EFFECTS OF HIPPOCAMPAL TRANSCRANIAL TEMPORAL INTERFERENCE STIMULATION ON SPATIAL NAVIGATION AND RELATED BRAIN OSCILLATIONS IN TBI AND HEALTHY INDIVIDUALS

Aims: Spatial navigation impairments are commonly reported amongst traumatic brain injury (TBI) patients; however, avenues for amelioration remain limited. Recently, transcranial temporal interference stimulation (tTIS) delivered to the hippocampal-entorhinal complex (HC-EC) was demonstrated to improve spatial navigation abilities in healthy individuals^1,2. Here, we investigate tTIS effects on navigation performance and associated oscillatory dynamics in TBI patients and healthy age-matched controls (HA). We expect intermittent theta-burst patterned tTIS (iTBS-tTIS) to improve navigation performance versus control stimulation conditions. Neurally, we expect increased frontal theta-band activity during planning and navigation versus stasis.
Methods: In this ongoing study (planned N=25 TBI, 25 HA) we deliver excitatory iTBS-tTIS, inhibitory continuous TBS-tTIS (cTBS-tTIS), or high-frequency control stimulation (HF, see Fig.1) to the individually-targeted right HC-EC while participants perform an established virtual-reality spatial navigation task consisting of encoding and recalling object locations in a virtual arena¹. High-density EEG is recorded during tTIS+task performance, and during resting state preceding and following tTIS+task.
Results: In line with previous findings, pilot data (N=2 healthy young adults) demonstrate improved trial time during iTBS versus HF stimulation (relative improvement pilot1: 18%, pilot2: 8%) or cTBS (pilot1: 17%, pilot2: 12%). Application of high-pass and low-pass hardware filters proved effective in minimizing tTIS-related artefacts in EEG recordings. Two TBI patients completed the experimental protocol, demonstrating study feasibility in patients.
Conclusions: This study will provide novel data on the behavioral and neural effects of hippocampal tTIS on spatial navigation and its cortical correlates. ¹Beanato et al., 2024, Science Advances; ²Zhao et al., 2025, Nature Communications

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