Transcranial ultrasonic stimulation (TUS) is an emerging technique that comes with the promise of non-invasive deep brain neuromodulation at unprecedented spatial precision, which may revolutionize the treatment of neurological and psychiatric disease. Two major challenges currently constitute roadblocks for a wider adoption of the technique in basic research and clinical application. On the one hand, the human skull bone causes significant reflection, aberration, and attenuation of the ultrasound waves and thus unintended spatial shifts and intensity reductions of the stimulation focus. Individual acoustic simulations are used to tackle this issue but require high quality bone imaging data from CT or special MR-sequences as well as empirical validation. On the other hand, the large parameter space of possible stimulation parameters needs to be explored to establish robust and effective neuromodulation protocols, while considering the known state-dependency of TUS neuromodulatory effects, existing biophysical safety limitations, and peripheral co-stimulation confounds. Empirical proof of both target exposure and neuronal target engagement is thus required to evaluate and correctly interpret TUS neuromodulatory effects. While the former requires specialized imaging techniques such as MR-thermometry and MR-based acoustic radiation force imaging (MR-ARFI), the latter can be achieved by combining TUS with established functional neuroimaging, electrophysiological, or other brain stimulation techniques. In my talk I will provide an introduction into both the fundamentals and the practical aspects of TUS application, discuss the promises and pitfalls of a combined application with EEG, fMRI, and TMS, and provide examples from ongoing TUS research in our lab.
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