Amygdala Hypoconnectivity and Emotional Blunting in Pediatric Moderate/Severe TBI

Objective: To test the hypothesis that limbic circuits are particularly vulnerable to traumatic brain injury (TBI), which may underlie the socioemotional dysfunction seen in this population. Background: Nearly 40% of survivors of TBI suffer from long-term disabilities including socioemotional dysfunction. Such disability often remains undetected and undertreated, partly because of gaps in understanding and targeting the neural circuitry responsible. Here, we leverage a componential framework from my prior work in healthy adults and patients with frontotemporal dementia in which I parsed socioemotional behavior into distinct, large-scale networks centralized on the amygdala. Design/Methods: We studied 19 patients (mean age: 17, SD +/− 2) 13–19 months after moderate/severe TBI recruited from 4 pediatric intensive care units as well as 44 well-matched healthy controls (HC). Resting-state fMRI and T1 MPRAGE images underwent typical preprocessing, denoising, coregistration, and analyses in CONN Toolbox to compare connectivity within the a priori amygdala resting-state networks across groups. Results: Patients with TBI demonstrated reduced connectivity within the medial amygdala network as compared to the HC group. This network contains structures involved in reward- and goal-based behavior. Patients with TBI who had the slowest interhemispheric transfer time on an ERP paradigm showed the greatest hypoconnectivity in this network, particularly with regions in the medial temporal and prefrontal cortices. Within the TBI group, those with the greatest medial amygdala hypoconnectivity showed the lowest emotional and behavioral reactivity on two independent parent report scales but connectivity had not association with a working memory. None of these findings could be explained by potential confounds. Conclusions: Medial amygdala circuitry might be particularly vulnerable to TBI, especially for those children with slower interhemispheric transfer time. This hypoconnectivity is likely clinically relevant in that it predicts differences in affective but not cognitive measures. It may be useful as a biomarker for neuropsychological function after TBI and a potential therapeutic target. Disclosure: Dr. Bickart has nothing to disclose. Dr. Olsen has nothing to disclose. Dr. Dennis has nothing to disclose. Dr. Babikian has nothing to disclose. Dr. Asarnow has nothing to disclose. Dr. Giza has nothing to disclose.