Effects of cathodal transcranial direct current stimulation on cortical spreading depression

The purpose of this study was to examine the effects of cathodal transcranial direct current stimulation (tDCS) on cortical spreading depression (CSD) in the rat cerebral cortex. CSD is a propagating wave of hyperexcitability that occurs in a number of neurological disorders characterized by excess cerebral excitability such as migraine, acute brain injury, or stroke. Since tDCS is a non-invasive method capable of inducing polarity-dependent changes in cortical excitability, we hypothesized that cathodal stimulation would prevent, attenuate, or change the characteristics of CSD. Forty Sprague-Dawley male rats were randomly divided into two stimulation condition groups: sham tDCS and cathodal tDCS. In both experimental groups, CSD was induced by applying potassium chloride onto cortical surface. Electroencephalogram (EEG) data was recorded during each experiment and subjected to analysis. CSD incidence was compared between the sham and cathodal tDCS group. We observed that significantly fewer CSD events were exhibited during cathodal tDCS relative to sham stimulation. Evaluation of CSD wave characteristics between experimental groups revealed no differences in propagation velocity, amplitude, or waveform of CSD, nor in the presence of neuronal silencing. The results of this study lend support for the use of cathodal tDCS as an effective method for reducing cortical excitability and provides the groundwork for future study of the mechanisms of tDCS and its treatment targets in neurological disorders whose symptoms are created or exacerbated by CSD

The effects of anodal transcranial direct current stimulation on cortical spreading depression

Cortical spreading depression (CSD) is a depolarizing wave that travels through the cerebral cortex, and is followed by an inhibition of cortical activity. The propagation of CSD elicits metabolic challenges in tissue that may be irrecoverable in an ischemic brain, and thus has implications in neurological disease. Limiting the incidence of CSD may be instrumental in limiting the extent of neuronal damage following brain injury. Transcranial direct current stimulation (tDCS) is a form of brain stimulation that alters the level of cortical activity. Anodal tDCS, which increases cortical excitability, is used to treat a variety of neurological syndromes but may have the potential to exacerbate certain pathologies. This contention has never been evaluated using in vivo brain recordings. This study seeks to determine the effects of anodal tDCS on CSD, a phenomenon common to many neurological disorders. CSD was induced in the rat cortex by administration of potassium chloride. Animals were subjected to either anodal tDCS or sham stimulation. Cortical electrical activity was monitored using an intracortical multielectrode array, and data was analyzed to measure the effects of anodal tDCS versus sham on CSD incidence, velocity, amplitude, and several other characteristics of the wave. The hypothesis of the study was that anodal tDCS would increase the incidence, velocity, and amplitude of the CSD wave. No significant effects of anodal tDCS on CSD were observed in this study. Results indicate that anodal tDCS does not increase the velocity, amplitude, or frequency of the spreading depression wave, nor does it interrupt the wave. These data have implications for the use of anodal tDCS in the treatment of neurological disorders associated with spreading depression

Bidirectional interactions between neuronal and hemodynamic responses to transcranial direct current stimulation (tDCS): challenges for brain-state dependent tDCS

Transcranial direct current stimulation (tDCS) has been shown to modulate cortical neural activity. During neural activity, the electric currents from excitable membranes of brain tissue superimpose in the extracellular medium and generate a potential at scalp, which is referred as the electroencephalogram (EEG). Respective neural activity (energy demand) has been shown to be closely related, spatially and temporally, to cerebral blood flow (CBF) that supplies glucose (energy supply) via neurovascular coupling. The hemodynamic response can be captured by near-infrared spectroscopy (NIRS), which enables continuous monitoring of cerebral oxygenation and blood volume. This neurovascular coupling phenomenon led to the concept of neurovascular unit (NVU) that consists of the endothelium, glia, neurons, pericytes, and the basal lamina. Here, recent works suggest NVU as an integrated system working in concert using feedback mechanisms to enable proper brain homeostasis and function where the challenge remains in capturing these mostly nonlinear spatiotemporal interactions within NVU during tDCS. Therefore, we propose EEG-NIRS-based whole-head monitoring of tDCS-induced neuronal and hemodynamic alterations for brain-state dependent tDCS

