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The investigators will examine compulsivity in those who have recovered from anorexia nervosa, using a multi-modal MRI study. The neural activation of key fronto-striatal areas will be explored using a task which examines set-shifting and reversal-learning, two key components of compulsivity. Additionally, the functional networks displayed during resting-state MRI will be examined between groups, as will the neurochemicals present (using Magnetic Resonance spectroscopy).
The investigators will perform four different MRI (Magnetic Resonance Imaging) scans during one scanning session on those who have recovered from anorexia nervosa (AN) and healthy controls.
Participants will come to the Warneford hospital for a 2.5 hour screening visit, which will consist of questionnaires and interviews to determine their medical and psychiatric history and current mood, along with a practice of the task they'll do in the scanner. Participants will also complete two tasks which measure compulsivity and can be correlated with their brain activity in the scans. The investigators will also go through a scanning safety form with participants at this time.
Participants will also attend a scanning visit, which will last 1.5 hours. One of the scans will look at how the brain responds to a particular task. This task will examine aspects of compulsivity (which is rigidly repeating actions that aren't rewarding) by using face and house stimuli (see reference 1).
The investigators will also perform a scan when participants are at rest, in order to see if there are differences in the way areas of the brain connect to each other who used to have AN. The scientific literature indicates that there may be differences in the some key brain networks, including one which is thought to be involved in reflection and the self (the default mode network), which might also be linked to compulsivity (see reference 2).
This study will also further investigate some initial pilot findings using Magnetic Resonance Spectroscopy, which allows researchers to examine the levels of different neurochemicals in the brain. It has been found that those with a current diagnosis of AN have lower levels of glutamate (a key brain chemical) compared to healthy controls, which is a finding we seek to extend in those who have recovered from AN (see reference 3).
Aims: The investigators aim to see whether there are differences in the brains of those who have recovered from anorexia compared to those who have never had an anorexia diagnosis. This will be both at rest, and whilst participants are doing a task which measures compulsivity, as compulsivity is thought to be a particular risk factor for eating disorders.
Value: If the investigators are able to identify differences, these might reflect underlying risk factors for eating disorders, which could lead to potential future treatments or prevention schemes.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Recovered from anorexia nervosa | Experimental | Women who have recovered from Anorexia Nervosa for over a year. BMI over 18.5, aged 18-40, scores on Eating Disorder Examination (EDE) within 1 standard deviation of the global mean. All these participants undergo an MRI scan. |
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| Healthy controls | Experimental | Healthy control women. BMI over 18.5, aged 18-40, scores on EDE within 1 standard deviation of the global mean. All these participants undergo an MRI scan. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MRI | Other | MRI scan, including structural imaging, functional imaging (both task-related and structural), and Magnetic Resonance Spectroscopy. |
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| Measure | Description | Time Frame |
|---|---|---|
| Blood Oxygen-Level Dependent (BOLD) signal whilst performing set-shifting and reversal-learning | BOLD signal differences between groups during the set-shifting and reversal-learning elements of a task: will be examined in orbitofrontal cortex, dorsolateral prefrontal cortex, and striatum. Analyse using a repeated measures ANOVA with region as within-subject factor and group as between-subject factor. Follow up significant interactions with paired t-tests. | 1 day (During MRI scan) |
| Measure | Description | Time Frame |
|---|---|---|
| Differences between groups in the connectivity of the fronto-parietal and default mode networks using independent components analysis, dual regression and permutation testing across the brain. | A resting state scan will be performed, and an Independent Components Analysis will be performed to identify networks. Dual regression using fronto-parietal and default mode network to test whether there are group differences. This procedure regresses the group-spatial-maps into each subject's 4D dataset to give a set of timecourses, then regresses these timecourses into the same 4D dataset to get a subject-specific set of spatial maps. Then, the researchers will compare the spatial maps across groups of subjects to look for group differences in connectivity across the brain, using randomise permutation testing. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Philip J Cowen, Prof | University of Oxford | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Psychiatry, University of Oxford | Oxford | Oxfordshire | OX3 7JX | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18635808 | Background | Chamberlain SR, Menzies L, Hampshire A, Suckling J, Fineberg NA, del Campo N, Aitken M, Craig K, Owen AM, Bullmore ET, Robbins TW, Sahakian BJ. Orbitofrontal dysfunction in patients with obsessive-compulsive disorder and their unaffected relatives. Science. 2008 Jul 18;321(5887):421-2. doi: 10.1126/science.1154433. | |
| 25324749 | Background |
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| ID | Term |
|---|---|
| D003192 | Compulsive Behavior |
| ID | Term |
|---|---|
| D007175 | Impulsive Behavior |
| D001519 | Behavior |
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All participants undero go an MRI scan, complete some questionnaires and two computer tasks. Participants are in two groups: those who have recovered from anorexia nervosa, and healthy control participants.
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| 1 day (During MRI scan) |
| The correlation of the default mode network and frontoparietal network activity with perseverative errors on the Wisconsin Card Sorting Task across groups | Correlate perseverative errors on Wisconsin Card Sorting Task with connectivity level of Default Mode Network (DMN) and frontoparietal network | 1 day (During MRI scan) |
| Investigate a difference in levels of glutamate between groups | Concentration of cortical glutamate in those who have recovered from anorexia relative to controls. Will be analysed using LCModel to quantify metabolites, then an independent samples t-test. | 1 day (During MRI scan) |
| Examine differences between groups on an impulsivity measure | Differences between scores on the Affective Go/No-Go Task. Analysed using a independent-samples t-test. | 1 day (During MRI scan) |
| Boehm I, Geisler D, King JA, Ritschel F, Seidel M, Deza Araujo Y, Petermann J, Lohmeier H, Weiss J, Walter M, Roessner V, Ehrlich S. Increased resting state functional connectivity in the fronto-parietal and default mode network in anorexia nervosa. Front Behav Neurosci. 2014 Oct 2;8:346. doi: 10.3389/fnbeh.2014.00346. eCollection 2014. |
| 27909746 | Background | Godlewska BR, Pike A, Sharpley AL, Ayton A, Park RJ, Cowen PJ, Emir UE. Brain glutamate in anorexia nervosa: a magnetic resonance spectroscopy case control study at 7 Tesla. Psychopharmacology (Berl). 2017 Feb;234(3):421-426. doi: 10.1007/s00213-016-4477-5. Epub 2016 Dec 1. |