Differential impact of stress on risk-taking behaviour in individuals using hippocampus versus caudate nucleus-dependent virtual navigation strategies

我们实验室以前的结果表明，与使用尾状核（反应学习者）的人相比，压力对使用海马体导航（空间学习者）的人有不同的影响。海马体对空间和情景记忆很重要，而尾状核则参与形成习惯和奖励寻求行为。我们以前已经表明，当儿童暴露于心理应激源（即，被告知护士将在30分钟内到达，用针头抽血），反应学习者显示皮质醇增加，皮质醇是肾上腺皮质释放的一种激素，而空间学习者则没有。皮质醇和压力会影响大脑结构，包括海马体，以及冒险等行为。此外，我们已经表明，在赌博任务中测量的冒险行为在反应学习者中也更高。因此，在目前的资助中，我们将研究压力对这两个人群的决策（包括冒险行为）产生影响的神经和激素机制，并评估针对海马体的空间记忆训练是否可以减轻冒险行为。 我们将首先测试心理压力源（即，要求人们在一组评估者面前说和做一个困难的数学问题）会导致皮质醇的增加，与空间学习者相比，这是一个成年人的反应。然后，我们将评估这种心理压力是否会增加冒险行为在赌博任务中的响应学习者相比，空间学习者。我们还将皮质醇应激反应的大小与冒险行为的水平相关联，以更好地理解这两个因素之间的关系。 然后将进行纵向空间记忆训练研究，其独特地靶向并增加海马体中的体积。我们将评估超过16周的空间记忆训练是否有能力减少空间学习者和反应学习者的冒险行为和皮质醇应激反应，并且测试是一个优先受益于这种训练的人群。我们还将收集训练前后的结构磁共振成像扫描，以评估海马灰质的增加，并将此测量与冒险行为的变化相关联。 这项资助将是理解参与竞争的多个记忆系统之间相互作用的基本神经和激素机制的基础，这些记忆系统对决策有直接影响。我们还将能够进一步评估经验依赖性训练是否能对这些神经机制产生积极影响。这项基础研究最终可以导致具体的认知干预措施，可以有利于加拿大人在生命的各个阶段的认知健康，通过进一步弥合啮齿动物和人类文献的作用，学习和记忆的压力。

Previous results from our laboratory have shown that stress has a different impact on people using the hippocampus when navigating (spatial learners) compared to those using the caudate nucleus (response learners). The hippocampus is important for spatial and episodic memory while the caudate nucleus is involved in forming habits and reward-seeking behaviour. We have previously shown that when children are exposed to a psychological stressor (i.e., being told a nurse was arriving in 30 minutes to draw blood with a needle), response learners display an increase in cortisol, a hormone released by the adrenal cortex, while spatial learners do not. Cortisol and stress have an impact on brain structures, including the hippocampus, and behaviours such as risk-taking. Further, we have shown that risk-taking behaviour as measured during a gambling task is also higher in people who are response learners. In the current grant, we will therefore investigate the neural and hormonal mechanisms by which stress has an impact on decision making, including risk-taking behavior, on these two populations and assess if spatial memory training targeting the hippocampus can mitigate risk-taking. We will first test if a psychological stressor (i.e., asking people to speak and perform a difficult math problem in front of a panel of evaluators) will cause an increase in cortisol amoungst adult response learners compared to spatial learners. We will then assess if this psychological stressor will increase risk-taking behaviour in a gambling task in response learners in comparison to spatial learners. We will also correlate the magnitude of the cortisol stress response with levels of risk-taking behaviour, to better understand the relationship between these two factors. A longitudinal spatial memory training study that uniquely targets and increases volume in the hippocampus will then be conducted. We will assess if spatial memory training over 16-weeks will have the ability to reduce risk-taking behaviour and cortisol stress response in both spatial and response learners, and test is one population preferentially benefits from such training. We will also collect structural magnetic resonance imaging scans before and after training to evaluate increases in hippocampal grey matter, and correlate this measure with changes in risk-taking behaviour. This grant will be fundamental to understand the basic neural and hormonal mechanisms involved in the interplay between competing multiple memory systems that have a direct impact on decision making. We will also be able to further evaluate if experience-dependent training can positively impact these neural mechanisms. This basic research can eventually lead to specific cognitive interventions that could benefit the cognitive health of Canadians at all stages of life, through further bridging the rodent and human literatures on the role of stress on learning and memory.