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

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 underexplored in this context. More generally, neuropathic pain has been associated with increased theta-band power and slowing of peak alpha frequency 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 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. Exploratory analyses showed a positive association between one measure of peak alpha frequency and pain intensity. However, inconsistent replication across spectral measures and tests indicates that these amputation and pain intensity-related findings should be interpreted with caution. For instance, results differed depending on the metric used (spectral maximum vs. center of gravity), highlighting the sensitivity of peak alpha frequency analyses to methodological choices. Together, these results suggest that resting-state EEG markers commonly reported in chronic pain do not straightforwardly generalize to PLP.