Hyperactivity and hyperconnectivity of the default network in schizophrenia and in first-degree relatives of persons with schizophrenia

By Susan L. Whitfield-Gabrieli, H. Thermenos, Snezana M Milanovic, M. Tsuang, Stephen V. Faraone, Robert W. McCarley, Martha Elizabeth Shenton, A. Green, Alfonso Nieto-Castanon, Peter S. LaViolette and 3 more. Proceedings of the National Academy of Sciences of the United States of America, 2009

1,453 citations recorded by the source corpus.

We examined the status of the neural network mediating the default mode of brain function, which typically exhibits greater activation during rest than during task, in patients in the early phase of schizophrenia and in young first-degree relatives of persons with schizophrenia. During functional MRI, patients, relatives, and controls alternated between rest and performance of working memory (WM) tasks. As expected, controls exhibited task-related suppression of activation in the default network, including medial prefrontal cortex (MPFC) and posterior cingulate cortex/precuneus. Patients and relatives exhibited significantly reduced task-related suppression in MPFC, and these reductions remained after controlling for performance. Increased task-related MPFC suppression correlated with better WM performance in patients and relatives and with less psychopathology in all 3 groups. For WM task performance, patients and relatives had greater activation in right dorsolateral prefrontal cortex (DLPFC) than controls. During rest and task, patients and relatives exhibited abnormally high functional connectivity within the default network. The magnitudes of default network connectivity during rest and task correlated with psychopathology in the patients. Further, during both rest and task, patients exhibited reduced anticorrelations between MPFC and DLPFC, a region that was hyperactivated by patients and relatives during WM performance. Among patients, the magnitude of MPFC task suppression negatively correlated with default connectivity, suggesting an association between the hyperactivation and hyperconnectivity in schizophrenia. Hyperactivation (reduced task-related suppression) of default regions and hyperconnectivity of the default network may contribute to disturbances of thought in schizophrenia and risk for the illness.

Subfields: Cognitive Neuroscience, Radiology, Nuclear Medicine and Imaging

View Paper: https://www.semanticscholar.org/paper/14ab6bcb0a029ab5daffab06ea960cd4e4de4d7a

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cognitive Neuroscience

In Radiology, Nuclear Medicine and Imaging

Citations in the corpus

A Meta-analysis of Functional Neuroimaging Studies of Self- and Other Judgments Reveals a Spatial Gradient for Mentalizing in Medial Prefrontal Cortex (2012, background): “, 2009) to schizophrenia (Whitfield-Gabrieli et al., 2009), post-traumatic”
Exploring the brain network: a review on resting-state fMRI functional connectivity. (2010, background): “…in examining cognitive disfunctioning in neurologic and psychiatric brain disorders (Bullmore and Sporns, 2009; Greicius, 2008) (Harrison et al., 2007; Rombouts et al., 2005) (Garrity et al., 2007; Lowe et al., 2008; Mohammadi et al., 2009; Whitfield-Gabrieli et al., 2009; Zhou et al., 2007b).”
Dysconnectivity in schizophrenia: where are we now? (2011, background): “lso reported frontal region dysconnectivity to other cortical and ubcortical areas, such as the parietal cortex, the cerebellum and he anterior cingulate gyrus (ACG) (Spence et al., 2000; Whalley t al., 2005;Whitfield-Gabrieli et al., 2009;Woodward et al., 2009; i et al., 2010).”
Criticality in the brain: A synthesis of neurobiology, models and cognition. (2017, background): “zophrenia is associated with less suppression of activity in the default-mode network when subjects engage in external tasks (Harrison et al., 2007; Meyer-Lindenberg et al., 2001; Nejad et al., 2011; Whitfield-Gabrieli et al., 2009). Dynamic insights into this loss of efficiency could draw from the ”
Schizophrenia, neuroimaging and connectomics (2012, background): “…disorder of hypo-connectivity (Alexander-Bloch et al., 2010; Fornito et al., 2011c; Lynall et al., 2010), hyper-connectivity (Salvador et al., 2007; Whitfield-Gabrieli et al., 2009), and a more generalized dysconnectivity syndrome involving both (Liu et al., 2008; Stephan et al., 2006; Wolf et…”
Anticorrelations in resting state networks without global signal regression (2011, neutral): “Abnormalities in these two anticorrelated networks have been found in patients with schizophrenia (Whit ﬁ eld-Gabrieli et al., 2009), ADHD (Castellanos et al., 2008), bipolar disorder (Chai et al., 2011), and Alzheimer's disease (Wang et al., 2007).”
Default mode network activity in schizophrenia studied at resting state using probabilistic ICA. (2012, background): “…although the evidence is not completely converging on this area and direction of effects differ across studies (Zhou et al., 2007; Kim et al., 2009; Whitfield-Gabrieli et al., 2009; Ongur et al., ity in schizophrenia studied at resting state using probabilistic ICA, 2010;Woodward et al., 2011).”
Conn: A Functional Connectivity Toolbox for Correlated and Anticorrelated Brain Networks (2012, neutral): “…is particularly useful for characterizing functional brain network differences in pediatric and clinical populations, such as schizophrenia (Whitfield-Gabrieli et al., 2009; Whitfield-Gabrieli and Ford 2012), ADHD (Castellanos et al., 2008), autism (Weng et al., 2010), depression (Greicius…”
Brain graphs: graphical models of the human brain connectome. (2011, background): “Similarly, it is difficult to explain why specific neuropsychiatric disorders, e.g., schizophrenia, have often been associated with a profile of both abnormally increased and decreased magnitude of connectivity across different brain regions (Rubinov et al. 2009, Whitfield-Gabrieli et al. 2009).”