The Influences of Eating and Fasting on Inhibitory Control in Bulimia Nervosa: A Computational Neuroimaging Study
Phase: NA
Conditions: Bulimia Nervosa
Sponsor: Icahn School of Medicine at Mount Sinai

The Influences of Eating and Fasting on Inhibitory Control in Bulimia Nervosa: 
A Computational Neuroimaging Study
PI: Laura Berner, PhD
NCT04409457
Document Date: 5-1-2025

The Influences of Eating and Fasting on 
Inhibitory Control in Bulimia Nervosa: A 
Computational Neuroimaging Study
Protocol Number: STUDY-19-00591
National Clinical Trial (NCT) Identified Number:  NCT04409457
Principal Investigator: Laura Berner, Ph.D.
GCO Number: 19-1047
Grant Number: 1K23MH118418-01
Funded by: National Institute of Mental Health (NIMH)
Protocol Version Number:  v.05.10.2023 
Effective Date: 5/1/2025
End Date:4/30/2026

NIH Protocol Template for Behavioral and Social Sciences Research
CONFIDENTIALITY STATEMENT
This document is confidential communication. Acceptance of this document constitutes agreement by the 
recipient that no unpublished information contained herein will be published or disclosed without prior 
approval of the Principal Investigator or other participating study leadership and as consistent with the NIH 
terms of award. 
Effective Date: 5/1/2025
End Date:4/30/2026

The Influences of Eating and Fasting on Inhibitory Control in Bulimia Nervosa: A 
Computational Neuroimaging Study
STUDY-19-00591
v.05.10.2023
i
Table of Contents
1
PROTOCOL SUMMARY......................................................................................................................................2
1.1
Synopsis..................................................................................................................................................2
1.2
Schema...................................................................................................................................................4
2
INTRODUCTION.................................................................................................................................................5
2.1
Study Rationale ......................................................................................................................................5
2.2
Background ............................................................................................................................................5
2.3
Risk/Benefit Assessment........................................................................................................................9
2.3.1
Known Potential Risks ........................................................................................................9
2.3.2
Known Potential Benefits .................................................................................................10
2.3.3
Description of Procedures Taken to Lessen the Probability or Magnitude of Risks .........10
3
OBJECTIVES AND ENDPOINTS .........................................................................................................................16
3.1
Objectives.............................................................................................................................................16
3.2
Study Endpoints ...................................................................................................................................18
4
STUDY DESIGN ................................................................................................................................................18
4.1
Overall Design ......................................................................................................................................18
4.2
End-of-Study Definition........................................................................................................................18
5
STUDY POPULATION .......................................................................................................................................19
5.1
Inclusion Criteria ..................................................................................................................................19
5.2
Exclusion Criteria..................................................................................................................................19
5.3
Strategies for Recruitment and Retention ...........................................................................................20
6
STUDY EXPERIMENTAL MANIPULATION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL.............................................................................................................................20
6.1
Participant Discontinuation/Withdrawal from the Study ....................................................................20
7
STUDY ASSESSMENTS AND PROCEDURES.......................................................................................................21
7.1
DESCRIPTION OF PROCEDURES BEING PERFORMED............................................................................21
7.2
Description of the Source Records that Will Be Used to Collect Data About Subjects ........................23
7.3
Adverse Events, INCIDENTAL FINDINGS, and OTHER POTENTIAL ISSUES ............................................25
8
STATISTICAL CONSIDERATIONS.......................................................................................................................25
8.1
Data Analysis Plan (Including Any Statistical procedures)....................................................................25
8.1.1
Hypothesis Testing............................................................................................................25
8.1.2
Exploratory Analyses and Potential Confounds................................................................26
8.2
POWER ANALYSIS (Sample Size Determination) ..................................................................................26
9
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ......................................................27
9.1
Regulatory, Ethical, and Study Oversight ConsiderationS....................................................................27
9.1.1
Informed Consent Process................................................................................................27
9.1.2
Confidentiality and Privacy...............................................................................................27
9.1.3
Future Use of Stored Specimens and Data.......................................................................27
9.1.4
Safety Oversight................................................................................................................27
10
REFERENCES....................................................................................................................................................27
Effective Date: 5/1/2025
End Date:4/30/2026

The Influences of Eating and Fasting on Inhibitory Control in Bulimia Nervosa: A 
Computational Neuroimaging Study
STUDY-19-00591
v.05.10.2023
2
1
PROTOCOL SUMMARY
1.1
SYNOPSIS 
Title:
The Influences of Eating and Fasting on Inhibitory Control in Bulimia Nervosa: 
A Computational Neuroimaging Study
IF Number
TE00000667 (Year 4)
IF2706030 (Year 3)
IF2645754 (Year 2)
IF2452740 (Year 1)
Study Description
Bulimia nervosa (BN) is a serious eating disorder characterized by a cycle of 
binge eating and behaviors designed to undo or counteract the effects of binge 
eating. In the past, studies have linked BN to problems with self-control, but it is 
not yet understood how individuals with the disorder can show both out-of-
control binge eating and dangerously overly controlled dietary restriction, like 
fasting. The purpose of this study is to investigate areas of the brain responsible
for self-control in adult women with BN compared to women who have never had
an eating disorder. More specifically, investigators are interested in whether 
individuals with BN show abnormal changes in brain activation (e.g., changes in 
blood flow and oxygen use) when they are trying to control their behaviors, and 
whether brain activity depends on how recently eating or fasting has occurred. 
Data collection will rely on a technology called functional magnetic resonance 
imaging (fMRI).
Objectives:
Primary Objective: To determine whether eating and fasting abnormally 
interfere with the capacity of individuals with BN to adaptively exert inhibitory 
control
Secondary Objective: To identify associations of BN symptom severity with 
state-specific frontostriatal activation
Endpoints:
Primary Outcome: Frontostriatal activation
We will compare the impact of fasting and eating on neural activation in 
women with BN and healthy controls. Specifically, we will compare groups on 
the influence of fasted and fed state on: 1) frontostriatal activation when 
correctly inhibiting responses and 2) frontostriatal signals for the anticipated 
need to stop (P(stop)) and inhibitory control prediction errors.
Secondary Outcome:
-
Stop signal task performance: We will compare the impact of fasting and 
eating on behavioral task performance in women with BN and healthy 
controls. We will specifically compare groups on stop signal reaction times 
and the percentage of correct stop trials.
-
Eating disorder symptom severity: We will examine, with the BN group, 
whether more severe binge eating/purging is associated with frontostriatal 
signals for P(stop) and inhibitory prediction errors in the fed vs. fasted 
state, and whether more severe dietary restriction is associated with 
frontostriatal signals for P(stop) and prediction errors in the fasted vs. fed 
state.
Effective Date: 5/1/2025
End Date:4/30/2026

The Influences of Eating and Fasting on Inhibitory Control in Bulimia Nervosa: A 
Computational Neuroimaging Study
STUDY-19-00591
v.05.10.2023
3
Other/Exploratory Outcome: Resting cerebral blood flow
We will compare the impact of fasting and eating across our two groups on 
resting cerebral blood flow, as measured by arterial spin labeling (ASL).
Study Population:
Estimated Enrollment): 500
Targeted Populations: Adults – Healthy Controls, Adults – Patients with 
Bulimia Nervosa
Age Ranges: 18 to 35 years
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Gender Eligibility Description:
The prevalence of bulimia nervosa is substantially greater in women than in 
men. Moreover, prior research suggest that men and women show different 
neural response patterns during the engagement of inhibitory control, and that 
satiety differentially impacts the neural function of men and women.
Phase or Stage:
N/A 
Description of 
Sites/Facilities Enrolling 
Participants:
Icahn School of Medicine at Mount Sinai
Description of Study 
Intervention/Experiment
al Manipulation:
Fasting state:
16 hours of fasting
Fed state:
Fed a standardized meal
Study Duration*:
5 years of grant
Participant Duration:
Anticipated over 7-10 days, but participants will be allowed up to 3 months for 
scheduling based on their availability for procedures.
Effective Date: 5/1/2025
End Date:4/30/2026

The Influences of Eating and Fasting on Inhibitory Control in Bulimia Nervosa: A 
Computational Neuroimaging Study
STUDY-19-00591
v.05.10.2023
4
1.2
SCHEMA
Phone Screen
Next Screening
fMRI Scan Visit 1
 
fMRI Scan Visit 2
Randomization 
(Participants are randomly assigned (in 
even numbers across the two groups) to 
fMRI scan order)
Total N = 500 per PPHS’ definition of enrollment); N = 60 (per NIH’s definition of 
enrollment)
Phone screen e-consenting process phone screen potential participants by inclusion and
Conduct full study e-consenting process, remote or in-person clinical interviews and in-person 
pre-scan screening and assessment; if eligible, schedule fMRI scanning visits
Participants with 
Bulimia Nervosa
n = 30
Fasted State: 
16 hours of fasting, fMRI scan
Fed State: 
Fed a standardized meal, fMRI scan
Participants without 
Bulimia Nervosa
n = 30 
Fed State: 
Fed a standardized meal, fMRI scan
Fasted State: 
16 hours of fasting, fMRI scan
Online self-report questionnaires
Effective Date: 5/1/2025
End Date:4/30/2026

The Influences of Eating and Fasting on Inhibitory Control in Bulimia Nervosa: A 
Computational Neuroimaging Study
STUDY-19-00591
v.05.10.2023
5
2
INTRODUCTION
2.1
STUDY RATIONALE 
Every year, 1.4 million years of healthy life are lost to disability or premature death associated 
with bulimia nervosa (BN), and up to half of adults with BN treated with first-line psychotherapies 
do not recover. Treatment-resistant binge eating and purging may be perpetuated by inhibitory 
control deficits linked to reduced activation in lateral prefrontal cortices (LPFC), anterior cingulate, 
and striatum. To date, however, neurocognitive studies of BN have not accounted for 1) the 
dynamic computational processes underlying inhibition or 2) the fact that individuals with BN 
oscillate between two extremes—under-controlled, excessive eating and over-controlled, 
restricted intake. This study proposes to examine the neurocomputational underpinnings of 
inhibitory control in fed and fasted states to test an explanatory model of BN symptoms and inform 
future context-dependent, targeted interventions for BN.
2.2
BACKGROUND 
Bulimia nervosa (BN) affects 1-3% of women [3-6] and is associated with high rates of disability 
and premature death [6-8]. Up to half of adults with BN treated with first-line psychotherapies do 
not recover, and characterization of the neural underpinnings of BN symptoms is essential to 
develop novel, targeted treatments. Data to date suggest out-of-control binge eating and purging 
(e.g., self-induced vomiting) [6] in BN may result, in part, from impaired control over behavioral 
responses (i.e., deficits in inhibitory control) and related reduced activation in frontostriatal circuits. 
However, our understanding of the role of inhibitory control in BN is limited in two critical ways. 
First, inhibitory control is a complex process that requires individuals to a) update expectations 
based on experience, and b) use updated expectations to adaptively adjust behavior [9]. These 
dynamic subcomponents of inhibitory control have not yet been studied in BN. Second, it is not 
clear how deficient frontostriatal activation could explain both out-of-control binge eating and the 
overcontrolled, dangerous restriction that typically occurs between binge/ purge episodes. 
Biologically-based explanatory models for the full spectrum of BN symptoms are lacking. This 
study hypothesizes that just as temporary fluctuations in disinhibition, in addition to stable, 
disinhibited traits, may contribute to substance use disorders [10], state-specific alterations in 
adaptive inhibitory control processes could contribute to BN. Metabolic state, or how recently a 
person has eaten, is a well-established modulator of inhibitory control in healthy individuals, yet 
surprisingly little is known about how metabolic state and inhibitory control interact in BN. This 
study is the first systematic test of whether eating and fasting influence inhibitory control 
abnormally in BN. This knowledge has potential for substantial impact, as it will 1) identify 
elements of the inhibitory control process that specifically may maintain problematic eating, and 
2) pinpoint when interventions designed to bolster inhibitory control may be most effective.
Neural Substrates of Inhibitory Control Processes in BN are Understudied. An imbalance between 
control and reward-related processes may contribute to BN [11, 12], but most neuroimaging 
research in BN to date has focused on reward circuitry [13-19]. Cognitive and motor cortico-
striato-thalamo-cortical (CSTC) loops involved in anticipating the need to control our cognitions 
and behavior [20] and ultimately inhibiting responses are understudied in BN. These control-
related processes recruit overlapping frontostriatal, cingulo-opercular, and frontoparietal 
networks, including dorsolateral and ventrolateral prefrontal cortices (DLPFC, VLPFC) [21-24], 
anterior cingulate cortex (ACC), dorsal striatum, the pre-supplementary motor area, insula, and 
Effective Date: 5/1/2025
End Date:4/30/2026

