A common neural signature of brain injury in concussion and subconcussion

Abstract

The midbrain is biomechanically susceptible to force loading from repetitive subconcussive head impacts (RSHI), is a site of tauopathy in chronic traumatic encephalopathy (CTE), and regulates functions (e.g., eye movements) often disrupted in concussion. In a prospective longitudinal design, we demonstrate there are reductions in midbrain white matter integrity due to a single season of collegiate football, and that the amount of reduction in midbrain white matter integrity is related to the amount of rotational acceleration to which players’ brains are exposed. We then replicate the observation of reduced midbrain white matter integrity in a retrospective cohort of individuals with frank concussion, and further show that variance in white matter integrity is correlated with levels of serum-based tau, a marker of blood-brain barrier disruption. These findings mean that noninvasive structural MRI of the midbrain is a succinct index of both clinically silent white matter injury as well as frank concussion.

The Role of Blood Biomarkers for Magnetic Resonance Imaging Diagnosis of Traumatic Brain Injury

“…In the mTBI cohort, a similar change in fractional anisotropy in the midbrain was also seen. In 13 of 29 subjects in the mTBI cohort, blood was collected within 72 h of injury and serum tau was inversely correlated with midbrain fractional anisotropy (r = −0.60, p < 0.033) [27].…”

“…Tomita et al showed that Tau is elevated in cases of DAI and has a sensitivity of 74.1 for diagnosing DAI [28]. Hirad et al showed that high serum Tau correlated with lower fractional anisotropy and hence disrupted white matter [27]. Moreover, Tau levels correlated with the number of strikes in concussed athletes, and thus may be a potential marker that is dose-dependent and congruent with the clinical reality of multiple impacts [27].…”

“…Hirad et al showed that high serum Tau correlated with lower fractional anisotropy and hence disrupted white matter [27]. Moreover, Tau levels correlated with the number of strikes in concussed athletes, and thus may be a potential marker that is dose-dependent and congruent with the clinical reality of multiple impacts [27]. Early studies from the TRACK-TBI pilot cohort have also shown that phospho-Tau shows good discriminability for chronic TBI versus healthy controls with an AUC of 0.963-1.00 [53].…”

Traumatic brain injury and methamphetamine: A double-hit neurological insult

“…Most radiological abnormalities following brain trauma occur in the frontal and temporal cortices, suggesting that anterior regions such as the PFC brain regions are highly susceptible to injury of varying severity [40,41]. The midbrain, which includes the VTA, represents another critical site of injury that sustains a decrease in white matter integrity post-TBI [42]. In addition, the hippocampus is one more highly vulnerable structural post brain trauma, with neurophysiological changes occurring weeks to months after TBI (see reviews [43,44]).…”

Toward a Global and Reproducible Science for Brain Imaging in Neurotrauma: The ENIGMA Adult Moderate/Severe Traumatic Brain Injury Working Group

“…There is a critical need to examine processes that reflect the phenomenon of "aging-with-TBI" and addressing this issue has become a priority in the study of TBI (see NIH Director's Messages for ADRD-FY19, 2018). Considerable investments have been made in characterizing the pathological sequelae of repetitive "subconcussive" head trauma (Hirad et al, 2019;McKee et al, 2016) and some efforts are underway to help characterize the clinical correlates of this pathology; however, AMS-TBI is inexplicably excluded from currently proposed case definitions of traumatic encephalopathy syndrome (Montenigro et al, 2014;Reams et al, 2016). As such, the community of AMS-TBI researchers is charged with: 1) establishing a shared nomenclature and operational definition of post-traumatic dementia in AMS-TBI, and 2) common methods and data sharing approaches specific to AMS-TBI so that imaging can be leveraged to advance discovery.…”