  Objective. While ultrasound is largely established for use in diagnostic
imaging and heating therapies, its application for neuromodulation is
relatively new and not well understood. The objective of the present study was
to investigate issues related to interactions between focused acoustic beams
and brain tissues to better understand possible limitations of transcranial
ultrasound for neuromodulation. Approach. A computational model of transcranial
focused ultrasound was constructed and validated against bench top experimental
data. The models were then incrementally extended to address and investigate a
number of issues related to the use of ultrasound for neuromodulation. These
included the effect of variations in skull geometry and gyral anatomy, as well
as the effect of transmission across multiple tissue and media layers, such as
scalp, skull, CSF, and gray/white matter on ultrasound insertion behavior. In
addition, a sensitivity analysis was run to characterize the influence of
acoustic properties of intracranial tissues. Finally, the heating associated
with ultrasonic stimulation waveforms designed for neuromodulation was modeled.
Main results. Depending on factors such as acoustic frequency, the insertion
behavior of a transcranial focused ultrasound beam is only subtly influenced by
the geometry and acoustic properties of the underlying tissues. Significance.
These issues are critical for the refinement of device design and the overall
advancement of ultrasound methods for noninvasive neuromodulation.
