Neural correlates of interference inhibition, action withholding and action cancelation in adult ADHD

Attention-Deficit/Hyperactivity Disorder (ADHD) is marked by inhibitory and attentional deficits which can persist into adulthood. Those deficits have been associated with dysfunctional fronto-striatal and fronto-parietal circuits. The present study sought to delineate neural correlates of component specific inhibitory deficits in adult ADHD using functional magnetic resonance imaging (fMRI). 20 adult ADHD patients and 24 matched healthy controls were included. Brain activation was assessed during three stages of behavioral inhibition, i.e. interference inhibition (Simon task), action withholding (Go/no-go task) and action cancelation (Stop-signal task). Behaviorally, ADHD patients were affected in all tasks. Impaired interference inhibition was associated with hypoactivation in parietal and medial frontal regions. During action withholding and cancelation ADHD patients displayed hypoactivation in a fronto-striatal network. These findings support the notion of at least two disturbed neural circuits in ADHD differentially associated with deficits in separate inhibitory subcomponents. Thereby, deficits in inhibitory subcomponents which are closely connected to response interference were related to hypofunction in more attention related circuits, while stopping related deficits were rather associated with hypofunction in inhibitory circuits.

[1]  T. B. Üstün,et al.  The Prevalence and Effects of Adult Attention Deficit/Hyperactivity Disorder on Work Performance in a Nationally Representative Sample of Workers , 2005, Journal of occupational and environmental medicine.

[2]  Martin Hautzinger,et al.  Beck Depressions-Inventar , 2006 .

[3]  J R Simon,et al.  Effect of conflicting cues on information processing: the 'Stroop effect' vs. the 'Simon effect'. , 1990, Acta psychologica.

[4]  Joshua M. Langberg,et al.  Evidence for higher reaction time variability for children with ADHD on a range of cognitive tasks including reward and event rate manipulations. , 2011, Neuropsychology.

[5]  G. Band,et al.  Inhibitory motor control in stop paradigms: review and reinterpretation of neural mechanisms. , 1999, Acta psychologica.

[6]  J. Nigg,et al.  Is ADHD a disinhibitory disorder? , 2001, Psychological bulletin.

[7]  R. Klein,et al.  Alerting, Orienting, and Executive Attention in Children With ADHD , 2011, Journal of attention disorders.

[8]  André Beauducel,et al.  Psychometrische Eigenschaften und Normen einer deutschsprachigen Fassung der Sensation Seeking-Skalen, Form V , 2003 .

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

[10]  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.

[11]  Janet B W Williams,et al.  Diagnostic and Statistical Manual of Mental Disorders , 2013 .

[12]  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.

[13]  R. Stieglitz,et al.  Reliabilität und Validität der Wender-Utah-Rating-Scale-Kurzform , 2003, Der Nervenarzt.

[14]  D. Stuss,et al.  Staying on the job: the frontal lobes control individual performance variability. , 2003, Brain : a journal of neurology.

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

[16]  M. Davidson.  Literature Review: ADHD in Adults , 2007 .

[17]  Jin Fan,et al.  The activation of attentional networks , 2005, NeuroImage.

[18]  Nikos Makris,et al.  Functional magnetic resonance imaging of methylphenidate and placebo in attention-deficit/hyperactivity disorder during the multi-source interference task. , 2008, Archives of general psychiatry.

[19]  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.

[20]  W. Reith,et al.  Impairment of fronto-striatal and parietal cerebral networks correlates with attention deficit hyperactivity disorder (ADHD) psychopathology in adults — A functional magnetic resonance imaging (fMRI) study , 2010, Psychiatry Research: Neuroimaging.

[21]  Yiping P. Du,et al.  The neural basis of sustained and transient attentional control in young adults with ADHD , 2009, Neuropsychologia.

[22]  G. Logan,et al.  Selective Inhibition in Children with Attention-Deficit Hyperactivity Disorder Off and On Stimulant Medication , 2003, Journal of abnormal child psychology.

[23]  Alexandra Philipsen,et al.  The estimated prevalence and correlates of adult ADHD in a German community sample , 2012, European Archives of Psychiatry and Clinical Neuroscience.

