Acute thalamic connectivity precedes chronic post-concussive symptoms in mild traumatic brain injury
Rebecca Woodrow, Stefan Winzeck, Andrea I. Luppi, Isaac Kelleher-Unger, Lennart R. B. Spindler, Lindsay Wilson, Virginia Newcombe, Jonathan Coles, Krisztina Amrein, Nada Anđelić, Lasse Andreassen, Audny Anke, Philippe Azouvi, Bo‐Michael Bellander, Habib Benali, András Büki, Alessio Caccioppola, Emiliana Calappi, Marco Carbonara, Giuseppe Citerio, Hans Clusmann, Mark Coburn, Jonathan Coles, Marta Correia, Endre Czeiter, Véronique De Keyser, Vincent Degos, Bart Depreitere, Live Eikenes, Erzsébet Ezer, Kelly Foks, Shirin Frisvold, Alexandre Ghuysen, Damien Galanaud, Ben Glocker, Asta K. Håberg, Iain Haitsma, Eirik Helseth, Peter J. Hutchinson, Evgenios Kornaropoulos, Noémi Kovács, Ana Kowark, Steven Laureys, Didier Ledoux, Hester F. Lingsma, Andrew I.R. Maas, Geoffrey T. Manley, David Menon, Tomas Menovsky, Benoît Misset, Visakh Muraleedharan, Ingeborg Nakken, Virginia Newcombe, Wibeke Nordhøy, József Nyirádi, Fabrizio Ortolano, Paul M. Parizel, Vincent Perlbarg, Paolo Persona, Wilco C. Peul, Jussi P. Posti, Louis Puybasset, Sophie Richter, Cecilie Røe, Olav Røise, Rolf Rossaint, Sandra Rossi, Daniel Rueckert, Toril Skandsen, Abayomi Sorinola, Emmanuel A. Stamatakis, Ewout W. Steyerberg, Nino Stocchetti, Riikka Takala, Viktória Tamás, Olli Tenovuo, Zoltán Vámos, Gregory Van der Steen, Wim Van Hecke, Thijs Vande Vyvere, Jan Verheyden, Anne Vik, Victor Volovici, Lars T. Westlye, Guy Williams, Stefan Winzeck, Peter Ylén, Tommaso Zoerle, David Menon, Emmanuel A. Stamatakis
Abstract
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.