  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 focused ultrasound (FUS) on ex vivo mouse hippocampal brain
slices. Approach: MicroElectrode Arrays (MEA) 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 $\mu$V), 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.
