling 567 tDCS 
sessions, no participants requested tDCS be stopped or required any medical intervention during or 
after stimulation. Notably, adverse effects did not differ between healthy individuals and patients 
(Poreisz, 2007). Safety testing of tDCS has found high tolerability and no reports of discomfort by 
participants when stimulating for 20 minutes at either 1 or 2mA for 20 minutes (Iyer, 2005). (5) 
Distress due to treatment procedures. Treatment of OCD with ERP involves patients facing situations 
which make them anxious, both directly and in their imaginations. 
 
D.  Protection of the Subject (include measures to minimize potential risks and to ensure 
 
confidentiality) 
 
D.1. Measures to minimize potential risks 
The following procedures will be followed to minimize risks to all participants: (1) To minimize risk 
of coercion, standard procedures will be followed in obtaining written informed consent. The 
voluntary nature of participation will be emphasized. Risks and benefits of participation will be 
explained, along with the rights of the participant, including the right to withdraw from the study at 
any time. Additionally, participants will be informed that should they choose to withdraw from the 
study, this will in no way affect care they receive at [Name] Hospital or their right to participate in 

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future research studies. (2) To minimize the risk of distress arising from the assessment procedure, 
study staff that has been adequately trained in the assessment battery will complete all assessments, 
and [the PIs] will supervise all assessors. (3) To minimize risks due to tDCS, all participants will be 
carefully screened prior to tDCS for contraindications to tDCS. Moreover, we will obtain a release to 
gather information from participants’ current medical providers for screening purposes and ongoing 
clinical record keeping. All tDCS will be administered by a trained member of the research staff under 
the supervision of a credentialed physician (Dr. [Name] or covering physician). Use of an electrically 
isolated power source (i.e., battery-powered DC stimulation device) also protects against delivery of 
more intense currents than intended. Participants will be closely observed for signs of skin burns, 
discomfort, or other stress. Participants will be closely monitored to ensuring the electrode sponges 
stay moist with saline in order to help prevent burns by improving electrode-to-skin contact. 
Participants will have the option of discontinuing the study at any time and will be explicitly 
instructed to inform the experimenters immediately if they experience any discomfort. The 
experimenter will inform the supervising physician about any participant who has significant skin 
discomfort or a skin lesion after current delivery. If there is any doubt about the mental or physical 
status of an individual after testing, the PI or other supervising physician will evaluate the 
participants and make a recommendation for follow-up care, if required. Telephone or in-person 
follow-up will be arranged as needed and will not be considered a protocol deviation. Adverse effects 
will be monitored regularly using the SAFTEE-SI. This measure includes symptoms of hypomania, 
including feeling hyper, unable to sit still, changes in appetite, and sleep disturbance, as well as a 
number of frequently reported side effects in clinical trials. Any participant judged on clinical 
grounds to have suffered adverse effects will thus be evaluated and treated as necessary and 
withdrawn from the study, if necessary. For each SAFTEE item, participants are asked to report how 
bothersome each symptom on the form has been for him/her in the past week, with response options 
"None," "Mild," "Moderate," or "Severe." Additionally, a single item inquires about how much all 
reported side-effects have bothered the participant or interfered with daily activities (response 
options: "No side effects," "Mildly," "Moderately," or "Markedly"). The SAFTEE-SI will be 
administered at baseline, once per week during the 5.5 week protocol, at post-treatment, and at 1 
month follow-up. At each administration, the evaluator will note items rated more bothersome than 
during the previous administration and will inquire further about each such item. The therapist or 
evaluator will also inquire in an open-ended fashion about any other adverse effects experienced 
which are not listed on the SAFTEE-SI and will document the nature and tolerability of any additional 
side-effects reported. For any item rated "severe," or if the participant reports that side effects are 
interfering with daily activities "markedly," the therapist or evaluator will notify Dr. [Name] MD (PI) 
(or covering physician) immediately. Dr. [Name] (or covering physician) will provide further 
evaluation as medically necessary and we will take appropriate safety measures such as study 
withdrawal and/or referral to higher level of clinical care, if necessary. Any item rated as "moderate" 
or "moderately" interfering will be reported to Dr. [Name] by the therapist or evaluator within 24 
hours. All other reported side-effects endorsed on the SAFTEE-SI will be discussed with Dr. [Name] 
during weekly meetings of study staff. Follow-up or further evaluation will occur as medically 
necessary.  (4) To minimize the risk of distress due to treatment procedures, we have selected a 
treatment which has been shown to be efficacious in reducing OCD symptoms. While this treatment 
involves clients placing themselves in situations which provoke anxiety, this is necessary and 
effective for clinical improvement and generally represents no more distress than in experienced in 
daily living for these individuals. Participants will be informed that they will be encouraged to 

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tolerate the discomfort during the sessions but that they can stop the exercises at any time. In the case 
of a participant who experiences extreme distress, clinical judgment and consultation will be used to 
determine whether the participant should be discontinued from the study. Participants who 
experience a significant worsening of symptoms during the study will be discontinued and referred 
for alternative treatment.  
 
