Targeting Attentional and Cognitive Control to Enhance the Transdiagnostic Treatment of Repetitive Negative Thinking
Phase: NA
Conditions: Obsessive-Compulsive Disorder, Generalized Anxiety Disorder, Major Depressive Disorder
Sponsor: Massachusetts General Hospital

Study Protocol and Statistical Analysis Plan (SAP) 
 
Study Title: 
Improving Attentional and Cognitive Control in the 
Psychological Treatment of Intrusive Thoughts 
 
Principal Investigator: 
Ryan J. Jacoby, PhD  
Assistant Professor 
Massachusetts General Hospital / Harvard Medical School 
Boston, MA, United States of America 
 
Ethical approval: 
Mass General Brigham Institutional Review Boards (protocol # 
2019P003768, approved on Approved: 01/21/20) 
 
ClinicalTrials.gov identifier: NCT04225624 
 
Funding: 
This study was funded by the National Institute of Mental 
Health (NIMH) under award number K23MH120351 (PI: 
Jacoby). The content is solely the responsibility of the authors 
and does not necessarily represent the official views of the 
National Institutes of Health. 
 
Document Date: 
November 28, 2023 (and annually reviewed thereafter) 
 
Author: 
Ryan J. Jacoby, PhD  
 
Version:  
Draft 1.0 
 
Notes: 
The detailed protocol describes both the pilot testing phase 
(Phase 1; n=3) and the randomized controlled trial phase (Phase 
2; n=62). The data reported on ClinicalTrials.gov is only for the 
participants Phase 2. 
 
  

PI: Ryan J. Jacoby, Ph.D. 
 
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Targeting Attentional and Cognitive Control 
 
 
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PARTNERS HUMAN RESEARCH COMMITTEE 
DETAILED RESEARCH PROTOCOL 
 
Targeting Attentional and Cognitive Control to Enhance the Transdiagnostic Treatment 
of Repetitive Negative Thinking 
 
 
1. BACKGROUND AND SIGNIFICANCE 
 
Although cognitive behavioral therapy (CBT) is an efficacious first-line intervention for individuals 
with affective disorders, 40% of patients receiving CBT are deemed non-responders,1–3 possibly 
suggesting that underlying factors are not being fully addressed. Repetitive negative thinking 
(RNT) is a cognitive process central to the etiology and maintenance of many forms of 
psychopathology, including: rumination in major depressive disorder (MDD),4 worry in 
generalized anxiety disorder (GAD),5 and mental rituals in obsessive compulsive disorder 
(OCD).6  RNT predicts poor treatment outcome and is a common residual symptom following 
CBT.7–20 Thus, there is an urgent and unmet need to identify the mechanistic targets underlying 
RNT to optimize treatment response and reduce the psychiatric burden and healthcare costs for 
patients with affective disorders.  
 
Given that a hallmark feature of RNT is difficulty controlling and disengaging from perseverative 
thoughts, recent theoretical models propose that deficits in attentional and cognitive control 
underlie RNT as fundamental biobehavioral targets.21–32 First, attentional control33 includes the 
ability to: (a) shift attention away (i.e., disengage) from stimuli depending on task demands, and 
(b) sustain focus on goal-relevant information.34,35 Furthermore, eye tracking can delineate the 
components and time course of attentional processes.36  Such measures harness gaze latency 
data (i.e., time to fixation) to distinguish between attentional engagement (i.e., shifting one’s 
gaze from neutral to emotional stimuli when prompted) and attentional disengagement (i.e., 
shifting from emotional to neutral stimuli). Disorders characterized by elevated RNT appear to be 
specifically associated with difficulty disengaging from negative affective stimuli.37–42 Additionally, 
one’s ability to sustain attention (i.e., maintaining focus once it has been established) in the face 
of distracting emotional stimuli may also become disrupted in affective disorders,43–45 but has 
been understudied in relation to RNT.  
 
Second, these attentional difficulties can be activated in one of two contexts that rely on the dual 
mechanisms of cognitive control.46 Cognitive control enables flexible allocation of mental 
resources (including attention) in the service of goal-directed behavior and is comprised of 
proactive (i.e., in preparation for a challenge) and reactive (i.e., in response to a challenge) 
contexts.47,48 Cognitive control capacity can be measured via event related potentials 
(ERPs),49 and ERP studies provide compelling evidence of altered cognitive processing in 
patients with depression, anxiety, and elevated RNT.43,50–54 Specifically, ERP cued task designs 
distinguish between (a) proactive and (b) reactive control. On the one hand, proactive control is 
initiated when a cue word indicates an upcoming conflict. Specifically, cue-locked N2 ERPs in 
anticipation of conflict have been linked to detection of novel stimuli and orienting of attention,55–
57 such that larger (more negative) amplitudes indicate the ability to allocate attentional/cognitive 
resources in proactive contexts. Reactive control, on the other hand, is initiated when responding 
to an emotional target stimulus. Specifically, target-locked N2, N450, and P300 ERPs in 
response to conflict are linked to the adjusting of cognitive control processes,49,58,59 such that 
larger (more negative N2, N450; more positive P300) amplitudes indicate the ability to allocate 

PI: Ryan J. Jacoby, Ph.D. 
 
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Targeting Attentional and Cognitive Control 
 
 
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resources in reactive contexts. Yet, overall, studies validating these targets of attentional and 
cognitive control in treatment are lacking. Accordingly, the current study will address this need. 
 
The Current Study 
We will test the hypothesis that enhancing attention regulation skills in a transdiagnostic 
intervention streamlined and adapted for RNT – Attention Regulation – Emotion Regulation 
Therapy (AR- ERT)31 – will significantly improve the proposed target of attentional/cognitive 
control relative to a supportive psychotherapy (SPT) control group. Specifically, AR-ERT builds 
attention regulation skills (i.e., the ability to flexibly shift and sustain attention) to teach 
patients exercises for Orienting their attention and Allowing the presence of negative emotions. 
Patients are taught to apply these skills to counteract reactive perseverative thinking when 
negative emotions arise and to proactively engage with emotion-laden situations that trigger 
RNT.  
 
The proposed project consists of two phases. In Phase I we will develop a streamlined version 
of ERT that is optimized to target attentional/cognitive control via attention regulation skills (AR-
ERT).31 In Phase II we will test this intervention in a pilot randomized controlled trial using a 
sample of 62 patients with elevated RNT. Specifically, we will assess target engagement of 
attentional/cognitive control (i.e., sensitivity of our target to intervention-induced change) utilizing 
eye-tracking and ERP data. By enhancing attention regulation, we propose that AR-ERT will 
significantly improve the target of attentional/cognitive control for individuals with elevated RNT 
relative to those assigned to 8-weeks of SPT. Second, we will test preliminary target 
validation, and hypothesize that improvements in attentional/cognitive control will be 
associated with improved RNT and psychiatric functioning outcomes. If our hypotheses are 
supported, we will identify a transdiagnostic target that can be engaged to optimize treatment 
response for individuals with elevated RNT, enhancing the generalizability of our findings for 
maximum public health impact. 
 
Innovation of the Proposed Study 
The proposed study is highly innovative in several ways: (1) This is the first project to 
test a streamlined, mechanism-informed, transdiagnostic treatment for RNT.60 (2) Our approach 
examines whether AR-ERT engages the target of attentional/cognitive control spanning multiple 
Research Domain Criteria (RDoC) units of analysis: behavioral (eye tracking fixations), 
electrophysiological (ERPs), self-report, and clinical interview. (3) In line with RDoC priorities, 
we will enroll individuals with elevated RNT, rather than those who meet diagnostic criteria for 
OCD, GAD, or MDD. This is important since RNT is a vulnerability factor for later 
psychopathology,4,61,62 and since we hope to examine future generalization to other conditions 
with RNT (e.g., post-traumatic stress disorder). 
 
2. SPECIFIC AIMS 
 
Primary Aim 
Aim 1: Demonstrate target engagement with AR-ERT.  
• 
Hypothesis 1: By enhancing attention regulation skills, AR-ERT will improve the 
biobehavioral target of attentional/cognitive control from pre- to post-treatment relative to 
a supportive psychotherapy (SPT) control group as measured by multi-method indices:  
a) Behavioral: disengagement and sustained attention in the presence of emotional 
stimuli as measured by eye tracking fixations and reaction time, 
b) Electrophysiological: proactive and reactive cue- and target-locked N2, N450, 
and P300 ERPs in a cued conflict monitoring task, and  

PI: Ryan J. Jacoby, Ph.D. 
 
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c) Self-report: perceived ability to shift and focus attention. 
 
Secondary Aim 
Aim 2: Assess if alteration in the hypothesized target is related to improvements in clinical 
outcomes (i.e., target validation).  
• 
Hypothesis 2a: AR-ERT will improve RNT (transdiagnostic and disorder-specific 
measures) and psychiatric functioning (OCD, GAD, MDD symptoms; functional 
impairment) from pre- to post-treatment relative to SPT, with gains maintained at 3-
month follow-up.  
• 
Hypothesis 2b: Improvements in pre/post attentional/cognitive control will be associated 
with pre/post improvements in RNT and psychiatric functioning.  
 
Exploratory Aim 
We will use source localization to investigate neural generators of ERPs and resting state 
functional connectivity, with a focus on the default mode and frontoparietal networks. 
 
3. SUBJECT SELECTION  
 
A total of 3 pilot participants in Phase I and 62 participants in Phase II with elevated repetitive 
negative thinking (RNT) will participate in the proposed study. Participants will be selected 
based on the inclusion/exclusion criteria described below: 
 
Inclusion criteria 
1) Adults ages 18-60 years old 
2) Right-handed, as assessed by the Edinburgh Handedness Inventory (score ≥ 61) 
3) Living in Massachusetts 
4) RNT in the form of mental rituals, worries, and/or depressive ruminations is the primary 
reason for seeking treatment (i.e., RNT is not better characterized by another disorder; 
e.g., post-traumatic stress disorder). Patients who present with multiple forms of RNT 
(e.g., mental rituals and worries), will be included to ensure generalizability and will be 
able to address each of these thinking patterns in treatment. 
5) RNT severe enough to warrant intervention based on: 
a. Moderate impairment on the Work and Social Adjustment Scale (WSAS total 
score ≥ 15 and ≥ 4 on any of the 5 sub-scales) 
b. Score above the clinical mean on the Perseverative Thinking Questionnaire – 
Past Week (PTQ-PW ≥ 37) 
6) Fluent in English, willing to provide informed consent, and willing to comply with the 
study protocol 
7) Access to a device with an internet connection, camera, and microphone (e.g., 
computer, smart phone, tablet) 
8) Comfortable and capable of using a computer and completing reaction-time tasks 
9) Psychiatric comorbidities not listed in exclusion criteria below will be allowed 
 
Exclusion criteria 
1. History of head injury resulting in prolonged loss of consciousness and/or neurological 
sequelae; History of seizures; History of stroke; Signs of increased intracranial pressure; 
Prior neurosurgical procedure 
2. Current or history of neurologic or psychiatric disease (e.g., dementia, brain damage, or 
other cognitive impairment), mental retardation, or borderline intellectual functioning that 
would interfere with ability to participate in the study 

