Evidence for thalamocortical circuit abnormalities and associated cognitive dysfunctions in underweight individuals with anorexia nervosa

Abstract

Anorexia nervosa (AN) is characterized by extremely low body weight resulting from pathological food restriction, and carries a mortality rate among the highest of any psychiatric illness. AN, particularly during the acute, underweight state of the illness, has been associated with abnormalities across a range of brain regions, including the frontal cortex and basal ganglia. Few studies of AN have investigated the thalamus, a key mediator of information flow through frontal-basal ganglia circuit loops. We examined both thalamic surface morphology using anatomical MRI and thalamo-frontal functional connectivity using resting-state functional MRI. Individuals with AN (n=28) showed localized inward deformations of the thalamus relative to healthy controls (HC, n=22), and abnormal functional connectivity between the thalamus and the dorsolateral and anterior prefrontal cortices. Alterations in thalamo-frontal connectivity were associated with deficits in performance on tasks probing cognitive control (Stroop task) and working memory (Letter-Number Sequencing (LNS) task). Our findings suggest that abnormalities in thalamo-frontal circuits may have a role in mediating aspects of cognitive dysfunction in underweight individuals with AN.