Electrical parameters of transcranial direct current stimulation that effectively alter cerebral blood flow in experimental animals: a systematic review (original) (raw)
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Recent therapeutic human studies testing transcranial direct current stimulation (tDCS) has shown promising results, although many questions remain unanswered. Translational research with experimental animals is an appropriate framework for investigating its mechanisms of action that are still undetermined. Nevertheless, animal and human studies are often discordant. Our aim was to review tDCS animal studies, examining and comparing their main fi ndings with human studies. We performed a systematic review in Medline and other databases, screening for animal studies in vivo that delivered tDCS. Studies in vitro and using other neuromodulatory techniques were excluded. We extracted data according to Animal Research: Reporting In Vivo Experiments (ARRIVE) guidelines for reporting in vivo animal research. Thus, we collected data on sample characteristics (size, gender, weight and specimen) and methodology (experimental procedures, experimental animals, housing and husbandry, as well as analysis). We also collected data on methods for delivering tDCS (location, size, current and current density of electrodes and electrode montage), experimental effects (polarity-, intensityand after-effects) and safety. Only 12 of 48 potentially eligible studies met our inclusion criteria and were reviewed. Quality assessment reporting was only moderate and studies were heterogeneous regarding tDCS montage methodology, position of active and reference electrodes, and current density used.
Safety parameter considerations of anodal transcranial Direct Current Stimulation in rats
A commonly referenced transcranial Direct Current Stimulation (tDCS) safety threshold derives from tDCS lesion studies in the rat and relies on electrode current density (and related electrode charge density) to support clinical guidelines. Concerns about the role of polarity (e.g. anodal tDCS), sub-lesion threshold injury (e.g. neuroinflammatory processes), and role of electrode montage across rodent and human studies support further investigation into animal models of tDCS safety. Thirty-two anesthetized rats received anodal tDCS between 0 and 5 mA for 60 min through one of three epicranial electrode montages. Tissue damage was evaluated using hemotoxylin and eosin (H&E) staining, Iba-1 immunohistochemistry, and computational brain current density modeling. Brain lesion occurred after anodal tDCS at and above 0.5 mA using a 25.0 mm 2 electrode (electrode current density: 20.0 A/m 2 ). Lesion initially occurred using smaller 10.6 mm 2 or 5.3 mm 2 electrodes at 0.25 mA (23.5 A/m 2 ) and 0.5 mA (94.2 A/ m 2 ), respectively. Histological damage was correlated with computational brain current density predictions. Changes in microglial phenotype occurred in higher stimulation groups. Lesions were observed using anodal tDCS at an electrode current density of 20.0 A/m 2 , which is below the previously reported safety threshold of 142.9 A/m 2 using cathodal tDCS. The lesion area is not simply predicted by electrode current density (and so not by charge density as duration was fixed); rather computational modeling suggests average brain current density as a better predictor for anodal tDCS. Nonetheless, under the assumption that rodent epicranial stimulation is a hypersensitive model, an electrode current density of 20.0 A/ m 2 represents a conservative threshold for clinical tDCS, which typically uses an electrode current density of 2 A/m 2 when electrodes are placed on the skin (resulting in a lower brain current density).
American Journal of Psychiatry and Neuroscience
Transcranial direct current stimulation (tDCS) is a type of electrical modulation of the nervous system activity which involves the uses of low current to stimulate specified areas of the brain using electrodes to the scalp. This study was carried out to investigate if tDCS which is being used in the treatment of various disorders of the brain could have any possible side effects that might be worse than the treated disorder or any effects of tDCS on the cytoarchitecture of the dorsolateral prefrontal cortex. A total of 32 adult male Wistar rats were used and were placed into 5 groups (A-E). Rats in group A were divided into two groups A (SHAM) (tDCS for 30seconds) and A (N-SHAM). Rats in groups B, C, D and E were stimulated for 5, 10, 15, and 20 minutes with 12Volt respectively for the duration of 14 days and the animals were euthanized on the last day of the experiment two hours post brain stimulation. The specimen were subjected to gross morphological analysis and basic demonstration of the DLPFC using H & E and special stains. There was no significant difference in the neuronal structure and the supporting cells of the brain across the groups A (SHAM), B (5MINS), C (10MINS), D (15MINS), E (20MINS) when compared with control group A (N-SHAM) which suggest that tDCS does not have any neurodegenerative effects and could be safe in its use as neuro-stimulator to enhance cognitive ability in healthy individuals.
