Effects of cranial electrotherapy stimulation on resting state brain activity

Jamie D Feusner, Sarah Madsen, Teena D Moody, Cara Bohon, Emily Hembacher, Susan Y Bookheimer, Alexander Bystritsky, Jamie D Feusner, Sarah Madsen, Teena D Moody, Cara Bohon, Emily Hembacher, Susan Y Bookheimer, Alexander Bystritsky

Abstract

Cranial electrotherapy stimulation (CES) is a U.S. Food and Drug Administration (FDA)-approved treatment for insomnia, depression, and anxiety consisting of pulsed, low-intensity current applied to the earlobes or scalp. Despite empirical evidence of clinical efficacy, its mechanism of action is largely unknown. The goal was to characterize the acute effects of CES on resting state brain activity. Our primary hypothesis was that CES would result in deactivation in cortical and subcortical regions. Eleven healthy controls were administered CES applied to the earlobes at subsensory thresholds while being scanned with functional magnetic resonance imaging in the resting state. We tested 0.5- and 100-Hz stimulation, using blocks of 22 sec "on" alternating with 22 sec of baseline (device was "off"). The primary outcome measure was differences in blood oxygen level dependent data associated with the device being on versus baseline. The secondary outcome measures were the effects of stimulation on connectivity within the default mode, sensorimotor, and fronto-parietal networks. Both 0.5- and 100-Hz stimulation resulted in significant deactivation in midline frontal and parietal regions. 100-Hz stimulation was associated with both increases and decreases in connectivity within the default mode network (DMN). Results suggest that CES causes cortical brain deactivation, with a similar pattern for high- and low-frequency stimulation, and alters connectivity in the DMN. These effects may result from interference from high- or low-frequency noise. Small perturbations of brain oscillations may therefore have significant effects on normal resting state brain activity. These results provide insight into the mechanism of action of CES, and may assist in the future development of optimal parameters for effective treatment.

Keywords: CES; default mode network; fMRI; fronto-parietal network; intrinsic connectivity networks; sensorimotor network.

Figures

Figure 1
Figure 1
Regions of decreased brain activity as a result of cranial electrotherapy stimulation (CES) for 0.5-Hz stimulation (blue), 100-Hz stimulation (yellow), and regions of overlap between the two frequencies (green).
Figure 2
Figure 2
Regional brain deactivation (BOLD percentage signal change ± SEM) associated with 0.5- and 100-Hz “on” CES stimulation versus baseline, based on local maxima from the voxel-wise analysis.
Figure 3
Figure 3
Time course of activation/deactivation block-by-block, averaged for regions for which there was overlap from all 11 participants’ leave-one-subject-out group activation maps (see Fig. S1).
Figure 4
Figure 4
Regions of altered connectivity with the posterior cingulate seed within the default mode network associated with 100-Hz stimulation. Regions of increased connectivity are depicted in yellow–orange and decreased connectivity are depicted in blue–light blue.

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