To minimize risk of clinical deterioration, we have excluded participants from entry into the study 
who have active suicidal or homicidal ideation. At baseline, participants will be provided with a set of 
emergency contact numbers, including phone numbers for local mental health care providers 
([Hospital Names]) One of the PIs or a covering clinician will also be available at all times to study 
participants in the event of a clinical emergency. All participants will be given oral and written 
information on how to reach the PIs in the case of such an emergency; participants will be told to 
contact research personnel by telephone or pager for any significant worsening of symptoms or 
adverse events, and may be seen for an additional evaluation, which will not be considered a protocol 
violation. We will assess suicide risk at baseline and every week using item 9 on the BDI-II to screen 
for suicidal ideation. Any presence (BDI-II item 9 > 0) or increase in suicidal ideation will result in a 
clinical assessment for suicide risk by the clinician and clinically appropriate steps will be taken (e.g., 
creating a plan for safety or higher level of clinical care, if necessary). We will monitor clinical 
symptoms weekly using the BDI, BAI, and Y-BOCS. In the event that a participant experiences 
significant symptom worsening (i.e., 25% increase of pre-randomization Y-BOCS), he or she will be 
more thoroughly evaluated and we will take appropriate safety measures such as study withdrawal 
or a higher level of clinical care, if necessary. Participants will be offered referrals to alternative 
treatment at study discontinuation. 
 
D.2. Measures to ensure confidentiality 
(2) To protect against breaches of confidentiality, all information collected from participants will be 
handled by staff trained in the responsible conduct of research who have passed ethics training via 
the CITI Course for the Protection of Human Subjects or the NIH Human Participants Protection 
Education for Research Teams training. Audio recordings of sessions will be immediately uploaded 
onto a secure research server and deleted from the audio recording device – these recordings will be 
identified by code number only. All study forms and data will be identified only by code numbers, 
and will be stored in locked file cabinets or on secure research servers. Identifying information 
(contact information, name, consent documents) will be separated from the research data and be 
stored separately in a different locked file cabinet. REDCap (Research Electronic Data Capture) will be 
used for data collection, entry and management.  REDCap, maintained by [Hospital] Data Center, is a 
secure, web application designed to support data capture for research studies, providing user-
friendly web-based case report forms, real-time data entry validation (e.g. for data types and range 
checks), audit trails and a de-identified data export mechanism to common statistical packages (SPSS, 
SAS, Stata, R/S-Plus).  All data collected and entered into REDCap will be identified only by patient 
ID; No PHI will be stored in REDCap.  All other computerized data, including digital audio files of 
assessments and treatment sessions, will be stored on a secure drive, password-protected, and will 
accessible only to research staff. These files will be transferred to the secure drive immediately 
following assessments and treatment sessions and deleted from the digital recording device. Digital 
audio files will be labeled only with subject ID number. Digital audio files will be erased at the end of 

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this study. No personal participant information will be presented in any publication or presentations 
resulting from this research. 
 
D.3. Data safety monitoring plan 
Procedures to protect participant confidentiality are described above (section D.2.).  [The PIs] will be 
responsible for supervision of data entry and management and training of study personnel. Hard 
copy data will be stored in a filing cabinet in one of the PI’s locked offices. Digital audio files will be 
stored on a secure server, and labeled only with participant unique identification code. In order to 
maintain anonymity in computer data files participants will be only listed with their unique 
identification code. The PI’s will monitor procedures for assuring participant privacy and 
confidentiality, and the quality and integrity of data collected.  Corrective action will be taken as 
needed.  Should any adverse events arise, the PI’s will be responsible for completing an Adverse 
Events Form and reporting Serious Adverse Events to the [Hospital Name] IRB within 24 hours of 
having received notice of the event. The PI will gather any information needed to investigate the 
event and to determine subsequent action. Any subsequent action will be documented and reported 
to the [Hospital Name] IRB. 
 
This study has also appointed a data safety monitoring board (DSMB). Members of the DSMB include 
[Name] (who will serve as DSMB Chair), [Name], and [Name]. Dr. [Name], of [Affiliation], has 
expertise in behavior therapy for OCD and statistics. Dr. [Name], of the [Affiliation], has expertise in 
OCD, neuromodulation, and clinical trials. Dr. [Name] has expertise in clinical bioethics, with a focus 
on neuroethics. This board convenes twice per year (unless more frequent meetings are deemed 
necessary) and is responsible for reviewing the research protocol and plans for data and safety 
monitoring, evaluating the progress of the trial, and inquiring for further information as necessary to 
accomplish their mission, and maintaining confidentiality during all phases of the trial including the 
monitoring, preparation of interim results, review and response to monitoring recommendation. As 
they deem necessary, the members of the DSMB will evaluate whether the presence of side effects or 
adverse consequences are significant enough to warrant amendment, suspension, or early termination 
of the study and will independently make recommendations to the PI to continue, to amend or to 
terminate the trial. 
 
E.  Potential Benefits  
The assessments included in this study are not intended to be diagnostic in nature and therefore will 
not be of any direct benefit to participants. Participants in the OCD group may receive benefit from 
receiving a treatment which has previously been shown to be efficacious in reducing OCD symptoms; 
however, response to treatment cannot be guaranteed.  
 
F.  Risk-Benefit Ratio  
Knowledge gained from this study has the potential to inform further development of improved 
treatment approaches for OCD, and future development of neurostimulation-based treatments for 
disorders of inhibitory control. Given the chronic and impairing nature of OCD and other disorders of 
inhibitory control, high patient burden, and high number of individuals who respond less than 
optimally to available treatments, the benefit of this knowledge clearly outweighs potential risks 
involved. 
 

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