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Modulation of brain activity with low intensity focused ultrasound

Abstract : Considering the extent of neurodegenerative diseases consequences on the society, focused ultrasound appears as a promising technique combining non-invasiveness, millimetric spatial accuracy and ability to reach deep brain structures. However, efforts still need to be made to amplify the effects of focused ultrasound neuromodulation, understand its mechanism and control the safety of the technique before moving towards human trials.The ultrasound propagation inside the brain of rodents and monkeys was first studied numerically to estimate the maximum intensity in the brain, the pressure distribution in the skull cavity and the thermal rise. To evaluate physiologically the ultrasound effects at the cellular level, the activity of individual neurons was measured on awake macaques during ultrasonic neuromodulation. To further increase the duration of the modulation, a longer sonication was tested successfully on macaques performing a visual task. Functional MRI was then used to highlight the connectivity changes between the stimulated area and distant cerebral regions. Finally, the advantages of ultrasound neurostimulation were combined with the efficiency of a neuroactive agent (GABA). Using microbubbles and ultrasound, the blood brain barrier was opened locally and reversibly in the visual cortex of anesthetized macaques to deliver an inhibitory neurotransmitter in the brain. The amplitude of the EEG response of the visual cortex to stimuli decreased after GABA injection, demonstrating the feasibility of delivering neuroactive drugs non-invasively and locally to any brain region.Overall, ultrasound parameters were optimized with both numerical tools and in vivo experiments to amplify neuromodulation effects while controlling the safety. This work opens the way to the development of novel therapeutic applications and new tools for connectivity studies
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  • HAL Id : tel-02015339, version 1

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Charlotte Constans. Modulation of brain activity with low intensity focused ultrasound. Acoustics [physics.class-ph]. Université Sorbonne Paris Cité, 2018. English. ⟨NNT : 2018USPCC006⟩. ⟨tel-02015339⟩

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