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3. Impaired (or uncorrected) vision, medical illness, or medical treatment that would likely 
interfere with participation 
4. Active suicidal or homicidal ideation, as assessed by the Structured Clinical Interview for 
DSM-5-Research Version (SCID-5-RV), Structured Interview Guide for the Hamilton 
Depression Rating Scale (SIGH-D), and/or score on the Beck Depression Inventory 
(BDI-II) suicide item (#9) ≥ 2, or any features requiring a higher level of care 
5. Lifetime psychotic disorder or bipolar disorder; as determined by SCID-5-RV 
6. Moderate substance or alcohol use disorder within the past 3 months that would 
interfere with treatment; as determined by SCID-5-RV 
7. Current Attention Deficit Hyperactivity Disorder (ADHD) that would complicate 
interpretation of performance on the attentional/cognitive target measures; as 
determined by SCID-5-RV 
8. Unstable dose of psychotropic medications (i.e., dose changes within 2 months of study 
baseline) or discontinuation of psychotropic medication less than 2 months prior to study 
baseline. Plans to initiate psychotropic medication or change dose during the study. 
Patients can be receiving psychotropic medication if they have taken a stable dose for at 
least two months before the study baseline assessment and the dose remains stable 
during the study to maximize generalizability of the sample. 
9. Current psychotherapy or plans to initiate such treatment during the study. 
10. Previous treatment with ≥ 4 sessions of cognitive behavioral therapy and/or 
mindfulness/meditation for obsessive compulsive disorder (OCD), generalized anxiety 
disorder (GAD), or depression 
 
Recruitment 
The study will recruit subjects who meet the above inclusion/exclusion criteria using 
approaches that are standard for clinical research studies and that the Massachusetts General 
Hospital (MGH) Center for OCD and Related Disorders has used successfully in previous 
clinical trials. Specifically, participants will be recruited via advertisement, clinician referral, and 
self-referral to the Center for OCD and Related Disorders. Our program is one of the largest in 
the world that treats individuals with OCD. In order to further strengthen feasibility, subjects with 
worries will be referred from the MGH Center for Anxiety and Traumatic Stress Disorders 
(CATSD) Program and subjects with depressive ruminations will be referred from the MGH 
Depression Clinical and Research Program (DCRP). 
 
Participants will also be recruited from the greater community to strengthen recruitment and 
diversify the sample. Specifically, we will advertise on the MGH Center for OCD and Related 
Disorders website and on other websites (e.g., Rally, the International Obsessive Compulsive 
Disorder Foundation). We will use the RSVP for Health and Research Match websites to identify 
potentially eligible individuals with OCD, GAD, or MDD. We will post flyers at MGH, in the 
Boston area, and surrounding towns. Our lab also advertises for our program more broadly in 
local media outlets (e.g., newspaper), the Boston subway, and buses (through the General 
Recruitment Protocol # 2009P002227). Our recruitment methods have been used successfully 
in previous studies, and we do not anticipate any difficulties obtaining the proposed sample. Our 
recruitment strategies also follow the guidelines on the National Institute of Health (NIH) website 
to ensure racial/ethnic diversity, and many of our recruitment strategies (e.g., newspaper 
advertisements) specifically will focus on minority groups. 
 
4. SUBJECT ENROLLMENT  
 
Pre-Screening Phase 

PI: Ryan J. Jacoby, Ph.D. 
 
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Our program has a pre-screening procedure that we will follow. First, interested 
participants will be directed to an online pre-screen electronically via REDCap™ which will 
include the Perseverative Thinking Questionnaire – Past Week (PTQ-PW) and the Work and 
Social Adjustment Scale (WSAS). Participants with scores indicating at least moderate levels of 
RNT (PTQ-PW ≥ 37; WSAS total score ≥ 15 and ≥ 4 on any of the 5 sub-scales) will be 
contacted by a highly trained research assistant to schedule a phone screening. This screening 
will include questions to assess for RNT symptoms (mental rituals, worries, ruminations) and 
determine whether study inclusion/exclusion criteria appear to be met. Those with who appear 
to meet study inclusion/exclusion criteria and who are interested in participating will be given 
information about the study. For potential subjects who are receiving psychotropic medication 
and/or concurrent therapy and wish to participate in our study (and we agree that this is a 
reasonable option), we may obtain their consent to contact their treating clinician to determine 
the appropriateness of study participation. Callers who do not meet study entry criteria or do not 
wish to participate will be referred for treatment in our program or elsewhere. We will track the 
number of screens, number of eligible subjects, and reasons for nonparticipation. We will have 
weekly meetings to discuss individuals who contact our program and their appropriate 
disposition.  
 
Email Policy. All emails sent to participants (e.g., to remind participants about study 
assessments, to provide participants with links to the REDCap surveys) will be sent from the 
study staff’s Partners/MGH email account, via “Send Secure” encrypted email or without Send 
Secure in cases where participants have opted out of Send Secure emails via the following 
Partners Privacy Office procedures: “Before sending or responding to an unencrypted email 
message to an individual, the individual must acknowledge understanding of, and agreement to 
accept the risks as communicated to them via the following language (this language must be 
copied into an email response to an individual, or may be read over the phone to the individual, 
or an individual could agree by reading this in person and signing this or simply agreeing 
verbally):” 
 
Opt out language: “The Partners standard is to send email securely.  This requires you 
to initially set up and activate an account with a password.  You can then use the 
password to access secure emails sent to you from Partners HealthCare.  If you prefer, 
we can send you “unencrypted” email that is not secure and could result in the 
unauthorized use or disclosure of your information.  If you want to receive 
communications by unencrypted email despite these risks, Partners HealthCare will not 
be held responsible. Your preference to receive unencrypted email will apply to emails 
sent from this research group/study only.” 
 
If a participant opts out of Send Secure emails, this decision (and the opt out date) will be 
documented in the participant’s research record. 
 
Screening Phase 
Individuals who appear eligible for and are interested in the study during the phone 
screen will then be scheduled for a screening assessment with the PI (Dr. Jacoby). The 
screening assessment will take place virtually using Healthcare Secure ZoomTM or over the 
phone (if this method is preferred by the participant). The PI (or doctoral-level delegate) will 
obtain informed consent using the e-consent module in REDCapTM, conduct a diagnostic clinical 
interview, and subjects will complete online self-report questionnaires (see Table 1 below for 
more detail). Finally, eligibility for the study will be confirmed by the PI. When interviewed 
patients do not qualify for or choose not to participate in the study, reasons will be documented. 
Altogether, the screening procedures will take an estimated 2.5 hours. 

PI: Ryan J. Jacoby, Ph.D. 
 
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5. STUDY PROCEDURES 
 
Overview 
This is a single-site study at the MGH Richard B. Simches Research Center (Boston, 
MA) and Athinoula A. Martinos Center for Biomedical Imaging (Charlestown, MA). Eligible 
participants will complete: (1) 3 electroencephalogram (EEG) sessions which record brain 
activity while participants sit at rest (i.e., resting state functional connectivity) and perform a 
computer task (2 hours), (2) 3 computer task sessions in which participants view a series of 
images (i.e., faces, scenes), and we measure where on the screen they are looking using an 
eye tracker and the sweatiness of their palms (60-90 min), (3) an 8-week therapy protocol (60 
minutes each) – with random assignment to either Attention Regulation – Emotion Regulation 
Therapy (AR-ERT) or supportive psychotherapy (SPT), and (4) 4 clinical assessment visits 
including clinician interviews and self-report measures at baseline (week 0), mid-treatment 
(week 4), post-treatment visit (week 8), and 3-month follow-up (week 20). The EEG sessions 
will take place at the Martinos Center and the computer task sessions will take place at the 
MGH Center for OCD and Related Disorders in Simches. Clinical assessments will take place 
virtually using Healthcare Secure ZoomTM, an encrypted and HIPAA-compliant video 
conferencing platform (or over the phone). Treatment visits will also take place virtually and will 
be conducted using Healthcare Secure ZoomTM (or over the phone). Twenty-four hours prior to 
EEG and computer task sessions, participants will be screened for COVID-19 symptoms by 
completing the MGB COVID-19 Prescreen Questions. Subjects will be given the option of 
combining the screening and baseline clinical assessment visits (if they are deemed eligible for 
the study after screening) and combining the mid-treatment and post-treatment clinical 
assessment visits to their treatment session visits (to reduce subject burden). Thus, study 
participation may only involve 16 total visits if such visits are combined. To avoid dropout, 
subjects will be paid $20 each for the baseline, mid-treatment, post-treatment, and 3-month 
follow-up clinical assessments, $20 each for the 3 EEG sessions, and $20 each for the 3 
computer task visits ($200 total). Participants who cannot afford to travel to the treatment facility 
will be provided with transportation fare (e.g., parking passes) to attend in-person study visits 
($12.50 x 3 computer task visits at the Simches Building + $7 x 3 EEG sessions at the Martinos 
Center = $58.50). 
If an enrolled participant has already completed the same clinician-administered within 
the past six months as part of a different study within the Center for OCD and Related 
Disorders, CATSD, or DCRP Programs, we may offer them the opportunity to consent to give us 
permission to access data from their previous screening assessment.  
 
Clinical Assessments 
Table 1 below shows the assessment schedule. Most measures are administered at 
baseline (week 0), midpoint (week 4), post-treatment (week 8), and 3-month follow-up (week 
20); each 1-1.5 hours. Additionally, certain measures will be administered weekly at therapy 
visits (10 minutes). These times are comparable to those in the clinic’s other treatment studies 
and have been well tolerated. All assessments are non-invasive and demonstrate good 
psychometric properties (e.g., internal consistency, construct validity). No data will be gathered 
from outside sources (e.g., medical records). To facilitate completion of assessments and 
increase quality of data, most assessments will be completed electronically via the online data 
collection site REDCapTM (described further in “Data Management” below). 
 
Diagnostic and Screening Measures 
 

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Structured Clinical Interview for DSM-5 Disorders - Research Version (SCID-5-RV)63: The 
SCID-5-RV is a reliable semi-structured instrument that is the standard in the field for 
diagnosing current and lifetime psychiatric disorders. The SCID-5-RV also includes a section for 
collecting demographic and historical data including information about lifetime suicidal ideation 
and behavior and psychiatric hospitalizations. The SCID-5-RV will be administered by the PI at 
the screening visit (using the online NetSCID) in order to characterize the sample and determine 
the presence of any exclusionary diagnoses. 
 
Test of Premorbid Functioning (TOPF)64: In order to screen for intellectual impairment, the 
TOPF will be administered at the baseline visit to estimate cognitive and memory functioning. 
 
