Abstract
ObjectivesPeople 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.MethodThirty-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.ResultsAlthough 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.ConclusionsPeople 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.
Highlights
Anorexia nervosa (AN) is a severe mental illness associated with a lifetime prevalence of 0.9% in females and 0.3% in males [1], and carries the highest mortality rate among psychiatric conditions [2]
Event-related analysis permitted the comparison of cognitive shift trials against those requiring maintenance of rule-sets and allowed assessment of trials representing learning. Both groups performed 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
Posterior cingulate cortex activity in healthy controls decreased whilst increasing in the Anorexia Nervosa group, whereas the right precuneus exhibited the opposite pattern
Summary
Anorexia nervosa (AN) is a severe mental illness associated with a lifetime prevalence of 0.9% in females and 0.3% in males [1], and carries the highest mortality rate among psychiatric conditions [2]. Using a functional magnetic resonance imaging (fMRI) coupled with a target-detection task, Zastrow et al [11] found decreased activation in AN in the fronto-striatal network when performing behavioural shifts independently of cognitive shift requirement These findings are corroborated by an activation likelihood estimation meta-analysis of nine voxel-based morphometry studies showing decreased grey matter volume in the right caudate and right lentiform nucleus in currently ill AN [12], and decreased ACC grey matter in recovered participants [13]. Zastrow et al demonstrated dominant activation of the right middle frontal gyrus and bilateral temporoparietal junction in AN, regions that form the fronto-parietal control network (FPCN; [14,15]) These observations suggest that inefficient cognitive setshifting in AN may be attributed to problematic behavioural shifting, characterised by greater cognitive supervisory control and aberrant function of motivation-related circuitry. A recent fMRI study using the Wisconsin Card Sorting Test (WCST) found differential activation during shifting as opposed to maintaining set in the inferior frontal gyrus and bilateral parahippocampal gyrus [16], demonstrating functional alterations associated with cognitive flexibility above that of behavioural flexibility
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