Default mode network activity in schizophrenia studied at resting state using probabilistic ICA

Mingoia, Gianluca; Wagner, Gerd; Langbein, Kerstin; Maitra, Raka; Smesny, Stefan; Dietzek, Maren; Burmeister, H; Reichenbach, Jürgen R.; Schlößer, R.; Gaser, Christian; Sauer, Heinrich; Nenadić, Igor

doi:10.1016/j.schres.2012.01.036

Cited by 118 publications

(82 citation statements)

References 34 publications

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“…The two fMRI subnetworks within the a-DMN showed preferential functional disconnectivity among disorders. The a-DMN-S1 subnetwork primarily containing dorsal-MPFC/ACC was impaired in only SZ probands, as is consistent with prior reports examining other measures of RS-DMN connectivity (16,17,54). Several genes had relatively high loading coefficients and/or multiple occurrences within the genetic network (e.g., CDH13 from the cadherin family, which had nine SNPs).…”

Section: Ica Derived Dmnssupporting

confidence: 87%

“…Connectivity within the DMN is compromised in multiple mental disorders including SZ and PBP (4,(15)(16)(17)(18)(19), although reports are inconsistent as to whether hypo-vs. hyperconnectivity (13,16,17,(19)(20)(21) within this circuit is related to risk of psychosis. Ongür et al (17) reported reduced MPFC resting-state DMN connectivity in both SZ and BP.…”

Section: Significancementioning

confidence: 99%

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Multivariate analysis reveals genetic associations of the resting default mode network in psychotic bipolar disorder and schizophrenia

Meda

Ruaño

Windemuth

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

218

159

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The brain's default mode network (DMN) is highly heritable and is compromised in a variety of psychiatric disorders. However, genetic control over the DMN in schizophrenia (SZ) and psychotic bipolar disorder (PBP) is largely unknown. Study subjects (n = 1,305) underwent a resting-state functional MRI scan and were analyzed by a two-stage approach. The initial analysis used independent component analysis (ICA) in 324 healthy controls, 296 SZ probands, 300 PBP probands, 179 unaffected first-degree relatives of SZ probands (SZREL), and 206 unaffected first-degree relatives of PBP probands to identify DMNs and to test their biomarker and/ or endophenotype status. A subset of controls and probands (n = 549) then was subjected to a parallel ICA (para-ICA) to identify imaging-genetic relationships. ICA identified three DMNs. Hypoconnectivity was observed in both patient groups in all DMNs. Similar patterns observed in SZREL were restricted to only one network. DMN connectivity also correlated with several symptom measures. Para-ICA identified five sub-DMNs that were significantly associated with five different genetic networks. Several top-ranking SNPs across these networks belonged to previously identified, well-known psychosis/mood disorder genes. Global enrichment analyses revealed processes including NMDA-related long-term potentiation, PKA, immune response signaling, axon guidance, and synaptogenesis that significantly influenced DMN modulation in psychoses. In summary, we observed both unique and shared impairments in functional connectivity across the SZ and PBP cohorts; these impairments were selectively familial only for SZREL. Genes regulating specific neurodevelopment/transmission processes primarily mediated DMN disconnectivity. The study thus identifies biological pathways related to a widely researched quantitative trait that might suggest novel, targeted drug treatments for these diseases.genetics | BSNIP | architecture | molecular S chizophrenia (SZ) and psychotic bipolar disorder (PBP) are common, serious, heritable, genetically complex illnesses, sharing multiple characteristics, including risk genes and abnormalities in cognition, neural function, and brain structure (1-4). However, despite recent advances, their underlying biological mechanisms are largely undetermined and may be shared across the two diagnostic groups. Recent large-scale analyses have used various statistical informatics strategies to dissect these biological underpinnings better (5, 6). A recent study using a pathwayenrichment strategy showed that genes involved in neuronal cell adhesion, synaptic formation, and cell signaling are overrepresented in SZ and bipolar disorder (BP) (6). Another study using an informatics-based approach identified several cohesive genetic networks related to axon guidance, neuronal cell mobility, and synaptic functioning as key players in schizophrenia (5).Although risk for psychotic illnesses is driven in small part by highly penetrant, often private mutations such as copy number variants, substantial...

