Diagnostic Task Specific Activations in Functional MRI and Aberrant Connectivity of Insula with Middle Frontal Gyrus Can Inform the Differential Diagnosis of Psychosis

Drozdstoy Stoyanov; Katrin Aryutova; Sevdalina Kandilarova; Rositsa Paunova; Zlatoslav Arabadzhiev; Anna Todeva-Radneva; Stefan Kostianev; Stefan Borgwardt

doi:10.3390/diagnostics11010095

Diagnostic Task Specific Activations in Functional MRI and Aberrant Connectivity of Insula with Middle Frontal Gyrus Can Inform the Differential Diagnosis of Psychosis

Diagnostics (Basel). 2021 Jan 8;11(1):95. doi: 10.3390/diagnostics11010095.

Authors

Drozdstoy Stoyanov¹, Katrin Aryutova¹, Sevdalina Kandilarova¹, Rositsa Paunova¹, Zlatoslav Arabadzhiev¹, Anna Todeva-Radneva¹, Stefan Kostianev², Stefan Borgwardt^{3

4}

Affiliations

¹ Department of Psychiatry and Medical Psychology, and Research Institute, Medical University Plovdiv, 4002 Plovdiv, Bulgaria.
² Department of Pathophysiology, and Research Institute, Medical University Plovdiv, 4002 Plovdiv, Bulgaria.
³ Klinik für Psychiatrie und Psychotherapie, Universität zu Lübeck, 23538 Lübeck, Germany.
⁴ Department of Psychiatry, University of Basel, 4001 Basel, Switzerland.

Abstract

We constructed a novel design integrating the administration of a clinical self-assessment scale with simultaneous acquisition of functional Magnetic Resonance Imaging (fMRI), aiming at cross-validation between psychopathology evaluation and neuroimaging techniques. We hypothesized that areas demonstrating differential activation in two groups of patients (the first group exhibiting paranoid delusions in the context of paranoid schizophrenia-SCH-and second group with a depressive episode in the context of major depressive disorder or bipolar disorder-DEP) will have distinct connectivity patterns and structural differences. Fifty-one patients with SCH (n = 25) or DEP (n = 26) were scanned with three different MRI sequences: a structural and two functional sequences-resting-state and task-related fMRI (the stimuli represent items from a paranoid-depressive self-evaluation scale). While no significant differences were found in gray matter volumes, we were able to discriminate between the two clinical entities by identifying two significant clusters of activations in the SCH group-the left Precuneus (PreCu) extending to the left Posterior Cingulate Cortex (PCC) and the right Angular Gyrus (AG). Additionally, the effective connectivity of the middle frontal gyrus (MFG), a part of the Dorsolateral Prefrontal Cortex (DLPFC) to the Anterior Insula (AI), demonstrated a significant difference between the two groups with inhibitory connection demonstrated only in SCH. The observed activations of PreCu, PCC, and AG (involved in the Default Mode Network DMN) might be indirect evidence of the inhibitory connection from the DLPFC to AI, interfering with the balancing function of the insula as the dynamic switch in the DMN. The findings of our current study might suggest that the connectivity from DLPFC to the anterior insula can be interpreted as evidence for the presence of an aberrant network that leads to behavioral abnormalities, the manifestation of which depends on the direction of influence. The reduced effective connectivity from the AI to the DLPFC is manifested as depressive symptoms, and the inhibitory effect from the DLPFC to the AI is reflected in the paranoid symptoms of schizophrenia.

Keywords: brain networks; connectivity; default mode network; depression; frontal cortex; insula; neuroimaging; neuropsychiatric disorders; precuneus; schizophrenia; translational neuroscience.