Customized Deep Brain Stimulation for a more efficient therapy of severe tremor
Final Report Abstract
We were able to address different scientific questions within this project, thereby extending the knowledge on Essential tremor. In a first step, we demonstrated that this very common tremor manifestation is distinguishable from PD-tremor using nothing but an accelerometer. This may be of clinical use preventing patients from additional diagnostic procedures. Yet, the more pronounced regularity of ET also facilitates peripheral signals to trigger DBS. In an additional study, we therefore established the therapeutic potential of a novel, phase-specific thalamic stimulation algorithm. Short DBS pulses delivered at particularly vulnerable phase angles within a tremor cycle (as recorded in the accelerometer) afforded significant tremor relief while halving the required amount of energy. Although still far from being ripe to replace current DBS pulse generators, it is conceivable that combined systems with high-frequency stimulation during tremor onset and the proposed adaptive stimulation in the course of tremulous muscular activity to prevent tremor breakthroughs may provide less side-effects and more comfort to ET-patients. In addition, these results may promote the search for intracerebral markers of neural synchrony in ET. In this context, we tried to furnish proof for two distinct markers that appear suitable for closed-loop stimulation systems in the future. In terms of brain networks responsible for tremor generation, our findings on the one hand implicate tremor emergence as principally associated with increased activation of frontal motor regions, whereas modulation of tremor amplitude rather relates to changes in cerebellar activity. SMA activity may therefore constitute a possible candidate that is easily accessible and could also be used for transcranial tremor therapies, as well. Otherwise, spiking activity in the ventrolateral thalamus may also constitute a marker for closed-loop stimulation. Our findings thus revealed that increased firing rates were followed by tremor exacerbation. Recording cellular spiking activity in the inferior parts of the thalamus or in areas immediately below may thus be indicative of imminent tremor increases and therefore of the necessity to induce stimulation to abolish postural tremor. Taken together, the applicant of this project was able to scrutinise clinically relevant questions. The expertise and the knowledge resulting from this project will be the basis of further research projects that are already ongoing and that will be conducted in cooperation with the centres in Oxford and London.
Publications
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(2017) The differentiated networks related to essential tremor onset and its amplitude modulation after alcohol intake. Experimental neurology 297 50–61
Pedrosa, David J.; Nelles, Christian; Brown, Peter; Volz, Lukas J.; Pelzer, Esther A.; Tittgemeyer, Marc; Brittain, John-Stuart; Timmermann, Lars
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(2017) Tremor stability index: a new tool for differential diagnosis in tremor syndromes. Brain : a journal of neurology 140 (7) 1977–1986
Di Biase, Lazzaro; Brittain, John-Stuart; Shah, Syed Ahmar; Pedrosa, David J.; Cagnan, Hayriye; Mathy, Alexandre; Chen, Chiung Chu; Martín-Rodríguez, Juan Francisco; Mir, Pablo; Timmerman, Lars; Schwingenschuh, Petra; Bhatia, Kailash; Di Lazzaro, Vincenzo
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(2016). Stimulating at the right time: phase-specific deep brain stimulation. Brain, 140(1), 132-145
Cagnan, H., Pedrosa, D.J., Little, S., Pogosyan, A., Cheeran, B., Aziz, T., ... & Brown, P.
