Mild blast TBI raises gamma connectivity, EEG power, and reduces GABA interneuron density
At least one traumatic brain injury (TBI) will be experienced by approximately 50-60 million of the worlds population in their lifetime and is the biggest cause of death and disability in those under 40. Mild traumatic brain injury (mTBI) can induce subtle changes but have long-lasting effects that may be difficult to detect through conventional neurological assessment, including standard clinical imaging techniques. These changes can lead to an increased risk of future neurodegeneration and emphasises the need to use more sensitive diagnostic tools such as EEG in order to identify injury and opportunities for therapeutic intervention. In this study, we investigated electrophysiological and histopathological changes in a rat model of mild blast-induced TBI. We used a 32-channel EEG electrode array to detect global and local changes in neural activity and functional connectivity in acute (3 to 4-hours) as well as chronic phases (1 and 3-months) post-injury. GABAergic inhibitory interneurons, crucial for maintaining an excitatory/inhibitory balance, were quantified using immunohistochemistry. Mild blast-induced TBI had minimal effects on resting power and connectivity at the acute timepoint but resulted in resting-state global power increases at all frequencies as well as a relative power increase in slow-wave frequencies in the chronic phase post-injury. Functional connectivity increases in the gamma frequency along with increases in power in the chronic phase pointed towards an alteration in the excitatory/inhibitory balance. Indeed, electrophysiological changes were associated with reduced density of GABAergic interneurons at 7-days, 1-month, and 3months post-injury, with a decrease in somatostatin-positive cell density in the 5th layer of all cortical regions of interest, and a parvalbumin decrease in the 5th layer of the primary auditory cortex. In contrast, the total number of neurons, measured by NeuN did not change significantly, thus demonstrating a biased impact on inhibitory interneuron populations. Our work demonstrates that the techniques and metrics of injury assessment employed in this study are sensitive enough to reflect the subtle changes present in mTBI and therefore hold potential clinical relevance. By using non-invasive EEG assessments and histopathology, we were able to reveal direct correlates and potential sources of the abnormalities caused by mild blast-induced TBI.