Spectral entropy indicates electrophysiological and hemodynamic changes in drug-resistant epilepsy - A multimodal MREG study

Abstract

Objective: Epilepsy causes measurable irregularity over a range of brain signal frequencies, as well as autonomic nervous system functions that modulate heart and respiratory rate variability. Imaging dynamic neuronal signals utilizing simultaneously acquired ultra-fast 10 Hz magnetic resonance encephalography (MREG), direct current electroencephalography (DC-EEG), and near-infrared spectroscopy (NIRS) can provide a more comprehensive picture of human brain function. Spectral entropy (SE) is a nonlinear method to summarize signal power irregularity over measured frequencies. SE was used as a joint measure to study whether spectral signal irregularity over a range of brain signal frequencies based on synchronous multimodal brain signals could provide new insights in the neural underpinnings of epileptiform activity.

Methods: Ten patients with focal drug-resistant epilepsy (DRE) and ten healthy controls (HC) were scanned with 10 Hz MREG sequence in combination with EEG, NIRS (measuring oxygenated, deoxygenated, and total hemoglobin: HbO, Hb, and HbT, respectively), and cardiorespiratory signals. After pre-processing, voxelwise SE_MREG was estimated from MREG data. Different neurophysiological and physiological subfrequency band signals were further estimated from MREG, DC-EEG, and NIRS: fullband (0-5 Hz, FB), near FB (0.08-5 Hz, NFB), brain pulsations in very-low (0.009-0.08 Hz, VLFP), respiratory (0.12-0.4 Hz, RFP), and cardiac (0.7-1.6 Hz, CFP) frequency bands. Global dynamic fluctuations in MREG and NIRS were analyzed in windows of 2 min with 50% overlap.

Results: Right thalamus, cingulate gyrus, inferior frontal gyrus, and frontal pole showed significantly higher SE_MREG in DRE patients compared to HC. In DRE patients, SE of cortical Hb was significantly reduced in FB (p = .045), NFB (p = .017), and CFP (p = .038), while both HbO and HbT were significantly reduced in RFP (p = .038, p = .045, respectively). Dynamic SE of HbT was reduced in DRE patients in RFP during minutes 2 to 6. Fitting to the frontal MREG and NIRS results, DRE patients showed a significant increase in SE_EEG in FB in fronto-central and parieto-occipital regions, in VLFP in parieto-central region, accompanied with a significant decrease in RFP in frontal pole and parietal and occipital (O2, Oz) regions.

Conclusion: This is the first study to show altered spectral entropy from synchronous MREG, EEG, and NIRS in DRE patients. Higher SE_MREG in DRE patients in anterior cingulate gyrus together with SE_EEG and SE_NIRS results in 0.12-0.4 Hz can be linked to altered parasympathetic function and respiratory pulsations in the brain. Higher SE_MREG in thalamus in DRE patients is connected to disturbances in anatomical and functional connections in epilepsy. Findings suggest that spectral irregularity of both electrophysiological and hemodynamic signals are altered in specific way depending on the physiological frequency range.

Keywords: EEG; Epilepsy; Irregularity; NIRS; Parasympathetic; Ultra-fast fMRI.

Fig. 1

Scanning, preprocessing and analysis with multimodal setup. A) MREG, EEG and NIRS methods separated. B) Voxelwise MREG signal after preprocessing and FIX. Temporal signals (global MREG, EEG, 32 channels, NIRS (Hbo, Hb, HbT) used in analysis, 10-min measures of all and 2-min sliding window measures of global MREG and NIRS. C) PSD calculated from all signals. D) SE calculated by Shannon's equation separately from all signals on chosen sub-bands (0.009–0.08 Hz, 0.12–0.4 Hz, 0.7–1.6 Hz, 0.08–5 Hz, 0–5 Hz). As a result SE value for all voxels in MREG and for global MREG signal, for EEG (all 32 leads, visualized in map), and for NIRS (Hbo, Hb, HbT). 0 < SE value <1. In SE_MREG: bright yellow = highest SE, dark red = lowest SE. In SE_EEG: purple = highest SE, bright blue = lowest SE. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 2

A) Average spectral entropy (SE) maps of FB MREG and FB MREG including FIX for DRE patients (n = 10) and HC (n = 10). Red illustrates the lowest and yellow the highest SE_MREG values (cut off 0.5). B) SE_MREG of FB MREG FIX was significantly higher in DRE patients than in HC in right thalamus, mid cingulate gyrus, inferior frontal gyrus, and frontal pole.

Fig. 3

Group-differences between DRE patients and HC in different SE measures, presented for 0–5 Hz, FB. Orange and yellow indicate a significant group-difference at p < 0.05(*), and p < 0.01 (**), respectively. A) Static SE_EEG for separate channels (mean ± STD) and spatial representation of EEG channels with indicators for increases in DRE patients. NIRS sensor indicated. B) SE_MREG map indicating an increase in frontal pole (where also NIRS sensor placed) and cingulate gyrus in DRE patients. C) SE_NIRS group differences in HbO, Hb (significantly lower in DRE patients), and HbT.

Fig. 4

Group-differences between DRE patients and HC in different SE measures presented for 0.12–0.4 Hz, RFP. Orange and yellow indicate a significant group-difference at p < 0.05(*), and p < 0.01 (**), respectively. A) Static SE_EEG for separate channels (mean ± STD) and spatial representation of EEG channels with indicators for increases in DRE patients. B) Dynamic sliding-window results in SE_MREG. C) Dynamic sliding-window results in SE_NIRS HbT.