Fig 6 - available via license: Creative Commons Attribution 4.0 International
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Experimental set-up. (a) Locations of the cannula electrodes on the skull. Sutures are presented as dotted lines. (b) Cross-sectional diagram shows that the cannula electrodes were fixed on the surface of the skull with dental cement. Anchor screw was placed in the skull to strengthen the fixation. The conductive gel was loaded before tTIS to increase the conductivity. (c) Plot of electrode-tissue impedance between two cannula electrodes versus various current frequencies. Data are presented as the mean±SD, n = 3. (d) Experimental set-up of the 2-pole and the 4-pole tTIS. The motor activation induced by the 2-pole tTIS was monitored by movement of contralateral forelimb and electromyography (EMG) signal from brachioradialis.
Source publication
Transcranial temporal interference stimulation (tTIS) has been proposed as a new neuromodulation technology for non-invasive deep-brain stimulation (DBS). However, few studies have detailed the design method of a tTIS device and provided system validation. Thus, a detailed design and validation scheme of a novel tTIS device for animal brain stimula...
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... tubes cut from 16G needles (O.D.: 1.7 mm; I.D.: 1.2 mm; length: 10.0 mm) were fixed with dental cement onto the surface of the intact skull above the right primary motor cortex (M1). The positions of the cannula electrodes relative to the bregma were anteroposterior (AP) 2.5 mm, mediolateral (ML) 4.0 mm, and AP −1.5 mm and ML 1.0 mm (Fig. 6a, b). The position of the cannula electrodes used to stimulate the M1 were determined according to the functional brain mapping reported in previous study [17]. When the cannula electrodes were place onto the intact skull, short pulses (biphasic square pulse, pulse width: 1 ms, pulse interval 10 s: amplitude: 0.1∼10.0 mA) were delivered to ...
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... electrodes were filled with conductive gel (SignaGel, Parker Laboratories, Fairfield, NJ, USA). The cannula electrodes were connected to the LCR-meter, and the impedance between the electrode pair was measured at various frequencies: 0.010, 0.100, 1, 10, and 100 kHz. The mean ± standard deviation (SD) among rats was calculated for presentation (Fig. ...
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... The cannula electrodes were connected to DHES to allow interfering currents to flow through the electrode pairs. I 1 at 2 kHz and I 2 at 2 kHz + f ( f = 3-, 5-, or 10-Hz interfering frequency) were simultaneously applied to the cannula electrode pair as 2-pole mode, or applied onto the cannula electrodes and surface electrodes as 4-pole mode (Fig. 6d). In the 4-pole mode, the surface electrode was adopted by trimming off the Ag/AgCl disc electrode (diameter: 10 mm) from the electrocardiogram adhesive electrode (COMDEK Industrial Corp., Taiwan). The current intensities for I 1 and I 2 were gradually increased at increments of 0.05 mA to determine the resting motor threshold (RMT) for ...
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... were anesthetized as previous described. The skull was exposed to place cannula electrodes, and a burr hole was drilled for electric field recording (Fig. 6a). The concentric recording electrode (SS80SNE-10; Microprobes for Life Science, MD, USA) was inserted through burr hole to reach various depth beneath the surface of the cortex (Fig. 11a). The current envelops were recorded during 2-pole or 4-pole tTIS (I 1 :0.5 mA, 2 kHz; I 2 :0.5 mA, 2.003 kHz) with sampling rate of 25 kHz (MP36, ...
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... was evaluated by observing electromyography (EMG) and movement of the contralateral forelimb. Rats were anesthetized with zoletil without xylazine as described above. EMG signals were collected using 27G stainless-steel needle electrodes inserted into the brachioradialis muscles in both forelimbs. Reference electrodes were inserted into the paws (Fig. 6d). The ground electrode was inserted into the base of the tail of a rat [18]. The EMG signal was amplified 2000-fold before filtering. A notch filter with a 60-Hz cutoff was applied to remove power-line noise. A bandpass filter at 20∼500 Hz was applied to eliminate motion artifacts lower than 10 Hz and high-frequency stimulation ...
