Pilot Study of Mobile Attention Training in Overweight Female Adolescents
Phase: NA
Conditions: Obesity, Overweight, Binge Eating, Healthy Volunteers
Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Version Date:  July 14, 2022 
Version: 
1.7 
 
Date of this submission: July 14, 2022 
Project Number 
17-CH-0014 
 
IND/IDE Number 
None 
 
IND/IDE Holder  
None 
To: 
Chair, IRB, NICHD  
Recommended by:  
 
, Clinical Director, NICHD 
 
 
, Clinical Director, NIDDK 
 
 
, Clinical Director, NIMH 
 
 
, Clinical Director, Clinical Center 
Study Title: 
Pilot Study of Mobile Attention Training in Overweight Female Adolescents  
 
Abbreviated Title: 
Mobile Attention Training 
 
Investigators: Please see “Attention Retraining Study Personnel List” 
 
Identifying Words:  obesity, binge, loss of control eating, adolescents 
 
Study type (check all that apply): 
 
      X      Archived biological specimens/medical information 
                Natural history; definition of phenotype, genotype/phenotype correlation 
               Prospective linkage/gene identification, NOT providing information to participants 
                Prospective linkage/gene identification, providing information provided to participants  
     X        Social science; assessments of knowledge, attitudes and behavior 
                Genetic counseling 
                Drugs or devices 
                Gene transfer 
     X        Other interventions 
Estimated Duration of Study: 2 years 
 
Subjects of Study:  
 
Description 
Number 
Sex 
Age 
Overweight youth with loss of control over eating 
40 
Female 
12-17 y/o at 
baseline 
Overweight youth without loss of control over eating 
40 
Female 
12-17 y/o at 
baseline 
Screened but not randomized 
40 
Female 
12-17 y/o when 
screened 
 

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Page 2 of 56 
Project Uses Ionizing Radiation:  
 No   
 Yes  
  
 
 Medically-indicated only 
  
 
 Research-related only (attach RSC/RDRC documentation) 
  
 
 Both (attach RSC/RDRC documentation) 
 
Durable Power of Attorney   
 No   
 Yes  
 
Multi-institutional Project 
 
 No   
 Yes  
 
Data and Safety Monitoring Board   No   
 Yes  
 
Technology Transfer Agreement  
 No   
 Yes  
 
Agreement 
type 
and 
number 
___MOUs 
for 
Research 
Collaborators 
at 
USUHS_______________ Expiration Date___August 2017__________ 
 
Samples are being stored  
 
 No   
 Yes  
 
Flesch-Kincaid reading level of consent form:  
  Assent Form (youth): 68 (7th – 8th grade) 
  Consent Form (parent/guardian): 60 (9th grade) 
 
Research participants to be seen at: 
         x     NIH only*  
 
 
                Off-site only 
 
 
                Both NIH* and off-site 
*Includes participants who physically come to the NIH Clinical Center and/or for 
whom specimens/data are analyzed by Clinical Center departments. If participants 
will be seen at NIH, a Medical Advisory Investigator must be indicated on the 1195 
form, unless this is a social science project with no clinical interventions. 
 
 
Collaborative Project: 
 
 
• FWA for each Institution:___X_not applicable_______________________ 
 
 
see 
http://ohrp.cit.nih.gov/search/asearch.asp#ASUR 
for 
assurance 
#s 
 
 
 

Version Date:  July 14, 2022 
 
Page 3 of 56 
Précis: 
 
Over 30% of adolescents are overweight and 20% are obese, but the mechanisms that produce 
excessive weight gain in youth remain incompletely elucidated. Some overweight youth appear 
to have an attention bias (AB: a tendency to attend selectively to stimuli that have acquired 
salience or meaning) toward highly palatable food that may lead to overeating. AB involves 
distinct cognitive processes, (1) unconscious reactions (UCR), reflecting initial attention capture 
evoked by salient stimuli, and (2) continued attention deployment (AD) to stimuli relevant to 
current goals. These rapidly evolving processes are associated with unique neurocircuitry best 
measured using high spatial resolution and temporal sensitivity. Magnetoencephalography 
(MEG) is a novel neuroimaging technology that has both excellent temporal and good spatial 
resolution, thus is uniquely and ideally suited to study neurocognitive mechanisms of AB. 
Reducing AB to palatable foods may help some overweight youth curb their consumption of 
energy-dense options. Attention retraining (AR) programs can be used to reduce AB and have 
been effective in reducing AB to unhealthy food in adults. Although most AR studies involve 
computers in the laboratory, using smartphones in the natural environment may be a particularly 
effective method to deliver AR to adolescents and measure AB using ecological momentary 
assessment. The first aim of the proposed study is to examine the impact the a 2-week smartphone 
AR program on AB in overweight adolescent (12-17 y/o) girls with and without loss of control 
(LOC) eating, defined as a subjective experience of a lack of control over what or how much one 
is eating. LOC is a distinct eating behavior phenotype in youth that is a risk factor for excess 
weight gain and disordered eating, and is much more prevalent among girls (vs. boys). 
Overweight youth who report LOC may be particularly susceptible to AB. Additionally, adults 
with LOC demonstrate AB toward socially threatening cues, such as angry or disapproving faces, 
and the AB to social threat may be relevant to the relationship between AB to food and 
overweight.  The second aim is to examine, using MEG, the effect of a 2-week smartphone AR 
program on neural responses to food cues. The third aim is to examine the effect of the AR 
program on food intake and body composition. An exploratory aim is to examine whether AB to 
socially threatening cues, moderates the effects of this novel intervention on AB to food cues, 
food intake, and body composition. The proposed study is innovative because no study to date 
has examined the impact of AR delivered in the natural environment on AB and its associated 
neurocircuitry using MEG in a group of youth prone to AB. These studies may help further 
characterize phenomenology of distinct obesity subtypes and may potentially identify an 
approach that could prevent undue weight gain in adolescent girls at risk for obesity. 
 
 

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II. Outline/Table of Contents: 
 
 
 
 
 
 
         Page 
 
I. 
Précis                                                                                                                 
3 
II. 
Table of Contents  
 
 
 
 
 
 
 
4 
III. 
Introduction 
 
 
 
 
 
 
 
 
5 
IV. 
Study Objectives 
9 
V. 
Specific Aims 
 
 
 
 
 
 
 
 
10 
VI. 
Study Design and Methods 
 
 
 
 
 
 
11 
a. Subject Enrollment 
 
 
 
 
 
 
 
11 
i. Eligibility Criteria for Participants 
 
 
 
 
11 
a. Inclusion Criteria 
11 
b. Exclusion Criteria 
 
 
 
 
 
12 
b. Procedures 
 13 
VII. 
Analysis of the Study/Oversight  
 
 
 
 
 
23 
a. Study Administration and Data Collection, Management, and Storage 
23 
b. Publication of Research Findings 
 
 
 
 
 
24 
c. Primary and secondary outcomes  
 
 
 
 
 
25 
d. Reason for Withdrawal/ Adverse Event Reporting  
 
 
26 
e. Determination of Sample Size and Analytic Plan 
 
 
 
26 
VIII. Human Participant Protections 
 
 
 
 
 
 
29 
a. Rationale for Subject Selection 
 
 
 
 
 
29 
b. Participation of Children and Other Vulnerable Populations  
 
30 
c. Screening Methodology 
 
 
 
 
 
 
30 
d. Risks/Benefits Analysis 
 
 
 
 
 
 
31 
i. Risks  
 
 
 
 
 
 
 
31 
ii. Benefits 
 
 
 
 
 
 
 
34 
iii. Assessment of Risk/Benefit Ratio 
 
 
 
 
34 
iv. Alternatives to Participation  
 
 
 
 
35 
e. Privacy and Confidentiality Provisions 
 
 
 
 
35 
f. Compensation  
 
 
 
 
 
 
 
36 
g. Consent/Assent Process 
 
 
 
 
 
 
36 
h. Pharmaceutical, Biologic and Device information 
 
 
 
40 
i. Recruitment Strategies 
 
 
 
 
 
 
41 
j. Description of Criteria for Withdrawal from Study  
 
 
41 
k. Re-evaluation of Study 
 
 
 
 
 
 
41 
l. Collection, Monitoring, Analysis and Reporting of Adverse Events  
41 
m. Conflicts of Interest  
 
 
 
 
 
 
43 
n. Monitoring Plan  
 
 
 
 
 
 
 
43 
IX. 
List of Appendices 
 
 
 
 
 
 
 
45 
X. 
Consent Documents 
 
 
 
 
 
 
 
46 
XI. 
References 
 
 
 
 
 
 
 
 
47 
 
 
 

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III. Introduction: 
List of Abbreviations: 
BMI:  
Body Mass Index 
LOC:   
Loss of control 
MEG:   
Magnetoencephalography 
AB:  
 
Attention bias 
AR:  
 
Attention retraining 
EMA:   
Ecological momentary assessment 
 
Obesity and Adolescence  
More than one-third of youth between ages 2 and 19 are overweight, defined as BMI (kg/m2) ≥ 
85th percentile for age and sex, and 17% are obese, defined as BMI ≥ 95th percentile for age and sex 
(1, 2). These numbers are alarming because excess weight places adolescents at high risk for 
impaired metabolic function (3), type 2 diabetes (4), and adult obesity (5-7). Adolescent obesity is 
also associated with psychological problems. Overweight and obese adolescents experience 
greater emotional, social, and behavioral problems compared to their non-overweight peers (8-10). 
There are positive associations between adolescent obesity and depression, anxiety, eating 
disorders, low self-esteem, and poor weight-related quality of life (10-12). 
A time of considerable biological, social, and cognitive change (13, 14), adolescence is a critical 
developmental stage for establishing behavior patterns. Unlike the eating behaviors of younger 
children that are largely under parental influence, adolescents typically exercise greater 
independence with regard to their food choices and eating habits (15). Adolescence is also a period 
when many disordered eating patterns manifest, particularly among girls (16). Understanding the 
mechanisms underlying eating behaviors and designing more effective interventions to decrease 
excessive food intake and reduce excess weight among adolescents are thus of paramount 
importance. The proposed study, of a novel and age-appropriate intervention, develops a targeted 
approach that may hold promise for wide dissemination. Targeted therapeutic approaches for 
subgroups with specific phenotypes have been recommended (17), and have the potential for 
greater effects. 
Attention Bias and its Neurocircuitry 
Attention bias (AB) refers to the tendency to attend selectively to stimuli that have acquired 
salience or meaning (18). ABs have been theorized to predispose individuals to psychopathology 
(19, 20), causing and/or maintaining anxiety (21), overeating (22, 23), and disordered eating 
attitudes (24). Incentive sensitization models (25, 26), based primarily on animal studies, propose 
that palatable food cues capture attention more readily and trigger food cravings when they carry 
a heightened incentive value. AB is hypothesized to lead to a pathological motivation for food 
and stimulate compulsive, out-of-control eating behavior in individuals who are biologically 
prone towards obesity (25, 26). Research generally finds a positive relationship between AB for 
palatable foods and overweight in adults (27-30). However, data in children are less clear (31, 
32).  

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Imaging studies of AB map neural correlates of two component processes: 1) unconscious 
reactions (UCRs) reflecting initial attention capture evoked by emotionally salient stimuli, and 2) 
attention deployment (AD) to stimuli relevant to current goals (33, 34). The UCR involves rapidly 
deployed sub-cortical circuitry encompassing medial temporal and striatal circuitry (25, 26, 33, 
34), depending on whether salient stimuli are attributed a negative or positive emotional valence. 
The AD involves brain regions that support task-related goal attainment, including the anterior 
cingulate cortex (ACC), orbital frontal cortex (OFC), and ventrolateral prefrontal cortex (vlPFC) 
(34). The neural processes involved in UCR and AD evolve in sequence and over short time scales 
(1-2 seconds), and are optimally captured by temporally sensitive methods (35).  
LOC Eating and Overweight  
LOC eating is defined as a subjective experience of a lack of control over what or how much one 
is eating, regardless of the amount reportedly consumed (36). LOC eating is endorsed by 
approximately 30% of overweight adolescents (37, 38) and is a salient risk factor for excess weight 
gain (39, 40), metabolic complications (41) and partial or full-syndrome binge eating disorder (42, 
43). LOC eating is a distinct eating behavior phenotype in youth. Compared to their peers without 
LOC, youth who report LOC are at twice the risk for overweight or obesity (39) and prospectively 
gain over 5 lbs. more per year (beyond healthy growth) (40). Although LOC eating has been 
reported with similar prevalence among Non-Hispanic White and minority groups including Non-
Hispanic Black and Hispanic youth (44, 45) some laboratory data demonstrate that non-Hispanic 
Black adolescent girls consume more during a laboratory meal compared to their non-Black 
counterparts (45). Thus, given that the childhood obesity rates have increased dramatically among 
Black youth (1, 46), it is important to consider the effects of race on LOC eating.  
LOC Eating and Attention Bias 
Notably, youth with LOC eating appear to have a bias toward highly palatable foods that may 
lead them to engage in LOC eating episodes. Our data (15, 47) and those of others (48) have 
demonstrated via self-report (15) and in the laboratory (49, 50), that youth with LOC eating 
select and consume more highly-palatable snack and dessert foods than youth without LOC. 
Similar to binge eating in adults (51, 52), the LOC phenotype involves overconsumption of 
palatable foods. Recent studies indicate that youth who binge eat demonstrate increased AB to 
food cues in laboratory tasks (53). Our data suggest that among youth with LOC eating, BMIz is 
positively associated with AB to highly palatable foods (Figure 1a), while the reverse is observed 
among youth without LOC (Figure 1b) (54).  

