Task-specific hypoactivation in prefrontal and temporoparietal brain regions during motor inhibition and task switching in medication-naive children and adolescents with attention deficit hyperactivity disorder.

OBJECTIVE A relatively small number of functional imaging studies of attention deficit hyperactivity disorder (ADHD) have shown abnormal prefrontal and striatal brain activation during tasks of motor response inhibition. However, the potential confound of previous medication exposure has not yet been addressed, and no functional imaging study exists to date on medication-naive children and adolescents with ADHD. The aim of this study was to investigate the neural substrates of a range of motor and cognitive inhibitory functions in a relatively large group of children and adolescents with ADHD who had never previously been exposed to medication. METHOD Nineteen boys with ADHD and 27 healthy age- and IQ-matched boys underwent functional MRI to compare brain activation during performance of tasks that assessed motor response inhibition (go/no go task), cognitive interference inhibition (motor Stroop task), and cognitive flexibility (switch task). RESULTS Boys with ADHD showed decreased activation in the left rostral mesial frontal cortex during the go/no go task and decreased activation in the bilateral prefrontal and temporal lobes and right parietal lobe during the switch task. No significant group differences were observed during motor Stroop task performance. CONCLUSION Abnormal brain activation was observed in medication-naive children and adolescents with ADHD during tasks involving motor inhibition and task switching, suggesting that hypoactivation in this patient group is unrelated to long-term stimulant exposure. Furthermore, functional abnormalities are task-specific and extend from frontostriatal to parietal and temporal cortices.

[1]  W. Horn,et al.  Sex differences in school-aged children with pervasive attention deficit hyperactivity disorder , 1989, Journal of abnormal child psychology.

[2]  K. Rubia.  The dynamic approach to neurodevelopmental psychiatric disorders: use of fMRI combined with neuropsychology to elucidate the dynamics of psychiatric disorders, exemplified in ADHD and schizophrenia , 2002, Behavioural Brain Research.

[3]  N. Meiran.  Reconfiguration of processing mode prior to task performance. , 1996 .

[4]  Jonquille Chantrey,et al.  Effect of repeated methylphenidate administration on presynaptic dopamine and behaviour in young adult rats , 2001, Journal of psychopharmacology.

[5]  Katya Rubia,et al.  Right inferior prefrontal cortex mediates response inhibition while mesial prefrontal cortex is responsible for error detection , 2003, NeuroImage.

[6]  Jin Fan,et al.  Response inhibition in adolescents diagnosed with attention deficit hyperactivity disorder during childhood: an event-related FMRI study. , 2004, The American journal of psychiatry.

[7]  P. Renshaw,et al.  Volumetric MRI analysis comparing subjects having attention-deficit hyperactivity disorder with normal controls , 1997, Neurology.

[8]  G H Glover,et al.  Selective effects of methylphenidate in attention deficit hyperactivity disorder: a functional magnetic resonance study. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[9]  R. Barkley.  Behavioral inhibition, sustained attention, and executive functions: constructing a unifying theory of ADHD. , 1997, Psychological bulletin.

[10]  D. F. Preston,et al.  SPECT Brain Imaging Abnormalities in Attention Deficit Hyperactivity Disorder , 1995, Clinical nuclear medicine.

[11]  E. Taylor,et al.  Neuropsychological analyses of impulsiveness in childhood hyperactivity , 2001, British Journal of Psychiatry.

[12]  Jagath C. Rajapakse,et al.  Quantitative Magnetic Resonance Imaging of Human Brain Development: Ages 4–18 , 1996 .

[13]  J Blumenthal,et al.  Brain Imaging of Attention Deficit/Hyperactivity Disorder , 2001, Annals of the New York Academy of Sciences.

[14]  Alan C. Evans,et al.  Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder. , 2002, JAMA.

[15]  Eric Taylor,et al.  Clinical foundations of hyperactivity research , 1998, Behavioural Brain Research.

[16]  B. J. Casey,et al.  Differential patterns of striatal activation in young children with and without ADHD , 2003, Biological Psychiatry.

[17]  T A Carpenter,et al.  Colored noise and computational inference in neurophysiological (fMRI) time series analysis: Resampling methods in time and wavelet domains , 2001, Human brain mapping.

