Repeat traumatic brain injury exacerbates acute thalamic hyperconnectivity in humans

Author:

Woodrow Rebecca E12ORCID,Menon David K13ORCID,Stamatakis Emmanuel A1ORCID, ,Amrein Krisztina,Andelic Nada,Andreassen Lasse,Anke Audny,Azouvi Philippe,Bellander BoMichael,Benali Habib,Buki Andras,Caccioppola Alessio,Calappi Emiliana,Carbonara Marco,Citerio Giuseppe,Clusmann Hans,Coburn Mark,Coles Jonathan,Correia Marta,Czeiter Endre,De Keyser Véronique,Degos Vincent,Depreitere Bart,Eikenes Live,Ezer Erzsébet,Foks Kelly,Frisvold Shirin,Galanaud Damien,Ghuysen Alexandre,Glocker Ben,Haberg Asta,Haitsma Iain,Helseth Eirik,Hutchinson Peter J,Kornaropoulos Evgenios,Kovács Noémi,Kowark Ana,Laureys Steven,Ledoux Didier,Lingsma Hester,Maas Andrew I R,Manley Geoffrey,Menon David K,Menovsky Tomas,Misset Benoit,Muraleedharan Visakh,Nakken Ingeborg,Newcombe Virginia,Nordhøy Wibeke,Nyirádi József,Ortolano Fabrizio,Parizel Paul M,Perlbarg Vincent,Persona Paolo,Peul Wilco,Posti Jussi P,Puybasset Louis,Richter Sophie,Roe Cecilie,Roise Olav,Rossaint Rolf,Ross Sandra,Rueckert Daniel,Singh Ranjit D,Skandsen Toril,Sorinola Abayomi,Stamatakis EmmanuelORCID,Steyerberg Ewout W,Stocchetti Nino,Takala Riikka,Tamás Viktória,Tenovuo Olli,Thibaut Aurore,Vámos Zoltán,Van der Steen Gregory,van Erp Inge A,Van Hecke Wim,Vande Vyvere Thijs,Verheyden Jan,Vik Anne,Volovici Victor,Westlye Lars T,Whitehouse Daniel,Williams Guy,Winzeck Stefan,Ylén Peter,Zoerle Tommaso

Affiliation:

1. University Division of Anaesthesia, University of Cambridge , Cambridge CB2 0SP , UK

2. Department of Clinical Neurosciences, University of Cambridge , Cambridge CB2 0QQ , UK

3. Wolfson Brain Imaging Centre, University of Cambridge , Cambridge CB2 0QQ , UK

Abstract

Abstract Repeated mild traumatic brain injury is of growing interest regarding public and sporting safety and is thought to have greater adverse or cumulative neurological effects when compared with single injury. While epidemiological links between repeated traumatic brain injury and outcome have been investigated in humans, exploration of its mechanistic substrates has been largely undertaken in animal models. We compared acute neurological effects of repeat mild traumatic brain injury (n = 21) to that of single injury (n = 21) and healthy controls (n = 76) using resting-state functional MRI and quantified thalamic functional connectivity, given previous identification of its prognostic potential in human mild traumatic brain injury and rodent repeat mild traumatic brain injury. Acute thalamocortical functional connectivity showed a rank-based trend of increasing connectivity with number of injuries, at local and global scales of investigation. Thus, history of as few as two previous injuries can induce a vulnerable neural environment of exacerbated hyperconnectivity, in otherwise healthy individuals from non-specialist populations. These results further establish thalamocortical functional connectivity as a scalable marker of acute injury and long-term neural dysfunction following mild traumatic brain injury.

Funder

European Union Seventh Framework Programme

Research and Technological Development

Stephen Erskine Fellowship at Queens’ College

Canadian Institute for Advanced Research

Royal College of Anaesthetists

National Institute for Health and Care Research

Medical Research Council UK

Publisher

Oxford University Press (OUP)

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