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Section: Ica Derived Dmnssupporting

confidence: 87%

Section: Significancementioning

confidence: 99%

Multivariate analysis reveals genetic associations of the resting default mode network in psychotic bipolar disorder and schizophrenia

Meda

Ruaño

Windemuth

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

218

159

View full text Add to dashboard Cite

show abstract

“…Interestingly, an association between abnormally increased functional connectivity and hyperactivation in the DMN has also been reported in schizophrenia patients (including those in the early phases of schizophrenia and schizoaffective and schizophreniform disorder) and may be part of the pathophysiology of schizophrenia and underlie risk for this disorder [41]. Furthermore, lower connectivity strength in the dlPFC (center of the TPN) and temporal areas, and hyperconnectivity in PFC (center of the DMN) in the resting state [50], are simultaneously found in medicated chronic patients, and are associated with negative symptoms. This study segregates different connectivity dysfunctions in schizophrenia patients and provides further evidence that aberrant hyperconnectivity in part of the DMN is correlated with the core pathophysiology of schizophrenia.…”

Section: Functional Connectivity In the Dmn In Schizophreniamentioning

confidence: 89%

A Review of the Functional and Anatomical Default Mode Network in Schizophrenia

et al. 2016

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Schizophrenia is a severe mental disorder characterized by impaired perception, delusions, thought disorder, abnormal emotion regulation, altered motor function, and impaired drive. The default mode network (DMN), since it was first proposed in 2001, has become a central research theme in neuropsychiatric disorders, including schizophrenia. In this review, first we define the DMN and describe its functional activity, functional and anatomical connectivity, heritability, and inverse correlation with the task positive network. Second, we review empirical studies of the anatomical and functional DMN, and anti-correlation between DMN and the task positive network in schizophrenia. Finally, we review preliminary evidence about the relationship between antipsychotic medications and regulation of the DMN, review the role of DMN as a treatment biomarker for this disease, and consider the DMN effects of individualized therapies for schizophrenia.

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“…The DMN describes a neural network that shows particularly high metabolic and neural activity in the resting state, [26][27][28][29][30] where resting-state brain activity is defined as the period in which the brain is not engaging with any external stimuli (eg, specific cognitive tasks 26 ). Many of the symptoms of schizophrenia have been attributed to the failure of functional integration or aberrant connectivity in the DMN.…”

Section: The Sense Of Agency and Schizophrenia: Phenomenology And Neumentioning

confidence: 99%

Is the Sense of Agency in Schizophrenia Influenced by Resting-State Variation in Self-Referential Regions of the Brain?

Robinson

Wagner

Northoff³

2015

SCHBUL

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Schizophrenia is a disturbance of the self, of which the attribution of agency is a major component. In this article, we review current theories of the Sense of Agency, their relevance to schizophrenia, and propose a novel framework for future research. We explore some of the models of agency, in which both bottom-up and top-down processes are implicated in the genesis of agency. We further this line of inquiry by suggesting that ongoing neurological activity (the brain's resting state) in self-referential regions of the brain can provide a deeper level of influence beyond what the current models capture. Based on neuroimaging studies, we suggest that aberrant activity in regions such as the default mode network of individuals with schizophrenia can lead to a misattribution of internally/externally generated stimuli. This can result in symptoms such as thought insertion and delusions of control. Consequently, neuroimaging can contribute to a more comprehensive conceptualization and measurement of agency and potential treatment implications.

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Default mode network activity in schizophrenia studied at resting state using probabilistic ICA

Cited by 118 publications

References 34 publications

Multivariate analysis reveals genetic associations of the resting default mode network in psychotic bipolar disorder and schizophrenia

Multivariate analysis reveals genetic associations of the resting default mode network in psychotic bipolar disorder and schizophrenia

A Review of the Functional and Anatomical Default Mode Network in Schizophrenia

Is the Sense of Agency in Schizophrenia Influenced by Resting-State Variation in Self-Referential Regions of the Brain?

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