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Movement disorders and deep brain stimulation

Movement disorders, such as Parkinson´s disease (PD), Essential Tremor (ET), Dystonia, Gilles de al Tourette Syndrome (GTS) are amongst the most common neurological disorders. Deep brain stimulation (DBS) has evolved into a very effective neuromodulatory surgical treatment for PD, ET and dystonia although the mechanisms of action are still poorly understood.

The Centre for Movement Disorders and Neuromodulation at the University Hospital Düsseldorf is based on a close collaboration of the Departments of Neurology and Neurosurgery and is one of the largest German DBS centres.

Deep Brain Stimulation

The clinical groups of Alfons Schnitzler, PI Neurology, and Jan Vesper, PI Functional Neurosurgery, are involved in current major clinical DBS trials of the German DBS Study Group on PD, cervical dystonia, tardive dystonia and have largely contributed to studies demonstrating the efficacy of DBS in PD (Deuschl, NEJM 2006; Witt, Lancet Neurol 2008), generalized dystonia (Kupsch, NEJM 2006), neurodegeneration with brain iron accumulation (Timmermann, Brain 2010), essential tremor (Barbe, Exp Neurol 2011).

In addition to its well established therapeutic efficacy, the DBS approach also provides unique direct neurophysiological access to the diseased brain to investigate underlying pathomechanisms. Several research groups in the NND focus on the pathophysiology of movement disorders and the mechanisms of DBS. Accumulating evidence indicates that abnormal oscillatory activity plays an important role in the pathophysiology of movement disorders (Schnitzler, Nat Rev Neurosci 2005).

PIs

The lab of Alfons Schnitzler studies the dynamics of oscillatory activity in basal ganglia thalamocortical loops in patients with movement disorders in order to identify disease-related and disease-specific abnormal patterns of activity. Non-invasive MEG and invasive local field potential recordings from post-operatively externalized DBS leads as well as combined MEG-LFP recordings are being performed. This sophisticated methodological set-up is currently established only in very few labs worldwide and provides the unique opportunity to study basal ganglia cortex interactions in humans at highest temporal and spatial resolution (Hirschmann, Neuroimage 2011).

Furthermore, recent findings suggesting a pathophysiological role of altered high frequency oscillations above 200 Hz (Özkurt, Exp Neurol 2011) are of particular relevance for future studies aiming at unraveling the mechanisms of DBS in PD, and exploit this knowledge to further advance DBS therapy into an adaptive neuromodulation method.

Other projects address oscillatory basal ganglia activity in Huntington´s disease (Groiss, Mov Disord 2011), altered network activity in GTS patients (Bäumer, Mov Disord 2010Franzkowiak, Mov Disord 2010) and effects of STN stimulation on auditory and somatosensory processing (Airaksinen, Hum Brain Mapp 2011), and on impulsive behavior in PD (Rogers, Exp Neurol 2011).

To better understand the functioning and the side effects of deep brain stimulation in Parkinson’s disease the group of Esther Florin uses whole head MEG measurements in combination with recordings from the deep brain stimulation electrode. By studying the functional connectivity across the whole brain, the aim is to identify network changes due to medication and deep brain stimulation in Parkinson’s disease.

The lab of Joseph P. Huston has a longstanding experience and extensive track record in behavioral neuropharmacology of the basal ganglia and animal models of PD (Schwarting, Prog Neurobiol 1996Pum, Neuroscience 2009; Chao, Brain Res Bull 2011Chao, Neuroscience 2011). His activities include the assessment of dopamine transporter and D2 receptor binding with small animal single-photon emission computed tomography in cooperation with the Clinic of Nuclear Medicine  (Nikolaus, Rev Neurosci 2011).

In collaboration with Jan Vesper he has established an animal model of DBS to explore together with the group of M. A. de Souza Silva behavioural, electrophysiological and biochemical effects of DBS in rodents.

Ongoing experiments characterise plasticity effects of DBS in basal different ganglia nuclei.