Table 1: Assessment Measures by Study Visits 
 
Measure 
Type 
Measure 
Admin by 
Week -1 
(Screen) 
Week 0  
(Baseline) 
Week 4 
(Mid-Tx) 
Week 8 
(Post-
Tx) 
Week 20    
(3MFU) 
Diagnosis 
& 
Screening 
SCID-5-RV 
PI 
X 
 
 
 
 
TOPF 
RA 
 
X 
 
 
 
Medical and Treatment History Logs 
PI 
X 
 
 
 
 
Demographics  
Self 
X 
 
 
 
 
EHI 
PI 
X 
 
 
 
 
 
Target  
(Cognitive/
Attentional 
Control) 
ACS 
Self 
 
X 
Weekly 
X 
X 
AEDT 
RA 
 
X 
X 
X 
 
EIT 
RA 
 
X 
X 
X 
 
CECT 
RA 
 
X 
X 
X 
 
Outcome 
(RNT) 
PTQ-PW 
Self 
X 
X* 
Weekly 
X 
X 
PSWQ 
Self 
 
X 
X 
X 
X 
RRS 
Self 
 
X 
X 
X 
X 
ROCS 
Self 
 
X 
X 
X 
X 
Symptoms 
Y-BOCS 
IE 
 
X 
X 
X 
X 
SIGH-A 
IE 
 
X 
X 
X 
X 
SIGH-D 
IE 
 
X 
X 
X 
X 
DOCS 
Self 
 
X 
X 
X 
X 
STAI-T 
Self 
 
X 
X 
X 
X 
BDI-II 
Self 
 
X 
X 
X 
X 
CGI-S/I: Clinician  
IE 
 
X 
X 
X 
X 
CGI-I: Patient 
Self 
 
 
Weekly 
X 
X 
Functioning 
WSAS 
Self 
X 
X* 
X 
X 
X 
Q-LES-Q-SF 
Self 
 
X 
X 
X 
X 
Safety 
BDI-II Suicide Item (#9) 
Self 
X 
 
Weekly 
 
 
CMED Log 
RA/Ther 
 
X 
Weekly 
X 
X 
CTHER Log 
RA/Ther 
 
X 
Weekly 
X 
X 
Life Events Questionnaire 
RA/IE 
 
X 
X 
X 
X 
AE Form / AE Log 
RA/Ther 
 
X 
Weekly 
X 
X 
Tx Details 
CEQ 
Self 
 
X 
Session 
3
 
 
CSQ-8 
Self 
 
 
 
X 
 
WAI-SR 
Self/Ther 
 
 
X 
 
 
Homework Compliance 
Self/Ther 
 
 
Weekly 
 
 
Adherence/Competence 
IRR 
 
 
Weekly 
 
 
Blinding Questionnaire 
Ther 
 
 
 
 
X 

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Measure 
Type 
Measure 
Admin by 
Week -1 
(Screen) 
Week 0  
(Baseline) 
Week 4 
(Mid-Tx) 
Week 8 
(Post-
Tx) 
Week 20    
(3MFU) 
Other 
Lifetime Medication History 
Self 
 
X 
 
 
 
IUS-12 
Self 
 
X 
X 
X 
X 
Health Behaviors Questionnaire 
RA 
 
X 
X 
X 
 
Post-EEG Questionnaire 
Self 
 
X 
X 
X 
 
COVID-19 Impact Scale 
Self 
 
X 
X 
X 
X 
eACS 
Self 
 
X 
X 
X 
X 
EQ-D 
Self 
 
X 
X 
X 
X 
ERQ 
Self 
 
X 
X 
X 
X 
Treatment Preference Form 
Self 
X 
 
 
 
 
Patient Feedback Questionnaire 
Self 
 
 
 
X 
 
After ART Usage and Additional Tx Form 
Self 
 
 
 
 
X 
 
*PTQ-PW and WSAS to be repeated at baseline if it has been >7 days since screening visit 
 
Medical and Treatment History Logs: This measure will be administered by the PI at the 
screening visit to assess for: (a) lifetime medical problems that are exclusionary in this study, 
and (b) treatment history with psychotropic medications within the last 2 months and lifetime 
psychosocial treatments to assess for current/lifetime treatment exclusions.  
 
Participants will also complete a Demographics self-report form to characterize the sample 
(e.g., gender, race, education, occupational status) and the Edinburgh-Handedness Inventory 
(EHI)65 rated by the PI to confirm handedness at the screening visit. 
 
Target Measures of Attentional/Cognitive Control 
 
Attentional Control Scale (ACS)33: The ACS a 20-item self-report instrument in the NIH 
Toolbox66 that measures participants’ perceived ability to (a) focus on relevant stimuli while 
ignoring distractors (e.g., “My concentration is good even if there is music in the room around 
me”), and (b) shift attention (e.g., “After being interrupted or distracted, I can easily shift my 
attention back to what I was doing before”). The ACS will be administered at the clinical 
assessment visits (baseline, mid-treatment, post-treatment, and 3-month follow-up) as well as 
weekly during the therapy visits. 
 
Attentional Engagement-Disengagement Task (AEDT)40: The AEDT will be used as a 
behavioral measure of attentional control. Two emotional faces are presented (happy, 
disgusted, and sad paired with neutral faces; Radboud Faces database)67 and eye tracking is 
measured; 72 trials. Half of trials measure (a) attentional engagement with emotional 
expressions (i.e., once participants fixate on the neutral face, a frame around the emotional face 
indicates they should shift their gaze), and the other half measure (b) attentional disengagement 
(i.e., shifting from emotional to neutral). Gaze latency (i.e., time to fixation) is the main outcome. 
This task has been linked to rumination68 and is sensitive to treatment.69 It is expected that 
individuals with RNT will display delayed disengagement (i.e., longer time to fixation) when 
shifting from negative to neutral stimuli (vs. from positive to neutral or from neutral to 
emotional)37–39 , which is expected to improve with ERT-AR. Eye movements will be recorded 
using a Tobii Pro X3-120 (described in “Equipment” below). The AEDT will be administered at 
the following timepoints: baseline (week 0), mid-treatment (week 4), and post-treatment (week 
8). Computer task sessions will occur within a 7-10-day window, but no longer than 14 days  
from each clinical assessment visit. 

PI: Ryan J. Jacoby, Ph.D. 
 
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Emotional Interference Task (EIT)70: The EIT measures difficulties sustaining attention in the 
presence of distressing emotional contexts. Participants view 40 neutral and 40 arousing (20 
pleasant and 20 unpleasant) photographs from the International Affective Picture System 
(IAPS)71 for 6 seconds each, in random order, with a 1-second interval between pictures (148 
trials). A high- or low-pitched tone is played either 1 or 4 seconds after each picture is 
presented, and participants are instructed to choose whether each tone is high or low by 
pressing a button as quickly as possible after each tone is played. Mean reaction times are 
calculated separately for pleasant, unpleasant, and neutral pictures. Emotional interference is 
then calculated separately for pleasant and unpleasant stimuli by subtracting mean reaction 
times recorded while viewing neutral pictures from mean reaction times recorded while viewing 
pleasant and unpleasant pictures. Faster reaction times reflect better ability to inhibit emotional 
interference while sustaining attention on the tone; we will also collect gaze data to validate for 
future research. Past research has indicated that patients with GAD demonstrate slower 
reaction times on the EIT vs. controls, and symptom improvement is associated with faster 
reaction times.43,72 The EIT will be administered at the following timepoints: baseline (week 0), 
mid-treatment (week 4), and post-treatment (week 8). Computer task sessions will occur within 
a 7-10-day window, but no longer than 14 days, from each clinical assessment visit. 
Psychophysiological Measurement. Galvanic Skin Response (GSR) will also be measured 
during the EIT at baseline, mid-treatment, and post-treatment. Biometric measurement of this 
psychophysiological index will be recorded using the iMotions platform.   
 
Cued Emotional Control Task (CECT)73: The CECT is an electrophysiological measure of 
cognitive control based on well-validated cognitive conflict paradigms (i.e., emotional Stroop,74 
Etkin Conflict Adaptation Task75). Each of the 216 trials begins with one of three 500ms word 
cues: “actual” to press a key to indicate the emotional expression of the upcoming target face 
(e.g., press “sad” to sad face); “opposite,” to indicate the emotion opposite the one expressed 
(e.g., press “happy” to sad face); or “press”, to press a key regardless of the expression. 
Targets are happy or sad emotional faces (500 ms; Karolinska Directed Emotional Faces 
dataset, KDEF).76 This allows for measurement of cued preparatory processes in anticipating an 
emotional stimulus (i.e., proactive control) vs. reactive control in responding to one, using cue- 
and target-locked ERPs, respectively. The difference in responding on high conflict (“opposite”) 
vs. low conflict (“actual”) trials isolates the process of cognitive control. Outcomes include the 
N2, N450, and P300 ERP amplitudes. Research with high trait ruminators demonstrates this 
task is associated with rumination54 and is sensitive to treatment.77 Individuals with RNT are 
expected to display reduced cue- and target-locked ERPs with negative faces, and 
improvement following AR-ERT would be indicated by less cognitive cost between low vs. high 
conflict trials. EEG data will be collected with a 96-channel EEG cap (BrainVision, LLC; 
described in “Equipment” below). Data from the CECT will be averaged to form the ERPs of 
interest.  
 
Source localization will rely on standardized Low Resolution Electromagnetic Tomography 
(sLORETA)78,79 to identify neural generators of each ERP component.79,80 We also will collect 8-
minutes of resting (task-free) EEG data, and exact LORETA (eLORETA) will be used to analyze 
resting state functional connectivity.81 
 
The CECT and resting state functional connectivity will be collected at the following timepoints: 
baseline (week 0), mid-treatment (week 4), and post-treatment (week 8). EEG sessions will 
occur within a 7-10-day window, but no longer than 14 days, from each clinical assessment visit. 
 
 

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Outcome Measures of Repetitive Negative Thinking (RNT) 
 
Perseverative Thinking Questionnaire – Past Week (PTQ-PW)82: The PTQ-PW is a 15-item 
self-report measure of transdiagnostic repetitive negative thinking within the past week. Items 
on the PTQ-PW are independent of disorder-specific content and inquire about thoughts as 
repetitive, intrusive, unproductive, and capturing mental capacity (e.g., “The same thoughts 
keep going through my mind again and again”). The PTQ-PW is our primary outcome measure. 
It will be administered at the screening visit to determine eligibility (PTQ-PW ≥ 37), the 
assessment visits (baseline *if more than 7 days has passed since screening, mid-treatment, 
post-treatment, and 3-month follow-up), and weekly during the therapy visits. 
 
Disorder-specific presentations of RNT will additionally be captured via the following measures, 
which will each be collected at the clinical assessment visits (baseline, mid-treatment, post-
treatment, and 3-month follow-up): 
 
Penn State Worry Questionnaire (PSWQ)83: The PSWQ is a 16-item self-report scale that 
measures the tendency to engage in excessive, uncontrollable, generalized worry (e.g., “I 
am always worrying about something”). 
 
Rumination Response Scale (RRS)84: The RRS is a 22-item self-report questionnaire that 
measures participant general responses to sad or depressed mood (e.g., “think about how 
sad you feel.”). 
 
Rumination on Obsessions and Compulsions Scale (ROCS)85: The ROCS is a 33-item 
self-report measure that assesses the frequency of various responses (e.g., “I distract 
myself with anything that comes to mind”) to intrusive thoughts or images in the past month. 
 
Symptom Measures 
 
The following gold-standard interview measures will be administered by the IE at the clinical 
assessment visits (baseline, mid-treatment, post-treatment, and 3-month follow-up) to assess 
OCD, GAD, and depression symptom severity respectively: 
 
Yale-Brown Obsessive Compulsive Scale (Y-BOCS)86,87: This 12-item rater-administered 
semi-structured scale includes a checklist of common obsessions and compulsions and 
rates severity (distress and impairment) of OCD symptoms over the past week.  
 
Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A)88: The 
SIGH-A is a 19-item structured, clinician-administered rating scale that provides an overall 
measure of generalized anxiety in the past week. 
 
