Abnormal functional activation and maturation of ventromedial prefrontal cortex and cerebellum during temporal discounting in autism spectrum disorder

People with autism spectrum disorder (ASD) have poor decision‐making and temporal foresight. This may adversely impact on their everyday life, mental health, and productivity. However, the neural substrates underlying poor choice behavior in people with ASD, or its’ neurofunctional development from childhood to adulthood, are unknown. Despite evidence of atypical structural brain development in ASD, investigation of functional brain maturation in people with ASD is lacking. This cross‐sectional developmental fMRI study investigated the neural substrates underlying performance on a temporal discounting (TD) task in 38 healthy (11–35 years old) male adolescents and adults with ASD and 40 age, sex, and IQ‐matched typically developing healthy controls. Most importantly, we assessed group differences in the neurofunctional maturation of TD across childhood and adulthood. Males with ASD had significantly poorer task performance and significantly lower brain activation in typical regions that mediate TD for delayed choices, in predominantly right hemispheric regions of ventrolateral/dorsolateral prefrontal cortices, ventromedial prefrontal cortex, striatolimbic regions, and cerebellum. Importantly, differential activation in ventromedial frontal cortex and cerebellum was associated with abnormal functional brain maturation; controls, in contrast to people with ASD, showed progressively increasing activation with increasing age in these regions; which furthermore was associated with performance measures and clinical ASD measures (stereotyped/restricted interests). Findings provide first cross‐sectional evidence that reduced activation of TD mediating brain regions in people with ASD during TD is associated with abnormal functional brain development in these regions between childhood and adulthood, and this is related to poor task performance and clinical measures of ASD. Hum Brain Mapp 38:5343–5355, 2017. © 2017 Wiley Periodicals, Inc.

[1]  John Suckling,et al.  Association Between the Probability of Autism Spectrum Disorder and Normative Sex-Related Phenotypic Diversity in Brain Structure , 2017, JAMA psychiatry.

[2]  D. Murphy,et al.  Autism spectrum disorder in adults: diagnosis, management, and health services development , 2016, Neuropsychiatric disease and treatment.

[3]  Kate Johnston,et al.  The mental health of individuals referred for assessment of autism spectrum disorder in adulthood: A clinic report , 2016, Autism : the international journal of research and practice.

[4]  D. Murphy,et al.  Does sex influence the diagnostic evaluation of autism spectrum disorder in adults? , 2016, Autism : the international journal of research and practice.

[5]  J. Lainhart Brain imaging research in autism spectrum disorders: in search of neuropathology and health across the lifespan , 2015, Current opinion in psychiatry.

[6]  Catherine J. Stoodley,et al.  Cerebellar gray matter and lobular volumes correlate with core autism symptoms , 2015, NeuroImage: Clinical.

[7]  Nicholas Lange,et al.  Longitudinal Volumetric Brain Changes in Autism Spectrum Disorder Ages 6–35 Years , 2015, Autism research : official journal of the International Society for Autism Research.

[8]  Catherine A. Sugar,et al.  Time Reproduction Performance Is Associated With Age and Working Memory in High‐Functioning Youth With Autism Spectrum Disorder , 2015, Autism research : official journal of the International Society for Autism Research.

[9]  Jan Peters,et al.  Reward-based decision making in pathological gambling: The roles of risk and delay , 2015, Neuroscience Research.

[10]  M. Brammer,et al.  Abnormal functional activation and maturation of fronto-striato-temporal and cerebellar regions during sustained attention in autism spectrum disorder. , 2014, The American journal of psychiatry.

[11]  Marieke Langen,et al.  Changes in the Development of Striatum Are Involved in Repetitive Behavior in Autism , 2014, Biological Psychiatry.

[12]  Vincent Giampietro,et al.  Disorder-specific functional abnormalities during temporal discounting in youth with Attention Deficit Hyperactivity Disorder (ADHD), Autism and comorbid ADHD and Autism , 2014, Psychiatry Research: Neuroimaging.

[13]  G. Fink,et al.  Differentiating neural reward responsiveness in autism versus ADHD , 2014, Developmental Cognitive Neuroscience.

[14]  Aleksandra Badura,et al.  The Cerebellum, Sensitive Periods, and Autism , 2014, Neuron.

[15]  K. Lim,et al.  Pubertal status associations with reward and threat sensitivities and subcortical brain volumes during adolescence , 2014, Brain and Cognition.

[16]  M. Knapp,et al.  Costs of autism spectrum disorders in the United Kingdom and the United States. , 2014, JAMA pediatrics.

