Plasticity and alterations of trunk motor cortex following spinal cord injury and non-stepping robot and treadmill training

Abstract

Spinal cord injury (SCI) induces significant reorganization in the sensorimotor cortex. Trunk motor control is crucial for postural stability and propulsion after low thoracic SCI and several rehabilitative strategies are aimed at trunk stability and control. However little is known about the effect of SCI and rehabilitation training on trunk motor representations and their plasticity in the cortex. Here, we used intracortical microstimulation to examine the motor cortex representations of the trunk in relation to other representations in three groups of chronic adult complete low thoracic SCI rats: chronic untrained, treadmill trained (but 'non-stepping') and robot assisted treadmill trained (but 'non-stepping') and compared with a group of normal rats. Our results demonstrate extensive and significant reorganization of the trunk motor cortex after chronic adult SCI which includes (1) expansion and rostral displacement of trunk motor representations in the cortex, with the greatest significant increase observed for rostral (to injury) trunk, and slight but significant increase of motor representation for caudal (to injury) trunk at low thoracic levels in all spinalized rats; (2) significant changes in coactivation and the synergy representation (or map overlap) between different trunk muscles and between trunk and forelimb. No significant differences were observed between the groups of transected rats for the majority of the comparisons. However, (3) the treadmill and robot-treadmill trained groups of rats showed a further small but significant rostral migration of the trunk representations, beyond the shift caused by transection alone. We conclude that SCI induces a significant reorganization of the trunk motor cortex, which is not qualitatively altered by non-stepping treadmill training or non-stepping robot assisted treadmill training, but is shifted further from normal topography by the training. This shift may potentially make subsequent rehabilitation with stepping longer or less successful.

Keywords: Activity/exercise induced plasticity; Motor cortex; Plasticity; Reorganization; Robot rehabilitation; Spinal cord injury; Trunk.

Figure 1:-

Comparison of example motor cortex maps from normal and adult spinalized rats. Maps show cortical areas from which forelimb, hindlimb and trunk musculature were recruited at 60–80 μA currents. Rostral is at the top of the map and bregma is at (0, 0). Numbers on the axis represents distance in mm. For comparison purposes all maps are presented as right cortex in the same orientation. Note the different shades for trunk representation as it overlaps with other regions. X – No non-facial motor response. (A) Normal Rat (B) Spinalized-Untrained (C) Spinalized–Treadmill trained (D) Spinalized – Robot trained.

Figure 2:-

Trunk Motor Area in all groups (A). Normalized Total Trunk Motor Area calculated as the number of sites in the cortex where any trunk response was obtained divided by the total nonfacial motor cortex sites and expressed as percentage (nonfacial motor cortex = total number of sites in the cortex where forelimb, neck, or trunk response was obtained). For normal rats, exclusive hindlimb sites were not included in calculating size of nonfacial motor cortex. Normal group is significantly different than spinalized groups. No significant difference between the three spinalized groups. (B). Normalized segmental Trunk Motor Area for Mid Thoracic (Low Thoracic or Lumbar) calculated as the number of sites in the cortex where any Mid Thoracic (Low Thoracic or Lumbar) response was obtained divided by the size of nonfacial motor cortex and expressed as percentage. Sites with co-activation of multiple segments (e.g. both mid thoracic and low thoracic) were counted as contributing to both representations. Normal group is significantly different than spinalized groups for all segments. No significant difference between the three spinalized groups. (C). Percentage Normalized Trunk Motor Area divided into Dorsal and Ventral overlap, Ventral only and Dorsal only. Normal group is significantly different than spinalized groups for Dorsal and Ventral overlap and Dorsal only. No significant difference between the three spinalized groups. (*p<0.05, 1-way ANOVA with Bonferroni corrected post hoc comparisons, ** p<0.05, t-test normal v/s all spinalized combined, *** p<0.05 1-way KRUSKAL WALLIS with Bonferroni corrected post hoc comparisons, curly brace indicates combined into 1 group, data expressed as mean ± SEM).

Figure 3:-

Coactivation density is defined as the total number of trunk EMG channels (trunk segments) co-activated per site (x,y) in the trunk motor cortex. (A). Total trunk coactivation density. Normal group is significantly different than spinalized groups. No significant difference between the three spinalized groups. (B). Segmental coactivation density for each segment. Normal group is significantly different than spinalized groups for Mid thoracic and Lumbar. No significant difference between the three spinalized groups. (C). Dorsal and Ventral coactivation density. Normal group is significantly different than spinalized groups for Ventral. No significant difference between the three spinalized groups. (*p<0.05, 1-way ANOVA with Bonferroni corrected post hoc comparisons, ** p<0.05, t-test normal v/s all spinalized combined, *** p<0.05, 1-way KRUSKAL WALLIS with Bonferroni corrected post hoc comparisons, curly brace indicates combined into 1 group, data expressed as mean ± SEM).

Figure 4:-

(A). Scatter plot showing center of gravity for trunk motor representation for each rat. For comparison purposes all points are presented as right cortex in the same orientation. Rostral is at the top of the map and bregma is at (0, 0). (B). Average center of gravity (medial/lateral and rostral/caudal). For medial/lateral location - No significant difference between the three spinalized groups for medial/lateral location. Normal group is significantly different than combined spinalized group for medial/lateral location. For rostral/caudal location - Normal group is significantly different than all spinalized groups. Spinalized untrained is significantly different than spinalized trained combined. Trunk motor sites divided based on relative location from bregma and expressed as (C) percentage of total trunk motor sites or (D) absolute number of sites. Normal group is significantly different than spinalized groups for absolute and percentage of trunk motor sites above bregma. No significant difference between the three spinalized groups for above bregma. No significant difference between the groups for trunk sites at bregma. Normal group is significantly different than spinalized groups for absolute and percentage of trunk motor sites below bregma. No significant difference between the three spinalized groups for percentage of trunk sites below bregma. For absolute trunk sites below bregma, spinalized untrained and spinalized treadmill trained significantly different than spinalized robot trained. (*p<0.05, 1-way ANOVA with Bonferroni corrected post hoc comparisons, ** p<0.05, t-test normal v/s all spinalized combined, *** p<0.05, t-test, **** p<0.05, t-test spinalized untrained v/s combined trained spinalized, curly brace indicates combined into 1 group data expressed as mean ± SEM).

Figure 5:-

Trunk motor sites divided based on coactivation with forelimb or hindlimb and expressed as percentage of total trunk sites. Normal group is significantly different than spinalized groups for forelimb coactivation and no coactivation (trunk only). No significant differences between the spinalized groups. Spinalized rats have no motor representation for hindlimb. (*p<0.05, 1-way ANOVA with Bonferroni corrected post hoc comparisons, data expressed as mean ± SEM).