The Influences of Eating and Fasting on Inhibitory Control in Bulimia Nervosa: A 
Computational Neuroimaging Study
STUDY-19-00591
v.05.10.2023
6
parietal regions.[25-31] When making food- related decisions that require control, DLPFC is 
specifically engaged [32]. Data from existing case-control studies of adult BN suggest reduced 
activation in frontostriatal regions (VLPFC, DLPFC, ACC, caudate and putamen) during inhibition, 
and that this dysfunction is associated with binge/purge symptoms [33, 34]. However, very few 
functional neuroimaging studies have focused on adults ill with BN, much less non-food-specific 
inhibitory control. Further, brain-behavior relationships are not consistent across studies: One 
study found reduced activation and impaired inhibitory performance in BN [33], while one 
adolescent study [35] and one adult study [34] found reduced activation in the context of intact 
performance. Reduced activation could thus reflect deficient or efficient processing during 
inhibition in BN. More nuanced behavioral measures and careful control of state-based factors 
are needed to clarify these inconsistencies. Moreover, past BN research that has focused on 
neural activation during successful and failed inhibition alone has likely missed subtle alterations 
in the dynamic inhibition process.
Dysfunctional Components of Adaptive Inhibitory Control May Perpetuate BN. Adaptive inhibitory 
control requires moment-to-moment decision-making about whether to engage in or stop a 
behavior, and using experience to update beliefs about how likely it is that inhibition will be 
required in the subsequent moment.[9] These computations can be quantified using Bayesian 
models. Such models, combined with fMRI, have identified blunted signals for the expected need 
to inhibit in the VLPFC, DLPFC, ACC, and caudate that distinguish substance users from controls 
and predict the onset of and relapse to problematic substance use.[36-38] Similarly altered 
frontostriatal signals for these computations may maintain BN. Prior work has documented 
attenuated signals for food-reward-related prediction errors in BN,[19] and individuals with BN 
show decision-making deficits [39-41] correlated with impaired control [40]. However, no study 
has investigated how altered signals for inhibitory control prediction errors and expectations may 
contribute to BN.
BN is a Disorder of Extreme Under- and Over-Control. Our understanding of inhibitory control 
processes in BN has been further limited by a sole focus on deficiencies. Indeed, hallmark loss-
of-control eating and frequent co-occurring impulsive behaviors [6, 42-44], along with most 
neurocognitive task performance findings [45], point to inhibitory control impairments in BN. 
However, some neurocognitive studies report intact inhibitory control abilities in BN [46]. 
Moreover, BN is characterized by rigid dietary restriction between binges and is associated with 
"traits" typical of "overcontrolled" populations—perfectionism and harm avoidance [47-50]. Data 
also suggest that impulsive "traits" decrease after binge/purge frequency reductions [51]. These 
discrepancies raise the possibility that control-related alterations in BN are state-dependent, 
rather than trait-like.
The Influences of Fasting and Eating on Inhibitory Control in BN are Unknown. Perhaps the most 
basic and relevant state changes in BN are the characteristic fluctuations between under-
controlled, excessive eating and over- controlled rigid restriction. Restraint theory and cognitive-
behavioral therapy (CBT) models of BN assume that these metabolic states are causally related—
that fasting and attempts to excessively control eating ("dietary restraint") precipitate binge eating 
and purging [52-54]. Supporting this notion, self-reported dietary restriction has been associated 
with binge/purge frequency [55-57], and reduced dietary restraint scores partially mediate 
improvements in binge eating and purging with CBT [58]. However, some studies have found an 
inverse or no association between restraint and binge eating [59-61], caloric restriction has been 
associated with reduced binge eating [62-64], and acute fasting does not increase intake at 
subsequent ad libitum meals in BN [2, 65, 66]. Conflicting findings may relate to the conflation of 
physiological states (e.g., fasted) and psychological states (e.g., deprived). Key variables in 
traditional models (restraint, restriction, binge eating, and purging) are clearly interrelated and 
Effective Date: 5/1/2025
End Date:4/30/2026

The Influences of Eating and Fasting on Inhibitory Control in Bulimia Nervosa: A 
Computational Neuroimaging Study
STUDY-19-00591
v.05.10.2023
7
salient for BN [67], but 30-50% of patients do not achieve symptom abstinence after completing 
the first-line, empirically-supported treatments based on these models [68, 69]. As BN is defined 
by cycles of avoidance and excessive consumption of food, imaging studies that investigate the 
neurobiological influence of metabolic state fluctuations are needed to refine models and improve 
interventions [70]. However, the state-specific imaging methods used to study other cyclical 
disorders (e.g., substance use, bipolar)[71, 72] have not yet been used to study individuals ill with 
BN.
One possibility is that BN is maintained by the same disinhibiting impact of fasting seen in healthy 
controls (HC). Higher hunger levels in HC are associated with poor inhibition on stop signal and 
food go/no-go tasks.[73, 74] After fasting, the cognitive control of desires for food requires greater 
DLFPC activation,[75] which may reflect an increased inhibitory demand. In BN, an exaggerated 
version of this increase in neural inhibitory demand may make sustained control especially difficult 
in a fasted state. An inability to successfully recruit frontostriatal resources to meet this demand 
could precipitate disinhibited behavior, including binge/purge episodes.
A second possibility is that prolonged periods of restriction in BN are maintained by abnormally 
enhanced control in a fasted state, but once eating has started, inhibitory control is abnormally 
compromised. Consistent with this possibility, women with BN show an abnormally reduced startle 
response (reflecting increased emotion regulation) to food cues after a fast, and an abnormally 
increased startle response (reflecting emotion dysregulation) after eating. [2] In addition, binge-
eating episodes are preceded by lower hunger ratings than are normal eating episodes,[76, 77] 
suggesting that loss-of-control eating may be uniquely precipitated by satiety. Other populations 
who struggle with overeating (e.g., obese individuals) show reduced lateral PFC responses to 
food images relative to controls when fed,[78] and women with obesity [79] and women with BN 
do not show normal increases in resting cerebral blood flow (CBF) in PFC regions after eating [1, 
80-83]. Thus, failure to effectively recruit inhibitory circuitry after eating initiation could leave urges 
to continue eating unchecked.
Proposed Theoretical Model: This application represents a critical next step for understanding the 
role of control- related abnormalities in the maintenance of BN. Existing theories view binge eating 
as the result of psychological effects of overcontrolled eating but do not 1) specify mechanisms 
that may maintain prolonged fasting, 2) account for changes in physiological state that occur with 
fasting and eating, or 3) directly specify the role of inhibitory control in symptom maintenance. 
The proposed model complements existing theories with hypotheses grounded in BN, obesity, 
and substance use neuroimaging literatures. Specifically, the model posits that individuals with 
BN have increased frontostriatal signals for the predicted need to inhibit (P(stop)) and prediction 
errors, and increased frontostriatal activation during response inhibition in the fasted state, all of 
which facilitate behavioral control and prolonged periods of dietary restriction. However, after 
eating, decreased frontostriatal signals for the predicted need to inhibit, decreased frontostriatal 
prediction error signals, and deficient frontostriatal activation contribute to impaired inhibition, a 
sense of loss of control over eating, and subsequent out-of-control purging. This combination 
promotes a cycle of extremes—prolonged fasting versus dysregulated eating and purging—
maintained by problematic, state- dependent neurocomputational mechanisms of adaptive 
control. Of note, this novel maintenance model only focuses on dietary restriction (not "dietary 
restraint"). It also does not specify factors that influence eating initiation, nor does the model focus 
on reward processes that closely interact with control processes and have been the focus of most 
prior BN imaging and preclinical studies [13, 19, 84-88]. These elements should be examined 
after the impact of fasting and eating on inhibitory control-related processes are studied. 
Longitudinal studies with individuals at risk for BN development will be critical in determining 
whether these hypothesized neural abnormalities precede or follow the onset of BN symptoms. 
Effective Date: 5/1/2025
End Date:4/30/2026

The Influences of Eating and Fasting on Inhibitory Control in Bulimia Nervosa: A 
Computational Neuroimaging Study
STUDY-19-00591
v.05.10.2023
8
Testing this model in adults with current BN will 1) help delineate when and what control- related 
neural alterations should be targeted with new treatment approaches (e.g., fed-state inhibitory 
prediction deficits) and 2) identify neurocomputational markers that can be investigated next as 
predictors of treatment outcome.
Effective Date: 5/1/2025
End Date:4/30/2026

The Influences of Eating and Fasting on Inhibitory Control in Bulimia Nervosa: A 
Computational Neuroimaging Study
STUDY-19-00591
v.05.10.2023
9
2.3
RISK/BENEFIT ASSESSMENT 
2.3.1 KNOWN POTENTIAL RISKS 
Risk of Targeted Advertising. There is a risk for participants who click on our study 
advertisement to receive additional information related to eating disorders, given how 
Facebook/Instagram and Google use their users' behavior to target them with future ads.
Risk of Breach of Confidentiality. There is a risk that information collected in our study could 
become known to individuals not involved in our study.
Risks of Fasting and Standardized Meal. There is a potential risk that fasting as part of pre-
scan study procedures could result in mild discomfort (e.g., tiredness, weakness, headache, 
dizziness) or might exacerbate eating disorder cognitions and increase distress in participants 
with eating disorders. In addition, although the standardized meal before the fed-state scan is not 
objectively large, participants with BN may be upset if they feel that they have overeaten during 
the standardized meal before the fed-state scan.
Risks of Venipuncture (for medical screening for BN participants) and Glucose Finger 
Prick (for all participants). There is minor discomfort associated with venipuncture, as well as 
potentially significant psychological distress, if the procedure is not well-handled. There is a small 
chance of bruising and a very small risk of infection with venipuncture and possibility of fainting.
Risks of Psychological and Cognitive Assessments/Standardized Meal. One possible risk is 
feeling uncomfortable while completing self-report or interview measures or the standardized 
meal. While most individuals do not experience such feelings, some may feel sad or anxious. In 
our experience with a wide range of patient and control populations, such feelings are typically 
transient and resolve before the completion of the testing.
Risks of MRI. According to the FDA, there is currently no evidence that MRI with approved 
scanners of up to 4 Tesla signal strength are associated with adverse effects. The specifications 
of the 3.0 T scanners at TMII (and the specific pulse sequences used for each protocol) meet all 
the stringent safety requirements of the regulatory bodies within and outside TMII. The risks 
associated with MRI scanning are as follows:
1) Exposure to MRI magnetic fields is not associated with any known adverse health effects. 
The primary risk of MRI is the possibility of undisclosed metal in the participants' body 
(pins, pacemakers, metal fragments in the eye) that could become dislodged by the 
magnet. Some individuals (10-15%) may experience unexpected claustrophobia when 
entering the magnet bore, or may notice the change in magnetic field upon entering or 
leaving the bore.
2) The acoustic noise associated with MR imaging is related to the mechanical movement of 
the gradient coils during the scanning process. The acoustic noise levels perceived by 
human subjects when undergoing MRI examination in our 3.0 Tesla magnet constitutes a 
non-significant risk; specifically, our system will not be operated in a way that will present 
more noise to human subjects than is recommended by the FDA.
3) There is also the potential for RF-induced local heating and for mild electric stimulation 
due to induced currents from rapidly switching gradients.
Effective Date: 5/1/2025
End Date:4/30/2026