Structured Interview Guide for the Hamilton Depression Rating Scale (SIGH-D)89: The 
SIGH-D is a 17-item clinician-administered measure of overall severity of depressive 
symptoms in the past week. 
 
The following self-report measures will also be administered at the clinical assessment visits 
(baseline, mid-treatment, post-treatment, and 3-month follow-up) to assess OCD, GAD, and 
depression symptom severity respectively: 
 
Dimensional Obsessive-Compulsive Scale (DOCS)90: The DOCS assesses the symptom 
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contamination, (b) responsibility for harm, injury, or bad luck, (c) unacceptable thoughts, and 
(d) concerns about symmetry, completeness and need for things to be “just right”. 
 
State Trait Anxiety Inventory-Trait (STAI-T)91: The STAI-T is a 20-item questionnaire of 
trait anxiety in which respondents are asked to rate the intensity of their feelings in general 
(e.g., “I am tense”). 
 
Beck Depression Inventory (BDI-II)92: This 21-item self-report inventory is a widely used 
measure of depression severity that assesses the affective, cognitive, motivational, 
vegetative, and psychomotor components of depression. 
 
Clinical Global Impression Scale – Severity and Impairment (CGI-S/I)93: The CGI-Severity 
(CGI-S) is a measure of the global severity of symptoms. It ranges from 1 (normal, not ill at all) 
to 7 (among the most extremely ill patients) and is commonly used in clinical trials. The CGI-S 
will be administered by the IE at the clinical assessment visits (baseline, mid-treatment, post-
treatment, and 3-month follow-up).  
 
The CGI-Improvement (CGI-I) is a global rating scale of improvement during treatment that 
ranges from 1 (very much improved) to 7 (very much worse). Subjects will complete a CGI-I for 
RNT symptoms (CGI-RNT) and for overall anxiety, mood, and mental health symptoms (CGI-
Global) at each therapy visit, at mid-treatment, post-treatment, and at 3-month follow-up. The IE 
will complete the CGI-RNT and CGI-Global at the following assessment visits: mid-treatment, 
post-treatment, and 3-month follow-up. The CGI-I will be used to determine whether subjects 
experience clinical deterioration and should be withdrawn from the study (see section on 
“Participant Withdrawal” below).  
 
Functioning and Quality of Life 
 
Work and Social Adjustment Scale (WSAS)94 The WSAS is a 5-item self-report scale 
assessing disability in work, home management, social leisure activities, private leisure 
activities, and the ability to form and maintain close relationships, each on 8-point scales. A 
composite score can be calculated by summing the five scales for a dimensional measure of 
global functional impairment that ranges from 0 to 40, in which higher scores denote greater 
disability. Specifically, WSAS total scores less than 15 indicate mild disability, between 15 and 
30 moderate disability, and greater than 30 severe disability. The WSAS will be administered at 
screening to determine eligibility (moderate impairment of RNT; WSAS total score ≥ 15 and ≥ 4 
on any of the 5 sub-scales) and at the clinical assessment visits (baseline *if more than 7 days 
has passed since screening, mid-treatment, post-treatment, and 3-month follow-up). 
 
Quality of Life Enjoyment and Satisfaction Questionnaire – Short Form (Q-LES-Q-SF)95: 
The Q-LES-Q-SF is a 16-item self-report measure of quality of life, often used in treatment 
studies, that focuses on social relationships, emotional well-being, physical health, leisure 
activities, work, school, and household duties. The Q-LES-Q-SF will be administered at the 
clinical assessment visits (baseline, mid-treatment, post-treatment, and 3-month follow-up). 
 
Assessment of Safety, Concomitant Treatment, and Adverse Events 
 
Beck Depression Inventory (BDI-II) – Suicide Item92: Item #9 of the BDI-II regarding suicidal 
thoughts or wishes will be given at screening to determine eligibility (scores ≥ 2 are 
exclusionary, “2 - I would like to kill myself” and “3 - I would kill myself if I had the chance”). This 
item also will be administered weekly to monitor suicidal ideation. 

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Concomitant Medication (CMED) Log: The RA will administer the CMED form at the clinical 
assessment visits (baseline, mid-treatment, post-treatment, and 3-month follow-up) and before 
each therapy session to probe for any changes in medications for mood, anxiety, sleep, or other 
psychological symptoms that may have occurred since the last session. Changes in 
psychotropic medications or dose are not allowed during the study. At each visit, the research 
coordinator will update the CMED Log to track all psychotropic medications, including dose. The 
therapist will review the completed CMED Log before each therapy session. 
 
Concomitant Therapy (CTHER) Log: The RA will administer the CTHER form at the clinical 
assessment visits (baseline, mid-treatment, post-treatment, and 3-month follow-up) and before 
each therapy session to probe for any changes in therapy that may have occurred since the last 
session. Changes in therapy are not allowed during the study. At each visit, the research 
coordinator will ask the subject whether they have started or stopped any mental health 
treatments such as counseling, therapy, or self-help programs to ensure that this does not occur 
without our knowledge. The therapist reviews the completed CTHER Log before each therapy 
session. 
 
Life Events Questionnaire: This form is administered by the RA and reviewed by the PI at the 
clinical assessment visits (baseline, mid-treatment, post-treatment, and 3-month follow-up) to 
assess whether any major life events occurred since the last assessment visit that might have 
had a psychological impact on the participant including: marriage, divorce or separation from 
spouse, death of a spouse/partner or other close family member, birth of a child, serious injury, 
diagnosis/progression of a medical illness or disease (e.g., COVID-19 exposure or diagnosis), 
loss/began new job. 
 
Adverse Events (AE) Form and Log: The AE Form will be administered by the RA during 
clinical assessment visits (baseline, mid-treatment, post-treatment, and 3-month follow-up) and 
by the therapist during treatment sessions to probe for any adverse events. Should the 
participant report an adverse event, the RA or therapist will log this information in the AE log 
while speaking to the participant. If there are any safety concerns during a clinical assessment, 
the RA will inform the IE of the adverse event. The RA and therapist will document any adverse 
events that occur during the study and the PI will review each event during weekly study 
meetings to discuss relatedness to treatment, severity, and corrective actions. We have used 
these forms in prior NIH-funded psychotherapy studies. 
 
Assessment of Treatment Credibility and Satisfaction: 
 
Credibility/Expectancy Questionnaire (CEQ)96: This 6-item self-report questionnaire has two 
subscales: (1) treatment rationale credibility (CEQ-C) is cognitively based (e.g., “How logical 
does the therapy offered to you seem?”), and (2) treatment expectancy (CEQ-E) is emotionally 
based (e.g., “How much do you really feel that therapy will help you to reduce your 
symptoms?”). The CEQ will be administered at the baseline clinical assessment visit (week 0) 
as well as at the start of session 3. 
 
Client Satisfaction Questionnaire (CSQ-8)97,98: This 8-item self-report questionnaire assesses 
satisfaction with clinical services received. The CSQ will be administered at the post-treatment 
clinical assessment visit (week 8).  
 
Working Alliance Inventory (WAI-SR)99: The WAI-SR is based on Bordin’s (1979) 
conceptualization of therapeutic alliance100 which includes three factors: (1) bond alliance (e.g., 

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“___ and I respect each other”), (2) goal alliance (e.g., “___ and I are working towards mutually 
agreed upon goals”), and (3) task alliance (e.g., “___ and I agree on what is important for me to 
work on”). Compared to the original 36-item WAI, the revised short version (WAI-SR) has an 
improved model fit in confirmatory factor analyses101. 
 
Homework Compliance: Therapists and patients are asked to rate the amount of between-
session homework participants completed on a scale from 1 (patient did not attempt the 
assigned homework) to 5 (patient did more of the assigned homework or its equivalent than was 
requested). Therapists and patients also rate effort made by the patient in completing the 
assignment on a scale from 0 (patient made no attempt to complete any homework) to 4 
(patient made maximal efforts to complete homework). Finally, therapists rate the relevance of 
the homework attempted to the patient’s particular problem on a scale from 0 (homework 
attempted was completely unrelated or not done) to 4 (homework attempted relevant to 
particular target problems). These measures have been used in previous studies of ERT31 and 
will be administered weekly at the therapy sessions. 
 
Adherence and Competence31,102: For supportive psychotherapy, manual adherence on a 
scale from 1 (not at all) to 7 (completely) and competent treatment delivery on a scale from 1 
(not at all) to 5 (completely) will be rated to ensure minimum scores of ≥ 6 on adherence and ≥ 4 
on competence for selected sessions (as described below under “Monitoring and Quality 
Assurance”). For attention regulation therapy, manual adherence will be rated on a scale from 0 
(did not address component/engage action) to 2 (addressed component/engaged action in more 
detail), and competent treatment delivery will be rated on a scale from 0 (therapist was not 
skillful or performed poorly) to 2 (therapist performed action very skillfully). The specific skills to 
be rated on this measure were developed during the study and submitted as an IRB 
amendment.  
 
Blinding Questionnaire: This measure will be completed by the IE at 3-month follow-up in order 
to assess whether they believe the participant has been assigned to AR-ERT or SPT and how 
strongly they believe this (i.e., somewhat or strongly). 
 
Other Assessments 
 
The Lifetime Medication History self-report form reviews lifetime medication treatment (i.e., 
prior to past 2 months).  
 
Intolerance of Uncertainty Scale (IUS-12)103: The IUS-12 is a self-report measure capturing 
reactions to uncertainty, ambiguity, and the future and consists of two subscales: (a) Prospective 
IU measures discomfort due to future unknowns and information gathering to increase certainty 
(e.g., “I always want to know what the future has in store for me”), and (b) Inhibitory IU measures 
avoidance and paralysis in the face of uncertainty (e.g., “When I am uncertain I can’t function 
very well”). The IUS-12 will be administered at the clinical assessment visits (baseline, mid-
treatment, post-treatment, and 3-month follow-up). 
 
Health Behaviors Questionnaire: This measure will be administered at the computer task 
visits (baseline, mid-treatment, post-treatment) in order to assess health-related behaviors 
participants may have engaged in over the past 24 hours that would affect interpretation of the 
physiological readings. 
 

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Post-EEG Questionnaire: This questionnaire probes whether participants were uncomfortable, 
anxious, sleepy, or inattentive during the EEG recording and will be administered directly after 
each EEG session (baseline, mid-treatment, post-treatment).  
 
COVID-19 Impact Scale: This 14-item self-report measure was created by members of the 
Center for OCD and Related Disorders and aims to assess the effect of the coronavirus 
pandemic on individuals in the past week. Individuals are instructed to rate the extent to which 
they agree/disagree with various statements (e.g., “I found it difficult to tolerate the uncertainty 
about whether I or a loved one would contract COVID-19”) on a scale from 1 (Strongly Disagree) 
to 5 (Strongly Agree). The COVID-19 Impact Scale will be administered at the clinical 
assessment visits (baseline, mid-treatment, post-treatment, and 3-month follow-up). 
 
Experiences Questionnaire - Decentering (EQ-D)104: In this 11-item subscale, individuals are 
asked to indicate how often they currently have various decentering experiences (e.g., “I am 
consciously aware of a sense of my body as a whole”) on a scale from 1 (Never) to 5 (All the 
time). The ED-Q will be administered at baseline, mid-treatment, post-treatment, and 3-month 
follow-up. 
 