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Fig 1a. Youth with LOC eating have a positive association between AB and BMI-z, p<.05. Fig 1b. No LOC eating 
youth have a non-significant negative association between AB to high palatable foods and BMI-z; Interaction 
p=.01, N=77. 
In adolescents, LOC severity is associated with cravings for palatable foods (55, 56), a self-
reported index of food cue AB. Youth with LOC eating report frequent eating in response to 
external food cues (16, 57-59), which is linked to food AB (60). The current obesogenic 
environment likely further strengthens AB to highly palatable foods and may lead to an irresistible, 
compulsive desire to eat that overwhelms self-regulatory capacity in youth with LOC. Thus, AB 
to palatable foods may provide an important mechanism by which LOC eating promotes excess 
weight gain.  
Youth with LOC eating may also be susceptible to attending selectively to socially threatening 
stimuli in the environment. ABs to threatening stimuli have been shown to contribute to the 
development and maintenance of anxiety disorders (61). There is also evidence that adults who 
engage in binge eating behaviors demonstrate greater AB toward socially threatening stimuli (such 
as angry faces) compared to healthy control participants (62, 63). This may be explained by 
interpersonal models of eating dysregulation that posit that social stressors, particularly 
interpersonal evaluation and conflict, precipitate LOC eating (64, 65). Thus, attentional bias 
toward socially threatening cues (e.g., disapproving facial expressions) might contribute to LOC 
eating via the interpersonal model (34). Youth with LOC eating report greater anxiety and social 
stress than youth without LOC eating (58, 66), and there is emerging evidence from neuroimaging 
studies that girls with LOC demonstrate heightened sensitivity toward social cues (67). Thus, it 
appears that heightened attention to threatening cues may moderate the relationship between food 
cue exposure and overconsumption, but the neurocognitive processes related to the potential ABs 
to social threat have not been examined in relation to eating patterns in youth. 
Neurocircuitry of Attention Bias and LOC Eating. To date, AB research has used either event-
related potentials to elucidate the temporal sequence of neural activity, or functional MRI (fMRI), 
providing high spatial resolution to determine key brain regions. In fMRI studies with adolescent 
girls, neural circuitry of the UCR (insula, ACC, OFC) and AD (vlPFC) were implicated during a 
food cue AB task (68). The striatum has also been shown to be central to food cue processing, 
reward value encoding, and AB (69-75). Upon exposure to palatable food (vs. neutral) cues, adults 
with binge eating have OFC, insula, and striatal hyperactivation – brain regions essential to UCR 
-1
0
1
2
3
4
-100
-50
0
50
100
150
BMI-z score
Attentional bias
-1
0
1
2
3
4
-100
-50
0
50
100
150
BMI-z score
Attentional bias
a. No LOC eating
b. LOC eating

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Page 8 of 56 
– relative to those without binge eating (76-78). There is also preliminary evidence that neural 
activation associated with exposure to social stress may be related to dysregulated eating patterns. 
In studies using fMRI, individuals with dysregulated eating patterns demonstrate hyperactivation 
in regions implicated in social threat processing, specifically the amygdala (AMY), ACC and the 
OFC (79). These regions are also implicated in the initial attention capture processes in attention 
bias literature (80). Compared to those without LOC, overweight adolescent girls with LOC eating 
demonstrate hypoactivation in the ventromedial PFC following an experience of interpersonal 
rejection (67). Thus, it is possible that AB to socially threating cues is one moderator of the neural 
response to appetizing and rewarding food cues, and subsequent overconsumption. The 
neurobiology of the ABs to socially threatening cues and the impact of such biases on the correlates 
of LOC eating have not been explored to date.  
Magnetoencephalography to examine Neural Mechanisms of Attention Bias 
Magnetoencephalography (MEG) is a novel neuroimaging technology that has both excellent 
temporal and good spatial resolution (81-83). MEG studies focusing on other types of ABs confirm 
the utility of MEG for differentiating between the neural components of these two consecutive AB 
processes (84). Thus, the use of MEG can help elucidate the neural bases of ABs toward food and 
threat in youth susceptible to such biases.  
Attention Retraining  
Attention bias modification methods have been studied in other fields, such as anxiety and 
substance use disorders. Attention retraining (AR), a method to reduce an unwanted AB, is 
effective at reducing AB to problem cues in other fields, such as anxiety and substance use in 
adults (85-87) and pediatric anxiety (88). AR has been shown to effectively reduce AB and intake 
of chocolate, a palatable food (89, 90), or to increase biases for and intake of healthy foods (91). 
Among adults, five retraining sessions had a lasting effect of reducing AB to food for at least a 
week after training was concluded (92). Additionally, there is preliminary evidence among adults 
with LOC eating that AR is effective in reducing attention bias and LOC eating episodes 
immediately and 3-months following delivery (93). There are no data in adolescents. One 
preliminary study of 20 overweight and obese children found that a single session of AR in the 
laboratory reduced AB and food intake (94). Yet, there are no data among youth with reported 
LOC eating – a subgroup that appears to have a particularly robust AB to palatable foods (54).  
Given the initially promising results from single sessions of AR to reduce AB youth (94), it is 
plausible that AR in the natural environment may have a potent effect. Learning theory posits that 
the development of new behaviors is strongly context dependent (95). The ubiquity of palatable 
unhealthy foods makes it necessary to provide an AR intervention that will generalize outside of 
the laboratory in order to impact AB and, ultimately, body weight.   
 
 
 
Mobile 
Attention 
Retraining 
Reduce attention bias to 
highly palatable foods 
Reduce LOC eating and 
consumption of highly 
palatable foods 

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Page 9 of 56 
 
Theoretically, interventions that occur in the natural environment may be more accessible, 
ecologically valid, and have greater impact on the key constructs that influence the outcome 
variable of interest (95). Importantly, adolescents use handheld technology as part of their daily 
communication and activities (60). Thus, AR delivered on a mobile phone will be less intrusive 
in, and more compatible with, their lifestyles than the inconvenience of multiple trips to the 
laboratory. Administering AR on smartphones may be a particularly promising approach because 
it is easy to administer multiple trainings per day. Additionally, more “doses” of AR may lead to 
greater reductions/reversals, or more sustained reductions/reversals, in AB (a reversal occurs when 
participants attend away from salient cues and toward neutral cues). For example, Hakamata and 
colleagues (96) and Beard and colleagues (97) reported that number of training sessions was 
associated with degree of reduction in AB or symptoms. “Distributed practice” over multiple 
sessions is generally more effective than “massed practice” at a smaller number of sessions in skill 
acquisition (98), and a primary feature of computer-based cognitive remediation interventions for 
both adults and adolescents is the use of a large number of individual training sessions (99). 
Therefore, retraining youth to attend away from palatable foods in their natural environment may 
have more robust impact on AB and consequently reduce LOC episodes and energy intake (Figure 
2).  
Attention Bias Retraining in Overweight Youth: Identifying Neural Underpinnings 
Loss of control (LOC) eating is a distinct behavioral phenotype in youth (36) and it is associated 
with AB toward highly palatable food (40, 49, 54), adiposity (37, 38), and weight gain over time 
(39, 40). Attention bias (AB) involves complex cognitive processes, unconscious reactions (UCR) 
and attention deployment (AD) (33, 34), each associated with unique neural correlates, best 
measured using high spatial resolution and temporally sensitive methods (35). Understanding the 
differences in neurocognitive mechanisms of AB to highly palatable food in youth with LOC 
eating compared to those without will help inform tailored treatments. These youth may also be at 
higher risk of AB to social threat, thus examining neurocognitive processes associated with 
appraisal of socially threatening cues may further the understanding of distinct subtypes of obesity. 
In the proposed study, we will examine the differences in neurocognitive responding to cues of 
highly palatable foods in youth with and without LOC eating using MEG, which offers both high 
spatial resolution and excellent temporal sequencing (84). It is also unknown how these 
neurocognitive processes are affected by an intervention aimed at modifying AB. Using MEG, the 
proposed study will elucidate the neurocognitive mechanisms of AB in youth with LOC eating, 
prior to and following a novel, age-appropriate intervention aimed at modifying AB. Additionally, 
we will explore whether AB to social threat is more pronounced in overweight youth with LOC 
compared to those without, and whether, if present, it moderates response to intervention.   
 
IV. Study Objectives 
Fig 2. Attention retraining in the natural environment reduces biases to highly palatable foods that, in turn, 
decreases LOC eating and consumption of highly palatable foods. 

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Primary objective 
No study to date has examined the impact of AR delivered in the natural environment on AB in a 
targeted group of youth specifically prone to ABs. Similarly, no study has examined the effect of 
AR on neurocircuitry of ABs to food using MEG. Overweight adolescent girls (age 12-17y) with 
and without LOC eating will be studied at baseline and again after completion of a 2-week double-
blind, randomized controlled trial of AR away from palatable (trigger) foods. The longer-term 
effects of AR on AB, neural responding, food intake, and body composition will also be examined 
at 3-month follow-up.  
Secondary objectives (Exploratory) 
To improve retention, all participants will receive the AR intervention and be followed for an 
additional 3 months. One exploratory objective of this study is to examine whether dose-response 
effects are present when the AR program is re-administered 3 months later. The effects of the AR 
received as a booster vs. AR received for the first time on AB and body composition will be 
examined. Given that ABs to social threat appear to be more pronounced in adults with LOC eating 
compared to those without LOC eating (62, 63), the second exploratory aim is to examine the 
moderating effects of AB to social threat on intervention effects. The third exploratory aim is to 
examine the LOC status (LOC vs. No-LOC girls) as a moderator of changes in AB, neural 
responsivity, food intake, and body composition following the AR program. Finally, given the 
increase in obesity among Black youth and some findings indicating that Black girls consume 
more in laboratory meals (45), the fourth exploratory objective is to explore the moderating effects 
of race on the study outcomes. 
 
V. Specific Aims 
Specific Aim #1: To examine the impact of a 2-week AR or control program on AB in overweight 
girls with and without LOC. 
Hypothesis 1: Youth randomized to AR will demonstrate a reduction in AB to palatable foods 
compared to those in the control condition in: (A) The laboratory based on visual probe task 
and eye tracking; (B) The natural environment based on smartphone data. 
Specific aim #2: To examine changes in neural responsivity following a 2-week AR or control 
period in overweight girls with and without LOC. 
Hypothesis 2A: Youth randomly assigned to AR will have improvements in “bottom-up” 
attention circuitry in response to palatable food images (striatum) during UCR: AR will lead 
to less activation, whereas there will be no change in “bottom-up” attention circuitry in youth 
given the control condition. 
Hypothesis 2B: Youth randomly assigned to AR will have improvements in “top down” 
attention circuitry (dorsal ACC, vlPFC, dlPFC) during AD: AR will lead to greater activation, 
whereas there will be no change in “top down” attention circuitry in girls given the control 
condition. 
Specific aim #3: To examine the effect of AR on food intake and body composition. 

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Hypothesis 3A: Youth randomized to AR will (i) Consume less energy from palatable foods 
in the laboratory test meal; (ii) Report lower levels of LOC eating in the natural environment 
(based on smartphone data); Hypothesis 3B: Youth randomized to AR will demonstrate less 
weight gain and adiposity compared to youth in control condition at 3-month follow-up. 
Exploratory aim #1: Examine whether dose-response effects are present for AB to palatable foods 
and body composition in participants who receive the AR program at 3 months as a booster 
compared to those who receive it for the first time. 
Exploratory aim #2: Examine the moderating effects of ABs to social threat (reaction times on 
the visual probe task, neural activation during the MEG session) on intervention effects (AB to 
food cues, food intake in the laboratory, and body composition). 
Exploratory aim #3: Examine the moderating effects of LOC status (LOC vs. No-LOC) on the 
effects of AR program on “bottom-up” and “top-down” attention circuitry, AB reaction times, 
food intake, and body composition. 
Exploratory aim #4: Examine the moderating effects of race on the effects of the AR program on 
attention bias, laboratory consumption, and weight/adiposity. 
 
VI. Study Design and Methods 
a. Subject Enrollment 
A maximum of 120 overweight/obese but otherwise healthy adolescent girls, age 12-17y, (in order 
to randomize 40 with LOC eating and 40 without LOC eating), will be recruited through mailings 
to families in the Washington, D.C. greater metropolitan area, a method that has shown success in 
our previous community-based and intervention studies of youth with LOC eating (40, 43, 47, 58, 
100).   
 
Eligibility Criteria 
Inclusion Criteria: 
Volunteers will qualify if they meet the following criteria: 
1. Age between 12 and 17 years (at the start of the study). 
2. Female sex. 
3. BMI at or above the 85th percentile for age and sex according to the Centers for Disease 
Control US Standards (101).  
4. Right handedness. 
LOC sample only: 
5. > 1 episodes of LOC eating during the past month prior to assessment, assessed using a 
clinical diagnostic interview for eating disorders 
No-LOC sample only: 
6. No episodes of LOC eating during the past month prior to assessment, assessed using a 
clinical diagnostic interview for eating disorders 

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Exclusion Criteria: 
Individuals will be excluded (and provided treatment referrals as needed) for the following 
reasons: 
1. An obesity-related health comorbidity requiring medical treatment, such as hypertension 
(defined by age-, sex-, and height-specific standards) or fasting hyperglycemia consistent 
with diabetes. 
2. Presence of other major illnesses: renal, hepatic, gastrointestinal, most endocrinologic 
(e.g., Cushing syndrome, untreated hyper- or hypothyroidism), hematological problems 
or pulmonary disorders (other than asthma not requiring continuous medication). Non-
serious medical illnesses, such as seasonal allergies, will be reviewed on a case-by-case 
basis.   
3. Regular use of any medication known to affect body weight or eating behavior (e.g., 
stimulants prescribed for attention deficit hyperactivity disorder, or ADHD). Medication 
use for non-serious conditions (e.g., acne) will be considered on a case-by-case basis.  
4. Current pregnancy or a history of pregnancy. 
5. A significant reduction in weight during the past three months, for any reason, exceeding 
5% of body weight. 
6. Presence in the child of any significant, full-threshold psychiatric disorder based on DSM 
criteria (102), such as schizophrenia, bipolar disorder, alcohol or substance abuse, 
anorexia or bulimia nervosa, or any other disorder that, in the opinion of the 
investigators, would impede competence or compliance or possibly hinder completion of 
the study. These individuals will not be permitted to enroll in the current study and will 
be referred for treatment. Individuals who present with other psychiatric disorders, 
including sub-threshold psychiatric disorders, will be permitted to enroll in the study. If, 
based on the opinion of the investigators, a participant requires treatment for his/her 
psychiatric symptoms, the individual will be referred for treatment. Participants who 
develop any psychiatric disorder or significant psychiatric symptoms at any follow-up 
assessment during the study will be excluded and be provided with treatment referrals.    
7. Current and regular substance use, including the use of alcohol and/or tobacco products 
(including e-cigarettes). 
8. A history of significant or recent brain injury that may considerably influence 
performance (i.e., any history of loss of consciousness ≥30 minutes associated with a 
head injury, any history of memory loss or hospitalization associated with a head injury, 
or ≥2 concussions within last year).  
9. Current involvement in a weight loss program, participating in psychotherapy aimed at 
weight loss or treatment of eating behavior (e.g., binge eating).  
10. All parents/guardians will be asked to indicate if their child has any food allergies. To be 
conservative, children who report allergies to gluten, nuts, dairy, fruit, or any other item 
in the array, will be excluded from the test meal portion of the study. 
11. A condition under which MEG is contradicted (e.g., metal in the body, pregnancy, 
claustrophobia, history of significant neurological insult or injury). 