[18]  E. Bullmore,et al.  Mapping Motor Inhibition: Conjunctive Brain Activations across Different Versions of Go/No-Go and Stop Tasks , 2001, NeuroImage.

[19]  D. Cohen,et al.  Broken brains or flawed studies? A critical review of ADHD neuroimaging research. , 2003 .

[20]  K. Tatsch,et al.  Attention deficit hyperactivity disorder: binding of [99mTc]TRODAT-1 to the dopamine transporter before and after methylphenidate treatment , 2000, European Journal of Nuclear Medicine.

[21]  M. Ernst,et al.  Neural substrates of decision making in adults with attention deficit hyperactivity disorder. , 2003, The American journal of psychiatry.

[22]  J. Raven,et al.  Manual for Raven's progressive matrices and vocabulary scales , 1962 .

[23]  Scott T. Grafton,et al.  Alterations in the functional anatomy of working memory in adult attention deficit hyperactivity disorder. , 2000, The American journal of psychiatry.

[24]  Suzanne E. Welcome,et al.  Cortical abnormalities in children and adolescents with attention-deficit hyperactivity disorder , 2003, The Lancet.

[25]  John Suckling,et al.  Global, voxel, and cluster tests, by theory and permutation, for a difference between two groups of structural MR images of the brain , 1999, IEEE Transactions on Medical Imaging.

[26]  Erik Ryding,et al.  Associations between cerebral blood‐flow measured by single photon emission computed tomography (SPECT), electro‐encephalogram (EEG), behaviour symptoms, cognition and neurological soft signs in children with attention‐deficit hyperactivity disorder (ADHD) , 2000 .

[27]  E. Bullmore,et al.  Hypofrontality in attention deficit hyperactivity disorder during higher-order motor control: a study with functional MRI. , 1999, The American journal of psychiatry.

[28]  Vinod Menon,et al.  Event-related FMRI evidence of frontotemporal involvement in aberrant response inhibition and task switching in attention-deficit/hyperactivity disorder. , 2004, Journal of the American Academy of Child and Adolescent Psychiatry.

[29]  Jaap Oosterlaan,et al.  How specific is a deficit of executive functioning for Attention-Deficit/Hyperactivity Disorder? , 2002, Behavioural Brain Research.

[30]  A M Dale,et al.  Optimal experimental design for event‐related fMRI , 1999, Human brain mapping.

[31]  M. Brammer,et al.  Neural correlates of switching set as measured in fast, event‐related functional magnetic resonance imaging , 2004, Human brain mapping.

[32]  E. Taylor,et al.  Performance of Children with Attention Deficit Hyperactivity Disorder (ADHD) on a Test Battery of Impulsiveness , 2007, Child neuropsychology : a journal on normal and abnormal development in childhood and adolescence.

[33]  Soo-Churl Cho,et al.  Regional cerebral perfusion abnormalities in attention deficit/hyperactivity disorder , 2002, European Archives of Psychiatry and Clinical Neuroscience.

[34]  Y. Miyashita,et al.  Common inhibitory mechanism in human inferior prefrontal cortex revealed by event-related functional MRI. , 1999, Brain : a journal of neurology.

[35]  R. Goodman.  The Strengths and Difficulties Questionnaire: a research note. , 1997, Journal of child psychology and psychiatry, and allied disciplines.

[36]  M. Iyo,et al.  Association of dopamine transporter loss in the orbitofrontal and dorsolateral prefrontal cortices with methamphetamine-related psychiatric symptoms. , 2003, The American journal of psychiatry.

[37]  S C Williams,et al.  Generic brain activation mapping in functional magnetic resonance imaging: a nonparametric approach. , 1997, Magnetic resonance imaging.

[38]  M. Brammer,et al.  Abnormal brain activation during inhibition and error detection in medication-naive adolescents with ADHD. , 2005, The American journal of psychiatry.

[39]  R. D. Oades,et al.  Frontal, temporal and lateralized brain function in children with attention-deficit hyperactivity disorder: a psychophysiological and neuropsychological viewpoint on development , 1998, Behavioural Brain Research.

[40]  S. Rauch,et al.  Anterior cingulate cortex dysfunction in attention-deficit/hyperactivity disorder revealed by fMRI and the counting stroop , 1999, Biological Psychiatry.