Cortical Neuromodulation of Remote Regions after Experimental Traumatic Brain Injury Normalizes Forelimb Function but is Temporally Dependent
Year: 2018
Type: article
Abstract: Traumatic brain injury (TBI) results in well-known, significant alterations in structural and functional connectivity. Although this is especially likely to occur in areas of pathology, deficits in function to and from remotely connected brain areas, or diaschisis, also occur as a consequence to local deficits. As a result, consideration of the network wiring of the brain may be required to design the most efficacious rehabilitation therapy to target specific functional networks to improve outcome. In this work, we model remote connections after controlled cortical impact injury (CCI) in the rat through the effect of callosal deafferentation to the opposite, contralesional cortex. We show rescue of significantly reaching deficits in injury-affected forelimb function if temporary, neuromodulatory silencing of contralesional cortex function is conducted at 1 week post-injury using the γ-aminobutyric acid (GABA) agonist muscimol, compared with vehicle. This indicates that subacute, injury-induced remote circuit modifications are likely to prevent normal ipsilesional control over limb function. However, by conducting temporary contralesional cortex silencing in the same injured rats at 4 weeks post-injury, injury-affected limb function either remains unaffected and deficient or is worsened, indicating that circuit modifications are more permanently controlled or at least influenced by the contralesional cortex at extended post-injury times. We provide functional magnetic resonance imaging (MRI) evidence of the neuromodulatory effect of muscimol on forelimb-evoked function in the cortex. We discuss these findings in light of known changes in cortical connectivity and excitability that occur in this injury model, and postulate a mechanism to explain these findings.
Source: Journal of Neurotrauma
Authors: Derek R. Verley, Daniel Torolira, Brittany A. Hessell, Richard L. Sutton, Neil G. Harris
Institution: University of California, Los Angeles
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: National Institutes of Health, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke, National Institute of Child Health and Human Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Brain Injury Research Center
OpenAlex ID: W2884064543