Time-Frequency Analysis of Somatosensory Evoked High-Frequency (600 Hz) Oscillations as an Early Indicator of Arousal Recovery after Hypoxic-Ischemic Brain Injury

Figures

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  Figure 1. Experiment protocol. (a) Placements for arterial catheter, somatosensory evoked potential (SSEP) stimulating electrodes, and electrocardiogram (ECG) recording electrodes. (b) electroencephalogram (EEG)/SSEP recording electrode placements. Electrodes A and B were placed on the primary somatosensory cortex hindlimb regions (anterior/posterior (AP): −2; midline/lateral (ML): ±2). Ground (G) and reference (R) electrodes were placed on top of the posterior parietal lobe (AP: −5; ML: ±3). (c) Experimental timeline. Created with Biorender.com.

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  Figure 2. Parameter extraction from high-frequency oscillations (HFOs) and SSEPs in the time and time-frequency domain. (a) Grand averaged (n = 11 subjects) HFO waveform during anesthesia washout. The largest peak-to-peak amplitude was extracted as the parameter. (b) Grand averaged SSEP waveform during anesthesia washout. The N10-P15 peak-to-peak amplitude was extracted as the parameter. (c) Continuous wavelet transform (CWT) successfully isolated HFOs as a single peak around 600 Hz and 13 ms in the time-frequency domain. The color axis represents the signal power at a particular time and frequency. The peak latency, peak frequency, peak power, and the total power in the normal time-frequency space (NTFS) were used to characterize HFOs in the time-frequency (TF) domain. (d) SSEPs in the time-frequency domain using CWT. SSEP formed a single peak around 100 Hz and 20 ms. Created with Biorender.com.

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  Figure 3. SSEP did not recover to the original waveform 60 min post-ROSC. (a) Evolution of SSEPs for group CA3 (n = 5 subjects). The x-axis spans from 10 ms before stimulation to 40 ms after stimulation. Each row represents one averaged SSEP waveform of 100 trials, and a twenty-second gap exists between subsequent rows. The y-axis spans from 0 min to 80 min since baseline. The onsets of CA and ROSC are highlighted with a red and a green line. The SSEP components are highlighted within the blue box. The N10 and P15 peak components were present before CA. During recovery, the N10 peak separated into two peaks, N7 and N10, and the P15 peak was preserved. (b) Evolution of SSEPs for group CA7 (n = 6 subjects) of CA. N10 separated into two peaks, N7 and N10, and the P15 peak was not preserved. Created with Biorender.com.

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  Figure 4. Normalized HFO peak-to-peak amplitudes recovered earlier and more robustly than normalized SSEP peak-to-peak amplitudes in the first 60 min post-ROSC (n = 11 subjects). The two-way repeated measure ANOVA test followed by a post hoc analysis found that the SSEP peak-to-peak amplitude was significantly different than baseline for the entire 60 min post-ROSC, and the HFO peak-to-peak amplitude was only significantly different for 1–15 min and 31–45 min post-ROSC. The difference between HFO and SSEP peak-to-peak amplitudes was statistically significant for all 60 min. * p < 0.05, ** p < 0.01, and *** p < 0.001. Created with Biorender.com.

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  Figure 5. TF representation of grand average HFOs (n = 11 subjects) at washout, CA, and recovery periods 1–15 min, 16–30 min, 31–45 min, 46–60 min post-ROSC. CWT was used to transform the time-domain HFOs into their TF domain representations. The scalogram for each block, or the absolute value of the CWT coefficients of HFOs, was plotted. The color scale represents the absolute value of the CWT coefficients, i.e., the power of the HFOs at a particular time and frequency. The HFOs formed a single peak around 13 ms post-stimulation and 600 Hz in the TF domain during washout. However, the TF peak dissipated after CA and gradually recovered but did not form a single peak by the end of 60 min of recovery. In addition, a sudden burst of HFOs was present during the 16–30 min block. Created with Biorender.com.

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  Figure 6. HFO NTFS power showed a significant decrease after 7 min of CA. (a) NTFS power evolution for group CA3 (n = 5). (b) NTFS power evolution for group CA7 (n = 6). * p < 0.05, ** p < 0.01. Created with Biorender.com.

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  Figure 7. HFO NTFS power showed significant separation between favorable (n = 6) and unfavorable (n = 5) outcome groups during the first 60 min post-ROSC. * p < 0.05, ** p < 0.01. Created with Biorender.com.

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  Figure 8. HFOs experienced a sudden burst post-ROSC for both outcome groups. The frequency spectrum of HFOs was plotted from 0 min to 60 min post-ROSC. The largest magnitude CWT coefficients for each frequency in the time window of 10 to 20 ms were extracted to represent the HFO spectrum. The left axis spans from 200 Hz to 1000 Hz; the right axis spans from 0 min to 60 min since ROSC; the vertical axis represents the magnitude of HFO at a particular frequency. (a) HFO spectrum for favorable outcome group. (b) HFO spectrum for unfavorable outcome group. (c) Peak burst time for both injury groups CA3 and CA7. * p < 0.05. Created with Biorender.com.