Subthalamic modulation of sequential working memory in Parkinson’s disease

• Applicant: Professor Dr. Thomas F. Münte
• Subject Area: Human Cognitive and Systems Neuroscience
• Term: from 2020 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 432259499

• Final Report Year: 2024

Final Report Abstract

The ability to organize representations in working memory in a sequential manner is vital for complex behaviors. Serial ordering in working memory is a fundamental aspect of cognitive processing, yet it has been largely overlooked in past research. Our previous studies have identified a neural network responsible for serial ordering, which includes areas such as the dorsolateral and ventrolateral prefrontal cortex, posterior parietal cortex, globus pallidus, thalamus, substantia nigra, cerebellum, and notably, the subthalamic nucleus (STN). We have also found that individuals with Parkinson’s disease (PD) show difficulties with serial ordering in working memory. The STN, a focal point for deep brain stimulation (DBS) in PD treatment, will play a central role in our current study. In the course of the project experimentally influenced the serial ordering network in patients with STN-DBS by having them perform a task with the stimulator turned on and off. Additionally, we also performed several fMRI experiments to further pinpoint the role of the STN (and other brain areas) in serial working memory. Based on the results of our fMRI studies we attempted to affect key cortical areas of the serial ordering network using robot-navigated theta-burst transcranial magnetic stimulation in healthy subjects. To summarize, we have established the role of the STN as a key player in serial working memory. These studies should be extended to assess the STN’s role in the different subdomains of executive functions.

Publications

• Age differences in the fronto-striato-parietal network underlying serial ordering. Neurobiology of Aging, 87, 115-124.
  Ye, Zheng; Zhang, Guanyu; Li, Shuaiqi; Zhang, Yingshuang; Xiao, Weizhong; Zhou, Xiaolin & Münte, Thomas F.
  
• The Role of the Subthalamic Nucleus in Sequential Working Memory in De Novo Parkinson's Disease. Movement Disorders, 36(1), 87-95.
  Ye, Zheng; Zhang, Guanyu; Zhang, Yingshuang; Li, Shuaiqi; Liu, Na; Zhou, Xiaolin; Xiao, Weizhong & Münte, Thomas F.
  
• Association of Locus Coeruleus and Substantia Nigra Pathology With Cognitive and Motor Functions in Patients With Parkinson Disease. Neurology, 97(10).
  Prasuhn, Jannik; Prasuhn, Michelle; Fellbrich, Anja; Strautz, Robert; Lemmer, Felicitas; Dreischmeier, Shalida; Kasten, Meike; Münte, Thomas F.; Hanssen, Henrike; Heldmann, Marcus & Brüggemann, Norbert
  
• Motor Sequence Learning Deficits in Idiopathic Parkinson’s Disease Are Associated With Increased Substantia Nigra Activity. Frontiers in Aging Neuroscience, 13.
  Tzvi, Elinor; Bey, Richard; Nitschke, Matthias; Brüggemann, Norbert; Classen, Joseph; Münte, Thomas F.; Krämer, Ulrike M. & Rumpf, Jost-Julian
  
• Subthalamic Nucleus Stimulation Impairs Sequence Processing in Patients with Parkinson’s Disease. Journal of Parkinson's Disease, 11(4), 1869-1879.
  Ye, Zheng; Hanssen, Henrike; Steinhardt, Julia; Tronnier, Volker; Rasche, Dirk; Brüggemann, Norbert & Münte, Thomas F.
  
• Altered alpha and theta oscillations correlate with sequential working memory in Parkinson’s disease. Brain Communications, 4(3).
  Ye, Zheng; Heldmann, Marcus; Herrmann, Lisa; Brüggemann, Norbert & Münte, Thomas F.
  
• Pramipexole modulates fronto-subthalamic pathway in sequential working memory. Neuropsychopharmacology, 48(5), 716-723.
  Heldmann, Marcus; Mönch, Eliana; Kesseböhmer, Antonia; Brüggemann, Norbert; Münte, Thomas F. & Ye, Zheng
  
• Cross-frequency and inter-regional phase synchronization in explicit transitive inference. Cerebral Cortex, 34(1).
  Heldmann, Marcus; Rohde, Lisa Suzanna; Münte, Thomas F. & Ye, Zheng