title: Lasting accelerative effects of 1 Hz and 20 Hz electrical stimulation on cortical spreading depression: relevance for clinical applications of brain stimulation.
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 x 2 x 3 factorial anova with repeated measures showed significant differences in the main effect of time (P < 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.
authors.affiliation: Harvard Center for Non-invasive Brain Stimulation and Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA. ffregni@bidmc.harvard.edu
authors.forename: Felipe
authors.initials: F
authors.lastname: Fregni
authors.forename: Katia K
authors.initials: KK
authors.lastname: Monte-Silva
authors.forename: Manuella B
authors.initials: MB
authors.lastname: Oliveira
authors.forename: Steven D
authors.initials: SD
authors.lastname: Freedman
authors.forename: Alvaro
authors.initials: A
authors.lastname: Pascual-Leone
authors.forename: Rubem C A
authors.initials: RC
authors.lastname: Guedes
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects*; D013181:Cortical Spreading Depression / Q000187:drug effects / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation; D007839:Functional Laterality / Q000502:physiology / Q000528:radiation effects; D008297:Male; D009431:Neural Conduction / Q000187:drug effects / Q000528:radiation effects; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013238:Stereotaxic Techniques; D013997:Time Factors
chemical_list: D011189:Potassium Chloride