Relationship between structural brainstem and brain plasticity and lower-limb training in spinal cord injury: a longitudinal pilot study

Michael Villiger, Patrick Grabher, Marie-Claude Hepp-Reymond, Daniel Kiper, Armin Curt, Marc Bolliger, Sabina Hotz-Boendermaker, Spyros Kollias, Kynan Eng, Patrick Freund, Michael Villiger, Patrick Grabher, Marie-Claude Hepp-Reymond, Daniel Kiper, Armin Curt, Marc Bolliger, Sabina Hotz-Boendermaker, Spyros Kollias, Kynan Eng, Patrick Freund

Abstract

Rehabilitative training has shown to improve significantly motor outcomes and functional walking capacity in patients with incomplete spinal cord injury (iSCI). However, whether performance improvements during rehabilitation relate to brain plasticity or whether it is based on functional adaptation of movement strategies remain uncertain. This study assessed training improvement-induced structural brain plasticity in chronic iSCI patients using longitudinal MRI. We used tensor-based morphometry (TBM) to analyze longitudinal brain volume changes associated with intensive virtual reality (VR)-augmented lower limb training in nine traumatic iSCI patients. The MRI data was acquired before and after a 4-week training period (16-20 training sessions). Before training, voxel-based morphometry (VBM) and voxel-based cortical thickness (VBCT) assessed baseline morphometric differences in nine iSCI patients compared to 14 healthy controls. The intense VR-augmented training of limb control improved significantly balance, walking speed, ambulation, and muscle strength in patients. Retention of clinical improvements was confirmed by the 3-4 months follow-up. In patients relative to controls, VBM revealed reductions of white matter volume within the brainstem and cerebellum and VBCT showed cortical thinning in the primary motor cortex. Over time, TBM revealed significant improvement-induced volume increases in the left middle temporal and occipital gyrus, left temporal pole and fusiform gyrus, both hippocampi, cerebellum, corpus callosum, and brainstem in iSCI patients. This study demonstrates structural plasticity at the cortical and brainstem level as a consequence of VR-augmented training in iSCI patients. These structural changes may serve as neuroimaging biomarkers of VR-augmented lower limb neurorehabilitation in addition to performance measures to detect improvements in rehabilitative training.

Keywords: lower limb; spinal cord injury; structural plasticity; tensor-based morphometry; virtual reality-augmented neurorehabilitation; voxel-based morphometry.

Figures

Figure 1
Figure 1
Performance improvements. Improvements of (A) 10 meter walking test (10 MWT), (B) Berg balance scale (BBS), (C) lower extremity motor score (LEMS) and (D) spinal cord independence measure (SCIM) in patients with incomplete spinal cord injury (iSCI) after 16–20 interactive training sessions during 4 weeks (post-training) and 12–16 weeks after training (follow-up). Individual results (blue) and means with standard deviations (red) are shown.
Figure 2
Figure 2
Cross-sectional structural changes (VBM/VBCT). Statistical parametric maps (thresholded at p < 0.001 uncorrected, for illustrative purposes) showing volume reductions in patients with iSCI compared with controls at baseline. (Left) Voxel-based morphometry (VBM): cerebellum and brainstem (medulla oblongata) and (right) voxel-based cortical thickness (VBCT): left primary motor cortex. The color bars indicate the t-scores.
Figure 3
Figure 3
Longitudinal structural changes (TBM). Overlay of statistical parametric maps (thresholded at p < 0.001 uncorrected, for illustrative purposes) showing correlations between volume increases measured by tensor-based morphometry (TBM) and clinical improvements in balance (BBS, red), lower extremity motor score (LEMS, yellow), and spinal cord independence measure (SCIM, green). The corresponding t-scores are indicated by the color bars. Correlations are shown in brainstem (left), hippocampus (middle), and left temporal gyrus and cerebellum (right).

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