Neurobiological Mechanisms of Transcranial Direct Current Stimulation for Psychiatric Disorders; Neurophysiological, Chemical, and Anatomical Considerations

Backgrounds: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique for the treatment of several psychiatric disorders, e.g., mood disorders and schizophrenia. Therapeutic effects of tDCS are suggested to be produced by bi-directional changes in cortical activities, i.e., increased/decreased cortical excitability via anodal/cathodal stimulation. Although tDCS provides a promising approach for the treatment of psychiatric disorders, its neurobiological mechanisms remain to be explored.Objectives: To review recent findings from neurophysiological, chemical, and brain-network studies, and consider how tDCS ameliorates psychiatric conditions.Findings: Enhancement of excitatory synaptic transmissions through anodal tDCS stimulation is likely to facilitate glutamate transmission and suppress gamma-aminobutyric acid transmission in the cortex. On the other hand, it positively or negatively modulates the activities of dopamine, serotonin, and acetylcholine transmissions in the central nervous system. These neural events by tDCS may change the balance between excitatory and inhibitory inputs. Specifically, multi-session tDCS is thought to promote/regulate information processing efficiency in the cerebral cortical circuit, which induces long-term potentiation (LTP) by synthesizing various proteins.Conclusions: This review will help understand putative mechanisms underlying the clinical benefits of tDCS from the perspective of neurotransmitters, network dynamics, intracellular events, and related modalities of the brain function.

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Preclinical Evidence for the Mechanisms of Transcranial Direct Current Stimulation in the Treatment of Psychiatric Disorders; A Systematic Review

Clinical EEG and Neuroscience ◽

10.1177/15500594211066151 ◽

2021 ◽

pp. 155005942110661

Author(s):

Yuji Yamada ◽

Tomiki Sumiyoshi

Keyword(s):

Systematic Review ◽

Psychiatric Disorders ◽

Direct Current ◽

Transcranial Direct Current Stimulation ◽

Experimental Studies ◽

Long Term Potentiation ◽

Therapeutic Effects ◽

Inclusion Criteria ◽

Direct Current Stimulation ◽

Anodal Stimulation

Backgrounds. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique for the treatment of several psychiatric disorders, eg, mood disorders and schizophrenia. Although tDCS provides a promising approach, its neurobiological mechanisms remain to be explored. Objectives. To provide a systematic review of animal studies, and consider how tDCS ameliorates psychiatric conditions. Methods. A literature search was conducted on English articles identified by PubMed. We defined the inclusion criteria as follows: (1) articles published from the original data; (2) experimental studies in animals; (3) studies delivering direct current transcranially, ie, positioning electrodes onto the skull. Results. 138 papers met the inclusion criteria. 62 papers deal with model animals without any dysfunctions, followed by 52 papers for neurological disorder models, and 12 for psychiatric disorder models. The most studied category of functional areas is neurocognition, followed by motor functions and pain. These studies overall suggest the role for the late long-term potentiation (LTP) via anodal stimulation in the therapeutic effects of tDCS. Conclusions. tDCS Anodal stimulation may provide a novel therapeutic strategy to particularly enhance neurocognition in psychiatric disorders. Its mechanisms are likely to involve facilitation of the late LTP.

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Applications of transcranial direct current stimulation in children and pediatrics

Reviews in the Neurosciences ◽

10.1515/revneuro-2016-0045 ◽

2017 ◽

Vol 28 (2) ◽

pp. 173-184 ◽

Cited By ~ 13

Author(s):

Guadalupe Nathzidy Rivera-Urbina ◽

Michael A. Nitsche ◽

Carmelo M. Vicario ◽

Andrés Molero-Chamizo

Keyword(s):

