SUMMARY

Focused ultrasound (FUS) offers an innovative, non-invasive technique for modulating neural activity deep within the brain. Yet, the progress in developing transcranial neuromodulation for clinical applications faces significant hurdles. The inherent complexity of the skull presents a substantial obstacle to the precise targeting of ultrasound waves, leading to focal aberration. While solutions utilizing phased arrays for aberration correction have been successful, the high cost of the phased arrays and their constant reliance on magnetic resonance imaging (MRI) pose significant roadblocks for widespread academic research and clinical translation. The second challenge lies in the current lack of a definitive consensus regarding the underlying mechanism of FUS-mediated neuromodulation. The current work proposes an efficient design of 3D-printed phase-only holograms and patient-specific registration for transcranial applications. In parallel, it attempts to understand FUS neuromodulation introducing novel tools and methodologies that leverage the principles of nonlinear acoustics.