灵长类灵活与习惯性决策中丘脑底核吻侧与尾侧的价值加工差异：对帕金森病认知功能障碍的启示
Differential value processing in the rostral and causal subthalamic nucleus during flexible and habitual decision-making in primates: Implications for cognitive dysfunction in Parkinson's disease
丘脑底核（STN）是帕金森病（PD）深部脑刺激（DBS）的主要靶区，可有效缓解运动症状。然而，STN-DBS也可诱发认知障碍，提示STN参与超越简单运动控制的认知功能。此外，解剖组织支持认知过程的功能分离，因为编码灵活价值和稳定价值的基底神经节亚区以拓扑方式投射到不同的STN亚区。然而，STN是否参与认知功能，以及若参与，STN各亚区如何差异化处理认知灵活性和习惯稳定性，仍不清楚。在此，我们揭示了STN的吻-尾侧功能组织，其分别差异化支持灵活价值更新和长期价值记忆，从而分别实现适应性和习惯性决策。吻侧STN（rSTN）的神经元优先编码灵活更新的价值，而尾侧STN（cSTN）的神经元优先编码稳定的长期价值记忆。值得注意的是，沿吻-尾侧轴失活STN产生了可分离的行为缺陷：rSTN失活选择性损害需要灵活价值更新的目标导向行为，而cSTN失活选择性破坏由长期价值记忆引导的习惯行为。总之，这些结果揭示了STN的吻-尾侧功能分离，其中rSTN支持目标导向行为，cSTN支持习惯行为。这些发现进一步为理解帕金森病中STN功能障碍或STN-DBS如何差异化影响超越运动控制的认知过程提供了框架。
在灵长类中用失活实验区分 STN 前后段对目标导向与习惯行为的因果作用，为理解 STN-DBS 的认知副作用提供了解剖框架。
The subthalamic nucleus (STN) is a major target region of deep brain stimulation (DBS) for Parkinson's disease (PD), effectively alleviating motor symptoms. However, STN-DBS can also induce cognitive impairments, suggesting that the STN contributes to cognitive functions beyond simple motor control. Furthermore, anatomical organization supports functional segregation of cognitive processes, as basal ganglia subregions encoding flexible and stable values topographically project to distinct STN subregions. Yet, whether the STN contributes to cognitive functions and, if so, how subregions of the STN differentially process cognitive flexibility and habitual stability remains unknown. Here, we reveal a rostral-caudal functional organization of the STN that differentially supports flexible value updating and long-term value memory, enabling adaptive and habitual decision-making, respectively. Neurons in the rostral STN (rSTN) preferentially encode flexibly updated values, whereas neurons in the caudal STN (cSTN) preferentially encode stable long-term value memories. Notably, inactivation of the STN along the rostral-caudal axis produced dissociable behavioral deficits: rSTN inactivation selectively impaired goal-directed behavior requiring flexible value updating, whereas cSTN inactivation selectively disrupted habitual behavior guided by long-term value memories. Together, these results reveal a rostral-caudal functional segregation of the STN, with the rSTN supporting goal-directed behavior and the cSTN supporting habitual behavior. These findings further provide a framework for understanding how STN dysfunction or STN-DBS in Parkinson's disease may differentially affect cognitive processes beyond motor control.
中文翻译还没有生成，先显示原文。
来源：bioRxiv · Neuroscience · biorxiv.org