Focal and Steerable Temporal Interference Stimulation of the Human Left Posterior Insula: A Proof-of-Concept Validation Using Intracranial Recordings in a Human Cadaver.

The insular cortex, especially its posterior subdivision, is a key hub for interoceptive, somatosensory, and nociceptive processing, making it a compelling target for neuromodulation. However, its depth within the lateral sulcus makes it difficult to reach selectively with conventional noninvasive brain stimulation. Temporal interference stimulation (TIS) can, in theory, focus low-frequency modulation onto deep structures, but experimental validation for the human insula is lacking. We tested whether a simple, simulation-guided TIS approach can focally and steerably modulate electric fields within the human insula. Using the TI Planning Tool, we designed anterior-posterior (AP) optimized, lateral-optimized, and non-optimized control montages and recorded induced fields from six intracranial depth electrodes spanning insular subregions in a fresh-frozen donated human body. TIS was delivered at 990 and 1000 Hz (10 Hz envelope) across five current-ratio conditions. The AP-optimized montage produced preferential envelope modulation in deep posterior insular contacts, an effect robust across contact-depth thresholds and stronger than for absolute field amplitude. Whereas varying the current ratio steered the modulation focus monotonically along the AP axis, control montages showed no such steering. These findings provide proof-of-concept evidence that simulation-guided TIS can focally target and steer stimulation within the human posterior insula.