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... electrode-tissue impedance was measured under various frequencies to test the conductance between the two cannula electrodes. A frequency-dependent decrease was observed (Fig. 6c). Impedances at 1 and 10 kHz, which corresponded to tTIS frequencies (several kHz), were 3.38±0.66 and 2.83±0.59 k, respectively. The impedance ranges fit the output-loading range of our current ...
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... Motor Activation by the 2-Pole tTIS: We explored the capability of tTIS generated by our DHES device to activate M1 and drive contralateral forelimb movement. Under anesthesia, the 2-pole tTIS was delivered via cannula electrodes that were positioned on the intact skull above M1 associated with the contralateral forelimb (Fig. 6d). When the pre-mixed currents (I 1 & I 2 ) penetrate the skull and generate the interfering electric field inside the M1, the corresponding motor evoked potentials and limb movement would be observed, just like the motor activation reported using cortical stimulation [18]. We first tested relationships of the current intensity and ...
Citations
... Recently, Grossman et al. [4] used "Temporal Interference" (TI) stimulation, which generated substantial interest (e.g. [5,[5][6][7][8][9][10][11][12][13]) due to its ability to target stimulation deep inside the brain, seemingly without causing shallow stimulation. This is surprising because electric currents tend to be higher closer to the electrodes than deeper in the brain. ...
... Understanding mechanisms is quite relevant as it can help, e.g., to understand which neurons exhibit TI stimulation [7] or how to optimize parameters of TI stimulation [6,16]. The question deserves urgent attention as efforts to use this technology in humans gain momentum [5,[10][11][12][13]. ...
Temporal interference (TI) stimulation is gaining tremendous interest as a non-invasive neurostimulation breakthrough. The observation is striking: pure sinusoid (generated in shallow brain regions) appears to cause no stimulation, whereas modulated sinusoid (generated in deeper brain regions) does. To understand its effects and mechanisms, we examine responses of different cell-types, excitatory pyramidal (Pyr) and inhibitory parvalbumin (PV) expressing neurons, to pure and modulated sinusoids, in intact network as well as in isolation. In intact network, we present data showing that PV neurons are much less likely than Pyr neurons to exhibit TI stimulation. Remarkably, in isolation, our data shows that almost all Pyr neurons stop exhibiting TI stimulation. We conclude that TI stimulation is largely a network phenomenon. Indeed, PV neurons have a substantially higher firing rate with pure 038 sinusoid (shallow brain) than with modulated sinusoid (deep brain), suggesting that in shallow regions, inhibitory PV neurons actively reduce firing of excitatory Pyr neurons. Additionally, we use computational models to study the (rare) neurons that do exhibit TI stimulation in isolation and observe that this can be explained by an integral-control based high-frequency current balance in the neural ion currents.
For decades, neuromodulation technology has demonstrated tremendous potential in the treatment of neuropsychiatric disorders. However, challenges such as being less intrusive, more concentrated, using less energy, and better public acceptance, must be considered. Several novel and optimized methods are thus urgently desiderated to overcome these barriers. In specific, temporally interfering (TI) electrical stimulation was pioneered in 2017, which used a low-frequency envelope waveform, generated by the superposition of two high-frequency sinusoidal currents of slightly different frequency, to stimulate specific targets inside the brain. TI electrical stimulation holds the advantages of both spatial targeting and non-invasive character. The ability to activate deep pathogenic targets without surgery is intriguing, and it is expected to be employed to treat some neurological or psychiatric disorders. Recently, efforts have been undertaken to investigate the stimulation qualities and translation application of TI electrical stimulation via computational modeling and animal experiments. This review detailed the most recent scientific developments in the field of TI electrical stimulation, with the goal of serving as a reference for future research.
