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

Abstract

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 in α-β spectral 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 with 50 Hz electrical and ultrasound pulses is capable of eliciting 100 Hz STN 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 pathological α-β power 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 in α-β power 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.

Simulation study on high spatio-temporal resolution acousto-electrophysiological neuroimaging

“…The underlying mechanisms of ultrasound neuromodulation are not well understood with multiple mechanisms being postulated to be active simultaneously (e.g. radiation force, intramembrane cavitation, thermal effects, ion channel mechanosensitivity [55][56][57][58][59][60][61]). However, the goal of AENI is to record endogenous activity, i.e.…”

“…the intrinsic activity and not the activity induced by ultrasonic activation. In future work, computational modeling of ultrasonic neuromodulation can be used to determine the region of the parameter space in which AENI is feasible without significant modulation of the endogenous activity [61][62][63]. Although a single 25 ms ultrasonic pulse was adopted in this study, signal reconstruction is still possible with pulsed ultrasonic fields with a signal period of 25 ms.…”

A Simulation Study on High Spatio-Temporal Resolution Acousto-Electrophysiological Neuroimaging

“…Indeed, the goal of AENI is to record endogenous activity by ultrasonically vibrating a region of interest, but ultrasound has been demonstrated to modulate brain activity in animals and humans [50], [51]. In future work, computational modeling of ultrasonic neuromodulation can be used to determine the region of the parameter space in which AENI is feasible without significant modulation of the endogenous activity [52]- [54]. Although a single 25 ms ultrasonic pulse was adopted in this study, signal reconstruction is still possible with pulsed ultrasonic fields with a signal period of 25 ms.…”

Dynamic modeling of neuromodulation techniques: Towards elaboration and individual specificity

“…Additionally, ultrasound stimulation was applied to a cortical-basal ganglia-thalamic neuronal network model in conjunction with electrical stimulation to investigate their combined efficacy in reducing the power of Beta oscillations [77]. Tarnaud et al further posited that theoretically, ultrasonic stimulation could be integrated with diverse control strategies to enhance the therapeutic outcomes of these modalities [77] and more effectively intervene in and manage neurological disorders.…”