Sources of Variability for Acoustic and Thermal Impacts of Transcranial Ultrasonic Neuromodulation in Humans

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2022-03-07

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en

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Low frequency transcranial ultrasonic stimulation is a novel technique to non-invasively stimulate the brain. Compared to transcranial magnetic and electric stimulation, it benefits from better target focality and deeper range. These features are the door to long sought-after breakthroughs for neuromodulation research and therapeutic treatments in humans. This potential can only be achieved if individual safety and dosing can be controlled. Here we quantified thermal and mechanical bioeffects, the two main safety considerations for transcranial ultrasonic stimulation, and established a pipeline for personalized dosing and safety estimation. Notably, we observe that the intensity and temperature vary significantly across individuals, with some subjects estimated to experience magnitudes more than four times as high as other subjects. We show that in two common neuromodulatory protocols used in humans the thermal rise in the skull stays within safe limits, but it is not negligible. For long-lasting repetitive stimulation protocols thermal rise was estimated at a maximum of 1.48 degrees Celsius, highlighting the importance of robust estimation of thermal risk. Moreover, we describe how the estimated impact strongly depends on the target region as well as the assumptions of the skull’s acoustic properties, varying over a factor of two. In contrast, and reassuringly, we show how expected uncertainty in transducer positioning has limited impact on acoustic intensity and how target focality can be maintained across multiple subjects. Together, these results highlight that individualized dosing and safety estimations are likely a necessary but also sufficient condition for transcranial ultrasonic stimulation in humans. KEYWORDS: NIBS, TUS, neuromodulation, numerical simulation, safety estimation

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Faculteit der Sociale Wetenschappen