Direct Current ◽

Transcranial Direct Current Stimulation ◽

Developmental Disorders ◽

Cortical Excitability ◽

Previous History ◽

Therapeutic Effects ◽

Clinical Effects ◽

Direct Current Stimulation ◽

Brain Functions ◽

History Of

AbstractTranscranial direct current stimulation (tDCS) is a neuromodulatory noninvasive brain stimulation tool with potential to increase or reduce regional and remote cortical excitability. Numerous studies have shown the ability of this technique to induce neuroplasticity and to modulate cognition and behavior in adults. Clinical studies have also demonstrated the ability of tDCS to induce therapeutic effects in several central nervous system disorders. However, knowledge about its ability to modulate brain functions in children or induce clinical improvements in pediatrics is limited. The objective of this review is to describe relevant data of some recent studies that may help to understand the potential of this technique in children with specific regard to effective and safe treatment of different developmental disorders in pediatrics. Overall, the results show that standard protocols of tDCS are well tolerated by children and have promising clinical effects. Nevertheless, treatment effects seem to be partially heterogeneous, and a case of a seizure in a child with previous history of infantile spasms and diagnosed epilepsy treated with tDCS for spasticity was reported. Further research is needed to determine safety criteria for tDCS use in children and to elucidate the particular neurophysiological changes induced by this neuromodulatory technique when it is applied in the developing brain.

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Different Current Intensities of Anodal Transcranial Direct Current Stimulation Do Not Differentially Modulate Motor Cortex Plasticity

Neural Plasticity ◽

10.1155/2013/603502 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 47

Author(s):

Dawson J. Kidgell ◽

Robin M. Daly ◽

Kayleigh Young ◽

Jarrod Lum ◽

Gregory Tooley ◽

...

Keyword(s):

Motor Cortex ◽

Direct Current ◽

Transcranial Direct Current Stimulation ◽

Cortical Excitability ◽

Short Interval ◽

Long Term Potentiation ◽

Anodal Tdcs ◽

Noninvasive Technique ◽

Direct Current Stimulation ◽

Intracortical Circuits

Transcranial direct current stimulation (tDCS) is a noninvasive technique that modulates the excitability of neurons within the motor cortex (M1). Although the aftereffects of anodal tDCS on modulating cortical excitability have been described, there is limited data describing the outcomes of different tDCS intensities on intracortical circuits. To further elucidate the mechanisms underlying the aftereffects of M1 excitability following anodal tDCS, we used transcranial magnetic stimulation (TMS) to examine the effect of different intensities on cortical excitability and short-interval intracortical inhibition (SICI). Using a randomized, counterbalanced, crossover design, with a one-week wash-out period, 14 participants (6 females and 8 males, 22–45 years) were exposed to 10 minutes of anodal tDCS at 0.8, 1.0, and 1.2 mA. TMS was used to measure M1 excitability and SICI of the contralateral wrist extensor muscle at baseline, immediately after and 15 and 30 minutes following cessation of anodal tDCS. Cortical excitability increased, whilst SICI was reduced at all time points following anodal tDCS. Interestingly, there were no differences between the three intensities of anodal tDCS on modulating cortical excitability or SICI. These results suggest that the aftereffect of anodal tDCS on facilitating cortical excitability is due to the modulation of synaptic mechanisms associated with long-term potentiation and is not influenced by different tDCS intensities.

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Transcranial Direct Current Stimulation: A Novel Neuromodulation Technique?

Bengal Journal of Psychiatry ◽

10.51332/bjp.2014.v19.i2.51 ◽

2014 ◽

pp. iv

Author(s):

Sujit Sarkhel

Keyword(s):

