[en] Chronic post-concussive 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 MRI and resting state functional MRI in 108 patients with a Glasgow Coma Scale (GCS) of 13-15 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 PET data. 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 post-concussive 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 serotonergic 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 post-concussive symptoms following mTBI, provide a basis for development of new therapies and facilitate precision medicine application of these therapies.
Disciplines :
Human health sciences: Multidisciplinary, general & others
Author, co-author :
Woodrow, Rebecca E ; University Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0SP, UK. ; Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0SP, UK.
Winzeck, Stefan; University Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0SP, UK. ; BioMedIA Group, Department of Computing, Imperial College, London SW7 2RH, UK.
Luppi, Andrea I ; University Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0SP, UK. ; Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0SP, UK. ; The Alan Turing Institute, London NW1 2DB, UK.
Kelleher-Unger, Isaac R; University Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0SP, UK. ; Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0SP, UK.
Spindler, Lennart R B; University Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0SP, UK. ; Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0SP, UK.
Wilson, J T Lindsay; Division of Psychology, University of Stirling, Stirling FK9 4LA, UK.
Newcombe, Virginia F J ; University Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0SP, UK.
Coles, Jonathan P ; University Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0SP, UK.
Menon, David K ; University Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0SP, UK. ; Wolfson Brain Imaging Centre, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
Stamatakis, Emmanuel A ; University Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0SP, UK.
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