Subthalamic Nucleus Stimulation Impairs Sequence Processing in Patients with Parkinson’s Disease

Article type: Research Article

Authors: Ye, Zheng^{a; b; *; 1} | Hanssen, Henrike^{b; 1} | Steinhardt, Julia^{b; c} | Tronnier, Volker^d | Rasche, Dirk^d | Brüggemann, Norbert^{b; e} | Münte, Thomas F.^{b; f; *}

Affiliations: [a] Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China | [b] Department of Neurology, University of Lübeck, Lübeck, Germany | [c] Institute of Endocrinology and Diabetes, University of Lübeck, Lübeck, Germany | [d] Department of Neurosurgery, University of Lübeck, Lübeck, Germany | [e] Institute of Neurogenetics, University of Lübeck, Lübeck, Germany | [f] Department of Psychology, University of Lübeck, Lübeck, Germany

Correspondence: [*] Correspondence to: Zheng Ye, Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Yueyang Road 320, Shanghai 200031, China. Tel.: +86 21 549 21929; E-mail: [email protected] and Thomas F. Münte, Department of Neurology, University of Lübeck, 23538 Lübeck, Germany. Tel.: +49 451 500 43400; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Background:Maintaining and manipulating sequences online is essential for language and memory. In Parkinson’s disease (PD), poor performance in sequencing tasks has been associated with basal ganglia dysfunction, especially subthalamic hyperactivity. Objective:This study is aimed to investigate the impact of high-frequency subthalamic nucleus (STN) deep brain stimulation (DBS) on sequence processing in PD. Methods:Twenty-nine patients with PD (17 women) completed a ‘before/after’ sentence task and a digit ordering task with STN DBS ON and OFF. In the sentence task, patients read a sequence of events expressed in the actual order of occurrence (‘after’ sentences) or reversed order (‘before’ sentences) for comprehension. In the digit task, patients recalled a sequence of ordered digits (ordered trials) or reordered and recalled random digits in ascending order (random trials). Volumes of tissue activated (VTAs) were estimated for the motor and associative STN. Results:Patients were slower with STN DBS ON versus OFF in both tasks, although their motor symptoms were significantly improved under DBS. In the sentence task, patients showed higher ordering-related reaction time costs (‘before’ > ‘after’) with DBS ON versus OFF. Moreover, patients with larger left associative VTAs, smaller total motor VTAs, and more daily exposure to dopaminergic drugs tended to show larger reaction time cost increases under DBS. In the digit ordering task, patients with too large or too small right associative VTAs tended to show larger reaction time cost increases under DBS. Conclusion:Stimulating the STN, especially its associative part, might impair sequence processing in language and memory.

Keywords: Parkinson’s disease, subthalamic nucleus, deep brain stimulation, sentence comprehension, temporal connectives, sequential working memory

DOI: 10.3233/JPD-212778

Journal: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 1869-1879, 2021