The Influences of Eating and Fasting on Inhibitory Control in Bulimia Nervosa: A 
Computational Neuroimaging Study
STUDY-19-00591
v.05.10.2023
10
2.3.2 KNOWN POTENTIAL BENEFITS 
Expected Direct Benefit to Subjects
Participants are not expected to derive benefits from participation.
Benefit to Society
Understanding the causes of eating disorders has been difficult because of the inaccessibility of 
the brain. Now neuroimaging technologies, such as fMRI, hold the promise of new insights into 
neurocircuit dysfunction that contributes to BN. This study may provide information about brain 
alterations that contribute to BN symptoms. Even our best treatments for BN fail to achieve 
remission in up to half of those treated, and a better understanding of the pathophysiology of BN 
may ultimately lead to better therapies.
2.3.3 DESCRIPTION OF PROCEDURES TAKEN TO LESSEN THE PROBABILITY 
OR MAGNITUDE OF RISKS
Informed Consent
Individuals who are interested in participating will undergo an initial phone screen. After an 
authorized member of the research team describes the research study to the potential participant 
(see attached Study Description), if the potential participant is still interested, a REDCap link to 
the electronic version of the approved phone screen consent will be sent to the prospective 
research subject for review. An authorized member of the research team will be on the phone 
with the potential participant as the e-consent form is reviewed using the attached script. If a 
written informed consent is obtained, the potential subject will provide their e-signature and 
name as well as the date of the consenting process on the e-consent form. After the subject 
submitted the form, the study staff member obtaining the consent will provide their signature, 
name, and the consenting date on the signed e-consent form and send a copy of the form to the 
participant via an encrypted email.
Individuals who are eligible to participate after the phone screen will be sent a REDCap link to the 
electronic version of the full-study consent form. These participants will first be scheduled for full-
study informed consent and psychodiagnostic screening interviews, either in person or via a 
HIPAA-compliant videoconference (Zoom), as specified in the HRP 503 form section 3. Study 
Design  Inclusion and Exclusion Criteria  How Participants will be Screened. At the start 
of this appointment, Dr. Berner or her delegate listed on this protocol will review the study protocol 
and obtain written informed consent using the full-study e-consent form. Voluntary written 
informed consent will be completed prior to completing study procedures in accordance with the 
PPHS of Mount Sinai. The consent process includes a description of the remaining screening 
procedures and pre-scan assessments, fMRI scanning procedures, and other study requirements 
and will be obtained in a closed office with only members of the research group present. No 
reference to the potential subject's identity will be made outside of closed quarters. The consent 
form includes an explanation of study procedures, their time commitments, risks and benefits, 
alternatives to participation, the confidentiality of information, and the rights of research subject. 
Participants will be given the opportunity to have all their questions answered. Participants' 
understanding of the protocol will be examined by direct questioning prior to their signing the 
consent forms. In addition, participants will be made aware that if they choose to participate, they 
must give consent to be audio-recorded as needed in the protocol. Again, if a written informed 
Effective Date: 5/1/2025
End Date:4/30/2026

The Influences of Eating and Fasting on Inhibitory Control in Bulimia Nervosa: A 
Computational Neuroimaging Study
STUDY-19-00591
v.05.10.2023
11
consent is obtained, the potential subject will provide their e-signature and name as well as the 
date of the consenting process on the e-consent form. After the subject submitted the form, the 
study staff member obtaining the consent will provide their signature, name, and the consenting 
date on the signed e-consent form and send a copy of the form to the participant via an encrypted 
email. All study related questions from study participants that a research staff member is unable 
to address will be referred to the Principal Investigator (Dr. Berner), or other co-investigators. No 
further information will be gathered until participants have provided written, signed informed 
consent.
Participants with BN will be informed that choosing not to participate in the study will not change 
or restrict their eligibility for treatment in the EWDP and will not jeopardize their relationship with 
any Mount Sinai subspecialist (if they were referred from within the health system). The ability of 
the participant to withdraw from the study at any time without consequence will be clearly stated 
and indicated in the consent form itself. After the participant consents and signs the informed e-
consent form, the psychodiagnostic screening interviews will be initiated. A copy of the consent 
form is provided to all participants. If the individual decides not to participate in this study, a 
project staff member will provide reasonable and timely assistance in obtaining an alternative 
referral, if applicable and so desired.
In summary, in the consent forms and discussions with study staff, participants are advised fully 
of the procedures to be used, the time commitments they require, the possible risks and benefits 
of the procedures, their right to refuse participation in the study without prejudice, and the name 
and telephone number of the Principal Investigator.
Confidentiality of Subjects' Responses
To minimize possible risk of breach of confidentiality, each study participant will be assigned, after 
consenting to phone screening (i.e., at the time of enrollment), a numeric code which will be used 
as the identifier for subsequent research related activities. All information collected, including self-
report questionnaires, psychological assessments, and imaging data will be identified solely by 
these ID numbers without any personal identifiers. No identifying information is printed on subject 
data forms or in individual data files. Access to the numbering system will be limited to Dr. Berner 
and research staff directly involved in the study. All research files are kept in locked file drawers 
and encrypted computer files on a secure server made available only to qualified personnel for 
research purposes. No verbal or written information concerning a subject will be released to 
anyone without expressed written consent by the subject. All audio-recorded interviews will be 
labeled with study ID numbers. Recordings will be stored for 5 years after the completion of the 
research study, and destroyed thereafter. Clinical data from optional treatment at the EWDP's 
clinical program will be kept in separate file cabinets from the study data. The clinical team at the 
EWDP will not be informed of the research findings about specific patients unless clinically 
indicated (e.g., threat to the patient's life) or the participant asks us to reveal the information via a 
written, signed release of information. However, an exception to confidentiality is a previously 
unreported or ongoing case of abuse (state agencies may need to be involved) or in cases where 
participants are judged to be a danger to themselves or others (see below). Participants are made 
aware of these exceptions in the consenting process.
No published or presented materials will identify patients by names, initials, or any other means 
that could be used to identify the participant. We quote information only by number in conference 
discussions, scientific reports, or publications, in order to maintain anonymity.
As part of consent procedures, participants will be advised of precautions taken to preserve 
confidentiality. Further, all individuals involved in data collection procedures (i.e., research staff) 
Effective Date: 5/1/2025
End Date:4/30/2026

The Influences of Eating and Fasting on Inhibitory Control in Bulimia Nervosa: A 
Computational Neuroimaging Study
STUDY-19-00591
v.05.10.2023
12
will be instructed to not divulge any information concerning participants to any person or agency 
without the written and explicit consent of the participant. All study staff will receive Human 
Subjects Protection training as well as HIPAA privacy training as required by the ISMMS PPHS 
before working with any participants. This approach to data security and confidentiality has been 
very effective in our past studies.
Risks specific to research procedures will be managed as follows: 
Fasting and Standardized Meal
It is unlikely that fasting overnight (16 hours before both scan visits, and, by the end of the fasted-
state scan, a total of 18 fasting hours) will be associated with significant risk, as prior research 
studies have demonstrated that individuals with BN can abstain from eating safely for 20-24 h 
(Mauler et al., 2006; Moreno-Domínguez et al., 2012). Nevertheless, we will take steps to protect 
against both physiological and psychological risks of fasting. All participants will be informed 
during screening that they will be asked to refrain from eating anything for up to 18 h total during 
study participation and will be able to decline participation if they are unwilling to abstain from 
eating for that amount of time. All participants will be provided with instructions about the fasting 
protocols for both scan visits (see attached) at the time of consenting and scheduling and will be 
reminded that they can discontinue their participation at any time.
We will protect against physiological risks of fasting for participants with BN by only including 
participants with BN who are medically stable in the study. A licensed MD’s determination of 
medical stability will be based on vitals sign assessment, anthropometric measurements, review 
of medical history, and, for participants with BN, review of lab results including a chemistry panel 
and complete blood count panel. In addition, participants will be provided with a handout (see 
attached) listing potential physical symptoms during the fast (tiredness, irritability, headaches, 
general weakness, mild nausea, constipation or diarrhea, bad breath, sleep disturbances, 
dizziness, water retention). Consistent with prior research, participants will be instructed to contact 
the research team in the event of minor side effects, but if more severe problems occur, or if they 
feel sick or uncomfortable continuing to fast, to stop fasting and eat something first, then contact 
the research team. If participants call us after business hours, our voicemail will remind 
participants of these instructions. In addition, this voicemail will instruct participants to eat 
something if they are unsure about whether their symptoms are mild enough to continue fasting. 
Participants will be informed of this in fasting instructions, as well.
Several study design decisions were specifically made to minimize psychological distress 
associated with the fasting periods: First, fasting is common for many women with BN, and the 
16-18-h duration of fasting across visits in this study falls in the middle of the 8-24 h range of the 
definition for the BN symptom of "fasting" used in self-report studies of BN (Fairburn, Cooper, & 
O'Connor, 2008; Stice et al., 2008). Therefore, it is unlikely that this duration of fasting will be 
atypical for the women with current BN included in our study. Second, because participants are 
asked to stop eating between 5:00 and 9:00 PM the night before scan visits, participants will likely 
be sleeping during half of the fasting period. Shift workers will be explicitly excluded from 
participating. Thus, participants will effectively only be missing one meal (breakfast) before the 
scans. Self-report data indicate that breakfast is the most frequently skipped meal of the day 
among both women with BN and controls (Masheb Robin, Grilo Carlos, & White Marney, 2010). 
Therefore, given the frequency of this behavior in the natural environment, we do not believe that 
it will affect the safety of the 16-18-h fasting periods. In addition, we will provide participants with 
a snack after post-scan self- report questionnaires are completed to minimize any fasting beyond 
the period necessary for study design. Study staff will conduct de-briefing at the conclusion of 
both scan visits to address any residual distress. Participants will be asked to notify research staff 
Effective Date: 5/1/2025
End Date:4/30/2026

The Influences of Eating and Fasting on Inhibitory Control in Bulimia Nervosa: A 
Computational Neuroimaging Study
STUDY-19-00591
v.05.10.2023
13
immediately should they start to feel excessively distressed as a result of fasting for the study, 
and will be encouraged to stop fasting and study participation will be discontinued if persistent 
distress is experienced.
Although the standardized meal before the fed-state scan is not objectively large, participants with 
BN may be upset if they feel that they have overeaten during the standardized meal before the 
fed-state scan. A member of the staff will be present during the standardized meal, and will be 
available to the subject if she does become upset.
Participants with BN who are not patients in the EWDP will be provided with treatment referrals 
during de-briefing at the end of participation, if participants are interested.
Risks of Venipuncture and Glucose Finger Prick
We have a firm policy to only attempt venipuncture/finger prick a maximum of twice on one 
occasion. In addition, we allow adequate time for the procedure, as necessitated by the individual 
subject. Very rarely will a subject be so anxious about venipuncture/finger prick that these studies 
are not feasible.
Psychological and Cognitive Assessments
Some study participants may become anxious or tearful because of the personal nature of 
questions asked during clinical interviews. All research team members are well trained in 
strategies to help alleviate and manage any participant distress that may be associated with 
responding to research questions and interviews. Clinical interviewers will exercise caution and 
sensitivity and terminate the interview as necessary to protect the emotional well-being of the 
study participant. Similarly, study participants who experience frustration during cognitive 
assessments will be reassured that they are there to do their best and that it does not matter how 
well they score.
They will be encouraged to continue but can stop completing these procedures at any time. If a 
participant becomes anxious or uncomfortable during the testing session and would like to 
discontinue her participation, the session will be terminated. In addition, participants will be offered 
periodic 5-minute breaks to minimize fatigue.
MRI-Related Issues
Computers and the interfacing devices will be checked regularly for proper and safe operation. 
Typically, 3 Tesla scanners have been measured to produce noise between 122-131 db. The 
potential risk of hearing loss associated with the noise generated during MRI is eliminated by 
using ear plugs (rated to reduce noise by 32 dB) and through the use of headphones (rated to 
reduce noise 30 dB).
Subjects will be strongly encouraged to move slowly when entering or exiting the magnetic field. 
The scanner bed has been designed to slowly move the subject to minimize the possibility of 
vertigo. Participants are assisted in exiting from the MRI gantry to prevent a possible stumble or 
fall.
RF-induced local heating is unlikely due to the software requirement that subject's weight is 
accurately recorded and used in determining the appropriate changes in gradients. Subjects are 
warned of the possibility of mild electric stimulation and are monitored throughout the session.
Effective Date: 5/1/2025
End Date:4/30/2026

