Evaluation of Specific Cortical Responses to Transcranial Temporal Interference Electrical Stimulation Using Simultaneous Functional Near-Infrared Spectroscopy.

Temporal interference (TI) stimulation is a novel non-invasive transcranial electrical stimulation (tES) that has been proposed for targeted deep brain stimulation. This study aims to present subjective sensation and objective neurophysiological evidence demonstrating the distinct modulation effect induced by TI-tES. A single-blind within-subject design was employed for this study. TI-tES was implemented on the left hippocampus, with high frequency tES (HF-tES) serving as the active control. Twenty healthy participants were recruited to participate in both TI-tES and HF-tES paradigms, with the order randomized and a separation of at least 7-day between sessions. A self-assessment scale was used to report the sensations and adverse effects immediately after stimulation. Additionally, functional near-infrared spectroscopy was used to record the cortical activity before, during, and after specific tES paradigms. The analysis focused on the patterns of brain activation and functional network. The results showed that both TI-tES and HF-tES paradigms were well-tolerated, with TI-tES (5.56%) resulting in lower scalp pain than HF-tES (33.33%). Increased activation and connectivity were observed in the sensorimotor cortices immediately following HF-tES. In contrast, TI-tES led to delayed activation increases in prefrontal and motor-related regions compared to HF-tES. Additionally, TI-tES resulted in an increased hemispheric autonomy index and dominant information flow in the prefrontal cortex. These findings show that TI-tES targeting the hippocampal region was associated with distinct cortical dynamics, potentially indicating indirect network-level modulation and reinforcement of top-down regulatory processes via the prefrontal cortex.