Department of Psychology and Psychology Clinical Neuroscience Center, University of New Mexico, Albuquerque, New Mexico, USA.
Department of Psychiatry and Behavioral Sciences, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA.
J Neurotrauma. 2021 Aug 15;38(16):2264-2274. doi: 10.1089/neu.2020.7363. Epub 2021 Jun 10.
Apathy is a common and impairing sequela of traumatic brain injury (TBI). Yet, little is known about the neural mechanisms determining in which patients apathy does or does not develop post-TBI. We aimed to elucidate the impact of TBI on motivational neural circuits and how this shapes apathy over the course of TBI recovery. Resting-state functional magnetic resonance imaging data were collected in patients with subacute mild TBI ( = 44), chronic mild-to-moderate TBI ( = 26), and nonbrain-injured control participants (CTRL; = 28). We measured ventromedial prefrontal cortex (vmPFC) functional connectivity (FC) as a function of apathy, using an vmPFC seed adopted from a motivated decision-making study in an independent TBI study cohort. Patients reported apathy using a well-validated tool for assaying apathy in TBI. The vmPFC-to-wholebrain FC was contrasted between groups, and we fit regression models with apathy predicting vmPFC FC. Subacute and chronic TBI caused increased apathy relative to CTRL, replicating previous work suggesting that apathy has an enduring impact in TBI. The vmPFC was functionally connected to the canonical default network, and this architecture did not differ between subacute TBI, chronic TBI, and CTRL groups. Critically, in TBI, increased apathy scores predicted decreased vmPFC-dorsal anterior cingulate cortex (dACC) FC. Last, we subdivided the TBI group based on patients above versus below the threshold for "clinically significant apathy," finding that TBI patients with clinically significant apathy demonstrated comparable vmPFC-dACC FC to CTRLs, whereas TBI patients with subthreshold apathy scores demonstrated vmPFC-dACC hyperconnectivity relative to both CTRLs and patients with clinically significant apathy. Post-TBI vmPFC-dACC hyperconnectivity may represent an adaptive compensatory response, helping to maintain motivation and enabling resilience to the development of apathy after neurotrauma. Given the role of vmPFC-dACC circuits in value-based decision making, rehabilitation strategies designed to improve this ability may help to reduce apathy and improve functional outcomes in TBI.
淡漠是创伤性脑损伤（TBI）的常见且致残的后遗症。然而，对于哪些患者在 TBI 后会出现淡漠，哪些患者不会出现淡漠，其神经机制知之甚少。我们旨在阐明 TBI 对动机神经回路的影响，以及这如何在 TBI 恢复过程中塑造淡漠。在亚急性轻度 TBI（n=44）、慢性轻度至中度 TBI（n=26）和非脑损伤对照参与者（CTRL；n=28）中收集了静息态功能磁共振成像数据。我们使用来自独立 TBI 研究队列中动机决策研究的vmPFC 种子来测量 vmPFC 功能连接（FC），作为评估 TBI 中淡漠的工具。患者使用一种经过充分验证的工具报告淡漠。将亚急性和慢性 TBI 与 CTRL 之间的 vmPFC 与全脑 FC 进行对比，并使用 vmPFC 预测 vmPFC FC 的回归模型进行拟合。亚急性和慢性 TBI 与 CTRL 相比，导致淡漠增加，这与先前的研究结果一致，表明淡漠在 TBI 中具有持久的影响。vmPFC 与经典的默认网络功能连接，并且这种结构在亚急性 TBI、慢性 TBI 和 CTRL 组之间没有差异。至关重要的是，在 TBI 中，增加的淡漠评分预测 vmPFC-背侧前扣带皮层（dACC）FC 减少。最后，我们根据患者是否高于或低于“临床显著淡漠”的阈值对 TBI 组进行了细分，发现具有临床显著淡漠的 TBI 患者与 CTRL 具有可比的 vmPFC-dACC FC，而具有亚临床淡漠评分的 TBI 患者与 CTRL 和具有临床显著淡漠的患者相比，vmPFC-dACC 过度连接。TBI 后 vmPFC-dACC 过度连接可能代表一种适应性补偿反应，有助于维持动机，并使神经创伤后对淡漠的发展具有弹性。鉴于 vmPFC-dACC 回路在基于价值的决策中的作用，旨在改善这种能力的康复策略可能有助于减少 TBI 中的淡漠并改善功能结果。