[17]  Nicholas Lange,et al.  Longitudinal changes in cortical thickness in autism and typical development. , 2014, Brain : a journal of neurology.

[18]  Warren K. Bickel,et al.  Remember the Future II: Meta-analyses and Functional Overlap of Working Memory and Delay Discounting , 2014, Biological Psychiatry.

[19]  C. Atance,et al.  Brief Report: Episodic Foresight in Autism Spectrum Disorder , 2014, Journal of autism and developmental disorders.

[20]  D. Bowler,et al.  Spatial Navigation Impairments Among Intellectually High-Functioning Adults With Autism Spectrum Disorder: Exploring Relations With Theory of Mind, Episodic Memory, and Episodic Future Thinking , 2013, Journal of abnormal psychology.

[21]  Matcheri S. Keshavan,et al.  A two-year longitudinal pilot MRI study of the brainstem in autism , 2013, Behavioural Brain Research.

[22]  V. Noreika,et al.  Timing deficits in attention-deficit/hyperactivity disorder (ADHD): Evidence from neurocognitive and neuroimaging studies , 2013, Neuropsychologia.

[23]  Herbert Roeyers,et al.  Temporal discounting of monetary rewards in children and adolescents with ADHD and autism spectrum disorders. , 2012, Developmental science.

[24]  H. Ring,et al.  Decision-making difficulties experienced by adults with autism spectrum conditions , 2012, Autism : the international journal of research and practice.

[25]  G. Dichter,et al.  Adults with autism spectrum disorders exhibit decreased sensitivity to reward parameters when making effort-based decisions , 2012, Journal of Neurodevelopmental Disorders.

[26]  Stephen R. Dager,et al.  Consensus Paper: Pathological Role of the Cerebellum in Autism , 2012, The Cerebellum.

[27]  G. Barker,et al.  Anatomy and aging of the amygdala and hippocampus in autism spectrum disorder: an in vivo magnetic resonance imaging study of Asperger syndrome , 2012, Autism research : official journal of the International Society for Autism Research.

[28]  G. Dichter,et al.  Reward circuitry function in autism spectrum disorders. , 2012, Social cognitive and affective neuroscience.

[29]  J. Piven,et al.  Early brain overgrowth in autism associated with an increase in cortical surface area before age 2 years. , 2011, Archives of general psychiatry.

[30]  Jan Peters,et al.  The neural mechanisms of inter-temporal decision-making: understanding variability , 2011, Trends in Cognitive Sciences.

[31]  D. Murphy,et al.  Autism in adults. New biologicial findings and their translational implications to the cost of clinical services , 2011, Brain Research.

[32]  E. Courchesne,et al.  Brain growth across the life span in autism: Age-specific changes in anatomical pathology , 2011, Brain Research.

[33]  D. Tranel,et al.  The amygdala and decision-making , 2011, Neuropsychologia.

[34]  L. Green,et al.  Modeling the effect of reward amount on probability discounting. , 2011, Journal of the experimental analysis of behavior.

[35]  M. Brammer,et al.  Maturation of limbic corticostriatal activation and connectivity associated with developmental changes in temporal discounting , 2011, NeuroImage.

[36]  Jan Peters,et al.  Episodic Future Thinking Reduces Reward Delay Discounting through an Enhancement of Prefrontal-Mediotemporal Interactions , 2010, Neuron.

[37]  Martin Wiener,et al.  The image of time: A voxel-wise meta-analysis , 2010, NeuroImage.

[38]  Teresa K. W. Wong,et al.  White matter fractional anisotrophy differences and correlates of diagnostic symptoms in autism. , 2009, Journal of child psychology and psychiatry, and allied disciplines.

[39]  J. Pekar,et al.  Decreased connectivity and cerebellar activity in autism during motor task performance. , 2009, Brain : a journal of neurology.

[40]  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.

[41]  Colin Camerer,et al.  Self-control in decision-making involves modulation of the vmPFC valuation system , 2009, NeuroImage.

[42]  D. Murphy,et al.  Executive functioning differences between adults with attention deficit hyperactivity disorder and autistic spectrum disorder in initiation, planning and strategy formation , 2009, Autism : the international journal of research and practice.

[43]  Brian Knutson,et al.  Dissociable neural representations of future reward magnitude and delay during temporal discounting , 2009, NeuroImage.

[44]  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.

[45]  Declan G. M. Murphy,et al.  Altered cerebellar feedback projections in Asperger syndrome , 2008, NeuroImage.