Major Depression ◽

Direct Current ◽

Brain Stimulation ◽

Transcranial Direct Current Stimulation ◽

Cortical Excitability ◽

Electrical Current ◽

Therapeutic Effects ◽

Direct Current Stimulation ◽

Non Invasive ◽

Direct Electrical Current

Transcranial direct current stimulation (tDCS) is a minimally invasive form of brainstimulation that uses direct electrical current to alter cortical excitability. During thisprocess, a weak, direct electrical current (1 to 2 mA) is applied using scalp surface electrodes.Anodal stimulation increases cortical excitability and cathodal stimulation decreases it. Thechanges in cortical excitability probably arise from the depolarization and hyperpolarization ofneurons.1 Interest in this treatment modality had begun way back in the 1960s but graduallywaned. Renewed interest began emerging in the 1990s following spurt in neuromodulationresearch using transcranial magnetic stimulation (TMS). Based on the theory of hypoactivityin left prefrontal cortex in depression, anodal tDCS has been applied to the left hemisphere toincrease activity and cathodal tDCS to the right hemisphere to decrease activity in order toresolve depression. Several open label and randomized controlled trials have been conductedto examine the efficacy of tDCS in treating major depression some of which have yieldedpositive results.2, 3, 4, tDCS has also been tried in Parkinson’s disease, schizophrenia, posttraumatic stress disorder and substance use. 5, 6,7 tDCS is a cheap and non-invasive techniquewith minimal side effects like headache and itchiness and redness at the site of stimulation.It will require few years of systematic research to find out whether tDCS emerges as a cheap,non-invasive and above all, effective method for treatment of psychiatric disorders or it goesinto oblivion as another “fancy” brain gadget!REFERENCES1. Bindman LJ, Lippold OC, Redfearn JW. The action of brief polarizing currents on the cerebral cortex ofthe rat (1) during current flow and (2) in the production of long-lasting after-effects. J Physiol. 1964; 172 :369-382.2. Boggio PS, Rigonatti SP, Ribeiro RB, et al. A randomized, double-blind clinical trial on the efficacy of cortical direct currentstimulation for the treatment of major depression. Int J Neuropsychopharmacol. 2008; 11 : 249-254.3. Brunoni AR, Ferrucci R, Bortolomasi M, et al. Transcranial direct current stimulation (tDCS) in unipolar vs. bipolar depressivedisorder. Prog Neuropsychopharmacol Biol Psychiatry. 2011; 35 : 96-101.4. Fregni F, Boggio PS, Nitsche MA, et al. Cognitive effects of repeated sessions of transcranial direct current stimulation in patientswith depression. Depress Anxiety. 2006; 23 : 482-484.5. Kuo MF, Paulus W, Nitsche MA. Therapeutic effects of non-invasive brain stimulation with direct currents (tDCS) in neuropsychiatricdiseases.Neuroimage. 2014; 85 : 948-9606. Jansen JM, Daams JG, Koeter MW, etal.Effects of non-invasive neurostimulation on craving : a meta-analysis. Neuroscience BiobehavRev 2013; 37 : 2472-24807. Marin MF, Camprodon JA, Dougherty DD, et al. Device-based brain stimulation to augment fear extinction : implications for PTSDtreatment and beyond. Depress Anxiety 2014; 10 : 1-10

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Transcranial direct current stimulation induces long-term potentiation-like plasticity in the human visual cortex

Translational Psychiatry ◽

10.1038/s41398-020-01134-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Lukas Frase ◽

Lydia Mertens ◽

Arno Krahl ◽

Kriti Bhatia ◽

Bernd Feige ◽

...

Keyword(s):

Psychiatric Disorders ◽

Mechanism Of Action ◽

Direct Current ◽

Transcranial Direct Current Stimulation ◽

Long Term Potentiation ◽

Constant Current ◽

Direct Current Stimulation ◽

Term Potentiation ◽

Significant Difference

AbstractTranscranial direct current stimulation (tDCS) is increasingly used as a form of noninvasive brain stimulation to treat psychiatric disorders; however, its mechanism of action remains unclear. Prolonged visual stimulation (PVS) can enhance evoked EEG potentials (visually evoked potentials, VEPs) and has been proposed as a tool to examine long-term potentiation (LTP) in humans. The objective of the current study was to induce and analyze VEP plasticity and examine whether tDCS could either modulate or mimic plasticity changes induced by PVS. Thirty-eight healthy participants received tDCS, PVS, either treatment combined or neither treatment, with stimulation sessions being separated by one week. One session consisted of a baseline VEP measurement, one stimulation block, and six test VEP measurements. For PVS, a checkerboard reversal pattern was presented, and for tDCS, a constant current of 1 mA was applied via each bioccipital anodal target electrode for 10 min (Fig. S1). Both stimulation types decreased amplitudes of C1 compared to no stimulation (F = 10.1; p = 0.002) and led to a significantly smaller increase (PVS) or even decrease (tDCS) in N1 compared to no stimulation (F = 4.7; p = 0.034). While all stimulation types increased P1 amplitudes, the linear mixed effects model did not detect a significant difference between active stimulation and no stimulation. Combined stimulation induced sustained plastic modulation of C1 and N1 but with a smaller effect size than what would be expected for an additive effect. The results demonstrate that tDCS can directly induce LTP-like plasticity in the human cortex and suggest a mechanism of action of tDCS relying on the restoration of dysregulated synaptic plasticity in psychiatric disorders such as depression and schizophrenia.

