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

Yuji Yamada,Tomiki Sumiyoshi

doi:10.3389/fnhum.2021.631838

Abstract

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.

Highlights

Transcranial direct current stimulation is a non-invasive method that modulates neural activities in the brain by delivering low-amplitude over a short period between electrodes
Sulpiride, a dopamine receptor blocker (Nitsche et al, 2006), suppresses the effects of anodal stimuli, while levodopa, a dopamine precursor (Kuo et al, 2008; MonteSilva et al, 2010), locally enhances excitement of certain synaptic transmissions (Kuo et al, 2008). These findings suggest that the action of Transcranial direct current stimulation (tDCS) may include regulation of dopamine transmissions
The hippocampi of mice receiving tDCS exhibit enhanced cAMP-responsive element binding protein (CREB) phosphorylation, and phosphorylated CREB at Ser133 binds to Brain-derived neurotrophic factor (BDNF) promoter I, and recruits of CREB-binding proteins. These findings suggest that anodal tDCS increases hippocampal Long-term potentiation (LTP) and memory via mechanisms related to BDNF genes (Podda et al, 2016; Yu et al, 2019)

Summary

Introduction

Transcranial direct current stimulation (tDCS) is a non-invasive method that modulates neural activities in the brain by delivering low-amplitude (usually no more than 2 mA) over a short period (no more than 30 min) between electrodes (anode and cathode). There has been a series of reports showing the ability of tDCS to ameliorate positive/negative symptoms of schizophrenia (Kim et al, 2019). Hallucinations (positive symptoms) (Hedges’g = 0.86) and negative symptoms (0.41) have been found to be improved by multi-session tDCS on the frontal or frontotemporal lobe (see montages in Table 1) twice daily for 5 days (Kim et al, 2019). Meta-analysis for cognitive function in patients with schizophrenia indicates the ability of multi-session tDCS on the prefrontal cortex (see montage in Table 1) to improve working memory (Hedges’g = 0.49), an important cognitive domain (Narita et al, 2020; Table 1)

Objectives

Results

Conclusion