Reduced Electroencephalogram Complexity in Postoperative Delirium

Abstract

Delirium is associated with electroencephalogram (EEG) slowing and impairments in connectivity. We hypothesized that delirium would be accompanied by a reduction in the available cortical information (ie, there is less information processing occurring), as measured by a surrogate, Lempil-Ziv Complexity (LZC), a measure of time-domain complexity. Two ongoing perioperative cohort studies (NCT03124303, NCT02926417) contributed EEG data from 91 patients before and after surgery; 89 participants were used in the analyses. After cleaning and filtering (0.1-50Hz), the perioperative change in LZC and LZC normalized (LZCn) to a phase-shuffled distribution were calculated. The primary outcome was the correlation of within-patient paired changes in delirium severity (Delirium Rating Scale-98 [DRS]) and LZC. Scalp-wide threshold-free cluster enhancement was employed for multiple comparison correction. LZC negatively correlated with DRS in a scalp-wide manner (peak channel r2 = .199, p < .001). This whole brain effect remained for LZCn, though the correlations were weaker (peak channel r2 = .076, p = .010). Delirium diagnosis was similarly associated with decreases in LZC (peak channel p < .001). For LZCn, the topological significance was constrained to the midline posterior regions (peak channel p = .006). We found a negative correlation of LZC in the posterior and temporal regions with monocyte chemoattractant protein-1 (peak channel r2 = .264, p < .001, n = 47) but not for LZCn. Complexity of the EEG signal fades proportionately to delirium severity implying reduced cortical information. Peripheral inflammation, as assessed by monocyte chemoattractant protein-1, does not entirely account for this effect, suggesting that additional pathogenic mechanisms are involved.

Keywords: Age-related pathology; Inflammation; Neurodegeneration.

Figure 1.

STROBE diagram. (A) Study design. Delirium severity (DRS) is collected during delirium assessments, both preoperative and postoperative visits. (B) Data are from IPODB2 and IPODB3 perioperative cohort studies.

Figure 2.

Delirium severity (DRS) is associated with decreased Lempel Ziv Complexity (LZC). Correlation of change in DRS with (A) LZC (n = 88) and (B) LZCn (n = 88) with statistically significant electrodes shown by white dots (corrected TFCE, p < .05). Example channel Spearman’s correlation plotted at 90th percentile effect size overlapping between LZC and LZCn, shown by white “X” in (A) and black “X” in (B) (channel 179).

Figure 3.

Delirium incidence is associated with decreased Lempel Ziv Complexity. Contrast between LZC of patients who do and do not incur delirium with statistically significant electrodes shown by white dots (corrected TFCE t-map p < .05). Analysis of (A) LZC and (B) LZCn (No-delirium n = 59, Delirium n = 30). Example 2-sided Wilcoxon rank sum test plotted at 90th percentile effect size overlapping between LZC and LZCn, shown by white “X” in (A) and black “X” in (B) (channel 136), *p < .01, **p < .001.

Figure 4.

Lempel Ziv Complexity correlation with MCP-1. (A) LZC analysis (n = 47) and (B) LZCn analysis (n = 47) with statistically significant electrodes shown by white dots (corrected TFCE p < .05). Example Spearman’s correlation plotted at 90th percentile effect size overlapping between LZC and LZCn, shown by white and black “X” (channel 87).