KFO 247:  Deep Brain Stimulation: Mechanisms, Physiology and Optimisation of Therapy

• Subject Area: Medicine
• Term: from 2010 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 160506045

Deep brain stimulation (DBS) is a well established therapy leading to improvement of motor symptoms and quality of life for a variety of movement disorders, such as Parkinson’s disease (PD), dystonia and tremor. Furthermore, first clinical trials examining DBS therapy in psychiatric patients are very promising. However, the exact mechanisms of action are not yet fully understood. On the other hand DBS therapy has paved the way for an innovative approach in neurophysiological research: in patients with implanted deep brain electrodes the neuronal activity can be recorded directly from the DBS target structures, thus offering a direct window to the working brain.
Within the framework of the Clinical Research Unit we intend to further elucidate the effects of DBS therapy in a broad interdisciplinary and translational approach. Our aims are to (1) investigate the mechanisms of action on a cellular level in animal models, (2) further elucidate the (patho-)physiology of cortex-basal ganglia loops in patients with movement disorders and (3) optimise the clinical application of DBS. In practical terms the effects of continuous DBS on synaptic plasticity and neuroprotection in animal experiments are to be studied.
To build a foundation for a general physiological concept about effects and side-effects of DBS, we plan to investigate the physiological role of the basal-ganglia (BG) during motor tasks, language processing and emotional stimulus processing. We intend to characterise the interplay of the BG and cortex by analysing functional and anatomical connectivity, the dynamics of long-range temporal correlations of oscillatory activity and to relate these changes to behavioural and motor deficits in patients. Additionally, we will perform two clinical trials to evaluate the efficacy of DBS with optimised targeting in patients with PD and depression.
In the long term, we expect a significant optimisation in DBS-therapy through these findings by more precise target detection and better fine-tuning of stimulation parameter e.g. through frequency-specific interference with pathological oscillations while maintaining physiological activity. Through the interaction of the participating scientists from different fields of research a multimodal and translational scientific approach to deep brain stimulation is made possible that promises to elucidate the mechanisms of action of DBS and consequentially bring a significant therapeutic optimisation where the most recent findings of animal experiments can be integrated instantly into the clinical research and the other way around questions and problems arising from clinical research can be tackled in animal models.

• DFG Programme: Clinical Research Units

Projects

• Biomarker bei idiopathischer Dystonie: Von optimierter Hochfrequenzstimulation zur Closed-Loop THS (Applicant Kühn, Andrea )
• Brückenprojekt zwischen KFO 247 und KFO 219 (Applicant Kühn, Andrea )
• Cortico-subcortical interactinons and local neuronal dynamics in Parkinson´s Disease (Applicant Curio, Gabriel )
• Dopaminerge Einflüsse auf subkortikale Oszillationen beim Belohnungslernen (Applicants Hamker, Fred Henrik ;  Kühn, Andrea )
• Emotionale Reizverarbeitung und Impulskontrolle in der Kortex - Basalganglien Schleife (Applicant Kühn, Andrea )
• Mechanismen nigraler Neuroprotektion und striataler Neuroplastizität nach chronischer STN-THS (Applicant Kupsch, Andreas )
• Mechanismen pathologischer Oszillationen in der Kortex-Basalganglien-Schleife und deren Modulation durch die tiefe Hirnstimulation im Parkinsonmodell der Ratte (Applicants Geiger, Jörg ;  van Riesen, Christoph )
• MRT-basierte Darstellung der anatomischen Konnektivität innerhalb der Kortex - Basalganglien Schleife (Applicant Draganski, Bogdan )
• Tiefe Hirnstimulation bei affektiven Störungen und deren Modellen (Applicant Winter, Christine )
• Wirkungen tiefer Hirnstimulation auf Sprech- und Sprachfunktionen (Applicant Klostermann, Fabian )
• Zelluläre Plastizität bei hochfrequenter Stimulation im Nucleus subthalamicus von Parkinson-Mäusen (Applicant Grantyn, Rosemarie )
• Zentrale Stellen und Verbrauchsmaterial der KFO (Applicant Kühn, Andrea )
• Zielpunktoptimierung bei STN-THS: STN-proper vs. caudale Zona incerta (Applicant Kühn, Andrea )

• Spokesperson: Professor Dr. Matthias Endres
• Leader: Professorin Dr. Andrea Kühn