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12. Non-English speaking participants will be excluded from the study as they may be unable 
to complete questionnaires and follow the instructions which are only provided in 
English.  
 
Appendix 1 provides the Eligibility Checklist.  
 
b. Procedures 
Study overview: Appendix 2 provides a schematic of the chronology of experimental 
procedures. The study will consist of a total of six visits.  
Visit #1: Screening. Following a 20-minute phone screen with the parent and the child (Appendix 
3), potentially eligible participants will be invited to the NIH for a screening visit to determine 
eligibility for the experimental portion of the study. The screening visit will be a half-day 
appointment. The following procedures will take place:  
1. Consent/assent. Study purposes, all testing procedures, and possible study risks will be 
described in detail. Interested families will sign IRB-approved assent and consent forms 
(see also Consent/Assent Process, page 36).  
2. Brief history, physical exam, and body measurements will be conducted by a trained 
practitioner (see Appendix 4 for the screening visit physical exam form). A brief 
psychiatric and health history of the participant will be obtained from a parent or guardian 
in order to identify medical issues prior to study participation. This will include the 
assessment of current parental (guardian) medical and/or psychiatric illness, in addition to 
birth history of participants and factors associated with prenatal stress. Waist 
circumference (in cm) will be measured, as will pubertal development according to the 
stages of Tanner (103, 104). Tanner breast staging (by inspection and palpation) and pubic 
hair staging (by inspection) will be used to categorize youth as those in pre-puberty (Tanner 
stage 1), early to mid-puberty (Tanner stages 2–3), or late puberty (Tanner stages 4–5). In 
cases in which the stage is discordant between the right and left breasts, the higher stage 
will be assigned. Measurements of vital signs (blood pressure, pulse, and temperature) 
height in triplicate by stadiometer, and weight by calibrated scale will be conducted. BMI 
will be calculated as weight in kilograms divided by the square of height in meters (kg/m2). 
BMI percentiles will be used to categorize participants as overweight (≥85th percentile) or 
obese (≥95th percentile) (105). A urine sample will be obtained from all participants and 
tested for pregnancy in postmenarcheal girls. 
3. Whole body Dual-Energy X-ray Absorptiometry (DXA) will assess fat, lean, and bone 
mass (Lunar iDXA, GE Healthcare) in a fasting state. DXA involves 0.003 mrem of 
radiation exposure per scan (total exposure for 3 scans: .0009 mrem).  
4. Youth Interviews. 
a. Eating Disorder Examination (EDE), Version 14 (106) (see Appendix 5) or the EDE 
adapted for children (children age < 14 years) (107) is a semi-structured 
psychodiagnostic interview of eating disorder psychopathology. The EDE is the “gold 

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Page 14 of 56 
standard” interview for diagnosing disordered eating. The overeating section will be 
administered to determine LOC presence and severity. The EDE is reliable and valid 
in adolescent samples (38, 59, 108, 109). Participants who report at least one episode 
of LOC eating in the past 28 days on the EDE, will be assigned to the LOC group. 
Participants who deny LOC episodes in the past 28 days will be assigned to the non-
LOC group. 
b. Physical Activity. To determine the average amount of moderate-to-vigorous physical 
activity each participant has engaged in within the previous week, children will be 
asked two items from the International Physical Activity Questionnaire (IPAQ) 
screening form (110). These data will be used to help determine the amount of the 
standardized breakfast shake for each participant in subsequent visits. See Appendix 6 
for the list of items.     
5. Youth Questionnaires. Youth will complete a battery of self-report questionnaires 
including the following (see Appendix 6 for the measures): 
a. Beck Depression Inventory (BDI) (111) is a widely used valid and reliable (112) 
questionnaire that measures self-reported severity of depressive symptoms. It has been 
shown to be internally consistent (alphas = .86 for psychiatric patients and .81 for 
nonpsychiatric subjects). Concurrent validity with other measures of depression for 
psychiatric patients has ranged between .72 and .73 and for nonpsychiatric individuals 
between .60 and .74. If participant endorses a positive screen (BDI ≥ 20), she will be 
further assessed for depression symptoms according to the DSM-5 criteria using a 
semi-structured interview (see Supplemental Assessment section below). Only girls 
who are at least 14-years-old will complete the BDI. 
b. Children’s Depression Inventory (CDI) (113, 114) assesses the presence and degree of 
childhood depressive symptoms and is a widely used measure with very good reliability 
and validity.  
c. DSM-5 Cross-Cutting Symptoms Measure (DCSM) (115) assesses mental health 
domains that are important across psychiatric diagnoses. The measure consists of 25 
questions that assess 12 psychiatric domains, including depression, anger, irritability, 
mania, anxiety, somatic symptoms, inattention, suicidal ideation/attempt, psychosis, 
sleep disturbance, repetitive thoughts and behaviors, and substance use. Each item asks 
the child to rate how much he or she has been bothered by the specific symptom during 
the past 2 weeks. The measure was found to be clinically useful and had good test-
retest reliability in the DSM-5 Field Trials in pediatric clinical samples across the 
United States. If the participant endorses symptoms consistent with the presence of one 
of DSM-5 disorders above threshold levels, she will be further assessed using a semi-
structured interview (see Supplemental Assessment section below). 
d. Food Preference Questionnaire (FPQ): This measure contains the foods that will 
comprise the buffet used for the test meals. These food items are embedded within a 
larger, general food preference list. The questionnaire evaluates whether foods used in 
the test meal array are acceptable (graded 5 or above on a 10-point Likert scale) to the 

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participant and has been shown to successfully identify food preferences in children 
(116). This measure is used to ensure that participants like (i.e., rated them 6 or above) 
at least 50% of the food items offered during their lunch test meals. 
e. State-Trait Anxiety Inventory for Children–A trait scale (STAIC) is a 20-item self-
report measure of trait anxiety with very good psychometric properties (117). A meta-
analysis revealed very good internal consistency for the trait scale (mean alpha 
coefficient = .89).  
f. Emotional Eating Scale - Children (EES) (118, 119) is a 25-item self-report measure 
used to assess the urge to cope with negative affect by eating.  It generates 3 subscales 
including: Anger/Anxiety/Frustration, Depression, and Unsettled. The EES-C has 
demonstrated good internal consistency, discriminant validity and construct validity. 
g. Eating in the Absence of Hunger Questionnaire for Children (EAH-C) consists of 14 
total items from which 3 subscales are factor-analytically derived: i) Negative Affect 
(6 items), ii) External Eating (4 items), and iii) Fatigue/Boredom (4 items). Items will 
be rated on a 5-point Likert scale ranging from 0=“never” to 4=“always.” The measure 
has demonstrated good internal consistency, convergent validity and temporal stability 
for all scales (120).  
h. The Reward-based Eating Drive Scale (REDS) (121) is a 9-item self-report 
questionnaire that is designed to measure reward-based eating symptoms. Individual 
items capture constructs of lack of control over eating, lack of satiety, and 
preoccupation with food. The REDS yielded a total score. The REDS has demonstrated 
excellent internal consistency, good test-retest reliability, and incremental validity to 
other reward-driven eating measures in adults (121). In the current study, participants’ 
responding to rewarding stimuli will be measured at the neural level (with MEG) and 
the cognitive level (with the food AB task), thus we will be able to validate this brief 
self-report scale against presumably more objective indices of reward-based eating.  
i. Questionnaire on Eating and Weight Patterns – Adolescent Version – DSM-5 (QEWP-
A-DSM-5) is a self-report measure based upon the adult Questionnaire on Eating and 
Weight Patterns – Revised to assess frequency of reported binge eating (122)(1). The 
QEWP-A has been adapted to capture LOC eating as well as binge episodes. The 
QEWP-A was been adapted to capture DSM-5 (102) eating disorders. This 
questionnaire is a screening tool designed to identify children with possible bulimia 
nervosa and binge eating disorder. 
j. Perceived Stress Scale (PSS) is a 14-item self-report questionnaire designed to measure 
the extent to which life events impact an individual’s level of perceived psychological 
stress. The scale is not used as a diagnostic tool, but as a comparison tool for intra-
sample participants. The items refer to life events that have occurred within the past 
month, targeting general events during this period (e.g. “In the last month, how often 
have you found that you could not cope with all the things that you had to do?”) The 
scale has been validated in both laboratory and community samples (123).  
k. Mindful Attention and Awareness Scale – Adolescents (MAAS-A). Mindful attention 

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or clear, present-moment awareness has gained increasing attention as a cognitive state 
highly relevant for stress and coping/stress-response (124). Adolescents will complete 
the 15-item MAAS questionnaire (125), adapted for adolescents (126), which assess 
one’s tendency to attend to present-moment experiences in everyday activities. The 
MAAS is internally reliable, distinguishes practitioners of mindfulness, and has 
concurrent and predictive validity for diminished negative affect (125-127).  
l. UPPS-P Impulsive Behavior Scale – Child Version (UPPS-R – C) is a 40-item self-
report questionnaire designed to measure features of impulsive behavior in adolescents 
(128). The UPPS-P (129) generates 4 subscales: a) Negative Urgency; b) Lack of 
Planning; c) Lack of Perseverance; and d) Sensation Seeking. Items will be rated on a 
4-point response scale ranging from 1 = “Not at all like me” to 4 = “Very much like 
me.” It has good psychometric properties (130). 
m. Monetary Choice Questionnaire (MCQ) (131) is a well validated and widely used self-
report measure of delayed reward discounting (DRD). Adolescents will make 27 
choices between smaller immediate rewards and larger delayed rewards.  
n. Anxiety Sensitivity Index – Revised (ASI-R): Anxiety sensitivity (AS) is a trait defined 
by fear of anxiety-related physical sensations (132, 133). The ASI-R is a 36-item self-
report measure assessing AS and is a revised and expanded version of the original 16-
item Anxiety Sensitivity Index (134). Individuals are presented with statements 
describing reactions to physical symptoms of anxiety (e.g. “It scares me when I feel 
faint”) and are asked to rate how strongly each item applies to them on a Likert scale 
ranging from 0 (“very little) to 4 (“very much”). Higher scores indicate greater AS, 
with scores ranging from 0 to 144. The ASI-R has demonstrated high internal 
consistency, good content validity, and adequate criterion validity in prior studies of 
nonclinical populations (135). Prior research suggests that AS is a distinct construct 
from trait anxiety and may contribute to the development or maintenance of a variety 
of psychological disorders, including social anxiety (136, 137). By assessing AS among 
a sample of healthy youth, we will be able to further examine the relationships between 
AS 
and 
other 
trait 
and 
state 
facets 
of 
anxiety. 
For participants who did not complete this questionnaire at screening, it will be 
completed at a later timepoint. Participants who have completed study visits will be 
contacted, re-consented and re-assented as required, and invited to complete the 
questionnaire via mail or the NIH Secure Email and File Transfer (SEFT) system. 
o. Supplemental Assessment (conducted only if the participant endorses items on the CDI 
or the DCSM suggestive of a DSM-5 disorder): 
The Schedule for Affective Disorders and Schizophrenia for School-Age Children 
(KSADS) (138). Portions of the KSADS will be used to assess psychiatric functioning 
and exclude participants with significant psychiatric co-morbidities that, in the opinion 
of the investigators, would impede competence or compliance or possibly hinder 
completion of the study. It will only be administered to participants who endorse a 
positive screen for depression, suicidal ideation, mania, psychosis, or substance use 
disorder on the DCSM. Individuals with these disorders will be referred for treatment 

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and excluded. Both current and lifetime history will be assessed. This measure is a 
reliable and valid diagnostic interview with good inter-rater reliability (93-100%) and 
excellent test-retest reliability for present and lifetime diagnoses of childhood and 
adolescent major depression, bipolar disorder, generalized anxiety, conduct disorder, 
and oppositional defiant disorder (k coefficients .77 to 1.00) listed in the DSM-IV-TR 
(139). See Appendix 7 for a copy of the KSADS.  
6. Parent study questionnaires. Parents/guardians will have access to computers and/or 
paper copies to complete these surveys about their child during their child’s visit (see 
Appendix 8 for measures). 
a. Child Behavior Checklist (CBCL) is a reliable and well-validated Child Behavior 
Checklist to assess their perceptions of their child’s internalizing and externalizing 
symptoms, as well as overall behavioral problems. 
b. Hollingshead Four-Factor Index of Socioeconomic Status (HI) (140) is a measure that 
assesses social status based upon four domains (marital status, employed status, 
educational attainment, and salary).  
c. Questionnaire on Eating and Weight Patterns – Parent about Child (QEWP-P-DSM-5): 
The QEWP-P-DSM-5 assesses parents’ perceptions of their children’s binge eating 
behaviors (141). This measure has been widely used and demonstrates sound 
psychometric properties (141). Items were modified slightly to ensure that criteria for 
binge eating disorder according to DSM-5 (102) are captured. 
d. Eating in the Absence of Hunger Questionnaire for Children – Parent Report about 
Child (EAH-P): Parents will report on their perceptions of their children’s EAH on the 
EAH-P. This form is a parallel version to the Eating in the Absence of Hunger 
Questionnaire for Children (EAH-C) (142). It consists of 14 total items from which 
there are 3 factor analytically-derived subscales that assess EAH in response to: i) 
Negative Affect (6 items), ii) External Eating (4 items), and iii) Fatigue/Boredom (4 
items). The EAH-P has demonstrated good internal consistency, convergent validity 
and temporal stability for all scales (143). The EAH-P also demonstrates good construct 
validity as parents’ reports of children's EAH in response to external cues has been 
significantly correlated with greater energy intake in laboratory EAH paradigms (120). 
Visit #2: Baseline Laboratory Session. The baseline lab will be scheduled within a week of the 
screening session. The baseline lab visit will be a half-day appointment that starts in the morning 
(from approx. 8AM to 1PM). Participants will be instructed to engage in an overnight fast starting 
at 10:00PM the night prior to the visit. The following procedures will take place:  
1. Phlebotomy. Blood will be drawn from participants by a phlebotomist or registered nurse 
for obesity-related measurements (e.g., acute care panel, hepatic panel, lipid panel, mineral 
panel, insulin, c-peptide, glycosylated hemoglobin, TSH, free T4, ESR, hsCRP), appetite-
regulating hormones (e.g., leptin, ghrelin, oxytocin), nutritional status (e.g., 25-
hydroxyvitamin D, iron), and hematological status (e.g., CBC), and samples to save for 
future research (75 mL). If desired, we will use ELA-Max cream so that the blood draw 
will hurt less. Total blood withdrawal will be within NIH pediatric guidelines (3.5mL/kg 

