Resting-State Isolated Effective Connectivity of the Cingulate Cortex as a Neurophysiological Biomarker in Patients with Severe Treatment-Resistant Schizophrenia

Abstract

<b>Background</b>: The neural basis of treatment-resistant schizophrenia (TRS) remains unclear. Previous neuroimaging studies suggest that aberrant connectivity between the anterior cingulate cortex (ACC) and default mode network (DMN) may play a key role in the pathophysiology of TRS. Thus, we aimed to examine the connectivity between the ACC and posterior cingulate cortex (PCC), a hub of the DMN, computing isolated effective coherence (iCoh), which represents causal effective connectivity. <b>Methods</b>: Resting-state electroencephalogram with 19 channels was acquired from seventeen patients with TRS and thirty patients with non-TRS (nTRS). The iCoh values between the PCC and ACC were calculated using sLORETA software. We conducted four-way analyses of variance (ANOVAs) for iCoh values with group as a between-subject factor and frequency, directionality, and laterality as within-subject factors and post-hoc independent <i>t</i>-tests. <b>Results</b>: The ANOVA and post-hoc <i>t</i>-tests for the iCoh ratio of directionality from PCC to ACC showed significant findings in delta (<i>t</i>₄₅ = 7.659, <i>p</i> = 0.008) and theta (<i>t</i>₄₅ = 8.066, <i>p</i> = 0.007) bands in the left side (TRS < nTRS). <b>Conclusion</b>: Left delta and theta PCC and ACC iCoh ratio may represent a neurophysiological basis of TRS. Given the preliminary nature of this study, these results warrant further study to confirm the importance of iCoh as a clinical indicator for treatment-resistance.