Biophysics of Temporal Interference Stimulation

Mirzakhalili, Ehsan; Barra, Beatrice; Capogrosso, Marco; Lempka, Scott F.

doi:10.1016/j.cels.2020.10.004

Cited by 93 publications

(178 citation statements)

References 89 publications

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“…Interestingly, temporal interference stimulation was only recently introduced, in Grossman et al (2017) . The concept of TI stimulation exploits physiological properties of neurons, namely that the neuronal membranes filter electrical signals of frequencies more than 1 kHz, limiting depolarization and stimulation properties above these frequencies ( Hutcheon and Yarom, 2000 ; Mirzakhalili et al, 2020 ). In our work presented here, we show that a crucial part of TI stimulation is the electrode orientation – not simply to move the spot of focal stimulation – but more importantly to move the orientation of electric field of the TI with respect to the orientation of the underlying structure to be stimulated.…”

Section: Introductionmentioning

confidence: 99%

Orientation of Temporal Interference for Non-invasive Deep Brain Stimulation in Epilepsy

et al. 2021

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In patients with focal drug-resistant epilepsy, electrical stimulation from intracranial electrodes is frequently used for the localization of seizure onset zones and related pathological networks. The ability of electrically stimulated tissue to generate beta and gamma range oscillations, called rapid-discharges, is a frequent indication of an epileptogenic zone. However, a limit of intracranial stimulation is the fixed physical location and number of implanted electrodes, leaving numerous clinically and functionally relevant brain regions unexplored. Here, we demonstrate an alternative technique relying exclusively on non-penetrating surface electrodes, namely an orientation-tunable form of temporally interfering (TI) electric fields to target the CA3 of the mouse hippocampus which focally evokes seizure-like events (SLEs) having the characteristic frequencies of rapid-discharges, but without the necessity of the implanted electrodes. The orientation of the topical electrodes with respect to the orientation of the hippocampus is demonstrated to strongly control the threshold for evoking SLEs. Additionally, we demonstrate the use of Pulse-width-modulation of square waves as an alternative to sine waves for TI stimulation. An orientation-dependent analysis of classic implanted electrodes to evoke SLEs in the hippocampus is subsequently utilized to support the results of the minimally invasive temporally interfering fields. The principles of orientation-tunable TI stimulation seen here can be generally applicable in a wide range of other excitable tissues and brain regions, overcoming several limitations of fixed electrodes which penetrate tissue and overcoming several limitations of other non-invasive stimulation methods in epilepsy, such as transcranial magnetic stimulation (TMS).

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Section: Introductionmentioning

confidence: 99%

Orientation of Temporal Interference for Non-invasive Deep Brain Stimulation in Epilepsy

et al. 2021

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“…This stimulation method has been conventionally applied to peripheral stimulation, such as sacral nerve stimulation ( Johnson and Tabasam, 2003 ; Beatti et al, 2011 ). TI can be considered for stimulation due to the low-pass filtering effect of the passive cell membrane that may be accompanied by rectification of the ionic part ( Middleton et al, 2006 ; Grossman et al, 2017 ; Mirzakhalili et al, 2020 ). If a current (a few kHz up to 10 kHz) is injected, the cell membrane in the brain may not readily follow the oscillation of the electric field.…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies have shown promising results for motor area stimulation in mice ( Grossman et al, 2017 ; Song et al, 2020 ). In addition, various efforts have been made to clarify the mechanism regarding biophysics using neural models ( Karimi et al, 2019 ; Cao and Grover, 2020 ; Howell and McIntyre, 2020 ; Mirzakhalili et al, 2020 ; Esmaeilpour et al, 2021 ). It is also relevant to incorporate and validate the effects of the interferential currents that are shaped by the anatomical and electrical properties of biological tissues ( Rampersad et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Multiscale Computational Model Reveals Nerve Response in a Mouse Model for Temporal Interference Brain Stimulation

2021

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There has been a growing interest in the non-invasive stimulation of specific brain tissues, while reducing unintended stimulation in surrounding regions, for the medical treatment of brain disorders. Traditional methods for non-invasive brain stimulation, such as transcranial direct current stimulation (tDCS) or transcranial magnetic stimulation (TMS), can stimulate brain regions, but they also simultaneously stimulate the brain and non-brain regions that lie between the target and the stimulation site of the source. Temporal interference (TI) stimulation has been suggested to selectively stimulate brain regions by superposing two alternating currents with slightly different frequencies injected through electrodes attached to the scalp. Previous studies have reported promising results for TI applied to the motor area in mice, but the mechanisms are yet to be clarified. As computational techniques can help reveal different aspects of TI, in this study, we computationally investigated TI stimulation using a multiscale model that computes the generated interference current pattern effects in a neural cortical model of a mouse head. The results indicated that the threshold increased with the carrier frequency and that the beat frequency did not influence the threshold. It was also found that the intensity ratio between the alternating currents changed the location of the responding nerve, which is in agreement with previous experiments. Moreover, particular characteristics of the envelope were investigated to predict the stimulation region intuitively. It was found that regions with high modulation depth (| maximum| − | minimum| values of the envelope) and low minimum envelope (near zero) corresponded with the activation region obtained via neural computation.

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“…[40] Another simulation study reported that TI stimulation might have effects other than activating neurons in the target area, such as conduction block in off-target areas. [41] However, no data about the actual effect of TI stimulation on human brains have been (which was not certified by peer review) is the author/funder. All rights reserved.…”

Section: Introductionmentioning

confidence: 99%

“…[40] Another simulation study reported that TI stimulation might have effects other than activating neurons in the target area, such as conduction block in off-target areas. [41]…”

Section: Introductionmentioning

confidence: 99%

High Gamma and Beta Temporal Interference Stimulation in the Human Motor Cortex Improves Motor Functions

Ma¹,

Xia

Zhang³

et al. 2021

Preprint

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Temporal interference (TI) stimulation is a new technique of noninvasive brain stimulation. Envelope-modulated waveforms with two high-frequency carriers can activate neurons in target brain regions without stimulating the overlying cortex, which has been validated in mouse brains. However, whether TI stimulation can work on the human brain has not been elucidate. In this study, this issue is investigated in the human primary motor cortex. Participants attended three sessions of TI stimulation during a random reaction time task (RRTT) or a serial reaction time task (SRTT). Motor cortex excitability was measured before and after TI stimulation. The results indicate that TI stimulation with different envelope frequencies influenced different motor functions. In the RRTT experiment, only 70 Hz TI stimulation had a promoting effect on the reaction time performance and excitability of the motor cortex compared to sham stimulation. Meanwhile, compared with the sham condition, only 20 Hz TI stimulation significantly facilitated motor learning in the SRTT experiment, which was significantly positively correlated with the increase in motor evoked potential. These results indicate that the envelope-modulated waveform of TI stimulation has a significant promoting effect on human motor functions, experimentally suggesting the effectiveness of TI stimulation in humans for the first time.

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Biophysics of Temporal Interference Stimulation

Cited by 93 publications

References 89 publications

Orientation of Temporal Interference for Non-invasive Deep Brain Stimulation in Epilepsy

Orientation of Temporal Interference for Non-invasive Deep Brain Stimulation in Epilepsy

Multiscale Computational Model Reveals Nerve Response in a Mouse Model for Temporal Interference Brain Stimulation

High Gamma and Beta Temporal Interference Stimulation in the Human Motor Cortex Improves Motor Functions

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