20-30% schizophrenia (SCZ) patients struggle with auditory verbal hallucinations (AVH) minimally responsive to pharmaceutical treatments. Add-on fronto-temporoparietal transcranial direct current stimulation (tDCS) is suggested to address persistent AVH in SCZ patients. High heterogeneity among existing randomized control trials for AVH treatment in SCZ and lack of empirical studies investigating tDCS action mechanism warrants a systematic investigation into the mechanistic basis of tDCS action. 

This study proposes and examines the brain’s neuroplasticity potential as biological phenomena driving treatment effects of tDCS. Using a randomized, double-blind, sham-controlled parallel-arm, pre-post design, changes in neuroplasticity potential with tDCS treatment for AVH in SCZ will be assessed. The four composite primary outcome measures of this study are: 

1) changes in N100-derived event-related-potential waveforms (neurophysiological), 

2) changes glutamine-glutamate levels (neurochemical), 

3) changes in resting-state functional connectivity (neuroimaging), and 

4) reduction in AVH severity (clinical). 

Secondary objectives of this study are: 

1) exploring the correlation between neurobiological measures of neuroplasticity changes induced by tDCS and clinical improvement in AVH to indicate the nature and strength of the relationship between the two; 

2) exploring the effect of verum (active) tDCS on early course versus late course SCZ patients will uncover if illness chronicity is a potential barrier to tDCS responsivity; and 

3) utilizing disorder-related (age at illness onset, medication, the severity of the symptom, etc.) and biographic (age, sex, years of education, etc.) features of the study sample towards predicting neuroplasticity modulation in the study sample.