The Influences of Eating and Fasting on Inhibitory Control in Bulimia Nervosa: A 
Computational Neuroimaging Study
STUDY-19-00591
v.05.10.2023
14
Exclusions will be made for the following: cardiac pacemaker, metal fragments in eyes/skin/body 
(shrapnel), history of being a metal worker/welder, history of eye surgery/eyes washed out 
because of metal, aortic aneurysm clips, prosthesis, by-pass surgery/coronary artery clips, 
hearing aid, heart valve replacement, subjects with a metallic IUD (birth control device), a shunt 
(ventricular or spinal), electrodes, metal plates/pins/screws/wires, or neuro/bio- stimulators 
(TENS unit), vision problems uncorrectable with lenses, claustrophobia, inability to lie still on one's 
back for approximately 90 minutes, prior neurosurgery, older tattoos with metal dyes, bigen hair 
dye and micro-bladed eyebrows, tattooed eyeliner or other makeup, unwillingness/inability to 
remove nose, ear, tongue or face jewelry, hair weaves or extensions, braces or permanent dental 
retainers, and women with a positive urine pregnancy test or who are currently lactating.
Participants will be carefully screened by our staff and again by research staff for any metal that 
could pose a danger, and the importance of this screening will be repeatedly emphasized. If there 
is a possibility of metal being present in the participant's body, the participant will be excluded. 
Participants' informed consent will be reviewed prior to scanning, and an additional safety check 
(for metal in the body) will be obtained prior to scanning. A metal detector will be used to confirm 
that participants are not carrying or wearing material (e.g., keys, coins, jewelry, clothing containing 
metal) that may be affected by the presence of a magnetic field. To prevent accidental entry of 
metallic objects into the imaging room/magnetic field during an MR imaging session, there are 
large warning signs at the entrance to the area of higher field strength.
Study participants will be asked questions pertaining to fear of closed spaces during the screening 
stage. However, should the participant become claustrophobic during the study or for any reason 
be unable to endure remaining in the scanner, the study will be terminated, and the participant 
will be removed from the scanner.
In addition, a urine pregnancy test will be performed immediately before study participation. No 
studies will be performed on pregnant or potentially pregnant women.
During scanning, subjects will be in voice contact with the research staff at all times and they are 
encouraged to promptly report any discomfort. Furthermore, our clinically trained research staff 
will be on the watch for signs of distress, anxiety or fatigue and terminate the study procedure 
should a subject display signs of distress.
Incidental Findings and Other Potential Issues
1.
If there is an indication that a participant needs immediate assistance, intervention, or a 
referral (e.g., suicidality, medical instability), the study staff member will help the participant to 
obtain these services or provide a referral. All participants will be informed that if they tell a 
study staff member or indicate on any assessments that they are thinking about hurting or 
killing themselves, research staff will ask more questions about these thoughts, and, based 
on their responses, staff may provide the participant with help to get treatment. This may 
include providing participants with information about treatment options, encouraging the 
participant to pursue treatment, working with the participant to contact her doctor or mental 
health provider, or working with the participant on a plan that may include getting her to an 
emergency room for safety. If this information is revealed during an in-person assessment or 
visit, the psychiatry fellow on call will be paged. If necessary, the participant will be taken to 
the emergency room or admitted. Although Dr. Berner will assist in this procedure, the primary 
decision about the best course of care will be made by clinical providers in these settings, not 
by the research team, in order to ensure that the participant gets the clinical attention that is 
Effective Date: 5/1/2025
End Date:4/30/2026

The Influences of Eating and Fasting on Inhibitory Control in Bulimia Nervosa: A 
Computational Neuroimaging Study
STUDY-19-00591
v.05.10.2023
15
customary in these cases and that the treatment is not biased. Some of these actions involve 
a breach of confidentiality to ensure participant safety, and this may be upsetting. This risk 
will be described ahead of time to participants in both the phone screen and full study e-
consent forms. All study staff will be trained by the principal investigator, a clinical 
psychologist, on procedures for the occurrence of suicidality among study participants to 
ensure that such cases are responded to in a clinically sensitive manner. If the research staff 
member conducting the research procedures feels unequipped to manage clinical issues that 
arise, Dr. Berner and/or Dr. Hildebrandt, also a licensed psychologist, will be contacted for 
consultation or supervision, or to directly intervene. 
2.
The discovery of a previously unknown psychiatric disorder during evaluation: If safety is 
compromised or could potentially be compromised, the procedure above will be followed. If 
safety is not compromised (e.g., the discovery of PTSD producing functional impairment in 
addition to BN), the patient will be notified and encouraged to seek help. If the patient agrees, 
a referral for evaluation by the C/L service or outpatient department will be made.
3.
All subjects in this study will be asked to provide a urine sample at both scan sessions to 
assess recent drug use and pregnancy. Participants are notified in advance that if they test 
positive for recent drug use or pregnancy they will not complete the scan. Unanticipated 
findings of potential medical significance uncovered during the course of the study, including 
a positive pregnancy test or an abnormal MRI, will be reported to Dr. Berner (the principal 
investigator) and Dr. Hildebrandt (co-investigator). The study participant will be informed of 
the test result and then referred to her physician. If the participant does not have a regular 
physician, an appropriate referral will be made. 
All members of the study team will be trained by the principal investigator on study procedures 
for handling incidental findings.
Targeted Advertising
BUMP's approach provides the highest level of data security and HIPAA compliance. Study 
advertisements distributed through Facebook, Instagram, and Google.com are linked to a landing 
page that provides additional information on the study. If a candidate is interested, they click on 
a button that takes them to a pre-screening form via REDCap. While BUMP manages the landing 
page, our research team entirely manages the REDCap survey.
With this approach, BUMP has no access to any candidate information, including names, ePHI, 
or IP addresses, and therefore do not require a HIPAA Business Associate Agreement (BAA), nor 
a Data Use Agreement (DUA).
Facebook, Instagram (owned by Facebook), and Google provide their users with control over how 
they are targeted with ads and what ads they see. Therefore, when individuals agree to these 
platforms' user agreements, they consent to be targeted for various types of targeted 
advertisements.
We will specifically target candidates via advertisements on these platforms using basic 
information provided by the user directly, such as gender, age, location, and interests. However, 
note that neither BUMP nor the study team has any access to any personally identifiable 
information during ad targeting. They also cannot capture any of this information when 
participants click on the study's ad. BUMP only receives anonymous and group-level summary 
information on total ad impressions, ad reach (i.e., the number of unique individuals reached), 
number of ad clicks/ landing page views, and "results" (i.e., the number of candidates who clicked 
Effective Date: 5/1/2025
End Date:4/30/2026

The Influences of Eating and Fasting on Inhibitory Control in Bulimia Nervosa: A 
Computational Neuroimaging Study
STUDY-19-00591
v.05.10.2023
16
on a landing page button and were sent to the research team's REDCap page). The only time a 
person's identity can be known is if they choose to post a public comment or question on 
Facebook or Instagram. BUMP always responds privately via Facebook or Instagram Messenger, 
never publicly on Facebook or Instagram itself.
Although the user agreements for Facebook, Instagram, and Google clearly indicate policies 
regarding how user information will be used for targeted advertising, we will provide all potential 
participants who inform us that they heard about our study from an online advertisement with 
additional information about the implications of seeing these advertisements.  Specifically, we will 
remind these individuals that the information they provided in these online platforms may have 
matched their profiles with our study's advertisement and that there is a possibility that they could 
be shown additional advertisements related to eating disorders as a result of their clicking on our 
ad. We will also remind participants that they can change their user settings to change how 
advertisements are shown to them. We also provide this information to all participants in the 
phone screening consent form as well as the study consent form.
3
OBJECTIVES AND ENDPOINTS 
3.1
OBJECTIVES
Every year, 1.4 million years of healthy life are lost to disability or premature death associated 
with bulimia nervosa (BN), and up to half of adults with BN treated with first-line psychotherapies 
do not recover. Treatment-resistant binge eating and purging may be perpetuated by inhibitory 
control deficits linked to reduced activation in lateral prefrontal cortices (LPFC), anterior cingulate, 
and striatum. To date, however, neurocognitive studies of BN have not accounted for 1) the 
dynamic computational processes underlying inhibition or 2) the fact that individuals with BN 
oscillate between two extremes—under-controlled, excessive eating and over-controlled, 
restricted intake. This study proposes to examine the neurocomputational underpinnings of 
inhibitory control in fed and fasted states to test an explanatory model of BN symptoms and inform 
future context-dependent, targeted interventions for BN.
Inhibitory control requires individuals to update expectations based on experience, and use 
updated expectations to adaptively adjust behavior. Neural signals for these dynamic 
subcomponents of inhibitory control can be quantified with computational neuroimaging and 
robustly predict outcome in other psychiatric disorders. However, they have not yet been used to 
study BN. In addition, it is not clear how inhibitory control deficits in BN could explain both out-of-
control binge eating and the over-controlled, dangerous restriction that typically occurs between 
binge/purge episodes. As has been proposed in substance use, BN may be associated with 
aberrant, state-based fluctuations in control that maintain bulimic behaviors. Metabolic state, or 
how recently a person has eaten, is an established modulator of inhibitory control in healthy 
individuals, yet surprisingly little is known about how metabolic state and inhibitory control interact 
in BN. In healthy adults, fasting deactivates LPFC and impairs inhibition, whereas eating 
increases LPFC activation and enhances inhibition. An exaggerated version of this normal fasted-
state disinhibition may increase the risk for binge/purge episodes when individuals with BN restrict 
their intake, but a neurobiological basis for this theory has not been tested. Conversely, in BN and 
other 
conditions 
characterized 
by 
overeating 
(e.g., 
obesity), 
neuroimaging 
and 
psychophysiological data suggest that food intake and satiety may in fact be abnormally 
Effective Date: 5/1/2025
End Date:4/30/2026

