Comparing the effects of transcranial alternating current and temporal interference (tTIS) electric stimulation through whole-brain mapping of c-Fos immunoreactivity

Venezia G Carmona-Barrón; Inés S Fernández Del Campo; José M Delgado-García; Antonio J De la Fuente; Ignacio Plaza Lopez; Miguel A Merchán

doi:10.3389/fnana.2023.1128193

Comparing the effects of transcranial alternating current and temporal interference (tTIS) electric stimulation through whole-brain mapping of c-Fos immunoreactivity

Front Neuroanat. 2023 Mar 13:17:1128193. doi: 10.3389/fnana.2023.1128193. eCollection 2023.

Authors

Venezia G Carmona-Barrón¹, Inés S Fernández Del Campo¹, José M Delgado-García², Antonio J De la Fuente¹, Ignacio Plaza Lopez¹, Miguel A Merchán¹

Affiliations

¹ Institute of Neuroscience of Castilla y Leon (INCYL), University of Salamanca, Salamanca, Spain.
² Neuroscience Division, University Pablo de Olavide (UPO), Sevilla, Spain.

Abstract

The analysis of the topography of brain neuromodulation following transcranial alternating current (AC) stimulation is relevant for defining strategies directed to specific nuclei stimulation in patients. Among the different procedures of AC stimulation, temporal interference (tTIS) is a novel method for non-invasive neuromodulation of specific deep brain targets. However, little information is currently available about its tissue effects and its activation topography in in vivo animal models. After a single session (30 min, 0.12 mA) of transcranial alternate current (2,000 Hz; ES/AC group) or tTIS (2,000/2,010 Hz; Es/tTIS group) stimulation, rat brains were explored by whole-brain mapping analysis of c-Fos immunostained serial sections. For this analysis, we used two mapping methods, namely density-to-color processed channels (independent component analysis (ICA) and graphical representation (MATLAB) of morphometrical and densitometrical values obtained by density threshold segmentation. In addition, to assess tissue effects, alternate serial sections were stained for glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule 1 (Iba1), and Nissl. AC stimulation induced a mild superficial increase in c-Fos immunoreactivity. However, tTIS stimulation globally decreased the number of c-Fos-positive neurons and increased blood brain barrier cell immunoreactivity. tTIS also had a stronger effect around the electrode placement area and preserved neuronal activation better in restricted areas of the deep brain (directional stimulation). The enhanced activation of intramural blood vessels' cells and perivascular astrocytes suggests that low-frequency interference (10 Hz) may also have a trophic effect.

Keywords: GFAP - glial fibrillary acidic protein; IBA1 - ionized calcium binding adaptor molecule 1; blood brain barrier (BBB); deep brain simulation; independent component analysis (ICA transform); rat - brain.

Grants and funding

This study was funded by the Spanish Ministry of Science and Innovation (Ministerio de Ciencia e Innovación—MICINN), through grant PID2020-117266RB-C21 awarded to MM and through PID201-122446NB-100 awarded to JD-G.