Abstract
Background: Alterations in intraoperative electroencephalography (EEG) alpha power and anesthetic dose-adjusted EEG alpha power (ADA-FP alpha power) have been associated with both preoperative cognitive impairment and postoperative delirium (POD) among older surgical patients, yet the neurologic underpinnings of alterations in these anesthetic brain response patterns are unknown. Methods: We conducted a single center prospective observational cohort study (ALADDIN), of older adults undergoing non-cardiac/non-cranial surgery, which included preoperative structural and resting state functional MRI, lumbar punctures to obtain CSF, 32 channel intraoperative EEG recordings, and repeated POD assessments. To account for anesthetic dose, frontoparietal EEG alpha power (ADA-FP alpha power) was adjusted using our established formula: [intraoperative alpha power]/(2.5 - end-tidal MAC fraction). Multivoxel pattern analysis (MVPA) with follow-up seed-to-voxel analyses identified functional connectivity patterns associated with intraoperative ADA-FP alpha power. Voxel-wise regression analysis with threshold free cluster estimation (TFCE) correction was used to evaluate associations between cortical thickness and ADA-FP alpha power. CSF biomarker values were obtained from NULISA proximity extension assays. Delirium incidence and severity was assessed with the 3-Minute Diagnostic Confusion Assessment Method (3D-CAM). Delirium severity area under the curve (AUC) during hospitalization was defined as the sum of all 3D-CAM delirium severity scores within the postoperative hospitalization period (for up to 7 days after surgery). The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) was used in cases of non-verbal/intubated patients. Results: ALADDIN enrolled 215 patients, of whom 168 underwent surgery and had high-quality intraoperative EEG data (44.6% female; mean age 70.9 years). MVPA showed that ADA-FP alpha power was associated with altered functional connectivity within the bilateral frontal poles, left superior frontal gyrus and the right superior parietal lobule (p-FWE < 0.05). Seed-to-voxel analyses revealed that higher ADA-FP alpha power was associated with increased connectivity between DMN MVPA regions and DMN, DAN and salience/ventral attention and decreased connectivity with visual regions. Conversely, right superior parietal lobule connectivity shifted towards greater DMN segregation and increased somatosensory/motor coupling (p-FWE < 0.05). Lower ADA-FP alpha power was also associated with lower cortical thickness in left occipitotemporal and superior parietal cortices (TFCE-corrected p < 0.05). ADA-FP alpha power was also lower among participants with (vs those without) postoperative ward/floor delirium (mean difference, 1.33; 95% CI, 0.22 to 2.44; p=0.019), and ADA-FP alpha power was inversely associated with peak delirium severity (spearman's rho = -0.26; 95% CI, -0.40 to -0.11; p <0.001) and delirium severity AUC (spearman's rho = -0.28; 95% CI, -0.42 to -0.13; p < 0.001). Discussion: These findings suggest a functional and structural neuroanatomic basis for the decreased EEG ADA-FP alpha power values seen among some older surgical patients, which may explain the association between decreased EEG ADA-FP alpha power and increased rates of both preoperative cognitive impairment and postoperative delirium. More specifically, these findings suggest that altered default mode and dorsal attention network connectivity is linked to decreased EEG ADA-FP alpha power and raise the possibility that preoperative/baseline functional connectivity alterations within these networks may play a role in delirium risk.
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