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The effects of transcranial direct current stimulation on gait in patients with Parkinson’s disease: a systematic review

Translational Neurodegeneration ◽

10.1186/s40035-021-00245-2 ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

Fateme Pol ◽

Mohammad Ali Salehinejad ◽

Hamzeh Baharlouei ◽

Michael A. Nitsche

Keyword(s):

Systematic Review ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Direct Current ◽

Transcranial Direct Current Stimulation ◽

Randomized Clinical Trials ◽

Cortical Excitability ◽

Experimental Studies ◽

Gait Rehabilitation ◽

Direct Current Stimulation

Abstract Background Gait problems are an important symptom in Parkinson’s disease (PD), a progressive neurodegenerative disease. Transcranial direct current stimulation (tDCS) is a neuromodulatory intervention that can modulate cortical excitability of the gait-related regions. Despite an increasing number of gait-related tDCS studies in PD, the efficacy of this technique for improving gait has not been systematically investigated yet. Here, we aimed to systematically explore the effects of tDCS on gait in PD, based on available experimental studies. Methods Using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) approach, PubMed, Web of Science, Scopus, and PEDro databases were searched for randomized clinical trials assessing the effect of tDCS on gait in patients with PD. Results Eighteen studies were included in this systematic review. Overall, tDCS targeting the motor cortex and supplementary motor area bilaterally seems to be promising for gait rehabilitation in PD. Studies of tDCS targeting the dorosolateral prefrontal cortex or cerebellum showed more heterogeneous results. More studies are needed to systematically compare the efficacy of different tDCS protocols, including protocols applying tDCS alone and/or in combination with conventional gait rehabilitation treatment in PD. Conclusions tDCS is a promising intervention approach to improving gait in PD. Anodal tDCS over the motor areas has shown a positive effect on gait, but stimulation of other areas is less promising. However, the heterogeneities of methods and results have made it difficult to draw firm conclusions. Therefore, systematic explorations of tDCS protocols are required to optimize the efficacy.

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Tracking the Effect of Cathodal Transcranial Direct Current Stimulation on Cortical Excitability and Connectivity by Means of TMS-EEG

Frontiers in Neuroscience ◽

10.3389/fnins.2018.00319 ◽

2018 ◽

Vol 12 ◽

Cited By ~ 14

Author(s):

Erica Varoli ◽

Alberto Pisoni ◽

Giulia C. Mattavelli ◽

Alessandra Vergallito ◽

Alessia Gallucci ◽

...

Keyword(s):

Direct Current ◽

Transcranial Direct Current Stimulation ◽

Cortical Excitability ◽

Direct Current Stimulation

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Gender-specific modulation of short-term neuroplasticity in the visual cortex induced by transcranial direct current stimulation

Visual Neuroscience ◽

10.1017/s0952523808080097 ◽

2008 ◽

Vol 25 (1) ◽

pp. 77-81 ◽

Cited By ~ 77

Author(s):

LEILA CHAIEB ◽

ANDREA ANTAL ◽

WALTER PAULUS

Keyword(s):

Sex Differences ◽

Visual Cortex ◽

Direct Current ◽

Transcranial Direct Current Stimulation ◽

Cortical Excitability ◽

Gonadal Hormones ◽

Study Data ◽

Short Term ◽

Direct Current Stimulation ◽

Significant Difference

Transcranial direct current stimulation (tDCS) is a non-invasive method of modulating levels of cortical excitability. In this study, data gathered over a number of previously conducted experiments before and after tDCS, has been re-analyzed to investigate correlations between sex differences with respect to neuroplastic effects. Visual evoked potentials (VEPs), phosphene thresholds (PTs), and contrast sensitivity measurements (CSs) are used as indicators of the excitability of the primary visual cortex. The data revealed that cathodally induced excitability effects 10 min post stimulation with tDCS, showed no significant difference between genders. However, stimulation in the anodal direction revealed sex-specific effects: in women, anodal stimulation heightened cortical excitability significantly when compared to the age-matched male subject group. There was no significant difference between male and female subjects immediately after stimulation. These results indicate that sex differences exist within the visual cortex of humans, and may be subject to the influences of modulatory neurotransmitters or gonadal hormones which mirror short-term neuroplastic effects.

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