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Prospects for transcranial temporal interference stimulation in humans: A computational study.

ABSTRACT: Transcranial alternating current stimulation (tACS) is a noninvasive method used to modulate activity of superficial brain regions. Deeper and more steerable stimulation could potentially be achieved using transcranial temporal interference stimulation (tTIS): two high-frequency alternating fields interact to produce a wave with an envelope frequency in the range thought to modulate neural activity. Promising initial results have been reported for experiments with mice. In this study we aim to better understand the electric fields produced with tTIS and examine its prospects in humans through simulations with murine and human head models. A murine head finite element model was used to simulate previously published experiments of tTIS in mice. With a total current of 0.776?mA, tTIS electric field strengths up to 383?V/m were reached in the modeled mouse brain, affirming experimental results indicating that suprathreshold stimulation is possible in mice. Using a detailed anisotropic human head model, tTIS was simulated with systematically varied electrode configurations and input currents to investigate how these parameters influence the electric fields. An exhaustive search with 88 electrode locations covering the entire head (146M current patterns) was employed to optimize tTIS for target field strength and focality. In all analyses, we investigated maximal effects and effects along the predominant orientation of local neurons. Our results showed that it was possible to steer the peak tTIS field by manipulating the relative strength of the two input fields. Deep brain areas received field strengths similar to conventional tACS, but with less stimulation in superficial areas. Maximum field strengths in the human model were much lower than in the murine model, too low to expect direct stimulation effects. While field strengths from tACS were slightly higher, our results suggest that tTIS is capable of producing more focal fields and allows for better steerability. Finally, we present optimal four-electrode current patterns to maximize tTIS in regions of the pallidum (0.37?V/m), hippocampus (0.24?V/m) and motor cortex (0.57?V/m).

SUBMITTER: Rampersad S

PROVIDER: S-EPMC6819277 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Prospects for transcranial temporal interference stimulation in humans: A computational study.

Rampersad Sumientra S Roig-Solvas Biel B Yarossi Mathew M Kulkarni Praveen P PP Santarnecchi Emiliano E Dorval Alan D AD Brooks Dana H DH

NeuroImage 20190829

Transcranial alternating current stimulation (tACS) is a noninvasive method used to modulate activity of superficial brain regions. Deeper and more steerable stimulation could potentially be achieved using transcranial temporal interference stimulation (tTIS): two high-frequency alternating fields interact to produce a wave with an envelope frequency in the range thought to modulate neural activity. Promising initial results have been reported for experiments with mice. In this study we aim to b ...[more]

PMID: 31473351

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Project description:Objective.Temporal interference stimulation (TIS) was proposed as a non-invasive, focal, and steerable deep brain stimulation method. However, the mechanisms underlying experimentally-observed suprathreshold TIS effects are unknown, and prior simulation studies had limitations in the representations of the TIS electric field (E-field) and cerebral neurons. We examined the E-field and neural response characteristics for TIS and related transcranial alternating current stimulation modalities.Approach.Using the uniform-field approximation, we simulated a range of stimulation parameters in biophysically realistic model cortical neurons, including different orientations, frequencies, amplitude ratios, amplitude modulation, and phase difference of the E-fields, and obtained thresholds for both activation and conduction block.Main results. For two E-fields with similar amplitudes (representative of E-field distributions at the target region), TIS generated an amplitude-modulated (AM) total E-field. Due to the phase difference of the individual E-fields, the total TIS E-field vector also exhibited rotation where the orientations of the two E-fields were not aligned (generally also at the target region). TIS activation thresholds (75-230 V m-1) were similar to those of high-frequency stimulation with or without modulation and/or rotation. For E-field dominated by the high-frequency carrier and with minimal amplitude modulation and/or rotation (typically outside the target region), TIS was less effective at activation and more effective at block. Unlike AM high-frequency stimulation, TIS generated conduction block with some orientations and amplitude ratios of individual E-fields at very high amplitudes of the total E-field (>1700 V m-1).Significance. The complex 3D properties of the TIS E-fields should be accounted for in computational and experimental studies. The mechanisms of suprathreshold cortical TIS appear to involve neural activity block and periodic activation or onset response, consistent with computational studies of peripheral axons. These phenomena occur at E-field strengths too high to be delivered tolerably through scalp electrodes and may inhibit endogenous activity in off-target regions, suggesting limited significance of suprathreshold TIS.

Project description:Transcranial ultrasonic stimulation (TUS) is rapidly emerging as a promising non-invasive neuromodulation technique. TUS is already well-established in animal models, providing foundations to now optimize neuromodulatory efficacy for human applications. Across multiple studies, one promising protocol, pulsed at 1000 Hz, has consistently resulted in motor cortical inhibition in humans (Fomenko et al., 2020). At the same time, a parallel research line has highlighted the potentially confounding influence of peripheral auditory stimulation arising from TUS pulsing at audible frequencies. In this study, we disentangle direct neuromodulatory and indirect auditory contributions to motor inhibitory effects of TUS. To this end, we include tightly matched control conditions across four experiments, one preregistered, conducted independently at three institutions. We employed a combined transcranial ultrasonic and magnetic stimulation paradigm, where TMS-elicited motor-evoked potentials (MEPs) served as an index of corticospinal excitability. First, we replicated motor inhibitory effects of TUS but showed through both tight controls and manipulation of stimulation intensity, duration, and auditory masking conditions that this inhibition was driven by peripheral auditory stimulation, not direct neuromodulation. Furthermore, we consider neuromodulation beyond driving overall excitation/inhibition and show preliminary evidence of how TUS might interact with ongoing neural dynamics instead. Primarily, this study highlights the substantial shortcomings in accounting for the auditory confound in prior TUS-TMS work where only a flip-over sham and no active control was used. The field must critically reevaluate previous findings given the demonstrated impact of peripheral confounds. Furthermore, rigorous experimental design via (in)active control conditions is required to make substantiated claims in future TUS studies. Only when direct effects are disentangled from those driven by peripheral confounds can TUS fully realize its potential for research and clinical applications.

Dataset Information

Prospects for transcranial temporal interference stimulation in humans: A computational study.

Publications

Prospects for transcranial temporal interference stimulation in humans: A computational study.

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