Dissociated functional brain abnormalities of inhibition in boys with pure conduct disorder and in boys with pure attention deficit hyperactivity disorder.

OBJECTIVE Inhibitory dysfunction may be a transdiagnostic etiopathophysiology of disruptive behavior disorders. Functional magnetic resonance imaging (fMRI) of inhibitory control has only been investigated in patients with attention deficit hyperactivity disorder (ADHD), including comorbidity with conduct disorder, showing frontal-striatal dysfunction. This study investigates differences and commonalities in functional neural networks mediating inhibitory control between medication-naive adolescents with pure conduct disorder and those with pure ADHD to identify biological markers that distinguish these clinically overlapping disorders. METHOD Event-related fMRI was used to compare brain activation of 13 boys with noncomorbid conduct disorder, 20 with noncomorbid ADHD, and 20 normal boys during an individually adjusted tracking stop task that measures the neural substrates of inhibition and stopping failure. RESULTS During successful inhibition, only patients with ADHD showed reduced activation in the left dorsolateral prefrontal cortex in relation to comparison subjects and patients with conduct disorder. During inhibition failures compared to go responses, both patient groups shared underactivation in the posterior cingulate gyrus in relation to comparison subjects. Patients with conduct disorder showed reduced activation in bilateral temporal-parietal regions compared to the other groups, which did not differ in this measure. CONCLUSIONS Patients with pure ADHD or pure conduct disorder show qualitative differences in their brain abnormality patterns during inhibitory control. Inhibition-mediating prefrontal regions appear to be specifically reduced in ADHD, whereas posterior temporal-parietal, performance monitoring networks are specifically dysfunctional in conduct disorder. The findings provide pioneering evidence that distinct neurobiological abnormalities may be underlying the overlapping behavioral phenotype of the two disruptive disorders.

[1]  B. J. Casey,et al.  Activation in Ventral Prefrontal Cortex is Sensitive to Genetic Vulnerability for Attention-Deficit Hyperactivity Disorder , 2006, Biological Psychiatry.

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

[3]  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.

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

[5]  H. Engeland,et al.  Response perseveration and sensitivity to reward and punishment in boys with oppositional defiant disorder , 2004, European Child & Adolescent Psychiatry.

[6]  Erik Willcutt,et al.  Towards an understanding of unique and shared pathways in the psychopathophysiology of ADHD. , 2005, Developmental science.

[7]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[8]  R. Blair,et al.  Neurocognitive models of aggression, the antisocial personality disorders, and psychopathy , 2001, Journal of neurology, neurosurgery, and psychiatry.

[9]  M. Brammer,et al.  Progressive increase of frontostriatal brain activation from childhood to adulthood during event‐related tasks of cognitive control , 2006, Human brain mapping.

[10]  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.

[11]  Daniel S Pine,et al.  Neural circuitry engaged during unsuccessful motor inhibition in pediatric bipolar disorder. , 2007, The American journal of psychiatry.

[12]  E. Bullmore,et al.  Functional frontalisation with age: mapping neurodevelopmental trajectories with fMRI , 2000, Neuroscience & Biobehavioral Reviews.

[13]  A. Nobre,et al.  Heterogeneity of Cingulate Contributions to Spatial Attention , 2001, NeuroImage.

[14]  P. Fenwick,et al.  The Aetiology of Aggression in Temporal-Lobe Epilepsy , 1988, British Journal of Psychiatry.

[15]  Yufeng Zang,et al.  Abnormal neural activity in children with attention deficit hyperactivity disorder: a resting-state functional magnetic resonance imaging study , 2006, Neuroreport.

[16]  H. van Engeland,et al.  Executive functioning in children: a comparison of hospitalised ODD and ODD/ADHD children and normal controls. , 2004, Journal of child psychology and psychiatry, and allied disciplines.

[17]  M. Garralda.  The Epidemiology of Childhood Hyperactivity , 1992 .

[18]  V. Hesselbrock,et al.  Subtypes of Family History and Conduct Disorder: Effects on P300 During the Stroop Test , 1999, Neuropsychopharmacology.

[19]  Michael P Milham,et al.  The neural correlates of attention deficit hyperactivity disorder: an ALE meta-analysis. , 2006, Journal of child psychology and psychiatry, and allied disciplines.

[20]  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.

[21]  Michael J. Brammer,et al.  Temporal Lobe Dysfunction in Medication-Naïve Boys With Attention-Deficit/Hyperactivity Disorder During Attention Allocation and Its Relation to Response Variability , 2007, Biological Psychiatry.

[22]  Wei Li,et al.  Larger deficits in brain networks for response inhibition than for visual selective attention in attention deficit hyperactivity disorder (ADHD). , 2005, Journal of child psychology and psychiatry, and allied disciplines.

[23]  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.

[24]  T. Banaschewski,et al.  Questioning inhibitory control as the specific deficit of ADHD – evidence from brain electrical activity , 2004, Journal of Neural Transmission.

[25]  G D Logan,et al.  Response inhibition in AD/HD, CD, comorbid AD/HD + CD, anxious, and control children: a meta-analysis of studies with the stop task. , 1998, Journal of child psychology and psychiatry, and allied disciplines.

[26]  Jinhu Xiong,et al.  Neuroimaging of inhibitory control areas in children with attention deficit hyperactivity disorder who were treatment naive or in long-term treatment. , 2006, The American journal of psychiatry.

[27]  A. Scheres,et al.  Response Inhibition and Measures of Psychopathology: A Dimensional Analysis , 2000, Child neuropsychology : a journal on normal and abnormal development in childhood and adolescence.

[28]  Aribert Rothenberger,et al.  Association of ADHD and conduct disorder--brain electrical evidence for the existence of a distinct subtype. , 2003, Journal of child psychology and psychiatry, and allied disciplines.

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

[30]  Manuel F. Casanova,et al.  Reduced temporal lobe volume in early onset conduct disorder , 2004, Psychiatry Research: Neuroimaging.

[31]  K. Rubia,et al.  Conduct Problems in Adolescence: Three Domains of Inhibition and Effect of Gender , 2006, Developmental neuropsychology.

[32]  Y. Zang,et al.  Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI , 2007, Brain and Development.

[33]  Philipp Sterzer,et al.  Abnormal neural responses to emotional visual stimuli in adolescents with conduct disorder , 2005, Biological Psychiatry.

[34]  M. Brammer,et al.  Linear age‐correlated functional development of right inferior fronto‐striato‐cerebellar networks during response inhibition and anterior cingulate during error‐related processes , 2007, Human brain mapping.

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

[36]  Brian Toone,et al.  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. , 2006, The American journal of psychiatry.

[37]  E. Taylor,et al.  Attention-deficit hyperactivity disorder and hyperkinetic disorder , 1998, The Lancet.