Identifying and Engaging Neuronal Oscillations by Transcranial Alternating Current Stimulation in Patients With Chronic Low Back Pain: A Randomized, Crossover, Double-Blind, Sham-Controlled Pilot Study

Abstract

Chronic pain is associated with maladaptive reorganization of the central nervous system. Recent studies have suggested that disorganization of large-scale electrical brain activity patterns, such as neuronal network oscillations in the thalamocortical system, plays a key role in the pathophysiology of chronic pain. Yet, little is known about whether and how such network pathologies can be targeted with noninvasive brain stimulation as a nonpharmacological treatment option. We hypothesized that alpha oscillations, a prominent thalamocortical activity pattern in the human brain, are impaired in chronic pain and can be modulated with transcranial alternating current stimulation (tACS). We performed a randomized, crossover, double-blind, sham-controlled study in patients with chronic low back pain (CLBP) to investigate how alpha oscillations relate to pain symptoms for target identification and whether tACS can engage this target and thereby induce pain relief. We used high-density electroencephalography to measure alpha oscillations and found that the oscillation strength in the somatosensory region at baseline before stimulation was negatively correlated with pain symptoms. Stimulation with alpha-tACS compared to sham (placebo) stimulation significantly enhanced alpha oscillations in the somatosensory region. The stimulation-induced increase of alpha oscillations in the somatosensory region was correlated with pain relief. Given these findings of successful target identification and engagement, we propose that modulating alpha oscillations with tACS may represent a target-specific, nonpharmacological treatment approach for CLBP. This trial has been registered in ClinicalTrials.gov (NCT03243084). PERSPECTIVE: This study suggests that a rational design of transcranial alternating current stimulation, which is target identification, engagement, and validation, could be a nonpharmacological treatment approach for patients with CLBP.

Keywords: Chronic low back pain; alpha oscillations; electroencephalography; transcranial alternating current stimulation.

Figure 1.

Stimulation montage, waveforms, and distributions of electric field in the brain. (A) Electrodes E1 and E2 delivered in-phase 10Hz-tACS with 1mA amplitude (zero-to-peak). Electrode E3 was used as the return electrode. (B) Normalized electric field distribution (V/m) by bifrontal 10Hz-tACS (top-view and left-top-view) in grey and white matter.

Figure 2.

Correlations between baseline alpha oscillations and clinical assessments (DVPRS and ODI). (A) Topographical distribution for DVPRS and ODI. Small black dots represent EEG channels with statistical significance (p<0.05, FDR corrected). (B) Scatter plot for correlated ODI and DVPRS (rho=0.6375, p=0.0025).

Figure 3.

Averaged topographical distribution of changes in spatially-normalized alpha oscillations for tACS (left), sham (middle), and the difference (right). Individual alpha frequency was used (IAF±1Hz) and small black dots represent EEG channels with statistical significance (p<0.05, FDR corrected).

Figure 4.

Topographical distribution of correlations between enhanced alpha oscillations and pain symptom changes. Small black dot represent EEG channels with statistical significance (p<0.05, FDR corrected).

Figure 5.

Changes in pain assessments (DVPRS and ODI) under stimulation conditions (tACS and sham). Statistical significance was assessed with the non-parametric Wilcoxon sign-rank test (*: p<0.05). Red symbol indicates an outlier.