A comprehensive characterization of cognitive performance, clinical symptoms, and cortical activity following mild traumatic brain injury (mTBI).

OBJECTIVE: The objective of this study was to investigate clinical symptoms, cognitive performance and cortical activity following mild traumatic brain injury (mTBI). METHODS: We recruited 30 individuals in the sub-acute phase post mTBI and 28 healthy controls with no history of head injury and compared these groups on clinical, cognitive and cortical activity measures. Measures of cortical activity included; resting state electroencephalography (EEG), task related EEG and combined transcranial magnetic stimulation with electroencephalography (TMS-EEG). Primary analyses investigated clinical, cognitive and cortical activity differences between groups. Exploratory analyses investigated the relationships between these measures. RESULTS: At 4 weeks' post injury, mTBI participants exhibited significantly greater post concussive and clinical symptoms compared to controls; as well as reduced cognitive performance on verbal learning and working memory measures. mTBI participants demonstrated alterations in cortical activity while at rest and in response to stimulation with TMS. CONCLUSIONS: The present study comprehensively characterized the multidimensional effect of mTBI in the sub-acute phase post injury, showing a broad range of differences compared to non-mTBI participants. Further research is needed to explore the relationship between these pathophysiologies and clinical/cognitive symptoms in mTBI.

Recovery of clinical, cognitive and cortical activity measures following mild traumatic brain injury (mTBI): A longitudinal investigation.

The mechanisms that underpin recovery following mild traumatic brain injury (mTBI) remain poorly understood. Identifying neurophysiological markers and their functional significance is necessary to develop diagnostic and prognostic indicators of recovery. The current study assessed 30 participants in the subacute phase of mTBI (10-31 days post-injury) and 28 demographically matched controls. Participants also completed 3 month (mTBI: N = 21, control: N = 25) and 6 month (mTBI: N = 15, control: N = 25) follow up sessions to track recovery. At each time point, a battery of clinical, cognitive, and neurophysiological assessments was completed. Neurophysiological measures included resting-state electroencephalography (EEG) and transcranial magnetic stimulation combined with EEG (TMS-EEG). Outcome measures were analysed using mixed linear models (MLM). Group differences in mood, post-concussion symptoms and resting-state EEG resolved by 3 months, and recovery was maintained at 6 months. On TMS-EEG derived neurophysiological measures of cortical reactivity, group differences ameliorated at 3 months but re-emerged at 6 months, while on measures of fatigue, group differences persisted across all time points. Persistent neurophysiological changes and greater fatigue in the absence of measurable cognitive impairment may suggest the impact of mTBI on neuronal communication may leads to increased neural effort to maintain efficient function. Neurophysiological measures to track recovery may help identify both temporally optimal windows and therapeutic targets for the development of new treatments in mTBI.

Investigation of neurobiological responses to theta burst stimulation during recovery from mild traumatic brain injury (mTBI).

OBJECTIVE: The ability of the brain to recover following neurological insult is of interest for mild traumatic brain injury (mTBI) populations. Investigating whether non-invasive brain stimulation (NIBS) can modulate neurophysiology and cognition may lead to the development of therapeutic interventions post injury. The purpose of this study was to investigate neurobiological effects of one session of intermittent theta burst stimulation (iTBS) to the dorsolateral prefrontal cortex (DLPFC) in participants recovering from mTBI. METHOD: Changes to neurophysiology were assessed with electroencephalography (EEG) and transcranial magnetic stimulation combined with EEG (TMS-EEG). Digit span working memory accuracy assessed cognitive performance. 30 patients were assessed within one-month of sustaining a mTBI and 26 demographically matched controls were assessed. Participants were also assessed at 3-months (mTBI: N = 21, control: N = 26) and 6-months (mTBI: N = 15, control: N = 24). RESULTS: Analyses demonstrated iTBS did not reliably modulate neurophysiological activity, and no differences in cognitive performance were produced by iTBS at any assessment time-point. CONCLUSIONS: Factors responsible for our null results are unclear. Possible limitations to our experimental design are discussed. SIGNIFICANCE: Our findings suggest additional research is required to establish the effects of iTBS on plasticity following mTBI, prior to therapeutic application. DATA AND CODE AVAILABILITY STATEMENT: We do not have ethical approval to make this data publicly available, as our approval predated our inclusion of such approvals (which we now do routinely).

Understanding individual variability in symptoms and recovery following mTBI: A role for TMS-EEG?

The pathophysiology associated with mild traumatic brain injury (mTBI) includes neurometabolic and cytoskeletal changes that have been shown to impair structural and functional connectivity. Evidence that persistent neuropsychological impairments post injury are linked to structural and functional connectivity changes is increasing. However, to date the relationship between connectivity changes, heterogeneity of persistent symptoms and recovery post mTBI has been poorly characterised. Recent innovations in neuroimaging provide new ways of exploring connectivity changes post mTBI. Namely, combined transcranial magnetic stimulation and electroencephalography (TMS-EEG) offers several advantages over traditional approaches for studying connectivity changes post TBI. Its ability to perturb neural function in a controlled manner allows for measurement of causal interactions or effective connectivity between brain regions. We review the current literature assessing structural and functional connectivity following mTBI and outline the rationale for the use of TMS-EEG as an ideal tool for investigating the neural substrates of connectivity dysfunction and reorganisation post mTBI. The diagnostic, prognostic and potential therapeutic implications will also be explored.