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Sunday, July 19 • 9:00pm - 10:00pm
P196: Robustness of ultrasonic modulation of the subthalamic nucleus to GABAergic perturbation

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Thomas Tarnaud
, Wout Joseph, Ruben Schoeters, Luc Martens, Timothy Van Renterghem, Emmeric Tanghe

Introduction: Deep brain stimulation (DBS) is a surgical treatment for movement and neuropsychiatric disorders. Here, the subthalamic nucleus (STN) is the most common target for the treatment of advanced Parkinson’s disease (PD). Although DBS has proven effective, the procedure is associated with surgical risks such as infection and haemorrhage. Consequentially, we investigated the possibility of using ultrasound (US) as a non-invasive and reversible alternative of conventional DBS. Here, we expand on our study on the spiking behaviour of a computational STN model [1], insonicated with continuous-wave and pulsed US of different intensities. In particular, the sensitivity of the simulated STN response to hyperpolarizing input (e.g., GABAergic globus pallidus afferents) is investigated. Methods: A computational model for insonication of the STN is created by combining the Otsuka-model of a plateau-potential generating STN neuron [2] with the bilayer sonophore model [3-4]. After careful validation of our model implementation by comparison with theoretical and experimental literature, simulations are performed of the STN- neuron insonicated with different ultrasonic intensities and pulse waveforms. The robustness of the simulated response to GABAergic input is tested by injecting brief hyperpolarizing currents. Results: Our model results predict intensity dependent spiking modes of the STN neurons. For continuous waveforms, three different observed spiking modes in order of increasing ultrasonic intensity are low-frequency spiking, high-frequency (>120 Hz) spiking with significant spike-frequency and spike-amplitude adaptation, and a silenced mode. Simulation results indicate that only the silenced mode is robust to brief hyperpolarizing input. In contrast, the STN response will saturate robustly to the pulse repetition frequency in pulsed US, for sufficiently large intensity and pulse repetition frequency. Conclusion: Model results of the ultrasonically stimulated plateau-potential generating STN predict intensity dependent spiking modes that could be useful for the treatment of PD. High-frequency spiking of the STN might “jam” pathological network activity or result in the creation of an information lesion due to short-term synaptic depression, which are potential mechanisms ascribed to conventional DBS. In contrast, the silenced mode in which the STN transmembrane potential is fixed to a stable plateau might be functionally equivalent to subthalamotomy and to depolarization blockage of STN efferents during DBS. The former and latter STN mode is induced robustly by pulsed and continuous wave US, respectively.


[1] Tarnaud, T., Joseph, W., Martens, L. and Tanghe, E., 2018. Computational Modeling of Ultrasonic Subthalamic Nucleus Stimulation. IEEE Transactions on Biomedical Engineering. [2] Otsuka, T., Abe, T., Tsukagawa, T., & Song, W. J. (2004). Conductance- based model of the voltage-dependent generation of a plateau potential in subthalamic neurons. Journal of neurophysiology, 92(1), 255-264. [3] Plaksin, M., Shoham, S. and Kimmel, E., 2014. Intramembrane cavitation as a predictive bio-piezoelectric mechanism for ultrasonic brain stimulation. Physical review X, 4(1), p.011004. [4] Lemaire, T., Neufeld, E., Kuster, N., & Micera, S. (2019). Understanding ultrasound neuromodulation using a computationally efficient and interpretable model of intramembrane cavitation. Journal of Neural Engineering, 16(4), 046007.

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Thomas Tarnaud

INTEC WAVES, University of Ghent - IMEC

Sunday July 19, 2020 9:00pm - 10:00pm CEST
Slot 15