K Pacheco-Barrios1, C B Pinto2, F G Saleh Velez3, D Duarte4, M E Gunduz2, M Simis5, A C Lepesteur Gianlorenco2, J L Barouh2, D Crandell6, M Guidetti7, L Battistella5, F Fregni8. 1. Neuromodulation Center and Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Universidad San Ignacio de Loyola, Vicerrectorado de Investigación, Unidad de Investigación para la Generación y Síntesis de Evidencias en Salud, Lima, Peru. 2. Neuromodulation Center and Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. 3. Neuromodulation Center and Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; University of Chicago Medical Center, Department of Neurology, University of Chicago, Chicago, IL, USA. 4. Neuromodulation Center and Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Psychiatry and Behavioural Neurosciences, McMaster University, Canada. 5. Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil. 6. Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA, USA. 7. Università degli Studi di Milano, Dipartimento di scienze della Salute, "Aldo Ravelli" Center for Neurotechnolgy and Experimental Brain Therapeutics, Milano, Italy. 8. Neuromodulation Center and Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: Fregni.Felipe@mgh.harvard.edu.
Abstract
OBJECTIVE: The role of motor cortex reorganization in the development and maintenance of phantom limb pain (PLP) is still unclear. This study aims to evaluate neurophysiological and structural motor cortex asymmetry in patients with PLP and its relationship with pain intensity. METHODS: Cross-sectional analysis of an ongoing randomized-controlled trial. We evaluated the motor cortex asymmetry through two techniques: i) changes in cortical excitability indexed by transcranial magnetic stimulation (motor evoked potential, paired-pulse paradigms and cortical mapping), and ii) voxel-wise grey matter asymmetry analysis by brain magnetic resonance imaging. RESULTS: We included 62 unilateral traumatic lower limb amputees with a mean PLP of 5.9 (SD = 1.79). We found, in the affected hemisphere, an anterior shift of the hand area center of gravity (23 mm, 95% CI 6 to 38, p = 0.005) and a disorganized and widespread representation. Regarding voxel-wise grey matter asymmetry analysis, data from 21 participants show a loss of grey matter volume in the motor area of the affected hemisphere. This asymmetry seems negatively associated with time since amputation. For TMS data, only the ICF ratio is negatively correlated with PLP intensity (r = -0.25, p = 0.04). CONCLUSION: There is an asymmetrical reorganization of the motor cortex in patients with PLP, characterized by a disorganized, widespread, and shifted hand cortical representation and a loss in grey matter volume in the affected hemisphere. This reorganization seems to reduce across time since amputation. However, it is not associated with pain intensity. SIGNIFICANCE: These findings are significant to understand the role of the motor cortex reorganization in patients with PLP, showing that the pain intensity may be related with other neurophysiological factors, not just cortical reorganization.
OBJECTIVE: The role of motor cortex reorganization in the development and maintenance of phantom limb pain (PLP) is still unclear. This study aims to evaluate neurophysiological and structural motor cortex asymmetry in patients with PLP and its relationship with pain intensity. METHODS: Cross-sectional analysis of an ongoing randomized-controlled trial. We evaluated the motor cortex asymmetry through two techniques: i) changes in cortical excitability indexed by transcranial magnetic stimulation (motor evoked potential, paired-pulse paradigms and cortical mapping), and ii) voxel-wise grey matter asymmetry analysis by brain magnetic resonance imaging. RESULTS: We included 62 unilateral traumatic lower limb amputees with a mean PLP of 5.9 (SD = 1.79). We found, in the affected hemisphere, an anterior shift of the hand area center of gravity (23 mm, 95% CI 6 to 38, p = 0.005) and a disorganized and widespread representation. Regarding voxel-wise grey matter asymmetry analysis, data from 21 participants show a loss of grey matter volume in the motor area of the affected hemisphere. This asymmetry seems negatively associated with time since amputation. For TMS data, only the ICF ratio is negatively correlated with PLP intensity (r = -0.25, p = 0.04). CONCLUSION: There is an asymmetrical reorganization of the motor cortex in patients with PLP, characterized by a disorganized, widespread, and shifted hand cortical representation and a loss in grey matter volume in the affected hemisphere. This reorganization seems to reduce across time since amputation. However, it is not associated with pain intensity. SIGNIFICANCE: These findings are significant to understand the role of the motor cortex reorganization in patients with PLP, showing that the pain intensity may be related with other neurophysiological factors, not just cortical reorganization.
