Effects of transcranial direct current stimulation coupled with repetitive electrical stimulation on cortical spreading depression.

We have recently shown that two techniques of brain stimulation - repetitive electrical stimulation (ES) (that mimics transcranial magnetic stimulation) and transcranial direct current stimulation (tDCS) - modify the velocity of cortical spreading depression (CSD) significantly. Herein we aimed to study the effects of these two techniques combined on CSD. Thirty-two Wistar rats were divided into four groups according to the treatment: sham tDCS/sham ES, sham tDCS/1 Hz ES, anodal tDCS/1 Hz ES, cathodal tDCS/1 Hz ES. Our findings show that 1 Hz ES reduced CSD velocity, and this effect was modified by either anodal or cathodal tDCS. Anodal tDCS induced larger effects than cathodal tDCS. Hereby CSD velocity was actually increased significantly after anodal tDCS/1 Hz ES. Our results show that combining two techniques of brain stimulation can modify significantly the effects of ES alone on cortical excitability as measured by the neurophysiological parameter of cortical spreading depression and therefore provide important insights into the effects of this new approach of brain stimulation on cortical activity.

After-effects of transcranial direct current stimulation (tDCS) on cortical spreading depression.

Abnormal cortical excitability influences susceptibility to cortical spreading depression (CSD) in migraine. Because transcranial direct current stimulation (tDCS) is capable of inducing lasting changes of cortical excitability, we investigated the after-effects of tDCS on the propagation velocity of CSD in the rat. Twenty-five anesthetised rats received either anodal, cathodal or sham tDCS. The stimulation was applied for 20 min at a current strength of 200 microA after the recording of three baseline CSD measurements. Starting 5 min after tDCS, a further three CSDs were elicited and CSD velocity recorded at intervals of 20 min. tDCS and CSD recording was performed under anaesthesia with chloralose and urethane. As compared to the baseline velocity of 3.14 mm/min, anodal tDCS induced a significant increase of propagation velocity during the first post-tDCS recording (3.49 mm/min). In contrast to anodal tDCS, neither cathodal tDCS nor sham tDCS, which consisted of an initial ramped DC stimulation lasting only 20 s, showed a significant effect on CSD propagation velocity. As anodal tDCS is known to induce a lasting increase of cortical excitability in the clinical setting, our results support the notion that CSD propagation velocity reflects cortical excitability. Since cortical excitability and susceptibility to CSD is elevated in migraine patients, anodal tDCS - by increasing cortical excitability - might increase the probability of migraine attack in these patients, even beyond the end of its application.

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

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.