Clinical & Biomedical Research, 2017
Introduction: The transcranial direct current stimulation (tDCS) is a non-invasive technique, which induces neuroplastic changes in the central nervous system of animals and humans. Furthermore, tDCS has been suggested as a therapeutic tool for pain management. The aim of this study was to standardize a non-invasive tDCS technique indexed by the nociceptive response of rats submitted to different conditions necessary to the tDCS application. Method: 60-day-old male Wistar rats (n=65), divided into 6 groups: control(C); non-active sham (NAS); active-sham (AS); active-sham restrained (ASR); non-active sham restrained (NASR); active tDCS treatment. Animals received treatment during 30 seconds (sham-active) or 20 minutes (restraint and tDCS)/8 days. Nociceptive threshold was assessed by Hot Plate test at baseline, immediately and 24h after the first session, immediately and 24h after the last session. Variance analysis of repeated measurements followed by Bonferroni was performed for intra-group comparison. Results: Physical restraint and 30 seconds stimulation (sham-tDCS) increased pain sensitivity (P≤0.05), and tDCS treatment was able to prevent the thermal hyperalgesia. Our original tDCS montage is similar to that used in the procedure with humans, because it is not an invasive technique. The electrodes are positioned on the head, and the animals are immobilized during the 20-minute treatment. As this procedure could involve behavior and neurochemical alterations due to stress induced by restriction (thus, it creates a research bias), we hypothesized that a 30-second electrical stimulus application (sham-tDCS) and the physical restriction used during tDCS treatment might alter nociceptive response in rats. Conclusion: There are methodological limitations in the present tDCS-technique. Although active-tDCS treatment is able to prevent these harmful effects, interference of these factors has to be considered during the results' analysis. Future adaptations of the tDCS-technique in rats are required to evaluate its therapeutic effects.
Neurological Research, 2013
Objective: Transcranial direct current stimulation (tDCS) induces polarity-specific changes of cerebral blood flow (CBF). To determine whether these changes are focally limited or if they incorporate large cortical regions and thus have the potential for a therapeutic application, we investigated the effects of cathodal tDCS on CBF in an established tDCS rat model with particular attention to the spatial extension in CBF changes using laser Doppler blood perfusion imaging (LDI). Methods: Twenty-one Sprague Dawley rats received a single 15-minute session of cathodal tDCS at current intensities of 200, 400, 600, or 700 μA applied over electrode contact areas (ECA) of 3·5, 7·0, 10·5, or 14·0 mm2. One animal died prior to the stimulation. Cerebral blood flow was measured prior and after tDCS with LDI in three defined regions of interest (ROI) over the stimulated left hemisphere (region anterior to ECA – ROI 1, ECA – ROI 2, region posterior to ECA – ROI 3). Results: A regional decrease i...
Notes on Human Trials of Transcranial Direct Current Stimulation between 1960 and 1998
Frontiers in human neuroscience, 2017
Background: Transcranial direct current stimulation (tDCS) is investigated to modulate neuronal function including cognitive neuroscience and neuropsychiatric therapies. While cases of human stimulation with rudimentary batteries date back more than 200 years, clinical trials with current controlled stimulation were published intermittently since the 1960s. The modern era of tDCS only started after 1998. Objectives: To review methods and outcomes of tDCS studies from old literature (between 1960 and 1998) with intention of providing new insight for ongoing tDCS trials and development of tDCS protocols especially for the purpose of treatment. Methods: Articles were identified through a search in PubMed and through the reference list from its selected articles. We included only non-invasive human studies that provided controlled direct current and were written in English, French, Spanish or Portuguese before the year of 1998, the date in which modern stimulation paradigms were impleme...
Investigating transcranial direct current stimulation and its therapeutic potential
2017
Transcranial direct current stimulation (tDCS) is a popular non-invasive brain stimulation technique, which has the potential to modulate cortical excitability. The effects of tDCS are known to outlast the stimulation period, and in some cases, repeated applications have been found to produce long lasting clinically relevant effects. The primary aim of this thesis was to explore the reliability and therapeutic potential of this technique. In Chapters 3 and 4 transcranial magnetic stimulation (TMS) was used to measure tDCS effects. These experiments revealed substantial variability regarding the way in which healthy adults responded to stimulation. Notably, there were differences between participants regarding the direction and magnitude of change in cortical excitability. Furthermore, even when group level effects were found reliably, there was substantial intra-subject variability across repeated testing sessions. Subsequent experiments in Chapters 5 and 6, explored the biological ...
Neurobiological effects of transcranial direct current stimulation: a review
Frontiers in psychiatry, 2012
Transcranial Direct Current Stimulation (tDCS) is a non-invasive brain stimulation technique that is affordable and easy to operate compared to other neuromodulation techniques. Anodal stimulation increases cortical excitability, while the cathodal stimulation decreases it. Although tDCS is a promising treatment approach for chronic pain as well as for neuropsychiatric diseases and other neurological disorders, several complex neurobiological mechanisms that are not well understood are involved in its effect. The purpose of this systematic review is to summarize the current knowledge regarding the neurobiological mechanisms involved in the effects of tDCS. The initial search resulted in 171 articles. After applying inclusion and exclusion criteria, we screened 32 full-text articles to extract findings about the neurobiology of tDCS effects including investigation of cortical excitability parameters. Overall, these findings show that tDCS involves a cascade of events at the cellular ...