Timing is everything: neural response dynamics during syllable processing and its relation to higher-order cognition in schizophrenia and healthy comparison subjects.

Successful linguistic processing requires efficient encoding of successively-occurring auditory input in a time-constrained manner, especially under noisy conditions. In this study we examined the early neural response dynamics to rapidly-presented successive syllables in schizophrenia participants and healthy comparison subjects, and investigated the effects of noise on these responses. We used magnetoencephalography (MEG) to reveal the time-course of stimulus-locked activity over bilateral auditory cortices during discrimination of syllable pairs that differed either in voice onset time (VOT) or place of articulation (POA), in the presence or absence of noise. We also examined the association of these early neural response patterns to higher-order cognitive functions. The M100 response, arising from auditory cortex and its immediate environs, showed less attenuation to the second syllable in patients with schizophrenia than healthy comparison subjects during VOT-based discrimination in noise. M100 response amplitudes were similar between groups for the first syllable during all three discrimination conditions, and for the second syllable during VOT-based discrimination in quiet and POA-based discrimination in noise. Across subjects, the lack of M100 attenuation to the second syllable during VOT-based discrimination in noise was associated with poorer task accuracy, lower education and IQ, and lower scores on measures of Verbal Learning and Memory and Global Cognition. Because the neural response to the first syllable was not significantly different between groups, nor was a schizophrenia-related difference obtained in all discrimination tasks, early linguistic processing dysfunction in schizophrenia does not appear to be due to general sensory input problems. Rather, data suggest that faulty temporal integration occurs during successive syllable processing when the signal-to-noise ratio is low. Further, the neural mechanism by which the second syllable is suppressed during noise-challenged VOT discrimination appears to be important for higher-order cognition and provides a promising target for neuroscience-guided cognitive training approaches to schizophrenia.

[1]  S. Jones,et al.  Mismatch negativity to single and multiple pitch-deviant tones in regular and pseudo-random complex tone sequences , 2002, Clinical Neurophysiology.

[2]  Risto Näätänen,et al.  Magnetoencephalography in studies of human cognitive brain function , 1994, Trends in Neurosciences.

[3]  M. Tervaniemi,et al.  Basic auditory dysfunction in dyslexia as demonstrated by brain activity measurements. , 2000, Psychophysiology.

[4]  D Sagi,et al.  Where practice makes perfect in texture discrimination: evidence for primary visual cortex plasticity. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[5]  R. Ilmoniemi,et al.  Magnetoencephalography-theory, instrumentation, and applications to noninvasive studies of the working human brain , 1993 .

[6]  M. Merzenich,et al.  Cortical auditory signal processing in poor readers. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[7]  Brian F. O'Donnell,et al.  Contributions of subtype and spectral frequency analyses to the study of P50 ERP amplitude and suppression in schizophrenia , 2005, Schizophrenia Research.

[8]  S. Kay,et al.  The positive and negative syndrome scale (PANSS) for schizophrenia. , 1987, Schizophrenia bulletin.

[9]  Brett A Clementz,et al.  Response to the first stimulus determines reduced auditory evoked response suppression in schizophrenia: single trials analysis using MEG , 2001, Clinical Neurophysiology.

[10]  Stephen J. Jones,et al.  Cortical processing of complex tone stimuli: mismatch negativity at the end of a period of rapid pitch modulation. , 1999, Brain research. Cognitive brain research.

[11]  D. Poeppel,et al.  Speech perception at the interface of neurobiology and linguistics , 2008, Philosophical Transactions of the Royal Society B: Biological Sciences.

[12]  M. Scherg,et al.  Intracerebral Sources of Human Auditory-Evoked Potentials , 1999, Audiology and Neurotology.

[13]  R. Hari,et al.  Auditory evoked transient and sustained magnetic fields of the human brain localization of neural generators , 1980, Experimental Brain Research.

[14]  F. Duffy,et al.  Auditory Evoked Responses to Single Tones and Closely Spaced Tone Pairs in Children Grouped by Reading or Matrices Abilities , 1999, Clinical EEG.

[15]  R. Kahn,et al.  Language lateralization in schizophrenia, an fMRI study , 2001, Schizophrenia Research.

[16]  Raquel E. Gur,et al.  Profile of auditory information-processing deficits in schizophrenia , 2009, Psychiatry Research.

[17]  V. Hazan,et al.  Speech Perception in Children with Specific Reading Difficulties (Dyslexia) , 1998, The Quarterly journal of experimental psychology. A, Human experimental psychology.

[18]  J. Vrba,et al.  Signal processing in magnetoencephalography. , 2001, Methods.

[19]  M M Merzenich,et al.  Auditory processing parallels reading abilities in adults. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[20]  T. Hendler,et al.  Reduced language lateralization in first-episode schizophrenia: An fMRI index of functional asymmetry , 2009, Psychiatry Research: Neuroimaging.

[21]  Peter F. Liddle,et al.  Abnormal processing of speech during oddball target detection in schizophrenia , 2003, NeuroImage.

[22]  W. Singer,et al.  Contribution of impaired early-stage visual processing to working memory dysfunction in adolescents with schizophrenia: a study with event-related potentials and functional magnetic resonance imaging. , 2007, Archives of general psychiatry.

[23]  P. Bolton,et al.  Speech-in-noise perception in high-functioning individuals with autism or Asperger's syndrome. , 2004, Journal of child psychology and psychiatry, and allied disciplines.

