Improved alpha-beta power reduction via combined electrical and ultrasonic stimulation in a parkinsonian cortex-basal ganglia-thalamus computational model

Objective. To investigate computationally the interaction of combined electrical and ultrasonic modulation of isolated neurons and of the parkinsonian cortex-basal ganglia-thalamus loop.Approach. Continuous-wave or pulsed electrical and ultrasonic neuromodulation is applied to isolated Otsuka plateau-potential generating subthalamic nucleus (STN) and Pospischil regular, fast and low-threshold spiking cortical cells in a temporally alternating or simultaneous manner. Similar combinations of electrical/ultrasonic waveforms are applied to a parkinsonian biophysical cortex-basal ganglia-thalamus neuronal network. Ultrasound-neuron interaction is modelled respectively for isolated neurons and the neuronal network with the NICE and SONIC implementations of the bilayer sonophore underlying mechanism. Reduction inα-βspectral energy is used as a proxy to express improvement in Parkinson's disease by insonication and electrostimulation.Main results. Simultaneous electro-acoustic stimulation achieves a given level of neuronal activity at lower intensities compared to the separate stimulation modalities. Conversely, temporally alternating stimulation with50 Hzelectrical and ultrasound pulses is capable of eliciting100 HzSTN firing rates. Furthermore, combination of ultrasound with hyperpolarizing currents can alter cortical cell relative spiking regimes. In the parkinsonian neuronal network, continuous-wave and pulsed ultrasound reduce pathological oscillations by different mechanisms. High-frequency pulsed separated electrical and ultrasonic deep brain stimulation (DBS) reduce pathologicalα-βpower by entraining STN-neurons. In contrast, continuous-wave ultrasound reduces pathological oscillations by silencing the STN. Compared to the separated stimulation modalities, temporally simultaneous or alternating electro-acoustic stimulation can achieve higher reductions inα-βpower for the same safety contraints on electrical/ultrasonic intensity.Significance. Focused ultrasound has the potential of becoming a non-invasive alternative of conventional DBS for the treatment of Parkinson's disease. Here, we elaborate on proposed benefits of combined electro-acoustic stimulation in terms of improved dynamic range, efficiency, spatial resolution, and neuronal selectivity.