PT  - JOURNAL ARTICLE
AU  - Megan E. Cosgrove
AU  - Jordan R. Saadon
AU  - Charles B. Mikell
AU  - Patricia L. Stefancin
AU  - Leor Alkadaa
AU  - Zhe Wang
AU  - Sabir Saluja
AU  - John Servider
AU  - Bayan Razzaq
AU  - Chuan Huang
AU  - Sima Mofakham
TI  - Thalamo-Prefrontal Connectivity Correlates with Early Command Following After Severe Traumatic Brain Injury
AID  - 10.1101/2022.01.06.475131
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.01.06.475131
4099  - http://biorxiv.org/content/early/2022/01/11/2022.01.06.475131.short
4100  - http://biorxiv.org/content/early/2022/01/11/2022.01.06.475131.full
AB  - 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.Competing Interest StatementThe authors have declared no competing interest.