BACKGROUND: Temporal interference stimulation (TIS) is a novel noninvasive electrical stimulation technique to focally modulate deep brain regions; a minimum of two high-frequency signals (f1 and f2 > 1 kHz) interfere to create an envelope-modulated signal at a deep brain target with the frequency of modulation equal to the difference frequency: Δf = |f2 - f1|. OBJECTIVE: The goals of this study were to verify the capability of TIS to modulate the subthalamic nucleus (STN) with Δf and to compare the effect of TIS and conventional deep brain stimulation (DBS) on the STN beta oscillations in patients with Parkinson's disease (PD). METHODS: DBS leads remained externalized after implantation, allowing local field potentials (LFPs) recordings in eight patients with PD. TIS was performed initially by two pairs (f1 = 9.00 kHz; f2 = 9.13 kHz, 4 mA peak-peak per pair maximum) of scalp electrodes placed in temporoparietal regions to focus the envelope signal maximum (Δf = 130 Hz) at the motor part of the STN target. RESULTS: The comparison between the baseline LFPs and recordings after TIS and conventional DBS sessions showed substantial suppression of high beta power peak after both types of stimulation in all patients. CONCLUSIONS: TIS has the potential to effectively modulate the STN and reduce the beta oscillatory activity in a completely noninvasive manner, as is traditionally possible only with intracranial DBS. Future studies should confirm the clinical effectiveness of TIS and determine whether TIS could be used to identify optimal DBS candidates and individualize DBS targets. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

1st Department of Neurology Masaryk University School of Medicine St Anne's Hospital Brno Czechia

Bioelectronics Materials and Devices Central European Institute of Technology Brno University of Technology Brno Czechia

Brain and Mind Research Program Central European Institute of Technology Masaryk University Brno Czechia

Department of Neurosurgery Masaryk University School of Medicine St Anne's Hospital Brno Czechia

Foundation for Research on Information Technologies in Society Zurich Switzerland

Institut de Neurosciences des Systèmes Aix Marseille University and INSERM Marseille France

Medico Surgical Unit Epileptology Functional and Stereotactic Neurosurgery Timone University Hospital Marseille France

Neuromodulation Technology Research International Clinical Research Center St Anne's University Hospital Brno Czechia

10.1002/mds.29967 PubMed

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