Abnormalities in gamma-band responses to language stimuli in first-degree relatives of children with autism spectrum disorder: an MEG study

BackgroundSynchronous neural oscillatory activity in the gamma range (30–80 Hz) has been shown to be abnormal in individuals with autism spectrum disorders (ASD) and their first-degree relatives in response to simple auditory stimuli. Gamma-band abnormalities in ASD probands have been seen in response to language stimuli, but this has not been investigated in first-degree relatives. This is of particular interest given that language impairments are a core symptom of ASD and may be part of the broad autism phenotype (BAP) seen in relatives.MethodsMagnetoencephalography recordings during a continuous word recognition task were obtained for 23 parents of a child with ASD (pASD) and 28 adult control participants. Total and evoked gamma-band activity, as well as inter-trial phase-locking factor (PLF), were measured in response to the task. Beta-band activity was also measured, due to its suggested role in language processing. Participants completed a series of language measures to assess the relationship between brain activity and language function, and lateralization of task-related activity was assessed.ResultsThe pASD group showed increased evoked gamma and beta activity, while controls had decreased evoked activity. Additionally, while both groups showed a reduction in total gamma power (commonly seen in language tasks), this reduction was more prominent in the control group. The pASD group demonstrated significantly worse performance on a measure of phonology compared to controls. Significant but distinct relationships were found between gamma/beta activity and language measures within the two groups. In addition, while the overall task generally elicited left lateralized responses, pASD showed greater left lateralization than controls in some regions of interest.ConclusionsAbnormalities in oscillatory responses to language were seen in pASD that are consistent with previous findings in ASD probands. Gamma-band responses to language stimuli have not previously been assessed in first-degree relatives of ASD probands and these findings are supportive of gamma-band activity as a heritable, neurophysiological biomarker of ASD. The possible relationship seen between language function and neural activity in the current study should be investigated further to assess if oscillatory response abnormalities may contribute to behavioural manifestations of the BAP.

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

[2]  Donald C. Rojas,et al.  Children and Adolescents with Autism Exhibit Reduced MEG Steady-State Gamma Responses , 2007, Biological Psychiatry.

[3]  Matthias M. Müller,et al.  Effects of picture repetition on induced gamma band responses, evoked potentials, and phase synchrony in the human EEG. , 2002, Brain research. Cognitive brain research.

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

[5]  W. Freiwald,et al.  Coherent oscillatory activity in monkey area v4 predicts successful allocation of attention. , 2005, Cerebral cortex.

[6]  Lucia Melloni,et al.  Brain Oscillations during Spoken Sentence Processing , 2012, Journal of Cognitive Neuroscience.

[7]  M. Aminoff Principles of Neural Science. 4th edition , 2001 .

[8]  W. Singer,et al.  Oscillatory responses in cat visual cortex exhibit inter-columnar synchronization which reflects global stimulus properties , 1989, Nature.

[9]  Daniel Gembris,et al.  Top-down attentional processing enhances auditory evoked gamma band activity , 2003, Neuroreport.

[10]  J. Rothwell Principles of Neural Science , 1982 .

[11]  J. Piven,et al.  Psychiatric disorder and the broad autism phenotype: evidence from a family study of multiple-incidence autism families. , 1999, The American journal of psychiatry.

[12]  C. Torrence,et al.  A Practical Guide to Wavelet Analysis. , 1998 .

[13]  B. Feige,et al.  High-frequency cortical responses reflect lexical processing: an MEG study. , 1996, Electroencephalography and clinical neurophysiology.

[14]  W. Singer,et al.  Performance- and Stimulus-Dependent Oscillations in Monkey Prefrontal Cortex During Short-Term Memory , 2009, Front. Integr. Neurosci..

[15]  A. Engel,et al.  Beta-band oscillations—signalling the status quo? , 2010, Current Opinion in Neurobiology.

[16]  Ron Dumont,et al.  Delis‐Kaplan Executive Function System , 2008 .

[17]  J. Edgar,et al.  Validating γ Oscillations and Delayed Auditory Responses as Translational Biomarkers of Autism , 2010, Biological Psychiatry.

[18]  Thomas E. Nichols,et al.  Thresholding of Statistical Maps in Functional Neuroimaging Using the False Discovery Rate , 2002, NeuroImage.

[19]  A. Papanicolaou,et al.  Magnetocephalography: a noninvasive alternative to the Wada procedure. , 2004, Journal of neurosurgery.

[20]  H. Otsubo,et al.  Neuromagnetic spectral distribution of implicit processing of words , 2001, Neuroreport.

