Disordered Corticolimbic Interactions During Affective Processing in Children and Adolescents at Risk for Schizophrenia Revealed by Functional Magnetic Resonance Imaging and Dynamic Causal Modeling

Diwadkar, Vaibhav A.; Wadehra, Sunali; Pruitt, Patrick; Keshavan, Matcheri S.; Rajan, Usha; Zajac-Benitez, Caroline; Eickhoff, Simon B.

doi:10.1001/archgenpsychiatry.2011.1349

Cited by 59 publications

(73 citation statements)

References 89 publications

(105 reference statements)

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“…It nevertheless has proven to be more sensitive in identifying abnormal biological signatures in risk-groups, where activation analyses were not. For example, using DCM we recently documented disordered cortical–limbic endogenous connectivity and contextual modulation during an emotional appraisal task in children of schizophrenia parents (34). Notably, this finding emerged despite widespread overlap in activation networks across risk and control groups.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, we used the variational Bayes method to estimate posterior probabilities of competing models. Bayesian parameter averages of coupling estimates (with a focus on modulatory coupling) were analyzed to determine potential differences in modulation as a function of attention and statistical significance was assessed using Bonferroni correction ( p < 0.05)(32, 34). …”

Section: Methodsmentioning

confidence: 99%

“…These differences in part constitute differences in the regional specialization of function between groups. Next, using DCM (33), we investigated differences between cortical–striatal network interactions using a competitive network identification framework based on Bayesian model selection (BMS) (38) and comparisons of Bayesian parameter averages (34, 39). fMRI data were collected in children and adolescents (8 years ≤ Age < 20 years) with a family history of psychiatric illness (bipolar disorder or schizophrenia) (henceforth HGR) and controls free of such history to the second degree [henceforth typical controls (TC)].…”

Section: Introductionmentioning

confidence: 99%

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Dysfunction and Dysconnection in Corticalâ€“Striatal Networks during Sustained Attention: Genetic Risk for Schizophrenia or Bipolar Disorder and its Impact on Brain Network Function

et al. 2014

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Abnormalities in the brain’s attention network may represent early identifiable neurobiological impairments in individuals at increased risk for schizophrenia or bipolar disorder. Here, we provide evidence of dysfunctional regional and network function in adolescents at higher genetic risk for schizophrenia or bipolar disorder [henceforth higher risk (HGR)]. During fMRI, participants engaged in a sustained attention task with variable demands. The task alternated between attention (120 s), visual control (passive viewing; 120 s), and rest (20 s) epochs. Low and high demand attention conditions were created using the rapid presentation of two- or three-digit numbers. Subjects were required to detect repeated presentation of numbers. We demonstrate that the recruitment of cortical and striatal regions are disordered in HGR: relative to typical controls (TC), HGR showed lower recruitment of the dorsal prefrontal cortex, but higher recruitment of the superior parietal cortex. This imbalance was more dramatic in the basal ganglia. There, a group by task demand interaction was observed, such that increased attention demand led to increased engagement in TC, but disengagement in HGR. These activation studies were complemented by network analyses using dynamic causal modeling. Competing model architectures were assessed across a network of cortical–striatal regions, distinguished at a second level using random-effects Bayesian model selection. In the winning architecture, HGR were characterized by significant reductions in coupling across both frontal–striatal and frontal–parietal pathways. The effective connectivity analyses indicate emergent network dysconnection, consistent with findings in patients with schizophrenia. Emergent patterns of regional dysfunction and dysconnection in cortical–striatal pathways may provide functional biological signatures in the adolescent risk-state for psychiatric illness.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Dysfunction and Dysconnection in Corticalâ€“Striatal Networks during Sustained Attention: Genetic Risk for Schizophrenia or Bipolar Disorder and its Impact on Brain Network Function

et al. 2014

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“…Here, increased connectivity has been consistently found in risk variant carriers of the COMT and MIR137 genes [43,44], however this alteration has not been reported in patients or relatives. To date the only positive connectivity finding for emotion processing that has been identified in schizophrenia relatives is derived from a DCM analysis, where the authors revealed a decreased driving input to the visual cortex and an increased modulatory inhibition between the limbic cortex and the PFC, suggesting a potential DCM-based intermediate phenotype for schizophrenia [45 ]. This observation raises the possibility that different functional connectivity measures may not be equally suitable for the detection of intermediate phenotypes across different task domains.…”

Section: Emotion Processingmentioning

confidence: 99%

Functional connectivity measures as schizophrenia intermediate phenotypes: advances, limitations, and future directions

Cao

Dixson

Meyer‐Lindenberg

et al. 2016

Current Opinion in Neurobiology

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“…Effective connectivity is noted as the most parsimonious “circuit diagram” replicating the observed dynamic relationships between acquired biological signals (102). Recent evidence suggests reduced effective thalamocortical (54) and frontal–limbic (103) effective connectivity in genetic risk groups. These and other studies establish a pattern of general brain network dysfunction in adolescents at genetic risk for schizophrenia, suggesting that dysfunction in cortical networks is a plausible “end-point” in a cascade of genetic and neurodevelopmental events.…”

Section: Brain Network Dysfunction In the Adolescent Risk State For Smentioning

confidence: 99%

Epigenetics, Stress, and Their Potential Impact on Brain Network Function: A Focus on the Schizophrenia Diatheses

et al. 2014

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The recent sociodevelopmental cognitive model of schizophrenia/psychosis is a highly influential and compelling compendium of research findings. Here, we present logical extensions to this model incorporating ideas drawn from epigenetic mediation of psychiatric disease, and the plausible effects of epigenetics on the emergence of brain network function and dysfunction in adolescence. We discuss how gene–environment interactions, effected by epigenetic mechanisms, might in particular mediate the stress response (itself heavily implicated in the emergence of schizophrenia). Next, we discuss the plausible relevance of this framework for adolescent genetic risk populations, a risk group characterized by vexing and difficult-to-explain heterogeneity. We then discuss how exploring relationships between epigenetics and brain network dysfunction (a strongly validated finding in risk populations) can enhance understanding of the relationship between stress, epigenetics, and functional neurobiology, and the relevance of this relationship for the eventual emergence of schizophrenia/psychosis. We suggest that these considerations can expand the impact of models such as the sociodevelopmental cognitive model, increasing their explanatory reach. Ultimately, integration of these lines of research may enhance efforts of early identification, intervention, and treatment in adolescents at-risk for schizophrenia.

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Disordered Corticolimbic Interactions During Affective Processing in Children and Adolescents at Risk for Schizophrenia Revealed by Functional Magnetic Resonance Imaging and Dynamic Causal Modeling

Cited by 59 publications

References 89 publications

Dysfunction and Dysconnection in Corticalâ€“Striatal Networks during Sustained Attention: Genetic Risk for Schizophrenia or Bipolar Disorder and its Impact on Brain Network Function

Dysfunction and Dysconnection in Corticalâ€“Striatal Networks during Sustained Attention: Genetic Risk for Schizophrenia or Bipolar Disorder and its Impact on Brain Network Function

Functional connectivity measures as schizophrenia intermediate phenotypes: advances, limitations, and future directions

Epigenetics, Stress, and Their Potential Impact on Brain Network Function: A Focus on the Schizophrenia Diatheses

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