Remote Changes in Cortical Excitability after Experimental Traumatic Brain Injury and Functional Reorganization

Although cognitive and behavioral deficits are well known to occur following traumatic brain injury (TBI), motor deficits that occur even after mild trauma are far less known, yet are equally persistent. This study was aimed at making progress toward determining how the brain reorganizes in response to TBI. We used the adult rat controlled cortical impact injury model to study the ipsilesional forelimb map evoked by electrical stimulation of the affected limb, as well as the contralesional forelimb map evoked by stimulation of the unaffected limb, both before injury and at 1, 2, 3, and 4 weeks after using functional magnetic resonance imaging (fMRI). End-point c-FOS immunohistochemistry data following 1 h of constant stimulation of the unaffected limb were acquired in the same rats to avoid any potential confounds due to altered cerebrovascular coupling. Single and paired-pulse sensory evoked potential (SEP) data were recorded from skull electrodes over the contralesional cortex in a parallel series of rats before injury, at 3 days, and at 1, 2, 3, and 4 weeks after injury in order to determine whether alterations in cortical excitability accompanied reorganization of the cortical map. The results show a transient trans-hemispheric shift in the ipsilesional cortical map as indicated by fMRI, remote contralesional increases in cortical excitability that occur in spatially similar regions to altered fMRI activity and greater c-FOS activation, and reduced or absent ipsilesional cortical activity chronically. The contralesional changes also were indicated by reduced SEP latency within 3 days after injury, but not by blood oxygenation level-dependent fMRI until much later. Detailed interrogation of cortical excitability using paired-pulse electrophysiology showed that the contralesional cortex undergoes both an early and a late post-injury period of hyper-excitability in response to injury, interspersed by a period of relatively normal activity. From these data, we postulate a cross-hemispheric mechanism by which remote cortex excitability inhibits ipsilesional activation by rebalanced cortical excitation-inhibition.