Abstract
Reorganization of primary motor cortex (M1) is well-described in long-term lower limb amputees. In contrast cortical reorganization during the rehabilitation period after amputation is poorly understood. Thirteen transtibial amputees and 13 gender matched control participants of similar age were recruited. Transcranial magnetic stimulation was used to assess corticomotor and intracortical excitability of M1 bilaterally. Neurophysiological assessments were conducted at admission, prosthetic casting, first walk and discharge. Gait variability at discharge was assessed as a functional measure. Compared to controls, amputees had reduced short-latency intracortical inhibition (SICI) for the ipsilateral M1 at admission (p = 0.01). Analysis across rehabilitation revealed SICI was reduced for the contralateral M1 at first walk compared to discharge (p = 0.003). For the ipsilateral M1 both short and long-latency intracortical inhibition were reduced at admission (p < 0.05) and prosthetic casting (p < 0.02). Analysis of the neurophysiology and gait function revealed several interesting relationships. For the contralateral M1, reduced inhibition at admission (p = 0.04) and first walk (p = 0.05) was associated with better gait function. For the ipsilateral M1, reduced inhibition at discharge (p = 0.05) was associated with poor gait function. This study characterized intracortical excitability in rehabilitating amputees. A dichotomous relationship between reduced intracortical inhibition for each M1 and gait function was observed at different times. Intracortical inhibition may be an appropriate cortical biomarker of gait function in lower limb amputees during rehabilitation, but requires further investigation. Understanding M1 intracortical excitability of amputees undertaking prosthetic rehabilitation provides insight into brain reorganization in the sub-acute post-amputation period and may guide future studies seeking to improve rehabilitation outcomes.
Highlights
Transtibial amputation of a lower limb has a significant effect on human function and requires extensive rehabilitation to restore mobility using a prosthetic limb
We explored the relationship between neurophysiological measures using transcranial magnetic stimulation (TMS) at key time points of rehabilitation and gait function at discharge using spatialtemporal gait variability measures (Vanicek et al, 2009; Parker et al, 2013)
The main findings of this study were that there was longitudinal modulation of intracortical inhibition in M1 bilaterally during prosthetic rehabilitation, which was associated with gait function in this group of transtibial amputees
Summary
Transtibial amputation of a lower limb has a significant effect on human function and requires extensive rehabilitation to restore mobility using a prosthetic limb. Paired-pulse TMS studies indicate reorganization of the contralateral cortex in long-term amputees is mediated by modulation of gamma-aminobutyric acid (GABA) receptor activity (Chen et al, 1998a; Schwenkreis et al, 2000). NMDA plays an important role in regulating the excitability of interneuronal circuits (Ziemann et al, 1998; Schwenkreis et al, 1999) and cortical reorganization is dependent on NMDA receptor-mediated activity (Kano et al, 1991; Garraghty and Muja, 1996). Both GABA and NMDA-receptor mediated responses may underpin cortical reorganization in post-acute lower limb amputees
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