Hyperactivity in motor response inhibition networks in unmedicated children with attention deficit-hyperactivity disorder

Abstract Objectives: Hypo/reduced activity in motor response inhibition (RI) cerebral networks was recently proposed as a promising specific neurobiological marker of attention deficit-hyperactivity disorder (ADHD). Before adopting such a pattern as a key diagnosis tool, we aim to replicate in an independent study the mechanisms underlying reduced RI-related activity in ADHD, after controlling for potentially confounding effects. Methods: In this fMRI study, we investigated the neural networks mediating successful and failed motor RI in children with ADHD and typically developing children (TDC) using the stop-signal task (SST) paradigm. Results: In contrast to hypofrontality predictions, children with ADHD exhibit increased neural activity during successful response inhibition in an RI-related brain network encompassing the indirect and/or hyperdirect pathways between the basal ganglia and cortex. Voxel-based morphometry analyses have further evidenced reduced grey matter volume in the left caudate in children with ADHD, which paralleled higher functional responses. Finally, connectivity analyses disclosed tighter coupling between a set of cortical regions and the right caudate as well as the right IFG, networks involved in successful RI. Conclusions: Hypo/reduced activity in RI cerebral networks in children with ADHD cannot at this time be considered as a systematic biomarker for ADHD.

[1]  G. Logan,et al.  Neural correlates of response inhibition in children with attention-deficit/hyperactivity disorder: A controlled version of the stop-signal task , 2015, Psychiatry Research: Neuroimaging.

[2]  Xiaoqi Huang,et al.  Functional MRI reveals different response inhibition between adults and children with ADHD. , 2015, Neuropsychology.

[3]  Hyoung F. Kim,et al.  Basal ganglia circuits for reward value-guided behavior. , 2014, Annual review of neuroscience.

[4]  Michael M. Plichta,et al.  Sequential inhibitory control processes assessed through simultaneous EEG–fMRI , 2014, NeuroImage.

[5]  M. Chakravarty,et al.  Mapping the development of the basal ganglia in children with attention-deficit/hyperactivity disorder. , 2014, Journal of the American Academy of Child and Adolescent Psychiatry.

[6]  T. Robbins,et al.  Inhibition and the right inferior frontal cortex: one decade on , 2014, Trends in Cognitive Sciences.

[7]  D. Jean,et al.  Random-effect analysis. , 2014 .

[8]  G. Salum,et al.  ADHD prevalence estimates across three decades: an updated systematic review and meta-regression analysis. , 2013, International journal of epidemiology.

[9]  Deanna Greenstein,et al.  Trajectories of Cerebral Cortical Development in Childhood and Adolescence and Adult Attention-Deficit/Hyperactivity Disorder , 2013, Biological Psychiatry.

[10]  Andrew Simmons,et al.  Pattern classification of response inhibition in ADHD: Toward the development of neurobiological markers for ADHD , 2013, Human brain mapping.

[11]  Daniel K. Leventhal,et al.  Canceling actions involves a race between basal ganglia pathways , 2013, Nature Neuroscience.

[12]  N. Skokauskas,et al.  Identifying a consistent pattern of neural function in attention deficit hyperactivity disorder: a meta-analysis , 2013, Psychological Medicine.

[13]  H. Hart,et al.  Meta-analysis of functional magnetic resonance imaging studies of inhibition and attention in attention-deficit/hyperactivity disorder: exploring task-specific, stimulant medication, and age effects. , 2013, JAMA psychiatry.

[14]  Michael P Milham,et al.  Toward systems neuroscience of ADHD: a meta-analysis of 55 fMRI studies. , 2012, The American journal of psychiatry.

[15]  R. Halari,et al.  A review of fronto-striatal and fronto-cortical brain abnormalities in children and adults with Attention Deficit Hyperactivity Disorder (ADHD) and new evidence for dysfunction in adults with ADHD during motivation and attention , 2012, Cortex.

[16]  N. Skokauskas,et al.  Meta‐analysis of structural MRI studies in children and adults with attention deficit hyperactivity disorder indicates treatment effects , 2012, Acta psychiatrica Scandinavica.

[17]  Katya Rubia,et al.  Gray matter volume abnormalities in ADHD: voxel-based meta-analysis exploring the effects of age and stimulant medication. , 2011, The American journal of psychiatry.

[18]  Stewart H Mostofsky,et al.  Variability in post-error behavioral adjustment is associated with functional abnormalities in the temporal cortex in children with ADHD. , 2011, Journal of child psychology and psychiatry, and allied disciplines.

