A Review of Effects of Spinal Cord Stimulation on Spectral Features in Resting-State Electroencephalography.

BACKGROUND: Spinal cord stimulation (SCS) is an effective therapy for patients with refractory chronic pain syndromes. Although studies have shown that SCS has both spinal and supraspinal effects, the current understanding of cortical effects is still limited. Neuroimaging techniques, such as magnetoencephalography (MEG) and electroencephalography (EEG), combined here as M/EEG, can reveal modulations in ongoing resting-state cortical activity. We aim to provide an overview of available literature on resting-state M/EEG in patients with chronic pain who have been treated with SCS. MATERIALS AND METHODS: We searched multiple online data bases for studies on SCS, chronic pain, and resting-state M/EEG. Primary outcome measures were changes in spectral features, combined with brain regions in which these changes occurred. RESULTS: We included eight studies reporting various SCS paradigms (tonic, burst, high-dose, and high-frequency stimulation) and revealing heterogeneity in outcome parameters. We summarized changes in cortical activity in various frequency bands: theta (4-7 Hz), alpha (7-12 Hz), beta (13-30 Hz), and gamma (30-44 Hz). In multiple studies, the somatosensory cortex showed modulation of cortical activity under tonic, burst, and high-frequency stimulation. Changes in connectivity were found in the dorsal anterior cingulate cortex, dorsolateral prefrontal cortex, and parahippocampus. CONCLUSIONS: The large heterogeneity observed in outcome measures is probably caused by the large variety in study designs, stimulation paradigms, and spectral features studied. Paresthesia-free paradigms have been compared with tonic stimulation in multiple studies. These studies suggest modulation of medial, lateral, and descending pathways for paresthesia-free stimulation, whereas tonic stimulation predominantly modulates lateral and descending pathways. Moreover, multiple studies have reported an increased alpha peak frequency, increased alpha power, and/or decreased theta power when SCS was compared with baseline, indicating modulation of thalamocortical pathways. Further studies with well-defined groups of responders and nonresponders to SCS are recommended to independently study the cortical effects of pain relief and SCS.

Heterogeneous Cortical Effects of Spinal Cord Stimulation.

OBJECTIVES: The understanding of the cortical effects of spinal cord stimulation (SCS) remains limited. Multiple studies have investigated the effects of SCS in resting-state electroencephalography. However, owing to the large variation in reported outcomes, we aimed to describe the differential cortical responses between two types of SCS and between responders and nonresponders using magnetoencephalography (MEG). MATERIALS AND METHODS: We conducted 5-minute resting-state MEG recordings in 25 patients with chronic pain with active SCS in three sessions, each after a one-week exposure to tonic, burst, or sham SCS. We extracted six spectral features from the measured neurophysiological signals: the alpha peak frequency; alpha power ratio (power 7-9 Hz/power 9-11 Hz); and average power in the theta (4-7.5 Hz), alpha (8-12.5 Hz), beta (13-30 Hz), and low-gamma (30.5-60 Hz) frequency bands. We compared these features (using nonparametric permutation t-tests) for MEG sensor and cortical map effects across stimulation paradigms, between participants who reported low (< 5, responders) vs high (≥ 5, nonresponders) pain scores, and in three representative participants. RESULTS: We found statistically significant (p < 0.05, false discovery rate corrected) increased MEG sensor signal power below 3 Hz in response to burst SCS compared with tonic and sham SCS. We did not find statistically significant differences (all p > 0.05) between the power spectra of responders and nonresponders. Our data did not show statistically significant differences in the spectral features of interest among the three stimulation paradigms or between responders and nonresponders. These results were confirmed by the MEG cortical maps. However, we did identify certain trends in the MEG source maps for all comparisons and several features, with substantial variation across participants. CONCLUSIONS: The considerable variation in cortical responses to the various SCS treatment options necessitates studies with sample sizes larger than commonly reported in the field and more personalized treatment plans. Studies with a finer stratification between responders and nonresponders are required to advance the knowledge on SCS treatment effects.

Neurophysiological oscillatory markers of hypoalgesia in conditioned pain modulation.

Introduction: Conditioned pain modulation (CPM) is an experimental procedure that consists of an ongoing noxious stimulus attenuating the pain perception caused by another noxious stimulus. A combination of the CPM paradigm with concurrent electrophysiological recordings can establish whether an association exists between experimentally modified pain perception and modulations of neural oscillations. Objectives: We aimed to characterize how CPM modifies pain perception and underlying neural oscillations. We also interrogated whether these perceptual and/or neurophysiological effects are distinct in patients affected by chronic pain. Methods: We presented noxious electrical stimuli to the right ankle before, during, and after CPM induced by an ice pack placed on the left forearm. Seventeen patients with chronic pain and 17 control participants rated the electrical pain in each experimental condition. We used magnetoencephalography to examine the anatomy-specific effects of CPM on the neural oscillatory responses to the electrical pain. Results: Regardless of the participant groups, CPM induced a reduction in subjective pain ratings and neural responses (beta-band [15-35 Hz] oscillations in the sensorimotor cortex) to electrical pain. Conclusion: Our findings of pain-induced beta-band activity may be associated with top-down modulations of pain, as reported in other perceptual modalities. Therefore, the reduced beta-band responses during CPM may indicate changes in top-down pain modulations.

Magnetoencephalography reveals increased slow-to-fast alpha power ratios in patients with chronic pain.

INTRODUCTION: Objective disease markers are a key for diagnosis and personalized interventions. In chronic pain, such markers are still not available, and therapy relies on individual patients' reports. However, several pain studies have reported group-based differences in functional magnetic resonance imaging, electroencephalography, and magnetoencephalography (MEG). OBJECTIVES: We aimed to explore spectral differences in resting-state MEG brain signals between patients with chronic pain and pain-free controls and to characterize the cortical and subcortical regions involved. METHODS: We estimated power spectral density over 5 minutes of resting-state MEG recordings in patients with chronic pain and controls and derived 7 spectral features at the sensor and source levels: alpha peak frequency, alpha power ratio (power 7-9 Hz divided by power 9-11 Hz), and average power in theta, alpha, beta, low-gamma, and high-gamma bands. We performed nonparametric permutation t tests (false discovery rate corrected) to assess between-group differences in these 7 spectral features. RESULTS: Twenty-one patients with chronic pain and 25 controls were included. No significant group differences were found in alpha peak frequency or average power in any frequency band. The alpha power ratio was significantly higher (P < 0.05) in patients with chronic pain at both the sensor and brain source levels. The brain regions showing significantly higher ratios included the occipital, parietal, temporal and frontal lobe areas, insular and cingulate cortex, and right thalamus. CONCLUSION: The alpha power ratio is a simple, promising signal marker of chronic pain, affecting an expansive range of cortical and subcortical regions, including known pain-processing areas.