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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- Manual for the Child Behavior Checklist and Revised Profile.University of Vermont, Department of Psychiatry, Burlington, VT1983
- Diagnostic and Statistical Manual of Mental Disorders.in: 4th ed. American Psychiatric Association, Washington DC1994 (DSM-IV)
- The cognitive neuroscience of response inhibition: relevance for genetic research in attention-deficit/hyperactivity disorder.Biol Psychiatry. 2005; 57: 1285-1292
- Behavioral inhibition, sustained attention and executive functions: constructing a unifying theory of ADHD.Psychol Bull. 1997; 21: 65-94
- The functional neuroanatomical correlates of response variability: evidence from a response inhibition task.Neuropsychologia. 2004; 42: 1910-1916
- Further evidence for family-genetic risk factors in attention deficit hyperactivity disorder: Patterns of comorbidity in probands and relatives in psychiatrically and pediatrically referred samples.Arch Gen Psychiatry. 1992; 49: 728-738
- Larger deficits in brain networks for response inhibition than for visual selective attention in attention deficit hyperactivity disorder (ADHD).J Child Psychol Psychiatry. 2005; 46: 94-111
- Biological contributions to the presentation and understanding of attention-deficit/hyperactivity disorder: a review.Clin Psychol Rev. 2001; 21: 907-929
- Region of interest analysis using an SPM toolbox [abstract].NeuroImage. 2002; 16
- The feasibility of a common stereotactic space for children and adults in fMRI studies of development.Neuroimage. 2002; 17: 184-200
- Anterior cingulate cortex dysfunction in attention-deficit/hyperactivity disorder revealed by fMRI and the Counting Stroop.Biol Psychiatry. 1999; 45: 1542-1552
- A developmental functional MRI study of prefrontal activation during performance of a go-nogo task.J Cogn Neurol. 1997; 9: 835-847
- Neuroscience of attention-deficit/hyperactivity disorder: the search for endophenotypes.Nat Rev Neurosci. 2002; 3: 617-628
- A review of the biological bases of ADHD: what have we learned from imaging studies?.Ment Retard Dev Disabil Res Rev. 2003; 9: 184-195
- A shift from diffuse to focal cortical activity with development.Dev Science. 2006; 9: 1-8
- Differential effects of DRD4 and DAT1 genotype on fronto-striatal gray matter volumes in a sample of subjects with Attention Deficit Hyperactivity Disorder, their unaffected siblings and controls.Molecular Psychiatry. 2005; 10: 678-685
- Magnetic Resonance Imaging of boys with Attention Deficit Hyperactivity Disorder and their unaffected siblings.J Am Acad Child Adolesc Psychiatry. 2004; 43: 332-340
- The effect of preceding context on inhibition: An event-related fMRI study.Neuroimage. 2002; 16: 449-453
- The development of neural systems involved in overriding behavioral responses: An event-related fMRI study.Dev Science. 2002; 5: F9-F16
- Differential patterns of striatal activation young children with and without ADHD.Biol Psychiatry. 2003; 53: 871-878
- Evidence for independent transmission in families for attention deficit hyperactivity disorder (ADHD) and learning disability: results from a family genetic study of ADHD.Am J Psychiatry. 1993; 150: 891-895
- Molecular Genetics of Attention-Deficit/Hyperactivity Disorder.Biol Psychiatry. 2005; 57: 1313-1323
- Right hemispheric dominance of inhibitory control: an event-related functional MRI study.Proc Natl Acad Sci USA. 1999; 96: 8301-8306
- Frontal lobe functioning in boys with attention deficit hyperactivity disorder.J Clin Psychol. 1992; 45: 427-446
- Molecular genetic aspects of attention-deficit/hyperactivity disorder.Neurosci Biobehav Rev. 2004; 28: 625-641
- Face repetition effects in implicit and explicit memory tests as measured by fMRI.Cerebral Cortex. 2002; 12: 178-186
- Common inhibitory mechanism in human inferior prefrontal cortex revealed by event-related functional MRI.Brain. 1999; 122: 981-991
- Event-related fMRI study of response inhibition.Hum Brain Mapp. 2001; 12: 100-109
- Abnormal brain activity related to performance monitoring and error detection in children with ADHD.Cortex. 2005; 41: 377-388
- Response inhibition in AD/HD, CD, comorbid AD/HD + CD, anxious and control children: a meta-analysis of studies with the stop task.J Child Psychol Psychiatry. 1998; 39: 411-426
- Hypofrontality in attention deficit hyperactivity disorder during higher-order motor control: a study with functional MRI.Am J Psychiatry. 1999; 156: 891-896
- Functional frontalisation with age: Mapping neurodevelopmental trajectories with age.Neurosci Biobehav Rev. 2000; 24: 13-19
- Abnormal brain activation during inhibition and error detection in medication-naive adolescents with ADHD.Am J Psychiatry. 2005; 162: 1067-1075
- Deficient inhibitory control in attention deficit hyperactivity disorder.J Abnormal Child Psychol. 1995; 23: 411-437
- Response inhibition in adolescents diagnosed with attention deficit hyperactivity disorder during childhood: an event-related FMRI study.Am J Psychiatry. 2004; 161: 1650-1657
- Brain activation gradients in ventrolateral prefrontal cortex related to persistence of ADHD in adolescent boys.J Am Acad Child Adolesc Psychiatry. 2005; 44: 47-54
- Alterations in the functional anatomy of working memory in adult attention deficit hyperactivity disorder.Am J Psychiatry. 2000; 157: 278-280
- Effects of family history and comorbidity on the neuropsychological performance of children with ADHD: preliminary findings.J Am Acad Child Adolesc Psychiatry. 1995; 34: 1015-1024
- Toward defining a neuropsychology of attention deficit-hyperactivity disorder: performance of children and adolescents from a large clinically referred sample.J Consult Clin Psychol. 1997; 65: 150-160
- How specific is a deficit of executive functioning for Attention-deficit/hyperactivity disorder?.Behav Brain Res. 2002; 130: 3-28
- NIMH Diagnostic Interview Schedule for Children version IV (NIMH DISC-IV): Description, differences from previous versions, and reliability of some common diagnoses.J Am Acad Child Adolesc Psychiatry. 2000; 39: 28-38
- Event-related FMRI evidence of frontotemporal involvement in aberrant response inhibition and task switching in attention-deficit/hyperactivity disorder.J Am Acad Child Adolesc Psychiatry. 2004; 43: 1430-1440
- Selective effects of methylphenidate in attention deficit hyperactivity disorder: a functional magnetic resonance study.Proc Natl Acad Sci U S A. 1998; 95: 14494-14499
- Wechsler Intelligence Scale for Children – Revised (WISC-R).Psychological Corporation, New York1974
- Validity of the executive function theory of attention-deficit/hyperactivity disorder: a meta-analytic review.Biol Psychiatry. 2005; 57: 1336-1346
Zang YF, Jin Z, Weng XC, Zhang L, Zeng YW, Yang L (2006): Functional MRI in attention-deficit hyperactivity disorder: Evidence for hypofrontality. Brain Dev 27:544–550.
Published online: May 24, 2006
Accepted: December 6, 2005
Received in revised form: November 18, 2005
Received: September 30, 2005
© 2006 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.