Simulating The Effects of Low Intensity Focused Ultrasound in Parkinson's Disease

Invasiveness limits current neuromodulation approaches for treating Parkinson's disease (PD). Low-intensity focused ultrasound (LIFUS) is a viable non-invasive alternative to modulate the cortico-subcortical networks involved in PD. In this study, an intramembrane cavitation model was used to simulate the effects of ultrasonic stimulation to the subthalamic nucleus in a simplified validated model of the cortico-subcortical network. Simulation results from single neuron and network models show the ultrasonic stimulus was effective in producing neuronal excitation in the subthalamic nucleus as well as modulation of activities in other nuclei of the network model (e.g., globus pallidus and thalamus). Additionally, depending on LIFUS parameters (i.e., amplitude and duty cycle) there was a reduction in beta-band parkinsonian oscillations to values close to the healthy condition. Exploratory tests of the stimulus parametric space revealed different operating ranges that could be used to optimize the therapeutic response to LIFUS. In conclusion, the membrane cavitation framework provides reasons to believe that LIFUS would be a potential therapeutic intervention to modulate neuronal circuits involved in PD without surgical procedures. Also, the model employed in the present study would be helpful in exploring other neuromodulation effects of ultrasound waves in neuronal circuits in the brain. However, it is important to validate the results from the computer simulations using both experiments with animal models and clinical trials with humans.