Disorder-specific functional abnormalities during sustained attention in youth with Attention Deficit Hyperactivity Disorder (ADHD) and with Autism

Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) are often comorbid and share behavioural-cognitive abnormalities in sustained attention. A key question is whether this shared cognitive phenotype is based on common or different underlying pathophysiologies. To elucidate this question, we compared 20 boys with ADHD to 20 age and IQ matched ASD and 20 healthy boys using functional magnetic resonance imaging (fMRI) during a parametrically modulated vigilance task with a progressively increasing load of sustained attention. ADHD and ASD boys had significantly reduced activation relative to controls in bilateral striato–thalamic regions, left dorsolateral prefrontal cortex (DLPFC) and superior parietal cortex. Both groups also displayed significantly increased precuneus activation relative to controls. Precuneus was negatively correlated with the DLPFC activation, and progressively more deactivated with increasing attention load in controls, but not patients, suggesting problems with deactivation of a task-related default mode network in both disorders. However, left DLPFC underactivation was significantly more pronounced in ADHD relative to ASD boys, which furthermore was associated with sustained performance measures that were only impaired in ADHD patients. ASD boys, on the other hand, had disorder-specific enhanced cerebellar activation relative to both ADHD and control boys, presumably reflecting compensation. The findings show that ADHD and ASD boys have both shared and disorder-specific abnormalities in brain function during sustained attention. Shared deficits were in fronto–striato–parietal activation and default mode suppression. Differences were a more severe DLPFC dysfunction in ADHD and a disorder-specific fronto–striato–cerebellar dysregulation in ASD.

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

[2]  J. Warm.  Sustained attention in human performance , 1984 .

[3]  L. Waterhouse,et al.  Sustained attention in children with autism , 1990, Journal of autism and developmental disorders.

[4]  A. Couteur,et al.  Autism Diagnostic Interview-Revised: A revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders , 1994, Journal of autism and developmental disorders.

[5]  G. Lyon,et al.  Attention, Memory, and Executive Function , 1995 .

[6]  J. A. Sergeant,et al.  A theory of attention: An information processing perspective , 1995 .

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

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

[9]  Andrew Simmons,et al.  Prefrontal involvement in temporal bridging and timing movement , 1998, Neuropsychologia.

[10]  J. Epstein,et al.  Revision and Restandardization of the Conners Teacher Rating Scale (CTRS-R): Factor Structure, Reliability, and Criterion Validity , 1998, Journal of abnormal child psychology.

[11]  R. Parasuraman.  The attentive brain , 1998 .

[12]  Judi E. See,et al.  Brain systems of vigilance. , 1998 .

[13]  E. Bullmore,et al.  Methods for diagnosis and treatment of stimulus‐correlated motion in generic brain activation studies using fMRI , 1999, Human brain mapping.

[14]  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.

[15]  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.

[16]  D. Trauner,et al.  Brief Report: Attention Differences in Asperger Syndrome , 2002, Journal of autism and developmental disorders.

[17]  Matthew K Belmonte,et al.  Functional anatomy of impaired selective attention and compensatory processing in autism. , 2003, Brain research. Cognitive brain research.

[18]  Eric Courchesne,et al.  Differential effects of developmental cerebellar abnormality on cognitive and motor functions in the cerebellum: an fMRI study of autism. , 2003, The American journal of psychiatry.

[19]  Katya Rubia,et al.  Motor Timing Deficits in Community and Clinical Boys with Hyperactive Behavior: The Effect of Methylphenidate on Motor Timing , 2003, Journal of abnormal child psychology.

[20]  Yoshihiro Miyake,et al.  Two types of anticipation in synchronization tapping. , 2004, Acta neurobiologiae experimentalis.

[21]  Christopher Gillberg,et al.  Autism spectrum disorders in children with normal intellectual levels: associated impairments and subgroups. , 2004, Developmental medicine and child neurology.

[22]  Herbert Roeyers,et al.  How specific are executive functioning deficits in attention deficit hyperactivity disorder and autism? , 2004, Journal of child psychology and psychiatry, and allied disciplines.

[23]  M. J. Meloy,et al.  The neural basis of the psychomotor vigilance task. , 2005, Sleep.

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

[25]  Olivier Bertrand,et al.  Listening in Silence Activates Auditory Areas: A Functional Magnetic Resonance Imaging Study , 2006, The Journal of Neuroscience.

[26]  M. Just,et al.  Functional connectivity in a baseline resting-state network in autism , 2006, Neuroreport.

[27]  Janet E. Lainhart,et al.  Comorbid Psychiatric Disorders in Children with Autism: Interview Development and Rates of Disorders , 2006, Journal of autism and developmental disorders.

[28]  John L Bradshaw,et al.  Visuospatial processing and the function of prefrontal-parietal networks in autism spectrum disorders: a functional MRI study. , 2006, The American journal of psychiatry.

[29]  B. Corbett,et al.  Autism and Attention Deficit Hyperactivity Disorder: Assessing Attention and Response Control with the Integrated Visual and Auditory Continuous Performance Test , 2006, Child neuropsychology : a journal on normal and abnormal development in childhood and adolescence.

[30]  Christoph Klein,et al.  Intra-Subject Variability in Attention-Deficit Hyperactivity Disorder , 2006, Biological Psychiatry.

