The Effects of Bimodal tDCS on Illness Severity, Insight, Functional Outcomes, Neurocognition and HRV in Schizophrenia

The study aimed to investigate the effects of bimodal anodal transcranial direct current stimulation (tDCS) over bilateral dorsolateral prefrontal cortex (DLPFC) on psychopathological symptoms, insight, psychosocial functioning, neurocognitive function and heart rate variability (HRV) in schizophrenia patients

Transcranial direct current stimulation encompasses the induction of a relatively weak constant current flow through the cerebral cortex via scalp electrodes . Dependent on stimulation polarity, this results in a modulation of cortical excitability and spontaneous neural activity.The technique was established in the 1950s and 1960s primarily in animals. In these early studies it was shown that subthreshold DC stimulation increases spontaneous neuronal activity if the anode is placed above or within the cortex, while exposure to cathodal polarity results in reduced activity. This is caused by a subthreshold membrane depolarization by anodal and a hyperpolarization by cathodal stimulation. It was demonstrated in humans that the after-effects of tDCS depend on modifications of N-methyl-D-aspartate (NMDA) receptor-efficacy. The after-effects of tDCS are blocked by the NMDA receptor antagonist dextromethorphan, and prolonged by the partial NMDA receptor-agonist D-cycloserine. This tDCS polarity-dependent alteration of NMDA receptor function seems to be initiated by the respective membrane potential shift and probably by the accompanying cortical activity modification,because it is prevented by the sodium channel blocker carbamazepine. Intraneuronal calcium concentration also contributes, because calcium channel antagonists eliminate the excitability-enhancing after-effects of anodal tDCS. Recently, unimodal anodal tDCS over left dorsolateral prefrontal cortex (DLPFC) has been found to improve psychopathological symptoms, cognitive deficits and insight of schizophrenia and also strengthen cardiac autonomic function in healthy subjects. Further studies using bimodal anodal tDCS over bilateral dorsolateral prefrontal cortex (DLPFC) and prefrontal cortex are needed.

Study design: randomized double-blind, sham-controlled study design.

Participants: 60 patients having a diagnosis of schizophrenia or schizoaffective were randomly allocated to receive 20 minutes of active 2-mA tDCS or sham stimulation twice a day on 5 consecutive weekdays. These participants were assessed at baseline, after intervention and in a three-months follow-up.

Active or sham stimulation: The present study used bimodal anodal tDCS over bilateral dorsolateral prefrontal cortex (DLPFC) and prefrontal cortex. One anode was placed with the middle of the electrode over a point midway between International 10-20 electrode positions F3 and Fp1 (left dorsolateral prefrontal cortex and left prefrontal cortex). The other was located over a point midway between F4 and Fp2 (right dorsolateral prefrontal cortex and left prefrontal cortex). An extracephalic positions were used for the reference electrodes (cathodes) in order to avoid confounding effects from inhibitory cathodal effects at other cortical sites. The reference electrodes were placed on bilateral forearms.

Others: see Arms and Interventions, Eligibility Criteria or Outcome Measures.

Eligibility Criteria:
Inclusion Criteria:

1. Eligible participants aged 20-65 with DSM-IV-TR-defined schizophrenia or schizoaffective disorder.
2. Duration of illness ≧ 1 year.
3. Being on an adequate therapeutic dose of antipsychotics and clinically stable (nonacute phase of illness) but symptomatic for at least 4 weeks prior to enrolment as defined by Clinical Global Impression-Severity of Illness scale (CGI-S) score ≦ 4 (at both screening and baseline).
4. Agreement to participate in the study and provide the written informed consent.

Exclusion Criteria:

1. Having current psychiatric comorbidity or active substance use disorder, in exception to caffeine and/or tobacco.
2. Having history of seizures.
3. Having contraindications for tDCS, e.g., implanted brain medical devices or metal in the head.
4. Having history of intracranial neoplasms or surgery, or a history of severe head injuries or cerebrovascular diseases.
5. Pregnancy or breastfeeding at enrollment.