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.

The Phenotypic Profile Associated With the FMR1 Premutation in Women: An Investigation of Clinical-Behavioral, Social-Cognitive, and Executive Abilities

“…Characterization of the cognitive phenotype associated with the PM is especially important for understanding the manifestation of the neurodegenerative disorder, FXTAS, which may reveal subclinical phenotypic markers that are evident in a subgroup of PM carriers who go on to develop the disorder, as dysexecutive symptoms are a hallmark of FXTAS, particularly in males (114). Nonetheless, females with the PM exhibit differences in EF symptoms even without a diagnosis of FXTAS (68,69,115,116). This study highlights the value of using self-report measures of EF in studies of the PM, as prior work has typically used online behavioral measures [e.g., see (113) for review].…”

Language processing skills linked to FMR1 variation: A study of gaze-language coordination during rapid automatized naming among women with the FMR1 premutation

“…While multiple areas of the brain are typically recruited during RAN, including executive, language, and motor networks, individuals with the PM may primarily utilize neural circuits supported by the language network, implicating reduced long-range connectivity and communication, which has previously been observed in the PM [61, 105, 106]. A similarly divergent profile has recently been reported between women with the PM and controls during an antisaccade task, where the relationship to underlying neural networks differed for these groups [59]. Further, differences in language dysfluencies but not in inhibition (a key executive skill) have also been reported among women with the PM [107].…”