title: Fronto-striatal dysfunction and potential compensatory mechanisms in male adolescents with fragile X syndrome.
abstract: Response inhibition is an important facet of executive function. Fragile X syndrome (FraX), with a known genetic etiology (fragile X mental retardation-1 (FMR1) mutation) and deficits in response inhibition, may be an ideal condition for elucidating interactions among gene-brain-behavior relationships. Functional magnetic resonance imaging (fMRI) studies have shown evidence of aberrant neural activity when individuals with FraX perform executive function tasks, though the specific nature of this altered activity or possible compensatory processes has yet to be elucidated. To address this question, we examined brain activation patterns using fMRI during a go/nogo task in adolescent males with FraX and in controls. The critical comparison was made between FraX individuals and age, gender, and intelligent quotient (IQ)-matched developmentally delayed controls; in addition to a control group of age and gender-matched typically developing individuals. The FraX group showed reduced activation in the right ventrolateral prefrontal cortex (VLPFC) and right caudate head, and increased contralateral (left) VLPFC activation compared with both control groups. Individuals with FraX, but not controls, showed a significant positive correlation between task performance and activation in the left VLPFC. This potential compensatory activation was predicted by the interaction between FMR1 protein (FMRP) levels and right striatal dysfunction. These results suggest that right fronto-striatal dysfunction is likely an identifiable neuro-phenotypic feature of FraX and that activation of the left VLPFC during successful response inhibition may reflect compensatory processes. We further show that these putative compensatory processes can be predicted by a complex interaction between genetic risk and neural function.
authors: Center for Interdisciplinary Brain Sciences Research (CIBSR), Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, USA. fumiko@stanford.edu
authors: Fumiko
authors: F
authors: Hoeft
authors: Arvel
authors: A
authors: Hernandez
authors: Sudharshan
authors: S
authors: Parthasarathy
authors: Christa L
authors: CL
authors: Watson
authors: Scott S
authors: SS
authors: Hall
authors: Allan L
authors: AL
authors: Reiss
mesh_terms: D000293:Adolescent; D000344:Afferent Pathways / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D000704:Analysis of Variance; D001931:Brain Mapping; D003342:Corpus Striatum / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology*; D005600:Fragile X Syndrome / Q000473:pathology* / Q000503:physiopathology*; D005625:Frontal Lobe / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology*; D007839:Functional Laterality; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007360:Intelligence / Q000502:physiology; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008606:Mental Processes / Q000502:physiology*; D008954:Models, Biological; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D011930:Reaction Time / Q000502:physiology
chemical_list: D010100:Oxygen