Physiological Consequences of Mild Traumatic Brain Injury in Individuals with Acute and Chronic Symptoms

Mild traumatic brain injury (mTBI) is the subject of increasing public health concern. Symptoms following mTBI, as well as risk factors for prolonged recovery, have been well-described. The physiological mechanisms behind these physical symptoms, and time course of recovery after injury, however, remain largely unknown. The purpose of this dissertation, therefore, was to assess the acute and chronic impact of mTBI on motor cortex function and associated neurotransmitter concentrations. A secondary goal of this dissertation was to establish the relationship between motor cortex function and the risk factors of female sex and APOE genotype in acute and chronic mTBI patients. Motor cortex function and neurotransmitter concentrations were assessed using transcranial magnetic stimulation and magnetic resonance spectroscopy, respectively. It was found that excitability, as assessed by the amplitude of the motor evoked potential (MEP), was lower in the Chronic group (participants with chronic symptoms from mTBI, lasting at least 3 months post-injury) compared to the control groups (p=0.02), but no differences in glutamate, the primary excitatory neurotransmitter, were found in the motor cortex between any group (p=0.93) or over time acutely following mTBI (p=0.70). Intracortical inhibition, as assessed by the duration of the cortical silent period (CSP), was higher in individuals acutely following mTBI (within 72 hours of mTBI diagnosis) and throughout two months of recovery (p=0.02), but no differences in GABA, the primary inhibitory neurotransmitter, were found in the motor cortex between any group (p=0.06) or over time following acute mTBI (p=0.57). There were no differences in MEP amplitude, CSP duration, glutamate concentration, or GABA concentration between males and females, or carriers of the apoε4 allele at any time point following mTBI (p≥0.10). This dissertation represents a compilation of studies which are among the first to document motor cortex excitability, intracortical inhibition, glutamate, and GABA concentrations in individuals with acute and chronic symptoms from mTBI. The data suggest a possible functional change longitudinally following mTBI, despite an expected neurochemical profile. Results from these studies suggest that humans may not follow the same neurometabolic timeline as the rodent model following mTBI. This dissertation contains previously published and unpublished co-authored material