Abstract
Focused ultrasound are considered to be a promising tool for the treatment of neurological conditions, overcoming the limitations of current neurostimulation techniques in terms of spatial resolution and invasiveness. Much evidence to support the feasibility of ultrasound activation of neurons at the systemic level has already been provided, but to this day, the biophysical mechanisms underlying ultrasound neurostimulation are still widely unknown. In order to be able to establish a clear and robust causality between acoustic parameters of the excitation and neurobiological characteristics of the response, it is necessary to work at the cellular level, or alternatively on very simple animal models. The study reported here responds to three objectives. Firstly, to propose a simple nervous model for the study of the ultrasound neurostimulation phenomenon, associated with a clear and simple experimental protocol. Secondly, to compare the characteristics of this model’s nervous response to ultrasound neurostimulation with its nervous response to mechanical and electrical stimulation. Thirdly, to study the role played by certain acoustic parameters in the success rate of the phenomenon of ultrasound stimulation. The feasibility of generating action potentials (APs) in the giant axons of an earthworm’s ventral nerve cord, using pulsed ultrasound stimuli (f = 1.1 MHz, Ncycles = 175–1150, PRF = 25–125 Hz, Npulses = 20, PA = 2.5–7.3 MPa), was demonstrated. The time of generation (TOG) of APs associated with ultrasound stimulation was found to be significantly shorter and more stable than the TOG associated with mechanical stimulation (p < 0.001). By applying a causal approach to interpret the results of this study, it was concluded that, in this model, the nervous response to focused ultrasound is initiated along the afferent neurons, in between the mechanosensors and the synaptic connections with the giant axons. Additionally, early results are provided, highlighting a trend for the success rate of ultrasound neurostimulation and number of APs triggered per response to increase with increasing pulse repetition frequency (p < 0.05 and p < 0.001, respectively), increasing pulse duration and increasing pulse amplitude.
Highlights
The gold standard for the treatment of neurological conditions, when they are related to the central nervous system, is electrical deep brain stimulation (DBS) or direct cortical stimulation
It is only recently that this field of study has seen renewed interest with several promising demonstrations of the feasibility of ultrasound-mediated induction of neuronal activity at the systemic level, using multiple animal models[20,21,22,23]. While all these findings are very promising for future therapeutic applications, the biophysical mechanisms underlying the phenomenon of ultrasound neurostimulation are still widely unknown
Focused ultrasound can repeatedly trigger the generation of action potentials (APs) in earthworm giant axons
Summary
The gold standard for the treatment of neurological conditions, when they are related to the central nervous system, is electrical deep brain stimulation (DBS) or direct cortical stimulation. In a practical guide published in 20121 Fitzgerald and Daskalasis showed how high frequency repetitive TMS applied to the left dorsolateral prefrontal cortex was an effective treatment for patients suffering from major depressive disorders, and how this treatment could benefit from a method enabling brain structures to be targeted in a more accurate and reliable way[2] If these promising results are confirmed, these techniques have the advantage of being much less invasive than DBS. It is only recently that this field of study has seen renewed interest with several promising demonstrations of the feasibility of ultrasound-mediated induction of neuronal activity at the systemic level, using multiple animal models[20,21,22,23] While all these findings are very promising for future therapeutic applications, the biophysical mechanisms underlying the phenomenon of ultrasound neurostimulation are still widely unknown
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