Frontostriatal dysfunction during response inhibition in Williams syndrome.
BACKGROUND
Williams syndrome (WS) has provided researchers with an exciting opportunity to understand the complex interplay among genes, neurobiological and cognitive functions. However, despite a well-characterized cognitive and behavioral phenotype, little attention has been paid to the marked deficits in social and behavioral inhibition. Here we explore the neural systems that mediate response inhibition in WS.


METHODS
We used functional MRI (fMRI) to obtain blood oxygenation level dependence (BOLD) signal maps during the performance of a Go/NoGo response inhibition task from 11 clinically and genetically diagnosed WS patients and 11 age- and gender-matched typically developing (TD) control subjects. Correlations between behavioral, neuropsychological measures, and BOLD signal were also conducted.


RESULTS
Although TD control subjects showed significantly faster response times, no group differences in behavioral accuracy were observed. Compared with control subjects, WS participants demonstrated significantly reduced activity in the striatum, dorsolateral prefrontal, and dorsal anterior cingulate cortices. These findings support the hypothesis that persons with WS fail to activate critical cortical and subcortical structures involved in behavioral inhibition.


CONCLUSIONS
Our results provide important evidence for reduced engagement of the frontostriatal circuits in WS and provide putative biological markers for the deficits in response inhibition and the unusual social phenotype.
Mobbs
Dean
D
Center for Interdisciplinary Brain Sciences Research, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California 94305-5719, USA.
Eckert
Mark A
MA
Mills
Debra
D
Korenberg
Julie
J
Bellugi
Ursula
U
Galaburda
Albert M
AM
Reiss
Allan L
AL
D000293:Adolescent; D000328:Adult; D001288:Attention / Q000502:physiology; D001931:Brain Mapping; D016022:Case-Control Studies; D004193:Discrimination Learning / Q000502:physiology*; D005260:Female; D005625:Frontal Lobe / Q000502:physiology / Q000503:physiopathology*; D006801:Humans; D007266:Inhibition, Psychological; D008279:Magnetic Resonance Imaging; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D017072:Neostriatum / Q000502:physiology / Q000503:physiopathology*; D009433:Neural Inhibition / Q000502:physiology; D009434:Neural Pathways / Q000502:physiology / Q000503:physiopathology; D011930:Reaction Time / Q000502:physiology; D012016:Reference Values; D018980:Williams Syndrome / Q000503:physiopathology*