The Influences of Eating and Fasting on Inhibitory Control in Bulimia Nervosa: A 
Computational Neuroimaging Study
STUDY-19-00591
v.05.10.2023
17
disinhibiting. This could create a fed-state vulnerability and make it difficult to stop eating after 
starting.
The overarching hypothesis of this research study is that in BN, frontostriatal function and 
inhibitory control are enhanced in the fasted state, but impaired in the fed state. This study 
proposes that this aberrant state-dependent activation promotes prolonged periods of dietary 
restriction punctuated by out-of-control binge/purge episodes. To test this hypothesis, this project 
will compare neural responses of 30 women with BN to 30 group-matched healthy controls (HC) 
at two counterbalanced scans (after a 16-h fast and after a standardized meal) using Bayesian 
ideal observer modeling of stop-signal task inhibition. To assess the clinical significance of 
metabolic-state sensitivity, this project will examine associations of neural response with symptom 
severity. This project will serve as a vehicle for formal training and mentorship in repeated-
measures neuroimaging methodology and analysis, computational modeling in psychiatry, and 
the neurobiology of BN symptoms. Characterizing the influences of eating and fasting on the 
control-related dysfunction that may contribute to maladaptive BN symptoms is critical to 
developing precise pathophysiological models and more accurate and effective treatments.
Aim 1: To determine whether eating and fasting abnormally interfere with the capacity of 
individuals with BN to adaptively exert inhibitory control
Hypothesis 1.1: Women with BN in the fed relative to fasted state will demonstrate impaired 
performance and deficient frontostriatal activation when inhibiting responses, whereas HC will 
show the opposite pattern. Hypothesis 1.2: In BN, frontostriatal signals for the trial-level 
anticipated need to stop (P(stop)) and Bayesian prediction errors will be reduced in the fed relative 
to fasted state. HC will show the opposite pattern. Associated Training: Goal 1: To develop 
expertise in repeated-measures neuroimaging and analysis, including measurement of potential 
state-based fMRI normalization factors (e.g., resting perfusion); Goal 2: To learn to independently 
conduct computational model-based analysis of fMRI data in eating disorders
Aim 2: To identify associations of BN symptom severity with state-specific frontostriatal 
activation
Hypothesis 2.1: In BN, more frequent binge eating and purging will be associated with lower 
frontostriatal signals for
P(stop) and prediction errors in the fed state relative to the fasted state.
Hypothesis 2.2: In BN, more severe dietary restriction will be associated with increased 
frontostriatal signals for P(stop) and prediction errors in the fasted state relative to the fed state.
Associated Training: Goal 1: To develop expertise in analysis and integration of repeated-
measures neuroimaging and clinical data; Goal 3: To expand my knowledge of the neurobiological 
mechanisms involved in the full spectrum of bulimic behaviors, specifically dietary restriction.
Findings are expected to inform novel treatments by 1) pinpointing which components of the 
inhibition process are altered in BN and 2) identifying states in which control-focused interventions 
may be most effective at interrupting the cycle of BN symptoms. We also may detect state-
independent neural alterations that represent stable BN biomarkers. This research and training 
are critical to launching my independent career as a translational clinical investigator who 
combines behavioral, psychological, and neuroimaging tools with sophisticated analytic 
approaches to inform treatment optimization. The proposed study will serve as the basis for a 
longitudinal R01 application powered to examine brain-based phenotypes over time and state-
specific predictors of outcome among a wider diagnostic spectrum of individuals who binge eat 
and purge.
 
Effective Date: 5/1/2025
End Date:4/30/2026

The Influences of Eating and Fasting on Inhibitory Control in Bulimia Nervosa: A 
Computational Neuroimaging Study
STUDY-19-00591
v.05.10.2023
18
3.2
STUDY ENDPOINTS
Primary Outcome: Frontostriatal activation
We will compare the impact of fasting and eating on neural activation in women with BN and 
healthy controls. Specifically, we will compare groups on the influence of fasted and fed state 
on: 1) frontostriatal activation when correctly inhibiting responses and 2) frontostriatal signals for 
the anticipated need to stop (P(stop)) and inhibitory control prediction errors.
Our sample size was selected based on the most rigorous analysis of this primary outcome 
measure (a Group x Visit x Trial Type linear mixed effects model). We simulated 1,000 datasets 
with a 3-way interaction (Group x Visit x Trial Type) and fitted a mixed effects model to each 
dataset; power to detect a large (d = .80) 3-way interaction with 30 women per group was 
estimated at over 80% with a two-sided alpha =.05. Results will serve as essential preliminary 
data for a larger, fully powered R01 application.
 
Secondary Outcomes:
-
Stop signal task performance: We will compare the impact of fasting and eating on 
behavioral task performance in women with BN and healthy controls. We will specifically 
compare groups on stop signal reaction times and the percentage of correct stop trials.
-
Eating disorder symptom severity: We will examine, with the BN group, whether more 
severe binge eating/purging is associated with frontostriatal signals for P(stop) and 
inhibitory prediction errors in the fed vs. fasted state, and whether more severe dietary 
restriction is associated with frontostriatal signals for P(stop) and prediction errors in the 
fasted vs. fed state.
Other/Exploratory Outcome: Resting cerebral blood flow
We will compare the impact of fasting and eating across our two groups on resting cerebral 
blood flow, as measured by arterial spin labeling (ASL).
4
STUDY DESIGN
4.1
OVERALL DESIGN
This study uses a two-group, repeated-measures design to investigate whether eating abnormally 
influences inhibitory control processes in BN. We propose to test this hypothesis in adult women 
with currently symptomatic BN compared with healthy controls and will probe inhibitory control 
circuits at two counterbalanced scans using computational modeling of stop-signal task inhibition 
(Aim 1). To assess the clinical significance of sensitivity to fasting and eating, we will examine 
whether state-specific altered neural function is associated with the severity of binge eating, 
purging, and fasting (Aim 2).
4.2
END-OF-STUDY DEFINITION
Completing the research described in this protocol will include a phone screening assessment, 
psychodiagnostic assessment, one in-person evaluation, online questionnaires, and two fMRI 
scans on two separate days.
Effective Date: 5/1/2025
End Date:4/30/2026

The Influences of Eating and Fasting on Inhibitory Control in Bulimia Nervosa: A 
Computational Neuroimaging Study
STUDY-19-00591
v.05.10.2023
19
5
STUDY POPULATION
5.1
INCLUSION CRITERIA
All Participants

Female

Aged 18 to 35 years

Currently between 85 and 130% of the expected weight for height based on the 
Metropolitan Life Insurance tables (attached)

Right-handed

English-speaking
Additional Inclusion Criteria for Women with BN

Meet DSM-5 criteria for bulimia nervosa (at least one binge eating episode and 
compensatory behavior episode per week on average for the past three months)

Medical stability, as determined by a licensed MD listed on the study protocol, based on 
vitals assessment and blood draw for complete blood count and chemistry panel
5.2
EXCLUSION CRITERIA
All Participants

Vitals outside of the following limits:
o
Temp: < 97 degrees F
o
Pulse: <40 or >100 bpm
o
BP lying, sitting, standing: Blood pressure < 90/60 mmHg and/or orthostatic 
increase in pulse of > 20 bpm or a drop in blood pressure of > 10-20 mmHg

Personal history/diagnosis (self-reported) of any metabolic disorder (i.e., diabetes (type 1 
or 2)) or gastrointestinal disorder

Reported current or past diagnosis of a chronic disease, defined as:
o
symptomatic coronary artery disease o coronary revascularization
o
myocardial infarction o unstable angina
o
stroke
o
transient ischemic attack o pulmonary embolism
o
peripheral vascular thromboembolism
o
chronic kidney disease stage III or higher o kidney stones
o
gallstones or gallbladder disease
o
chronic obstructive pulmonary disease o immunodeficiency
o
solid organ transplant o thyroid dysfunction
o
cancer of any type other than cancer of the skin excluding melanoma o blood 
disorder
o
uncontrolled asthma

Current fever, upper respiratory infection, vertigo, regular fainting spells (at least once 
monthly), persistent diarrhea, blood in stools, vomiting blood

Any medication used to lower blood glucose or antidiabetic medications (metformin, 
sulfonylureas, 
Glucagon-like 
peptide-1 
GLP-1 
analogues 
[i.e. 
exenatide], 
thiazolidinediones or DPP-IV inhibitors [i.e. 'gliptins']); medications affecting weight, 
appetite or gut motility (i.e. domperidone, cisapride, orlistat, phentermine, topiramate)
Effective Date: 5/1/2025
End Date:4/30/2026

The Influences of Eating and Fasting on Inhibitory Control in Bulimia Nervosa: A 
Computational Neuroimaging Study
STUDY-19-00591
v.05.10.2023
20

Undertaking any form of medical treatment which may interfere with study variables (e.g. 
chemotherapy)

Shift work

Pregnancy or planned pregnancy during the study period, or lactation

Current or past neurological disorder

History of a seizure or history of head trauma with loss of consciousness

Full Scale IQ under 75

Allergy to any of the ingredients in or unwillingness to consume the standardized meal or 
unwillingness to drink water during the fasting period

Any contraindication for fMRI (e.g., non-removable metallic objects in the body, known 
claustrophobia)
Additional Exclusion Criteria for BN Women

Meet DSM-5 diagnostic criteria for any current comorbid Axis I diagnosis except: 
depressive disorders (Persistent Depressive Disorder (PDD) or Major Depressive 
Disorder (MDD)), Generalized Anxiety Disorder (GAD), or Social Anxiety Disorder (SAD)

Primary diagnosis of MDD, GAD, or SAD, as assessed by the Structured Clinical Interview 
for DSM-5 Research Version

Meet criteria for a substance/alcohol use disorder in the last 3 months
Change in psychiatric medication or dose within the past 6 weeks 
Additional Exclusion Criteria for Healthy Controls

Current or past diagnosis of any Axis I psychiatric disorder

Current or past binge eating (including any endorsed history of a sense of loss of control 
over eating, regardless of eating episode size) or compensatory behaviors (including self-
induced vomiting, laxative or diuretic misuse, weight- loss medication use) or fasting to 
control shape or weight

Any active attempts at weight loss in the last 3 months (including dieting, elimination or 
restriction of certain foods to lose weight, fasting, weight loss medications)

Reported weight loss or gain > 4 kg in the last 3 months

Psychotropic medications in the last 3 months
5.3
STRATEGIES FOR RECRUITMENT AND RETENTION
Please see the HRP 503 form section 3. Study Design  a) Recruitment Methods for detailed 
recruitment strategies.
6
STUDY EXPERIMENTAL MANIPULATION DISCONTINUATION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL
6.1
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY
Participants are free to withdraw from participation in the study at any time upon request. Please 
further details in the HRP 503 form section 3. Study Design  i) Procedures for Subjects to 
Request Withdrawal.
Effective Date: 5/1/2025
End Date:4/30/2026

The Influences of Eating and Fasting on Inhibitory Control in Bulimia Nervosa: A 
Computational Neuroimaging Study
STUDY-19-00591
v.05.10.2023
21
The Principal Investigator, the sponsor, or the institution may stop subjects' participation at any 
time without their permission. Please further details in the HRP 503 form section 3. Study Design 
 i) Procedures for Investigator to Withdraw Subjects.
7
STUDY ASSESSMENTS AND PROCEDURES
7.1
DESCRIPTION OF PROCEDURES BEING PERFORMED
Screening Procedures
Please see the HRP 503 form section 3. Study Design  Inclusion and Exclusion Criteria  
How Participants will be Screened for further details on the study’s screening procedures.  
Interested individuals will first complete a brief initial screening (~15 min via phone). The purpose 
of this brief screen is to quickly exclude individuals who meet clear-cut exclusion criteria.
Individuals who are still interested in and are eligible to participate after phone screening will next 
complete full study consenting (please see HRP 503 form section 9. Consent Process  Where 
and When Consent Will Be Obtained) and, after providing written informed consent, semi-
structured psychodiagnostic interviews in person at the EWDP clinic or via a HIPAA-compliant 
videoconference (Zoom).
The standardized structured diagnostic interviews are designed to assess past and present eating 
disorder symptomatology and concomitant psychopathology. Individuals eligible after these initial 
assessments will also complete the Borderline Personality Disorder (BPD) Module from the 
Structured Clinical Interview for DSM-5 Personality Disorders to assess for comorbid BPD 
symptoms and diagnosis. The full battery of interviews takes about 2.5 hours to complete. The 
clinical interviews will be audio-recorded, and 15% will be randomly selected for interrater 
reliability assessment.
Participants who are deemed eligible after phone screening and diagnostic interviews will be 
asked to complete remaining screening assessments and pre-scan procedures in person at the 
EWDP clinic. These remaining assessments take approximately 1.5 hours total and include height 
and weight measurement and a neuropsychological test that assesses Full-scale IQ (WASI-II; 
designed to assess general cognitive ability as groups will be matched on full scale IQ and 
individuals with IQ under 75 will be excluded). In addition, height and weight will be measured for 
all participants. For participants with BN, the in-person screening will also include a medical 
stability screening that includes vitals assessment and drawing 2 teaspoons of blood for basic 
laboratory tests (e.g., CBC, Chem7).
At the end of the first in-person visit, participants will also complete the Patient Health 
Questionnaire–9 (PHQ-9) and will practice and complete computerized decision-making tasks, 
and pre-task state measures:

