Children and Adolescents with Autism Exhibit Reduced MEG Steady-State Gamma Responses

BACKGROUND Recent neuroimaging studies of autism have indicated reduced functional connectivity during both cognitive tasks and rest. These data suggest long-range connectivity may be compromised in this disorder, and current neurological theories of autism contend disrupted inter-regional interactions may be an underlying mechanism explaining behavioral symptomatology. However, it is unclear whether deficient neuronal communication is attributable to fewer long-range tracts or more of a local deficit in neural circuitry. This study examines the integrity of local circuitry by focusing on gamma band activity in auditory cortices of children and adolescents with autism. METHODS Ten children and adolescents with autism and 10 matched controls participated. Both groups listened to 500 ms duration monaural click trains with a 25 ms inter-click interval, as magnetoencephalography was acquired from the contralateral hemisphere. To estimate 40 Hz spectral power density, we performed time-frequency decomposition of the single-trial magnetic steady-state response data using complex demodulation. RESULTS Children and adolescents with autism exhibited significantly reduced left hemispheric 40 Hz power from 200-500 ms post-stimulus onset. In contrast, no significant between group differences were observed for right hemispheric cortices. CONCLUSIONS The production and/or maintenance of left hemispheric gamma oscillations appeared abnormal in participants with autism. We interpret these data as indicating that in autism, particular brain regions may be unable to generate the high-frequency activity likely necessary for binding and other forms of inter-regional interactions. These findings augment connectivity theories of autism with novel evidence that aberrations in local circuitry could underlie putative deficiencies in long-range neural communication.

[1]  L. Lotspeich,et al.  White matter structure in autism: preliminary evidence from diffusion tensor imaging , 2004, Biological Psychiatry.

[2]  R. Tuchman,et al.  Epilepsy and epileptiform EEG: association with autism and language disorders. , 2000, Mental retardation and developmental disabilities research reviews.

[3]  U. Frith,et al.  Why do autistic individuals show superior performance on the block design task? , 1993, Journal of child psychology and psychiatry, and allied disciplines.

[4]  M. Frotscher,et al.  Fast synaptic inhibition promotes synchronized gamma oscillations in hippocampal interneuron networks , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[5]  Uta Frith,et al.  Reading for meaning and reading for sound in autistic and dyslexic children , 1983 .

[6]  R. McCarley,et al.  Abnormal Neural Synchrony in Schizophrenia , 2003, The Journal of Neuroscience.

[7]  J. Mills,et al.  The frequency-modulation following response in young and aged human subjects , 2002, Hearing Research.

[8]  M. Hasselmo,et al.  Gamma frequency-range abnormalities to auditory stimulation in schizophrenia. , 1999, Archives of general psychiatry.

[9]  N. Minshew,et al.  Neuropsychologic functioning in autism: Profile of a complex information processing disorder , 1997, Journal of the International Neuropsychological Society.

[10]  Simon Baron-Cohen,et al.  A test of central coherence theory: linguistic processing in high-functioning adults with autism or Asperger syndrome: is local coherence impaired? , 1999, Cognition.

[11]  Tatiana Foroud,et al.  Linkage disequilibrium between the beta frequency of the human EEG and a GABAA receptor gene locus , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[12]  F. Happé Autism: cognitive deficit or cognitive style? , 1999, Trends in Cognitive Sciences.

[13]  R. Traub,et al.  A mechanism for generation of long-range synchronous fast oscillations in the cortex , 1996, Nature.

[14]  C. Barthélémy,et al.  Cortical auditory processing and communication in children with autism: electrophysiological/behavioral relations. , 2003, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[15]  M. Reite,et al.  Smaller left hemisphere planum temporale in adults with autistic disorder , 2002, Neuroscience Letters.

[16]  Caroline C Brown,et al.  The temporal binding deficit hypothesis of autism , 2002, Development and Psychopathology.

[17]  V. Mountcastle The columnar organization of the neocortex. , 1997, Brain : a journal of neurology.

[18]  B. Grothe,et al.  Temporal processing in sensory systems , 2000, Current Opinion in Neurobiology.

[19]  L. Gustafsson Inadequate cortical feature maps: A neural circuit theory of autism , 1997, Biological Psychiatry.

[20]  T W Picton,et al.  Human auditory steady state potentials. , 1984, Ear and hearing.

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

[22]  Ruth A. Carper,et al.  Autism and Abnormal Development of Brain Connectivity , 2004, The Journal of Neuroscience.

