The effect of transcranial direct-current stimulation on cortical coherence patterns in patients with major depression

Major depressive disorder is one of the most common psychiatric disorders that has cognitive, emotional, and behavioral symptoms. The disorder is associated with abnormalities in the cortical activity of the brain. Many neuropsychiatric diseases, such as depression, are associated with abnormal connectivity functions in the neural networks of the brain. These abnormalities can be analyzed using a variety of tools, including electroencephalography (EEG) and quantitative electroencephalography (QEEG). The coherence pattern is one of the components calculated by the QEEG and is a scale that examines the coordination of connectivity across areas of the brain. There are two types of coherence abnormalities in depression including the high intracranial coherence between bands; & the low coherence abnormality between hemispheres in bands. It is hypothesized that the differences observed in the coherence patterns of depressed patients are mainly due to the increase in functional short-distance connectivity in the left hemisphere and long-distance connectivity in the right hemisphere. This increase has been interpreted as a mechanism of adaptation and compensation in order to overcome the inefficiency of the integration of cortical activities. Research has shown that EEG-based functional connectivity change following transcranial direct current stimulation (tDCS). The aim of the study was to investigate the effect of tDCS on the cortical coherence patterns of patients with major depressive disorder.

Methods 

A sample of 36 patients were selected through structured interview by psychiatrists based on the criteria specified in DSM-5, by purposive sampling procedure based on including (age range 18 to 40 years, at least 9th grade education, minimum duration of 3 months from disorder onset and right handed) and excluding criteria (psychotic illness, mental retardation, history of seizures or epilepsy, head trauma, concomitant use of other disorders, concomitant use of drugs). All participants were assigned randomly in one of the research groups: recipient transcranial direct electrical stimulation (experimental group), the group receiving pseudo direct transcranial electrical stimulation (sham group) and the waiting list group (without any intervention). All participants were matched based on age, severity and duration of the disease. All participants completed the Beck depression inventory and their brain activity was recorded using a 19-channel EEG. Then, the data related to the subjects' brain waves for cortical coherence analysis were converted into quantitative electroencephalography by Neurogide software. After these steps, the subjects of the experimental group and the sham stimulation group were introduced to the process of treatment sessions. The experimental group (tDCS) received electrical stimulation by single-site method. In this stimulation, the anode electrode was placed in the left DLPFC region and the cathode electrode was placed in the right DLPFC region. This stimulation was presented to the subjects with a current of 2 mA, for a duration of 20 minutes and for 10 consecutive days. Subjects were then re-evaluated by EEG. The sham excitation group was such that the anodal electrodes were placed on the left DLPFC and the cathodal electrode on the right DLPFC. Subjects were then stimulated for 30 seconds, after which the device was turned off and received no stimulation; But the electrodes were attached to the subjects' heads until the end of twenty minutes, and the subjects were unaware of the lack of stimulation. At the end of ten sessions, the electrical activity of the subjects in this group (stimulation sham) was recorded again by EEG device. The waiting list group was also recorded by the EEG device at the same time with the interventions on the experimental groups and the false stimulation in two phases apart (10 days) by the EEG device. To analyze the results, the method of multivariate analysis of variance with repeated measures was used in the design of a 7 * 3 * 2 * 2 * 3, in which 3 expresses between group variables (tDCS groups, sham stimulation and waiting list). 2 represents the within group variable of experimental condition (pre and post-test), other within group variable are including the cerebral hemispheres (right and left), brain areas (anterior, central and posterior) and different bands of electrical activity (Delta, Theta, Alpha 1, Alpha 2 and Beta 1, Beta 2, Beta 3).

