Comparing Neural Responses to Food Images in EDNOS Patients and Healthy Controls Using fMRI

Study Overview
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Brief Summary
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Currently, there is not a robust, testable neural model available that sufficiently explains the development and maintenance of anorexia nervosa (AN) a severe, often fatal, adolescent-onset eating disorder. Using state of the art neuroimaging and neuropsychological techniques, our objective is to identify neural mechanisms in the adolescent brain underlying AN. This is of high clinical relevance in as much as it will provide a robust platform for a diagnostic battery so that physicians can identify those who are prone to develop AN at a very early stage of life. The aim of this research plan is: 1) To develop knowledge of cognitive dysfunction in adolescents who have recently been diagnosed with AN, with a battery of cognitive tests during a series of clinical visits. 2) To provide a scientific basis for our knowledge about how the brain of an adolescent with an eating disorder differs from that of a healthy adolescent, by conducting functional and structural magnetic resonance imaging on adolescent females with AN.

Detailed Description
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Adolescents with eating disorders have debilitating cognitive disturbances that impact on their social, educational and physical health. One cognitive trait that is found to form core cognitive disturbances in AN is superior working memory (WM). WM is the ability to ruminate on a cognitive strategy while attending to the details of another task, excluding non-relevant stimuli, and is linked to activation of the dorsolateral prefrontal cortex (DLPFC). By administering functional Magnetic Resonance Imaging (fMRI) we have recently found that females with AN have increased activation in the DLPFC and reduced appetitive brain responses when thinking about eating food shown in visual images. This suggests that the increased WM capacity in AN may serve to suppress food intake, but this has not yet been clarified. In line with this assumption, we have also shown that restraint of appetite in those with AN was linked to greater plasticity in the DLPFC. Furthermore, Transcranial Magnetic Stimulation (TMS) of the DLPFC reduces appetitive responses to food stimuli in adults with eating disorders. Conversely, we have shown that being obese is linked to reduced structure and abnormal function in the DLPFC, as well as reduced attentional control/WM performance. Therefore, it is likely that DLPFC-related WM function is associated with eating disorders, particularly cognitive restraint of appetite. It is likely that the interaction between appetitive brain regions and specific prefrontal cortex (PFC) cognitions determines whether an adolescent develops anorexia nervosa. We aim to provide neuropsychological and brain imaging measures showing how a specific cognitive function is linked to early-onset disordered eating behaviour, and we will do this before and after standard clinical treatment. We suggest that such understanding could enable school nurses to use the unique paradigm we use in our fMRI study, to detect illness before it damages the child's life and becomes difficult to treat. The study has now been increased to include genetic components to examine the genetic and epigenetic variation for genes found to be linked with eating disorders.

Official Title
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Comparing Neural Responses to Explicit and Subliminal Food Images in EDNOS Patients and Healthy Controls Using fMRI

Conditions
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Eating Disorders

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females Age 13 - 18 yrs Right handed For controls: BMI within the normal range For patients: Be admitted to treatment for an eating disorder Exclusion Criteria: On medication Suffering from any other illnesses Left handed Metal implants which can impact the fMRI image Severe claustrophobia Pregnancy Smoker Regular alcohol drinker

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Eating disorder<br>Patients currently in treatment for eating disorders. | |
| Healthy Controls<br>Age- and gender matched healthy controls. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure functional differences in adolescents with eating disorders and healthy controls. | The analysis of each groups' neural activity will be carried out with statistical parametric mapping (SPM) implemented in Matlab. This will compare the statistical parametric maps between the group using ANOVAs, ANCOVAs and t-tests. | This is measured during scanning shortly after patient admittance to treatment, and one year later. Controls have their scans shortly after being recruited to the study, then again 1 year later. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure structural differences in adolescents with eating disorders and healthy controls. | To determine any structural differences, matlab will be used. With this one can upload the T1 structural scanning data and determine the volume of each subject's brain, and even compute the volume of each tissue (CBF, white matter and grey matter). | This is measured during scanning shortly after patient admittance to treatment, and one year later. Controls have their scans shortly after being recruited to the study, then again 1 year later. | 
| Develop knowledge of cognitive dysfunction in adolescents with eating disorders. | Any cognitive dysfunction will be measured with a working memory task in the scanner (N-back task). Further, various clinical variables will be measured with the use of questionnaires such as Eating Disorder Examination Questionnaire (EDEQ), Perceived Stress Scale (PSS), Montgomery-Åsberg Depression Rate Scale (MADRS), Eating Disorder Inventory (EDI), Barratts Impulsivity Scale (BIS), Obsessive Compulsive Inventory - Revised (OCI R), and Multidimensional Perfectionism Scale (MPS). | The cognitive measures are conducted shortly after recruitment of the study. The subjects are given the questionnaires upon their first meeting, and are posted back to us shortly after. | 
| To examine whether clinical variables can predict neural activity. | The analysis of each groups' neural activity will be carried out with statistical parametric mapping (SPM) implemented in Matlab. This will compare the statistical parametric maps between the group using ANOVAs, ANCOVAs and t-tests. The clinical variables will be measured with the use of questionnaires such as Eating Disorder Examination Questionnaire (EDEQ), Perceived Stress Scale (PSS), Montgomery-Åsberg Depression Rate Scale (MADRS), Eating Disorder Inventory (EDI), Barratts Impulsivity Scale (BIS), Obsessive Compulsive Inventory - Revised (OCI R), and Multidimensional Perfectionism Scale (MPS). These will be used in a multiple regression analysis carried out in SPM to see whether there is any correlation between the scores of the questionnaires and the brain activity of the groups. | The neural activity is measured during scanning shortly after subject recruitment, and one year later. The clinical measurements are measured with questionnaires given to them on their first meeting after recruitment, which are later posted back to us. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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EDNOS, adolescents, eating disorder, anorexia nervosa