Neural network functional connectivity during and after an episode of delirium

OBJECTIVE: Delirium is a common and potentially life-threatening clinical syndrome. The authors investigated resting-state functional connectivity in patients with delirium to elucidate possible neural mechanisms underlying this disorder. METHOD: Twenty-two patients underwent initial functional MRI at rest during an episode of delirium. Of these patients, 14 completed follow-up scans after the episode resolved. Twenty-two comparison subjects without delirium also underwent scanning. The authors assessed cortical functional connectivity using the seed region of the posterior cingulate cortex and functional connectivity strengths between a priori subcortical regions related to acetylcholine and dopamine on data from 20 initial and 13 follow-up scans. RESULTS: Dorsolateral prefrontal cortex activity and posterior cingulate cortex activity were inversely correlated in comparison subjects but strongly correlated in patients during an episode of delirium as indicated by increased functional connectivity between the two regions. Although precuneus activity was positively correlated with posterior cingulate cortex activity in comparison subjects, the correlation was further increased in patients during an episode of delirium, and the increment was associated with less severity and shorter duration of delirium. Functional connectivity strengths of the intralaminar thalamic and caudate nuclei with other subcortical regions were reduced during an episode of delirium but recovered after resolution of the episode. CONCLUSIONS: These findings suggest that the disruption in reciprocity of the dorsolateral prefrontal cortex with the posterior cingulate cortex and reversible reduction of functional connectivity of subcortical regions may underlie the pathophysiology of delirium. In addition, enhanced integration in the posteromedial cortices may account for facilitating the rapid improvement of delirium.ope