Emotion Regulation Questionnaire (ERQ)105: The ERQ is a 10-item self-report measure of 
emotion regulation that includes statements related to cognitive reappraisal (e.g., “When I’m 
faced with a stressful situation, I make myself think about it in a way that helps me stay calm”) as 
well as expressive suppression (e.g., “I control my emotions by not expressing them”). 
Individuals are asked to rate the extent to which they disagree/agree with these statements on a 
scale from 1 (Strongly disagree) to 7 (Strongly agree). The ERQ will be administered at baseline, 
mid-treatment, post-treatment, and 3-month follow-up. 
 
Emotional Attentional Control Scale (eACS)106: This 14-item self-report measure, which was 
adapted from the original 20-item Attentional Control Scale (ACS), assesses modulation of 
attentional control in emotional contexts. Individuals rate each item on a 4-point scale from 0 
(almost never) to 4 (always). The eACS will be administered at baseline, mid-treatment, post-
treatment, and 3-month follow-up. 
 
Treatment Preference Form: This self-report form aims to capture the degree to which each 
participant prefers a given treatment condition (AR-ERT or SPT) before they are randomized. 
Participants are made aware that this form will have no bearing on treatment assignment and will 
not be viewed until after the participant has completed treatment. 
 
Patient Feedback Questionnaire: This questionnaire allows participants to provide feedback 
on their experience during treatment, including general satisfaction with their treatment condition 
and treatment length, which aspects of therapy they found most confusing or most helpful, and 
usefulness of the therapy website and forms. This self-report questionnaire will be administered 
at post-treatment only.  
 
After ART Usage and Additional Treatment Form: This self-report form asks participants to 
report their usage and the usefulness of the study website, and probes for the need for additional 
treatment at the 3-month follow up assessment.  
 
Equipment 
 
Eye-tracking data will be collected during the AEDT and EIT tasks. The eye tracking 
equipment will be located in a dedicated office within the OCD Program. We will use a Tobii Pro 
X3-120 screen-based eye tracker (The Tobii Group, Danderyd, Sweden) which samples eye-

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gaze coordinates at 120 Hz. Eye tracking data will be transmitted via USB 3.0 to a LAN with 
External Processing Unit and converted to visual fixation data using the iMotions Biometric 
Research Platform (Boston, MA, USA).  
The electroencephalogram (EEG) equipment is located at the MGH Martinos Center 
(Charlestown, MA). EEG data will be acquired using BrainVision software (Brain Products 
GmbH, Gilching, Germany) that is installed in a dedicated behavioral testing laboratory. The 
EEG amplifier is an actiCHamp active amplification system (24-bit battery, up to 1000 Hz 
sampling rate). It is used with actiCAP EEG caps, which are fitted with 32-electrode modules. 
Our system is configured for use with 96 electrodes (3 modules) to provide dense scalp 
coverage, which is helpful for spatially localizing event related potentials (ERPs) and is 
necessary for accurate source localization. The cap can be fit to a participant in about 30 
minutes to provide an individualized and comfortable fit for each person. The actiCHamp system 
uses active electrodes and gel to minimize impedance and maximize signal-to-noise ratio (SNR); 
impedances will be kept under 30 kOhms to ensure high SNR. The N2 and N450 ERP 
components will be measured at midline frontal (Fz) and central (Cz) sites, while the P300 will be 
measured at a midline parietal site (Pz). Digitization of three-dimensional electrode positions will 
be accomplished via the BrainVision CapTrak system. Data processing and analysis will occur 
offline using BrainVision Analyzer 2.0 and MatLab (Natick, MA, USA). 
 
Randomization 
At the baseline visit, eligible subjects will be randomized (1:1 in parallel) to AR-ERT or 
SPT using the REDCapTM database. 
 
Treatment 
For all participants, treatment will consist of 8 weekly sessions provided via Healthcare 
Secure ZoomTM that are 60 minutes in duration. Eight sessions is the length of ERT currently 
being tested,107,108 allowing us to directly compare our effect sizes with the full package. All 
sessions are individual treatment (no group treatment). 
 
Attention Regulation – Emotion Regulation Therapy (AR-ERT)  
A brief, manualized version of individual Emotion Regulation Therapy (ERT) focused on 
the Attention Regulation module will be administered to patients randomized to AR-ERT. 
Specifically, the 8-session protocol will be a streamlined version of ERT, which tested as part of 
a NIH-sponsored R34:MH070682. The full protocola engages several active mechanisms (i.e., 
attention regulation, metacognitive regulation, reward/threat processing) and an 8-session 
version of this full treatment is currently being studied; however, in order to test the target of 
attentional/cognitive control, we are focusing solely on attention regulation skills: (a) Orienting 
(i.e., the ability to flexibly shift attention) via mindfulness of the breath (sessions 1-4), and (b) 
Allowing (i.e., the ability to sustain attention despite unpleasant emotional experiences) via 
mindfulness of thoughts and emotions (sessions 5-8). Treatment will also include lessons for 
practicing these skills in two different contexts: (a) reactive: reviewing challenging (i.e., emotion-
laden) situations that have happened in the past week in which attention regulation skills could 
have been applied to counter automatic reactive RNT responses (sessions 1-4) as well as (b) 
proactive: preparing for challenging situations that may happen in the future in which skills could 
be implemented (sessions 5-8).  
 
Specifically, session 1 provides patients with a model of how RNT maintains emotions, presents 
between-session self-monitoring of RNT, and introduces the attention regulation skill of 
Orienting via mindfulness of the breath. In sessions 2-4, Orienting skills continue to be 
practiced. Patients review their self-monitoring forms to detect triggers and consequences of 
RNT. They also conduct in-session imaginal rehearsal of situations from the past week that 

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didn’t go as planned in order to explore effective alternatives (i.e., earlier cue detection of RNT; 
how attention regulation skills could have been applied to counteract RNT). Session 5 begins 
the second half of treatment, in which the skill of Allowing is introduced via mindfulness of 
thoughts and emotions. In addition, proactive strategies are taught to prepare for emotion-laden 
situations that trigger RNT that patients may be avoiding, have withdrawn from, or that RNT 
prevents them from fully experiencing. Specifically, session 5 includes in-session imaginal 
rehearsal of upcoming situations that the patient wants to engage in, including confronting 
imagined difficulties and feared outcomes. In sessions 6-7, Allowing will continue to be 
practiced. Proactive imagery exercises also continue and additionally involve in vivo proactive 
exercises to approach situations that typically trigger RNT. Finally, session 8 includes a 
summary of patients’ gains, relapse prevention, and processing of termination. Home practice 
assignments are assigned after each session. Materials needed to complete between-session 
assignments will be emailed to participants using REDCap as well as housed on a website 
(https://mghocd.org/art/). This website will not store any data; instead, it will simply host links to 
various materials (e.g., links to PDFs for them to download, links to pre-recorded session recap 
videos summarizing the skills associated with that session, and links to REDCap surveys). The 
website (hosted by Wordpress) will require a passcode to enter (“attention”), which will only be 
shared with participants receiving Attention Regulation - Emotion Regulation Therapy. 
 
Supportive Psychotherapy (SPT) 
 
To control for nonspecific therapy elements (e.g., expectancies, demand characteristics), 
half of participants will be randomized to SPT.109–113 SPT is one of the most common 
psychological therapies provided in the community for affective disorders,114 and thus is a 
credible control condition (which will minimize attrition), yet it is not hypothesized to engage the 
target of attentional/cognitive control. SPT is also acceptable from a safety perspective, as it 
allows close patient monitoring. Manualized SPT has been used as the control condition in other 
NIH-funded studies in our program. 
 
SPT focuses on therapeutic interactions and techniques that are nonspecific and common to 
psychotherapies (e.g., reflective listening, expression of empathy), and sessions are non-
directive and conversational, with content driven by the patient.115 SPT focuses on maintaining, 
improving, and restoring self-esteem and adaptive coping skills, and on reflecting and 
expressing emotions about current life issues. The intent is to help patients learn to cope with 
external and internal (psychological) challenges.115–117 SPT emphasizes the therapeutic 
relationship and self-esteem as vehicles for patient improvement.115,116 Session content may 
include discussion of relationships and emotions (related and unrelated to RNT symptoms). 
SPT therapists take an empathic and validating stance so that patients are comforted when 
upset and supported when coping with distressing feelings. Specific SPT techniques include 
communicating positive regard for the patient through verbal and nonverbal behavior; using a 
relaxed conversational style in the therapy; providing empathy, praise, and encouragement; 
clarification; ventilation (allowing the patient to express intense feelings); and absolution (i.e., 
normalizing minor inadequacies to eliminate guilt).  
 
Adjunctive Services and Attrition Prevention (ASAP) 
In addition to the scheduled AR-ERT and SPT sessions, each participant will be 
permitted up to two ASAP sessions. An ASAP session addresses subject crises or unusual 
circumstances/needs that may arise, with the goal of subject retention. This strategy has been 
implemented successfully in other large federally funded randomized controlled trials in our 
clinic. 
 
6. BIOSTATISTICAL ANALYSIS 

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Overview 
Data acquisition and analytics approaches will be performed by Dr. Jacoby under the 
supervision of biostatistician Dr. David Schoenfeld. To characterize our sample, data will be 
displayed graphically, and summary statistics (e.g., means and frequencies) will be calculated 
for all variables, including demographic and clinical descriptors. Descriptive statistics and 
exploratory graphing (e.g., scatter plots) will be used to assess normality, skew, and outliers on 
all measures. Continuous measures will be transformed if necessary, to satisfy assumptions of 
normality and homogeneity of variance.  
 
Baseline differences between the treatment arms (AR-ERT vs. SPT) in demographic and other 
potential prognostic variables will be examined using chi-square analyses for discrete variables 
and ANOVA for continuous variables. While randomization tends to produce well-balanced 
treatment samples, if we find significant differences in potentially important baseline variables, 
we will include these variables as covariates in subsequent multivariate analyses. Candidate 
covariates for adjustment include baseline values of RNT (PTQ-PW score), symptom measures 
(Y-BOCS, SIGH-A, SIGH-D), and use of psychotropic medication (yes/no). Additional covariates 
that are unlikely to moderate treatment effect, but nonetheless will be examined for 
completeness, include: age, gender, education, race/ethnicity (majority vs. minority as we do not 
anticipate recruiting enough subjects from any one minority group to perform analyses for 
specific groups). If effects of gender and/or minority status are found that might be clinically 
meaningful, even if not statistically significant, we will report these to guide future research. 
Frequencies of adverse events (with 95% confidence intervals) will be calculated by treatment 
arm and type of event. We also will compare treatment groups on baseline credibility/expectancy 
of treatment and post-treatment satisfaction. A two-tailed p value <.05 will be considered 
evidence of statistical significance for the primary outcome.  
 
Missing Data  
Our multi-level generalized linear modeling (GLM) approach (described below under 
“Primary Analyses”) uses an intent-to-treat analysis that includes all participants, regardless of 
missing data (increasing power and generalizability), and it provides accurate estimates of 
regression coefficients in small samples.118,119 Despite our best efforts to retain participants, we 
do expect dropouts (i.e., subjects who are lost to follow-up or withdraw early from the study for 
reasons described below under “Participant Withdrawal”). We will attempt to perform all 
scheduled assessments for subjects who are withdrawn from the protocol and will provide 
financial incentives for participation in assessments.  
 
