A failure of left temporal cortex to specialize for language is an early emerging and fundamental property of autism.

Failure to develop normal language comprehension is an early warning sign of autism, but the neural mechanisms underlying this signature deficit are unknown. This is because of an almost complete absence of functional studies of the autistic brain during early development. Using functional magnetic resonance imaging, we previously observed a trend for abnormally lateralized temporal responses to language (i.e. greater activation on the right, rather than the expected left) in a small sample (n = 12) of sleeping 2-3 year olds with autism in contrast to typically developing children, a finding also reported in autistic adults and adolescents. It was unclear, however, if findings of atypical laterality would be observed in a larger sample, and at even earlier ages in autism, such as around the first birthday. Answers to these questions would provide the foundation for understanding how neurofunctional defects of autism unfold, and provide a foundation for studies using patterns of brain activation as a functional early biomarker of autism. To begin to examine these issues, a prospective, cross-sectional design was used in which brain activity was measured in a large sample of toddlers (n = 80) during the presentation of a bedtime story during natural sleep. Forty toddlers with autism spectrum disorder and 40 typically developing toddlers ranging in age between 12-48 months participated. Any toddler with autism who participated in the imaging experiment prior to final diagnosis was tracked and diagnoses confirmed at a later age. Results indicated that at-risk toddlers later diagnosed as autistic display deficient left hemisphere response to speech sounds and have abnormally right-lateralized temporal cortex response to language; this defect worsens with age, becoming most severe in autistic 3- and 4-year-olds. Typically developing children show opposite developmental trends with a tendency towards greater temporal cortex response with increasing age and maintenance of left-lateralized activation with age. We have now demonstrated lateralized abnormalities of temporal cortex processing of language in autism across two separate samples, including a large sample of young infants who later are diagnosed with autism, suggesting that this pattern may reflect a fundamental early neural developmental pathology in autism.

[1]  Shozo Kojima,et al.  Cerebral laterality for phonemic and prosodic cue decoding in children with autism , 2009, Neuroreport.

[2]  U. Frith,et al.  The neuropsychology of autism. , 1996, Brain : a journal of neurology.

[3]  C. Price The anatomy of language: a review of 100 fMRI studies published in 2009 , 2010, Annals of the New York Academy of Sciences.

[4]  S. Bryson,et al.  Clinical Assessment and Management of Toddlers With Suspected Autism Spectrum Disorder: Insights From Studies of High-Risk Infants , 2009, Pediatrics.

[5]  Elizabeth Redcay,et al.  Functional neuroimaging of speech perception during a pivotal period in language acquisition. , 2008, Developmental science.

[6]  J. Mehler,et al.  Sounds and silence: An optical topography study of language recognition at birth , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[7]  J C Gore,et al.  Neonatal auditory activation detected by functional magnetic resonance imaging. , 2001, Magnetic resonance imaging.

[8]  M. Just,et al.  Cortical activation and synchronization during sentence comprehension in high-functioning autism: evidence of underconnectivity. , 2004, Brain : a journal of neurology.

[9]  W. Roberts,et al.  Language lateralization development in children with autism: Insights from the late field magnetoencephalogram , 2005, Neuroscience Letters.

[10]  Helen Tager-Flusberg,et al.  Language Assessment and Development in Toddlers with Autism Spectrum Disorders , 2008, Journal of autism and developmental disorders.

[11]  C. Lord,et al.  Early Indicators of Autism Spectrum Disorders in the Second Year of Life , 2004, Journal of Autism and Developmental Disorders.

[12]  Ralph-Axel Müller,et al.  Underconnected, but how? A survey of functional connectivity MRI studies in autism spectrum disorders. , 2011, Cerebral cortex.

[13]  Marcel Adam Just,et al.  Theory of Mind disruption and recruitment of the right hemisphere during narrative comprehension in autism , 2008, Neuropsychologia.

[14]  G. Dawson,et al.  A comparison of hemispheric asymmetries in speech-related brain potentials of autistic and dysphasic children , 1989, Brain and Language.

[15]  P. Hagoort,et al.  Neural correlates of pragmatic language comprehension in autism spectrum disorders. , 2009, Brain : a journal of neurology.

[16]  M. Sigman,et al.  Improvement in Cognitive and Language Skills from Preschool to Adolescence in Autism , 2005, Journal of autism and developmental disorders.

[17]  Michael S. Gaffrey,et al.  Atypical [corrected] participation of visual cortex during word processing in autism: an fMRI study of semantic decision. , 2007, Neuropsychologia.

[18]  Russell A. Poldrack,et al.  Altered Functional Connectivity in Frontal Lobe Circuits Is Associated with Variation in the Autism Risk Gene CNTNAP2 , 2010, Science Translational Medicine.

