Cuttoli Romain Durand-de, Sweis Brian M
bioRxiv. 2024 May 14:2024.05.12.593597. doi: 10.1101/2024.05.12.593597.
How mood interacts with information processing in the brain is thought to mediate the maladaptive behaviors observed in depressed individuals. However, the neural mechanisms underlying impairments in emotion-cognition interactions are poorly understood. This includes influencing the balance between how past-sensitive vs. future-looking one is during decision-making. Recent insights from the field of neuroeconomics offer novel approaches to study changes in such valuation processes in a manner that is biologically tractable and readily translatable across species. We recently discovered that rodents are sensitive to "sunk costs" - a feature of higher cognition previously thought to be unique to humans. The sunk costs bias describes the phenomenon in which an individual overvalues and escalates commitment to continuing an ongoing endeavor, even if suboptimal, as a function of irrecoverable past (sunk) losses - information that, according to classic economic theory, should be ignored. In the present study, mice were exposed to chronic social defeat stress paradigm, a well-established animal model used for the study of depression. Mice were then tested on our longitudinal neuroeconomic foraging task, Restaurant Row. We found mice exposed to this severe stressor displayed an increased sensitivity to sunk costs, without altering overall willingness to wait. Mice were then randomly assigned to receive a single intraperitoneal injection of either saline or ketamine (20 mg/kg). We discovered that stress-induced hypersensitivity to sunk costs was renormalized following a single dose of ketamine. Interestingly, in non-defeated mice, ketamine treatment completely abolished sunk cost sensitivity, causing mice to no longer value irrecoverable losses during re-evaluation decisions who instead based choices solely on the future investment required to obtain a goal. These findings suggest that the antidepressant effects of ketamine may be mediated in part through changes in the processing of past-sensitive information during on-going decision-making, reducing its weight as a potential source of cognitive dissonance that could modulate behavior and instead promoting more future-thinking behavior.
情绪如何与大脑中的信息处理相互作用被认为介导了在抑郁症患者中观察到的适应不良行为。然而，情绪 - 认知相互作用受损背后的神经机制仍知之甚少。这包括在决策过程中影响一个人对过去敏感与对未来关注之间的平衡。神经经济学领域的最新见解提供了新颖的方法来研究这种估值过程中的变化，其方式在生物学上易于处理且易于跨物种转化。我们最近发现啮齿动物对“沉没成本”敏感——这是一种以前被认为是人类独有的高级认知特征。沉没成本偏差描述了这样一种现象，即个体过度重视并加大对继续进行一项正在进行的努力的投入，即使该努力并非最优，这是不可挽回的过去（沉没）损失的函数——根据经典经济理论，这些信息应该被忽略。在本研究中，小鼠暴露于慢性社会挫败应激范式，这是一种用于研究抑郁症的成熟动物模型。然后让小鼠在我们的纵向神经经济学觅食任务“餐厅街”上进行测试。我们发现暴露于这种严重应激源的小鼠对沉没成本的敏感性增加，而不改变总体等待意愿。然后将小鼠随机分配接受单次腹腔注射生理盐水或氯胺酮（20毫克/千克）。我们发现，单剂量氯胺酮后，应激诱导的对沉没成本的超敏反应恢复正常。有趣的是，在未受挫败的小鼠中，氯胺酮治疗完全消除了沉没成本敏感性，使小鼠在重新评估决策时不再重视不可挽回的损失，而是仅根据实现目标所需的未来投资来做出选择。这些发现表明，氯胺酮的抗抑郁作用可能部分是通过在持续决策过程中对过去敏感信息处理的变化来介导的，减少其作为可能调节行为的认知失调潜在来源的权重，转而促进更多的前瞻性思维行为。