[24]  J. Jonides,et al.  Interference resolution: Insights from a meta-analysis of neuroimaging tasks , 2007, Cognitive, affective & behavioral neuroscience.

[25]  Stuart J Johnstone,et al.  Inhibitory motor control in children with attention-deficit/hyperactivity disorder: event-related potentials in the stop-signal paradigm , 2003, Biological Psychiatry.

[26]  J. Henderson,et al.  Executive functions and ADHD in adults: evidence for selective effects on ADHD symptom domains. , 2005, Journal of abnormal psychology.

[27]  Sharon Morein-Zamir,et al.  The Effect of Methylphenidate on Three Forms of Response Inhibition in Boys with AD/HD , 2003, Journal of abnormal child psychology.

[28]  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.

[29]  T. Robbins,et al.  Impulsivity, Compulsivity, and Top-Down Cognitive Control , 2011, Neuron.

[30]  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.

[31]  Maneesh C. Patel,et al.  Distinct frontal systems for response inhibition, attentional capture, and error processing , 2010, Proceedings of the National Academy of Sciences.

[32]  Yiping P. Du,et al.  Attentional Control Activation Relates to Working Memory in Attention-Deficit/Hyperactivity Disorder , 2010, Biological Psychiatry.

[33]  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.

[34]  S. Whiteside,et al.  The Five Factor Model and impulsivity: using a structural model of personality to understand impulsivity , 2001 .

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

[36]  J. Kenemans,et al.  Perceptual and response interference in children with attention-deficit hyperactivity disorder, and the effects of methylphenidate. , 1999, Psychophysiology.

[37]  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.

[38]  J. Monterosso,et al.  Effect of methylphenidate on Stroop Color–Word task performance in children with attention deficit hyperactivity disorder , 2006, Psychiatry Research.

[39]  J. Buitelaar,et al.  Executive functioning in adult ADHD: a meta-analytic review , 2005, Psychological Medicine.

[40]  M. J. Emerson,et al.  The Unity and Diversity of Executive Functions and Their Contributions to Complex “Frontal Lobe” Tasks: A Latent Variable Analysis , 2000, Cognitive Psychology.

[41]  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.

[42]  G. Logan,et al.  Restraint and Cancellation: Multiple Inhibition Deficits in Attention Deficit Hyperactivity Disorder , 2007, Journal of abnormal child psychology.

[43]  M Zaitsev,et al.  Point spread function mapping with parallel imaging techniques and high acceleration factors: Fast, robust, and flexible method for echo‐planar imaging distortion correction , 2004, Magnetic resonance in medicine.

[44]  J. Patton,et al.  Factor structure of the Barratt impulsiveness scale. , 1995, Journal of clinical psychology.

[45]  J. Nigg.  On inhibition/disinhibition in developmental psychopathology: views from cognitive and personality psychology and a working inhibition taxonomy. , 2000, Psychological bulletin.

[46]  Jason B. Mattingley,et al.  Methylphenidate But Not Atomoxetine or Citalopram Modulates Inhibitory Control and Response Time Variability , 2011, Biological Psychiatry.

[47]  R. Kessler,et al.  Cross-national prevalence and correlates of adult attention-deficit hyperactivity disorder. , 2007, The British journal of psychiatry : the journal of mental science.

[48]  Jin Fan,et al.  Cognitive and Brain Consequences of Conflict , 2003, NeuroImage.

[49]  Jin Fan,et al.  Testing the behavioral interaction and integration of attentional networks , 2009, Brain and Cognition.

[50]  P. Wender,et al.  [Reliability and validity of the Wender-Utah-Rating-Scale short form. Retrospective assessment of symptoms for attention deficit/hyperactivity disorder]. , 2003, Der Nervenarzt.

[51]  Hiroki M. Morimoto,et al.  Functional dissociation in right inferior frontal cortex during performance of go/no-go task. , 2009, Cerebral cortex.

[52]  K Konrad,et al.  Neuropsychological and behavioural disinhibition in adult ADHD compared to borderline personality disorder , 2007, Psychological Medicine.

[53]  R. Kahn,et al.  Function of striatum beyond inhibition and execution of motor responses , 2005, Human brain mapping.