Generalized labeled magnitude scale (gLMS) ratings of hunger and satiety

VAS ratings of fatigue, urge to overeat, urge to binge eat (BN only), urge to purge (BN 
only)

Positive and Negative Affect Schedule (PANAS)
Effective Date: 5/1/2025
End Date:4/30/2026

The Influences of Eating and Fasting on Inhibitory Control in Bulimia Nervosa: A 
Computational Neuroimaging Study
STUDY-19-00591
v.05.10.2023
22

Spielberger State-Trait Anxiety Inventory (STAI-S)

State Difficulties in Emotion Regulation Scale (S-DERS)
Self-Report Battery
Between the first in-person visit and the scanning visits, participants will be asked to complete a 
battery of self-report questionnaires online via REDCap to provide timely symptom measures. 
These surveys will be administered online to avoid transcription errors and allow participants to 
complete questionnaires when most convenient for them. These widely used, well-validated 
self-report questionnaires take approximately 1 hour to complete. The battery includes 
standardized psychological measures designed to assess current anxiety symptoms, 
personality pathology and temperament, impulse control and eating-disorder related symptoms 
(see below). Data collected from the questionnaires will be used to measure the severity of any 
current symptoms in the BN versus healthy controls and correlate these scores with neural 
responses and behavioral task performance.
Neuroimaging Scans
Participants will be asked to refrain from using alcohol or any substances they may occasionally 
use (e.g., marijuana), for 7 days prior to scanning.
Methods will closely replicate those used to study anorexia nervosa and bulimia nervosa: Fasted 
and fed-state scans will be scheduled no more than one week apart in a counterbalanced order 
between groups. Participants will be instructed to consume nothing besides water the night before 
scans. Therefore, the only difference between counterbalanced fasted and fed-state scan days 
will be the consumption of a standardized meal immediately before scanning on the fed-scan day. 
To balance feasibility and safety with ecological validity, we will conduct scans on both fasted-
state and fed-state visits starting between 9:00 AM and 1:00 PM.
Several studies of BN and obesity have successfully implemented similar at-home fasts (9 h-20 
h in duration). On fed scan days, participants will consume a standardized meal over 15 min [30% 
daily caloric needs (30 kcal/ kg), ~450–500 kcal] 45 min before scanning. As in prior research in 
remitted eating disorder samples, portions will be adjusted for each participant based on their 
body mass index. Scanning will begin 30 minutes after meal completion. Participants will be 
informed of these eating schedule requirements over the phone during pre-screening and will only 
eligible to participate if they are willing to comply with these study procedures and (in the case of 
BN participants) if their vitals and labs indicate that they are medically stable. Participants will be 
instructed to consume their last food 16 hours before their scheduled scan start (i.e., between 
5:00 and 9:00 PM the night before, depending on scheduled scan time). Participants with BN will 
be instructed to refrain from purging (self-induced vomiting or laxative or diuretic use) during the 
fasting periods before scanning.
Upon arrival at the TMII, at both scan visits, participants will first complete a Scan Day Visit 
Questionnaire, and overnight fasting status will be confirmed via interview regarding food intake. 
We will also measure blood glucose via finger-prick. Criteria for interpreting blood glucose will be 
consistent with that used in our prior studies: Specifically, glucose levels that are 70-100 mg/dL 
are considered a normal fasting glucose range. Participants will be informed that upon arrival for 
each session they will be asked to report on their recent food consumption, and that they will be 
asked to provide a blood sample to demonstrate compliance.
All subjects in this study will be asked to provide a urine sample at the scan session to assess 
recent drug use and pregnancy. Participants are notified in advance that if they test positive for 
recent drug use or pregnancy they will not complete the scan.
Effective Date: 5/1/2025
End Date:4/30/2026

The Influences of Eating and Fasting on Inhibitory Control in Bulimia Nervosa: A 
Computational Neuroimaging Study
STUDY-19-00591
v.05.10.2023
23
Before and after the fMRI scan, subjects will complete self-reports on their current state in targeted 
areas such as mood, anxiety, fatigue, and feelings of hunger or satiety:

Generalized labeled magnitude scale (gLMS) ratings of hunger and satiety, fatigue, 
urge to overeat, urge to binge eat (BN only), urge to purge (BN only)

Positive and Negative Affect Schedule (PANAS)

Spielberger State-Trait Anxiety Inventory (STAI-S)

State Difficulties in Emotion Regulation Scale (S-DERS)
Information collected will be examined in correlation with behavioral performance and neural 
responses to decision- making tasks. Subjects will perform an inhibitory control task and two 
decision-making tasks at both scanning study visits. During the scan, visual stimuli are projected 
from a computer onto a screen in the scan room, and participants hear auditory stimuli via 
headphones and log their responses to visual and auditory stimuli using a button response box 
for both tasks. The remainder of scan time consists of structural sequences and resting state 
sequences during which the subject is asked to lie still and stay awake. A fixation cross is 
displayed during this portion. The imaging procedure involves lying quietly on a table for 
approximately 1.5 hours. No pain or discomfort results from this procedure.
On both scan days, participants will be offered a granola bar snack after scanning is complete.
At the conclusion of study participation, we will provide a customized written set of referrals, which 
includes low-fee, full-fee, and insurance-based options that include both Mount Sinai and external 
treatment sources. We are available to discuss follow-up with any of these options and 
communicate this availability to participants. However, as we are not providing treatment in this 
study, we will not engage in formal case management for participants.
During these cognitive tasks, participants will have the opportunity to earn a bonus between $0 
and $15. Monetary bonuses are a common technique in behavioral economics that help to ensure 
that participants' behavior is ecologically valid and as true to life as possible. It also helps to 
minimize the risk of boredom and fatigue that participants will face when playing these games. 
Depending on the task, these bonuses are either calculated based upon a cumulative score, 
meaning participants bank up small rewards over the course of the task, or they receive the full 
payout from a randomly selected trial. The full details for how these bonuses are calculated is 
made clear to the participants in the instruction screens of the individual tasks.
7.2
DESCRIPTION OF THE SOURCE RECORDS THAT WILL BE USED TO 
COLLECT DATA ABOUT SUBJECTS
Names of Standardized Instruments (Psychiatric Measures):

Structured Clinical Interview for DSM-5, Research Version (SCID-5-RV)

Eating Disorder Examination (EDE; abbreviated version that only includes the diagnostic 
items for BN)

Borderline Personality Disorder (BPD) Module from the Structured Clinical Interview for 
DSM-5 Personality Disorders

Wechsler Abbreviated Scale of Intelligence, Second Edition (WASI-II), 2-subtest version

Patient Health Questionnaire –9 (PHQ-9)

Spielberger State-Trait Anxiety Inventory (STAI-T)
Effective Date: 5/1/2025
End Date:4/30/2026

The Influences of Eating and Fasting on Inhibitory Control in Bulimia Nervosa: A 
Computational Neuroimaging Study
STUDY-19-00591
v.05.10.2023
24

Restricting Subscale of the Eating Pathology Symptoms Inventory (EPSI)

Behavioral Activation System Scales (BIS/BAS)

Barratt Impulsiveness Scale-Version 11 (BIS-11)

Difficulties in Emotion Regulation Scale (DERS)

UPPS-P Impulsive Behavior Scale

Affective Lability Scale

Eating Expectancies Inventory (EEI)

Eating Disorders Inventory (EDI) weight history questions

Power of Food Scale (PFS)

Eating Loss of Control Scale (ELOCS)

Eating Disorder Examination Questionnaire (EDE-Q)

Eating Disorder Flexibility Index Questionnaire (EDFLIX)

Multidimensional Assessment of Interoceptive Awareness (MAIA)

Loss-of-control over eating scale, brief version (LOCES-B)

U.S. Household Food Security Survey Module

Self-Reported Behavior Automaticity Index (SRBAI)

Cash Choice Task

Generalized labeled magnitude scale (gLMS) ratings of hunger, satiety, fatigue, urge to 
overeat, urge to binge eat (BN only), urge to purge (BN only)

Positive and Negative Affect Schedule (PANAS)

Spielberger State Anxiety Inventory (STAI-S)

State Difficulties in Emotion Regulation Scale (S-DERS)

Coronavirus Anxiety Scale (CAS)
Description of Instruments Created by Research Team:
All instruments created by the research team are included with this submission.

Supplemental interview to evaluate eating disorder history adapted from SCID Eating 
Disorders Module: This form provides a more structured scoresheet for information 
collected during the eating disorders section of the SCID-5, and includes specific boxes 
for the collection of information about worst, past, and current eating disorder symptom 
frequencies. The interview also includes a timeline to facilitate determination of whether a 
participant meets criteria for BN or may instead meet criteria for another eating disorder 
based on their history (e.g., the binge-eating/purging subtype of anorexia nervosa, in 
partial remission)

Scan Visit Day Questionnaire: This brief questionnaire assesses sleep, caffeine 
consumption, menstrual status, and last eating disorder behaviors before scanning

Medical screening form: This form assesses current and past medical diagnoses and 
includes a review of systems relevant to the study. It also includes space to log results of 
measured vitals. A licensed MD listed on the study protocol will review this form for all 
participants.

COVID-19 Testing Questions: These questions assess subjects' COVID-19 testing and 
status in the past 3 months
Neurocognitive Tasks:

Stop signal task

Go/no-go reinforcement learning task
Effective Date: 5/1/2025
End Date:4/30/2026

The Influences of Eating and Fasting on Inhibitory Control in Bulimia Nervosa: A 
Computational Neuroimaging Study
STUDY-19-00591
v.05.10.2023
25

Demand selection task

Social decisions task

Flexibility task
Magnetic Resonance Imaging:

MRI data will be acquired following Human Connectome Project (HCP) Young Adult 
protocols on a Siemens 3T MAGNETOM Skyra scanner.

The session includes:
1) a whole brain T1-weighted anatomical scan
2) a whole-brain resting ASL scan
3) a whole-brain resting BOLD scan
4) task-based T2*-weighted multiband EPI scans (1 if a neuromelanin-sensitive scan 
is conducted, 2 if not)
5) phase maps to correct field inhomogeneities.
6) a neuromelanin-sensitive (gradient-echo pulse with magnetization transfer) scan
7.3
ADVERSE EVENTS, INCIDENTAL FINDINGS, AND OTHER POTENTIAL 
ISSUES
Please see the HRP 503 form section 4. Provisions for Research Related Harm/Injury  
Incidental Findings and Other Potential Issues and Provisions for Research Related Harm 
/ Injury for details on the procedures the research team will implement to handle and report 
adverse events, incidental findings, and other potential issues.
8
STATISTICAL CONSIDERATIONS 
8.1
DATA ANALYSIS PLAN (INCLUDING ANY STATISTICAL PROCEDURES)
8.1.1 HYPOTHESIS TESTING
Hypothesis 1.1) BN in the fed relative to fasted state will demonstrate impaired performance and 
deficient frontostriatal activation when inhibiting responses, whereas HC will show the opposite 
pattern. Behavioral analyses will examine state-dependent group differences in stop signal 
reaction time and % correct stop trials. Neuroimaging analyses will examine the impact of eating 
on activation during successful inhibition, regardless of the anticipated probability of the upcoming 
need to stop (P(stop)). Linear mixed effects (LME) models will be used for both sets of analyses.
Hypothesis 1.2) In BN, frontostriatal signals for the anticipated need to stop (P(stop)) and 
inhibitory prediction errors will be reduced in the fed relative to fasted state. HC will show the 
opposite pattern. Group x Visit x Trial Type LME analyses will examine how eating impacts group 
differences in P(stop)-modulated inhibitory activation (i.e., activation during Stop versus Go trials) 
and group differences in P(stop) activation, regardless of trial type. Group x Visit LME analyses 
will examine how eating impacts group differences in signed and unsigned prediction errors. We 
will examine both signed and unsigned prediction errors as each may provide unique information 
to inform behavioral adjustment: Unsigned prediction errors capture the overall mismatch 
between one's internal model of prediction and the actual outcome, whereas signed prediction 
Effective Date: 5/1/2025
End Date:4/30/2026

