Temporal interference (TI) is a strategy for non-invasive steerable stimulation of neurons deep in the brain using multiple kHz-range electric fields with a difference frequency within the range of neural activity. Here we report the validation of the TI stimulation concept in humans. We used electric field modelling and measurements in a human cadaver to verify that the locus of the transcranial TI stimulation can be steerably focused in the hippocampus with minimal exposure to the overlying cortex. We then used functional magnetic resonance imaging (fMRI) to investigate physiological changes in hippocampal activity during stimulation. TI modulated hippocampal activity during the performance of an episodic memory task. In an additional study, prolonged exposure to TI stimulation improved episodic memory accuracy in a healthy human cohort. Our findings demonstrate the utility of TI stimulation by non-invasively modulating hippocampal neural activity in humans.

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