The KFO 247 (Clinical Research Unit 247)

Deep brain stimulation (DBS) can lead to remarkable and sustained improvement of motor symptoms in patients with Parkinson’s disease (PD), dystonia and tremor. Furthermore, the first trials of DBS in psychiatric disorders heralded promising results. However, the exact mechanism of action is still not yet understood.

The Clinical Research Unit (Klinische Forschergruppe, KFO) 247 – funded by the German Research Foundation (DFG) and the Charité – University Medicine Berlin – aims to further elucidate the mechanism of action of DBS in order to improve therapeutic efficacy in patients treated with DBS. To this end, we initiated a set of translational and interdisciplinary projects combining pre clinical animal studies (Project 1, 2 and 10) and neurophysiologic research in patients (Projects 3, 4, 5, 6, 8, 10) to cover mechanisms of action of DBS on a cellular level as well as on a systems physiology level. In two clinical trials (Project 9 and 10) we evaluate novel DBS target points to optimize DBS as a clinical tool in patients with Parkinson’s disease and therapy refractory depression (TRD).

In particular, the animal studies examine effects of continuous DBS on synaptic plasticity, neuroprotection and neurogenesis. With the systems physiology approach we study effects and adverse effects of DBS on motor, cognitive and affective functions in patients. Here we investigate basal ganglia (BG) physiology during motor tasks, speech and emotional processing. We will characterize the interplay between BG and cortex through i) their spatio-temporal dynamics of frequency specific oscillations ii) the analysis of their anatomical and functional connectivity and iii) their relationship to motor and behavioural features in patients with DBS. In our two clinical trials we evaluate the efficacy of DBS in novel target points in patients with PD and TRD. Hereby we aim to significantly optimize DBS therapy by better knowledge of DBS target points and by adjusting DBS parameters on an individual basis, e.g. through exact frequency specific interference with pathological oscillations while maintaining physiologic activity.