Transcranial Direct Current Stimulation For Schizophrenia And Prediction Of Its Effect

Schizophrenia is a mental disorder characterized by psychotic symptoms, mood changes, and cognitive impairments. Although its mechanism has not been fully clarified, several types of intervention, such as antipsychotic treatments and electroconvulsive therapy, have been used. However, they are not always effective, and some symptoms often remain treatment-resistant, indicating a need for the development of a novel approach.

Neuromodulation is defined as alterations of neural activity with targeted delivery of a stimulus into the brain. Methods of neuromodulation include non-invasive approaches such as transcranial magnetic stimulation, as well as invasive devices such as spinal cord stimulation and deep brain stimulation. Among them, transcranial direct current stimulation (tDCS) is feasible and safe, sending a weak and direct electrical current to the brain through electrodes. tDCS changes cortical excitability and has been suggested to modulate cortico-subcortical/cortico-cortical pathways. In schizophrenia, connectivity in the frontoparietal and inter-hemispheric networks is decreased, providing a rationale for beneficial effects of tDCS on some of the symptoms. In a previous study, we have reported the beneficial effects of tDCS on psychotic symptoms.

Prediction of the effect tDCS

On the other hand, there has been no way to predict clinical benefits of tDCS before administration, which may let doctors perform “unnecessary intervention.” We hypothesized that neural activity of some brain areas would be related to effects of tDCS on psychosis. We administered 10 sessions of tDCS for 26 patients with schizophrenia and examined whether oxy-hemoglobin concentrations measured by near-infrared spectroscopy (NIRS) at baseline could predict the effect on psychosis one month after the treatment. At baseline, oxy-hemoglobin concentrations throughout verbal fluency tasks were measured by a 52-channel NIRS instrument. At baseline and one month after the tDCS treatment, psychosis was measured by the Positive and Negative Syndrome Scale (PANSS), commonly used for evaluation of psychotic symptoms of schizophrenia.

Data analysis demonstrated a significant negative correlation between oxy-hemoglobin concentrations of left temporoparietal regions at baseline vs. changes of PANSS scores. This means that patients with a greater response to neural activity in left temporoparietal regions tend to get better treatment outcomes with tDCS. This is the first study to show the potential ability of NIRS to predict the effect of tDCS beforehand.

So, what is the mechanism brain activities at baseline influence the utility of tDCS in the treatment of psychosis? In a previous study, schizophrenia patients with auditory-verbal hallucinations showed reduced functional connectivity within the left temporoparietal junction compared with healthy control subjects. In the current study, activities of left temporoparietal regions were correlated with a change in psychotic symptoms after treatment with tDCS. These findings may suggest relations of left temporoparietal regions to the putative mechanisms by which psychotic symptoms are developed.

In conclusions, we demonstrated a correlation between activity in left temporoparietal cortical regions and the ability of tDCS to treat psychotic symptoms in schizophrenia. Our study suggests that NIRS provides a biomarker of the utility of tDCS in the treatment of schizophrenia.

These findings are described in the article entitled The effect of transcranial direct current stimulation on psychotic symptoms of schizophrenia is associated with oxy-hemoglobin concentrations in the brain as measured by near-infrared spectroscopy: A pilot study, recently published in the Journal of Psychiatric Research.

This work was conducted by Zui Narita from Johns Hopkins Bloomberg School of Public Health, Takamasa Noda, Shiori Setoyama, Takuma Inagawa from the National Center Hospital, and Kazuki Sueyoshi, Tomiki Sumiyoshi from Department of Preventive Intervention for Psychiatric Disorders, National Institute of Mental Health, affiliated with the National Center of Neurology and Psychiatry.

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