Aberrant motor cortical plasticity in antipsychotic-resistant schizophrenia: A cross-sectional study using transcranial direct current and magnetic stimulation

Background Persistence of positive symptoms despite adequate antipsychotic treatment is a clinically challenging situation in schizophrenia. Impaired cortical plasticity is hypothesized to underlie the antipsychotic resistance in schizophrenia. This study evaluated High-Definition-tDCS (HD-tDCS) driven motor cortical plasticity using short-interval cortical inhibition (SICI) paired-pulse protocol in schizophrenia. Methods Fifty-three individuals with antipsychotic-resistant schizophrenia (ARS) and 31 healthy subjects underwent transcranial magnetic stimulation-electromyography (TMS-EMG) evaluation before and after (10, 20, 30, and 40 min) of a single session of cathodal HD-tDCS (2 mA; 20 min) over the left M1 area. Cortical plasticity was determined as a change in SICI & SI1_mV (Motor Evoked Potential at 1 mV). The effect of time and group was assessed using linear mixed-effects models. Results A group*time interaction ( t = 2.23) was noted in SICI at 40th minute after cathodal HD-tDCS, revealing that patients with ARS had significantly poorer and ill-sustained motor cortical excitatory changes following cathodal HD-tDCS compared to healthy controls. Furthermore, clozapine-resistant, ie, Ultra Resistant Schizophrenia (URS) participants exhibited poorer plasticity compared to first-line antipsychotic resistant [Cohen's d = 0.764, p = 0.004]. Conclusion The results reaffirm the finding of impaired motor cortical plasticity in ARS. Additionally, we note that URS with a higher symptom burden, treatment resistance and poorer functioning had the poorest motor cortical plasticity. Future studies could explore the potential of cortical plasticity as a predictive, mechanistic, and theranostic biomarker.