Abstract
BACKGROUND: Postoperative delirium is associated with increased morbidity, mortality, future cognitive decline, or dementia. Understanding the neural mechanisms that differentiate individual brain vulnerabilities is critical for future therapeutic development and prevention of postoperative delirium. We investigated the hypothesis that impaired resting state functional connectivity indicates predisposition to delirium. METHODS: Preoperative blood oxygen level-dependent functional MRI data were collected from 120 participants (>65 yr, 52 female) undergoing major elective non-intracranial surgery. Denoised blood oxygen level-dependent signal time-series for 400 cortical regions were used to calculate resting state functional connectivity within and between canonical resting state networks. We used a support vector machine to determine whether resting state functional connectivity across higher-order cortical networks was predictive of postoperative delirium. RESULTS: Group comparisons revealed significantly decreased within-network connectivity in salience-ventral attention, cognitive control, and default mode network in participants with postoperative delirium (n=31) compared with non-delirious participants (n=89; non-parametric permutation test, 1000 iterations, P<0.05). We found overall weaker connectivity within the default mode network and specific differences across the sub-networks of the default mode which overlap with higher-order cognitive processing. Supervised machine learning identified that the visual and salience-ventral attentional networks predicted postoperative delirium incidence with an accuracy of 68%. CONCLUSIONS: Resting state functional connectivity is a neural correlate of vulnerability to postoperative delirium. Disrupted resting state connectivity within higher-order cognitive association areas, including the default mode network, salience attention, and cognitive control networks, was specifically correlated with delirium. CLINICAL TRIAL REGISTRATION: NCT01980511 and NCT03124303.