Transcranial focused ultrasound (TUS) offers a noninvasive and reversible approach to manipulate brain circuits, potentially transforming our understanding of brain function and treatments for brain dysfunction. However, the human head significantly attenuates and distorts ultrasound, making it challenging to deliver precise and controlled intensities into the brain. This study addresses this issue by developing a direct measurement approach called Relative Through-Transmit (RTT), which can be repeatedly applied to the human brain. RTT uses ultrasonic scans to measure and compensate for the attenuation of ultrasound by all obstacles within the ultrasound path, including the skull, hair, and acoustic coupling. The method is parameter-free and personalized to each subject, accurately restoring intended ultrasound intensities inside ex-vivo human skulls. RTT enables effective modulation of deep brain regions in humans, as demonstrated by its ability to modulate fMRI Blood Oxygen Level Dependent (BOLD) activity in disease-relevant deep brain regions. This tool opens the door to controlled and personalized applications of low-intensity ultrasound for neuromodulation and drug delivery in humans. The study also highlights the robustness of RTT with respect to hardware, target location, and ultrasound intensity levels, making it a promising method for safe and effective clinical applications.Transcranial focused ultrasound (TUS) offers a noninvasive and reversible approach to manipulate brain circuits, potentially transforming our understanding of brain function and treatments for brain dysfunction. However, the human head significantly attenuates and distorts ultrasound, making it challenging to deliver precise and controlled intensities into the brain. This study addresses this issue by developing a direct measurement approach called Relative Through-Transmit (RTT), which can be repeatedly applied to the human brain. RTT uses ultrasonic scans to measure and compensate for the attenuation of ultrasound by all obstacles within the ultrasound path, including the skull, hair, and acoustic coupling. The method is parameter-free and personalized to each subject, accurately restoring intended ultrasound intensities inside ex-vivo human skulls. RTT enables effective modulation of deep brain regions in humans, as demonstrated by its ability to modulate fMRI Blood Oxygen Level Dependent (BOLD) activity in disease-relevant deep brain regions. This tool opens the door to controlled and personalized applications of low-intensity ultrasound for neuromodulation and drug delivery in humans. The study also highlights the robustness of RTT with respect to hardware, target location, and ultrasound intensity levels, making it a promising method for safe and effective clinical applications.