A causal study of the phenomenon of ultrasound neurostimulation applied to an in vivo invertebrate nervous model

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.

Effects of Noninvasive Low-Intensity Focus Ultrasound Neuromodulation on Spinal Cord Neurocircuits In Vivo

“…Further studies have confirmed that low-intensity focused ultrasound (LIFU) activates neurocircuits in both model organisms and humans. Indeed, pulsed focused ultrasonic stimulation has been shown to effectively induce nerve responses and action potentials in the giant fibers of invertebrate animals [ 14 , 15 ]. Moreover, precise stimulation of the deep brain nuclei and modulation of brain neuronal activity [ 16 – 19 ] have been shown to induce muscle contraction of the limbs of rats and rabbits, as verified by electromyography (EMG) [ 20 , 21 ].…”

Effect of Therapeutic Ultrasound on the Release of Insulin, Glucagon, and Alpha‐Amylase from Ex Vivo Pancreatic Models

“…In addition, low‐intensity applications of US have been increasingly explored for safe and efficient stimulation and modulation of cellular activity 15–17 . Though much of the work in this field has been focused on applications for neurostimulation/neuromodulation, 18,19 US can also be used to regulate the activity of other excitable cells such as pancreatic endocrine cells 15,20,21 …”

An Integrated 2D Ultrasound Phased Array Transmitter in CMOS With Pixel Pitch-Matched Beamforming

“…Where N is the number of transducers of a squared 2D phased array. To avoid grating lobes in the field of view of the transducer array, d must respect the condition given by (2), where θmax is the maximum of θXZ and θYZ [30]. For θmax of ±90°, d has a minimum value at λ/2.…”

“…EVERAGING decades of technological advances in the field of ultrasound medical diagnostic imaging, new ultrasound biomedical applications are now emerging, such as ultrasound neuromodulation [1][2][3][4][5][6] and ultrasonic power delivery and communication for medical implants [7][8][9][10][11][12][13][14]. These applications benefit from the attractive properties of ultrasound energy propagation and interaction with tissue, such as low scattering, low attenuation, and safe energy levels.…”