Missing data rates and patterns will be assessed by treatment arm. Reason(s) for missing data 
will be documented, and we will evaluate reasons for dropout, study withdrawal, and loss-to-
follow-up by treatment group. We will attempt to ascertain if missingness is occurring at random 
by evaluating factors associated with dropout for potential attrition bias. We will also compare 
study dropouts to study completers on demographic and clinical variables. Finally, we will use 
sensitivity analyses to quantify the impact of missing data.120 
 
Data Processing 
For behavioral tasks that include reaction times (e.g., the Emotional Interference Task 
[EIT]), we will remove reaction times <150ms given that such responses are rare and likely 
represent errors.121  Eye position fixations from the Attentional Engagement-Disengagement 
Task (AEDT) sampled at 120Hz will be converted to visual fixation data using standard criteria 
(i.e., minimum duration 100ms; minimum radius 1 degree).122  
Eye-blink artifacts will be removed from scalp-recorded EEG data on the Cued 

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Emotional Control Task (CECT) and during the resting-state period (0.1-100Hz, sample rate = 
256Hz) using established procedures,123 and gross artifacts will be rejected by visual inspection. 
For the CECT, cue- and target-locked event related potentials (ERPs) will be formed by 
segmenting EEG data around cue and stimulus onsets (from -200 ms to 1000 ms post-stimulus) 
and averaging the segments. Start and end points for the components of interest are: (a) cue-
locked N2: 200-350ms post-cue; (b) target-locked N2: 200-350ms post-target; (c) target-locked 
N450: 400-500ms post-target; (d) target-locked P300: 300-600ms post-target.49 ERPs will be 
rejected if there is significant artifact (e.g., amplitude ± 100 μV) at any electrode on a given trial. 
Artifact-free mean amplitudes (μV) will be extracted for ERP analyses. Additionally, 
nonoverlapping, artifact-free 2-second epochs from the resting-state period will be extracted for 
source localization analyses. Building on recent source localization studies,80,124 seeds from key 
regions within the frontoparietal (FPN) and default mode (DMN) networks will be selected to 
create regions of interest (ROIs) based on previous published methods125,126 and drawing from 
the Montreal Neurological Institute 305 template.127 We will then compute EEG source-based 
functional connectivity using exact Low Resolution Electromagnetic Tomography (eLORETA) 
software.78 
 
Primary Analyses 
Due to the nested structure of the data (i.e., 4 assessments per participant), we will use 
a multi-level generalized linear modeling (GLM) approach to address each of our hypotheses.  
 
Hypothesis 1: Target Engagement. To test whether participants who receive AR-ERT show 
greater improvements in attentional/cognitive control relative to those who receive SPT, we will 
run a series of GLM analyses for each index of our attentional/cognitive control target:  
1) Behavioral: (a) attentional disengagement (i.e., latency of shift in gaze from emotional 
to neutral face surrounded by the frame; AEDT), and (b) sustained attention (i.e., 
difference in reaction times to tones following a negative vs. neutral stimulus on the EIT),  
2) Electrophysiological: (a) proactive cognitive control in anticipation of conflict (i.e., cue-
locked N2 ERP amplitudes on “opposite” vs. “actual” trials; CECT), and (b) reactive 
cognitive control in response to conflict (i.e., target-locked N2, N450, and P300 ERP 
amplitudes after the “opposite” vs. “actual” cue; CECT), 
3) Self-report: Attentional Control Scale (ACS). 
 
We will analyze each target index individually without adjusting for multiple testing128 in order to 
be inclusive in identifying targets for future studies (e.g., R61/R33 proposal). Analyses will be 
modeled as the GLM equivalent of 2 x 3 ANOVAs with treatment condition (AR-ERT vs. SPT), 
time (pre-, mid-, post-treatment), and their interaction as fixed effects; the primary contrast of 
interest will be treatment difference at week 8 (post-treatment).129 Repeated measures per 
person will be modeled with either an auto-correlation, Toeplitz, or unstructured covariance 
matrix (choosing the best model based on AIC and BIC).  
 
Hypothesis 2a: Treatment Efficacy. To examine whether repetitive negative thinking (RNT) 
and psychiatric functioning improve during AR-ERT, we will also use GLM. Analyses will be 
modeled as the GLM equivalent of 2 x 4 ANOVAs with treatment condition (AR-ERT vs. SPT), 
time (pre-, mid-, post-treatment, follow-up), and their interaction as fixed effects; the primary 
contrast of interest will be treatment difference at week 8 (post-treatment), and a secondary 
outcome contrast will be at week 20 (3-month follow-up). Outcomes include:  
1) Repetitive Negative Thinking: (a) Perseverative Thinking Questionnaire – Past Week 
(PTQ-PW; primary outcome), (b) Rumination Response Scale (RRS), (c) Penn State 
Worry Questionnaire (PSWQ), and (d) Rumination on Obsessions and Compulsions 
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2) Clinical Symptoms: (a) Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and 
Dimensional Obsessive-Compulsive Scale (DOCS), (b) Structured Interview Guide for 
the Hamilton Anxiety Rating Scale (SIGH-A) and State Trait Anxiety Inventory-Trait 
(STAI-T), (c) Structured Interview Guide for the Hamilton Depression Rating Scale 
(SIGH-D) and Beck Depression Inventory (BDI-II), and (d) Clinical Global Impression 
Scale – Severity (CGI-S). 
3) Psychiatric Functioning: (a) Work and Social Adjustment Scale (WSAS), and (b) 
Quality of Life Enjoyment and Satisfaction Questionnaire – Short Form (Q-LES-Q-SF). 
 
Hypothesis 2b: Target Validation. To examine the extent to which alteration in the 
hypothesized target (attentional/cognitive control) is related to improvements in clinical RNT 
outcomes, we will compute change scores from pre- to post-treatment for both the target (i.e., 
AEDT, EIT, CECT, ACS) and outcome measures (i.e., PTQ-PW [primary outcome], RRS, 
PSWQ, ROCS, Y-BOCS, DOCS, SIGH-A, STAI-T, SIGH-D, BDI-II, CGI-S, WSAS, Q-LES-Q-
SF). Pearson’s correlations between changes in target and changes in outcome measures will 
then be computed (i.e., a completers-only analysis).  
 
Exploratory Source Localization Analyses 
We will also conduct exploratory source localization analyses with a focus on the 
frontoparietal (FPN) and default mode (DMN) networks. Based on previous research 
demonstrating changes in the anterior cingulate cortex (ACC) over the course of psychosocial 
treatment130,131 and indicating that increased activity in this region predicts better treatment 
outcomes,79,132–134 we will test the following: 
1. Whether changes in ACC activation are demonstrated pre/post treatment using GLM 
(i.e., predicting a main effect of time) and whether treatment group (AR-ERT vs. SPT) 
moderates this effect (i.e., treatment group x time interaction).  
2. Whether baseline (week 0) rostral ACC (rACC) theta (4.5-7 Hz) current density predicts 
greater reduction in RNT and symptom severity as measured by the PTQ-PW and 
disorder-specific measures using GLM (i.e., predicting a rACC theta x time interaction) 
and whether treatment group (AR-ERT vs. SPT) moderates this effect (i.e., treatment 
group x rACC theta x time interaction). 
 
Finally, source localization analyses will be used to investigate the neural generators of scalp-
recorded EEG signals during the CECT, with a focus on the dorsal anterior cingulate cortex 
(dACC) and dorsolateral prefrontal cortex (DLPFC) given their roles in conflict monitoring 
(dACC) and conflict resolution (DLPFC), respectively.57,58,135–139 
 
Power Analysis and Sample Size 
In prior studies,31,140 ERT significantly improved mean levels of attentional control (ACS, 
our self-report target; 15.6%) and reduced RNT (PTQ-PW, our primary outcome; 37.2%) from 
pre- to post-treatment; with effect sizes of Hedge’s g = 1.65 and 2.36 respectively in an open 
trial. ERT also significantly reduced worry (PSWQ; 34.8%) and rumination (RRS; 17.6%); with 
effect sizes of Hedge’s g = 1.50 and 0.74 respectively compared to a waitlist control group with 
contact. Our electrophysiological and behavioral targets of attentional/cognitive control have 
also demonstrated sensitivity to intervention in previous studies.40,77,141 Sixty-two patients with 
elevated RNT (to balance power with recruitment feasibility) will enter the study to have a 
sample of 52 with attrition, which is reasonable given previous 85% retention rates of ERT at 
post-treatment (our primary endpoint).31 Based on power calculations (i.e., one-way ANOVA at 
post-treatment, assuming a 1:1 randomization to AR-ERT vs. SPT), with n = 52 completers, we 
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which is within range of the previous studies cited above. Finally, with 52 people at the end of 
treatment, we can detect correlations between target and outcome measures of .38 or greater.  
 
7. RISKS AND DISCOMFORTS 
 
The following are potential risks/discomforts that participants may experience in this study: 
 
1) Assessments and Questionnaires. During the study assessments, participants may 
feel bored or tired completing some of the questionnaires or computer tasks. They also 
might experience some discomfort, embarrassment, or anxiety from discussing personal 
material and completing self-report questionnaires. Likewise, some participants may feel 
uncomfortable about having assessment sessions digitally recorded and reviewed by 
study staff (which is necessary for rater supervision as well as assessment of the 
reliability of ratings).  
 
2) EEG. There are no known or foreseeable risks or side effects associated the EEG 
procedures. The EEG sensors (Brain Products GmbH, Gilching, Germany) have been 
approved by the U.S. Food and Drug Administration (FDA) for research purposes and will 
be operated within the standards reviewed and accepted by the FDA. Participants may 
experience some discomfort because we may have to gently scrape the skin in order to 
receive clear signals from the EEG electrodes. 
 
3) Computer tasks. Some of the scenes that participants will view during the Emotional 
Interference Task (EIT) involve emotionally evocative images of violence, death, 
blood/gore, and sex (from the International Affective Picture System [IAPS] dataset) and 
may generate distress. 
 
4) Treatment. The treatment offered in this study may make some individuals temporarily 
distressed during procedures that involve confronting the content of their repetitive 
negative thoughts and associated emotions of depression and anxiety (e.g., mindfulness 
of thoughts and emotions; imaginal rehearsal tasks); however, these procedures rarely 
make subjects significantly distressed, and participants will be able to manage the 
intensity of these exercises along with their therapist. Participants may also experience 
an increase in distress due to the natural waxing and waning of OCD, anxiety, and 
depression symptoms; however, participants will be carefully monitored, and measures 
will be taken to minimize potential risks during the project period (as discussed in 
“Protection Against Risks” below).  
 
5) Privacy and Confidentiality. Breach of confidentiality represents a potential risk; 
however, the greatest care will be taken to prevent this from occurring (as discussed in 
“Protection Against Risks” below). In the informed consent process, we will also inform 
participants of the legal limits to privacy and confidentiality including: (1) if we believe 
participants are at serious risk of harming themselves or another person, (2) if we learn of 
ongoing abuse or neglect of a child, disabled, or elderly person, and (3) if we receive a 
subpoena or court order. We currently have an active Business Associate Agreement 
with a Statement of Work for iMotions Inc to be able to share coded data collected and 
analyzed using their software platform (i.e., the eye tracking data) for data support 
purposes. 
 