[19]  A. Aron.  From Reactive to Proactive and Selective Control: Developing a Richer Model for Stopping Inappropriate Responses , 2011, Biological Psychiatry.

[20]  S. Mostofsky,et al.  A Preliminary Neuroimaging Study of Preschool Children with ADHD , 2011, The Clinical neuropsychologist.

[21]  M. Brammer,et al.  Disorder‐specific dysfunctions in patients with attention‐deficit/hyperactivity disorder compared to patients with obsessive‐compulsive disorder during interference inhibition and attention allocation , 2011, Human brain mapping.

[22]  Rozmin Halari,et al.  Disorder‐specific inferior prefrontal hypofunction in boys with pure attention‐deficit/hyperactivity disorder compared to boys with pure conduct disorder during cognitive flexibility , 2010, Human brain mapping.

[23]  M. Vink,et al.  On the Role of the Striatum in Response Inhibition , 2010, PloS one.

[24]  Carsten Nicolas Boehler,et al.  Pinning down response inhibition in the brain — Conjunction analyses of the Stop-signal task , 2010, NeuroImage.

[25]  B. Peterson,et al.  Basal ganglia surface morphology and the effects of stimulant medications in youth with attention deficit hyperactivity disorder. , 2010, The American journal of psychiatry.

[26]  C. Mulert,et al.  Neural correlates (ERP/fMRI) of voluntary selection in adult ADHD patients , 2010, European Archives of Psychiatry and Clinical Neuroscience.

[27]  Vincent Giampietro,et al.  Reduced activation and inter-regional functional connectivity of fronto-striatal networks in adults with childhood Attention-Deficit Hyperactivity Disorder (ADHD) and persisting symptoms during tasks of motor inhibition and cognitive switching. , 2010, Journal of psychiatric research.

[28]  J. Chikazoe.  Localizing performance of go/no-go tasks to prefrontal cortical subregions , 2010, Current opinion in psychiatry.

[29]  C. Lebiere,et al.  Conditional routing of information to the cortex: a model of the basal ganglia's role in cognitive coordination. , 2010, Psychological review.

[30]  Jodi D. Edwards,et al.  Preliminary fMRI findings on the effects of event rate in adults with ADHD , 2010, Journal of Neural Transmission.

[31]  L. Pessoa,et al.  Interactions between cognition and motivation during response inhibition , 2010, Neuropsychologia.

[32]  J. Sweeney,et al.  Neural correlates of response inhibition in pediatric bipolar disorder and attention deficit hyperactivity disorder , 2010, Psychiatry Research: Neuroimaging.

[33]  G. Bush,et al.  Anterior Cingulate Volumetric Alterations in Treatment-Naïve Adults With ADHD , 2010, Journal of attention disorders.

[34]  Ian H. Robertson,et al.  Functional developmental changes underlying response inhibition and error-detection processes , 2009, Neuropsychologia.

[35]  Chaozhe Zhu,et al.  Abnormal resting-state functional connectivity patterns of the putamen in medication-naïve children with attention deficit hyperactivity disorder , 2009, Brain Research.

[36]  Katya Rubia,et al.  Disorder‐specific dysfunction in right inferior prefrontal cortex during two inhibition tasks in boys with attention‐deficit hyperactivity disorder compared to boys with obsessive–compulsive disorder , 2009, Human brain mapping.

[37]  J. Jolles,et al.  Differences in feedback- and inhibition-related neural activity in adult ADHD , 2009, Brain and Cognition.

[38]  M. Bellgrove,et al.  Insights into the neural basis of response inhibition from cognitive and clinical neuroscience , 2009, Neuroscience & Biobehavioral Reviews.

[39]  Jan Gläscher,et al.  Visualization of Group Inference Data in Functional Neuroimaging , 2009, Neuroinformatics.

[40]  B. Biswal,et al.  Functional connectivity of human striatum: a resting state FMRI study. , 2008, Cerebral cortex.

[41]  A. Turken,et al.  Left inferior frontal gyrus is critical for response inhibition , 2008, BMC Neuroscience.

[42]  Vincent Giampietro,et al.  Dissociated functional brain abnormalities of inhibition in boys with pure conduct disorder and in boys with pure attention deficit hyperactivity disorder. , 2008, The American journal of psychiatry.

[43]  T. Robbins,et al.  The neuropsychopharmacology of action inhibition: cross-species translation of the stop-signal and go/no-go tasks , 2008, Psychopharmacology.

[44]  J. Crawford,et al.  An index-based short form of the WAIS-III with accompanying analysis of reliability and abnormality of differences. , 2008, The British journal of clinical psychology.

