Methods and systems for transcranial ultrasound neuromodulation as well as targeting such neuromodulation in the brain are disclosed. Automated transcranial Doppler imaging (aTCD) of blood flow in the brain is performed and one or more 3-dimensional maps of the neurovasculature are generated. Ultrasound energy is delivered transcranially in conjunction to induce neuromodulation. One or more brain regions for neuromodulation are targeted by using brain blood vessel landmarks identified by aTCD components. The landmarks are used for initial targeting of the neuromodulation to one or more brain regions of interest and/or for maintaining neuromodulation targeting despite user or device movements. Acoustic contrast agents may be employed to generate broadband ultrasound waves locally at the site of target cells. Transcranial ultrasound neuromodulation may be achieved by having confocal ultrasound waves differing in acoustic frequency by a frequency effective for neuromodulation interfere to generate vibrational forces in the brain that induce neuromodulation.
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