Transcranial ultrasonic stimulation modulates single-neuron discharge in macaques performing an antisaccade task

Abstract

Background Low intensity transcranial ultrasonic stimulation (TUS) has been demonstrated to non-invasively and transiently stimulate the nervous system. Although US neuromodulation has appeared robust in rodent studies, the effects of US in large mammals and humans have been modest at best. In addition, there is a lack of direct recordings from the stimulated neurons in response to US. Our study investigates the magnitude of the US effects on neuronal discharge in awake behaving monkeys and thus fills the void on both fronts. Objective/hypothesis In this study, we demonstrate the feasibility of recording action potentials in the supplementary eye field (SEF) as TUS is applied simultaneously to the frontal eye field (FEF) in macaques performing an antisaccade task. Results We show that compared to a control stimulation in the visual cortex, SEF activity is significantly modulated shortly after TUS onset. Among all cell types 40% of neurons significantly changed their activity after TUS. Half of the neurons showed a transient increase of activity induced by TUS. Conclusion Our study demonstrates that the neuromodulatory effects of non-invasive focused ultrasound can be assessed in real time in awake behaving monkeys by recording discharge activity from a brain region reciprocally connected with the stimulated region. The study opens the door for further parametric studies for fine-tuning the ultrasonic parameters. The ultrasonic effect could indeed be quantified based on the direct measurement of the intensity of the modulation induced on a single neuron in a freely performing animal. The technique should be readily reproducible in other primate laboratories studying brain function, both for exploratory and therapeutic purposes and to facilitate the development of future clinical TUS devices.

Abstract via europepmc.

Flags from extraction

• exposures[0].free_field.pressure_kpa — Values (0.76 MPa monkey Y, 0.31 MPa monkey L) are from Table 1 'Equivalent PNP in free water', not from a single contiguous sentence; quoted the corresponding in-brain PNP sentence for context and reconstructed the table row separately in provenance.notes.
• exposures[0].in_situ.isppa_w_cm2 — ISPPA values (5.6, 1.9 W/cm2) are derived by the authors from the simulated in-brain peak negative pressure using ISPPA=P^2/2ρc with water's ρ and c; recorded as in-situ since the pressure used in the calculation is the simulated brain (FEF) pressure, not the free-water pressure.
• exposures[0].timing.pulse_repetition_frequency_hz — Set to null: each stimulation event is a single isolated 100-ms tone burst (occurring once every 5 behavioural trials), not a periodic pulse train, so a within-sonication PRF/duty cycle is not defined.
• randomised — Paper does not state whether the every-5th-trial TUS delivery schedule (with jittered 3s+ inter-trial gaps) constitutes randomisation.
• auditory_control — No mention of auditory masking or control for auditory confounds in this paper.