[21]  E Courchesne,et al.  Attention function and dysfunction in autism. , 2001, Frontiers in bioscience : a journal and virtual library.

[22]  Karl J. Friston,et al.  EEG and MEG Data Analysis in SPM8 , 2011, Comput. Intell. Neurosci..

[23]  Wolf Singer,et al.  Neuronal Synchrony: A Versatile Code for the Definition of Relations? , 1999, Neuron.

[24]  Timothy P.L. Roberts,et al.  Spectral–temporal analysis of cortical oscillations during lexical processing , 2011, Neuroreport.

[25]  C. Lajonchere,et al.  Genetic heritability and shared environmental factors among twin pairs with autism. , 2011, Archives of general psychiatry.

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

[27]  J. Kaiser,et al.  Human gamma-frequency oscillations associated with attention and memory , 2007, Trends in Neurosciences.

[28]  D. Mathalon,et al.  Event-related EEG time-frequency analysis: an overview of measures and an analysis of early gamma band phase locking in schizophrenia. , 2008, Schizophrenia bulletin.

[29]  Joseph Piven,et al.  Defining key features of the broad autism phenotype: A comparison across parents of multiple‐ and single‐incidence autism families , 2008, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[30]  G. Karmos,et al.  Entrainment of Neuronal Oscillations as a Mechanism of Attentional Selection , 2008, Science.

[31]  Antoine J. Shahin,et al.  Brain oscillations during semantic evaluation of speech , 2009, Brain and Cognition.

[32]  John O. Willis,et al.  Peabody Picture Vocabulary Test–Third Edition , 2008 .

[33]  A. Bailey,et al.  Contextual integration the unusual way: a magnetoencephalographic study of responses to semantic violation in individuals with autism spectrum disorders , 2008, The European journal of neuroscience.

[34]  Luc H. Arnal,et al.  Transitions in neural oscillations reflect prediction errors generated in audiovisual speech , 2011, Nature Neuroscience.

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

[36]  C Pantev,et al.  A high-precision magnetoencephalographic study of human auditory steady-state responses to amplitude-modulated tones. , 2000, The Journal of the Acoustical Society of America.

[37]  A. B. Hollingshead,et al.  Four factor index of social status , 1975 .

[38]  Philippe Kahane,et al.  Task‐related gamma‐band dynamics from an intracerebral perspective: Review and implications for surface EEG and MEG , 2009, Human brain mapping.

[39]  Joseph K. Torgesen,et al.  Comprehensive Test of Phonological Processing , 1997 .

[40]  Karl J. Friston,et al.  Electromagnetic source reconstruction for group studies , 2008, NeuroImage.

[41]  S. Nagarajan,et al.  Sensory Processing in Autism: A Review of Neurophysiologic Findings , 2011, Pediatric Research.

[42]  Lisa B. Wilson,et al.  Transient and steady-state auditory gamma-band responses in first-degree relatives of people with autism spectrum disorder , 2011, Molecular autism.

[43]  Marko Wilke,et al.  LI-tool: A new toolbox to assess lateralization in functional MR-data , 2007, Journal of Neuroscience Methods.

[44]  Tatiana A. Stroganova,et al.  Excess of High Frequency Electroencephalogram Oscillations in Boys with Autism , 2007, Biological Psychiatry.

[45]  O. Bertrand,et al.  Oscillatory gamma activity in humans and its role in object representation , 1999, Trends in Cognitive Sciences.

[46]  Michael W. Spratling,et al.  Disordered visual processing and oscillatory brain activity in autism and Williams Syndrome , 2001, Neuroreport.

[47]  B. Bogerts,et al.  Altered evoked γ-band responses as a neurophysiological marker of schizophrenia? , 2011, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[48]  Sue Fletcher-Watson,et al.  A review of methods in the study of attention in autism , 2010 .

[49]  T. Picton,et al.  The effect of attention on the auditory steady-state response. , 2004, Neurology & clinical neurophysiology : NCN.

[50]  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.

[51]  S. I. Lee,et al.  Assessment of Language Dominance by Event-Related Oscillatory Changes in an Auditory Language Task: Magnetoencephalography Study , 2010, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[52]  Peter F. Liddle,et al.  Changes in brain network activity during working memory tasks: A magnetoencephalography study , 2011, NeuroImage.

[53]  Toshiki Yoshimine,et al.  Effects of the emotional connotations in words on the frontal areas—A spatially filtered MEG study , 2007, NeuroImage.