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per single draw, 7 mL/kg per 6 weeks) since participants will have minimum age 12y and 
will be eligible to join the study only if BMI exceeds the 85th percentile for age (BMI must 
be more than 20.9 kg/m2), weight will always exceed 40 kg; thus up to 140 cc may be 
obtained at a single blood draw. 
2. Standard breakfast shake. Participants will receive a standard breakfast shake, the 
amount of which (21% of estimated daily energy needs) is determined by measured body 
weight, height, age and average activity level in the previous week. The shake will consist 
of 17% protein, 16% fat and 67% carbohydrate. This is a standardized procedure to reduce 
the effect of hunger on AB to food. If the participant has lactose intolerance, lactase pills 
will be administered at the beginning of the visit or a lactose-free shake will be offered. 
3. Hunger/satiety and mood rating. Immediately before and after the breakfast shake, and 
after the food cue attention bias task, youth will rate their hunger and satiety states using 
the visual analog scales, ranging from 1 to 10 (“not at all” to “extremely). Mood will be 
assessed using the validated and reliable Brunel Mood Scale (BRUMS) (144, 145). The 
respondent indicates to what extent they feel a variety of different mood descriptors “right 
now.” The mood descriptors in the BRUMS are rated on 5-point Likert scales. Guilt, an 
emotion that may be particularly salient for LOC episodes (146), will be assessed using 
items from the Guilt subscale of the PANAS-X (147) following procedures from prior 
EMA studies (146). Copies of these measures can be found in Appendix 6. 
4. MEG Session with the Food Cue and Social Threat AB Visual Probe Task and Eye-
Tracking. Eligible youth will participate in both the food cue and the social threat AB task 
while undergoing the MEG scan (see Appendix 9). The order of exposures will be 
counterbalanced across participants. 
a. The Food Cue AB task (see Appendix 10) will consist of 180 trials in which pairs of 
color photographs are presented on a computer screen (10). Pairs are drawn from high 
palatable (HP) foods, low palatable (LP) foods, and non-food (NF) control stimuli 
consisting of emotionally neutral images of household items. Across the task, the 180 
trials were divided into three pairing categories (60 of each): HP-LP, HP-NF, and LP-
NF. There are 15 such pairings and each pair is presented 4 times with location of 
stimuli and location of probe fully crossed. The order of stimulus will be randomized. 
For each trial, stimuli are presented side-by-side (500 ms) after which both images 
disappear and a probe appears in a location previously occupied by 1 of the 2 pictures 
(500 ms). The probe consists of a left or a right arrow, and participants are instructed 
to press the left arrow button if pointing left, and the right arrow button if pointing right 
and told to respond as quickly and accurately as possible. To minimize automaticity, 
the inter-trial interval will be randomly jittered across 3 durations of 100ms, 150ms, or 
500ms.  
b. The Social Threat AB task (84) (see Appendix 11) will examine neural responses 
during a social threat visual-probe paradigm with angry, happy, and neutral faces (11), 
which have been used extensively in pediatric samples between the ages of 9-17 years 
(148-150). Normed face images will be taken from the NimStim Face Stimulus Set 
(151). Visual-probe paradigms assess attention bias by presenting stimulus pairs 

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followed by a probe that requires a response. Pairs of each face combination (angry-
neutral, happy-neutral, neutral-neutral) will be presented in randomized order. After 
the image pair disappears, a probe appears in one of the previously occupied photo 
locations. Youth respond with a right or left sided key-press to indicate the orientation 
of the probe. The response mapping of probe orientation will be counterbalanced across 
participants. Youth will be instructed to respond as quickly and accurately as possible 
to the probe. Trials consist of a mixture of incongruent trials (when the probe replaces 
the neutral face image), congruent trials (when the probe replaces the emotional face 
image), and neutral trials (when two identical neutral facial expression appear and the 
probe location is insignificant). 
c. Eye-tracking will be performed with the Tobii TX300. This system uses infrared 
reflections from the pupil and a 300 Hz camera and can withstand substantial head 
movements within a restricted area that eliminates the need for chin rest or other head 
restraint. Tobii software interfaces with Eprime, which enables flexible experimental 
design implementation. Duration, frequency and latency of fixations will be tabulated 
in each experimental condition and combined with reaction time (RT) measures. The 
combination of RT and visual fixation metrics will provide a detailed portrait of 
attention allocation under these experimental conditions.  
d. MEG Recording. Brain magnetic fields will be recorded with the 275-channel 
OMEGA system. Participants will sit in the magnetically shielded recording room with 
their heads in a helmet covered with 275 SQUID sensors. Head position within the 
magnetometer will be determined before and after each MEG session by digitizing the 
position of three indicator coils that are attached to the preauricular and the nasion 
fiducial points. The positions define the coordinate system for the signals and allow for 
post-hoc correction of head movement artifacts. Digital photographs of the fiducial 
points will also be taken to localize the same points on the participant's anatomical MRI 
scan. Consistent with prior MEG studies in pediatric samples and in populations not 
previously studied (84, 152), MEG data will be sampled at 600 Hz (bandwidth 0-150 
Hz). MEG recording will last for approximately 45 minutes (Appendix 9). 
5. Laboratory test meal. Youth will complete rating scales for hunger, fullness, state mood, 
and food craving (47, 48). They then receive tape-recorded instructions to “Let yourself go 
and eat as much as you want” from a multi-array test meal (9,835 kcal). This well-validated 
paradigm has been used in pediatric (47) and adult (52) studies. Rating scales are repeated 
post-meal. Consumption is calculated by weighing each item before and after the meal. 
Energy content and macronutrient composition for each item will be determined according 
to data from the U.S.D.A. Nutrient Database for Standard Reference and information 
supplied by food manufacturers. The sample meal is presented in a photograph in 
Appendix 12. 
6. An Anatomical MRI will be performed on one of the Clinical Center’s Phillips 3T 
scanners (MR2 or MR4). Standard imaging parameters will be used including acquisition 
of T1 weighted structural images for co-registration (see Appendix 9 for details on MRI 
acquisition and preprocessing). If the MRI scanner is not available during participant’s 

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second session, participants will be asked to return for a brief visit to perform the 
anatomical MRI scan. Contingent on the availability of the scanner, the participants may 
be scheduled to complete the anatomical MRI on a day separate from their study visit. They 
will be compensated for their time. A urine sample will be obtained from all participants 
and tested for pregnancy on the day of the participant’s anatomical MRI scan. If a 
participant has undergone an anatomical MRI scan at the NIH of sufficient quality in the 
preceding two months, she will not be required to complete another MRI anatomical scan 
as part of this study. 
7. Smartphone training. Participants will be given the mobile devices with attention 
retraining or the control program. Before they leave the laboratory, they will be trained in 
the use of the mobile devices and provided with contact information of the study staff to 
aid with troubleshooting of any problems that might arise. The training will take 
approximately 20 minutes. 
 
Attention Retraining or Control Program with Ecological Momentary Assessment (EMA) in 
the Natural Environment for 2 Weeks. Participants will be randomized in blocks of 8 with 
stratification for LOC status (LOC vs. no-LOC), race/ethnicity (Hispanic/Non-Hispanic, 
Black/White), and age (12-14; >14) to attention retraining or control programs carefully matched 
for intensity of interaction. In addition to three attention retraining or control trials administered 
on the smartphone each day, attention bias will be assessed once a day. Each of the four daily trials 
will also include an EMA component in which participants answer questions regarding their eating 
patterns and mood in real time. A sample administration schedule for a school day is presented in 
Figure 3. 
 
 
 
Figure 3. Sample administration schedule. 
 
On school days, youth will be signaled to complete AR/control trainings and EMA assessments 
pre-school (Training 1) and immediately post-school (Training 2). They will also be signaled 2 
more times (at random) between 3:30 pm (or end of school day) and bedtime, once for training 
(Training 3) and once for AB assessment (in random order). Bedtime will be set individually with 
each participant based on the participant’s and participant’s parent’s preference. Adolescents tend 
to go to sleep between 10:45PM and 11PM on school nights (153), therefore the latest bedtime 
offered will be 10:30PM. Bedtimes will be offered in 30-minute increments and the earliest 
bedtime available will be 7:30PM. ,. In sum, on each study day participants will be scheduled to 
complete 3 AR/Control trainings (80 trials each) and one AB assessment (40 trials). On non-
school days, the same schedule will be used except that the first training may be delayed by up 
to 2 h. A different picture set will be used on each day (order randomized over time), and 
assessments will occur using pictures on which youth were scheduled to receive training. With 

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>70% compliance, participants will complete ~30 AR/Control trainings during the two weeks, 
and AB will be assessed ~10 times during the study. 
1. Attention retraining / control program on smartphone. For the attention retraining task, 
the probe always replaces the neutral picture. There is a perfect correlation between picture 
type and probe location. Over time, individuals assigned to the attention retraining group 
should learn to attend away from the highly palatable pictures. For the control, the probe 
is equally likely to replace the food picture and the neutral picture. There is no correlation 
between picture type and probe location, and no training of attention should occur. This 
control has been used in previous attention retraining studies (154, 155). It ensures that: 1) 
the duration of attention retraining and control trials should not differ; 2) attention 
retraining and control participants receive equal practice on the motoric aspects of the 
visual probe tasks; and 3) attention retraining and control participants are exposed to the 
same food and neutral stimuli.  
2. Attention bias assessment on smartphone. Attention bias assessed via a visual probe task 
will be a difference score (measured in msec) reflecting the difference in response times to 
probes that replace highly palatable food with neutral stimuli. Attention bias data from 
assessments with >25% errors will be excluded. Following Kerst & Waters, an item will 
assess how many times the participant reported being interrupted during 
trainings/assessments (Response options: No, 1, 2, 3, 4+ times), so that data from 
assessments with a large number of interruptions can be excluded (155). On the attention 
bias assessments, faster responses to probes that replace highly palatable food pictures 
indicates an attention bias toward highly palatable food (i.e., attention has shifted to highly 
palatable food stimuli leading to faster responses on probes that replace highly palatable 
food), whereas faster responses to probes that replace neutral pictures indicates an attention 
bias away from highly palatable food.  
3. Ecological Momentary Assessment. LOC eating (“since the last assessment”) will be 
assessed during EMA with previous methods using items assessing the adolescent’s 
perceived “level of control,” “loss of control,” and the sensation of “out of control” if they 
ate (on a 1-5 scale, “No, not at all” to “Yes, very much,” with 4 or 5 on any item coded as 
presence of LOC eating).  Mood will be assessed using visual analog scales (see Appendix 
13 for a list of EMA questions). 
 
Visit #3: Post-Smartphone Program Laboratory Session. This visit will take place two weeks 
after Visit #2, at the conclusion of the 2-week attention retraining protocol. Procedures will be a 
combination of those from Visits #1 and #2, and will be conducted using the same methods and 
procedures described above:  
1. BMI and waist circumference. 
2. MEG Session with the AB Visual Probe Tasks and Eye-Tracking.  
3. Laboratory test meal. 
 
Visit #4: 3-month follow-up. This visit will take place approximately 3 months following visit 

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#3. Changes in weight/fat mass and eating behavior will be assessed at this visit. To increase 
retention, all girls will be offered the attention retraining program if they complete Visit #4. All 
the procedures will be conducted using the same method as in the previous visits: 
1. BMI and waist circumference; a urine sample will be obtained from all participants and 
tested for pregnancy in postmenarcheal girls. 
2. DXA scan. 
3. MEG session with the AB Visual Probe Tasks and Eye-Tracking. 
4. Laboratory test meal. 
5. Eating Disorder Examination (EDE), Version 14. 
 
AR for all: Attention Retraining with EMA in the Natural Environment for 2 Weeks. 
Participants will be offered the attention retraining program for two weeks as a “booster.” All 
participants will receive attention retraining at this point in the study. The attention retraining will 
be conducted using the same method as in the previous intervention.   
 
Visit #5: Post-AR for all follow-up. This visit will take place 2 weeks after Visit #4, at the end 
of the 2-week booster attention retraining intervention. All the procedures will be conducted using 
the same method as in the previous visits: 
1. BMI and waist circumference. 
2. MEG session with AB Visual Probe Tasks and Eye-Tracking. 
 
Visit #6: 6-month follow-up. This visit will take place approximately 3 months following Visit 
#5, and/or 6 months following Visit #3. All the procedures will be conducted using the same 
method as in the previous visits: 
1. BMI and waist circumference; a urine sample will be obtained from all participants and 
tested for pregnancy in postmenarcheal girls. 
2. History and physical exam as done in Visit #1 (see Appendix 14 for follow-up physical 
exam form). 
3. DXA scan. 
4. MEG session with AB Visual Probe Tasks and Eye-Tracking. 
5. Laboratory test meal. 
6. Eating Disorder Examination (EDE), Version 14. 
 
Study Discontinuation and Closure 
 
This study may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause.  Written notification, documenting the reason for study suspension or 
termination, will be provided by the suspending or terminating party to study participants, 
investigator, funding agency, and regulatory authorities.  If the study is prematurely terminated 
or suspended, the Principal Investigator (PI) will promptly inform study participants, the 
Institutional Review Board (IRB), and NICHD Clinical Director and will provide the reason(s) 

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for the termination or suspension.  Study participants will be contacted, as applicable, and be 
informed of changes to study visit schedule. 
 
Circumstances that may warrant termination or suspension include, but are not limited to: 
 
• 
Determination of unexpected, significant, or unacceptable risk to participants 
• 
Insufficient compliance to protocol requirements 
• 
Data that are not sufficiently complete and/or evaluable 
 
Study may resume once concerns about safety, protocol compliance, and data quality are 
addressed, and satisfy the NICHD Clinical Director and IRB. 
 
