Altered cortical alpha modulations and connectivity in complex regional pain syndrome

Chronic pain alters resting-state cerebral alpha rhythms (8-12 Hz), including whole-brain slowing of peak alpha frequency (PAF). Nevertheless, how the power of brain activity at PAF (PAF power) or across the entire alpha frequency range (alpha power) is decreased or increased compared to healthy controls (HC) varies greatly across pain phenotypes. The brain regions exhibiting such alterations and their association with the pain severity experienced by patients are also unclear. The study addressed this question in participants experiencing complex regional pain syndrome (CRPS; 19 females and 10 males) against pain-free HC (14 females and 15 males). Resting-state magnetoencephalography imaging was used to estimate the power spectral density of neurophysiological activity across the cortex to identify group differences in alpha activity. The study found decreased alpha power and slower PAF in patients with CRPS, especially over bilateral posteromedial regions including the precuneus, paracentral and superior parietal cortices. In CRPS, pain severity was associated with the suppression of PAF power in the medial and lateral prefrontal cortex (PFC) and orbitofrontal cortex (OFC). Furthermore, the same PFC and OFC areas showed increased interregional alpha-band functional connectivity in patients with CRPS. Although the greatest pain-related alpha alterations mapped to sensory-discriminative areas, including the posteromedial cortex, PFC alpha activity encoded subjective CRPS pain severity. Hyperconnectivity between medial PFC and OFC further emphasized the affective-motivational nature of CRPS pain. Overall, these findings highlight the multiple functional roles of alpha activity in nociplastic conditions such as CRPS and provide potential targets for neuromodulatory interventions. PERSPECTIVE: Complex regional pain syndrome (CRPS) is a debilitating disorder driven by altered brain processes. The authors characterize deviations in alpha brain activity in CRPS compared to healthy controls which could inform the development of novel neuromodulation therapies.