Epilepsy Treatment Using Neuromodulation by Non-Invasive Temporal Interference Stimulation

Project Information

EMUNITI

Grant agreement ID: 101088623

DOI

10.3030/101088623

EC signature date 24 November 2023

Start date 1 December 2023

End date 30 November 2028

Funded under

• European Research Council (ERC)

Total cost

€ 1 996 925,00

EU contribution

€ 1 996 925,00

Coordinated by

FAKULTNI NEMOCNICE U SV ANNY V BRNE
Czechia

Periodic Reporting for period 1 - EMUNITI (Epilepsy Treatment Using Neuromodulation by Non-Invasive Temporal Interference Stimulation)

Reporting period: 2023-12-01 to 2026-05-31

Summary of the context and overall objectives of the project

Epilepsy is a neurological disorder characterised by recurrent, unprovoked seizures with existing therapies facing limitations. Funded by the European Research Council, the EMUNITI project bridges engineering and clinical neurology to create a groundbreaking, non-invasive brain stimulation device based on temporal interference technology. This technology delivers electrical signals to the brain at specific positions around the scalp which interfere in a way that blocks seizure-provoking brain activity. Researchers will generate a clinical prototype and evaluate it in epilepsy patients for both diagnostic purposes, such as seizure localisation, and therapeutic intervention. The ultimate goal is to extend temporal interference applications beyond epilepsy.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

The most significant achievements encompass groundbreaking publications and translational impacts. First, Missey et al. (2026) in Brain Stimulation demonstrated non-invasive TIS suppression of epileptic biomarkers (IEDs and FR) in MTLE patients, with statistically significant reductions (p<0.05) and carry-over effects, marking a clinical milestone in non-invasive epilepsy modulation – therapeutic modulation of epilepsy is the absolute primary goal of EMUNITI and this paper demonstrates it is absolutely possible. Second, Botzanowski et al. (2025) introduced multipolar TIS (mTI), enabling focal deep brain stimulation in primates and rodents, with electrophysiological evidence of superior colliculus activation—published in Bioelectronic Medicine and advancing neuromodulation precision – this paper is a technological achievement as it take the technology a step further in deep brain focality. Third, Lamoš et al. (2025) showed TIS reduces STN beta activity in PD patients equivalently to DBS, via LFP recordings, published in Movement Disorders, highlighting therapeutic equivalence. Fourth, Missey et al. (2025) in bioRxiv revealed bidirectional memory modulation via TIS, enhancing (5 Hz) or impairing (130 Hz) recall in humans, with fMRI confirming network-specific effects.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Several achievements represent breakthroughs beyond the state-of-the-art. The most notable is in Missey et al. (2026, Brain Stimulation), where TIS suppressed epileptic biomarkers more effectively than sham kilohertz stimulation, revealing biophysical distinctions: amplitude-modulated envelopes penetrated deeper without depth-dependent attenuation, unlike unmodulated kHz fields. This unplanned finding—emerging from comparative sham controls—advances neuromodulation by demonstrating TIS's unique subthreshold mechanism for focal, non-invasive therapy in epilepsy, surpassing traditional tACS/tDCS limitations. Similarly, mTI in Botzanowski et al. (2025) decoupled focality from intensity, a first in non-invasive stimulation, enabling scalable targeting in primates—unexpectedly effective in awake behavioral tasks without disrupting performance.
In memory, Missey et al. (2025, bioRxiv) achieved bidirectional modulation via frequency-specific TIS, advancing cognitive neuroscience beyond invasive studies by non-invasively altering hippocampal-neocortical networks. These breakthroughs reduce invasiveness in neurology, with potential for broader applications in disorders like PD, dementia and Alzheimer's.