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

<b>Background/Objectives</b>: 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 stim...

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Main Authors: Guilherme J. M. Lacerda, Lucas Camargo, Fernanda M. Q. Silva, Marta Imamura, Linamara R. Battistella, Felipe Fregni
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/13/5/1015
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author Guilherme J. M. Lacerda
Lucas Camargo
Fernanda M. Q. Silva
Marta Imamura
Linamara R. Battistella
Felipe Fregni
author_facet Guilherme J. M. Lacerda
Lucas Camargo
Fernanda M. Q. Silva
Marta Imamura
Linamara R. Battistella
Felipe Fregni
author_sort Guilherme J. M. Lacerda
collection DOAJ
description <b>Background/Objectives</b>: 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. <b>Methods</b>: 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). <b>Results</b>: 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. <b>Conclusions</b>: 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.
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spelling doaj-art-b73a93e8eb6a4b698d9c5b53b8caab5f2025-08-20T03:14:45ZengMDPI AGBiomedicines2227-90592025-04-01135101510.3390/biomedicines13051015Defective Intracortical Inhibition as a Marker of Impaired Neural Compensation in Amputees Undergoing RehabilitationGuilherme J. M. Lacerda0Lucas Camargo1Fernanda M. Q. Silva2Marta Imamura3Linamara R. Battistella4Felipe Fregni5Instituto de Medicina Física e Reabilitação, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 04116-030, SP, BrazilNeuromodulation Center, Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USANeuromodulation Center, Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USAInstituto de Medicina Física e Reabilitação, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 04116-030, SP, BrazilInstituto de Medicina Física e Reabilitação, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 04116-030, SP, BrazilNeuromodulation Center, Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA<b>Background/Objectives</b>: 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. <b>Methods</b>: 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). <b>Results</b>: 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. <b>Conclusions</b>: 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.https://www.mdpi.com/2227-9059/13/5/1015lower-limb amputationneuroplasticityneurophysiological biomarkerstranscranial magnetic stimulation
spellingShingle Guilherme J. M. Lacerda
Lucas Camargo
Fernanda M. Q. Silva
Marta Imamura
Linamara R. Battistella
Felipe Fregni
Defective Intracortical Inhibition as a Marker of Impaired Neural Compensation in Amputees Undergoing Rehabilitation
Biomedicines
lower-limb amputation
neuroplasticity
neurophysiological biomarkers
transcranial magnetic stimulation
title Defective Intracortical Inhibition as a Marker of Impaired Neural Compensation in Amputees Undergoing Rehabilitation
title_full Defective Intracortical Inhibition as a Marker of Impaired Neural Compensation in Amputees Undergoing Rehabilitation
title_fullStr Defective Intracortical Inhibition as a Marker of Impaired Neural Compensation in Amputees Undergoing Rehabilitation
title_full_unstemmed Defective Intracortical Inhibition as a Marker of Impaired Neural Compensation in Amputees Undergoing Rehabilitation
title_short Defective Intracortical Inhibition as a Marker of Impaired Neural Compensation in Amputees Undergoing Rehabilitation
title_sort defective intracortical inhibition as a marker of impaired neural compensation in amputees undergoing rehabilitation
topic lower-limb amputation
neuroplasticity
neurophysiological biomarkers
transcranial magnetic stimulation
url https://www.mdpi.com/2227-9059/13/5/1015
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