1 Children's Learning Institute and Department of Pediatrics, University of Texas Health Science Center at Houston, Houston, Texas.
2 Department of Pediatric Surgery, University of Texas Health Science Center at Houston, Houston, Texas.
J Neurotrauma. 2019 Jun;36(11):1738-1751. doi: 10.1089/neu.2018.6071. Epub 2019 Mar 6.
Pre-frontal limbic circuitry is vulnerable to effects of stress and injury. We examined microstructure of pre-frontal limbic circuitry after traumatic brain injury (TBI) or extracranial injury (EI) and its relation to post-traumatic stress symptoms (PTSS). Participants aged 8 to 15 years who sustained mild to severe TBI ( = 53) or EI ( = 26) in motor vehicle incidents were compared with healthy children ( = 38) in a prospective longitudinal study. At the seven-week follow-up, diffusion tensor imaging was obtained in all groups; injured children completed PTSS ratings using a validated scale. Using probabilistic diffusion tensor tractography, pathways were seeded from bilateral amygdalae and hippocampi to estimate the trajectory of white matter connecting them to each other and to targeted pre-frontal cortical (PFC) regions. Microstructure was estimated using fractional anisotropy (FA) in white matter and mean diffusivity (MD) in gray matter. Pre-frontal limbic microstructure was similar across groups, except for reduced FA in the right hippocampus to orbital PFC pathway in the injured versus healthy group. We examined microstructure of components of pre-frontal limbic circuitry with concurrently obtained PTSS cluster scores in the injured children. Neither microstructure nor PTSS scores differed significantly in the TBI and EI groups. Across PTSS factors, specific symptom clusters were related positively to higher FA and MD. Higher hyperarousal, avoidance, and re-experiencing symptoms were associated with higher FA in amygdala to pre-frontal and hippocampus to amygdala pathways. Higher hippocampal MD had a central role in hyperarousal and emotional numbing symptoms. Age moderated the relation of white and gray matter microstructure with hyperarousal scores. Our findings are consistent with models of traumatic stress that implicate disrupted top-down PFC and hippocampal moderation of overreactive subcortical threat arousal systems. Alterations in limbic pre-frontal circuitry and PTSS place children with either brain or body injuries at elevated risk for both current and future psychological health problems.
前额叶边缘回路容易受到压力和损伤的影响。我们研究了创伤性脑损伤（TBI）或颅外损伤（EI）后前额叶边缘回路的微观结构及其与创伤后应激症状（PTSS）的关系。这项前瞻性纵向研究比较了在机动车事故中遭受轻度至重度 TBI（n=53）或 EI（n=26）的 8 至 15 岁儿童与健康儿童（n=38）。在 7 周的随访中，所有组均进行了弥散张量成像；受伤儿童使用经过验证的量表完成了 PTSD 评分。使用概率弥散张量纤维束追踪，从双侧杏仁核和海马体播种路径，以估计将它们彼此连接以及连接到目标前额皮质（PFC）区域的白质轨迹。使用白质中的各向异性分数（FA）和灰质中的平均弥散度（MD）来估计微观结构。前额叶边缘的微观结构在各组之间相似，除了与健康组相比，损伤组右侧海马体到眶额 PFC 路径的 FA 降低。我们检查了损伤儿童同时获得的 PTSD 聚类评分的前额叶边缘回路成分的微观结构。TBI 和 EI 组的微观结构和 PTSD 评分均无显著差异。在 PTSD 因素中，特定的症状集群与更高的 FA 和 MD 呈正相关。更高的警觉性、回避和再体验症状与杏仁核到前额叶和海马体到杏仁核的路径中更高的 FA 相关。更高的海马体 MD 在警觉性和情绪麻木症状中起核心作用。年龄调节了白质和灰质微观结构与警觉性评分之间的关系。我们的发现与创伤性应激模型一致，该模型暗示了前额叶皮质和海马体的自上而下调节作用受损，过度反应的皮质下威胁唤醒系统。边缘-前额叶回路的改变和 PTSD 使大脑或身体受伤的儿童面临当前和未来心理健康问题的风险增加。
