The Efficacy of Therapies for Phantom Limb Pain in Amputees Assessed via Functional Magnetic Resonance Imaging (fMRI) and Electroencephalography (EEG) Measures of Cortical Reorganization: A Scoping Review.

Phantom limb pain (PLP) is a prevalent and debilitating condition affecting most amputees, attributable to complex maladaptive neuroplastic changes of the peripheral and central nervous system components. Cortical reorganization, particularly within the primary motor (M1) and somatosensory (S1) cortices, has been proposed as the central phenomenon underlying PLP. Neuroimaging modalities such as functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) provide objective measures for evaluating these neuroplastic changes and assessing treatment efficacy. This scoping review aims to evaluate nonpharmacologic therapies for PLP and to obtain objective, evidence-based measures of clinical benefit. Three databases (Embase, Ovid MEDLINE, and Web of Science) were searched for peer-reviewed English-language articles published between 2015 and 2025 that included fMRI and EEG measurements to determine the efficacy of treatments in upper- and lower-extremity amputees. Search terms included "amputation," "cortical reorganization," "rehabilitation," "therapy," "treatment," and "phantom limb." A total of 565 articles were initially identified. After removing duplicates, 392 articles were screened, 39 full texts reviewed for eligibility, and seven determined to meet the inclusion criteria. The findings suggest that effective interventions were generally associated with changes in cortical organization of M1 and S1 regions. Mirror therapy (MT) trials showed consistent reductions in PLP, accompanied by normalization of maladaptive sensorimotor activity. Brain stimulation techniques exhibited strong neuromodulatory effects, with significant pain reduction and corresponding changes in cortical excitability and thalamocortical networks. Prosthetic use and augmented reality (AR) therapies demonstrated functional cortical adaptations, though their correlation with pain reduction was less consistent. Overall, many studies demonstrated parallel improvements in pain and cortical reorganization. It is concluded that nonpharmacologic therapies for PLP are frequently associated with measurable changes in cortical organization, particularly within the M1 and S1 cortices, highlighting the role of neuroplasticity in both the pathogenesis and treatment of PLP. However, the relationship between cortical changes and PLP reduction remains inconsistent, suggesting that PLP is a multifactorial, network-level condition involving primary, secondary, and subcortical regions. These findings highlight the potential of fMRI and EEG as objective measures of treatment response and their role as potential biomarkers. This scoping review reinforces the need for further research to better define mechanisms and optimize targeted, multimodal treatment strategies.