Identifying large-scale brain networks in fragile X syndrome.
OBJECTIVE
Fragile X syndrome (FXS) is an X-linked neurogenetic disorder characterized by a cognitive and behavioral phenotype resembling features of autism spectrum disorder. Until now, research has focused largely on identifying regional differences in brain structure and function between individuals with FXS and various control groups. Very little is known about the large-scale brain networks that may underlie the cognitive and behavioral symptoms of FXS.


OBJECTIVE
To identify large-scale, resting-state networks in FXS that differ from control individuals matched on age, IQ, and severity of behavioral and cognitive symptoms.


METHODS
Cross-sectional, in vivo neuroimaging study conducted in an academic medical center. Participants (aged 10-23 years) included 17 males and females with FXS and 16 males and females serving as controls.


METHODS
Univariate voxel-based morphometric analyses, fractional amplitude of low-frequency fluctuations (fALFF) analysis, and group-independent component analysis with dual regression.


RESULTS
Patients with FXS showed decreased functional connectivity in the salience, precuneus, left executive control, language, and visuospatial networks compared with controls. Decreased fALFF in the bilateral insular, precuneus, and anterior cingulate cortices also was found in patients with FXS compared with control participants. Furthermore, fALFF in the left insular cortex was significantly positively correlated with IQ in patients with FXS. Decreased gray matter density, resting-state connectivity, and fALFF converged in the left insular cortex in patients with FXS.


CONCLUSIONS
Fragile X syndrome results in widespread reductions in functional connectivity across multiple cognitive and affective brain networks. Converging structural and functional abnormalities in the left insular cortex, a region also implicated in individuals diagnosed with autism spectrum disorder, suggests that insula integrity and connectivity may be compromised in FXS. This method could prove useful in establishing an imaging biomarker for FXS.
Center for Interdisciplinary Brain Sciences Research, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California.
Scott S
SS
Hall
Heidi
H
Jiang
Allan L
AL
Reiss
Michael D
MD
Greicius
D000293:Adolescent; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology; D002648:Child; D005260:Female; D005600:Fragile X Syndrome / Q000473:pathology / Q000503:physiopathology*; D059907:Functional Neuroimaging; D006801:Humans; D007360:Intelligence / Q000502:physiology; D008297:Male; D036421:Nerve Fibers, Unmyelinated / Q000473:pathology; D009434:Neural Pathways / Q000503:physiopathology; D059906:Neuroimaging; D055815:Young Adult