In addition to the above practices, our study will be under compliance with the HIPAA 
(Health Insurance Portability and Accountability Act) rules governing the Partners 

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Healthcare system. All participants who enroll in this study will be given an electronic 
copy of the HIPAA privacy notice and will be asked to sign an acknowledgement of 
receipt and authorization form. 
 
Protection Against Risks 
The following procedures will be implemented to protect participants against risks: 
 
1) Informed Consent. Informed consent will be obtained at the virtual screening visit using 
IRB-approved e-consent forms. After participants read the consent form, the PI (Dr. 
Jacoby) or doctoral-level delegate will paraphrase each segment of the consent form 
and answer any questions. Participants will be clearly informed of the voluntary and 
confidential nature of their participation, the potential risks and benefits of the study, and 
their right to terminate treatment at any time without penalty. There will be a clause 
included in the informed consent form concerning the audio taping of assessments and 
therapy sessions for reliability. As of February 2022, participants will be shown sample 
images from the IAPS database so they can decide whether to participant in the EIT task 
since the images may be distressing. Participants already enrolled prior to this change 
will not be re-consented because they have already seen the task and know what it 
entails. If the participant agrees to participate in the study, the consent form will be 
signed by the research participant and the PI using the e-consent module in REDCapTM. 
Each participant will be emailed a copy of the signed and dated consent forms.  
 
2) Assessments and Treatment. The IEs will make every attempt to help participants feel 
comfortable when discussing sensitive material. Participants will have as much time as 
needed to complete study questionnaires and may skip any questions they do not want 
to answer. The therapist will work with the participant to ensure sessions are tolerable 
and appropriate in terms of risk and distress. 
 
3) EEG. The experimenters will make every attempt to help participants feel comfortable 
during the EEG and will check in with participants regarding their comfort level during the 
set-up of the EEG sensors. Participants can ask to pause or stop the EEG session at 
any time, for any reason. 
 
4) Computer tasks. Participants will be shown two sample images from the same 
database at the screening visit so they can decide whether to participate in the EIT. If 
they choose to participate in the task, they are also told that it is alright to look away 
during the task if they find these images too disturbing. 
 
5) Privacy and Confidentiality. The following methods will be used to protect the 
confidentiality of information provided by participants: 
a) Data will be encoded using Participant IDs and not names. IDs will be assigned 
sequentially and unrelated to name, social security number, or other easily 
identified information. 
b) Names will not be included in digital recordings, in computerized data files, or in 
any published reports. 
c) Digital recordings for reliability, adherence, and competence will be stored 
securely in a password-protected drive within the Center for OCD and Related 
Disorders and destroyed after completion of the study.  
d) Study data will be reviewed only by pre-designated study personnel or, if 
necessary, by institutional, state or federal regulatory personnel. 

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e) All personnel will be trained in research confidentiality procedures and will be 
educated about the importance of strictly protecting participants’ rights to 
confidentiality.  
f) Many procedures will be used to protect the security of data collected via 
REDCapTM, the platform for electronic data capture that will be used in this study. 
REDCapTM is deployed on a secured server. All network connections to the 
server are encrypted using high strength cyphers of at least 128 bits. The 
hardware is owned by MGH/Harvard Medical School (HMS) and administered by 
several computer professionals employed by the MGH/HMS.  
g) MGH is accredited by the Association for the Accreditation of the Human 
Research Protection Programs Inc. (AAHRP), indicating that it is an institution 
that has regulations and policies in place to ensure protection of research 
participants and their confidentiality that exceed federal requirements for 
safeguarding participants.  
h) Data shared with iMotions Inc for data support purposes will only include 
participants’ coded alphanumeric study IDs and the key to the coded data (linking 
study ID and participants’ identifiable information) will not be shared. Thus, 
iMotions will not have the ability to link the data to individual participants. Files 
will be shared via PHS Secure File Transfer. 
i) Any data that is shared with other collaborators in the future would only be done 
so after executing a formal Data Use Agreement from Massachusetts General 
Hospital (MGH). As part of this process, the final dataset would be stripped of 
any identifiers that would permit linkages to individual research participants prior 
to release for sharing (i.e., coded). Additionally, given the sensitive nature of 
psychiatric symptoms and diagnosis and our relatively small sample size, we 
would make the data and associated documentation available to users only 
under a data-sharing agreement that provides for: (1) a well-described 
justification for the use of the data; (2) a commitment to using the data only for 
research purposes (under purview of an institutional IRB) and not to identify any 
individual participant; (3) a commitment to securing the data using appropriate 
computer technology; (4) a commitment to not transfer the data to other users; 
and (5) a commitment to destroying the data after analyses are completed. In 
compliance with NIH guidelines, data sharing would be done in a timely fashion 
(i.e., no later than the acceptance for publication of the main findings for the final 
dataset). 
j) Due to the NIH-funding for this study, a Certificate of Confidentiality will 
automatically be obtained. 
k) All necessary precautions will be taken to ensure participant privacy while 
conducting virtual study visits over ZoomTM. Healthcare Secure ZoomTM includes 
built in protections such as chat encryption, mandatory waiting rooms, and 
disablement of video recordings. 
 
6) Emergencies and Suicidality. Because patients with affective disorders can also 
experience suicidal thinking and behaviors, we will carefully implement safety 
precautions including:  
a) Patients who are actively suicidal at the screening visit (as assessed by the 
SCID-5-RV, SIGH-D, and/or score on the BDI-II suicide item #9 ≥ 2) will be 
excluded from the study. 
b) Screening procedures will also exclude any individuals at potentially greater risk 
for psychiatric deterioration or an adverse outcome, or who are not clinically 
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inclusion/exclusion criteria above, individuals will be excluded if they have active 
and clinically significant homicidality or any features requiring a higher level of 
care. 
c) As part of the informed consent process, participants will be asked if they are 
willing to provide contact information for two friends or family members and to 
give permission to have the research team call or write to these individuals in the 
case of an emergency (i.e., if we have concerns about their wellbeing). 
d) Suicidality will be closely monitored with the BDI-II suicide item (#9) and clinician 
inquiry at each visit. 
e) Patients at higher risk will be withdrawn from the study as described in the next 
section below. 
f) Dr. Jacoby (or covering clinician in her absence) will be available 24/7 to 
participants in the event of a clinical emergency; this will be clearly 
communicated orally and in writing to study participants (i.e., the consent form 
describes how to reach the investigators in an emergency). Participants will be 
referred for a higher level of care as needed. 
g) In the event that a study staff member witnesses behaviors such as abuse or 
neglect of children or the elderly while conducting a virtual study visit via ZoomTM, 
they will report this to the PI who will consult with the Office of General Council 
and follow hospital policy for reporting such behaviors. 
 
7) Participant Withdrawal. Subjects may be withdrawn from the study for any of the 
following reasons:  
a) A significantly deteriorating clinical course, such as emergence of active suicidal 
ideation or a need for hospitalization.  
b) Score of ≥ 2 on the BDI-II suicide item (#9) and subsequent evaluation by the PI 
indicating it would be unsafe for the patient to remain in the study. 
c) Score of 6 (much worse) or 7 (very much worse) on the CGI-I for 3 consecutive 
weeks and therapist and PI judgment that remaining in the study is not in the 
subject’s best interest; a patient may be withdrawn sooner than this, if in the 
judgment of the therapist and PI, this is in the patient’s best interest.  
d) PIs' decision that withdrawal from the study is in the subject's best interest.  
e) Subject's decision to withdraw. 
 
Subjects who require medication changes or begin other types of therapy (e.g., family 
therapy) will be kept in the study even though such events violate study procedures. We 
will compare outcome data for compliant and non-compliant subjects. 
 
The PI will discuss and agree upon the withdrawal of any subject with the therapist and 
Dr. Wilhelm. The reason for withdrawal or dropout will be documented, and the subject 
will be referred for appropriate treatment. Except for subjects who withdraw consent to 
participate, all who are withdrawn or drop out of the study will be asked to complete all 
remaining assessments. We will educate subjects about the importance of completing all 
scheduled assessments and will provide payment as described above to encourage 
retention. As mentioned above, participants will be asked if they are willing to provide 
contact information for two friends or family members and to give permission to have the 
research team call or write to these individuals if contact between the participant and the 
research team is lost. 
 
The above procedures have been used in previous research studies and were effective in 
protecting our research participants against risk. Therefore, we anticipate that these procedures 

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will be effective in our proposed study. In the unlikely event that a participant experiences a 
research-related injury, the study PI will arrange for appropriate treatment. 
 
8. POTENTIAL BENEFITS 
 
Participants may benefit from the comprehensive diagnostic assessment provided at the outset 
of the study. Patients with RNT may also benefit by experiencing relief from their symptoms. For 
participants assigned to AR-ERT, this treatment includes elements that have been shown to 
lead to decreased symptomatology in mood and anxiety disorders, and to improve quality of life 
and functional impairment. For participants assigned to SPT, this therapy is commonly offered 
by community clinicians for affective disorders, and thus is comparable to services patients 
might receive elsewhere. SPT is also acceptable from a safety perspective, as it allows for close 
monitoring.  
 
Indirect benefits of the study include increased knowledge regarding treatment for RNT that will 
improve interventions for future patients and decreased impact of psychiatric illnesses 
characterized by RNT on society (i.e., reduced health care costs and disability). The knowledge 
to be gained by the proposed research has enormous public health importance because RNT is 
highly prevalent in the general population, and excessive healthcare costs are being spent on 
treatments that are not optimally effective. Mood and anxiety disorders are among the most 
common and disabling mental health conditions world-wide, and given their high comorbidity, 
prioritizing the understanding and treatment of shared characteristics like RNT may lead to more 
efficacious interventions for a broader range of patients. Although cognitive behavioral therapy 
is considered an effective first line intervention, many patients receiving this treatment are 
deemed non-responders, suggesting that underling factors – such as RNT, which remains a 
residual symptom – are not being fully addressed. Thus, by engaging biobehavioral targets of 
attentional/cognitive control posited to underlie RNT and measuring target engagement and 
validation of this mechanism with a multi-method approach (i.e., ERPs, eye tracking), this study 
has great potential to improve the precision of RNT and emotion-focused therapies for affective 
disorders.  
 
The risks that this study poses to participants are reasonable in relation to the importance of 
knowledge that may be expected to result because psychiatric disorders characterized by RNT 
are common, can be severe, and are often chronic. Thus, risks of discomfort associated with 
treatment are offset by the potential benefit of reduction of symptoms and improvement in 
mood, functioning, and quality of life for these patients. As such, the benefits of this study far 
outweigh the potential risks.  
 