[19]  M. Tomasello,et al.  Variability in early communicative development. , 1994, Monographs of the Society for Research in Child Development.

[20]  H. Obrig,et al.  Shedding light on words and sentences: Near-infrared spectroscopy in language research , 2012, Brain and Language.

[21]  A. Friederici,et al.  Lateralization of auditory language functions: A dynamic dual pathway model , 2004, Brain and Language.

[22]  Janet F. Werker,et al.  Cross-language speech perception: Initial capabilities and developmental change. , 1988 .

[23]  C. Rice Prevalence of autism spectrum disorders - Autism and Developmental Disabilities Monitoring Network, United States, 2006. , 2009, Morbidity and mortality weekly report. Surveillance summaries.

[24]  K. Loveland,et al.  Speech acts and the pragmatic deficits of autism. , 1988, Journal of speech and hearing research.

[25]  Lucie Hertz-Pannier,et al.  Nature and nurture in language acquisition: anatomical and functional brain-imaging studies in infants , 2006, Trends in Neurosciences.

[26]  D. Pisoni,et al.  Infants' Recognition of the Sound Patterns of Their Own Names , 1995, Psychological science.

[27]  Rafael Malach,et al.  Disrupted Neural Synchronization in Toddlers with Autism , 2011, Neuron.

[28]  Alfred Anwander,et al.  Neuroanatomical prerequisites for language functions in the maturing brain. , 2011, Cerebral cortex.

[29]  Michael S. Gaffrey,et al.  Erratum to “Atypical participation of visual cortex during word processing in autism: An fMRI study of semantic decision” [Neuropsychologia 45 (2007) 1672–1684] , 2007, Neuropsychologia.

[30]  A L Alexander,et al.  Decreased Left Posterior Insular Activity during Auditory Language in Autism , 2010, American Journal of Neuroradiology.

[31]  M. Sigman,et al.  Functional organization of perisylvian activation during presentation of sentences in preverbal infants , 2006, Proceedings of the National Academy of Sciences.

[32]  K. Pierce Early functional brain development in autism and the promise of sleep fMRI , 2011, Brain Research.

[33]  E. Fombonne,et al.  Parental recognition of developmental abnormalities in autism , 1998, European Child & Adolescent Psychiatry.

[34]  J. Hutsler The specialized structure of human language cortex: Pyramidal cell size asymmetries within auditory and language-associated regions of the temporal lobes , 2003, Brain and Language.

[35]  S. Hepburn,et al.  Pragmatic language profiles of school-age children with autism spectrum disorders and Williams syndrome. , 2007, American journal of speech-language pathology.

[36]  M. Huotilainen,et al.  Hemodynamic responses to speech and music in newborn infants , 2009, Human brain mapping.

[37]  Vanessa Hus,et al.  The Autism Diagnostic Observation Schedule—Toddler Module: A New Module of a Standardized Diagnostic Measure for Autism Spectrum Disorders , 2009, Journal of autism and developmental disorders.

[38]  P. Jusczyk,et al.  Some Beginnings of Word Comprehension in 6-Month-Olds , 1999 .

[39]  S. Dehaene,et al.  Functional Neuroimaging of Speech Perception in Infants , 2002, Science.

[40]  T. Sejnowski,et al.  Irresistible environment meets immovable neurons , 1997, Behavioral and Brain Sciences.

[41]  Nimesh Patel,et al.  Surveillance for violent deaths--national violent death reporting system, 16 States, 2006. , 2009, Morbidity and mortality weekly report. Surveillance summaries.

[42]  Alan C. Evans,et al.  Interhemispheric anatomical differences in human primary auditory cortex: probabilistic mapping and volume measurement from magnetic resonance scans. , 1996, Cerebral cortex.

[43]  J L Lancaster,et al.  Automated Talairach Atlas labels for functional brain mapping , 2000, Human brain mapping.

[44]  B. Anderson,et al.  Anatomic asymmetries of the posterior superior temporal lobes: a postmortem study. , 1999, Neuropsychiatry, neuropsychology, and behavioral neurology.

[45]  M. Torrens Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268 , 1990 .

[46]  Y. Samson,et al.  Autism severity and temporal lobe functional abnormalities , 2005, Annals of neurology.

[47]  Sally Ozonoff,et al.  Autism and family home movies: a comprehensive review. , 2006, Journal of developmental and behavioral pediatrics : JDBP.

[48]  Elizabeth Redcay,et al.  Deviant Functional Magnetic Resonance Imaging Patterns of Brain Activity to Speech in 2–3-Year-Old Children with Autism Spectrum Disorder , 2008, Biological Psychiatry.

[49]  P. Kuhl,et al.  Foreign-language experience in infancy: Effects of short-term exposure and social interaction on phonetic learning , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[50]  Fumitaka Homae,et al.  Prosodic processing in the developing brain , 2007, Neuroscience Research.

