Quantifying the heritability of task-related brain activation and performance during the N-back working memory task: A twin fMRI study

Blokland, Gabriëlla A.M.; McMahon, Katie L.; Hoffman, Jan; Zhu, Gu; Meredith, Matthew; Martin, Nicholas G.; Thompson, Paul M.; Zubicaray, Greig I. de; Wright, Margaret J.

doi:10.1016/j.biopsycho.2008.03.006

Cited by 126 publications

(122 citation statements)

References 66 publications

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“…These data extend other recent reports that provide heritability estimates for task-based functional MRI (38)(39)(40), because default-mode connectivity is thought to index more fundamental aspects of brain function than activation evoked by cognitive demands (2,3). Given that default-mode connectivity is readily measureable in nonhuman primates (12), the current results also facilitate the use of resting-state imaging in genetic investigations with animal models.…”

Section: Discussionsupporting

confidence: 84%

Genetic control over the resting brain

Glahn

Winkler

Kochunov

et al. 2010

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

455

405

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The default-mode network, a coherent resting-state brain network, is thought to characterize basal neural activity. Aberrant defaultmode connectivity has been reported in a host of neurological and psychiatric illnesses and in persons at genetic risk for such illnesses. Whereas the neurophysiologic mechanisms that regulate defaultmode connectivity are unclear, there is growing evidence that genetic factors play a role. In this report, we estimate the importance of genetic effects on the default-mode network by examining covariation patterns in functional connectivity among 333 individuals from 29 randomly selected extended pedigrees. Heritability for default-mode functional connectivity was 0.424 ± 0.17 (P = 0.0046). Although neuroanatomic variation in this network was also heritable, the genetic factors that influence default-mode functional connectivity and gray-matter density seem to be distinct, suggesting that unique genes influence the structure and function of the network. In contrast, significant genetic correlations between regions within the network provide evidence that the same genetic factors contribute to variation in functional connectivity throughout the default mode. Specifically, the left parahippocampal region was genetically correlated with all other network regions. In addition, the posterior cingulate/precuneus region, medial prefrontal cortex, and right cerebellum seem to form a subnetwork. Default-mode functional connectivity is influenced by genetic factors that cannot be attributed to anatomic variation or a single region within the network. By establishing the heritability of default-mode functional connectivity, this experiment provides the obligatory evidence required before these measures can be considered as endophenotypes for psychiatric or neurological illnesses or to identify genes influencing intrinsic brain function.default mode | functional MRI | heritability | resting state networks

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Section: Discussionsupporting

confidence: 84%

Genetic control over the resting brain

Glahn

Winkler

Kochunov

et al. 2010

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

455

405

View full text Add to dashboard Cite

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“…In contrast to work on fMRI in hippocampus and amygdala and genetic risk for schizophrenia, previous work from our group and others has shown that excessive BOLD activation in the DLPFC for a fixed level of executive cognition is related to the genetic risk architecture of schizophrenia, constituting an intermediate biologic phenotype (Blokland et al, 2008;Callicott et al, 2003a). This phenomenon is presumed to reflect basic molecular aspects of cortical microcircuit 'tuning' or signal to noise, and has been referred to as 'cortical inefficiency' (Callicott et al, 2003b).…”

Section: Introductionmentioning

confidence: 85%

Effect of Schizophrenia Risk-Associated Alleles in SREB2 (GPR85) on Functional MRI Phenotypes in Healthy Volunteers

Radulescu¹,

Sambataro

Mattay

et al. 2012

Neuropsychopharmacol

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Genetic variants in GPR85 (SREB2: rs56080411 and rs56039557) have been associated with risk for schizophrenia. Here, we test the hypothesis that these variants impact on brain function in normal subjects, measured with functional magnetic resonance imaging (fMRI) paradigms that target regions with greatest SREB2 expression (hippocampal formation and amygdaloid complex). During a facial emotion recognition paradigm, a significant interaction of rs56080411 genotype by sex was found in the left amygdaloid complex (male risk allele carriers showed less activation than male homozygotes for the non-risk allele, while females showed the opposite pattern). During aversive encoding of an emotional memory paradigm, we found that risk allele carriers for rs56080411 had greater activation in the right inferior frontal gyrus. Trends in the same direction were present for rs56039557 in the right occipital cortex and right fusiform gyrus. During a working memory paradigm, a significant sex-by-genotype interaction was found with male risk allele carriers of rs56080411 having inefficient activation within the left dorsolateral prefrontal cortex (DLPFC), compared with same sex non-risk carriers, while females revealed an opposite pattern, despite similar levels of performance. These data suggest that risk-associated variants in SREB2 are associated with phenotypes similar to those found in patients with schizophrenia in the DLPFC and the amygdala of males, while the pattern is opposite in females. The findings in females and during the emotional memory paradigm are consistent with modulation by SREB2 of brain circuitries implicated in mood regulation and may be relevant to neuropsychiatric conditions other than schizophrenia.

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“…40,64,88 Heritability: The n-back heritability seems high, at 72.9% for accuracy and 56.4% for reaction time, as found in healthy twins. 89 State independence: Impairment in the n-back task has been reported in patients with schizophrenia at various illness stages, [90][91][92] before and after antipsychotic treatment 92 and independent of illness duration. 91 Cosegregation with illness within family: Cosegregation is suggested by evidence that this impairment is present in relatives of patients with schizophrenia, who perform better than probands.…”

Section: N-back Taskmentioning

confidence: 99%