title: Aberrant function of learning and cognitive control networks underlie inefficient cognitive flexibility in anorexia nervosa: a cross-sectional fMRI study.
abstract: OBJECTIVE
  People with Anorexia Nervosa exhibit difficulties flexibly adjusting behaviour in response to environmental changes. This has previously been attributed to problematic behavioural shifting, characterised by a decrease in fronto-striatal activity. Additionally, alterations of instrumental learning, which relies on fronto-striatal networks, may contribute to the observation of inflexible behaviour. The authors sought to investigate the neural correlates of cognitive flexibility and learning in Anorexia Nervosa.
  
  
  METHODS
  Thirty-two adult females with Anorexia Nervosa and thirty-two age-matched female control participants completed the Wisconsin Card Sorting Task whilst undergoing functional magnetic resonance imaging. Event-related analysis permitted the comparison of cognitive shift trials against those requiring maintenance of rule-sets and allowed assessment of trials representing learning.
  
  
  RESULTS
  Although both groups performed similarly, we found significant interactions in the left middle frontal gyrus, precuneus and superior parietal lobule whereby blood-oxygenated-level dependent response was higher in Anorexia Nervosa patients during shifting but lower when maintaining rule-sets, as compared to healthy controls. During learning, posterior cingulate cortex activity in healthy controls decreased whilst increasing in the Anorexia Nervosa group, whereas the right precuneus exhibited the opposite pattern. Furthermore, learning was associated with lower blood-oxygenated-level dependent response in the caudate body, as compared to healthy controls.
  
  
  CONCLUSIONS
  People with Anorexia Nervosa display widespread changes in executive function. Whilst cognitive flexibility appears to be associated with aberrant functioning of the fronto-parietal control network that mediates between internally and externally directed cognition, fronto-striatal alterations, particularly within the caudate body, were associated with instrumental learning. Together, this shows how perseverative tendencies could be a substrate of multiple high-order processes that may contribute to the maintenance of Anorexia Nervosa.
authors.affiliation: King's College London, Institute of Psychiatry, Department of Psychological Medicine, London, United Kingdom.
authors.forename: Nick P
authors.initials: NP
authors.lastname: Lao-Kaim
authors.affiliation: King's College London, Institute of Psychiatry, Department of Psychological Medicine, London, United Kingdom.
authors.forename: Leon
authors.initials: L
authors.lastname: Fonville
authors.affiliation: King's College London, Institute of Psychiatry, Department of Neuroimaging, London United Kingdom.
authors.forename: Vincent P
authors.initials: VP
authors.lastname: Giampietro
authors.affiliation: King's College London, Institute of Psychiatry, Department of Neuroimaging, London United Kingdom; NIHR Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, King's College London, London, United Kingdom.
authors.forename: Steven C R
authors.initials: SC
authors.lastname: Williams
authors.affiliation: King's College London, Institute of Psychiatry, Department of Neuroimaging, London United Kingdom; NIHR Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, King's College London, London, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Simmons
authors.affiliation: King's College London, Institute of Psychiatry, Department of Psychological Medicine, London, United Kingdom.
authors.forename: Kate
authors.initials: K
authors.lastname: Tchanturia
mesh_terms: D000293:Adolescent; D000328:Adult; D000856:Anorexia Nervosa / Q000473:pathology / Q000503:physiopathology*; D001931:Brain Mapping; D016022:Case-Control Studies; D003071:Cognition; D003342:Corpus Striatum / Q000473:pathology / Q000503:physiopathology*; D003430:Cross-Sectional Studies; D056344:Executive Function; D005260:Female; D005625:Frontal Lobe / Q000473:pathology / Q000503:physiopathology*; D006179:Gyrus Cinguli / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007858:Learning; D008279:Magnetic Resonance Imaging; D009415:Nerve Net / Q000473:pathology / Q000503:physiopathology; D009483:Neuropsychological Tests; D010296:Parietal Lobe / Q000473:pathology / Q000503:physiopathology*