Abstract
Recovery of consciousness after traumatic brain injury (TBI) is heterogeneous and difficult to predict. Structures such as the thalamus and prefrontal cortex are thought to be important in facilitating consciousness. We sought to investigate whether the integrity of thalamo-prefrontal circuits, assessed via diffusion tensor imaging (DTI), was associated with the return of goal-directed behavior after severe TBI. We classified a cohort of severe TBI patients (N = 25, 20 males) into Early and Late/Never outcome groups based on their ability to follow commands within 30 days post-injury. We assessed connectivity between whole thalamus, and mediodorsal thalamus (MD), to prefrontal cortex (PFC) subregions including dorsolateral PFC (dlPFC), medial PFC (mPFC), anterior cingulate (ACC), and orbitofrontal (OFC) cortices. We found that the integrity of thalamic projections to PFC subregions (L OFC, L and R ACC, and R mPFC) was significantly associated with Early command-following. This association persisted when the analysis was restricted to prefrontal-mediodorsal (MD) thalamus connectivity. In contrast, dlPFC connectivity to thalamus was not significantly associated with command-following. Using the integrity of thalamo-prefrontal connections, we created a linear regression model that demonstrated 72% accuracy in predicting command-following after a leave-one-out analysis. Together, these data support a role for thalamo-prefrontal connectivity in the return of goal-directed behavior following TBI.
Highlights
Patients with severe traumatic brain injury (TBI), defined as initial Glasgow Coma Scale (GCS) < 8 and loss of consciousness for at least 24 h, recover consciousness at variable intervals [1, 2]
We found that fractional anisotropy (FA), a measure of tract integrity, was significantly lower in the Late/Never group for whole thalamus connectivity to left and right ACC, right medial PFC (mPFC), and left OFC
We investigated the role of the thalamo-prefrontal circuit in recovery of command-following, and goaldirected behavior, after TBI
Summary
Patients with severe traumatic brain injury (TBI), defined as initial Glasgow Coma Scale (GCS) < 8 and loss of consciousness for at least 24 h, recover consciousness at variable intervals [1, 2]. Consciousness is required for voluntary behavior, less is known about what brain circuits support the languageguided control needed to follow verbal commands. The absence of this voluntary behavior, is not a prerequisite for consciousness, as a subset of these patients may display cognitivemotor dissociation [17]. We hypothesized that thalamic input (in particular MD) to PFC is important for recovery of consciousness and command-following after severe TBI. We assessed the integrity of thalamocortical projections on dMRI of TBI patients and developed a model for predicting command-following based on tractography analysis of these connections
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