VII. Analysis of the Study/Oversight  
a. Study Administration and Data Collection, Management and Storage 
Roles and Responsibilities of Study Investigators and Key Research Personnel are specified in the 
Monitoring Plan (see below). Data collected from participants in this research study will be saved 
and may be used for future analyses related to eating behavior, attention bias and neural circuitry 
related to both. This testing may be done by research laboratories that are not at the NIH.  Prior to 
transfer of data to non-NIH collaborators, a material transfer agreement (MTA) with the outside 
institution will be established. The PI will provide the IRB with a listing of MTA’s that have been 
established under these provisions at the time of the Continuing Review, but including a record of 
each such collaboration in the study protocol.   
Data collected from all components of the current protocol will be coded with identifying 
information stored in a protected database to which only the NIH research team will have access. 
This code will be used for labeling samples and data for storage.  The purpose of retaining the code 
is to permit the NIH research team to link clinically-significant findings with a subject so that the 
subject can be informed and appropriate follow-up arranged if medically indicated and to allow 
for examination of additional research questions in the future. Scientific collaborators (non-
investigators), to whom coded samples and data may be sent for future studies, will not have access 
to subject names or other identifying information. If unauthorized disclosure of identifying 
information linked with samples or data occurs, the IRB will be notified by the Principal 
Investigator. 
The principal investigator and the co-investigators will have access to all identifiable participant 
records. Records containing personal identifiers will be maintained consistent with the security 
measures required by the NIH. We will follow guidelines developed by the NIH for projects funded 
by the Federal Government. Prior to managing data, all identifying information including name 
and address will be removed. 
The smartphone attention bias data and the ecological momentary assessment (EMA) data will be 
collected via the “Colors” software. “Colors” runs on a Windows-based or Android-based 
smartphones. The “Colors” software has been reviewed by Mr. William Hermach (NIMH ISSO) 
and received a Certification to Operate on February 18, 2016 (see Appendix 15). The smartphones 

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compatible with the “Colors” software will be purchased by the NICHD. The “Colors” program 
can administer reaction time (RT) tasks, individually or in combination, to include the visual probe 
(VP) task, Stroop, Implicit Association Test, Go No-Go task, and Rapid Visual Information 
Processing Task. A native code app is currently used, written in C# in the Windows Mobile 
environment. Data are collected in a local database and transmitted to the Cloud Server in near 
real time. De-identified participant and study profiles are created on the Cloud Server via a .NET 
browser based application. The “Colors” application data can be protected by 2048 bit SSL 
encryption for all participant submitted data. The administration of the application is protected by 
dual authentication to servers behind a network firewall. Reliability of reaction time and attentional 
bias assessed on mobile devices has been good (156, 157). An app in an ongoing attention 
retraining study of smokers using the proposed platform has generated nearly 10,000 completed 
trainings and assessments (as of December 2015). On this platform, the estimated internal 
reliability of mean reaction time computed using split-half r is >.95 (see also (156, 157). The 
program has been used successfully in non-smokers, smokers, heroin/cocaine addicts undergoing 
detoxification, and recovering alcoholics. The program has also been used successfully to 
administer attentional retraining (155). To the best of our knowledge, this is the most sophisticated 
software currently being used for the assessment of cognitive biases in ecological momentary 
assessment studies. The attention bias smartphone data will be co-managed by Dr. Andrew Waters, 
an Associate Investigator on this protocol, at the Uniformed Services University. The EMA data 
will be co-managed by Drs. Andrew Waters, an Associate Investigator on this protocol, at the 
Uniformed Services University. Dr. Scott Engel will provide consultation to the research team 
regarding the set-up of the EMA protocol, data collection, and analysis. Dr. Engel will have access 
to no identifiable participant information and will assist in interpretation of the data being collected 
throughout the study.  Consultation with Dr. Engel will occur primarily via phone and email, as he 
is located off-site at the Neuropsychiatric Research Institute in Fargo, ND. Dr. Crosby will provide 
statistical support working with de-identified data.  
Data from the MEG acquisition computer will be transferred to the analysis computer and then 
copied to DVD and external hard drive. DVD’s will be labeled with the assigned participant ID, 
date, and session type (i.e., social threat or food cue). Each participant’s data will be stored on the 
secure RAID serve for several weeks and then permanently deleted. All participant data files will 
be labeled with the participant’s ID. Electronic data will be password protected and accessible only 
by authorized study personnel. Electronic (de-identified) data will be backed up daily and stored 
at a secure server. All hardcopy data will be locked in Dr. Yanovski’s storage cabinets in research 
offices at the NIH CRC and will be accessible only by authorized study personnel. All data will 
be collected specifically for the purpose of the current proposed research project. 
Data will be stored for a minimum of 3 years after completion of analyses for this study.  
Furthermore, in compliance with federal law, records will be maintained until all subjects enrolled 
in the study have reached a minimum age of 23 years. Subjects may choose to withdraw from the 
study at any time and may request for stored data to be destroyed.  All withdrawals from the study 
will be documented and included in the annual report for continuing review by the IRB. 
b. Publication of Research Findings 
We estimate that several publications will result from this study; for example, comparison of 

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changes in neural responding and attention bias in LOC and No-LOC girls assigned to the AR vs. 
control condition, as well as the impact of these potential changes on eating behaviors and body 
composition over time. The impact of the booster intervention will also be evaluated. Findings will 
be submitted to peer-reviewed journals, and data will be deposited as required by governmental 
rules. 
c. Primary Outcomes 
Specific Aim 1: Examine change in attention bias following a 2-week attention retraining or 
control period. 
i. 
Primary outcomes: Change in laboratory measured attention bias (i.e., reaction times 
to palatable foods at the baseline laboratory visit vs. the post-EMA visit), 
ii. 
Secondary outcomes: Change in EMA-measured attention bias over time (2-week 
period), laboratory measured AB to social threat (i.e., reaction times to threatening 
stimuli at the baseline laboratory visit vs. the post-EMA visit), 
Specific Aim 2: Examine changes in neural responsivity following a 2-week attention retraining 
or control period. 
i. 
Primary outcomes: Change in neural activity during attention bias task paradigm 
at the baseline laboratory visit vs. post-EMA visit. 
ii. 
Secondary outcomes: Neural activity during the social threat AB task. 
Specific Aim 3: Examine the effect of attention retraining on food intake and body composition. 
i. 
Primary outcomes:  Change in the energy intake at the buffet meal, change in 
adiposity/body composition (DXA) from the baseline visit to the post-EMA visit. 
ii. 
Secondary outcomes: Change in self-reported eating patterns (EDE), number of 
LOC episodes measured via EMA and clinical interview,  
Exploratory Aim 1: Examine whether dose-response effects are present for attention bias to 
palatable foods and body composition in participants who receive the attention retraining program 
at 3 months as a booster compared to those who receive it for the first time. 
i. 
Primary outcomes: Change in laboratory measured attention bias (i.e., reaction 
times to palatable foods at the baseline laboratory visit vs. the post-EMA visit), 
adiposity/body composition (DXA) 
ii. 
Secondary outcomes: Change in EMA-measured attention bias over time (2-week 
period), self-reported eating patterns (EDE), number of LOC episodes measured via 
EMA and clinical interview. 
Exploratory Aim 2: Examine ABs to social threat (measured as reaction time, eye tracking, and 
neural activation on the AB to social threat visual probe task at baseline), and potential moderating 
effects of AB to social threat on intervention effects. 
i. 
Outcomes: Change in energy intake at the buffet meal, adiposity/body composition 
(DXA).  

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Exploratory Aim 3: Examine LOC status (LOC vs. No-LOC) on primary outcomes. 
i. Outcomes: Change in neural activity during attention bias task paradigm at the 
baseline laboratory visit vs. post-EMA visit, change in laboratory measured 
attention bias (i.e., reaction times to palatable foods at the baseline laboratory visit 
vs. the post-EMA visit), change in food intake, change in adiposity/body 
composition (DXA) 
Exploratory Aim 4: Examine effects of race on primary outcomes. 
a. Outcomes: Laboratory measured attention bias (i.e., reaction times to palatable foods 
at the baseline laboratory visit vs. the post-EMA visit), the energy intake at the buffet 
meal, adiposity/body composition (DXA). 
d. Reasons for Withdrawal/Adverse Event Reporting: Participants will be examined briefly on 
the phone during the initial screening, and more extensively during the screening visit (Visit #1) 
as well as the follow-up visits. Participants will be excluded and/or referred for treatment if 
appropriate, as previously described. Identification of a current and significant psychiatric disorder 
at the time of enrollment will result in an appropriate referral to a mental health professional and 
study exclusion. Noncompliance with study procedures may lead to withdrawal of study 
participants. Other events that may lead to study withdrawal include pregnancy or serious 
unanticipated complications, including development of any medical problem listed in the 
exclusion criteria. Please see Section 16: Reporting of Unanticipated Problems, Adverse Events 
and Protocol Deviations for more details regarding adverse event reporting. 
 
f. Determination of Sample Size and Analytic Plan 
Sample Size: Sample size estimation is based on the power analysis for the first Specific Aim. 
This is a pilot study to test a novel promising intervention for a targeted group of youth at high 
risk for adult obesity. Eighty overweight girls, 40 with LOC eating and 40 without LOC eating, 
will be randomized, out of 120 recruited. Meta-analytic studies of AR effect on attention bias (e.g., 
to appetite [food, alcohol], or threatening stimuli) in adults found large effects of AR (d = .80–
1.41) on attention bias reductions (96, 97) and medium effects (d = .51-.61) of AR on behavioral 
outcomes (96, 97). Based on recommended equations for estimating sample size (158, 159) when 
using general linear model, and assuming 35% attrition due to unusable visual probe or MEG data 
(based on pilot data and prior MEG studies in youth), this sample size will provide >80% power 
to detect  medium to large effects (83, 152, 160). 
 
Preliminary Analyses: 
1. Anatomical MRI data processing will be done with AFNI software (see Appendix 9). 
Structural scans will be spatially normalized to standard Talairach space. 
2. Raw MEG data will be filtered using third gradient reference coils with fixed weights. A 
broad frequency band (1-30 Hz) will be used for primary analyses, following procedures 
from prior MEG studies in new populations (83, 152, 160). Fixed frequency smoothing 

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and transformation will be applied to obtain oscillatory power estimates. Oscillatory power 
activity will be calculated by subtracting the baseline activity (1000ms immediately prior 
to stimulus onset) from the activity evoked during the UCR and AD periods, respectively 
(84). The synthetic aperture magnetometry (SAM) beamformer technique (161) will be 
applied to produce a 3D representation of brain activity by calculating the oscillatory power 
activity for individual voxels (7 mm). Using the anatomical MRI, normalized SAM data 
will be co-registered and transformed into Talairach space in AFNI software. Based on our 
hypotheses, a priori brain regions will be selected for examination. Pseudo F-ratios – an 
index of 3D oscillatory power activity – for the regions-of-interest will be used in analyses 
(see Appendix 9). 
3. EMA data will be collected using a specialized platform designed to collect EMA on 
mobile devices. Data are collected in a local database and transmitted to the Cloud Server 
in real time. Participant and study profiles are created on the Server and exported from the 
Server by an administrative user. On this platform, the estimated internal reliability of mean 
RT computed using split-half r is >.95 (156, 157). 
4. Missing Data and Attrition: AR and control will be compared on study completion vs. early 
termination using logistic regression controlling for age, sex, race, lean mass, adiposity, 
and height (“covariates”). Multiple imputation based upon fully conditional Markov chain 
Monte Carlo modeling (162) will be used to impute missing data on non-EMA 
assessments. Primary analyses will be based upon imputed data except for EMA analyses. 
Sensitivity analyses will use all available data (i.e. no imputation) and maximum likelihood 
imputation and results will be compared across methods. Although data preprocessing and 
analytic methods can mitigate artifacts to some extent, excessive participant movement 
remains a problem. Structural MRI / MEG will be excluded if there is movement > 2.5 mm 
during respective sessions. At NIH, pediatric fMRI / MEG studies typically have 30-40% 
attrition in youth due to excessive movement. Thus, attrition rate of 35% is assumed in 
power analyses. 
 
Primary Analyses: 
Specific Aim 1 
a. Hypothesis 1: Youth randomized to AR and control conditions will be compared on: 
1. Post-smartphone program lab visit and the 3-month follow-up visit reaction time 
data from dot probe task will be  using a general linear model (or appropriate 
generalized linear model depending upon distribution diagnostics) controlling for 
baseline visit reaction time data from dot probe task, and covariates (order effects, 
age, race, and BMIz). 
2. Reaction time data from EMA 
Specific Aim 2 
a. Hypothesis 2: General linear model adjusting for baseline neural activity and covariates 
(order effects, age, race, and BMIz), will be used to analyze  

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1. Post-smartphone visit amd 3-month follow-up visit neural activity in response to 
palatable food cues in the “bottom-up” attention circuitry (ventral ACC, OFC, 
insula, and striatum) in the unconscious reaction period. 
2. Post-smartphone visit and 3-month follow-up visit neural activity in response to 
palatable food cues in the “top-down” attention circuitry (dorsal ACC, vlPFC, 
dlPFC) in the attention deployment period. 
 
Specific Aim 3 
a. Hypothesis 3A: Youth randomized to AR and control groups will be compared on  
1. Post-smartphone program lab energy intake from laboratory test meal using a 
general linear model (or appropriate generalized linear model depending upon 
distribution diagnostics) controlling for the baseline visit energy intake and 
covariates 
2. The daily number of LOC episodes using a generalized estimating equations (GEE) 
model with a negative binomial response function controlling for baseline LOC 
episodes and covariates. The model will include a main effect for group, and a 
group-by-time interaction. Analyses use all available data (no imputation). We will 
also examine LOC as a continuous daily dependent variable (mean of 3 LOC 
items). 
3. BMI and adiposity at the 3-month follow-up visit using a general linear model (or 
appropriate generalized linear model depending upon distribution diagnostics) 
controlling for baseline lab visit and the post-smartphone program lab visit BMI 
and adiposity. 
Exploratory Aim 1 
a. Youth randomized to AR (who receive the AR program at 3 months as a booster) 
will be compared to controls (who receive AR for the first time) at post-booster 
visit and the 6-month follow-up visit on BMI, adiposity, and energy intake using a 
general linear model (or appropriate generalized linear model depending upon 
distribution diagnostics) controlling for Visit #2 measurement 
Exploratory Aim 2 
b. Moderation analyses will be conducted using reaction times from the baseline 
social threat AB task as well as neural correlates of social threat ABs when the 
outcome variable is change in AB to food cues following the intervention, energy 
intake, and body composition. 
Exploratory Aim 3 
c. Moderation analyses will be conducted considering LOC status (LOC vs. no-LOC) 
when the outcome variables are: change in neural activity, change in reaction times 
on the food AB task, and change in food intake during the laboratory test meal from 

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baseline to post-intervention/3-month follow-up in AR vs. control condition, as 
well as and change in body composition from baseline to 3-month follow-up in AR 
vs. control condition.  
Exploratory Aim 4 
d. Moderation analyses will be conducted considering race (Black vs. non-Black) 
when the outcome variable is AB to palatable food, energy intake, and 
adiposity/body composition. 
 
