Spatio-temporal characterization of causal electrophysiological activity stimulated by single pulse focused ultrasound: an ex vivo study on hippocampal brain slices

Abstract

Objective. The brain operates via generation, transmission and integration of neuronal signals and most neurological disorders are related to perturbation of these processes. Neurostimulation by focused ultrasound (FUS) is a promising technology with potential to rival other clinically used techniques for the investigation of brain function and treatment of numerous neurological diseases. The purpose of this study was to characterize spatial and temporal aspects of causal electrophysiological signals directly stimulated by short, single pulses of FUS on ex vivo mouse hippocampal brain slices. Approach. Microelectrode arrays (MEAs) are used to study the spatio-temporal dynamics of extracellular neuronal activities both at the single neuron and neural networks scales. Hence, MEAs provide an excellent platform for characterization of electrical activity generated, modulated and transmitted in response to FUS exposure. In this study, a novel mixed FUS/MEA platform was designed for the spatio-temporal description of the causal responses generated by single 1.78 MHz FUS pulses in ex vivo mouse hippocampal brain slices. Main results. Our results show that FUS pulses can generate local field potentials (LFPs), sustained by synchronized neuronal post-synaptic potentials, and reproducing network activities. LFPs induced by FUS stimulation were found to be repeatable to consecutive FUS pulses though exhibiting a wide range of amplitudes (50–600 μV), durations (20–200 ms), and response delays (10–60 ms). Moreover, LFPs were spread across the hippocampal slice following single FUS pulses thus demonstrating that FUS may be capable of stimulating different neural structures within the hippocampus. Significance. Current knowledge on neurostimulation by ultrasound describes neuronal activity generated by trains of repetitive ultrasound pulses. This novel study details the causal neural responses produced by single-pulse FUS neurostimulation while illustrating the distribution and propagation properties of this neural activity along major neural pathways of the hippocampus.

Mechanistic insights into ultrasonic neurostimulation of disconnected neurons using single short pulses

“…A possible cause for the increased amplitude is that longer bursts of multiple APs are generated in the responsive neurons, but this has not been verified. These results align with previous in-vitro [25,43,45,48] and in-vivo studies [20,63e65] showing stimulation efficacy increases with pressure.…”

“…This is in line with Tyler et al ( 2008) [17], showing AP disruption eliminates the response to US in hippocampal slices. This was also shown in connected networks [41,43,50].…”

Neurostimulation success rate of repetitive‐pulse focused ultrasound in an in vivo giant axon model: An acoustic parametric study

“…The approach presented in this study can be virtually replicated on any neural model and has guided our group in carrying such investigations on more complex in vitro and ex vivo vertebrate neural models. 60 As a result, we will also seek to compare the activation dynamics of FUS stimulation of the earthworm model with those governing other giant axon models such as the squid and/or lobster models.…”

“…This distinction led to differences in response latencies between the two stimulation modalities and could also have a significant impact on their respective NSR s. While electrical stimulation is only regulated by the activation of the giant fibers, FUS stimulation could be regulated by the activation properties of both the giant fibers and the afferent nerves. The approach presented in this study can be virtually replicated on any neural model and has guided our group in carrying such investigations on more complex in vitro and ex vivo vertebrate neural models 60 . As a result, we will also seek to compare the activation dynamics of FUS stimulation of the earthworm model with those governing other giant axon models such as the squid and/or lobster models.…”

Review of Noninvasive or Minimally Invasive Deep Brain Stimulation

“…Low-energy FUS increased conduction velocity and compound action potential in the excised sciatic nerves of a bullfrog (Tsui et al, 2005 ). In microelectrode arrays for observing the spatiotemporal dynamics of extracellular neuronal activities after FUS, local field potential spread across hippocampal sections (Suarez-Castellanos et al, 2021 ).…”