[31]  D. Murphy,et al.  Neural Correlates of Executive Function in Autistic Spectrum Disorders , 2006, Biological Psychiatry.

[32]  Guido Gerig,et al.  Cortical Gray and White Brain Tissue Volume in Adolescents and Adults with Autism , 2006, Biological Psychiatry.

[33]  Kristina M. Visscher,et al.  The neural bases of momentary lapses in attention , 2006, Nature Neuroscience.

[34]  Edward T. Bullmore,et al.  Change detection in children with autism: An auditory event-related fMRI study , 2006, NeuroImage.

[35]  Vinod Menon,et al.  Parietal attentional system aberrations during target detection in adolescents with attention deficit hyperactivity disorder: event-related fMRI evidence. , 2006, The American journal of psychiatry.

[36]  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.

[37]  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.

[38]  Katherine A. Johnson,et al.  Dissociation in performance of children with ADHD and high-functioning autism on a task of sustained attention , 2007, Neuropsychologia.

[39]  N. Minshew,et al.  The new neurobiology of autism: cortex, connectivity, and neuronal organization. , 2007, Archives of neurology.

[40]  Godfrey D Pearlson,et al.  An FMRI auditory oddball study of combined-subtype attention deficit hyperactivity disorder. , 2007, The American journal of psychiatry.

[41]  F. Castellanos,et al.  Spontaneous attentional fluctuations in impaired states and pathological conditions: A neurobiological hypothesis , 2007, Neuroscience & Biobehavioral Reviews.

[42]  Gereon R Fink,et al.  Structural brain abnormalities in adolescents with autism spectrum disorder and patients with attention deficit/hyperactivity disorder. , 2007, Journal of child psychology and psychiatry, and allied disciplines.

[43]  E. Loth,et al.  Brain morphometry volume in autistic spectrum disorder: a magnetic resonance imaging study of adults , 2008, Psychological Medicine.

[44]  Keith M. Shafritz,et al.  The Neural Circuitry Mediating Shifts in Behavioral Response and Cognitive Set in Autism , 2008, Biological Psychiatry.

[45]  R. Frances.  Facial emotion processing in criminal psychopathy: Preliminary functional magnetic resonance imaging study , 2008 .

[46]  G. Baird,et al.  Psychiatric disorders in children with autism spectrum disorders: prevalence, comorbidity, and associated factors in a population-derived sample. , 2008, Journal of the American Academy of Child and Adolescent Psychiatry.

[47]  S. Debener,et al.  Default-mode brain dysfunction in mental disorders: A systematic review , 2009, Neuroscience & Biobehavioral Reviews.

[48]  David M. Rocke,et al.  Examining executive functioning in children with autism spectrum disorder, attention deficit hyperactivity disorder and typical development , 2009, Psychiatry Research.

[49]  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.

[50]  R. Halari,et al.  Impulsiveness as a timing disturbance: neurocognitive abnormalities in attention-deficit hyperactivity disorder during temporal processes and normalization with methylphenidate , 2009, Philosophical Transactions of the Royal Society B: Biological Sciences.

[51]  M J Brammer,et al.  Clinical and anatomical heterogeneity in autistic spectrum disorder: a structural MRI study , 2009, Psychological Medicine.

[52]  Rozmin Halari,et al.  Methylphenidate normalises activation and functional connectivity deficits in attention and motivation networks in medication-naïve children with ADHD during a rewarded continuous performance task , 2009, Neuropharmacology.

[53]  Rozmin Halari,et al.  Disorder-specific dissociation of orbitofrontal dysfunction in boys with pure conduct disorder during reward and ventrolateral prefrontal dysfunction in boys with pure ADHD during sustained attention. , 2009, The American journal of psychiatry.

[54]  Jan K. Buitelaar,et al.  Shared heritability of attention-deficit/hyperactivity disorder and autism spectrum disorder , 2010, European Child & Adolescent Psychiatry.

[55]  S. Murphy.  Using functional neuroimaging to investigate the mechanisms of action of selective serotonin reuptake inhibitors (SSRIs). , 2010, Current pharmaceutical design.

[56]  Kerstin Konrad,et al.  Is the ADHD brain wired differently? A review on structural and functional connectivity in attention deficit hyperactivity disorder , 2010, Human brain mapping.

[57]  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.

[58]  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.

[59]  Marisa O. Hollinshead,et al.  The organization of the human cerebral cortex estimated by intrinsic functional connectivity. , 2011, Journal of neurophysiology.

[60]  C. McDougle,et al.  Structural and functional magnetic resonance imaging of autism spectrum disorders , 2011, Brain Research.

[61]  B. Franke,et al.  A review on cognitive and brain endophenotypes that may be common in autism spectrum disorder and attention-deficit/hyperactivity disorder and facilitate the search for pleiotropic genes , 2011, Neuroscience & Biobehavioral Reviews.

[62]  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.

[63]  Katya Rubia,et al.  “Cool” Inferior Frontostriatal Dysfunction in Attention-Deficit/Hyperactivity Disorder Versus “Hot” Ventromedial Orbitofrontal-Limbic Dysfunction in Conduct Disorder: A Review , 2011, Biological Psychiatry.

[64]  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.

[65]  Michael J. Brammer,et al.  Developmental effects of reward on sustained attention networks , 2011, NeuroImage.

[66]  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.

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

[68]  John O. Willis,et al.  Wechsler Abbreviated Scale of Intelligence , 2014 .