Evaluation of short interval cortical inhibition and intracortical facilitation from the dorsolateral prefrontal cortex in patients with schizophrenia.

ABSTRACT

GABAergic and glutamatergic dysfunction in the dorsolateral prefrontal cortex (DLPFC) are thought to be the core pathophysiological mechanisms of schizophrenia. Recently, we have established a method to index these functions from the DLPFC using the paired transcranial magnetic stimulation (TMS) paradigms of short interval intracortical inhibition (SICI) and facilitation (ICF) combined with electroencephalography (EEG). In this study, we aimed to evaluate neurophysiological indicators related to GABAA and glutamate receptor-mediated functions respectively from the DLPFC in patients with schizophrenia using these paradigms, compared to healthy controls. Given that these activities contribute to cognitive functions, the relationship between the TMS-evoked potential (TEP) modulations by SICI/ICF and cognitive/clinical measures were explored. Compared to controls, patients showed reduced inhibition in P60 (t22 = -4.961, p < 0.0001) by SICI and reduced facilitation in P60 (t22 = 5.174, p < 0.0001) and N100 (t22 = 3.273, p = 0.003) by ICF. In patients, the modulation of P60 by SICI was correlated with the longest span of the Letter-Number Span Test (r = -0.775, p = 0.003), while the modulation of N100 by ICF was correlated with the total score of the Positive and Negative. Syndrome Scale (r = 0.817, p = 0.002). These findings may represent the pathophysiology, which may be associated with prefrontal GABAA and glutamatergic dysfunctions, in the expression of symptoms of schizophrenia.