Kilohertz Transcranial Magnetic Perturbation (kTMP): A New Non-invasive Method to Modulate Cortical Excitability

Labruna, Ludovica; Merrick, Christina; Inglis, Ben; Ivry, Richard B.; Sheltraw, Daniel

doi:10.1101/2021.11.17.465477

Cited by 4 publications

(4 citation statements)

References 106 publications

(139 reference statements)

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“…Recent work has also proposed adapting temporal interference to other modalities, including transcranial magnetic stimulation (TMS) 44,45 . The neurophysiological effects of these methods have not yet been fully characterized, but users will still need to contend with similar issues related to sub-optimal electrode/coil placement and incomplete demodulation.…”

Section: Discussionmentioning

confidence: 99%

Temporal interference stimulation disrupts spike timing in the primate brain

Vieira,

Krause,

Pack

2024

Nat Commun

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Electrical stimulation can regulate brain activity, producing clear clinical benefits, but focal and effective neuromodulation often requires surgically implanted electrodes. Recent studies argue that temporal interference (TI) stimulation may provide similar outcomes non-invasively. During TI, scalp electrodes generate multiple electrical fields in the brain, modulating neural activity only at their intersection. Despite considerable enthusiasm for this approach, little empirical evidence demonstrates its effectiveness, especially under conditions suitable for human use. Here, using single-neuron recordings in non-human primates, we establish that TI reliably alters the timing, but not the rate, of spiking activity. However, we show that TI requires strategies—high carrier frequencies, multiple electrodes, and amplitude-modulated waveforms—that also limit its effectiveness. Combined, these factors make TI 80 % weaker than other forms of non-invasive brain stimulation. Although unlikely to cause widespread neuronal entrainment, TI may be ideal for disrupting pathological oscillatory activity, a hallmark of many neurological disorders.

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Section: Discussionmentioning

confidence: 99%

Temporal interference stimulation disrupts spike timing in the primate brain

Vieira,

Krause,

Pack

2024

Nat Commun

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“…Recent work has also proposed adapting temporal interference to other modalities, especially transcranial magnetic stimulation (TMS) (e.g., Khalifa et al, 2023; Labruna et al, 2023). The neurophysiological effects of these methods have not yet been fully characterized, but users will still need to contend with similar issues related to sub-optimal electrode/coil placement and incomplete demodulation.…”

Section: Discussionmentioning

confidence: 99%

Temporal interference stimulation disrupts spike timing in the primate brain

Vieira,

Krause,

Pack

2023

Preprint

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SummaryElectrical stimulation can regulate brain activity, producing clear clinical benefits, but focal and effective neuromodulation often requires surgically implanted electrodes. Recent studies argue that temporal interference (TI) stimulation may provide similar outcomes non-invasively. During TI, scalp electrodes generate multiple electrical fields in the brain, modulating neural activity only where they overlap. Despite considerable enthusiasm for this approach, little empirical evidence demonstrates its effectiveness, especially under conditions suitable for human use. Here, using single-neuron recordings in non-human primates, we show that TI reliably alters the timing of spiking activity. However, we find that the strategies which improve the focality of TI — high frequencies, multiple electrodes, and amplitude-modulated waveforms — also limit its effectiveness. Combined, they make TI 80% weaker than other forms of non-invasive brain stimulation. Although this is too weak to cause widespread neuronal entrainment, it may be ideally suited for disrupting pathological synchronization, a hallmark of many neurological disorders.

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“…However, as shown by Vöröslakos et al [10] in TES, it is very unlikely to achieve focal and deep TMS using two TMS coils. More recently, Labruna et al reported TMS at kilohertz [39]. Nevertheless, the E-field intensity was <10 V/m, making it improbable to elicit a suprathreshold response through temporal summation.…”

Section: Previous Studies Employing High-frequency Pulse Trainsmentioning

confidence: 99%

“…The proposed method requires activating multiple TMS coils at ultra-high frequencies and relatively high intensities, potentially elevating the risk of inducing seizures compared to traditional TMS methods. In the study conducted by Labruna et al, up to 5 kHz pulses were applied, yet these pulses were of notably low intensity (<10 V/m) [39]. A series of studies by Ugawa and colleagues employing the quadri-pulse paradigm offer insights into the safety aspects of ultra-high frequency TMS [41][42][43].…”

Section: Safety Considerationsmentioning

confidence: 99%

Ultra-high frequency repetitive TMS at subthreshold intensity induces suprathreshold motor response via temporal summation

Nguyen,

Li,

Hoffman

et al. 2024

J. Neural Eng.

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Objective. The transcranial magnetic stimulation (TMS) coil induces an electric field that diminishes rapidly upon entering the brain. This presents a challenge in achieving focal stimulation of a deep brain structure. Neuronal elements, including axons, dendrites, and cell bodies, exhibit specific time constants. When exposed to repetitive TMS pulses at a high frequency, there is a cumulative effect on neuronal membrane potentials, resulting in temporal summation. This study aims to determine whether TMS pulse train at high-frequency and subthreshold intensity could induce a suprathreshold response. Approach. As a proof of concept, we developed a TMS machine in-house that could consistently output pulses up to 250 Hz, and performed experiments on 22 awake rats to test whether temporal summation was detectable under pulse trains at 100, 166, or 250 Hz. Main results. Results revealed that TMS pulses at 55% maximum stimulator output (MSO, peak dI/dt = 68.5 A/s at 100% MSO, pulse width = 48 s) did not induce motor responses with either single pulses or pulse trains. Similarly, a single TMS pulse at 65% MSO failed to evoke a motor response in rats; however, a train of TMS pulses at frequencies of 166 and 250 Hz, but not at 100 Hz, successfully triggered motor responses and MEP signals, suggesting a temporal summation effect dependent on both pulse intensities and pulse train frequencies. Significance. We propose that the temporal summation effect can be leveraged to design the next-generation focal TMS system: by sequentially driving multiple coils at high-frequency and subthreshold intensity, areas with the most significant overlapping E-fields undergo maximal temporal summation effects, resulting in a suprathreshold response.

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Kilohertz Transcranial Magnetic Perturbation (kTMP): A New Non-invasive Method to Modulate Cortical Excitability

Cited by 4 publications

References 106 publications

Temporal interference stimulation disrupts spike timing in the primate brain

Temporal interference stimulation disrupts spike timing in the primate brain

Temporal interference stimulation disrupts spike timing in the primate brain

Ultra-high frequency repetitive TMS at subthreshold intensity induces suprathreshold motor response via temporal summation

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