Development of feedback-controlled neuromodulation strategies for the treatment of intractable repetitive hyperkinetic movement disorders
Tourette syndrome, presenting worldwide with a prevalence of approximately 1%, is a neurodevelopmental disorder characterized by the presence of chronic tics and is often associated with a broad spectrum of behavioural disorders including obsessive?compulsive disorder, hyperactivity, impulsivity, attention deficit, anxiety and depression. Many of these patients are refractory to current treatments and improved strategies are urgently required. Deep brain stimulation has shown promise in the treatment of the most challenging patients. However, with only a limited understanding of its underlying pathology, there is little agreement on the best to stimulation targets and parameters. Further, ?conventional?, continuous stimulation poorly matches the temporal presentation of symptoms and may be associated with stimulation induced side effects. We believe that the future of deep brain stimulation will entail the targeted modulation of only those brain regions implicated in the disease process at only those times that are required to treat the symptoms. In this multi-disciplinary and translational proposal we describe the steps necessary (i) to infer the cellular disturbances which underpin symptom presentation, (ii) to elucidate the electrophysiological biomarkers which identify the onset of tics, (iii) design the necessary algorithms and hardware necessary to deliver responsive neural stimulation to abort tic manifestation and (iv) implement and test this strategy in animal models before further application in patients. The proposed methods of this novel transversal and international scientific consortium include the combined resources of international experts in optogenetics (Partner 3), animal behavior (Partner 1), clinical and animal experimental deep brain stimulation (Partners 1, 2 and 4), advanced signal analysis and hardware design (Partner 2) and Tourette syndrome (Partners 1 and 4). Through this interdisciplinary collaboration we believe we can contribute significantly to the improved understanding and treatment of this debilitating disease.
therapy, Optogenetics, Animal models, Electrophisiological approaches, Behavioural methodologies, anxiety disorders, Electrical and magnetic brain stimulation, obsessive compulsive disorders, Tourette Syndrome, closed-loop deep brain stimulation
2014 - 2018
Christine Winter (Coordinator)