title: Genetic effects on the cerebellar role in working memory: same brain, different genes?
abstract: Over the past several years, evidence has accumulated showing that the cerebellum plays a significant role in cognitive function. Here we show, in a large genetically informative twin sample (n=430; aged 16-30years), that the cerebellum is strongly, and reliably (n=30 rescans), activated during an n-back working memory task, particularly lobules I-IV, VIIa Crus I and II, IX and the vermis. Monozygotic twin correlations for cerebellar activation were generally much larger than dizygotic twin correlations, consistent with genetic influences. Structural equation models showed that up to 65% of the variance in cerebellar activation during working memory is genetic (averaging 34% across significant voxels), most prominently in the lobules VI, and VIIa Crus I, with the remaining variance explained by unique/unshared environmental factors. Heritability estimates for brain activation in the cerebellum agree with those found for working memory activation in the cerebral cortex, even though cerebellar cyto-architecture differs substantially. Phenotypic correlations between BOLD percent signal change in cerebrum and cerebellum were low, and bivariate modeling indicated that genetic influences on the cerebellum are at least partly specific to the cerebellum. Activation on the voxel-level correlated very weakly with cerebellar gray matter volume, suggesting specific genetic influences on the BOLD signal. Heritable signals identified here should facilitate discovery of genetic polymorphisms influencing cerebellar function through genome-wide association studies, to elucidate the genetic liability to brain disorders affecting the cerebellum.
authors.affiliation: Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Australia; Centre for Advanced Imaging, University of Queensland, Brisbane, Australia; School of Psychology, University of Queensland, Brisbane, Australia. Electronic address: gabriella.blokland@uqconnect.edu.au.
authors.forename: Gabriëlla A M
authors.initials: GA
authors.lastname: Blokland
authors.affiliation: Centre for Advanced Imaging, University of Queensland, Brisbane, Australia.
authors.forename: Katie L
authors.initials: KL
authors.lastname: McMahon
authors.affiliation: Laboratory of Neuro Imaging, Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Thompson
authors.affiliation: Brain & Mind Research Institute, The University of Sydney, Sydney, Australia.
authors.forename: Ian B
authors.initials: IB
authors.lastname: Hickie
authors.affiliation: Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Australia.
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.affiliation: School of Psychology, University of Queensland, Brisbane, Australia.
authors.forename: Greig I
authors.initials: GI
authors.lastname: de Zubicaray
authors.affiliation: Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Australia; School of Psychology, University of Queensland, Brisbane, Australia.
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Wright
mesh_terms: D000293:Adolescent; D000328:Adult; D002531:Cerebellum / Q000502:physiology*; D005260:Female; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology*; D009415:Nerve Net / Q000502:physiology*; D014427:Twins / Q000235:genetics*; D055815:Young Adult
keywords: Cerebellum; Functional MRI; Genetics; Heritability; Twin study; Working memory