title: Disassociation between brain activation and executive function in fragile X premutation females.
abstract: Executive dysfunction has been demonstrated among premutation (PM) carriers (55-199 CGG repeats) of the Fragile X mental retardation 1 (FMR1) gene. Further, alterations to neural activation patterns have been reported during memory and comparison based functional magnetic resonance imaging (fMRI) tasks in these carriers. For the first time, the relationships between fMRI neural activation during an interleaved ocular motor prosaccade/antisaccade paradigm, and concurrent task performance (saccade measures of latency, accuracy and error rate) in PM females were examined. Although no differences were found in whole brain activation patterns, regions of interest (ROI) analyses revealed reduced activation in the right ventrolateral prefrontal cortex (VLPFC) during antisaccade trials for PM females. Further, a series of divergent and group specific relationships were found between ROI activation and saccade measures. Specifically, for control females, activation within the right VLPFC and supramarginal gyrus correlated negatively with antisaccade latencies, while for PM females, activation within these regions was found to negatively correlate with antisaccade accuracy and error rate (right VLPFC only). For control females, activation within frontal and supplementary eye fields and bilateral intraparietal sulci correlated with prosaccade latency and accuracy; however, no significant prosaccade correlations were found for PM females. This exploratory study extends previous reports of altered prefrontal neural engagement in PM carriers, and clearly demonstrates dissociation between control and PM females in the transformation of neural activation into overt measures of executive dysfunction. Hum Brain Mapp 38:1056-1067, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: School of Psychological Sciences and Monash Institute of Cognitive and Clinical Neurosciences, Monash University, Melbourne, Victoria, Australia.
authors.forename: Annie L
authors.initials: AL
authors.lastname: Shelton
authors.affiliation: School of Psychological Sciences and Monash Institute of Cognitive and Clinical Neurosciences, Monash University, Melbourne, Victoria, Australia.
authors.forename: Kim
authors.initials: K
authors.lastname: Cornish
authors.affiliation: School of Psychological Sciences and Monash Institute of Cognitive and Clinical Neurosciences, Monash University, Melbourne, Victoria, Australia.
authors.forename: Meaghan
authors.initials: M
authors.lastname: Clough
authors.affiliation: Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Sanuji
authors.initials: S
authors.lastname: Gajamange
authors.affiliation: Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Scott
authors.initials: S
authors.lastname: Kolbe
authors.affiliation: School of Psychological Sciences and Monash Institute of Cognitive and Clinical Neurosciences, Monash University, Melbourne, Victoria, Australia.|Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Joanne
authors.initials: J
authors.lastname: Fielding
mesh_terms: D000328:Adult; D001931:Brain Mapping; D003072:Cognition Disorders / Q000209:etiology*; D056344:Executive Function / Q000502:physiology*; D005133:Eye Movements / Q000502:physiology; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics; D005600:Fragile X Syndrome / Q000150:complications* / Q000235:genetics / Q000473:pathology*; D007839:Functional Laterality; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D009483:Neuropsychological Tests; D010100:Oxygen; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000503:physiopathology; D011930:Reaction Time / Q000235:genetics; D012044:Regression Analysis; D055815:Young Adult
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D010100:Oxygen
keywords: FMR1; executive function; fMRI; fragile X; ocular motor