VIII. Human Participant Protection  
a. Rationale for Subject Selection 
Girls ages 12-17 years with BMI ≥ 85th percentile are included in the present study. To test the 
effects of the intervention on particular subtypes of overweight youth, half of the participants will 
have to endorse LOC eating episodes. The rationale for the inclusion of youth between the ages of 
12 and 17 years is because LOC eating behaviors often emerge during this developmental period 
(163-165). Adolescence is also a period when many disordered eating patterns manifest, 
particularly among girls (16). Youth who endorse even infrequent LOC episodes are at higher risk 
for gaining excess weight in prospective studies (40, 100), placing them at risk for developing 
more severe health complications of the cardiovascular and endocrine systems in later life. 
Understanding the mechanisms of eating behaviors and designing more effective interventions to 
decrease excessive food intake and reduce excess weight among adolescents are thus of paramount 
importance. The proposed study, of a novel and age-appropriate intervention, develops a targeted 
approach that may hold promise for wide dissemination. Targeted therapeutic approaches for 
subgroups with specific phenotypes have been recommended (17), and have the potential for 
greater effects. Should this pilot study have positive results, other groups, including boys and 
younger children, should be studied. 
Youth of all races and ethnicities will be eligible. LOC eating is reported with similar prevalence 
among Non-Hispanic White and minority groups including Non-Hispanic Black and Hispanic 
youth (44, 45). Of particular concern are data indicating that childhood obesity rates have increased 
dramatically among Hispanic and Non-Hispanic Black youth (1, 46). Thirty-six percent of Non-
Hispanic Blacks (2-19y), for example, are currently overweight or obese compared to 32% of Non-
Hispanic White youth (166). Non-Hispanic Blacks remain at a higher risk for serious obesity-
related health comorbidities (46, 167). Some laboratory studies have found that Black girls 
consume more during a laboratory meal compared to their non-Black counterparts (45). Despite 
these important racial/ethnic variations in weight-related concerns, there are limited data on eating 
behavior-related endophenotypes for pediatric obesity among non-White youth. Historically, non-
White girls have been underrepresented in psychological research, and limited sample sizes may 
preclude meaningful investigations of racial/ethnic differences. Our previous studies have 
consistently attracted about equal proportions of Non-Hispanic White and Non-Hispanic Black 
youth. It is expected, given our recruitment procedures targeting individuals living in the greater 
metropolitan Washington D.C. area, that we will recruit similar rates of minority participants. 
Indeed, Washington, D.C. is very diverse: 35% Non-Hispanic White, 48.8% Non-Hispanic Black, 

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9.9% Hispanic, and 3% Asian, among others. Therefore, we expect to continue our ability to recruit 
substantial numbers of racially/ethnically diverse youth (see Planned Enrollment Table for 
estimates of minority enrollment).  
b. Participation of Children and Other Vulnerable Populations 
The study involves many procedures that have previously been approved by IRBs as minimal risk, 
including anthropometric and body composition measurements, psychological testing, brain 
imaging, and laboratory cognitive tasks. The cognitive tasks and questionnaires are of no greater 
risk than that of taking a mathematics examination at school. The physical measurements are 
likewise not considered to be outside of usual activities that children normally undergo. The 
protocol takes into account psychological as well as physical discomfort, and provisions have been 
made for soliciting the assent of children and the permission of parents. The PI and all members 
of the study team will emphasize to participants that they are able to withdraw from the study at 
any time without penalty. All participants are carefully debriefed and written procedures for 
managing unusual circumstances (e.g., subject distress or suicidality) are in place. We request that 
consent from one parent is sufficient unless there is joint legal custody for medical decision-
making of a child, in which case both parents must give their permission. Exceptions may include 
if one parent has since died, become incompetent, or is not reasonably available. Consent forms 
include waivers of confidentiality for suicidality, homicidal ideation, and child and elder abuse, 
for which we are mandated reporters. The screening portion of the study protocol will begin with 
a discussion of confidentiality and its limitations. Specific written procedures have been developed 
for handling cases that necessitate a breach of confidentiality. Children’s screening questionnaires 
and interviews will be reviewed by a research team member conducting the appointment before 
participants leave the NIH. Participating youth will be immediately referred for a psychiatric 
consultation at the NIH and referred for outside treatment as recommended if the child endorses 
suicidality or psychosis at any point. The study team will work with the psychiatrist to ensure that 
all distressed participants are given a list of referrals that include hotlines and crisis centers, and 
we also will facilitate referrals to counseling services if the situation calls for this. Depending on 
the individual circumstances, the appropriate authorities such as a parent/guardian will be 
contacted. Jack Yanovski, MD, PhD or Marian Tanofsky-Kraff, PhD will be immediately 
contacted for consultation if suicidality, suspected child abuse, or homicidal ideation issues arise. 
Suspected child abuse is reported to Social Services; the Social Work department will be contacted 
to assist with needed evaluation and referrals. Given the small and temporary nature of risks posed 
to participants, we believe that the knowledge to be gained outweighs the risks and inconveniences 
of this study. 
c. Screening Methodology 
A number of methods will be used to screen for the psychiatric and health concerns noted above, 
including a brief phone screen (during which we will ask parents/guardians about their children’s 
psychiatric and medical concerns) and a screening visits at the Clinical Center (during which a 
medical and psychiatric history interview and physical exam will be conducted, and a 
questionnaire assessing DSM-5 psychological disorders will be administered). Research staff 
facilitating the psychiatric interviews will review youths’ surveys for critical item endorsement 
(e.g., suicidal ideation) and follow-up as appropriate. If suicidality is endorsed, research staff will 

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conduct a follow-up evaluation to determine the appropriate course of action (i.e., referrals for 
treatment or request onsite psychiatric consultation). Urinary analyses will be used to ensure that 
postmenarcheal girls are not pregnant. If they are, they will not be eligible to participate in the 
current study. Parents will be informed that girls who are found to be pregnant become 
emancipated minors for the purpose of health care decision-making, and that the child, not the 
parent, will be told about a positive pregnancy test. 
 
d. Risk/Benefits Analysis 
Risks: We do not anticipate that the current study will pose serious risks to participants’ physical 
or psychological/emotional health. Potential mild risks and inconveniences are:  
1. The completion of questionnaires, behavioral paradigms and interviews involves no 
appreciable risk. However, it is possible that participants may experience slight discomfort 
as a result of being asked to fill out questionnaires or respond to queries about stress, mood, 
and eating. They may also become frustrated while completing the behavioral tasks 
designed to assess their attentional processes. If the wording of some questions makes the 
child uncomfortable, the participant is not required to answer that particular question. 
Similarly, participants will be informed of their right to not complete any test or task during 
any visit. Additionally, questionnaires, behavioral paradigms and interviews may cause 
inconvenience because of the time required for testing.  
2. Psychiatric issues. If, based upon the study team’s opinion, there is evidence of the 
development of a serious psychiatric disorder or signs of suicidality, participants (including 
children and parents/caregivers) will be immediately referred for a psychiatric consultation 
at the NIH and referred for outside treatment as recommended. If a participant is in need 
of an urgent evaluation (e.g., is actively suicidal with a plan to carry out such actions) while 
on the NIH premises, an on-call NIH attending psychiatrist will be contacted for an 
immediate consultation and intervention until the participant can be safely referred for 
outside treatment.  
3. Confidentiality of discussions during the screening, experimental, and ecological 
momentary assessment portions of the study will be honored. The materials obtained from 
the participants will be used exclusively for this research project. All personal information 
on participants will be kept confidential and stored in locked filing cabinets and password 
protected computers in the laboratory and offices of Dr. Yanovski. All offices are secured 
with locks. However, each participant will be informed that if the PI or any other study 
team member learns of any planned actions or current behaviors that may be detrimental 
to his/her health or the safety or health of others, the information will be shared with the 
participant’s parent/guardian and/or the appropriate authorities.  
4. Body fat measurements by dual-energy x-ray absorptiometry (DXA) have no 
significant known risk, other than the inconvenience of the time required. Volunteers 
undergo DXA scanning using the iDXA system (GE Healthcare, Madison WI). To perform 
the DXA scan, the subject will be placed between the collimated X-ray source and the 
detector. This is achieved by having the subject lie down on a cushioned table and 

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remaining still for 5-10 minutes. The X-ray source and detector are contained in a C-arm 
construction that is moved to cover the participant. At all times, the child can see, and be 
seen by, a person standing nearby. A parent may safely be in the room and be in visual and 
auditory contact with the child. The participant is also in constant voice contact with the 
operating personnel. Fat, bone, and muscle will be determined during a total body scan. An 
external standard, simulating bone, fat, and muscle, is scanned along with the participant. 
This standard allows calculation of total body fat, muscle, bone, and percentage body fat. 
DXA involves passing a collimated X-ray beam of 45 and 105 keV through the subject and 
collecting the X-rays that pass through the participant with a standard X-ray detector. Since 
the delivery and attenuation of the X-rays are measured separately for the two principal 
energies, the procedure allows the differentiation of substances in their path if the 
attenuation coefficients of these substances are known. According to the manufacturer’s 
specifications, DXA scanning for body composition using the array beam delivers 0.003 
mrem total body radiation.  
5. Radiation exposure. This research study involves exposure to radiation from three DXA 
scans (at baseline, 3-months, and 6-months). This radiation exposure is not necessary for 
medical care and is for research purposes only. Although each organ will receive a different 
dose, the total amount of radiation exposure participants will receive yearly from this study 
each year is equal to a uniform whole-body exposure of 0.009 mrem for child subjects This 
calculated value is known as the “effective dose” and is used to relate the dose received by 
each organ to a single value. The amount of radiation participants will receive in this study 
is well below the dose guideline established by the NIH Radiation Safety Committee for 
child (less than 500 mrem per year) or adult (less than 5000 mrem per year) research 
subjects. For comparison, the average person in the United States receives a radiation 
exposure of 300 mrem per year from natural background sources, such as from the sun, 
outer space, and from radioactive materials that are found naturally in the earth’s air and 
soil. The effective dose that participants will receive from participation in this research 
study is less than the amount normally received in one day from these natural sources. For 
more information about radiation and examples of exposure levels from other sources, 
participants will, upon request, be given a copy of the pamphlet called, An Introduction to 
Radiation for NIH Research Subjects. This protocol has been submitted for approval by 
the Radiation Safety Committee. 
6. Urine collection methods involve no risk but may be inconvenient because of the time 
required for collection. If participants have difficulty voiding, they will be offered water 
and asked to try again at a later time. Parents will be informed that girls who are found to 
be pregnant become emancipated minors for the purpose of health care decision-making, 
and that the child, not the parent, will be told about a positive pregnancy test. 
7. Phlebotomy procedures involve <75 mL of blood withdrawal once over the course of the 
study, which is below the NIH guideline for a safe amount of blood withdrawal. This 
guideline is based upon body weight, and for a 70 pound child, the maximum amount of 
blood that can be taken is 1⁄2 pint (225 mL) every six weeks. Drawing blood may be 
painful, and a small bruise may form at any site where the blood is taken. The risk of 
infection or fainting is very small. Inflammation or clotting of a vein also may rarely occur. 

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We will offer ELA-Max cream in an effort to reduce any pain. An area of white or a red 
rash that usually goes away within a few hours may be seen after use of ELA-Max. 
8. Structural MRI. Individuals are at risk for injury from the MRI magnet if they have 
implanted electrical devices, brain stimulators, some types of dental implants, metallic 
prostheses (including metal pins and rods, heart valves, and cochlear implants), aneurysm 
clips, permanent eyeliner, implanted delivery pumps, or shrapnel fragments. For this 
reason, participants will be screened for these contraindications before having any scan. If 
they have any risk for injury, they will not receive an MRI scan. In addition, all magnetic 
objects (for example, watches, coins, jewelry, and credit cards) must be removed before 
entering the MRI scan room. Individuals with fear of confined spaces may become anxious 
during an MRI. The noise from the scanner is loud enough to damage hearing; therefore, 
participants having an MRI scan will be fitted with hearing protection. On the day of the 
MRI scan, a urine sample will be obtained from all participants and tested for pregnancy. 
There are no known long-term risks of MRI scans.   
9. Magnetoencephalography (MEG) recording is not associated with special risks or 
inconveniences. MEG recording is a risk-free, non-invasive technique. The sensory stimuli 
(images of objects and food) are carefully controlled and well below discomfort or seizure 
inducing levels. However, some youth might get anxious during the recording, from being 
in a new testing environment, or might find the 20-minute attention bias paradigm stressful 
or tiresome. Prior experience with 37 anxious and non-anxious children and adolescents 
indicate that the MEG session is not distressing. Similarly, prior experience with 103 
children and adolescents has revealed no such instances of distress during either of the 
attention bias paradigms using social threat and food cue stimuli. There could be mild 
discomfort with cleaning the scalp to put the electrodes on or with washing hair after the 
test. Should a participant become distressed, a psychiatrist or on-call attending will be 
available.  
10. Attention Retraining (AR)/Control and Ecological Momentary Assessment (EMA) on 
the smartphone, as implemented in the current protocol, should involve no risk. 
Participants’ EMA responses are password protected to ensure the security of the 
information they provide. A participant may be asked why she is responding to one of the 
scheduled recordings in the study. Study staff will discuss this possibility and brainstorm 
with the participant what an acceptable response may be for her in this situation. It is 
possible that someone could see a participant’s responses by taking the phone away or 
peering over a shoulder before he or she finishes submitting responses. Participants may 
feel uncomfortable if someone else sees their responses. As such, participants will be 
encouraged to respond in a private setting. Research staff as needed, will stay in close 
contact with the participants during the two weeks of momentary data collection. If the 
participant has any problems or concerns, she can contact study staff immediately. 
11. Food ingestion under controlled conditions involves no risk and is not expected to cause 
any participant discomfort. Participants who indicate they do not like the foods to be 
offered will not be studied. Participants will feel somewhat hungry and possibly irritable if 
they typically eat before approximately 9-10AM, when the breakfast shake is roughly 

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scheduled to be administered. When conducting feeding studies, participants may suffer 
from food allergies that restrict the types of foods they are able to eat. If the participant has 
lactose intolerance, lactase pills will be administered at the beginning of the visit. Similarly, 
certain ethical and religious beliefs may limit participants from eating foods on the array. 
In these cases, we will substitute foods that are of equivalent nutritional value and within 
the same food group. The proposed study will be carried out at the NIH CRC, where there 
are ample medical resources (including the NIH critical care team) should an unanticipated 
event occur. Metabolic cooks preparing and measuring foods for test meals have yearly 
HACCP food safety training that focuses upon safe food handling, proper temperatures, 
hand washing, and using gloves when handling food. All dietitians also have had training 
in weighing/processing foods for controlled feeding studies to ensure consistency in the 
method and presentation.  
12. Time required. Time commitment will vary depending on the parts of the study 
participants decide to participate in, as well as eligibility. The screening visit (Visit #1) 
requires approximately 5 hours on the part of the study participant and their 
parent/guardian. If they are eligible following this visit, youth will be asked to return to the 
NIH CRC within one week for a baseline laboratory session (Visit #2) to participate in the 
attention bias and MEG component of the protocol. This visit will take approximately 4 
hours to complete. At the end of that visit, youth will receive instructions on completing 
the attention training and EMA portion of the protocol using the smartphones. For that 
portion of this protocol, youth will be asked to respond to various prompts on their 
smartphones 4x/day for approximately 5 minutes, for 14 days. Estimated time required to 
respond to all of these prompts is 20 minutes per day (for a total of 280 min or nearly 5 
hours). Time commitment for the post-EMA visit (Visit #3) is approximately 4 hours, 4 
hours for follow-up 1 (Visit #4), and 4 hours for follow-up #3 (Visit #6).  
 
