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Individually customized transcranial temporal interference stimulation for focused modulation of deep brain structures: a simulation study with different head models.

ABSTRACT: Temporal interference (TI) stimulation was recently proposed that allows for the stimulation of deep brain structures with neocortical regions being minimally stimulated. For human brain modulation, TI current patterns are known to be considerably affected by the complex structures of the human head, and thus, it is hard to deliver TI current to a specific deep brain region. In this study, we optimized scalp electrode configurations and injection currents that can deliver maximum TI stimulation currents to a specific deep brain region, the head of the right hippocampus in this study, considering the real anatomical head structures of each individual. Three realistic finite element (FE) head models were employed for the optimization of TI stimulation. To generate TI current patterns, two pairs of scalp electrodes were selected, which carry two sinusoidally alternating currents with a small frequency difference. For every possible combination of electrode pairs, optimal injection currents delivering the maximal TI currents to the head of the right hippocampus were determined. The distribution of the optimized TI currents was then compared with that of the unoptimized TI currents and the conventional single frequency alternating current stimulation. Optimization of TI stimulation parameters allows for the delivery of the desired amount of TI current to the target region while effectively reducing the TI currents delivered to cortical regions compared to the other stimulation approaches. Inconsistency of the optimal stimulation conditions suggest that customized stimulation, considering the individual anatomical differences, is necessary for more effective transcranial TI stimulation. Customized transcranial TI stimulation based on the numerical field analysis is expected to enhance the overall effectiveness of noninvasive stimulation of the human deep brain structures.

SUBMITTER: Lee S

PROVIDER: S-EPMC7366675 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Individually customized transcranial temporal interference stimulation for focused modulation of deep brain structures: a simulation study with different head models.

Lee Sangjun S Lee Chany C Park Jimin J Im Chang-Hwan CH

Scientific reports 20200716 1

Temporal interference (TI) stimulation was recently proposed that allows for the stimulation of deep brain structures with neocortical regions being minimally stimulated. For human brain modulation, TI current patterns are known to be considerably affected by the complex structures of the human head, and thus, it is hard to deliver TI current to a specific deep brain region. In this study, we optimized scalp electrode configurations and injection currents that can deliver maximum TI stimulation ...[more]

PMID: 32678264

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Project description: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).

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:BackgroundLow-intensity transcranial focused ultrasound (tFUS) has emerged as a new non-invasive modality of brain stimulation with the potential for high spatial selectivity and penetration depth. Anesthesia is typically applied in animal-based tFUS brain stimulation models; however, the type and depth of anesthesia are known to introduce variability in responsiveness to the stimulation. Therefore, the ability to conduct sonication experiments on awake small animals, such as rats, is warranted to avoid confounding effects of anesthesia.ResultsWe developed a miniature tFUS headgear, operating at 600 kHz, which can be attached to the skull of Sprague-Dawley rats through an implanted pedestal, allowing the ultrasound to be transcranially delivered to motor cortical areas of unanesthetized freely-moving rats. Video recordings were obtained to monitor physical responses from the rat during acoustic brain stimulation. The stimulation elicited body movements from various areas, such as the tail, limbs, and whiskers. Movement of the head, including chewing behavior, was also observed. When compared to the light ketamine/xylazine and isoflurane anesthetic conditions, the response rate increased while the latency to stimulation decreased in the awake condition. The individual variability in response rates was smaller during the awake condition compared to the anesthetic conditions. Our analysis of latency distribution of responses also suggested possible presence of acoustic startle responses mixed with stimulation-related physical movement. Post-tFUS monitoring of animal behaviors and histological analysis performed on the brain did not reveal any abnormalities after the repeated tFUS sessions.ConclusionsThe wearable miniature tFUS configuration allowed for the stimulation of motor cortical areas in rats and elicited sonication-related movements under both awake and anesthetized conditions. The awake condition yielded diverse physical responses compared to those reported in existing literatures. The ability to conduct an experiment in freely-moving awake animals can be gainfully used to investigate the effects of acoustic neuromodulation free from the confounding effects of anesthesia, thus, may serve as a translational platform to large animals and humans.

Dataset Information

Individually customized transcranial temporal interference stimulation for focused modulation of deep brain structures: a simulation study with different head models.

Publications

Individually customized transcranial temporal interference stimulation for focused modulation of deep brain structures: a simulation study with different head models.

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