Disruption of the ascending arousal network in acute traumatic disorders of consciousness

Objective To determine whether ascending arousal network (AAn) connectivity is reduced in patients presenting with traumatic coma. Methods We performed high-angular-resolution diffusion imaging in 16 patients with acute severe traumatic brain injury who were comatose on admission and in 16 matched controls. We used probabilistic tractography to measure the connectivity probability (CP) of AAn axonal pathways linking the brainstem tegmentum to the hypothalamus, thalamus, and basal forebrain. To assess the spatial specificity of CP differences between patients and controls, we also measured CP within 4 subcortical pathways outside the AAn. Results Compared to controls, patients showed a reduction in AAn pathways connecting the brainstem tegmentum to a region of interest encompassing the hypothalamus, thalamus, and basal forebrain. When each pathway was examined individually, brainstem-hypothalamus and brainstem-thalamus CPs, but not brainstem-forebrain CP, were significantly reduced in patients. Only 1 subcortical pathway outside the AAn showed reduced CP in patients. Conclusions We provide initial evidence for the reduced integrity of axonal pathways linking the brainstem tegmentum to the hypothalamus and thalamus in patients presenting with traumatic coma. Our findings support current conceptual models of coma as being caused by subcortical AAn injury. AAn connectivity mapping provides an opportunity to advance the study of human coma and consciousness.