Visuospatial working memory in children and adolescents with 22q11.2 deletion syndrome; an fMRI study

Rayna Azuma,Fiona Z Ambery,Vincent Giampietro,Michael J Brammer,Beate Glaser,Declan G M Murphy,Robin G Morris,Quinton Deeley,Michael J Owen,Linda E Campbell,Kieran C Murphy,Steven C R Williams,Angela F Stevens,Eileen M Daly

doi:10.1007/s11689-009-9008-9

Abstract

22q11.2 deletion syndrome (22q11DS) is a genetic disorder associated with a microdeletion of chromosome 22q11. In addition to high rates of neuropsychiatric disorders such as schizophrenia and attention deficit hyperactivity disorder, children with 22q11DS have a specific neuropsychological profile with particular deficits in visuospatial and working memory. However, the neurobiological substrate underlying these deficits is poorly understood. We investigated brain function during a visuospatial working memory (SWM) task in eight children with 22q11DS and 13 healthy controls, using fMRI. Both groups showed task-related activation in dorsolateral prefrontal cortex (DLPFC) and bilateral parietal association cortices. Controls activated parietal and occipital regions significantly more than those with 22q11DS but there was no significant between-group difference in DLPFC. In addition, while controls had a significant age-related increase in the activation of posterior brain regions and an age-related decrease in anterior regions, the 22q11DS children showed the opposite pattern. Genetically determined differences in the development of specific brain systems may underpin the cognitive deficits in 22q11DS, and may contribute to the later development of neuropsychiatric disorders.

Highlights

22q11.2 deletion syndrome (22q11DS) is a genetic disorder associated with a microdeletion of chromosome 22q11
The 22q11DS volunteers were recruited through the 22q11 (UK) Support group and the Behavioural Genetics Clinic at the Maudsley Hospital/Institute of Psychiatry, Kings College London. 22q11DS was diagnosed by fluorescence in-situ hybridisation (FISH) using the N25 probe (Oncor Inc)
Task performance was assessed as the percentage of correct responses for the spatial working memory (SWM) task

Summary

Introduction

22q11.2 deletion syndrome (22q11DS) is a genetic disorder associated with a microdeletion of chromosome 22q11. In addition to high rates of neuropsychiatric disorders such as schizophrenia and attention deficit hyperactivity. Psychological Medicine, Institute of Psychiatry, King’s College London, Section of Brain Maturation (PO50), DeCrespigny Park, London SE5 8AF, UK. Campbell Centre for Brain and Mental Health Research, University of Newcastle, Officers Quarters Complex, James Fletcher Hospital, Newcomen Street, Newcastle NSW 2300, Australia disorder, children with 22q11DS have a specific neuropsychological profile with particular deficits in visuospatial and working memory. The neurobiological substrate underlying these deficits is poorly understood. Brain Image Analysis Unit, Institute of Psychiatry, King’s College London, Department of Biostatistics & Computing (PO22), DeCrespigny Park, London SE5 8AF, UK

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