Transcranial temporal interference stimulation (tTIS) aims to non-invasively stimulate deep brain regions by manipulating certain electrical properties of electrical stimulation (Grossman et al., 2017). Specifically, tTIS is based on applying pairs of sinusoidal current signals with slightly different high frequencies simultaneously (e.g., 2 kHz and 2.005 kHz). The frequencies used must be higher than regular neural frequencies (i.e., > 600 Hz), whilst also penetrating skull and brain tissue (Oostendorp et al., 2000; von Conta et al., 2021). Stimulation in such high frequencies alone does not appear to induce a measurable increase in neural activity (Hutcheon and Yarom, 2000; Bikson et al., 2004).
Introduction to Temporal Interference
Where the electric currents from each electrode pair intersect an electric field is generated with an average carrier frequency (e.g., 2.005 kHz). Furthermore, the resulting electric field will exhibit amplitude modulation, (i.e., a change in peak electric field) at the envelope beat frequency (i.e., the difference between the two applied frequencies - in the example depicted in Figure 1 it would be 10 Hz; Esmaeilpour et al., 2021). This beat frequency is the target stimulation frequency and is maximal when the both signals overlap with the same strength and equivalent field vector directionality (von Conta et al., 2021). The weaker of the two fields used to generate the interference field, and their respective alignments determines the overall strength of the “interference” (Rampersad et al., 2019).
(Figure 1: Esmaeilpour et al., 2021)
The ability to non-invasively electrically target deep brain areas precisely, without also stimulating cortical regions outside of the ROI remains a challenge in humans. Grossman and colleagues (2017) demonstrated in the hippocampus of mice that tTIS triggers neural firing at the beat frequency, without stimulating the overlaying cortex. The translation of these findings from animal models to humans has had several recent advancements (e.g., Rampersad et al., 2019; von Conta et al., 2021). For example, Rampersad and colleagues (2019) have demonstrated optimal electrode placement and current patterns to target the palladium, hippocampus and motor cortex. Their simulations indicate that whilst field strengths in tTIS are weaker compared to tACS, the steerability and focality are far superior in tTIS.
These findings have been taken a step further from simulations to trials in humans. A recent study has compared traditional tACS with tTIS in humans, reporting on the individual differences induced (von Conta et al., 2021). In alignment with simulations from other groups tTIS was found to show greater focality of subcortical stimulation compared to tACS, with cortical areas proximal to the stimulation electrodes showing lower co-stimulation. von Conta and colleagues (2021) showed a large degree of variability of the electric field distribution between individuals both generally in the brain as well as within (and between) target ROIs. The authors recommend individualised electrode montages to achieve comparable electric field strengths in the target ROIs across individuals. Thus, this study highlighted the importance of a-priori simulation of effects using individual structural MRI scans.
- Interindividual variability of electric fields during transcranial temporal interference stimulation (tTIS). Jill von Conta, Florian H. Kasten, Branislava Ćurčić-Blake, André Aleman, Axel Thielscher & Christoph S. Herrmann. Scientific Reports. October 2021
- Temporal interference stimulation targets deep brain regions by modulating neural oscillations.. Zeinab Esmaeilpour, Greg Kronberg, Davide Reato, Lucas C.Parra, Marom Bikson. Brain Stimulation. February 2021
- Prospects for transcranial temporal interference stimulation in humans: a computational study. Rampersad, Sumientra, Biel Roig-Solvas, Mathew Yarossi, Praveen P. Kulkarni, Emiliano Santarnecchi, Alan D. Dorval, and Dana H. Brooks. NeuroImage. 2019
- Noninvasive deep brain stimulation via temporally interfering electric fields. Nir Grossman , David Bono, Nina Dedic, Suhasa B Kodandaramaiah, Andrii Rudenko, Ho-Jun Suk, Antonino M Cassara, Esra Neufeld, Niels Kuster, Li-Huei Tsai, Alvaro Pascual-Leone, Edward S Boyden. Cell. 2017
- Effects of uniform extracellular dc electric fields on excitability in rat hippocampal slices in vitro. Marom Bikson, Masashi Inoue, Hiroki Akiyama, Jackie K. Deans, John E. Fox, Hiroyoshi Miyakawa, John G. R. Jefferys. Journal of Physiology. May 2004
- The conductivity of the human skull: results of in vivo and in vitro measurements. Oostendorp, Thom F., Jean Delbeke, and Dick F. Stegeman. IEEE Transactions on Biomedical Engineering. November 2000
- Resonance, oscillation and the intrinsic frequency preferences of neurons. Bruce Hutcheon and Yosef Yarom. Trends Neuroscience. May 2000