Differential connectivity between core hubs underlying demanding executive functions in schizophrenia compared to autism and control adults

Sofia Morais^1,2Otília C. d'Almeida¹Daniela Jardim Pereira^1,2Alexandre Sayal^1,2Bruno Direito¹João Pereira¹Salomé Caldeira²Sofia Meneses²Graça Areias²Vanessa Girão²Catarina Bettencourt²Antonio Ferreira Macedo^1,2Miguel Castelo-Branco^1*

• ¹Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), Coimbra, Portugal
• ²Unidade Local de Saude de Coimbra, Coimbra, Portugal

Introduction: Schizophrenia (SCZ) and autism spectrum disorder (ASD) are neurodevelopmental disorders with similar impairments in several neuropsychological domains, namely in executive function, hampering their differential diagnosis. We asked if brain activation and connectivity patterns within central nodes of the frontoparietal network (FPN), critical for executive control, are distinctively altered in these clinical populations during a working-memory task (n-back). Methods: Forty-five male adults (15 SCZ,15 ASD,15 controls) matched for age, sex, education level, and handedness, underwent 3T brain fMRI during a n-back executive task. We functionally defined three core hubs of the FPN (primary outcome measure: dorsolateral prefrontal cortex -DLPFC and intraparietal sulcus -IPS), and the insula (secondary outcomes), a relevant connecting hub of the salience network (SN). Results: The SCZ group showed higher activation for IPS compared to controls. No significant differences were observed between SCZ and ASD. In contrast, we found significant connectivity differences which were higher for the SCZ group, particularly between the DLPFC-IPS and insula-IPS. Differences between SCZ and ASD dominated in the left hemisphere. Discussion: The distinct cortical activation and connectivity patterns in SCZ (increased connectivity within FPN and FPN-SN), as compared to ASD and controls, are consistent with a fundamental change in executive function in psychosis.