At first, an attempt was made to evaluate the effectiveness of tDCS on reducing the severity of depressive symptoms in participants. The results of one-way analysis of covariance show that the tDCS in comparison with sham group and waiting list, also compared to the pretest, significantly reduced the severity of depressive symptoms in participants. Although the sham group also showed a decrease in symptoms, these changes were not as significant. Also, multivariate analysis of variance with repeated measures was used to compare the scores of intra-hemispheric and intra-hemispheric coherence and the interaction of its factors. The results show that the main effect of activity bands and brain areas were significant. The results also show that the interactive effect of hemisphere * group, condition * hemisphere * group, condition * regions, condition * hemisphere * band * group, regions * band, condition * regions * band and condition * hemisphere * regions * band were significant. However, based on the significant interactions obtained, the interaction related to the condition * band * region * group is significant. It caused electrical differences in different areas of the brain between the experimental groups. They showed a reduction in symptoms, but these changes were not as significant as the stimulus-receiving group. Also, multivariate analysis of variance with repeated measures was used to compare the scores of intra-hemispheric and intra-hemispheric coherence and the interaction of its factors. To follow this interactive effect, the multivariate analysis of variance test was used. The results of this analysis showed that direct transcranial electrical stimulation caused the coherence pattern in the anterior, central and posteriorly in different electrical bands in the experimental group (tDCS) have significant changes compared to the two groups of sham stimulation and waiting list. The post hoc test was used to examine more accurately the differences between the mean scores of experimental groups (tDCS), sham stimulation and waiting list in the hemispheric coherence pattern between groups. The findings of this analysis showed that the experimental group (tDCS) performed better in cerebral coherence than the sham when receiving extracranial stimulation, compared with the waiting list group. In other words, electrical stimulation significantly reduces the coherence in brain bands, especially theta, alpha and beta bands in all three anterior, central and posterior regions, except alpha 1 band in the anterior and posterior regions compared to the sham stimulation group and the list group.

The results showed that there are significant interactions on coherence modulation based on brain areas (anterior, posterior and central) in different bands (delta, theta, alpha 1, alpha 2, beta 1, beta 2 and beta 3) and between groups (real stimulation, sham stimulation and waiting list) after tDCS. The findings of the present study showed that stimulation of tDCS led to a decrease in coherence in different bands of electrical activity, especially theta, alpha 2 and beta bands; This decrease in coherence was more significant in the central areas than in the anterior and posterior regions. Based on the findings of the present study, it should be acknowledged that transcranial stimulation has been effective in reducing intracranial coherence of patients in theta, alpha and beta bands.It has been shown that there is an inverse relationship between positive and negative emotions in brain waves, with positive emotion associated with high beta activity and low alpha activity in the left frontal cortex and low beta and high alpha activity in the right frontal cortex; Whereas in depression when emotion is negative, high alpha and beta activity is reported in the left frontal cortex and low alpha and beta activity is reported in the right frontal cortex. In fact, high alpha activity in the left frontal cortex means less left frontal cortex activity and superior hemispheric activity, in which people are less affected by positive emotions, which indicates that a biological background for depression is provided.These coherence patterns represent the activity of brain regions involved in specific sensory processing patterns in patients in a way that plays a significant role in autobiographical memory and the relationship between abstract and concepts. The excitatory effects of the anodal electrode on the areas receiving the stimulus are the product of a change in the excitability of the neuron due to the polarization of the membrane-resting potassium and a rapid change in the ion density below the electrode location.

Ethical considerations

Compliance with ethical guidelines
In order to observe the principles of research ethics, before starting the research, an informed consent form that explained the objectives and the process of the research, was provided to the participants. The information of all participants was coded with respect to the principle of confidentiality. This research has an ethical code from the Research Ethics Committee of Tabriz University of Medical Sciences with the ID (IR.TBZMED.REC.1396.385) and a clinical trial code (IRCT20180704040344N1).

Authors’ Contributions

Seyed Ali Arabi (first author) has presenting the initial research plan, collecting information and preparing the initial framework of the article, his contribution was about 35%. Gholamreza Chalabianloo (second and responsible author) contributed in data analysis, article writing and all correspondence and correction of the article and monitoring the research implementation process, his contribution was about 40%. Reza Abdi (third author) contributed through assistance in writing the article and supervising the performance, his contribution was about 25%.

No financial support has been received from any organization for this research.

Acknowledgments

This article is based on the master's thesis of cognitive sciences in Azarbaijan Shahid Madani University, Seyed Ali Seyed Arabi, with the guidance of Dr. Gholamreza Chalbianlou and the advice of Dr. Reza Abdi. The authors consider it their duty to express their gratitude to all the patients participating in this study who finally made it possible for them to cooperate. We also thank the esteemed staff of Bozorgmehr Neuroscience Treatment Center for their assistance in recording brain activity and performing interventions. We would also like to thank the Vice Chancellor for Research and the Director of Graduate Studies of Azarbaijan Shahid Madani University for supporting the implementation of this dissertation.

Conflict of interest

This study did not have any conflict of interest.