Lasting accelerative effects of 1 Hz and 20 Hz electrical stimulation on cortical spreading depression: relevance for clinical applications of brain stimulation

Authors

  • Felipe Fregni,

    1. Harvard Center for Non-invasive Brain Stimulation and Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA
    Search for more papers by this author
  • Katia K. Monte-Silva,

    1. Laboratory of Neurophysiology and Nutrition, Department of Nutrition, Federal University of Pernambuco State, Recife, Brazil
    Search for more papers by this author
  • Manuella B. Oliveira,

    1. Laboratory of Neurophysiology and Nutrition, Department of Nutrition, Federal University of Pernambuco State, Recife, Brazil
    Search for more papers by this author
  • Steven D. Freedman,

    1. Harvard Center for Non-invasive Brain Stimulation and Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA
    Search for more papers by this author
  • Alvaro Pascual-Leone,

    1. Harvard Center for Non-invasive Brain Stimulation and Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA
    Search for more papers by this author
  • Rubem C. A. Guedes

    1. Laboratory of Neurophysiology and Nutrition, Department of Nutrition, Federal University of Pernambuco State, Recife, Brazil
    Search for more papers by this author

Dr Felipe Fregni, as above.
E-mail: ffregni@bidmc.harvard.edu

Abstract

Clinical applications of brain stimulation have been increasing during the last decade; however, the mechanisms of action remain unknown. One proposed mechanism of action is that repetitive stimulation modulates cortical excitability. Herein, we explore the question of whether repetitive electric stimulation increases cortical excitability as indexed by the cortical spreading depression. Twenty-four Wistar rats were divided into three groups according to the treatment: sham, 1-Hz and 20-Hz stimulation. Stimulation was applied to the left frontal cortex through a pair of epidurally implanted silver-wire electrodes. The cortical spreading depression-features were analysed at three time points (one day before, one day after and 2 weeks after treatment) in both the stimulated and unstimulated hemisphere. A 3 × 2 × 3 factorial anova with repeated measures showed significant differences in the main effect of time (< 0.0001), hemisphere (P = 0.0002) and stimulation group (P = 0.008). The interaction between time vs. hemisphere vs. stimulation group was also significant (P < 0.0001). Posthoc analysis demonstrated that 1-Hz and 20-Hz repetitive electrical stimulation significantly increased the velocity of cortical spreading depression in the stimulated hemisphere. Furthermore, 20-Hz stimulation showed a greater effect on cortical spreading depression compared to 1-Hz stimulation. The results show that 1-Hz and 20-Hz repetitive electrical stimulation results in an increase in cortical spreading depression velocity that is associated with the frequency and the hemisphere of stimulation. Furthermore, the effects are found to be long lasting. We believe that these findings have strong relevance to support the clinical application of therapies involving electrical stimulation for diseases of reduced cortical excitability.

Ancillary