The Influences of Eating and Fasting on Inhibitory Control in Bulimia Nervosa: A 
Computational Neuroimaging Study
STUDY-19-00591
v.05.10.2023
26
errors provide additional information about the directionality of this mismatch, which may bias an 
individual to be more or less cautious (i.e., oriented more toward stopping or going).
Hypotheses 2.1 & 2.2) More severe binge eating and purging will be associated with lower 
frontostriatal signals for P(stop) and inhibitory prediction errors in the fed vs. fasted state; more 
severe dietary restriction will be associated with increased frontostriatal signals for P(stop) and 
prediction errors in the fasted vs. fed state. Within the BN group, Symptom Severity x Visit 
generalized LMEs will test how eating impacts the relations between self-report measures (binge 
eating, purging, and fasting frequencies) and activation associated with each neurocomputational 
regressor of interest. We will examine whether areas from this analysis overlap with clusters 
identified in Aim 1 to assess the potential contribution of illness severity to group differences in 
activation.
8.1.2 EXPLORATORY ANALYSES AND POTENTIAL CONFOUNDS
1) Resting CBF: ASL data will be subjected to Group x Visit LMEs a) restricted to masks of 
Aim 1 LME results and b) across the whole brain. If whole-brain mean CBF differences are 
observed, Aim 1 analyses will be repeated covarying for CBF.7 However, localized 
differences in CBF that overlap with Aim 1 results will further inform BOLD signal 
interpretation.
2) Illness Duration: We will test the association between months with BN and neural measures 
of interest.
3) BN Comorbidity and Treatment: Depending on final sample composition, post-hoc tests will 
examine a) group differences controlling for MDD, GAD, and SAD b) group differences 
excluding comorbid MDD, GAD, and SAD or c) associations of PHQ-9 and STAI-T scores 
with group differences in activation. Potentially confounding effects of treatment-seeking 
status will be evaluated in a similar manner.
4) Additional Measures of BN Symptom Severity and State Emotion/Arousal: Analyses 
described for Hypotheses 2.1 and 2.2 will be repeated using the pre-scan state measures.
5) Functional Connectivity: Psychophysiological interaction analyses will interrogate state-
specific frontostriatal connectivity during stop-signal inhibition.
6) We will explore group differences in performance and/or brain activation during the other 
decision-making neurocognitive tasks and associations of these measures with BN clinical 
symptoms.
8.2
POWER ANALYSIS (SAMPLE SIZE DETERMINATION)
Our sample size was selected based on the most rigorous analysis of our primary outcome 
measure (a Group x Visit x Trial Type LME). FMRI studies using inhibitory control tasks report 
large BN vs. HC effect sizes (mean striatum d = .82; mean PFC d = .96),62, 167 and our pilot 
data from remitted BN and HC suggest a large Group x Visit x Inhibitory Difficulty interaction in 
the DLPFC (d = .83). Prior work using the proposed Bayesian models to study substance  
dependence report large Group x P(stop)-modulated Trial Type (Stop*P(stop), Go*P(stop)) 
interactions in the DLPFC (d = .90) and caudate (d = .81).20 Based on these prior data, we 
expect large Group x Visit x Trial Type frontostriatal  interactions.  Using computed Stop*P(stop)  
and Go*P(stop) regressors from the DLPFC and caudate from this prior study of substance 
dependence,  we determined beta estimates were normally distributed with homogeneous  
variance across groups. We simulated 1,000 datasets with a 3-way interaction (Group x Visit x 
Effective Date: 5/1/2025
End Date:4/30/2026

The Influences of Eating and Fasting on Inhibitory Control in Bulimia Nervosa: A 
Computational Neuroimaging Study
STUDY-19-00591
v.05.10.2023
27
Trial Type) and fitted a mixed effects model to each dataset; power to detect a large (d = .80) 3-
way interaction with 30 women per group was estimated at over 80% with two-sided alpha =.05.
9
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
9.1
REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS
9.1.1  INFORMED CONSENT PROCESS
The study involves two consenting processes: phone screen and full study consenting processes. 
Please see the HRP 503 form section 9. Consent Process  Where and When Consent will 
be Obtained for details on these consenting processes. 
9.1.2  CONFIDENTIALITY AND PRIVACY
Please see the HRP 503 form section 3. Study Design  f) Data Storage, Transmission and 
Confidentiality and section 6. Provisions to Protect the Privacy Interests of Subjects for 
details.
9.1.3  FUTURE USE OF STORED SPECIMENS AND DATA 
Please see the HRP 503 form section 3. Study Design  e) Specimen Banking for Future 
Uses Not Part of This Project, and f) Data Storage, Transmission and Confidentiality for 
details.
9.1.4  SAFETY OVERSIGHT
Please see the HRP 503 form section 3. Study Design  g) Data and Safety Monitoring Plan, 
and h) For Other Projects With Greater Than Minimal Risk A Monitoring Plan Must Be 
Provided for details. 
9.1.4.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES 
Please see the HRP 503 form section 3. Study Design  f) Data Storage, Transmission and 
Confidentiality  Data Storage for details
10 REFERENCES 
1. Nozoe, S., et al., Comparison of regional cerebral blood flow in patients with eating disorders. 
Brain Research Bulletin, 1995. 36(3): p. 251-255.
Effective Date: 5/1/2025
End Date:4/30/2026

The Influences of Eating and Fasting on Inhibitory Control in Bulimia Nervosa: A 
Computational Neuroimaging Study
STUDY-19-00591
v.05.10.2023
28
2. Mauler, B.I., et al., Affect regulation and food intake in bulimia nervosa: emotional responding 
to food cues after deprivation and subsequent eating. J Abnorm Psychol, 2006. 115(3): p. 567-
79.
3. American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders: 
Fouth Edition, Text Revision (DSM-IV-TR). 2000, Washington, DC: American Psychiatric 
Association.
4. Hudson, J.I., et al., The prevalence and correlates of eating disorders in the National 
Comorbidity Survey replication. Biological Psychiatry, 2007. 61(3): p. 348-358.
5. Keski-Rahkonen, A., et al., Incidence and outcomes of bulimia nervosa: a nationwide 
population-based study. Psychological Medicine, 2009. 39(05): p. 823-831.
6. American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders: 
Fifth Edition (DSM-5). 2013, Washington. D.C.: American Psychiatric Association.
7. Wonderlich, S.A. and J.E. Mitchell, Eating disorders and comorbidity: Empirical, conceptual, 
and clinical implications. Psychopharmacology Bulletin, 1997. 33(3): p. 381-390.
8. Keel, P. and T. Brown, Update on course and outcome in eating disorders. Int J Eat Disord, 
2010. 43: p. 195-204.
9. Shenoy, P. and A.J. Yu, Rational Decision-Making in Inhibitory Control. Frontiers in Human 
Neuroscience, 2011. 5: p. 48.
10. Jones, A., et al., Fluctuating Disinhibition: Implications for the Understanding and Treatment 
of Alcohol and Other Substance Use Disorders. Frontiers in Psychiatry, 2013. 4: p. 140.
11. Berner, L. and R. Marsh, Frontostriatal circuits and the development of bulimia nervosa. 
Front Behav Neurosci, 2014. 17(8): p. 395.
12. Wierenga, C., et al., Are extremes of consumption in eating disorders related to an altered 
balance between reward and inhibition? Front Behav Neurosci, 2014. 9(8): p. 410.
13. Frank, G., et al., Altered structural and effective connectivity in anorexia and bulimia nervosa 
in circuits that regulate energy and reward homeostasis. Transl Psychiatry, 2016. 6(11): p. 
e932.
14. Frank, G.K.W., Altered brain reward circuits in eating disorders: chicken or egg? Current 
psychiatry reports, 2013. 15(10): p. 396.
15. Monteleone, A.M., et al., Altered processing of rewarding and aversive basic taste stimuli in 
symptomatic women with anorexia nervosa and bulimia nervosa: An fMRI study. Journal of 
Psychiatric Research, 2017. 90: p. 94-101.
16. Simon, J.J., et al., Neural signature of food reward processing in bulimic-type eating 
disorders. Social Cognitive and Affective Neuroscience, 2016. 11(9): p. 1393-1401.
17. Wagner, A., et al., Altered striatal response to reward in bulimia nervosa after recovery. 
International Journal of Eating Disorders, 2010. 43(4): p. 289-294.
18. Weygandt, M., et al., Diagnosing different binge-eating disorders based on reward-related 
brain activation patterns. Human Brain Mapping, 2012. 33(9): p. 2135-2146.
19. Frank, G.K.W., et al., Altered temporal difference learning in bulimia nervosa. Biological 
Psychiatry, 2011. 70(8): p. 728-735.
20. Hu, S. and C.-S.R. Li, Neural Processes of Preparatory Control for Stop Signal Inhibition. 
Human brain mapping, 2012. 33(12): p. 2785-2796.
Effective Date: 5/1/2025
End Date:4/30/2026

The Influences of Eating and Fasting on Inhibitory Control in Bulimia Nervosa: A 
Computational Neuroimaging Study
STUDY-19-00591
v.05.10.2023
29
21. Chikazoe, J., et al., Functional dissociation in right inferior frontal cortex during performance 
of go/no-go task. Cerebral Cortex, 2009. 19(1): p. 146-152.
22. Chikazoe, J., et al., Activation of right inferior frontal gyrus during response inhibition across 
response modalities. Journal of Cognitive Neuroscience, 2007. 19(1): p. 69-80.
23. Hampshire, A., et al., The role of the right inferior frontal gyrus: inhibition and attentional 
control. Neuroimage, 2010. 50: p. 1313-1319.
24. Miller, E.K. and J.D. Cohen, An integrative theory of prefrontal cortex function. Annual 
Review of Neuroscience, 2001. 24: p. 167-202.
25. Chambers, C.D., H. Garavan, and M.A. Bellgrove, Insights into the neural basis of response 
inhibition from cognitive and clinical neuroscience. Neuroscience and biobehavioral reviews, 
2009. 33(5): p. 631-46.
26. Aron, A.R., From reactive to proactive and selective control: developing a richer model for 
stopping inappropriate responses. Biological Psychiatry, 2011. 69(12): p. e55-e68.
27. Wager, T.D., et al., Common and unique components of response inhibition revealed by 
fMRI. Neuroimage, 2005. 27(2): p. 323-40.
28. Sebastian, A., et al., Neural correlates of interference inhibition, action withholding and 
action cancelation in adult ADHD. Psychiatry Research: Neuroimaging, 2012. 202(2): p. 132-
141.
29. Swick, D., V. Ashley, and U. Turken, Are the neural correlates of stopping and not going 
identical? Quantitative meta-analysis of two response inhibition tasks. Neuroimage, 2011. 56(3): 
p. 1655-1665.
30. Dosenbach, N.U., et al., Distinct brain networks for adaptive and stable task control in 
humans. Proceedings of the National Academy of Sciences of the United States of America, 
2007. 104(26): p. 11073-8.
31. Haber, S.N., Corticostriatal Circuitry, in Neuroscience in the 21st Century, D.W. Pfaff and 
N.D. Volkow, Editors. 2016, Springer New York: New York, NY. p. 1-21.
32. Hare, T.A., C.F. Camerer, and A. Rangel, Self-control in decision-making involves 
modulation of the vmPFC valuation system. Science, 2009. 324(5927): p. 646-648.
33. Marsh, R., et al., Deficient activity in the neural systems that mediate self-regulatory control 
in bulimia nervosa. Archives of General Psychiatry, 2009. 66(1): p. 1-13.
34. Skunde, M., et al., Neural signature of behavioural inhibition in women with bulimia nervosa. 
Journal of Psychiatry & Neuroscience, 2016. 41(5): p. E69.
35. Marsh, R., et al., An fMRI study of self-regulatory control and conflict resolution in 
adolescents with bulimia nervosa. American Journal of Psychiatry, 2011. 168(11): p. 1210-1220.
36. Harlé, K.M., et al., Altered Neural Processing of the Need to Stop in Young Adults at Risk for 
Stimulant Dependence. The Journal of Neuroscience, 2014. 34(13): p. 4567-4580.
37. Harlé, K.M., et al., Bayesian neural adjustment of inhibitory control predicts emergence of 
problem stimulant use. Brain, 2015. 138(11): p. 3413-3426.
38. Harle, K., A. Yu, and M. Paulus, Bayesian Neural Adjustment of "the Need to Stop" Predicts 
Relapse in Methamphetamine-Dependent Individuals. Biological Psychiatry, 2017. 81(10): p. 
S359.
Effective Date: 5/1/2025
End Date:4/30/2026

