Cortical and subcortical changes in resting-state functional connectivity before and during an episode of postoperative delirium

Objective: Delirium is an acute brain failure related to uncertain problems in neural connectivity, including aberrant functional interactions between remote cortical regions. This study aimed to elucidate the underlying neural mechanisms of delirium by clarifying the changes in resting-state functional connectivity induced by postoperative delirium using imaging data scanned before and after surgery. Method: Fifty-eight patients with a femoral neck fracture were preoperatively scanned using resting-state functional magnetic resonance imaging. Twenty-five patients developed postoperative delirium, and 14 of those had follow-up scans during delirium. Eighteen patients without delirium completed follow-up scans 5 or 6 days after surgery. We assessed group differences in voxel-based connectivity, in which the seeds were the posterior cingulate cortex, medial prefrontal cortex and 11 subcortical regions. Connections between the subcortical regions were also examined. Results: The results showed four major findings during delirium. Both the posterior cingulate cortex and medial prefrontal cortex were strongly connected to the dorsolateral prefrontal cortex. The posterior cingulate cortex had hyperconnectivity with the inferior parietal lobule, whereas the medial prefrontal cortex had hyperconnectivity with the frontopolar cortex and hypoconnectivity with the superior frontal gyrus. Connectivity of the striatum with the anterior cingulate cortex and insula was increased. Disconnections were found between the lower subcortical regions including the neurotransmitter origins and the striatum/thalamus in the upper level. Conclusions: Our findings suggest that cortical dysfunction during delirium is characterized by a diminution of the anticorrelation between the default mode network and task-positive regions, excessive internal connections in the posterior default mode network and a complex imbalance of internal connectivity in the anterior default mode network. These dysfunctions can be attributed to the loss of reciprocity between the default mode network and central executive network associated with defective function in the salience network, which might be closely linked to aberrant subcortical neurotransmission-related connectivity and striato-cortical connectivity.