Resting-State Networks in Schizophrenia

Abstract

Schizophrenia has been conceptualized as a disorder of altered brain connectivity (i.e. dysconnectivity). Until relatively recently, it was not feasible to test dysconnectivity hypotheses of schizophrenia in vivo. Resting-state functional magnetic resonance imaging (fMRI) is a powerful tool for mapping functional networks of the brain, such as the default mode network (DMN), and investigating the systems-level pathology of neurological and psychiatric disorders. In this article, we review the latest findings from resting-state fMRI studies on schizophrenia. Despite the wide array of methods used and heterogeneity of patient samples, several tentative conclusions may be drawn from the existing literature. 1) Connectivity of the DMN is altered in schizophrenia. Findings vary across studies; however, a majority of investigations reported hyper-connectivity of the DMN. 2) Resting-state connectivity of the prefrontal cortex (PFC) is reduced in schizophrenia, particularly intra-PFC connectivity. 3) Cortical-subcortical networks, including thalamocortical, frontolimbic, and cortico-cerebellar networks are altered in schizophrenia. 4) Preliminary findings indicate that functional connectivity within auditory/language networks and the basal ganglia is related to specific clinical symptoms, including auditory- verbal hallucinations and delusions. 5) Whole-brain network topology measures based on graph theory indicate that functional brain networks in schizophrenia are characterized by reduced small-worldness, lower degree connectivity of brain hubs, and decreased modularity. 6) Some of the alterations in functional connectivity observed in probands are present in unaffected relatives, raising the possibility that functional dysconnectivity is an endophenotype related to genetic risk for schizophrenia. Combined, these findings provide broad support for dysconnectivity theories of schizophrenia. We conclude our review with a discussion of the limitations of the existing literature and potentially important areas of future research.

Identifying 22q11.2 Deletion Syndrome and Psychosis Using Resting-State Connectivity Patterns

“…A recent model postulates that the salience network, composed of ACC and anterior insula, prevents the appropriate switch of attention between internal self-referential thinking and external attention to relevant stimuli in schizophrenia (Menon 2011). This hypothesis is further sustained by several reports showing an altered pattern of deactivation of the DMN during a task in schizophrenic patients (Garrity et al 2007) and in populations at genetic (Whitfield-Gabrieli et al 2009;Karbasforoushan and Woodward 2012) or clinical risk for psychosis (Shim et al 2010;Fryer et al 2013). Finally, a role of the ACC in mediating fronto-temporal connectivity and inducing compensatory mechanisms has also been hypothesized in the schizophrenic prodrome.…”

“…Indeed, cognitive functions do not depend only on the independent functioning of specialized brain regions but also on the their connectivity and capacity of integration (Bullmore and Sporns 2009;Sporns et al 2005). For instance brain networks alterations have already been linked to differences in cognitive abilities (Li et al 2009;van den Heuvel et al 2009;Wu et al 2013;Cole et al 2012) and to several psychiatric disorders including Alzheimer disease (Filippi and Agosta 2011;Greicius 2008), depression (Greicius 2008), and schizophrenia (Karbasforoushan and Woodward 2012).…”

Reduced specialized processing in psychotic disorder: a graph theoretical analysis of cerebral functional connectivity

“…There are two general methods to measure resting‐state functional connectivity: (1) seed‐based correlation analysis, which is hypothesis‐driven; and (2) independent component analysis (ICA), which is a multivariate, model‐free, data‐driven method (Karbasforoushan and Woodward 2012). More recently, another method for analyzing resting‐state fMRI at a whole brain level has been introduced, called graph theory.…”

“…Recently, graph theoretical methods have been applied to better understand the brain and its dysconnectivity in psychiatric disorders, such as schizophrenia (Karbasforoushan and Woodward 2012). These few studies have shown that patients with schizophrenia have alterations in diverse topological properties of the functional human brain network with respect to controls (Liu et al.…”

Inefficient Neural Self-Stabilization: A theory of spontaneous resolutions and recurrent relapses in psychosis

“…Ketamine, an agent that produces nearly all of the core symptoms of schizophrenia in healthy humans, produces robust hyperconnectivity involving the prefrontal cortex [125][126][127][128][129][130] . In particular, this resting-state hyperconnectivity involves a set of brain regions that constitute the 'default-mode network' 122,131,132 . These regions characteristically show an elevated level of activity at rest, and appear relative deactivated when an individual is engaged in task performance 133 .…”