Authors: Cees P van der Schans; Jan H B Geertzen; Tanneke Schoppen; Pieter U Dijkstra Journal: J Pain Symptom Manage Date: 2002-10 Impact factor: 3.612
Authors: N Birbaumer; W Lutzenberger; P Montoya; W Larbig; K Unertl; S Töpfner; W Grodd; E Taub; H Flor Journal: J Neurosci Date: 1997-07-15 Impact factor: 6.167
Authors: Sandra Preissler; Johanna Feiler; Caroline Dietrich; Gunther O Hofmann; Wolfgang H R Miltner; Thomas Weiss Journal: Cereb Cortex Date: 2012-04-17 Impact factor: 5.357
Authors: Sandra Preißler; Désirée Thielemann; Caroline Dietrich; Gunther O Hofmann; Wolfgang H R Miltner; Thomas Weiss Journal: Front Hum Neurosci Date: 2017-06-20 Impact factor: 3.169
Authors: Kevin Pacheco-Barrios; Paulo Sampaio de Melo; Karen Vasquez-Avila; Alejandra Cardenas-Rojas; Paola Gonzalez-Mego; Anna Marduy; Joao Parente; Ingrid Rebello Sanchez; Pablo Cortez; Meghan Whalen; Luis Castelo-Branco; Felipe Fregni Journal: Princ Pract Clin Res Date: 2021-12-23
Authors: Kevin Pacheco-Barrios; Alejandra Cardenas-Rojas; Paulo S de Melo; Anna Marduy; Paola Gonzalez-Mego; Luis Castelo-Branco; Augusto J Mendes; Karen Vásquez-Ávila; Paulo E P Teixeira; Anna Carolyna Lepesteur Gianlorenco; Felipe Fregni Journal: Princ Pract Clin Res Date: 2021-12-27
Authors: Paulo E P Teixeira; Kevin Pacheco-Barrios; Muhammed Enes Gunduz; Anna Carolyna Gianlorenço; Luis Castelo-Branco; Felipe Fregni Journal: Neurophysiol Clin Date: 2021-02-26 Impact factor: 3.734
Authors: Marcel Simis; Marta Imamura; Paulo S de Melo; Anna Marduy; Kevin Pacheco-Barrios; Paulo E P Teixeira; Linamara Battistella; Felipe Fregni Journal: Sci Rep Date: 2021-12-14 Impact factor: 4.379
Authors: Mohamed Adil Shah Khoodoruth; Maria Anayali Estudillo-Guerra; Kevin Pacheco-Barrios; Azan Nyundo; Gina Chapa-Koloffon; Sami Ouanes Journal: Front Psychiatry Date: 2022-04-14 Impact factor: 5.435
Authors: Kevin Pacheco-Barrios; Daniel Lima; Danielle Pimenta; Eric Slawka; Alba Navarro-Flores; Joao Parente; Ingrid Rebello-Sanchez; Alejandra Cardenas-Rojas; Paola Gonzalez-Mego; Luis Castelo-Branco; Felipe Fregni Journal: Brain Netw Modul Date: 2022-06-29
Authors: D Duarte; C C C Bauer; C B Pinto; F G Saleh Velez; M A Estudillo-Guerra; K Pacheco-Barrios; M E Gunduz; D Crandell; L Merabet; F Fregni Journal: Psychiatry Res Neuroimaging Date: 2020-07-24 Impact factor: 2.493