Participants and their parents/guardians will be informed in detail of all potential risks during the 
informed consent/assent process.  
Benefits: While the psychiatric screening measures and the structural MRI scan may uncover 
potential health problems, these procedures are not intended to provide participants with 
information above and beyond data gleaned from their providers’ standard health-related 
assessments. The attention retraining program is an experimental intervention, thus a change in 
eating patterns as a result of participation cannot be guaranteed. Thus, individuals may not directly 
benefit from participating in the current protocol. Nonetheless, this research has the potential to 
help others by defining risk factors for excessive weight gain among children. This research has 
the potential to inform prevention and intervention efforts for a significant subset of children. 
Assessment of Risk/Benefit Ratio: Overall, there are a number of potential benefits, not just to 
study participants but also to the larger population of child and adolescent girls who are at higher 
risk for excessive weight gain by virtue of their engagement in disinhibited eating behavior. The 
risks for participants include possible distress related to thinking about mood and problematic 
eating behaviors. We do not anticipate this to occur in most participants, and frequent contact with 
participants during the study visits will enable early detection of potential distress in study 

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participants. If a participant reports, or demonstrates symptoms suggestive of, increased distress 
related to her participation in the study, the study team will consider whether it is in her best interest 
to continue study participation. Participants have the right to withdraw from the study at any time. 
For both physical and psychological problems, study participation will enable the participant to be 
screened for clinically-significant pathology, and in cases where identified, may facilitate 
treatment.  
In the literature, there are reports of healthy children who have undergone each of these tests in 
IRB-approved studies. Individually, all of the procedures proposed as part of this protocol are of 
low risk. The investigators have further taken many steps to minimize potential discomfort, for 
instance by providing the lead investigators’ extensive contact information to the participant in the 
event that problems arise outside of office hours while completing the EMA assessments. 
Furthermore, children are routinely required to complete cognitive tests during school. We believe 
the study outlined in this protocol is reasonably commensurate with those children may be exposed 
to in their actual or expected medical, dental, psychological, social, or educational experiences. 
Additionally, all participants are offered the attention retraining program at their 3-month follow-
up, regardless of their original group assignment at baseline. This is to ensure that all participants 
may receive the potential benefit of this experimental program. We therefore believe that the 
benefits to both individual participants as well as the larger population of adolescents with eating-
pathology outweigh the risks to individual participants. 
We believe that the IRB should indicate that permission of one parent is sufficient for this research 
to be conducted. 
Alternatives to Participation: Participants in this study may receive a brief experimental 
intervention – an attention retraining program – or a control program. They will be randomly 
assigned to either the intervention or the control condition in a double-blind design. At the 3-month 
follow-up (Visit #4), participants will be offered a booster intervention and if they elect to complete 
it, and all participants will receive the intervention regardless of the initial group assignment.  
Participants and their families will be informed that they may be eligible for other studies in 
children who are at risk for adult obesity. The study team will inform the participants of any such 
studies taking place at the NIH. They will also be provided with the link to www.clinicaltrials.gov 
to review the ongoing clinical studies. For participants interested in treatment for mood, disordered 
eating or weight management, treatment referrals will be provided. 
e. Privacy and Confidentiality 
Data obtained from the participants will be used exclusively for this research project. Samples and 
data will be coded. The PI and the co-investigators will have access to identifiable participant 
records. Records containing personal identifiers will be maintained consistent with the security 
measures required by the NIH. We will follow guidelines developed by the NIH for projects funded 
by the Federal Government. Prior to managing data, all identifying information including name 
and address will be removed. All data for the project will be processed and stored by the study 
team. Electronic data will be password protected and accessible only by authorized study 
personnel. Electronic (de-identified) data will be backed up daily and stored at a secure server. All 
hardcopy data will be locked in Dr. Yanovski’s storage cabinets in research offices at the NIH 

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CRC and will be accessible only by authorized study personnel. All data will be collected 
specifically for the purpose of the current proposed research project. Finally, despite that a number 
of precautions will be taken to ensure participant confidentiality, data collection in any study is 
accompanied by threat to privacy and confidentiality. Precautions to be taken against violation of 
confidentiality are described.  
Participants will receive mobile devices (i.e., smartphones) that they will be asked to carry with 
them and complete assessments, either self-initiated or randomly signaled, as part of the ecological 
momentary assessment (EMA) portion of the protocol. Regarding AR/Control Program and EMA, 
Dr. Waters has worked closely for a number of years with a Houston-based company to develop 
the “Colors” software to administer cognitive assessments and cognitive interventions using EMA. 
The “Colors” software has been issued a Certification to Operate by the NIMH ISSO on February 
18, 2016 (see Appendix 15). The software can administer reaction time tasks on mobile devices, 
individually or in combination, to include the visual probe task to measure attention bias, Stroop, 
Implicit Association Test, and Go No-Go task.  For the proposal, a “native code" app will be used, 
written in C# in the Windows Mobile environment, using an Android-based smartphone. Data are 
collected in a local database and transmitted to the Cloud Server in realtime. De-identified 
participant and study profiles are created on the Cloud Server via a .NET browser based 
application. The “Colors” application data can be protected by 2048 bit SSL encryption for all 
participant submitted data. The administration of the application is protected by dual authentication 
to servers behind a network firewall. The smartphones that participants receive for the duration of 
the study will be purchased by NICHD. 
All research activities will be conducted in as private a setting as possible. Only the staff essential 
to the research procedures will be present during the visits. 
f. Research and Travel Compensation 
Participants will be compensated for any burden endured via study participation, including time 
and inconvenience. Adolescents will receive $70 for each visit, for a potential total of $420. The 
check for each session will be sent upon completion of the procedures for the respective session. 
Participants also receive up to $172 for completing the training program: $30 per week (if at least 
80% of assessments are complete) and $2 for each completed smartphone assessment (there are 
56 assessments total). This applies to the baseline program and the “booster” program 3 months 
later, for a potential total of $344. This amount is calculated when the participant returns to NIH 
for the post-EMA session and the check is sent when the procedure for the respective post-EMA 
sessions are completed. The total compensation that the participants may receive as a result of 
completing all the procedures in the study is $764. Additionally, some participants may be 
scheduled for the anatomical scan on a day separate from their study visit, contingent on the 
availability of the scanner. Those participants will be compensated an additional $50 for their time 
and inconvenience. If a participant withdraws early from any component of the study, she will be 
paid $20 per hour of study protocol completion. 
g. Consent/Assent Process and Documentation 
In obtaining and documenting informed consent, all study staff will comply with applicable 
regulatory requirements (e.g., 45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56) and will adhere 

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to ICH GCP. 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the 
study and continues throughout the individual’s study participation. Consent and Assent forms will 
be Institutional Review Board (IRB)-approved and the participant (and/or parent/guardian) will be 
asked to read and review the documents. The principal investigator or associate investigators/Key 
Study Personnel with appropriate expertise will obtain written, active consent before the Screening 
Visit or as the first activity conducted at the Screening Visit (Visit #1). The purpose of the project, 
all testing procedures, and study components, and of their rights as research participants, will be 
described in detail in terms suited to the participant’s comprehension. Potential participants will 
be informed that the purpose of the study is to explore how the brain works during cognitive tasks 
and whether training attention away from unhealthy foods might help youth consume less of those 
foods. The NIH informed consent and assent forms will be signed. Potential participants and their 
parents will also be informed of the possible risks and inconveniences of the study. The 
investigator will answer any questions that may arise. The investigator will also explain the study 
assent form to minors using appropriate language. Sufficient time and opportunity will be given 
for discussion of the research as well as to answer any questions all may have, taking care to 
minimize or eliminate the perception of coercion or undue influence. Consent forms include 
waivers of confidentiality for suicide, child abuse, and homicide, for which we are mandated 
reporters. 
Participants will have the opportunity to carefully review the written consent form and ask 
questions before signing. The participants will have the opportunity to discuss the study with their 
family or surrogates and given time to think about it prior to agreeing to participate. The participant 
(or parent/guardian) will sign the informed consent document prior to any procedures being done 
specifically for the study. Participants will be informed that participation is voluntary and that they 
may withdraw from the study at any time, without prejudice. The rights and welfare of the 
participants will be protected by emphasizing to them that the quality of their medical care will 
not be adversely affected if they decline to participate in this study. The informed consent form 
(and assent if applicable) will be signed before the participant undergoes any study-specific 
procedures. The investigator-designated research professional obtaining the consent (and assent if 
applicable) must also sign the informed consent and assent form (if applicable). A copy of the 
informed consent/assent documents will be given to the participants for their records. The 
informed consent process will be documented in the medical record (including the date), and the 
original completed forms will be kept in the participant’s medical record with a copy in their 
research chart. 
Informed consent documents (and assent documents, if applicable) may be printed to sign and date 
in ink, or the electronic documents may be signed with a hand signature using a finger, mouse or 
stylus via an approved platform. Participants may be asked to complete the consent process 
electronically via iMed and Docusign, which are both 21 CFR Part 11 compliant.  Once identity 
is confirmed, consents can be electronically signed, date-stamped, and routed to the PI for 
electronic signature. Once the PI has logged into the secure site and digitally signed the consent, a 
pdf of the signed consent is created. As is done for forms signed in ink, the participant will be 
provided with a copy of the signed document, and can also contact our study staff to obtain a hard 
copy of the consent at any point in this process. 

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Parents or guardians will be given a signed copy of the consent and assent form for their records. 
Youth will be required to sign an informed consent form confirming their desire to continue their 
participation in the current protocol should they turn 18 years during the course of the study. In 
the unlikely event that the parents/guardians of protocol-eligible subjects cannot travel to the NIH 
Clinical Center for a considerable period of time, the PI or other protocol staff designated to obtain 
consent will obtain informed consent by a telephone conversation. Consent may be obtained via 
telephone and/or another electronic process, rather than in person. In such cases, the written signed 
consent will be faxed and/or mailed and made part of the patients' NIH records. No research 
procedures will commence until the investigator has confirmed that written, legally effective 
consent has been obtained. 
For assent of children 
 
All adolescent participants are expected to be able to comprehend and be included in all 
discussions about the trial. Age-appropriate language will be used to describe the procedures and 
tests involved in this study, along with the risks, discomforts, and benefits of participation. All 
child study participants, who will be between age 12 and <18 years will be asked to sign an age-
appropriate assent form. The consent/assent process will be documented in the child’s medical 
record. All children will be contacted after they have reached the age of 18y to determine 
whether they wish to continue participating in the trial; informed consent will be obtained from 
them at that time. 
 
Telephone consent 
 
In certain instances, the PI or designee will obtain informed consent by a telephone or video 
conversation with a protocol-eligible subject who cannot travel to the NIH Clinical Center for a 
considerable period of time.  A parent/guardian will be involved if the subject is <18 years of 
age. 
 
The informed consent document will be sent to the subject by mail, email, or fax. An explanation 
of the study will be provided over the telephone or other electronic media after the subject has 
had the opportunity to read the consent form. The informed consent form will be signed and 
dated.  
 
The original informed consent document will be sent back to the consenting investigator who 
will sign and date the consent form with the date the consent was returned. 
 
A fully executed copy will be returned via mail for the subject’s records. 
 
The informed consent process will be documented on a progress note by the consenting 
investigator. 
 
The investigator will confirm that, when required, written legally effective consent has been 
obtained prior to initiating any study interventions. 

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Telephone assent 
 
The informed consent and assent documents will be sent to the parents/guardian and child. An 
explanation of the study will be provided over the telephone after the parents/guardian and child 
have had the opportunity to read the documents. Age-appropriate language will be used to 
discuss the study with the child. The parents/guardian will sign and date the informed consent. 
The child will sign and date that form. All children will be contacted after they have reached the 
age of 18y to determine whether they wish to continue in the trial and informed consent will be 
obtained from them at that time. 
 
The original signed informed consent and assent documents will be sent back to the consenting 
investigator who will sign and date the consent form with the date the consent was returned. 
 
A fully executed copy will be returned via mail to the subject. 
 
The informed consent and assent process will be documented on a progress note by the 
consenting investigator.   
 
Consent for minors when they reach the age of majority 
 
When a pediatric subject reaches age 18y, continued participation (including ongoing 
interactions with the subject or continued analysis of identifiable data) will require that consent 
be obtained from the now adult with the standard protocol consent document to ensure legally 
effective informed consent has been obtained. 
 
If reconsent is not feasible, we request waiver of informed consent to continue to use data and/or 
specimens for those individuals who become lost to follow up or who have been taken off study 
prior to reaching the age of majority. 
 
Requirements for Waiver of Consent consistent with 45 CFR 46.116 (d): 
(1) The research involves no more than minimal risk to the subjects. 
a. Analysis of samples and data from this study involves no additional risks to 
subjects. 
(2) The research could not practicably be carried out without the waiver or alteration. 
a. Considering the length of time between the minor’s last contact with the 
research team and their age of majority, it will likely be very difficult to locate 
them again. A significant reduction in the number of samples analyzed is 
likely to impact the quality of the research.  
(3) As the research involves using identifiable private information or identifiable 
biospecimens, the research could not practicably be carried out without using such 
information or biospecimens in an identifiable format.  

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a. Though the purpose of future studies cannot yet be known, they often involve 
the correlation of clinical outcomes and clinical interventions with laboratory 
studies.  Such information would be unavailable if access to medical record 
numbers was unavailable.  
(4) The waiver or alteration will not adversely affect the rights and welfare of the 
subjects. 
a. Retention of these samples or data does not affect the welfare of subjects.  
(5) Whenever appropriate, the subjects will be provided with additional pertinent 
information after participation. 
a. We only request a waiver of consent for those subjects who have been lost to 
follow-up or who have been taken off study prior to reaching the age of 
majority. 
 