[54]  Catherine Tallon-Baudry,et al.  Induced γ-Band Activity during the Delay of a Visual Short-Term Memory Task in Humans , 1998, The Journal of Neuroscience.

[55]  Toshiki Yoshimine,et al.  Determination of language dominance with synthetic aperture magnetometry: comparison with the Wada test , 2004, NeuroImage.

[56]  Cynthia R. Johnson,et al.  Attentional Processes in Autism , 2001, Journal of autism and developmental disorders.

[57]  J. Porta‐Etessam,et al.  [Language and aphasias]. , 1997, Revista de neurologia.

[58]  C. Gillberg,et al.  A twin study of autism in Denmark, Finland, Iceland, Norway and Sweden. , 1989, Journal of child psychology and psychiatry, and allied disciplines.

[59]  C D Tesche,et al.  Signal-space projections of MEG data characterize both distributed and well-localized neuronal sources. , 1995, Electroencephalography and clinical neurophysiology.

[60]  J. Mitchell Comprehensive Test of Phonological Processing , 2001 .

[61]  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.

[62]  A. Engel,et al.  Cognitive functions of gamma-band activity: memory match and utilization , 2004, Trends in Cognitive Sciences.

[63]  S. Baron-Cohen,et al.  Visual attention in autism families: 'unaffected' sibs share atypical frontal activation. , 2010, Journal of child psychology and psychiatry, and allied disciplines.

[64]  Giri P. Krishnan,et al.  The effect of selective attention on the gamma-band auditory steady-state response , 2007, Neuroscience Letters.

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

[66]  R. Dean,et al.  TEST REVIEW: Dean C. Delis, Edith Kaplan & Joel H. Kramer, Delis Kaplan Executive Function System (D-KEFS), The Psychological Corporation, San Antonio, TX, 2001. $415.00 (complete kit) , 2006 .

[67]  Arnaud Delorme,et al.  EEGLAB: an open source toolbox for analysis of single-trial EEG dynamics including independent component analysis , 2004, Journal of Neuroscience Methods.

[68]  A. Bailey,et al.  Autism: The Phenotype in Relatives , 1998, Journal of autism and developmental disorders.

[69]  Ron Dumont,et al.  Expressive Vocabulary Test , 2008 .

[70]  J. Pernier,et al.  Induced gamma-band activity during the delay of a visual short-term memory task in humans. , 1998, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[71]  W. McMahon,et al.  Superior Temporal Gyrus, Language Function, and Autism , 2007, Developmental neuropsychology.

[72]  Madhukar H. Trivedi,et al.  The pattern of sensory processing abnormalities in autism , 2006, Autism : the international journal of research and practice.

[73]  K. Reinikainen,et al.  Selective attention enhances the auditory 40-Hz transient response in humans , 1993, Nature.

[74]  J. Sarvas Basic mathematical and electromagnetic concepts of the biomagnetic inverse problem. , 1987, Physics in medicine and biology.

[75]  Toshiki Yoshimine,et al.  Gamma-band desynchronization in language areas reflects syntactic process of words , 2003, Neuroscience Letters.

[76]  H. Jasper,et al.  The ten-twenty electrode system of the International Federation. The International Federation of Clinical Neurophysiology. , 1999, Electroencephalography and clinical neurophysiology. Supplement.

[77]  Peter Teale,et al.  BMC Psychiatry BioMed Central Research article Use of antipsychotics and benzodiazepines in patients with psychiatric emergencies: Results of an observational trial , 2008 .

[78]  William W. Graves,et al.  Where is the semantic system? A critical review and meta-analysis of 120 functional neuroimaging studies. , 2009, Cerebral cortex.

[79]  J. Rabe-Jabłońska,et al.  [Affective disorders in the fourth edition of the classification of mental disorders prepared by the American Psychiatric Association -- diagnostic and statistical manual of mental disorders]. , 1993, Psychiatria polska.

[80]  B. Pennington,et al.  Impairments in phonological processing and nonverbal intellectual function in parents of children with autism , 2008, Journal of clinical and experimental neuropsychology.

[81]  T. Elbert,et al.  Relationship of transient and steady-state auditory evoked fields. , 1993, Electroencephalography and clinical neurophysiology.

[82]  J. Piven,et al.  Personality and language characteristics in parents from multiple-incidence autism families. , 1997, American journal of medical genetics.

[83]  A. Bailey,et al.  Autism as a strongly genetic disorder: evidence from a British twin study , 1995, Psychological Medicine.

[84]  S Makeig,et al.  Human auditory evoked gamma-band magnetic fields. , 1991, Proceedings of the National Academy of Sciences of the United States of America.