Resting-State Theta and Alpha Oscillations in Amputation and Phantom Limb Pain: A Pre-Registered High-Density EEG Study

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Abstract

Phantom limb pain (PLP) affects a substantial portion of individuals with limb amputation, yet its neural mechanisms remain poorly understood. While neuroimaging studies have predominantly employed functional magnetic resonance imaging and magnetoencephalography, resting-state EEG could offer complementary insight into intrinsic brain oscillations but remains largely unexplored in this specific context. More generally, chronic and neuropathic pain have been associated with increased theta-band (4–8 Hz) power and reduced peak alpha frequency (8–13 Hz), but whether these patterns extend to PLP is unknown. Here, we conducted a pre-registered cross-sectional investigation of high-density resting-state EEG (58 channels) in 19 intact controls, 6 amputees without PLP, and 13 amputees with PLP. We employed mixed-effects models with bootstrap inference, multiple sensitivity analyses, and exploratory cluster-based permutation testing. Across primary and sensitivity analyses, we found no evidence for a robust association between the presence of PLP and either theta power or peak alpha frequency. Amputation-related differences in the alpha band reached statistical significance in some analyses, suggesting possible alpha-band alterations associated with limb loss rather than pain per se. An exploratory analysis within the PLP group showed a positive association between one measure of peak alpha frequency and pain intensity. However, inconsistent replication across spectral measures and statistical approaches indicates that these amputation and pain intensity-related findings should be interpreted with caution and require confirmation in larger, well-powered studies. Together, these results suggest that resting-state EEG markers commonly reported in chronic pain do not straightforwardly generalize to PLP.

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