[23]  G. Buzsáki,et al.  Gamma (40-100 Hz) oscillation in the hippocampus of the behaving rat , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[24]  S. Baron-Cohen,et al.  Does the autistic child have a “theory of mind” ? , 1985, Cognition.

[25]  S. Baron-Cohen,et al.  Enhanced discrimination of novel, highly similar stimuli by adults with autism during a perceptual learning task. , 1998, Journal of child psychology and psychiatry, and allied disciplines.

[26]  Terence W. Picton,et al.  Temporal integration in the human auditory cortex as represented by the development of the steady-state magnetic field , 2002, Hearing Research.

[27]  Uta Frith,et al.  Theory of mind , 2001, Current Biology.

[28]  L. Wing,et al.  Severe impairments of social interaction and associated abnormalities in children: Epidemiology and classification , 1979, Journal of autism and developmental disorders.

[29]  M. O'riordan,et al.  Enhanced discrimination in autism , 2001 .

[30]  S. Baron-Cohen,et al.  Superior visual search in autism. , 2001, Journal of experimental psychology. Human perception and performance.

[31]  S. Bryson,et al.  Comprehension of concrete and abstract words in autistic children , 1990, Journal of autism and developmental disorders.

[32]  J. DeFelipe Chandelier cells and epilepsy. , 1999, Brain : a journal of neurology.

[33]  U. Frith Autism: Explaining the Enigma , 2005 .

[34]  M Hämäläinen,et al.  Neuromagnetic steady-state responses to auditory stimuli. , 1989, The Journal of the Acoustical Society of America.

[35]  M. Annett Left, right, hand and brain : the right shift theory , 1985 .

[36]  C. Frith,et al.  Autism, Asperger syndrome and brain mechanisms for the attribution of mental states to animated shapes. , 2002, Brain : a journal of neurology.

[37]  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.

[38]  D. Buxhoeveden,et al.  Minicolumnar pathology in dyslexia , 2002, Annals of neurology.

[39]  D. Buxhoeveden,et al.  Disruption in the Inhibitory Architecture of the Cell Minicolumn: Implications for Autisim , 2003, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[40]  N Papp,et al.  Critical evaluation of complex demodulation techniques for the quantification of bioelectrical activity. , 1977, Biomedical sciences instrumentation.

[41]  P. Teale,et al.  Reduced laterality of the source locations for generators of the auditory steady-state field in schizophrenia , 2003, Biological Psychiatry.

[42]  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.

[43]  S. Baron-Cohen The extreme male brain theory of autism , 2002, Trends in Cognitive Sciences.

[44]  B. Pennington,et al.  Executive function deficits in high-functioning autistic individuals: relationship to theory of mind. , 1991, Journal of child psychology and psychiatry, and allied disciplines.

[45]  Judy R Dubno,et al.  The amplitude-modulation following response in young and aged human subjects , 2001, Hearing Research.

[46]  Jean-Louis Adrien,et al.  Hypersensitivity to acoustic change in children with autism: electrophysiological evidence of left frontal cortex dysfunctioning. , 2002, Psychophysiology.

[47]  M. Reite,et al.  Planum Temporale Volume in Children and Adolescents with Autism , 2005, Journal of autism and developmental disorders.

[48]  Andrew E. Switala,et al.  Minicolumnar pathology in autism , 2002, Neurology.

[49]  H. Yamasue,et al.  Delayed automatic detection of change in speech sounds in adults with autism: A magnetoencephalographic study , 2005, Clinical Neurophysiology.

[50]  F. Happé Central coherence and theory of mind in autism: Reading homographs in context , 1997 .

[51]  R. McCarley,et al.  Neural synchrony indexes disordered perception and cognition in schizophrenia. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[52]  B Horwitz,et al.  The cerebral metabolic landscape in autism. Intercorrelations of regional glucose utilization. , 1988, Archives of neurology.

[53]  Karsten Hoechstetter,et al.  BESA Source Coherence: A New Method to Study Cortical Oscillatory Coupling , 2003, Brain Topography.

[54]  S. Baron-Cohen,et al.  Are people with autism and Asperger syndrome faster than normal on the Embedded Figures Test? , 1997, Journal of child psychology and psychiatry, and allied disciplines.

[55]  U. Frith,et al.  An islet of ability in autistic children: a research note. , 1983, Journal of child psychology and psychiatry, and allied disciplines.