Do Complexity Measures of Frontal EEG Distinguish Loss of Consciousness in Geriatric Patients Under Anesthesia?

FIGURE 1. Characterizing loss of response (LOR) using electroencephalogram (EEG) analysis. (A) EEGs were recorded from F7 during induction with propofol and fentanyl anesthesia in geriatric patients receiving beta-adrenergic blockade. We selected continuous artifact-free 20 s clips from before (red) and after (blue) patients lost response to verbal commands. (B) We analyzed these clips using multitaper spectral analysis. In this patient (PT09) an increase in lower frequencies and a decrease in higher frequencies from before to after LOR can be observed. (C) To view the dynamics of the spectral changes through time we plotted a normalized spectrogram starting 2 min before LOR to 2 min after LOR. We can see the increase in lower frequencies and decrease in higher frequencies coordinates well with the LOR timestamp. (D) We tested several complexity measures of time-delayed embeddings (attractors). An awake attractor (red) looks less ellipsoidal than the anesthetized attractor (blue). (E) One method we used to quantify change in attractors before and after LOR is by fitting the attractor with an ellipsoid solid of revolution. We then calculate the ratio of the minimum and maximum radii.

FIGURE 2. Spectral characteristics before and after loss of response (LOR). (A) Example of multitaper spectrum from four patients pre- (red) and post- (blue) LOR. Note the increases in alpha and decrease in gamma activity following LOR. The shaded region represents the 95% confidence interval. We computed several standard spectral measures pre- and post-LOR. (B) Spectral edge frequency has been shown to correlate with anesthetic depth; however, we did not observe a significant difference. (C) We observed a significant increase in alpha activity after LOR (p = 0.015 corrected). (D) We observed a significant decrease in gamma activity after LOR (p = 0.03 corrected).

FIGURE 3. 1/f spectral changes occur with loss of response. We fit each patient’s spectral power to c/fα, where α and c were free parameters representing the quickness of frequency decay and an arbitrary constant, respectively. Panel (A) shows these plots for three patients, before and after LOC. (B) Values of α for each subject, pre-LOR and post-LOR. (C) Overall, we observed that 71% of the patients show an increase in α after LOR.

FIGURE 4. Quantifying dynamical attractors before and after loss of response (LOR). (A) We created time-delayed embeddings (attractors) from 20 s continuous clips. A shape change from thicker, less-ellipsoidal attractors before LOR (red) to flatter, more ellipsoidal attractors after LOR (blue) was observed and is shown here for 6 patients. We quantified the difference in attractors using both correlation dimension and our ellipse radius ratio (ERR). (B) We did not observe a significant difference in correlation dimension in 3 dimensions, nor did we observe a significant difference in correlation dimension in 5 dimensions (C). (D) We did observe a significant difference in our ERR measure from before to after LOR (p = 0.04 corrected). The ∗ indicates significant difference between pre-LOR and post-LOR measures at p < 0.05 corrected.

FIGURE 5. Attractor shape changes are embedding delay dependent. (A) Attractors from PT02 shown at 4, 52, 1000, and 2500 ms. The shape change in the attractor is not observed at higher embedding delays. We tested whether our attractor characterization analyses correlated with embedding delay. We computed correlation dimension and ellipse radius ratio (ERR) at 10 different delays from 4 to 2500 ms. (B) No significant changes in correlation dimension were observed from before to after LOR for any embedding delay nor was correlation dimension correlated with the embedding delay. Here we show results from the 3D correlation dimension calculation. (C) We observed a significant correlation between the ERR and embedding delay (rspearman = 0.17, p = 0.04) and a significant difference in the ERR between pre- and post-LOR for 4 ms and 8 ms delays (p4 = 0.017 corrected, p8 = 0.04 corrected). The ∗ indicates a significant difference between the measured values before and after loss of response at that embedding delay at p < 0.05 corrected.

FIGURE 6. Multiscale entropy reveals scale-dependent complexity change after loss of response. (A) Sample Entropy (SampEn) shows a decrease in complexity at short scale factors which monotonically increases until medium scale (rspearman = 0.45, p < 10-3) and then decreases toward 0 (rspearman = -0.31, p < 10-3). Here, the solid black line represents the mean. (B) At the shortest scale, the difference in SampEn between post-LOR and pre-LOR conditions is not significantly different from chance as measured by the median, but is when measured by mean (p = 0.04, percentile permutation test).