[46]  Camelia M. Kuhnen,et al.  Nucleus accumbens activation mediates the influence of reward cues on financial risk taking , 2008, Neuroreport.

[47]  Jonathan D. Cohen,et al.  Functional Imaging of Decision Conflict , 2008, The Journal of Neuroscience.

[48]  D. Amaral,et al.  Neuroanatomy of autism , 2008, Trends in Neurosciences.

[49]  G. Lehmkuhl,et al.  Child and Adolescent Psychiatry and Mental Health Inhibition, Flexibility, Working Memory and Planning in Autism Spectrum Disorders with and without Comorbid Adhd-symptoms , 2008 .

[50]  D. Schacter,et al.  Remembering the past to imagine the future: the prospective brain , 2007, Nature Reviews Neuroscience.

[51]  Fiona Toal,et al.  Women with autistic-spectrum disorder: magnetic resonance imaging study of brain anatomy , 2007, British Journal of Psychiatry.

[52]  A. Minassian,et al.  Adults with Autism Show Increased Sensitivity to Outcomes at Low Error Rates During Decision-Making , 2007, Journal of autism and developmental disorders.

[53]  Jean-Baptiste Poline,et al.  Analysis of a large fMRI cohort: Statistical and methodological issues for group analyses , 2007, NeuroImage.

[54]  M. Reite,et al.  Regional gray matter volumetric changes in autism associated with social and repetitive behavior symptoms , 2006, BMC psychiatry.

[55]  Ernst Pöppel,et al.  Temporal processing deficits in high-functioning children with autism. , 2004, British journal of psychology.

[56]  R. Murray,et al.  The cerebellum and decision making under uncertainty. , 2004, Brain research. Cognitive brain research.

[57]  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.

[58]  G. Dawson,et al.  Performance on Cambridge Neuropsychological Test Automated Battery Subtests Sensitive to Frontal Lobe Function in People with Autistic Disorder: Evidence from the Collaborative Programs of Excellence in Autism Network , 2004, Journal of autism and developmental disorders.

[59]  H Meltzer,et al.  Using the Strengths and Difficulties Questionnaire (SDQ) to screen for child psychiatric disorders in a community sample , 2003, International review of psychiatry.

[60]  Eric Courchesne,et al.  Cerebral Lobes in Autism: Early Hyperplasia and Abnormal Age Effects , 2002, NeuroImage.

[61]  L. Green,et al.  Area under the curve as a measure of discounting. , 2001, Journal of the experimental analysis of behavior.

[62]  E. Courchesne,et al.  Evidence for a cerebellar role in reduced exploration and stereotyped behavior in autism , 2001, Biological Psychiatry.

[63]  T S Critchfield,et al.  Temporal discounting: basic research and the analysis of socially important behavior. , 2001, Journal of applied behavior analysis.

[64]  B. Leventhal,et al.  The Autism Diagnostic Observation Schedule—Generic: A Standard Measure of Social and Communication Deficits Associated with the Spectrum of Autism , 2000, Journal of autism and developmental disorders.

[65]  A. Gilchrist,et al.  Social and Psychiatric Functioning in Adolescents with Asperger Syndrome Compared with Conduct Disorder , 2000, Journal of autism and developmental disorders.

[66]  H. de Wit,et al.  Delay or probability discounting in a model of impulsive behavior: effect of alcohol. , 1999, Journal of the experimental analysis of behavior.

[67]  James D. A. Parker,et al.  The Revised Conners' Parent Rating Scale (CPRS-R): Factor Structure, Reliability, and Criterion Validity , 1998, Journal of abnormal child psychology.

[68]  H. de Wit,et al.  Determination of discount functions in rats with an adjusting-amount procedure. , 1997, Journal of the experimental analysis of behavior.

[69]  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.

[70]  D. Goldberg,et al.  A scaled version of the General Health Questionnaire , 1979, Psychological Medicine.

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

[72]  E. Fehr,et al.  Development of Behavioral Control and Associated vmPFC-DLPFC Connectivity Explains Children's Increased Resistance to Temptation in Intertemporal Choice. , 2016, Cerebral cortex.

[73]  A. Odum,et al.  Experimental manipulations of delay discounting & related processes: an introduction to the special issue. , 2015, Journal of the experimental analysis of behavior.

[74]  S. Haber,et al.  The Reward Circuit: Linking Primate Anatomy and Human Imaging , 2010, Neuropsychopharmacology.

[75]  Laurence Steinberg,et al.  Age differences in future orientation and delay discounting. , 2009, Child development.

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

[77]  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.

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