Imbalance in positive and negative acceleration ratio of alpha oscillation in patients with complex regional pain syndrome

Abstract

Objectives: To elucidate the functional characteristics of the brain in the presence of chronic pain using electroencephalography (EEG), with a focus on the dynamics of neural excitation and inhibition.

Methods: Resting-state EEG was performed in: 17 patients with complex regional pain syndrome (CRPS) who exhibited chronic pain higher than 20 on the visual analogue scale (VAS), 6 patients with reduced CRPS symptoms and chronic pain less than 20 on VAS, and healthy age-matched controls. For the analysis, 50 s of electroencephalogram (EEG) signals were extracted from EEG recordings during wakefulness and rest with eyes closed. The envelope of the alpha frequency band was calculated by examining the positive and negative accelerations of the envelope oscillation, ratio of positive (Ap) to negative (An) accelerations (Ap-An ratio), and mean amplitude of the envelope. Comparisons were made between patients and controls, and correlations between these EEG measures and the subjective pain VAS were evaluated.Significant differences in the value of Ap, An and Ap-An ratio were observed at temporal and central electrodes between patients with pain symptoms and controls. Those with reduced CRPS symptoms exhibited a distinct Ap-An ratio at the majority of electrodes when compared with those exhibiting chronic pain.

Conclusions: Distinct patterns in alpha wave envelope dynamics, reflecting excitatory and inhibitory activities, were associated with chronic pain in patients with CRPS. The pain-relieved state of CRPS suggested that a new balance of activities was established. This relationship indicated a potential association between altered alpha oscillation characteristics and the subjective experience of pain.

Significance: This study introduces a novel method for analyzing alpha oscillation envelopes, providing new insights into the neural pathophysiology of chronic pain in CRPS patients. This approach has the potential to enhance our understanding of the alterations in brain function that occur under chronic pain conditions.

Keywords: Chronic pain; Cortex; E-I balance; Electroencephalography.

Fig. 1

Conceptual illustration of the present study. Top: Neural oscillator models, consisting of nonlinear equations of oscillation, and second-order derivatives, which can correspond to inhibitory or excitatory forces. Note: The equations are not equations for the alpha wave envelope, but simple oscillator model equations for illustrative purposes. Middle: Envelope of alpha oscillation is shaped by the interplay between excitation and inhibition within neural circuits, encompassing cortical, subcortical, and network structures. Arrows denote the positive (Ap) and negative (An) accelerations, which are the second-order time derivatives of the alpha envelope. Alpha oscillation and the envelope function to transmit information, and imbalance of excitation and inhibition may occur in brain areas of patients with complex regional pain syndrome (CRPS).

Fig. 2

Waveform analysis procedures. In this study, the resting-state EEG was processed from A to C. A: EEG signals filtered by the alpha bandpass filter between 8 and 13 Hz (black line). B: Absolute amplitude of alpha activity (blue line) and peak envelope (red line). C: Second derivative of envelope (red line). (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 3

Comparisons of acceleration values between CRPS patients with pain VAS higher than 20 (red cilums) and controls (blue columns) at each electrode. A: Ap-An ratio: ratio of Ap divided by An. The Ap-An ratio at T4 was greater in patients than controls (p = 0.0445). B: Ap (acceleration positive) value. C: An (acceleration negative) value. Both Ap (p < 0.0001) and An (p < 0.0001) values were lower in patients than controls at Cz. *p < 0.05, FDR. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 4

Comparisons of acceleration values between CRPS patients with pain VAS less than 20 (yellow columns) and controls (blue columns) at each electrode: A: Ap-An ratio: ratio of Ap divided by An. The Ap-An ratio was lower at O2 (p = 0.0486), T1 (0.0384), O1 (0.0321), F3 (0.0254), T6 (0.0302), Fz (0.0325), P3 (0.0319), P4 (0.0355), and Cz (0.0338). B: Ap (acceleration positive) value. C: An (acceleration negative) value. There was no significant difference in Ap and An values for each electrode. *p < 0.05, FDR. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 5

Comparisons of mean envelope amplitude between patients and controls. A: Comparisons of mean envelope amplitude between patients with pain VAS higher than 20 (red columns) and controls (blue columns). Multiple comparisons showed that the values at C3 (p = 0.0330), Cz (0.0357), P4 (0.0329), and Pz (0.0299) were smaller in the patients than controls (p < 0.05, FDR). B: The mean envelope amplitude differed between patients with pain VAS less than 20 (yellow columns) and controls (blue columns). No difference was found at any electrode. *p < 0.05, FDR. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 6

Correlation between mean acceleration values and the pain VAS for all electrodes. A: Ap-An ratio: ratio of Ap divided by An. B: Ap (acceleration positive) value. C: An (acceleration negative) value. D: Amplitude of the envelope of alpha waves. Red circles indicate patient participants with pain VAS higher than 20 (n = 17). Yellow circles indicate patient participants with pain VAS less than 20 (n = 6), and their EEG was re-measured after improvement in subjective pain symptoms of CRPS. The correlation between the mean Ap-An ratio for all electrodes in the patients (n = 23) and pain VAS was significant. A correlation curve is shown for the correlation between the Ap-An ratio and pain VAS. Pain VAS did not correlate with mean Ap and An values or the envelope amplitude for all electrodes. r; Pearson's correlation coefficient, *p < 0.05.

Fig. 7

The correlation between the Ap-An ratio and pain VAS at each electrode for all patients with CRPS. Significant positive correlations were noted between the Ap-An ratio and pain VAS at multiple electrodes, including P3 (r = 0.634, p = 0.0197, FDR), T6 (0.622, 0.0131), T1 (0.612, 0.0108), P4 (0.610, 0.0086), T3 (0.566, 0.0164), and Cz (0.563, 0.0146), after multiple comparisons.