Local and Distributed fMRI Changes Induced by 40 Hz Gamma tACS of the Bilateral Dorsolateral Prefrontal Cortex: A Pilot Study

Abstract

Over the past few years, the possibility of modulating fast brain oscillatory activity in the gamma (γ) band through transcranial alternating current stimulation (tACS) has been discussed in the context of both cognitive enhancement and therapeutic scenarios. However, the effects of tACS targeting regions outside the motor cortex, as well as its spatial specificity, are still unclear. Here, we present a concurrent tACS-fMRI block design study to characterize the impact of 40 Hz tACS applied over the left and right dorsolateral prefrontal cortex (DLPFC) in healthy subjects. Results suggest an increase in blood oxygenation level-dependent (BOLD) activity in the targeted bilateral DLPFCs, as well as in surrounding brain areas affected by stimulation according to biophysical modeling, i.e., the premotor cortex and anterior cingulate cortex (ACC). However, off-target effects were also observed, primarily involving the visual cortices, with further effects on the supplementary motor areas (SMA), left subgenual cingulate, and right superior temporal gyrus. The specificity of 40 Hz tACS over bilateral DLPFC and the possibility for network-level effects should be considered in future studies, especially in the context of recently promoted gamma-induction therapeutic protocols for neurodegenerative disorders.

Figure 1

Experimental paradigm. (a) Schematic example of MRI-compatible tES device setup. (1) Details of electrode arranged in the cap, (2) CMS/DRL mastoid electrodes for impedance check, (3) and (4) MRI -compatible touchproof connector, (5) patch panel connection, (6) Starstim cable adaptor. (b) Overview of the tACS-fMRI experimental session. (c) Electrode positions and phase. (d) Normal electric field (normE) simulated on a single-subject template Colin27. (E) En binary mask thresholded at 0.8 and used as mask for the second-level analysis.

Figure 2

Primary and secondary on-target effect of tACS. (a) The normE-field used as mask for the second-level analysis is shown. (b) BOLD signal changes under the electrodes (DLPFC) during the stimulation, thus comparing the on blocks to the off blocks. No significant BOLD changes are shown comparing the off blocks to the on blocks. (c) A surface brain representation of the resulted nodes is shown. More details on the brain activation peaks are reported in Table 1. Right is the right side of the brain.

Figure 3

Off-target effect of tACS. (a) Significant BOLD changes that resulted from the whole brain analysis are shown in visual cortices, subgenual cortex, right temporal cortex, and SMA. (b) No significant results are shown in the absence of tACS (off > on). The results are masked for grey matter. More details on brain activation peaks are reported on Table 2. Images are presented in neurological convention (i.e., right brain is right in the figure).

Figure 4

Anatomical mapping of on-target results. Qualitative overlap between the Glasser Atlas and the map of BOLD activations during 40 Hz tACS (orange) is shown. Activations on primary target bilaterally (^∗), as well as the secondary impact on regions predicted by the biophysical modeling (^), such as the ACC and right premotor cortex, are reported.

Figure 5

Anatomical mapping of off-target results. Qualitative overlap between the Glasser Atlas and the BOLD changes outside the stimulated areas (orange) shows changes in the primary and secondary visual areas, auditory cortex, subgenual cingulate cortex, and SMA.

Figure 6

Network mapping of primary and secondary on-target results. (a, b) Show the network mapping of the clusters' peak in the prefrontal cortices. The regions correspond to the left and right dorsolateral prefrontal cortex (MNI coordinates (x, y, z): 34, 34, and 18; -30, 32, and 26). The mapping of the clusters' peak in the premotor cortex (MNI coordinates (x, y, z): 14, 6, and 64) and ACC (MNI coordinates (x, y, z): -20, 22, and 34) are reported in (c) and (d), respectively. R: right; L: left.

Figure 7

Network mapping of off-targets results. The figure shows the functional connectivity of the bilateral occipital cortices (a, b), corresponding to the right and left fusiform gyrus (MNI coordinates (x, y, z): -36, -70, and -18; 56, -58, and -14), of the supplementary motor area (c) (MNI coordinates (x, y, z): 14, 6, and 64); of the superior temporal gyrus (d) (MNI coordinates (x, y, z): 66, -8, and 4) and of the subgenual cortex (e) (MNI coordinates (x, y, z): 4, 4, and -24). R: right; L: left.