Department of Psychology, West Virginia University, Morgantown, WV, USA.
Department of Psychology, West Virginia University, Morgantown, WV, USA.
Brain Res. 2019 Feb 1;1704:103-113. doi: 10.1016/j.brainres.2018.10.004. Epub 2018 Oct 5.
Traumatic brain injury (TBI) affects 2.8 million people annually in the United States, with significant populations suffering from ongoing cognitive dysfunction. Impairments in decision-making can have major implications for patients and their caregivers, often enduring for years to decades, yet are rarely explored in experimental TBI. In the current study, the Rodent Gambling Task (RGT), an Iowa Gambling Task analog, was used to assess risk-based decision-making and motor impulsivity after TBI. During testing, rats chose between options associated with different probabilities of reinforcement (sucrose) or punishment (timeout). To determine effects of TBI on learned behaviors versus the learning process, rats were trained either before, or after, a bilateral frontal controlled cortical impact TBI, and then assessed for 12 weeks. To evaluate the degree to which monoamine systems, such as dopamine, were affected by TBI, rats were given an amphetamine challenge, and behavior recorded. Injury immediately and chronically decreased optimal decision-making, and biased rats towards both riskier, and safer (but suboptimal) choices, regardless of prior learning history. TBI also increased motor impulsivity across time, reflecting ongoing neural changes. Despite these similarities in trained and acquisition rats, those that learned the task after injury demonstrated reduced effects of amphetamine on optimal decision-making, suggesting a lesser role of monoamines in post-injury learning. Amphetamine also dose-dependently reduced motor impulsivity in injured rats. This study opens up the investigation of psychiatric-like dysfunction in animal models of TBI and tasks such as the RGT will be useful in identifying therapeutics for the chronic post-injury period.
创伤性脑损伤 (TBI) 每年影响美国 280 万人，其中相当一部分人持续存在认知功能障碍。决策障碍可能对患者及其护理人员产生重大影响，通常持续数年至数十年，但在实验性 TBI 中很少得到探索。在当前的研究中，使用啮齿动物赌博任务 (RGT)，即爱荷华赌博任务的模拟实验，来评估 TBI 后的风险决策和运动冲动。在测试过程中，大鼠在与不同强化概率（蔗糖）或惩罚（超时）相关的选项之间进行选择。为了确定 TBI 对学习行为和学习过程的影响，大鼠在双侧额皮质控制撞击 TBI 之前或之后进行训练，然后进行 12 周评估。为了评估单胺系统（如多巴胺）是否受到 TBI 的影响，大鼠接受了安非他命挑战，并记录了行为。损伤即刻和慢性降低了最佳决策，使大鼠偏向于风险更高和安全性更高（但非最优）的选择，无论之前的学习历史如何。TBI 还随着时间的推移增加了运动冲动，反映了持续的神经变化。尽管在训练和获得大鼠中存在这些相似之处，但那些在损伤后学习任务的大鼠表现出安非他命对最佳决策的影响降低，表明单胺类物质在损伤后学习中的作用较小。安非他命还剂量依赖性地降低了损伤大鼠的运动冲动。这项研究开启了在 TBI 动物模型和 RGT 等任务中研究类似精神病障碍的可能性，这将有助于确定慢性损伤后时期的治疗方法。
