Using intracranial recording, stimulation, and computational modeling to map role of the subthalamic nucleus in human decision making

丘脑底核(STN)的深部脑刺激(DBS)已被证明在 改善帕金森病(PD)患者的许多运动症状。与其积极的一面形成对比 除了运动效应，许多研究都发现了STN DBS的认知副作用。这并不令人惊讶，因为 众所周知，STN参与认知和运动神经回路。但尽管如此，认知领域的星展银行 部分STN在治疗认知障碍方面只产生了轻微的效果，如强迫症- 强迫症(OCD)。这些截然不同的观察与知识中的两个缺陷有关：1)如何 STN中的神经活动与认知功能的正常和异常有关，以及2)STN的DBS如何 改变认知功能和神经活动之间的关系，从而导致功能障碍。来研究这些 关系，在这个提议中，电生理方法将与来自 数学心理学研究各种二选一决策(TCD)任务中的行为和决策。 在TCD任务中，激活的认知过程已经被很好地模拟并用Ratcliff扩散法进行研究 决策模型(DDM)。DDM允许使用基于模型的方法将神经活动与认知联系起来 允许强大推论的过程。DDM需要从大量试验中收集的数据才能生成 对决策过程的准确估计符合正确决策和不正确决策的反应时间分布。 然而，人类的侵入性记录仅从术中或围手术期情况下获得 限制可以在任何一个受试者身上进行的数据量和实验操作的数量。 最近，FDA批准了能够记录神经的Percept植入式脉冲发生器(IPG) 植入DBS电极的活动开启或关闭刺激。在这项提案中，患有这种疾病的帕金森病患者 植入并连接到STN DBS电极的IPG将被招募并被要求参与行为 同时对他们的神经活动进行监测的实验达到了两个目的。第一个目标是使用DDM来 了解来自STN的神经信号如何在三种情况下与决策过程相关：何时选择 涉及冲突，当选择不涉及冲突时，以及当选择需要抑制行动时。这个 提案探讨了这些关系如何随着强调响应准确性的指令而发生变化 超速行驶。第一个实验将确定与STN活动相关的认知过程。在 第二个目标，该提案探讨了当STN的DBS打开时，这些关系是如何改变的。在……里面 这些实验中，DDM被用来理解决策过程和神经之间的关系 涉及冲突的TCD任务与不涉及冲突的TCD任务之间的活动改变是不同的，以及这些任务 只有在需要权衡精确度和速度的情况下，关系才会改变。这将有助于了解 临床医生如何最好地应用DBS改善心理健康疾病的认知功能并避免其认知 DBS用于治疗运动障碍时的副作用。

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been shown to be effective in ameliorating many of the motor symptoms in patients with Parkinson Disease (PD). In contrast to its positive motor effects, many studies have uncovered cognitive side effects of STN DBS. This is not surprising as the STN is known to be involved in cognitive as well as motor neural circuits. But despite this, DBS of the cognitive portions of the STN has only resulted in modest effects on treatment of cognitive disorders such as obsessive- compulsive disorder (OCD). These contrasting observations relate to two deficiencies in knowledge: 1) how neural activity in the STN relates to both normal and abnormal cognitive function, and 2) how DBS of the STN alters the relationship between cognitive function and neural activity to cause dysfunction. To examine these relationships, in this proposal, electrophysiological methods will be combined with decision-making models from mathematical psychology to study behavior and decision-making in a variety of two-choice decision (TCD) tasks. The cognitive processes active in TCD tasks have been well modeled and studied using Ratcliff’s diffusion decision model (DDM). The DDM allows the use a model-based approach to relate neural activity to cognitive processes to allow powerful inferences. The DDM requires data collected from large number of trials to generate accurate estimates of decision process fits to distributions of reaction times for correct and incorrect decisions. However, invasive recordings in humans are only obtained from intraoperative or perioperative situations which limit the amount of data and number of experimental manipulations that could be performed in any one subject. Recently, the FDA approved the Percept implantable pulse generator (IPG) that is capable of recording neural activity from implanted DBS electrodes on or off stimulation. In this proposal, patients with PD who have had this IPG implanted and connected to a STN DBS electrode will be recruited and asked to participate in behavioral experiments while their neural activity is monitored to achieve two aims. The first aim is to use the DDM to understand how neural signals from the STN relate to decision processes in three scenarios: when choices involve conflict, when choosing does not involve conflict, and when choosing requires inhibition of action. The proposal explores how these relationships change in response to instructions emphasizing response accuracy over speed. The first experiments will identify the cognitive processes that are related to STN activity. In the second aim, the proposal explores how these relationships are changed when DBS of the STN is turned on. In those experiments, the DDM is used to understand how the relationship between decision processes and neural activity is altered differentially between TCD tasks that involve conflict than those that don’t and whether these relationships are altered only in situations that demand tradeoff of accuracy over speed. This will help inform clinician how to best apply DBS to improve cognitive function in mental health disease and avoid its cognitive side effects when DBS is used in treating movement disorders.