Activation in Ventral Prefrontal Cortex is Sensitive to Genetic Vulnerability for Attention-Deficit Hyperactivity Disorder

Rudolf Magnus Institute of Neuroscience, Department of Child and Adolescent Psychiatry, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
Biological Psychiatry (Impact Factor: 10.26). 12/2006; 60(10):1062-70. DOI: 10.1016/j.biopsych.2005.12.020
Source: PubMed


Attention-deficit hyperactivity disorder (ADHD) is a heritable neuropsychiatric disorder, associated with atypical patterns of brain activation in functional imaging studies. Neuroimaging measures may serve as an intermediate phenotype in genetic studies of ADHD, as they are putatively more closely linked to gene expression than a clinical diagnosis.
We used rapid, mixed-trial, event-related functional magnetic resonance imaging (fMRI) to investigate changes in brain activation during a go no-go task in boys with ADHD, their unaffected siblings, and matched control subjects.
On the hardest inhibitory trials in our task, children and adolescents with ADHD had lower accuracy than control subjects, whereas their unaffected siblings did not. Control subjects activated a network of regions, including ventral prefrontal and inferior parietal cortex. Both children and adolescents with ADHD and their unaffected siblings showed decreased activation in these areas, as well as fewer correlations between performance and activation.
These findings suggest that the magnitude of activation during successful inhibitions is sensitive to genetic vulnerability for ADHD in a number of regions, including ventral prefrontal cortex. If this can be replicated in future studies, this suggests that neuroimaging measures related to inhibitory control may be suitable as intermediate phenotypes in studies investigating gene effects in ADHD.

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    • "in progress that takes this approach ) , and all have been with children and ado - lescents . Those studies show familial effects such that siblings who did not meet diagnostic criteria for ADHD showed reduced activity compared to unrelated controls in the ACC and ventrolateral pre - frontal cortex , as well as the parietal cortex and cerebellum ( Durston et al . , 2006 ; Mulder et al . , 2008 ) . These studies used performance of a go / no - go task , which is often used to measure inhibitory aspects of executive control ."
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    • "Lower connectivity between M1 and the frontal eye fields, areas associated with visual attention ( Schall, 2004 ), and the left postcentral gyrus, a key component of the neural network involved in working memory ( du Boisgueheneuc et al., 2006 ), could be linked to deficits in visual attention and working memory observed in children with ADHD ( Martinussen et al., 2005 ; Swanson et al., 1991 ). Decreased FC in the inferior frontal gyri could play a part in the motor inhibition difficulties associated with ADHD ( Cao et al., 2006 ; Zang et al., 2007 ), which is further supported by previous task-related fMRI studies ( Booth et al., 2005 ; Durston et al., 2006 ; Liakakis et al., 2011 ). Previous imaging research has reported reduced grey matter volume of the left insular cortex in children with ADHD ( Brieber et al., 2007 ). "
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