Acute thalamic connectivity precedes chronic post-concussive symptoms in mild traumatic brain injury.

Chronic postconcussive symptoms are common after mild traumatic brain injury (mTBI), and are difficult to predict or treat. Thalamic functional integrity is particularly vulnerable in mTBI, and may be related to long-term outcomes, but requires further investigation. We compared structural magnetic resonance imaging (MRI) and resting state functional MRI in 108 patients with a Glasgow Coma Scale (GCS) of 13 to 15 and normal CT, and 76 controls. We examined whether acute changes in thalamic functional connectivity were early markers for persistent symptoms, and explored neurochemical associations of our findings using data from positron emission tomography. Of the mTBI cohort, 47% showed incomplete recovery 6 months post-injury. Despite the absence of structural changes, we found acute thalamic hyperconnectivity in mTBI, with specific vulnerabilities of individual thalamic nuclei. Acute fMRI markers differentiated those with chronic postconcussive symptoms, with time- and outcome-dependent relationships in a sub-cohort followed longitudinally. Moreover, emotional and cognitive symptoms were associated with changes in thalamic functional connectivity to known dopaminergic and noradrenergic targets, respectively. Our findings suggest that chronic symptoms can have a basis in early thalamic pathophysiology. This may aid identification of patients at risk of chronic postconcussive symptoms following mTBI, provide a basis for development of new therapies, and could facilitate precision medicine application of these therapies.