Temporal Interference Stimulation Can Enhance or Disrupt Human Memory Encoding as a Function of Brain Location and Frequency

Missey, F.; Jouval-Missey, E.; de Araujo e Silva, M.; Arantes, A.; Lubrano, C.; Trajlinek, J.; Studnicka, O.; Klus, S.; Violante, I. R.; Boly, M.; Jirsa, V.; Tononi, G.; Pedersen, N. P.; Drane, D. L.; Williamson, A.

doi:10.1101/2025.09.22.677714

bioRxiv · 10.1101/2025.09.22.677714

Temporal Interference Stimulation Can Enhance or Disrupt Human Memory Encoding as a Function of Brain Location and Frequency

Missey, F.·Jouval-Missey, E.·de Araujo e Silva, M.·Arantes, A.·Lubrano, C.·Trajlinek, J.·Studnicka, O.·Klus, S.·Violante, I. R.·Boly, M.·Jirsa, V.·Tononi, G.·Pedersen, N. P.·Drane, D. L.·Williamson, A.

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Abstract

Visual memory relies on synchronized interactions and rhythms between the medial temporal lobes and neocortical brain regions. Non-invasive manipulation of memory-related brain regions, specifically deeper temporal lobe regions, has been limited by the lack of precision of non-invasive neuromodulation - when targeting deeper structures, the cortex is always stimulated, never deeper structures in isolation. Temporal Interference (TI) stimulation, a novel non-invasive technique, uses high-frequency carrier fields to deliver targeted, physiologically relevant neuromodulation via amplitude-modulated envelopes at specific brain regions. Here, we investigate TIs impact on figure memory encoding in 70 healthy participants using the Rey-Osterrieth and Taylor Complex Figure tasks, with TI applied in several brain regions independently and simultaneously - allowing investigation of combinations of medial temporal lobe and neocortical brain regions. Interestingly, higher frequency TI envelopes (130 Hz offset) targeting bilateral hippocampi and temporal cortices significantly impair recall (p = 6.54e-04), while lower frequency TI envelopes (5 Hz offset) targeting only the bilateral hippocampi significantly enhance recall (p = 0.0447). Stimulation using other combinations of medial temporal lobe and neocortical regions showed no effect, underscoring the critical role of frequency and focality of non-invasive brain stimulation and correct target selection. Finally, functional MRI reveals strong differences between the effects of 130 Hz and 5 Hz envelopes, specifically in hippocampal BOLD signals, brain connectivity, default mode, and attentional networks. These findings demonstrate TIs ability to bidirectionally modulate memory encoding through precise frequency and target tuning, offering a powerful tool for cognitive neuroscience and potential therapeutic applications for memory disorders. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=80 SRC="FIGDIR/small/677714v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@8e9db3org.highwire.dtl.DTLVardef@1135a3corg.highwire.dtl.DTLVardef@189345dorg.highwire.dtl.DTLVardef@ccca8f_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical Abstract:C_FLOATNO Temporal Interference stimulation for bidirectional memory modulation assessed via behavioral testing and MRI scanning. C_FIG

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Missey, F., Jouval-Missey, E., de Araujo e Silva, M., Arantes, A., Lubrano, C., Trajlinek, J., Studnicka, O., Klus, S., Violante, I. R., Boly, M., Jirsa, V., Tononi, G., Pedersen, N. P., Drane, D. L., Williamson, A.. 2025-09-22. Temporal Interference Stimulation Can Enhance or Disrupt Human Memory Encoding as a Function of Brain Location and Frequency. https://doi.org/10.1101/2025.09.22.677714

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