Disability, atrophy and cortical reorganization following spinal cord injury

Patrick Freund, Nikolaus Weiskopf, Nick S Ward, Chloe Hutton, Angela Gall, Olga Ciccarelli, Michael Craggs, Karl Friston, Alan J Thompson, Patrick Freund, Nikolaus Weiskopf, Nick S Ward, Chloe Hutton, Angela Gall, Olga Ciccarelli, Michael Craggs, Karl Friston, Alan J Thompson

Abstract

The impact of traumatic spinal cord injury on structural integrity, cortical reorganization and ensuing disability is variable and may depend on a dynamic interaction between the severity of local damage and the capacity of the brain for plastic reorganization. We investigated trauma-induced anatomical changes in the spinal cord and brain, and explored their relationship to functional changes in sensorimotor cortex. Structural changes were assessed using cross-sectional cord area, voxel-based morphometry and voxel-based cortical thickness of T1-weighted images in 10 subjects with cervical spinal cord injury and 16 controls. Cortical activation in response to right-sided (i) handgrip; and (ii) median and tibial nerve stimulation were assessed using functional magnetic resonance imaging. Regression analyses explored associations between cord area, grey and white matter volume, cortical activations and thickness, and disability. Subjects with spinal cord injury had impaired upper and lower limb function bilaterally, a 30% reduced cord area, smaller white matter volume in the pyramids and left cerebellar peduncle, and smaller grey matter volume and cortical thinning in the leg area of the primary motor and sensory cortex compared with controls. Functional magnetic resonance imaging revealed increased activation in the left primary motor cortex leg area during handgrip and the left primary sensory cortex face area during median nerve stimulation in subjects with spinal cord injury compared with controls, but no increased activation following tibial nerve stimulation. A smaller cervical cord area was associated with impaired upper limb function and increased activations with handgrip and median nerve stimulation, but reduced activations with tibial nerve stimulation. Increased sensory deficits were associated with increased activations in the left primary sensory cortex face area due to median nerve stimulation. In conclusion, spinal cord injury leads to cord atrophy, cortical atrophy of primary motor and sensory cortex, and cortical reorganization of the sensorimotor system. The degree of cortical reorganization is predicted by spinal atrophy and is associated with significant disability.

Figures

Figure 1
Figure 1
Spinal cord atrophy following SCI. (A) T1-weighted scan of the brain and cervical spinal cord showing the region of cross-sectional cord area measurement (within white horizontal bars). (B and C) Cord area in a control and subject with SCI, respectively. (D) Box and whisker plots showing a 30% reduction in cord area in subjects with SCI compared with controls.
Figure 2
Figure 2
Statistical parametric maps (thresholded at P < 0.001, uncorrected for display purposes only) showing regions of white matter and grey matter volume reduction in subjects with SCI compared with controls. (A) Smaller white matter volume in the pyramids and the left cerebellar peduncle and (B) smaller grey matter volume (yellow) and reduced cortical thickness (red) in the leg area of primary motor cortex and primary sensory cortex. Note, the overlap (orange) and the different areas detected with VBCT in addition to the VBM analysis.
Figure 3
Figure 3
Graphs showing significant correlations between clinical measures of upper limb function and lower cord area (cross sectional) in subjects with SCI. (A) Dominant hand 9-Hole Peg Test and cord area; (B) Non-dominant hand 9-Hole Peg Test and cord area; (C) ARAT and cord area; and (D) Maximum voluntary contraction and cord area.
Figure 4
Figure 4
Statistical parametric maps showing the results of the regression analyses of clinical measures of upper limb function and grey matter volume in subjects with SCI. (A) Region of increased grey matter volume in left leg area of primary motor cortex associated with lower grip strength (maximum voluntary contraction) of the dominant hand (P = 0.014, corrected for multiple comparisons within region of interest). (B) Region of increased grey matter volume and slower performance of the 9-Hole Peg Test (9HPT) of the dominant hand (P = 0.001, corrected for multiple comparisons within region of interest). Note that scatter plots are depicted for illustrative purposes showing the associations between the grey matter volume of each individual subjects with SCI plotted against the upper limb motor performance from each subject with SCI. Improved motor function corresponds to higher values for maximum voluntary contraction and lower values for 9-Hole Peg Test (along the x-axis). GM = grey matter.
Figure 5
Figure 5
Statistical parametric maps (thresholded at P < 0.001, uncorrected for display purposes only) showing regions of increased task-related brain activity in subjects with SCI compared with controls. (A) Increased BOLD response during right-sided handgrip in contralateral left leg area of primary motor cortex and (B) during right-sided median nerve stimulation in contralateral left face area of primary sensory cortex.
Figure 6
Figure 6
Statistical parametric maps (thresholded at P < 0.001, uncorrected for display purposes only) showing negative associations between cord area and (A) increased task-related BOLD signal in the left leg area of primary motor cortex during right-sided handgrip and (B) in the left face area of primary sensory cortex during right-sided median nerve stimulation. (C) Cord area was positively associated with normal task-related BOLD signal in the leg area of primary sensory cortex during tibial nerve stimulation. SCA = cord cross sectional area.
Figure 7
Figure 7
Sensory deficits are associated with increased BOLD signal in primary sensory cortex. (A) Statistical parametric maps (thresholded at P < 0.001, uncorrected for display purposes only) showing associations between task-related brain activity and sensory deficits in subjects with SCI in primary sensory cortex. (B) Parameter estimates from each individual subject with SCI for the main effect of median nerve stimulation plotted against light touch and pinprick score from each subject with SCI (along the x-axis) for the circled regions in A.

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