Intensity-Dependent Changes in Quantified Resting Cerebral Perfusion with Multiple Sessions of Transcranial DC Stimulation

Transcranial direct current stimulation (tDCS) to the left prefrontal cortex has been shown to produce broad behavioral effects including enhanced learning and vigilance. Still, the neural mechanisms underlying such effects are not fully understood. Furthermore, the neural underpinnings of repeated stimulation remain understudied. In this work, we evaluated the effects of the repetition and intensity of tDCS on cerebral perfusion [cerebral blood flow (CBF)]. A cohort of 47 subjects was randomly assigned to one of the three groups. tDCS of 1- or 2-mA was applied to the left prefrontal cortex on three consecutive days, and resting CBF was quantified before and after stimulation using the arterial spin labeling MRI and then compared with a group that received sham stimulation. A widespread decreased CBF was found in a group receiving sham stimulation across the three post-stimulation measures when compared with baseline. In contrast, only slight decreases were observed in the group receiving 2-mA stimulation in the second and third post-stimulation measurements, but more prominent increased CBF was observed across several brain regions including the locus coeruleus (LC). The LC is an integral region in the production of norepinephrine and the noradrenergic system, and an increased norepinephrine/noradrenergic activity could explain the various behavioral findings from the anodal prefrontal tDCS. A decreased CBF was observed in the 1-mA group across the first two post-stimulation measurements, similar to the sham group. This decreased CBF was apparent in only a few small clusters in the third post-stimulation scan but was accompanied by an increased CBF, indicating that the neural effects of stimulation may persist for at least 24 h and that the repeated stimulation may produce cumulative effects

Occipital transcranial direct current stimulation in episodic migraine patients: effect on cerebral perfusion

Cerebral blood flow differs between migraine patients and healthy controls during attack and the interictal period. This study compares the brain perfusion of episodic migraine patients and healthy controls and investigates the influence of anodal transcranial direct current stimulation (tDCS) over the occipital cortex. We included healthy adult controls and episodic migraineurs. After a 28-day baseline period and the baseline visit, migraine patients received daily active or sham anodal tDCS over the occipital lobe for 28 days. All participants underwent a MRI scan at baseline; migraineurs were also scanned shortly after the stimulation period and about five months later. At baseline, brain perfusion of migraine patients and controls differed in several areas; among the stimulated areas, perfusion was increased in the cuneus of healthy controls. At the first visit, the active tDCS group had an increased blood flow in regions processing visual stimuli and a decreased perfusion in other areas. Perfusion did not differ at the second follow-up visit. The lower perfusion level in migraineurs in the cuneus indicates a lower preactivation level. Anodal tDCS over the occipital cortex increases perfusion of several areas shortly after the stimulation period, but not 5 months later. An increase in the cortical preactivation level could mediate the transient reduction of the migraine frequency.Trial registration: NCT03237754 (registered at clincicaltrials.gov; full date of first trial registration: 03/08/2017)

Electromagnetic interventions as a therapeutic approach to spreading depression

Spreading depression (SD) is a slow propagating wave of depolarization that can spread throughout the cortex in the event of brain injury or any general energy failure of the brain. Massive cellular depolarization causes enormous ionic and water shifts and silences synaptic transmission in the affected tissue. Large amounts of energy are required to restore ionic gradients and are not always met. When these energetic demands are not met, brain tissue damage can occur. The exact mechanism behind initiation and propagation of SD are unknown, but a general model is known. It may be possible to prevent or delay the onset of SD using non-invasive electromagnetic techniques. Transcranial magnetic stimulation (TMS), electrical stimulation (ES), and transcranial direct coupled stimulation (tDCS) could be used to decrease neuronal excitability in different ways. In theory, any technique that can reduce cortical excitability could suppress SD initiating or propagating

tDCS‐Induced Analgesia and Electrical Fields in Pain‐Related Neural Networks in Chronic Migraine

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93711/1/j.1526-4610.2012.02141.x.pd