[54]  D. Glahn,et al.  Electrophysiological effects of stimulant treatment on inhibitory control in children with attention-deficit/hyperactivity disorder. , 2007, Journal of child and adolescent psychopharmacology.

[55]  Tobias Egner,et al.  Separate conflict-specific cognitive control mechanisms in the human brain , 2007, NeuroImage.

[56]  George Bush,et al.  Attention-Deficit/Hyperactivity Disorder and Attention Networks , 2010, Neuropsychopharmacology.

[57]  R. C. Oldfield.  The assessment and analysis of handedness: the Edinburgh inventory. , 1971, Neuropsychologia.

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

[59]  M. Åsberg,et al.  A New Depression Scale Designed to be Sensitive to Change , 1979, British Journal of Psychiatry.

[60]  Joseph Biederman,et al.  What Is the Prevalence of Adult ADHD? Results of a Population Screen of 966 Adults , 2005, Journal of attention disorders.

[61]  S Thesen,et al.  Prospective acquisition correction for head motion with image‐based tracking for real‐time fMRI , 2000, Magnetic resonance in medicine.

[62]  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.

[63]  Xun Liu,et al.  Common and distinct neural substrates of attentional control in an integrated Simon and spatial Stroop task as assessed by event-related fMRI , 2004, NeuroImage.

[64]  Adam R Aron,et al.  Methylphenidate improves response inhibition in adults with attention-deficit/hyperactivity disorder , 2003, Biological Psychiatry.

[65]  J. Kenemans,et al.  Disentangling deficits in adults with attention-deficit/hyperactivity disorder. , 2005, Archives of general psychiatry.

[66]  Diane Swick,et al.  Are the neural correlates of stopping and not going identical? Quantitative meta-analysis of two response inhibition tasks , 2011, NeuroImage.

[67]  M. Brammer,et al.  Methylphenidate Normalizes Fronto-Striatal Underactivation During Interference Inhibition in Medication-Naïve Boys with Attention-Deficit Hyperactivity Disorder , 2011, Neuropsychopharmacology.

[68]  G. Logan,et al.  On the ability to inhibit simple and choice reaction time responses: a model and a method. , 1984, Journal of experimental psychology. Human perception and performance.

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

[70]  J. Uekermann,et al.  German validation of the Conners Adult ADHD Rating Scales (CAARS) II: Reliability, validity, diagnostic sensitivity and specificity , 2012, European Psychiatry.

[71]  R. Chao,et al.  DSM‐IV‐TR: Diagnostic and Statistical Manual of Mental Disorders , 2013 .

[72]  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.

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

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

[75]  J. Hebebrand,et al.  German Validation of the Conners Adult ADHD Rating Scales–self-report (CAARS-S) I: Factor Structure and Normative Data , 2010, European Psychiatry.

[76]  Stewart H. Mostofsky,et al.  Increased intra-individual reaction time variability in attention-deficit/hyperactivity disorder across response inhibition tasks with different cognitive demands , 2009, Neuropsychologia.

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

[78]  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.

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

[80]  Hinderk M. Emrich,et al.  Neuronal correlates of ADHD in adults with evidence for compensation strategies – a functional MRI study with a Go/No-Go paradigm , 2010, German medical science : GMS e-journal.

[81]  Rozmin Halari,et al.  Shared and disorder-specific prefrontal abnormalities in boys with pure attention-deficit/hyperactivity disorder compared to boys with pure CD during interference inhibition and attention allocation. , 2009, Journal of child psychology and psychiatry, and allied disciplines.

[82]  J. Buitelaar,et al.  To act or not to act, that's the problem: primarily inhibition difficulties in adult ADHD. , 2010, Neuropsychology.

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

[84]  Vincent Giampietro,et al.  Fronto-striatal underactivation during interference inhibition and attention allocation in grown up children with attention deficit/hyperactivity disorder and persistent symptoms , 2011, Psychiatry Research: Neuroimaging.

[85]  J. Kenemans,et al.  Methylphenidate Restores Link Between Stop-Signal Sensory Impact and Successful Stopping in Adults with Attention-Deficit/Hyperactivity Disorder , 2009, Biological Psychiatry.