The Influences of Eating and Fasting on Inhibitory Control in Bulimia Nervosa: A 
Computational Neuroimaging Study
STUDY-19-00591
v.05.10.2023
30
39. Brogan, A., D. Hevey, and R. Pignatti, Anorexia, bulimia, and obesity: shared decision 
making deficits on the Iowa Gambling Task (IGT). J Int Neuropsychol Soc, 2010. 16(4): p. 711-
715.
40. Brand, M., et al., Neuropsychological correlates of decision making in patients with bulimia 
nervosa. Neuropsychology, 2007. 21(6): p. 742-750.
41. Chan, T.W.S., et al., Differential impairments underlying decision making in anorexia 
nervosa and bulimia nervosa: A cognitive modeling analysis. International Journal of Eating 
Disorders, 2014. 47(2): p. 157-167.
42. Paul, T., et al., Self-injurious behavior in women with eating disorders. American Journal of 
Psychiatry, 2002. 159(3): p. 408-11.
43. Holderness, C.C., J. Brooks-Gunn, and M.P. Warren, Co-morbidity of eating disorders and 
substance abuse review of the literature. International Journal of Eating Disorders, 1994. 16(1): 
p. 1-34.
44. Kaltiala-Heino, R., et al., Bulimia and impulsive behaviour in middle adolescence. 
Psychotherapy & Psychosomatics., 2003. 72(1): p. 26-33.
45. Wu, M., et al., Inhibitory control in bulimic-type eating disorders: a systematic review and 
meta-analysis. PLoS ONE, 2013. 8(12): p. e83412.
46. Wu, M., et al., Inhibitory control in bulimic-type eating disorders: a systematic review and 
meta-analysis. PLoS One, 2013. 8(12): p. e83412.
47. Bulik, C.M., et al., The relation between eating disorders and components of perfectionism. 
Am J Psychiatry, 2003. 160(2): p. 366-8.
48. Lilenfeld, L.R., et al., Eating disorders and personality: A methodological and empirical 
review. Clinical psychology review, 2006. 26(3): p. 299-320.
49. Frank, G., et al., Heightened fear of uncertainty in anorexia and bulimia nervosa. Int J Eat 
Disord, 2012. 45(2): p. 227-232.
50. Diaz-Marsa, M., J.L. Carrasco, and J. Saiz, A study of temperament and personality in 
anorexia and bulimia nervosa. J Personal Disord, 2000. 14(4): p. 352-9.
51. Ames-Frankel, J., et al., Personality disorder diagnoses in patients with bulimia nervosa: 
clinical correlates and changes with treatment. J Clin Psychiatry, 1992. 53(3): p. 90-96.
52. Fairburn, C.G., Cognitive Behavior Therapy and Eating Disorders. 2008, New York: Guilford 
Press.
53. Polivy, J. and C. Herman, Dieting and binging: A causal analysis. American Psychologist, 
1985. 40(2): p. 193-201.
54. Loth, K.A., et al., Could the resource depletion model of self#control help the field to better 
understand momentary processes that lead to binge eating? International Journal of Eating 
Disorders, 2016. 49(11): p. 998-1001.
55. Coniglio, K., et al., Time to Eat! Less Regular Eating Pattersn in Individuals who Binge 
and/or Purge, in International Conference on Eating Disorders. 2017: Prague.
56. Zunker, C., et al., Ecological momentary assessment of bulimia nervosa: Does dietary 
restriction predict binge eating? Behav Brain Res & Therapy, 2011. 49(10): p. 714-717.
57. Stice, E., et al., Fasting increases risk for onset of binge eating and bulimic pathology: a 5-
year prospective study. J Abnorm Psychol, 2008. 117(4): p. 941-946.
Effective Date: 5/1/2025
End Date:4/30/2026

The Influences of Eating and Fasting on Inhibitory Control in Bulimia Nervosa: A 
Computational Neuroimaging Study
STUDY-19-00591
v.05.10.2023
31
58. Wilson, G., et al., Cognitive-behavioral therapy for bulimia nervosa: time course and 
mechanisms of change. J Cons Clin Psychol, 2002. 70(2): p. 267-274.
59. Byrne, S.M. and N.J. McLean, The cognitive-behavioral model of bulimia nervosa: a direct 
evaluation. Int J Eat Disord, 2002. 31(1): p. 17-31.
60. Lampard, A.M., et al., An evaluation of the enhanced cognitive-behavioural model of bulimia 
nervosa. Behaviour Research and Therapy, 2011. 49(9): p. 529-535.
61. Lowe, M.R., et al., The relationship of weight suppression and dietary restraint to binge 
eating in bulimia nervosa. International Journal of Eating Disorders, 2007. 40: p. 640-644.
62. Stice, E., et al., Relation of successful dietary restriction to change in bulimic symptoms: a 
prospective study of adolescent girls. Health Psychology, 2006. 25(3): p. 274-281.
63. Stice, E., et al., Effects of a weight maintenance diet on bulimic symptoms in adolescent 
girls: an experimental test of the dietary restraint theory. Health Psychology, 2005. 24(4): p. 
402-412.
64. Lowe, M.R., D.H. Gleaves, and K.P. Murphy-Eberenz, On the relation of dieting and 
bingeing in bulimia nervosa. Journal of Abnormal Psychology, 1998. 107(2): p. 263-271.
65. Telch, C. and W. Agras, The effects of short-term food deprivation on caloric intake in 
eating-disordered subject. Appetite, 1996. 26(221-234).
66. Moreno-Domínguez, S., et al., Impact of Fasting on Food Craving, Mood and Consumption 
in Bulimia Nervosa and Healthy Women Participants. European Eating Disorders Review, 2012. 
20(6): p. 461-467.
67. DuBois, R.H., et al., A network analysis investigation of the cognitive-behavioral theory of 
eating disorders. Behaviour Research and Therapy, 2017. 97: p. 213-221.
68. Mitchell, J.E., S. Agras, and S. Wonderlich, Treatment of bulimia nervosa: Where are we 
and where are we going? International Journal of Eating Disorders, 2007. 40(2): p. 95-101.
69. Wilson, G.T., C.M. Grilo, and K.M. Vitousek, Psychological treatment of eating disorders. 
American Psychologist, 2007. 62(3): p. 199-216.
70. Pennesi, J.-L. and T.D. Wade, A systematic review of the existing models of disordered 
eating: Do they inform the development of effective interventions? Clinical Psychology Review, 
2016. 43: p. 175-192.
71. Jasinska, A.J., et al., Factors modulating neural reactivity to drug cues in addiction: a survey 
of human neuroimaging studies. Neuroscience & Biobehavioral Reviews, 2014. 38: p. 1-16.
72. Rive, M.M., et al., State-dependent differences in emotion regulation between unmedicated 
bipolar disorder and major depressive disorder. JAMA Psychiatry, 2015. 72(7): p. 687-696.
73. Loeber, S., et al., Hunger modulates behavioral disinhibition and attention allocation to food-
associated cues in normal-weight controls. Appetite, 2013. 71: p. 32-39.
74. Bartholdy, S., et al., Task-Based and Questionnaire Measures of Inhibitory Control Are 
Differentially Affected by Acute Food Restriction and by Motivationally Salient Food Stimuli in 
Healthy Adults. Frontiers in Psychology, 2016. 7: p. 1303.
75. Hollmann, M., et al., Neural correlates of the volitional regulation of the desire for food. Int J 
Obes, 2012. 36(5): p. 648-655.
Effective Date: 5/1/2025
End Date:4/30/2026

The Influences of Eating and Fasting on Inhibitory Control in Bulimia Nervosa: A 
Computational Neuroimaging Study
STUDY-19-00591
v.05.10.2023
32
76. Haedt-Matt, A. and P. Keel, Revisiting the affect regulation model of binge eating: a meta-
analysis of studies using ecological momentary assessment. Psychol Bull, 2011. 137(4): p. 660-
681.
77. Waters, A., A. Hill, and G. Waller, Bulimics' responses to food cravings: is binge-eating a 
product of hunger or emotional state? Behav Res Ther, 2001. 39(8): p. 877-886.
78. Martens, M.J., et al., Increased sensitivity to food cues in the fasted state and decreased 
inhibitory control in the satiated state in the overweight. The American Journal of Clinical 
Nutrition, 2013. 97(3): p. 471-479.
79. Le, D.S.N., et al., Less activation in the left dorsolateral prefrontal cortex in the reanalysis of 
the response to a meal in obese than in lean women and its association with successful weight 
loss. The American Journal of Clinical Nutrition, 2007. 86(3): p. 573-579.
80. Gautier, J., et al., Effect of satiation on brain activity in obese and lean women. Obesity 
Research, 2001. 9(11): p. 676-684.
81. Gautier, J., et al., Differential brain responses to satiation in obese and lean men. Diabetes, 
2000. 49(5): p. 838-846.
82. Hinton, E., et al., Neural contributions to the motivational control of appetite in humans. Eur 
J Neuroscience, 2004. 20(5): p. 1411-1418.
83. Tataranni, P.A., et al., Neuroanatomical correlates of hunger and satiation in humans using 
positron emission tomography. Proc Natl Acad Sci U S A, 1999. 96(8): p. 4569-4574.
84. Frank, G., et al., Alterations in brain structures related to taste reward circuitry in ill and 
recovered anorexia nervosa and in bulimia nervosa. Am J Psychiatry, 2013. 170(10): p. 1152-
1160.
85. Wagner, A., et al., Altered striatal response to reward in bulimia nervosa after recovery. Int J 
Eat Disord, 2010. 43(4): p. 289-294.
86. Avena, N. and M. Bocarsly, Dysregulation of brain reward systems in eating disorders: 
Neurochemical information from animal models of binge eating, bulimia nervosa, and anorexia 
nervosa. Neuropharm, 2012. 63: p. 87-96.
87. Bohon, C. and E. Stice, Reward abnormalities among women with full and subthreshold 
bulimia nervosa: A functional magnetic resonance imaging study. Int J Eat Disord, 2010.
88. Bohon, C. and E. Stice, Reward abnormalities among women with full and subthreshold 
bulimia nervosa: A functional magnetic resonance imaging study. International Journal of Eating 
Disorders, 2011. 44(7): p. 585-595.
89. Fairburn, C., Z. Cooper, and M. O'Connor, Eating disorder examination. In : Fairburn CG, 
editor. Cognitive Behavior Therapy and Eating Disorders, 16th edition.  New York: Guilford 
Press, pages 265-308. 2008.
90. Masheb Robin, M., M. Grilo Carlos, and A. White Marney, An examination of eating patterns 
in community women with bulimia nervosa and binge eating disorder. International Journal of 
Eating Disorders, 2010. 44(7): p.618-6
Effective Date: 5/1/2025
End Date:4/30/2026