Abstract
Background:Temporal interference (TI) stimulation of the brain generates amplitude-modulated electric fields oscillating in the kHz range with the goal of non-invasive targeted deep brain stimulation. Yet, the current intensities required in human (sensitivity) to modulate deep brain activity and if superficial brain region are spared (selectivity) at these intensities remains unclear.Objective:We developed an experimentally constrained theory for TI sensitivity to kHz electric field given the attenuation by membrane low-pass filtering property, and for TI selectivity to deep structures given the distribution of modulated and unmodulated electric fields in brain.Methods:The electric field threshold to modulate carbachol-induced gamma oscillations in rat hippocampal slices was determined for unmodulated 0.05–2 kHz sine waveforms, and 5 Hz amplitude-modulated waveforms with 0.1–2 kHz carrier frequencies. The neuronal effects are replicated with a computational network model to explore the underlying mechanisms, and then coupled to a validated current-flow model of the human head.Results:Amplitude-modulated electric fields are stronger in deep brain regions, while unmodulated electric fields are maximal at the cortical regions. Both experiment and model confirmed the hypothesis that spatial selectivity of temporal interference stimulation depends on the phasic modulation of neural oscillations only in deep brain regions. Adaptation mechanism (e.g. GABAb) enhanced sensitivity to amplitude modulated waveform in contrast to unmodulated kHz and produced selectivity in modulating gamma oscillation (i.e. Higher gamma modulation in amplitude modulated vs unmodulated kHz stimulation). Selection of carrier frequency strongly affected sensitivity to amplitude modulation stimulation. Amplitude modulated stimulation with 100 Hz carrier frequency required ~5 V/m (corresponding to ~13 mA at the scalp surface), whereas, 1 kHz carrier frequency ~60 V/m (~160 mA) and 2 kHz carrier frequency ~80 V/m (~220 mA) to significantly modulate gamma oscillation. Sensitivity is increased (scalp current required decreased) for theoretical neuronal membranes with faster time constants.Conclusion:The TI sensitivity (current required at the scalp) depends on the neuronal membrane time-constant (e.g. axons) approaching the kHz carrier frequency. TI selectivity is governed by network adaption (e.g. GABAb) that is faster than the amplitude-modulation frequency. Thus, we show neuronal and network oscillations time-constants determine the scalp current required and the selectivity achievable with TI in humans.
Highlights
Temporal Interference (TI) stimulation delivers high frequency sinusoidal stimulation to multiple electrodes on the scalp, where small differences in frequency (e.g. 2 and 2.10 kHz) between responsive to amplitude-modulated high-frequency electric fields compared to unmodulated electric field; 3) the current intensity requirement at the scalp level to produce sufficiently strong amplitude-modulated kHz fields deep in the brain.The effects of electrical stimulation on neuronal oscillations are often analyzed because of their sensitivity to external electric fields [5e7] and involvement in a broad range of cognitive functions and diseases [8e10]
We showed that temporal interference stimulation depends on the value of phasic modulation of neural oscillations in deep brain regions, as opposed to steady increases driven by unmodulated kHz fields at the cortex
Temporal interference stimulation has been promoted as a tool to selectively modulate neural activity in deep brain regions [1]
Summary
Temporal Interference (TI) stimulation delivers high frequency (kHz) sinusoidal stimulation to multiple electrodes on the scalp, where small differences in frequency (e.g. 2 and 2.10 kHz) between responsive to amplitude-modulated high-frequency electric fields compared to unmodulated electric field (selectivity); 3) the current intensity requirement at the scalp level to produce sufficiently strong amplitude-modulated kHz fields deep in the brain (sensitivity).The effects of electrical stimulation on neuronal oscillations are often analyzed because of their sensitivity to external electric fields [5e7] and involvement in a broad range of cognitive functions and diseases [8e10]. Conventional transcranial Alternating Current Stimulation (tACS) applies ~2 mA at the scalp level, producing electric fields up to ~0.8 V/m in the human brain [11]. In animal models, such small sinusoidal electric fields can modulate oscillations at stimulation frequencies below 100 Hz [6,12e15] but not for weak kHz frequency stimulation [15,16]. Results: Amplitude-modulated electric fields are stronger in deep brain regions, while unmodulated electric fields are maximal at the cortical regions Both experiment and model confirmed the hypothesis that spatial selectivity of temporal interference stimulation depends on the phasic modulation of neural oscillations only in deep brain regions. We show neuronal and network oscillations time-constants determine the scalp current required and the selectivity achievable with TI in humans
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call