9. MONITORING AND QUALITY ASSURANCE 
 
Therapist Training and Supervision 
All treatment will be provided by masters- or doctoral-level mental health professionals 
experienced in cognitive behavioral techniques like AR-ERT, experienced in SPT, and familiar 
with affective disorders. We carefully considered the advantages and disadvantages of 
therapists providing one treatment but not the other (nesting within conditions) versus providing 
both treatments (crossing therapists with conditions).142 To assure equivalence of therapist 
training and competence, study therapists will provide therapy to patients in both conditions 
(AR-ERT and SPT). 
Therapists will receive rigorous training before treating study patients. First, therapists 
will read the treatment manuals, related reading materials on AR-ERT and SPT, and readings 
on RNT. Therapists will then have to pass (i.e., 90% correct) a knowledge test about their 

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reading material. Therapists will attend a training led by Dr. Jacoby that consists of: (1) a 
discussion of the phenomenology and other important aspects of RNT, (2) an overview of 
implementation of the study protocol, (3) training on the manualized treatments, which will 
include slide presentations, role plays, and discussion, and (4) a discussion of the 
distinctiveness of the two treatments. To ensure ongoing high-quality treatment, therapists in 
each condition will receive weekly supervision from the PI (Dr. Jacoby) in AR-ERT and SPT. 
Care will be taken in supervision to ensure that specific AR-ERT techniques are not introduced 
into SPT. 
 
Monitoring of Treatment Fidelity 
All treatment sessions will be digitally audio recorded. A doctoral-level independent 
adherence rater will rate 5% of randomly selected sessions at regular intervals during the study 
using our adherence and competence measures described above. This will be done to ensure 
adherence to the treatment manuals (to minimize the risk that techniques implemented in AR-
ERT are delivered in the SPT condition; i.e., therapist drift), consistency of treatment delivery, 
and competent delivery of the treatments. The adherence rater will have experience with both 
AR-ERT and SPT and will be further trained and supervised by Dr. Jacoby. He/she will attend 
the initial therapist training activities described above and will watch the training tapes of AR-
ERT and SPT. Descriptive statistics on adherence and competence ratings will be obtained. 
 
Independent Evaluator (IE) Qualifications and Ensuring IE Blindness 
A blinded evaluation of outcomes by an IE is essential to obtain unbiased information on 
treatment efficacy. IEs will have a masters or doctoral degree in psychology or a related mental 
health field. We will take many steps to ensure that IEs remain blind to treatment condition 
throughout the study for all participants. IEs will not be told the treatment assignment for any 
participant. IEs will be trained to focus on outcome measurement only and to avoid any 
discussion of what treatment subjects are receiving. Moreover, patients will be reminded at each 
IE assessment not to discuss their treatment with the IE. Therapists and study staff will be 
regularly reminded of this as well. Supervisory discussions about treatment will occur in 
separate meetings attended only by therapists and supervising clinicians. Treatment and 
assessment recordings will be kept in separate locations. Furthermore, the IE will be asked to 
guess the treatment condition of each participant after the completion of the follow-up 
assessments or, for dropouts, after the last treatment session. 
 
Establishing and Monitoring Interrater Reliability 
The study team has extensive experience with the measures used in this study. Training 
and reliability checks will be done to ensure that IEs conduct ratings in a uniform way. IEs will 
first receive instruction in the Y-BOCS, SIGH-A, SIGH-D, and CGI-I/S from Dr. Jacoby in an 
initial study start-up meeting. Subsequently, IEs will rate Y-BOCS, SIGH-A, SIGH-D, and CGI-
I/S training tapes of interviews conducted by Dr. Jacoby. IEs will be certified when they reach 
reliability criteria with Dr. Jacoby for these measures (defined by ICCs ≥.8). 
To maintain inter-rater reliability during the study and reduce rater drift, all assessments 
will be audio recorded. A senior member of the OCD Program’s staff will review and rate 5% of 
randomly selected digitally recorded interviews at regular intervals during the study. If reliability 
with this rater falls below the above criteria, we will institute retraining procedures. Dr. Wilhelm 
will also conduct weekly supervision meetings with IEs during which assessment interviews 
from the past week will be discussed. Any problems in interview content and diagnostic 
disagreements will be addressed during supervision. Reliability statistics will be included in our 
publications. 
 

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Research Team Meetings  
In addition to the study start up meetings described above, the PI and clinical research 
assistant will meet weekly to discuss the study, including recruitment, new subjects to ensure 
inclusion/exclusion criteria are met, withdrawal of any subjects, any safety issues, and other 
topics. 
 
Data and Safety Monitoring Board (DSMB) 
 
 
In order to provide the most comprehensive protection of participants, we will establish a 
formal data and safety monitoring board (DSMB). The DSMB will be comprised of 3 members 
who have expertise in clinical trials, anxiety, mood, and OC spectrum disorders, are not 
affiliated in any other way with the proposed project, and do not have an affiliation with the 
MGH/Harvard Medical School. Board members will consist of: 
 
1) Eric Storch, Ph.D., Professor of Psychiatry and Behavioral Sciences, Baylor College of 
Medicine 
2) Alicia Meuret, Ph.D., Associate Professor in Clinical Psychology and Director of the 
Anxiety and Depression Research Center at Southern Methodist University 
3) Adam Lewin, Ph.D. Associate Professor and Director OCD & Related Disorders 
Program, University of South Florida 
 
All board members are very familiar with safety and ethical concerns related to human subjects 
in clinical research. The DSMB will meet twice per year (by conference call) to review the 
study’s progress, enrollment, deidentified group-level data for differential rates in key outcomes, 
and adverse events. They will be responsible for monitoring rates of enrollment and study 
retention, patient safety, and data confidentiality and entry. The DSMB will provide guidance to 
the PI (Dr. Jacoby) who will then be responsible for executing the data and safety monitoring 
plan and complying with the reporting requirements. The PI will provide a summary of the 
DSMB report to the NIH on an annual basis as part of the progress report. The DSMB report will 
include participants’ sociodemographic characteristics, expected versus actual recruitment 
rates, treatment retention rates, any quality assurance or regulatory issues that occurred during 
the past year, summary of adverse events, and any actions or changes with respect to the 
protocol. The DSMB report will include, when available, the results of analyses that have been 
conducted. 
 
Adverse Events Reporting 
 
Based on information from previous studies involving EEG, clinical assessment, and treatment, 
the following adverse events are expected, as described in the consent form and reviewed in 
detail above in Section 3C: 
1. Becoming tired or uncomfortable answering assessments and questionnaires 
2. Discomfort from scraping skin on the scalp during EEG procedures 
3. Distress from the computerized images during the eye-tracking task 
4. Temporary increase in anxiety or depression during treatment 
5. Possible loss of privacy (e.g., due to contacting an emergency-contact or due to legal 
limits of confidentiality) 
 
An IRB approved AE Tracking log will be administered by the RA and reviewed by the PI at the 
clinical assessment visits (baseline, mid-treatment, post-treatment, and 3-month follow-up) to 
probe for any adverse events that occurred since the last visit. 
 

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Adverse events and Unanticipated problems will be reported to the MGB IRB in accordance with 
its policy. Specifically, in accordance with guidelines of the Office for Human Research 
Protections (OHRP) and NIMH, reporting of adverse events will occur to (1) the MGH IRB, (2) 
the NIMH program officer, (3) OHRP, and (4) the DSMB as follows: 
 
1) Unexpected serious adverse events (SAE) related to study participation (e.g., death, 
life threatening AE, suicide attempt, inpatient hospitalization) will be reported within 5 
business days of the study team first learning of a death and within 10 business days 
of the study team becoming aware of a non-death SAE. 
2) Any other unanticipated problems involving risks to subjects or others will be reported 
within 10 business days of the study team becoming aware of the event. 
3) All adverse events and SAEs that are deemed expected or unrelated to the study will 
be summarized in twice-annual progress reports for the DSMB and in annual 
progress reports for the NIMH and IRB. 
 
Documentation to be submitted for reportable events will include: 
• 
Identifying information for the research protocol (e.g., project title, investigator’s name, 
and the grant/contract number) 
• 
The date on which the event occurred and the date at which the PI became aware of the 
event 
• 
A detailed description of the event and impact on the participant(s) 
• 
A detailed description of the measures taken (including clinical) in response to the event 
(if any) 
• 
Confirmation that the appropriate monitoring entities and regulatory bodies have been 
notified as needed 
• 
A description of any changes to the protocol or other corrective actions that have been 
taken or are proposed in response to the event 
 
Data Management 
 
 
REDCap™ (Research Electronic Data Capture) is a free, secure, HIPAA-compliant web-
based application hosted by the Partners HealthCare Research Computing, Enterprise 
Research Infrastructure & Services (ERIS) group. Vanderbilt University, with collaboration from 
a consortium of academic and non-profit institutional partners, has developed this software 
toolset and workflow methodology for electronic collection and management of research and 
clinical study data. Data collection projects rely on a study-specific data dictionary defined by 
members of the research team with planning assistance from Harvard Catalyst | The Harvard 
Clinical and Translational Science Center EDC Support Staff. The iterative development and 
testing process result in a well-planned data collection strategy for individual studies. Using 
REDCap, the research team can also design web-based surveys and engage potential 
respondents using a variety of notification methods. REDCap provides flexible features that can 
be used for a variety of research projects and provides an intuitive interface to enter data with 
real time validation (automated data type and range checks). The system offers easy data 
manipulation with audit trails, reports for monitoring and querying participant records, and an 
automated export mechanism to common statistical packages (SPSS, SAS, Stata, R/S-Plus). 
 
 
Scales are completed securely via the internet by using any device with standard web 
access and browsers. Participants and/or research staff will enter scale responses directly into 
REDCap electronic assessment forms. Using 256 bit RSA Secure Socket Layer (SSL) 
encryption, approved users will be logged-in to machines using secured browsers behind the 
Partners Healthcare Systems IS corporate firewall. Staff will have a unique identifying key that 
will link them to the electronic study forms. This unique ID will be used in addition to a randomly 

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generated secure password that only the staff person will have. Thus, under supervision by 
staff, each subject will only have access to complete his/her own scales and will not be able to 
view data from any other subjects. 
 
 
Responses entered by subjects will be transmitted to and stored in a secured database 
at MGH. This database will be configured in REDCap by the database administrator who will set 
up strict permissions to maintain confidentiality. Dr. Susanne Hoeppner will assist with creating 
logical checks to identify data inconsistencies, omissions, and errors in real-time. Issues 
identified will trigger queries, and problems will be resolved promptly. Emails will be 
automatically sent to research assistants when scales are completed so any missing data can 
be examined. Data will be backed up automatically nightly and downloaded from REDCap into 
SPSS for analysis.  
 
 
Data collected from two instruments will be stored outside of the REDCapTM system. 
Specifically, data collected at screening from the clinician-administered computerized SCID-5-
RV (NetSCID-5) will be saved within the TeleSage, Inc. system. TeleSage, Inc. ensures the 
privacy and confidentiality of NetSCID data using a rigorous set of procedures. Each participant 
is associated with a unique NetSCID project and its affiliated organization, as well as a coded 
participant ID. All data are stored on a Secured Socket Layer (SSL) HIPAA-compliant web 
server, encrypted at rest and geo-redundant data backup on a separate HIPAA-compliant 
database. Data is downloaded in encrypted format by users via a secure data download page. 
In addition, participant responses on the BDI-II at the 3-month follow-up time-point will be stored 
electronically utilizing the Q-global software system by Pearson, Inc. All data will be coded using 
a corresponding participant ID and stored on Pearson’s servers or those of its affiliates and/or 
authorized vendors and will only be accessible by authorized employees, agents and 
contractors of Pearson and its affiliates and authorized vendors.  
 
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