Subthalamic modulation of sequential working memory in Parkinson’s disease

保持以适当的序列顺序排列工作记忆表征的能力对于复杂行为至关重要。工作记忆中的序列排序是心理操作的一个核心方面，但这一点在以往的研究中被忽视了。在以前的研究中，我们已经定义了一个神经网络，它是序列排序的基础，包括背外侧和腹外侧前额叶皮层、后顶叶皮层、苍白球、丘脑、黑质、小脑，重要的是，丘脑底核（subthalamic nucleus，简称STN）。此外，我们已经证明了帕金森病（PD）患者的工作记忆中的序列排序受损。脑深部电刺激（DBS）治疗帕金森病的靶点是脑干。在当前项目中，将使用STN-DBS患者，通过在刺激器打开和关闭的情况下执行排序任务，对串行排序网络进行因果调制。将在fMRI版本的任务中使用运行的刺激器对一部分患者进行测试。此外，在一组手术后电极导线外置的患者中，我们将直接从序列中记录，期望在序列排序过程中找到不同错误类别的神经特征。最后，我们将通过机器人导航的theta脉冲串经颅磁刺激对健康受试者的串行排序网络的核心皮层节点进行调制，目前的工作将为一个在很大程度上被忽视的认知过程提供关键的新知识，工作记忆中的串行排序，以及潜在的神经过程。特别是，它将通过干扰序列排序网络的皮层下（NST）和皮层（背外侧和腹外侧PFC，后顶叶皮层）节点来提供因果关系证据。

Maintaining the ability to arrange working memory representations in an appropriate serial order is crucial for complex behavior. Serial ordering within working memory constitutes one core aspect of mental manipulation, yet this aspect has been largely neglected in previous research. In previous studies, we have defined a neural network that underlies serial ordering including the dorsolateral and ventrolateral prefrontal cortex, posterior parietal cortex, globus pallidus, thalamus, substantia nigra, cerebellum and importantly, the subthalamic nucleus (STN). Moreover, we have demonstrated an impairment of serial ordering in working memory in patients with Parkinson’s disease (PD). The STN is the target of deep brain stimulation (DBS) in PD. Patients with STN-DBS will be used in the current project to causally modulate the serial ordering network by performing an ordering task with stimulator switched on and off. A subset of patients will be tested with running stimulator in an fMRI-version of the task. Moreover, in a group of patients with externalized electrode leads after the operation we will record directly from the STN with the expectation to find neural signatures of different error categories during serial ordering. Finally, we will modulate core cortical nodes of the serial ordering network by robot-navigated theta-burst transcranial magnetic stimulation in healthy participants.The current work will deliver crucial novel knowledge on a largely neglected cognitive process, serial ordering within working memory, and the underlying neural processes. In particular, it will provide causal evidence by interfering with subcortical (STN) and cortical (dorsolateral and ventrolateral PFC, posterior parietal cortex) nodes of the serial ordering network.