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

丘脑底核（subthalamic nucleus，DBS）的脑深部电刺激（Deep brain stimulation，DBS）已被证明对 改善帕金森病（PD）患者的许多运动症状。与其积极的 运动影响，许多研究已经发现了认知副作用的DBS。这并不奇怪，因为 众所周知，神经元参与认知和运动神经回路。但尽管如此， 但是，部分药物对治疗认知障碍，如强迫症， 强迫症（OCD）。这些相反的观察与知识的两个缺陷有关：1）如何 脑内的神经活动与正常和异常的认知功能有关，以及2）脑内的DBS如何 改变认知功能和神经活动之间的关系，导致功能障碍。审查这些 关系，在这项建议中，电生理学方法将与决策模型相结合， 数学心理学研究各种二选一决策（TCD）任务中的行为和决策。 TCD任务中的认知过程已经被拉特克利夫扩散模型很好地模拟和研究 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活动相关联。 过程，以允许强大的推理。DDM需要从大量试验中收集数据，以生成 决策过程的准确估计符合正确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获得， 限制数据量和可以在任何一个受试者中进行的实验操作的数量。 最近，FDA批准了Percept植入式脉冲发生器（IPG），能够记录神经 植入的DBS电极在刺激开启或关闭时的活动。在这项提案中，患有PD的患者 将招募植入IPG并连接至植入式DBS电极的IPG，并要求其参与行为测试。 实验，同时监测他们的神经活动，以实现两个目标。第一个目标是使用DDM来 了解神经信号如何从神经元与决策过程中的三个场景：当选择 当选择不涉及冲突时，当选择需要抑制行动时。的 该提案探讨了这些关系如何在响应强调响应准确性的指令时发生变化 超速。第一个实验将确定与活动相关的认知过程。在 第二个目标，该提案探讨了当DBS打开时，这些关系如何改变。 在这些实验中，DDM被用来理解决策过程和神经网络之间的关系。 活动的改变差异TCD任务，涉及冲突比那些不，以及这些是否 仅在需要在精度和速度之间进行权衡的情况下才改变关系。这将有助于通知 临床医生如何最好地应用DBS来改善心理健康疾病的认知功能， 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.