Non-English-Speaking Participants 
Non-English-speaking participants will be excluded from the study as they may be unable to 
complete questionnaires and follow the instructions which are only provided in English. If an 
English-speaking participant with a non-English speaking parent is eligible for enrollment, the 
parent will be provided with the CC Short Written Consent Form for Non-English-Speaking 
Research Participants in the participant’s native language and a verbal explanation of the purpose, 
procedures and risks of the study as described in MAS Policy M77-2, NIH HRPP SOP 12 and 45 
CFR 46.117(b)(2). The IRB-approved English consent form will serve as basis for the verbal 
explanation of the study. The investigator will obtain an interpreter unless the investigator is fluent 
in the prospective participant’s language. The interpreter will be someone who is independent of 
the participant (i.e., not a family member). Interpretation services provided by the CC will be used. 
The interpreter will interpret all oral communications (English to target language and conversely) 
between Investigator and Participant, facilitate discussions, and ensure understanding. 
The IRB-approved English consent form will be signed by the investigator obtaining consent and 
a witness to the oral presentation. The CC Short Written Consent Form will be signed by the 
participant and a witness who observed the presentation of information. The interpreter may sign 
the consent document as the witness for both documents and, in this case, will note “Interpreter” 
under the signature line. A copy of both signed forms will be provided to the participant to take 
home. The investigator obtaining consent will document the consent process in the participant’s 
medical record, including the name of the interpreter.  
h. Pharmaceutical, Biological, and Device Information 
Participants will receive mobile devices (i.e., smartphones) that they will be asked to carry with 
them and complete assessments, either self-initiated or randomly signaled, as part of the ecological 
momentary assessment (EMA) portion of the protocol. Regarding EMA, Dr. Waters has worked 
closely for a number of years with a Houston-based company to develop the “Colors” software to 
administer cognitive assessments and cognitive interventions using EMA. The software can 
administer reaction time tasks on mobile devices, individually or in combination, to include the 

Version Date:  July 14, 2022 
 
Page 41 of 56 
visual probe task to measure attention bias, Stroop, Implicit Association Test, and Go No-Go task. 
The program been used successfully in non-smokers, smokers, heroin/cocaine addicts undergoing 
detoxification, and recovering alcoholics. The program has also been used successfully to 
administer attentional retraining (155). To the best of our knowledge, this is the most sophisticated 
software currently being used for the assessment of cognitive biases in ecological momentary 
assessment studies. 
i. Recruitment Strategies 
Participants will be recruited through mailings to families in the Washington, D.C. greater 
metropolitan area, a successful method for our community- and intervention-based studies of youth 
with LOC eating (40, 43, 47, 58, 100). The advertisements will also be distributed on the local 
school and youth organization listservs (with permission), posted on the local bulletin boards (e.g., 
libraries, supermarkets, fitness clubs) with permission, and posted on free online social media (e.g., 
Facebook, Twitter, Instagram, LISTSERVs, ResearchMatch, CC News/NIH Record) and online 
services such as “Craigslist” and “Facebook.” These recruitment strategies have been highly 
effective in previous studies. Participants will call the phone number associated with the study and 
be pre-screened on the phone before attending the screening session. It is anticipated that on 
average three participants per week will be screened, and two participants per week will be 
enrolled. See Appendix 16 for a study recruitment methods. See Appendix 17 and Appendix 18 
for the sample recruitment materials.  
j. Description of Criteria for Withdrawal from the Study 
Participants will be examined briefly on the phone during the initial screening, and more 
extensively during the screening visit (Visit #1) as well as the follow-up visits. Participants will 
be excluded and/or referred for treatment if appropriate, as previously described. Identification of 
a current and significant psychiatric disorder at the time of enrollment will result in an appropriate 
referral to a mental health professional and study exclusion. Noncompliance with study procedures 
may lead to withdrawal of study participants. Other events that may lead to study withdrawal 
include pregnancy or serious unanticipated complications, including development of any medical 
problem listed in the exclusion criteria. Please see Section 16: Reporting of Unanticipated 
Problems, Adverse Events and Protocol Deviations for more details regarding adverse event 
reporting. 
k. Re-evaluation of the Study 
During and after the first several participants participate in the proposed procedures, data 
collection will be monitored closely to ensure that data are being collected as proposed. For 
example, we will download data from our first participant’s computerized attention bias tasks and 
magnetoencephalography, as well as her smartphone reaction time task data to ensure that these 
data are computing as expected. Adjustments, as needed, will be made to the procedures to obtain 
the data proposed in the current protocol. In such cases, a request to amend the protocol will be 
submitted to the IRB. 
l. Collection, monitoring, analysis and reporting of adverse events 
1. Data and Safety Monitoring: Since the study does not involve administration of any 

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pharmaceutical agents, but rather administration of a low-risk cognitive intervention, and the 
procedures are of little risk, we propose that a formal DSMB is not required, and the 
investigators and IRB can adequately supervise this study. Data and safety will be monitored 
by Dr. Jack Yanovski, the Principal Investigator. Dr. Yanovski is responsible for coordinating 
data collection and will review the data for accuracy and completeness within 30 days of each 
subject visit, including review of patient consent documents. An evaluation of patient 
recruitment, accrual, and retention as specified in the protocol will be ongoing. Review of 
literature and results of related studies will be assessed throughout the study for any impact 
on patient safety or ethical questions. 
All IRB documentation can be found in the NIH Integrated Research Information System 
(iRIS). Dr. Jack Yanovski is responsible for maintaining IRB documentation, including 
records of all reviews of the study and submissions to the IRB. Dr. Tanofsky-Kraff is 
responsible for facilitating the sending of paperwork (e.g. Amendments to the protocol) for 
review by USUHS as per the established IRB Authorization Agreement), to ensure that 
Department of Defense requirements are met. Dr. Tanofsky-Kraff will also be responsible for 
returning paperwork from USUHS regarding protocol actions to Dr. Yanovski. This protocol 
does not meet the criteria as outlined in the NIH HRPP SOP 17 for data to be submitted to a 
monitoring committee. Clinical Trial Studies (non IND/IDE) will have random audits 
performed 
by 
the 
NICHD 
Office 
of 
the 
Clinical 
Director 
(https://science.nichd.nih.gov/confluence/display/ocd/Protocol+Navigation). Dr. Yanovski 
will maintain subjects’ records for at least three years after completion of the study.   
2. Quality Assurance: The Principal Investigator, Dr. Jack Yanovski, will perform the quality 
assurance monitoring. The NICHD Standard Operating Procedure for Intramural Clinical 
Protocol Monitoring (rev. 5.20.2015) will be followed. 
3. Reporting of unanticipated problems, adverse events, and protocol deviations:  
Adverse events: We expect that the risk for an adverse event during this protocol will be below 
the “Rare but Serious (Event Rate < 1%)” category. 
Event Characterization and Reporting to the IRB and Clinical Director (CD): Unanticipated 
problems, non-compliance, and other reportable events will be reported to the NIH IRB as per 
Policy 801. All adverse events occurring during the study, including those observed by or 
reported to the research team, will be recorded. All adverse events (serious and non-serious, 
expected and unexpected) will be reported to the IRB at the annual continuing review in the 
form of electronic data sheets or summary language. 
This study involves an intervention/social science protocol, with multiple participant 
encounters. The six-month protocol may involve up to 6 separate encounters (depending on 
eligibility for participation in experiments), all of which involve little risk. Thus, we expect 
few adverse events to occur as a direct result of participating in our research protocol. 
However, the majority of our participant will report recent disordered eating behavior 
(specifically LOC eating), which has been prospectively associated with onset of threshold 
binge eating disorder and psychosocial problems. Thus, we would expect that a significantly 
higher proportion of youth in our LOC eating group would experience the onset of threshold 

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mental health disorders. Thus, we will anticipate and monitor for the following adverse 
events: 1) onset of threshold psychiatric disorders, and 2) suicidal thoughts. Should any of 
these events occur, youth (and their parents/guardians if under 18 y) will be notified and they 
will not be considered reportable adverse events.  
m. Conflicts of Interest:  
NIH guidelines on conflict of interest have been distributed to all investigators. There are no 
conflicts-of-interest to report for NIH investigators. Non-NIH investigators will abide by the 
conflict-of-interest policies of their own institutions. 
n. Monitoring Plan:  
1.   Purpose 
The purpose of this Monitoring Plan is to describe the rationale and process for the 
collection, recording, and verification of data for NICHD Protocol “Mobile Attention 
Retraining.” 
2.   Objectives 
a. To establish a monitoring plan to ensure the protocol data are in compliance with 
Good Clinical Practice (GCP), Institutional Review Board (IRB) and Data Safety 
Monitoring Committee policies, and Federal regulations.  
b. To ensure the validity, accuracy and integrity of the data 
 
 
3.   Study Staff Responsibilities  
 
Jack A. Yanovski, MD, PhD (the principal investigator) is responsible for all aspects of the 
study. Some responsibilities may be delegated to the current Associate Investigators. 
 
Delegation of responsibility will be documented on a study staff Signature and 
Delegation of Responsibility Log. 
 
4.   Source Documentation and Case Report Forms 
 
The Principal Investigator (Jack A. Yanovski, MD, PhD) and co-investigators as 
specified above, are responsible for coordinating data collection and will review the data for 
accuracy and completeness within seven days of each subject visit, including review of 
patient consent documents. 
 
The Principal Investigator (Jack A. Yanovski, MD, PhD) along with study co-
investigators will conduct the monitoring. Patient consent documents, primary outcome 
and safety laboratory results and diagnostic test results will be monitored for accuracy, 
correct dating, and agreement between case report forms and source documents. As case 
report forms are entered electronically into the NICHD Clinical Trials Database, the 

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computer system contains logs indicating changes made and the circumstances leading to 
these changes.  
 
5.   IRB and DSMC Documentation  
 
All IRB documentation can be found in iRIS. The Principal Investigator, Jack A. 
Yanovski, MD, PhD, is responsible for maintaining IRB correspondence related to this 
protocol, including records of all reviews of the study and submissions to the IRB.  
 
Dr. Tanofsky-Kraff is responsible for IRB documentation at USUHS, which also reviews 
this research.  
 
This protocol does not meet the criteria as outlined in the NIH HRPP SOP 17 for data to 
be submitted to a data safety monitoring committee. The PI and IRB can provide 
adequate oversight for this trial. 
 
Clinical Trial Studies (non IND/IDE) will have random audits performed by the NICHD 
Office of the Clinical Director (policy: 
https://science.nichd.nih.gov/confluence/display/ocd/Protocol+Navigation). 
 
6.   FDA Documentation  
Not Applicable – no IND. 
 
7.   Adverse Event Procedures and Documentation  
 
Unanticipated problems, non-compliance, and other reportable events will be reported to 
the NIH IRB and the Clinical Director (CD) using iRIS, in accordance with Policy 801. 
When iRIS is not available, the NIH Problem Report Form will be used. 
(https://federation.nih.gov/ohsr/nih/ohrdocs/NIH_Problem_Report_Form_Fillable_DDIR
_v1_6-11-13_508.pdf).   
 
An aggregated summary of all UP’s, PD’s, UADE’s, and AE’s will be reported to the 
IRB at the time of Continuing Review (CR). 
 
8. Study Completion 
Upon completion of the study Jack A. Yanovski, MD, PhD will retain possession of the 
electronic Protocol Binder in a secure location. HHS regulations require that subjects’ 
records be maintained for at least three years after completion of a study. Since subjects of 
this investigation are children, even longer record retention is required. All records will be 
retained until all participants have reached age 23.  
 
 

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IX. List of Appendices 
 
• Appendix 1: Eligibility Checklist 
• Appendix 2: Timeline of Procedures 
• Appendix 3: Phone Screen 
• Appendix 4: Screening Visit Physical Exam Form 
• Appendix 5:  Eating Disorder Examination (EDE) and Eating Disorder Examination 
adapted for Children (ChEDE) 
• Appendix 6: Youth Questionnaires   
 
 
       
• Appendix 7: Supplemental Assessment  
• Appendix 8: Parent Questionnaires   
• Appendix 9: MEG and MRI  
• Appendix 10: Food Cue Attention Bias Task 
• Appendix 11: Social Threat Attention Bias Task 
• Appendix 12: Laboratory Meal Image 
• Appendix 13: EMA Questions 
• Appendix 14: Follow-up Physical Exam Form 
• Appendix 15: Certification to Operate for “Colors” software 
• Appendix 16: Study recruitment methods 
• Appendix 17: Recruitment materials 
• Planned Enrollment Table 
 
 
 

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X. Consent Documents 
 
• Adult consent for minor subject 
• Child subject assent 
• Consent for child who becomes 18-years-old during the study 
 
 
 
 
 
 
 

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XI. References 
 
1. 
Ogden CL, Carroll MD, Lawman HG, Fryar CD, Kruszon-Moran D, Kit BK, et al. Trends 
in Obesity Prevalence Among Children and Adolescents in the United States, 1988-1994 Through 
2013-2014. JAMA. 2016;315(21):2292-9. 
2. 
Ogden CL, Kuczmarski RJ, Flegal KM, Mei Z, Guo S, Wei R, et al. Centers for Disease 
Control and Prevention 2000 Growth Charts for the United States: Improvements to the 1977 
National Center for Health Statistics Version. Pediatrics. 2002;109:45-60. 
3. 
Weiss R, Dziura J, Burgert T, Tamborlane W, Taksali S, Yeckel C, et al. Obesity and the 
metabolic syndrome in children and adolescents. New Englan Journal of Medicine. 
2004;350:2362-74. 
4. 
Dietz WH. Health Consequences of Obesity in Youth: Childhood Predictors of Adult 
Disease. Pediatrics. 1998;101:518-25. 
5. 
Field A, Cook N, Gillman M. Weight status in childhood as a predictor of becoming 
overweight or hypertensive in early adulthood. Obesity research. 2005;13:163-9. 
6. 
Freedman DS, Dietz WH, Srinivasan SR, Berenson GS. The Relation of Overweight to 
Cardiovascular Risk Factors Among Children and Adolescents: The Bogalusa Heart Study. 
Pediatrics. 1999;103:1175-82. 
7. 
Whitaker RC, Wright JA, Pepe MS, Seidel KD, Dietz WH. Predicting obesity in young 
adulthood from childhood and parental obesity. The New England journal of medicine. 
1997;337:869-73. 
8. 
Crow S, Eisenberg ME, Story M, Neumark-Sztainer D. Psychosocial and behavioral 
correlates of dieting among overweight and non-overweight adolescents. Journal of Adolescent 
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