Subthalamic modulation of sequential working memory in Parkinson’s disease

保持以适当的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纵的一个核心方面，但在以往的研究中，这一方面基本上被忽视了。在以前的研究中，我们已经定义了一个神经网络，它包括背外侧和腹外侧额叶皮质、顶后皮质、苍白球、丘脑、黑质、小脑以及重要的丘脑底核(STN)。此外，我们还发现帕金森氏病(PD)患者的工作记忆中存在顺序排列的障碍。帕金森病的STN是深部脑刺激(DBS)的靶点。在目前的项目中，STN-DBS患者将被用来通过在刺激器打开和关闭的情况下执行订购任务来因果地调制序列订购网络。一部分患者将在这项任务的fMRI版本中使用跑步刺激器进行测试。此外，在一组术后有外置电极导联的患者中，我们将直接从STN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，我们将通过健康参与者的机器人导航的theta-Burst经颅磁刺激来调节序列排序网络的核心皮质节点。目前的工作将提供关于一个被很大程度上忽视的认知过程、工作记忆中的序列排序以及潜在的神经过程的关键新知识。特别是，它将通过干扰序列排序网络的皮质下(STN)和皮质(背外侧和腹外侧PFC，顶后皮质)节点提供因果证据。

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.