Triple-Network Dysconnectivity in Patients With First-Episode Psychosis and Individuals at Clinical High Risk for Psychosis

Abstract

Objective In the triple-network model, the salience network (SN) plays a crucial role in switching between the default-mode network (DMN) and the central executive network (CEN). Aberrant patterns of triple-network connectivity have been reported in schizophrenia patients, while findings have been less consistent for patients in the early stages of psychotic disorders. Thus, the present study examined the connectivity among the SN, DMN, and CEN in first-episode psychosis (FEP) patients and individuals at clinical high risk (CHR) for psychosis.Methods Thirty-nine patients with FEP, 78 patients with CHR for psychosis, and 110 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging. We compared the SN, DMN, and CEN connectivity patterns of the three groups. The role of the SN in networks with significant connectivity differences was examined by mediation analysis.Results FEP patients showed lower SN-DMN and SN-CEN (cluster-level F=5.83, false discovery rate [FDR] corrected-p=0.001) connectivity than HCs. There was lower SN-DMN connectivity (cluster-level F=3.06, FDR corrected-p=0.053) at a trend level in CHR subjects compared to HCs. Between HCs and FEP patients, mediation analysis showed that SN-DMN connectivity was a mediator between group and SN-CEN connectivity. Additionally, SN-CEN connectivity functioned as a mediator between group and SN-DMN connectivity.Conclusion Aberrant connectivity between the SN and DMN/CEN suggests disrupted network switching in FEP patients, although CHR subjects showed trend-level SN-DMN dysconnectivity. Our findings suggest that dysfunctional triple-network dynamics centered on the SN can appear in patients in the early stages of psychotic disorders.

Aberrant cortico-thalamo-cerebellar network interactions and their association with impaired cognitive functioning in patients with schizophrenia

“…The triple network model suggests that in psychosis, SAL failure to detect salient stimuli and its inappropriate mediation and modulation of the engagement between a task-negative network, the DMN, and a task-positive network, the CEN, eventually lead to impaired functioning in the patients 72 , 73 . Such abnormal cortical network interactions, often hypoconnectivity, have been repeatedly reported in schizophrenia patients 72 , 74 , FEP patients 51 , 75 , and CHR individuals 51 , 76 as well. It is noteworthy to mention that in triple network dynamics, the SAL, also known as the ventral attention or cingulo-opercular network, plays a crucial role in detecting and interpreting salient stimuli and modulating two other networks depending on its interpretation.…”

“…Higher-order cognitive networks, including the default mode network (DMN), salience network (SAL), central executive network (CEN), and dorsal attention network (DAN), are suggested to be engaged in a wider range of complex cognition 40 – 44 . However, patients with schizophrenia have shown abnormal functional interactions within and among these cortical intrinsic networks, often correlated with poor cognitive functioning 45 – 51 , indicating abnormal orchestration of the brain on a large scale. Notably, efforts have been made to apply the functional network properties of the cerebellum and thalamus 52 – 55 and have found dysfunctional thalamic and cerebellar connectivity patterns to cortical networks in patients with schizophrenia 56 , 57 .…”

Exploring causal mechanisms of psychosis risk

“…CHR-P individuals have altered brain structure ( Luna et al, 2022 , Merritt et al, 2021a ) and function ( Luna et al, 2022 ) compared to healthy controls. There is some evidence that these alterations in CHR-P represent an intermediate stage between healthy controls and FEP ( Kim et al, 2022 , Kindler et al, 2018 , Korda et al, 2022 ), but this evidence is inconsistent ( Oliver et al, 2023 , Schifani et al, 2017 , Zhao et al, 2022 ).…”