The present invention relates to methods and systems for achieving effective neuromodulation by transcranial ultrasound (bioTU). Embodiments of the invention include methods and systems for selecting, generating, and delivering transcranial ultrasound to the brain of a living subject. Methods and systems are described for determining the effect of bioTU on brain function. Certain embodiments of the present invention include methods and systems for measuring at least one quantifiable metric of brain activity, cognitive function, or physiology in order to optimize the ultrasound waveforms delivered. In an embodiment, the invention uses a closed-loop design to iteratively improve the effectiveness of bioTU waveforms delivered.
