Multipair transcranial temporal interference stimulation for improved focalized stimulation of deep brain regions: A simulation study

Responses of Model Cortical Neurons to Temporal Interference Stimulation and Related Transcranial Alternating Current Stimulation Modalities

“…For example, in the spherical coordinate system used in this study, E 1 and E 2 with given polar angles ( θ 1,2 ) and co-varying azimuths ( φ 1 −φ 2 = constant) span a fixed angle, but the thresholds vary significantly (Figure S6–S8 and S12–S13). Therefore, the E-fields obtained along specific directions in computational models, whether for maximum modulation (Huang and Parra, 2019) or in a pre-determined orientation (Grossman et al, 2017; Rampersad et al, 2019; Song et al, 2021), cannot predict the stimulation effects of TIS, and optimization using E-field simulation alone (Huang et al, 2020; Lee et al, 2022) is unlikely to produce the same results as when considering the effects of the E-field on neurons.…”

“…Some subsequent modeling studies, however, explored unrelated mechanisms by which TIS modulates ongoing neural activity in the regime of subthreshold field strength of conventional tACS (Esmaeilpour et al, 2021; Howell and McIntyre, 2020), whereas other studies explored axonal targets that are less relevant for transcranial stimulation (Gomez-Tames et al, 2021; Howell and McIntyre, 2020; Mirzakhalili et al, 2020). The TIS E-fields and their effect on neurons have been analyzed in one dimension (1D), either along the direction of largest modulation depth or in a predetermined direction such as the radial direction of the gray matter or along fiber bundles in the white matter (Esmaeilpour et al, 2021; Gomez-Tames et al, 2021; Grossman et al, 2017; Howell and McIntyre, 2020; Huang and Parra, 2019; Lee et al, 2020, 2022; Mirzakhalili et al, 2020; Rampersad et al, 2019; Song et al, 2021). However, the complex three-dimensional (3D) morphology of cortical neurons could significantly affect activation by exogenous E-fields (Aberra et al, 2020).…”

“…Computational studies of suprathreshold TIS have focused on activation of isolated axons (fibers of passage) (Gomez-Tames et al, 2021; Howell and McIntyre, 2020; Mirzakhalili et al, 2020), which do not fully capture effects on cortical neurons. Moreover, the combination of the two TIS current waveforms results is a three-dimensional (3D) time-varying E- field distribution that can interact in complex ways with the 3D morphology of cortical neurons (Aberra et al, 2020), but the TIS E-fields and their effect on neurons have only been analyzed in one dimension (1D), either along the direction of largest modulation depth or in a predetermined direction such as the radial direction of the gray matter or along fiber bundles in the white matter (Esmaeilpour et al, 2021; Gomez-Tames et al, 2021; Grossman et al, 2017; Howell and McIntyre, 2020; Huang and Parra, 2019; Lee et al, 2020, 2022; Mirzakhalili et al, 2020; Rampersad et al, 2019; Song et al, 2021).…”

“…For example, modulation of ongoing neural activity by TIS was studied in the regime of subthreshold field strength of conventional tACS (Esmaeilpour et al, 2021; Howell and McIntyre, 2020), and activation of isolated axons (fibers of passage) was characterized, which does not fully capture the effect on cortical neurons (Gomez-Tames et al, 2021; Howell and McIntyre, 2020; Mirzakhalili et al, 2020). Further, while the complex three-dimensional (3D) morphology of cortical neurons could significantly affect activation by exogenous E-fields (Aberra et al, 2020), the TIS E-fields and their effect on neurons have only been analyzed in one dimension (1D), either along the direction of largest modulation depth or in a predetermined direction such as the radial direction of the gray matter or along fiber bundles in the white matter (Esmaeilpour et al, 2021; Gomez-Tames et al, 2021; Grossman et al, 2017; Howell and McIntyre, 2020; Huang and Parra, 2019; Lee et al, 2020, 2022; Mirzakhalili et al, 2020; Rampersad et al, 2019; Song et al, 2021).…”

“…Moreover, the combination of the two TIS current waveforms results is a three-dimensional (3D) time-varying Efield distribution that can interact in complex ways with the 3D morphology of cortical neurons (Aberra et al, 2020), but the TIS E-fields and their effect on neurons have only been analyzed in one dimension (1D), either along the direction of largest modulation depth or in a predetermined direction such as the radial direction of the gray matter or along fiber bundles in the white matter (Esmaeilpour et al, 2021;Gomez-Tames et al, 2021;Grossman et al, 2017;Howell and McIntyre, 2020;Huang and Parra, 2019;Lee et al, 2020Lee et al, , 2022Mirzakhalili et al, 2020;Rampersad et al, 2019;Song et al, 2021). Translation of TIS from animal studies to clinical applications poses further challenges.…”