Abstract
Schizophrenia is characterized by aberrant intrinsic functional connectivity (iFC) within and between intrinsic connectivity networks (ICNs), including the Default Mode- (DMN), Salience- (SN), and Central Executive Network (CEN). The anterior insula (AI) of the SN has been demonstrated to modulate DMN/CEN interactions. Recently, we found that the dependence of DMN/CEN interactions on SN’s right AI activity is altered in patients with schizophrenia in acute psychosis and related to psychotic symptoms, indicating a link between aberrant AI, DMN, CEN, and psychosis. However, since structural alterations of the insula are also present during psychotic remission and associated with negative symptoms, impaired AI interaction might be relevant even for psychotic remission and corresponding symptoms. Twelve patients with schizophrenia during psychotic remission (SR) and 12 healthy controls were assessed using resting-state fMRI and psychometric examination. High-model-order independent component analysis of fMRI data revealed ICNs including DMN, SN, and CEN. Scores of iFC within (intra-iFC) and between (inter-iFC) distinct subsystems of the DMN, SN, and CEN were calculated, compared between groups and correlated with the severity of symptoms. Intra-iFC was altered in patients’ SN, DMN, and CEN, including decreased intra-iFC in the left AI within the SN. Patients’ inter-iFC between SN and CEN was increased and correlated with the severity of negative symptoms. Furthermore, decreased intra-iFC of the left AI correlated with both severity of negative symptoms and increased inter-iFC between SN and CEN. Our result provides first evidence for a relationship between AI dysfunction and altered between-network interactions in schizophrenia during psychotic remission, which is related to the severity of negative symptoms. Together with our previous results, data suggest specific SN/DMN/CEN reorganization in schizophrenia with distinct insular pathways for distinct symptom dimensions.
Highlights
Schizophrenia is a severe mental disorder associated with aberrant functional and structural connectivity within and between intrinsic connectivity networks (ICNs), including the Default Mode(DMN), Salience- (SN), and Central Executive Network (CEN) (Menon, 2011; Palaniyappan and Liddle, 2012)
INTRINSIC CONNECTIVITY NETWORKS: INTRA- AND INTER-intrinsic functional connectivity (iFC) In general, both intra-iFC and inter-iFC were almost perfectly in line with findings of Allen et al (2011), indicating that the basic functional architecture of SN, DMN, and CEN was present in both groups
Intra-iFC Automated component selection, which was based on spatial templates representing subsystems of the DMN, SN, and CEN, revealed seven components of interest for each individual: the SN was represented in one component
Summary
Schizophrenia is a severe mental disorder associated with aberrant functional and structural connectivity within and between intrinsic connectivity networks (ICNs), including the Default Mode(DMN), Salience- (SN), and Central Executive Network (CEN) (Menon, 2011; Palaniyappan and Liddle, 2012). ICNs are characterized by spatially consistent functional connectivity (FC) of intrinsic brain activity (Fox and Raichle, 2007; Allen et al, 2011). The DMN includes primarily the ventromedial prefrontal cortex, the posterior cingulate cortex, bilateral inferior parietal cortex, and the middle temporal lobe and is involved in self-related/internally oriented processes (Buckner et al, 2008). The CEN includes mainly the dorsolateral prefrontal cortex and posterior parietal cortex and is involved in goal-directed/externally oriented tasks (Fox and Raichle, 2007). Alterations in FC have been reported for DMN as well as CEN during both rest
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