[45]  James J. Pekar,et al.  Functional Magnetic Resonance Imaging Evidence for Abnormalities in Response Selection in Attention Deficit Hyperactivity Disorder: Differences in Activation Associated with Response Inhibition but Not Habitual Motor Response , 2008, Journal of Cognitive Neuroscience.

[46]  G. Logan,et al.  Converging Evidence for a Fronto-Basal-Ganglia Network for Inhibitory Control of Action and Cognition , 2007, The Journal of Neuroscience.

[47]  Keith M. Shafritz,et al.  ADHD- and medication-related brain activation effects in concordantly affected parent-child dyads with ADHD. , 2007, Journal of child psychology and psychiatry, and allied disciplines.

[48]  Michael J. Kofler,et al.  Attention-Deficit/Hyperactivity Disorder and Behavioral Inhibition: A Meta-Analytic Review of the Stop-signal Paradigm , 2007, Journal of abnormal child psychology.

[49]  S. Faraone,et al.  Meta-Analysis of Structural Imaging Findings in Attention-Deficit/Hyperactivity Disorder , 2007, Biological Psychiatry.

[50]  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.

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

[52]  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.

[53]  J. Halperin,et al.  Revisiting the role of the prefrontal cortex in the pathophysiology of attention-deficit/hyperactivity disorder. , 2006, Psychological bulletin.

[54]  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.

[55]  Nicole M Dudukovic,et al.  Altered neural substrates of cognitive control in childhood ADHD: evidence from functional magnetic resonance imaging. , 2005, The American journal of psychiatry.

[56]  B. Pennington,et al.  Validity of the Executive Function Theory of Attention-Deficit/Hyperactivity Disorder: A Meta-Analytic Review , 2005, Biological Psychiatry.

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

[58]  J. Kenemans,et al.  A meta-analytic review of stopping performance in attention-deficit/hyperactivity disorder: deficient inhibitory motor control? , 2005, Journal of abnormal psychology.

[59]  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.

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

[61]  Joshua W. Brown,et al.  Monitoring and Control of Action by the Frontal Lobes , 2002, Neuron.

[62]  A. Nambu,et al.  Functional significance of the cortico–subthalamo–pallidal ‘hyperdirect’ pathway , 2002, Neuroscience Research.

[63]  Karl J. Friston,et al.  Classical and Bayesian Inference in Neuroimaging: Applications , 2002, NeuroImage.

[64]  N. Tzourio-Mazoyer,et al.  Automated Anatomical Labeling of Activations in SPM Using a Macroscopic Anatomical Parcellation of the MNI MRI Single-Subject Brain , 2002, NeuroImage.

[65]  Yu-Shin Ding,et al.  Therapeutic Doses of Oral Methylphenidate Significantly Increase Extracellular Dopamine in the Human Brain , 2001, The Journal of Neuroscience.

[66]  Darin D Dougherty,et al.  Dopamine transporter density in patients with attention deficit hyperactivity disorder , 1999, The Lancet.

[67]  E. Rolls.  The functions of the orbitofrontal cortex , 1999, Brain and Cognition.

[68]  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.

[69]  N. Volkow,et al.  Dopamine transporter occupancies in the human brain induced by therapeutic doses of oral methylphenidate. , 1998, The American journal of psychiatry.

[70]  Karl J. Friston,et al.  Psychophysiological and Modulatory Interactions in Neuroimaging , 1997, NeuroImage.

[71]  N. Ryan,et al.  Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data. , 1997, Journal of the American Academy of Child and Adolescent Psychiatry.

[72]  T. Carr,et al.  Inhibitory Processes in Attention, Memory and Language , 1994 .

[73]  Yvonne Koch,et al.  Inhibitory Processes In Attention Memory And Language , 2016 .

[74]  G. Logan,et al.  On the ability to inhibit thought and action: general and special theories of an act of control. , 2014, Psychological review.

[75]  J. Crawford,et al.  An index-based short-form of the WISC-IV with accompanying analysis of the reliability and abnormality of differences. , 2010, The British journal of clinical psychology.

[76]  Anqi Qiu,et al.  Basal ganglia volume and shape in children with attention deficit hyperactivity disorder. , 2009, The American journal of psychiatry.

[77]  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.

[78]  R. Poldrack,et al.  Cortical and Subcortical Contributions to Stop Signal Response Inhibition: Role of the Subthalamic Nucleus , 2006, The Journal of Neuroscience.

[79]  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.

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

[81]  Karl J. Friston,et al.  A unified statistical approach for determining significant signals in images of cerebral activation , 1996, Human brain mapping.