Effects of transcranial direct current stimulation (tDCS) on human regional cerebral blood flow

Abstract

Transcranial direct current stimulation (tDCS) can up- and down-regulate cortical excitability depending on current direction, however our abilities to measure brain-tissue effects of the stimulation and its after-effects have been limited so far. We used regional cerebral blood flow (rCBF), a surrogate measure of brain activity, to examine regional brain-tissue and brain-network effects during and after tDCS. We varied the polarity (anodal and cathodal) as well as the current strength (0.8 to 2.0mA) of the stimulation. Fourteen healthy subjects were randomized into receiving either anodal or cathodal stimulation (two subjects received both, one week apart) while undergoing Arterial Spin Labeling (ASL) in the MRI scanner with an alternating off-on sampling paradigm. The stimulating, MRI-compatible electrode was placed over the right motor region and the reference electrode over the contralateral supra-orbital region. SPM5 was used to process and extract the rCBF data using a 10mm spherical volume of interest (VOI) placed in the motor cortex directly underneath the stimulating scalp electrode. Anodal stimulation induced a large increase (17.1%) in rCBF during stimulation, which returned to baseline after the current was turned off, but exhibited an increase in rCBF again in the post-stimulation period. Cathodal stimulation induced a smaller increase (5.6%) during stimulation, a significant decrease compared to baseline (-6.5%) after cessation, and a continued decrease in the post-stimulation period. These changes in rCBF were all significant when compared to the pre-stimulation baseline or to a control region. Furthermore, for anodal stimulation, there was a significant correlation between current strength and the increase in rCBF in the on-period relative to the pre-stimulation baseline. The differential rCBF after-effects of anodal (increase in resting state rCBF) and cathodal (decrease in resting state rCBF) tDCS support findings of behavioral and cognitive after-effects after cathodal and anodal tDCS. We also show that tDCS not only modulates activity in the brain region directly underlying the stimulating electrode but also in a network of brain regions that are functionally related to the stimulated area. Our results indicate that ASL may be an excellent tool to investigate the effects of tDCS and its stimulation parameters on brain activity.

Figure 1. Experimental Design

Interleaved tDCS-off and tDCS-on design while acquiring ASL images, where two ASL images were acquired at each on phase and two ASL images were acquired at each off phase, beginning with a baseline consisting of three ASL acquisitions.

Figure 2. VOI Placement

Positioning of VOI underneath the stimulating electrode (visualized by using an MRI compatible marker) in a subject’s spatially normalized brain. One can clearly see in the three orthogonal projections how well the electrode position of C4 corresponded to the precentral gyrus position

Figure 3. Anodal rCBF changes

Changes in rCBF over time in a typical subject fitted with the anodal montage, showing immediate, reproducible, and significant increases in rCBF during stimulation in our VOIs, with subsequent decreases to pre-stimulus levels and a tendency to rise back up again. The on-phases are between the green dotted lines.

Figure 4. Cathodal rCBF changes

Changes in rCBF over time in a typical subject fitted with the cathodal montage, showing reproducible but modest (compared to anodal stimulation – see Figure 3) increases in rCBF during stimulation with subsequent decreases to below pre-stimulus levels and a tendency for continued decrease in rCBF. The ON phases are clearly marked.

Figure 5. Average rCBF changes during and after the anodal and cathodal stimulation

Average changes in rCBF (normalized to zero) for the first OFF-ON-OFF of anodal and cathodal stimulation across all subjects. The description 1^st off and 2^nd OFF refers to the two acquisitions after the end of the stimulation and reflects the trend in rCBF after the stimulation has been turned off.

Figure 6. Correlating rCBF changes with current strength (anodal condition)

Correlating current strength with rCBF changes in the ON, first OFF, and second OFF time point for anodal montages.

Figure 7. Correlating rCBF changes with current strength (cathodal condition)

Correlating current strength with CBF changes in the ON, first OFF, and second OFF time point for cathodal montages.

Figure 8. CBF changes in a network of brain regions for the anodal condition

Averaged distribution of CBF response across the entire brain space correlated with the timecourse obtained from the VOI under the electrode for the anodal condition. Significant correlations (p<0.001, uncorrected at the group level) were overlaid onto a single spatially standardized brain.

Figure 9. Voxel-wise whole brain analysis of ON vs OFF for the anodal condition

Significant voxels (p<0.001, uncorrected at the group level) were overlaid onto a single spatially standardized brain. Besides the strong activation of the precentral gyrus, there were also very small clusters of voxels in the premotor, and parietal cortex on the ipsilateral hemisphere.