Nicolas Wattiez1, Charlotte Constans2, Thomas Deffieux2, Pierre M Daye1, Mickael Tanter2, Jean-François Aubry3, Pierre Pouget4. 1. Institut du Cerveau et de la Moelle épinière, UMRS 975 INSERM, CNRS 7225, UMPC, Paris, France. 2. Institut Langevin Ondes et Images, ESPCI ParisTech, CNRS 7587, UMRS 979 INSERM, Paris, France. 3. Institut Langevin Ondes et Images, ESPCI ParisTech, CNRS 7587, UMRS 979 INSERM, Paris, France. Electronic address: jean-francois.aubry@espci.fr. 4. Institut du Cerveau et de la Moelle épinière, UMRS 975 INSERM, CNRS 7225, UMPC, Paris, France. Electronic address: pierre.pouget@upmc.fr.
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.
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.
Authors: Mike D Menz; Patrick Ye; Kamyar Firouzi; Amin Nikoozadeh; Kim Butts Pauly; Pierre Khuri-Yakub; Stephen A Baccus Journal: J Neurosci Date: 2019-06-13 Impact factor: 6.167