# Defective Intracortical Inhibition as a Marker of Impaired Neural Compensation in Amputees Undergoing Rehabilitation

## TL;DR

This study finds that reduced cortical inhibition in the brain is linked to phantom limb pain in amputees, suggesting impaired neural compensation.

## Contribution

The study identifies reduced short intracortical inhibition (SICI) as a marker of maladaptive neuroplasticity in amputees with phantom limb pain.

## Key findings

- Reduced SICI correlates with the presence of phantom limb pain but not its intensity.
- Longer amputation duration is associated with disrupted SICI, indicating long-term plasticity changes.
- Increased MEP amplitude is linked to reduced functional independence in amputees.

## Abstract

Background/Objectives: Lower-limb amputation (LLA) leads to disability, impaired mobility, and reduced quality of life, affecting 1.6 million people in the USA. Post-amputation, motor cortex reorganization occurs, contributing to phantom limb pain (PLP). Transcranial magnetic stimulation (TMS) assesses changes in cortical excitability, helping to identify compensatory mechanisms. This study investigated the association between TMS metrics and clinical and neurophysiological outcomes in LLA patients. Methods: A cross-sectional analysis of the DEFINE cohort, with 59 participants, was carried out. TMS metrics included resting motor threshold (rMT), motor-evoked potential (MEP) amplitude, short intracortical inhibition (SICI), and intracortical facilitation (ICF). Results: Multivariate analysis revealed increased ICF and rMT in the affected hemisphere of PLP patients, while SICI was reduced with the presence of PLP. A positive correlation between SICI and EEG theta oscillations in the frontal, central, and parietal regions suggested compensatory mechanisms in the unaffected hemisphere. Increased MEP was associated with reduced functional independence. Conclusions: SICI appears to be a key factor linked to the presence of PLP, but not its intensity. Reduced SICI may indicate impaired cortical compensation, contributing to PLP. Other neural mechanisms, including central sensitization and altered thalamocortical connectivity, may influence PLP’s severity. Our findings align with those of prior studies, reinforcing low SICI as a marker of maladaptive neuroplasticity in amputation-related pain. Additionally, longer amputation duration was associated with disrupted SICI, suggesting an impact of long-term plasticity changes.