Effects of cranial electrotherapy stimulation on resting state brain activity

Feusner, J. D., Madsen, S., Moody, T. D., Bohon, C., Hembacher, E., Bookheimer, S. Y. and Bystritsky. Effects of cranial electrotherapy stimulation on resting state brain activity. Brain and Behavior. Pp 1-10, 2012. Download article.

Session II–7

Jamie Feusner, M.D.1, Teena Moody, Ph.D.1, Emily Hembacher, B.A.,2, Susan Bookheimer, Ph.D.1, Alexander Bystritsky, M.D, Ph.D.1

1University of California, Los Angeles, 2University of California, Davis

Background: Cranial electrotherapy stimulation (CES) is a Food and Drug Administration approved treatment for insomnia, depression and anxiety that consists of pulsed, alternating microcurrent applied to the head using electrodes placed on the earlobes.1,2 The mechanism of action of CES remains unclear. The objective of this study was to determine the immediate effects of CES stimulation on resting state brain activity.

Methods: We performed functional magnetic resonance imaging (fMRI) simultaneously with CES stimulation in 11 healthy male and female subjects. The experiment consisted of “on” stimulation blocks alternating with “off” blocks for each of 0.5 Hz and 100 Hz pulse frequencies, while subjects rested with their eyes closed. We conducted a voxel-wise and a region-of-interest analysis of the thalamus, as well as a psychophysiological interaction analysis3 to examine effects on functional connectivity in resting state networks. We also investigated relationships between current intensity and activation patterns using subjects’ individualized current as a regressor.

Results: Stimulation of 0.5 Hz was associated with decreased activation in bilateral precuneus, supplementary motor area (SMA), posterior cingulate, pre- and postcentral gyrus and the left frontal pole and middle frontal gyrus. 100 Hz stimulation was associated with decreased activation in bilateral SMA and precentral gyrus, right superior parietal lobule, and the right supramarginal gyrus. Current intensity for 0.5 Hz was associated with greater activity in the left SMA, right anterior cingulate cortex, bilateral lateral occipital cortex and the right occipital pole. Changes in brain activity in the thalamus were not significant. The psychophysiological interaction analysis for 100 Hz demonstrated increased connectivity associated with stimulation between the posterior cingulate seed and the left precuneus and right middle frontal gyrus. There was decreased connectivity in the right frontal pole and right posterior middle frontal gyrus. (Results for the connectivity analysis for 0.5 Hz are pending.)

Conclusions: CES stimulation is associated with cortical deactivation for 0.5 Hz and 100 Hz frequencies in bilateral frontal, parietal and posterior midline regions. Current intensity may be less critical than frequency of stimulation in relation to cortical deactivation. There appeared to be significant effects on some but not all nodes of the default mode network, suggesting that CES may affect resting state functional coupling. Future studies will need to explore the longer-term effects of daily treatment in relation to clinical improvement, and how brain deactivationrelates to previously observed decreases in electroencephalogram (EEG) frequencies,4 in order to further understand the therapeutic mechanism of action.

Source of Funding: Saban Family Foundation.

Literature References:

1. Klawansky S, et al. Meta-analysis of randomized controlled trials of cranial electrostimulation: efficacy in treating selected psychological and physiological conditions. J Nerv Ment Dis 1995;183(7):478–84.

2. Bystritsky A, et al. A pilot study of cranial electrotherapy stimulation for generalized anxiety disorder. J Clin Psychiatry 2008;69(3):412–7.

3. Friston KJ, et al. Psychophysiological and modulatory interactions in neuroimaging. Neuroimage 1997; 6(3):218–29.

4. Schroeder MJ, et al. Quantitative analysis of the electroencephalogram during cranial electrotherapy stimulation. Clin Neurophysiol 2001;112(11):2075–83.