Reorganization of Motor Cortex after Controlled Cortical Impact in Rats and Implications for Functional Recovery

Abstract

We report the results of controlled cortical impact (CCI) centered on the caudal forelimb area (CFA) of rat motor cortex to determine the feasibility of examining cortical plasticity in a spared cortical motor area (rostral forelimb area, RFA). We compared the effects of three CCI parameter sets (groups CCI-1, CCI-2, and CCI-3) that differed in impactor surface shape, size, and location, on behavioral recovery and RFA structural and functional integrity. Forelimb deficits in the limb contralateral to the injury were evident in all three CCI groups assessed by skilled reach and footfault tasks that persisted throughout the 35-day post-CCI assessment period. Nissl-stained coronal sections revealed that the RFA was structurally intact. Intracortical microstimulation experiments conducted at 7 weeks post-CCI demonstrated that RFA was functionally viable. However, the size of the forelimb representation decreased significantly in CCI-1 compared to the control group. Subdivided into component movement categories, there was a significant group effect for proximal forelimb movements. The RFA area reduction and reorganization are discussed in relation to possible diaschisis, and to compensatory functional behavior, respectively. Also, an inverse correlation between the anterior extent of the lesion and the size of the RFA was identified and is discussed in relation to corticocortical connectivity. The results suggest that CCI can be applied to rat CFA while sparing RFA. This CCI model can contribute to our understanding of neural plasticity in premotor cortex as a substrate for functional motor recovery.

Restoration of function after brain damage using a neural prosthesis

“…Rats in all three groups received a CCI injury over the M1 forelimb area (5). Postmortem histological analysis confirmed that lesion size was comparable across groups (SI Results).…”

“…2A). After forelimb preference was determined, a removable Plexiglas wall was used to force the animal to use only the preferred forelimb (5). Trials were recorded with a digital camcorder for playback and analysis.…”

“…This area in the frontal cortex shares many properties with primary motor cortex (M1) of primates; injury to M1 results in long-term impairment in reaching and grasping functions (5). Traditionally, it has been thought that impairment occurs because M1 provides substantial outputs to the motor apparatus in the spinal cord, thus directly affecting motor output function.…”

“…The rostral forelimb area (RFA) is a premotor area in the rodent's frontal cortex that shares many properties with PM of primates and is thought to participate in recovery of function after injury to M1 (5,(7)(8)(9). PM areas are so-named because the principal target of their output fibers is M1 (10).…”

Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation

“…The effects of TBI are by nature heterogeneous, but moderate-to-severe TBIs can result in chronic deficits in motor function [77,78]. Recovery of motor function is associated with plasticity in spared motor circuits [79][80][81], and VNS paired with rehabilitation may enhance this plasticity to support recovery. Pruitt et al [82] evaluated whether VNS therapy could improve recovery of motor function in a controlled cortical impact model of severe TBI.…”