[51]  K. Pierce,et al.  Detecting, studying, and treating autism early: the one-year well-baby check-up approach. , 2011, The Journal of pediatrics.

[52]  Ruth A. Carper,et al.  Longitudinal Magnetic Resonance Imaging Study of Cortical Development through Early Childhood in Autism , 2010, The Journal of Neuroscience.

[53]  H. Seldon Structure of human auditory cortex. I. Cytoarchitectonics and dendritic distributions , 1981, Brain Research.

[54]  F. Gilles,et al.  Left-right asymmetries of the temporal speech areas of the human fetus. , 1977, Archives of neurology.

[55]  Y. Samson,et al.  Perception of complex sounds in autism: abnormal auditory cortical processing in children. , 2004, The American journal of psychiatry.

[56]  G. Dehaene-Lambertz,et al.  Common Neural Basis for Phoneme Processing in Infants and Adults , 2004, Journal of Cognitive Neuroscience.

[57]  H. Goldstein,et al.  Validity and reliability of the communication and symbolic behavior scales developmental profile with very young children. , 2002, Journal of speech, language, and hearing research : JSLHR.

[58]  M. Rutter,et al.  A comparative study of infantile autism and specific development receptive language disorder. I. The children. , 1975, The British journal of psychiatry : the journal of mental science.

[59]  Helen Tager-Flusberg,et al.  Language laterality in autism spectrum disorder and typical controls: A functional, volumetric, and diffusion tensor MRI study , 2010, Brain and Language.

[60]  N. Geschwind,et al.  Human Brain: Left-Right Asymmetries in Temporal Speech Region , 1968, Science.

[61]  Ralph-Axel Müller,et al.  Atypical functional lateralization of language in autism spectrum disorders , 2008, Brain Research.

[62]  C. Chabris,et al.  Brain activation during semantic processing in autism spectrum disorders via functional magnetic resonance imaging , 2006, Brain and Cognition.

[63]  Michael S. Gaffrey,et al.  A typical participation of visual cortex during word processing in autism: An fMRI study of semantic decision , 2007, Neuropsychologia.

[64]  P. Kuhl,et al.  Infants show a facilitation effect for native language phonetic perception between 6 and 12 months. , 2006, Developmental science.

[65]  J. Buitelaar,et al.  Intact Spectral but Abnormal Temporal Processing of Auditory Stimuli in Autism , 2009, Journal of autism and developmental disorders.

[66]  J. Sebat,et al.  Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene. , 2008, American journal of human genetics.

[67]  P. Kuhl,et al.  Infant speech perception activates Broca's area: a developmental magnetoencephalography study , 2006, Neuroreport.

[68]  I. Rapin,et al.  Update on the language disorders of individuals on the autistic spectrum , 2003, Brain and Development.

[69]  C. Lord,et al.  Neologisms and idiosyncratic language in autistic speakers , 1991, Journal of autism and developmental disorders.

[70]  James Lani,et al.  Mullen Scales of Early Learning (MSEL) , 2010 .

[71]  C. Barthélémy,et al.  Auditory associative cortex dysfunction in children with autism: evidence from late auditory evoked potentials (N1 wave–T complex) , 1999, Clinical Neurophysiology.

[72]  M. Rutter,et al.  A Comparative Study of Infantile Autism and Specific Developmental Receptive Language Disorder , 1975, British Journal of Psychiatry.

[73]  Alan C. Evans,et al.  Positional and surface area asymmetry of the human cerebral cortex , 2009, NeuroImage.

[74]  P. D. Eimas,et al.  Speech Perception in Infants , 1971, Science.

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

[76]  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.

[77]  R. Müller,et al.  Brain Mapping of Language and Auditory Perception in High-Functioning Autistic Adults: A PET Study , 1999, Journal of autism and developmental disorders.

[78]  K. Loveland,et al.  The functions of immediate echolalia in autistic children: A developmental perspective , 1988, Journal of autism and developmental disorders.

[79]  S. F. Witelson,et al.  Left hemisphere specialization for language in the newborn. Neuroanatomical evidence of asymmetry. , 1973, Brain : a journal of neurology.

[80]  M. Dapretto,et al.  Neural basis of irony comprehension in children with autism: the role of prosody and context. , 2006, Brain : a journal of neurology.

[81]  H. Seldon Structure of human auditory cortex. II. Axon distributions and morphological correlates of speech perception , 1981, Brain Research.

[82]  Eric Courchesne,et al.  Localized enlargement of the frontal cortex in early autism , 2005, Biological Psychiatry.

[83]  P. Kuhl Brain Mechanisms in Early Language Acquisition , 2010, Neuron.