Structural and functional motor cortex asymmetry in unilateral lower limb amputation with phantom limb pain

K Pacheco-Barrios; C B Pinto; F G Saleh Velez; D Duarte; M E Gunduz; M Simis; A C Lepesteur Gianlorenco; J L Barouh; D Crandell; M Guidetti; L Battistella; F Fregni

doi:10.1016/j.clinph.2020.06.024

Structural and functional motor cortex asymmetry in unilateral lower limb amputation with phantom limb pain

Clin Neurophysiol. 2020 Oct;131(10):2375-2382. doi: 10.1016/j.clinph.2020.06.024. Epub 2020 Jul 15.

Authors

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

Affiliations

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.

Keywords: Cortical mapping; Magnetic resonance imaging; Phantom limb pain.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Adult
Amputation, Surgical
Amputees
Brain Mapping
Cortical Excitability / physiology*
Cross-Sectional Studies
Evoked Potentials, Motor / physiology
Female
Functional Laterality / physiology*
Gray Matter / diagnostic imaging*
Humans
Lower Extremity / physiopathology*
Magnetic Resonance Imaging
Male
Middle Aged
Motor Cortex / diagnostic imaging
Motor Cortex / physiopathology*
Phantom Limb / diagnostic imaging
Phantom Limb / physiopathology*
Transcranial Magnetic Stimulation

Grants and funding

R01 HD082302/HD/NICHD NIH HHS/United States