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

Eating Disorders Clinical Trial

— ANfMRI  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01882023
• Other study ID #: anfmri40
• Status: Recruiting
• Start date: May 2011
• Est. completion date: December 2027

Study information

• Verified date: November 2023
• Source: Uppsala University
• Contact: Christina Zhukovsky, MMed
• Email: christina.zhukovsky[@]neuro.uu.se
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: December 2027
• Est. primary completion date: December 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 13 Years to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Eating Disorders
• Feeding and Eating Disorders

Locations

Country	Name	City	State
Sweden	Röntgenavdelningen, Uppsala Academic Hospital	Uppsala	Uppsala Län

Sponsors (1)

Lead Sponsor	Collaborator
Uppsala University

Country where clinical trial is conducted

Sweden, 

References & Publications (15)

Andrews SC, Hoy KE, Enticott PG, Daskalakis ZJ, Fitzgerald PB. Improving working memory: the effect of combining cognitive activity and anodal transcranial direct current stimulation to the left dorsolateral prefrontal cortex. Brain Stimul. 2011 Apr;4(2):84-9. doi: 10.1016/j.brs.2010.06.004. Epub 2010 Jul 11. — View Citation

Brooks SJ, Barker GJ, O'Daly OG, Brammer M, Williams SC, Benedict C, Schioth HB, Treasure J, Campbell IC. Restraint of appetite and reduced regional brain volumes in anorexia nervosa: a voxel-based morphometric study. BMC Psychiatry. 2011 Nov 17;11:179. doi: 10.1186/1471-244X-11-179. — View Citation

Brooks SJ, Benedict C, Burgos J, Kempton MJ, Kullberg J, Nordenskjold R, Kilander L, Nylander R, Larsson EM, Johansson L, Ahlstrom H, Lind L, Schioth HB. Late-life obesity is associated with smaller global and regional gray matter volumes: a voxel-based morphometric study. Int J Obes (Lond). 2013 Feb;37(2):230-6. doi: 10.1038/ijo.2012.13. Epub 2012 Jan 31. — View Citation

Brooks SJ, O'Daly O, Uher R, Friederich HC, Giampietro V, Brammer M, Williams SC, Schioth HB, Treasure J, Campbell IC. Thinking about eating food activates visual cortex with reduced bilateral cerebellar activation in females with anorexia nervosa: an fMRI study. PLoS One. 2012;7(3):e34000. doi: 10.1371/journal.pone.0034000. Epub 2012 Mar 27. — View Citation

Brooks SJ, O'Daly OG, Uher R, Friederich HC, Giampietro V, Brammer M, Williams SC, Schioth HB, Treasure J, Campbell IC. Differential neural responses to food images in women with bulimia versus anorexia nervosa. PLoS One. 2011;6(7):e22259. doi: 10.1371/journal.pone.0022259. Epub 2011 Jul 20. — View Citation

Brooks SJ, O'Daly OG, Uher R, Schioth HB, Treasure J, Campbell IC. Subliminal food images compromise superior working memory performance in women with restricting anorexia nervosa. Conscious Cogn. 2012 Jun;21(2):751-63. doi: 10.1016/j.concog.2012.02.006. Epub 2012 Mar 11. — View Citation

Gaudio S, Carducci F, Piervincenzi C, Olivo G, Schioth HB. Altered thalamo-cortical and occipital-parietal- temporal-frontal white matter connections in patients with anorexia and bulimia nervosa: a systematic review of diffusion tensor imaging studies. J Psychiatry Neurosci. 2019 Sep 1;44(5):324-339. doi: 10.1503/jpn.180121. — View Citation

Gaudio S, Olivo G, Beomonte Zobel B, Schioth HB. Altered cerebellar-insular-parietal-cingular subnetwork in adolescents in the earliest stages of anorexia nervosa: a network-based statistic analysis. Transl Psychiatry. 2018 Jul 6;8(1):127. doi: 10.1038/s41398-018-0173-z. — View Citation

Olivo G, Solstrand Dahlberg L, Wiemerslage L, Swenne I, Zhukovsky C, Salonen-Ros H, Larsson EM, Gaudio S, Brooks SJ, Schioth HB. Atypical anorexia nervosa is not related to brain structural changes in newly diagnosed adolescent patients. Int J Eat Disord. 2018 Jan;51(1):39-45. doi: 10.1002/eat.22805. Epub 2017 Dec 7. — View Citation

Olivo G, Swenne I, Zhukovsky C, Tuunainen AK, Saaid A, Salonen-Ros H, Larsson EM, Brooks SJ, Schioth HB. Preserved white matter microstructure in adolescent patients with atypical anorexia nervosa. Int J Eat Disord. 2019 Feb;52(2):166-174. doi: 10.1002/eat.23012. Epub 2019 Jan 24. — View Citation

Olivo G, Swenne I, Zhukovsky C, Tuunainen AK, Salonen-Ros H, Larsson EM, Gaudio S, Brooks SJ, Schioth HB. Reduced resting-state connectivity in areas involved in processing of face-related social cues in female adolescents with atypical anorexia nervosa. Transl Psychiatry. 2018 Dec 13;8(1):275. doi: 10.1038/s41398-018-0333-1. — View Citation

Olivo G, Wiemerslage L, Swenne I, Zhukovsky C, Salonen-Ros H, Larsson EM, Gaudio S, Brooks SJ, Schioth HB. Correction: Limbic-thalamo-cortical projections and reward-related circuitry integrity affects eating behavior: A longitudinal DTI study in adolescents with restrictive eating disorders. PLoS One. 2017 Apr 20;12(4):e0176646. doi: 10.1371/journal.pone.0176646. eCollection 2017. — View Citation

Olivo G, Wiemerslage L, Swenne I, Zhukowsky C, Salonen-Ros H, Larsson EM, Gaudio S, Brooks SJ, Schioth HB. Limbic-thalamo-cortical projections and reward-related circuitry integrity affects eating behavior: A longitudinal DTI study in adolescents with restrictive eating disorders. PLoS One. 2017 Mar 1;12(3):e0172129. doi: 10.1371/journal.pone.0172129. eCollection 2017. Erratum In: PLoS One. 2017 Apr 20;12 (4):e0176646. — View Citation

Olivo G, Zhou W, Sundbom M, Zhukovsky C, Hogenkamp P, Nikontovic L, Stark J, Wiemerslage L, Larsson EM, Benedict C, Schioth HB. Resting-state brain connectivity changes in obese women after Roux-en-Y gastric bypass surgery: A longitudinal study. Sci Rep. 2017 Jul 26;7(1):6616. doi: 10.1038/s41598-017-06663-5. — View Citation

Van den Eynde F, Claudino AM, Mogg A, Horrell L, Stahl D, Ribeiro W, Uher R, Campbell I, Schmidt U. Repetitive transcranial magnetic stimulation reduces cue-induced food craving in bulimic disorders. Biol Psychiatry. 2010 Apr 15;67(8):793-5. doi: 10.1016/j.biopsych.2009.11.023. Epub 2010 Jan 8. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	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.
Secondary	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.