[24]  平野 昭吾 Abnormal neural oscillatory activity to speech sounds in schizophrenia : a magnetoencephalography study , 2009 .

[25]  D. Braff,et al.  Mismatch negativity deficits are associated with poor functioning in schizophrenia patients. , 2005, Archives of general psychiatry.

[26]  Risto Näätänen,et al.  Central auditory dysfunction in schizophrenia as revealed by the mismatch negativity (MMN) and its magnetic equivalent MMNm: a review. , 2009, The international journal of neuropsychopharmacology.

[27]  R. Kahn,et al.  Language lateralization in female patients with schizophrenia: an fMRI study , 2003, Schizophrenia Research.

[28]  V D Calhoun,et al.  Auditory oddball deficits in schizophrenia: an independent component analysis of the fMRI multisite function BIRN study. , 2009, Schizophrenia bulletin.

[29]  Daniel C. Javitt,et al.  Reading impairment and visual processing deficits in schizophrenia , 2006, Schizophrenia Research.

[30]  Acknowledgements , 1992, Experimental Gerontology.

[31]  Warren H Meck,et al.  Cortico-striatal Representation of Time in Animals and Humans This Review Comes from a Themed Issue on Cognitive Neuroscience Edited Evidence from Patient Populations and Electrical Potentials Neuroimaging Evidence Using Fmri and Pet , 2022 .

[32]  N. Kraus,et al.  Neurobiologic responses to speech in noise in children with learning problems: deficits and strategies for improvement , 2001, Clinical Neurophysiology.

[33]  G. A. Miller,et al.  Schizophrenia diagnosis and anterior hippocampal volume make separate contributions to sensory gating. , 2008, Psychophysiology.

[34]  David L. Braff,et al.  Preattentive Sensory Processing as Indexed by the MMN and P3a Brain Responses is Associated with Cognitive and Psychosocial Functioning in Healthy Adults , 2007, Journal of Cognitive Neuroscience.

[35]  H. Renvall,et al.  Impaired processing of rapid stimulus sequences in dyslexia , 2001, Trends in Cognitive Sciences.

[36]  G. A. Miller,et al.  Lateralization of auditory sensory gating and neuropsychological dysfunction in schizophrenia. , 2003, The American journal of psychiatry.

[37]  H M Sussman The Representation of Stop Consonants in Three-Dimensional Acoustic Space , 1991, Phonetica.

[38]  M. Kisley,et al.  Deficits in auditory and visual temporal perception in schizophrenia , 2002, Cognitive neuropsychiatry.

[39]  A. Aleman,et al.  Hearing a voice in the noise: auditory hallucinations and speech perception , 2007, Psychological Medicine.

[40]  T. Q. Irigaray,et al.  Intellectual abilities in Alzheimer's disease patients: Contributions from the Wechsler Abbreviated Scale of Intelligence (WASI) , 2010 .

[41]  K Sekihara,et al.  NUTMEG: a neuromagnetic source reconstruction toolbox. , 2004, Neurology & clinical neurophysiology : NCN.

[42]  William P. Hetrick,et al.  Temporal processing dysfunction in schizophrenia , 2008, Brain and Cognition.

[43]  R. Klein,et al.  The evidence for a temporal processing deficit linked to dyslexia: A review , 1995, Psychonomic bulletin & review.

[44]  Gina R. Kuperberg,et al.  Functional Magnetic Resonance Imaging Reveals Neuroanatomical Dissociations During Semantic Integration in Schizophrenia , 2008, Biological Psychiatry.

[45]  T. Baldeweg,et al.  Mismatch negativity potentials and cognitive impairment in schizophrenia , 2004, Schizophrenia Research.

[46]  Walter Ritter,et al.  Associated deficits in mismatch negativity generation and tone matching in schizophrenia , 2000, Clinical Neurophysiology.

[47]  Kiyoto Kasai,et al.  Phonetic mismatch negativity predicts verbal memory deficits in schizophrenia , 2006, Neuroreport.

[48]  John J. Foxe,et al.  The neural substrates of impaired prosodic detection in schizophrenia and its sensorial antecedents. , 2007, The American journal of psychiatry.

[49]  W. Dreschler,et al.  ICRA noises: artificial noise signals with speech-like spectral and temporal properties for hearing instrument assessment. International Collegium for Rehabilitative Audiology. , 2001, Audiology : official organ of the International Society of Audiology.

[50]  N. Kraus Auditory Pathway Encoding and Neural Plasticity in Children with Learning Problems , 2001, Audiology and Neurotology.

[51]  D. Poeppel,et al.  Auditory evoked M100 reflects onset acoustics of speech sounds , 1998, Brain Research.

[52]  L. C. Bidwell,et al.  Differential activation patterns of occipital and prefrontal cortices during motion processing: Evidence from normal and schizophrenic brains , 2008, Cognitive, affective & behavioral neuroscience.

[53]  D. Javitt,et al.  Encoding vs. retention: Differential effects of cue manipulation on working memory performance in schizophrenia , 2007, Schizophrenia Research.

[54]  B Wible,et al.  Abnormal neural encoding of repeated speech stimuli in noise in children with learning problems , 2002, Clinical Neurophysiology.

[55]  T. Picton,et al.  The N1 wave of the human electric and magnetic response to sound: a review and an analysis of the component structure. , 1987, Psychophysiology.

[56]  Robert Freedman,et al.  The genetics of sensory gating deficits in schizophrenia , 2003, Current psychiatry reports.

[57]  T. Carrell,et al.  Auditory Neurophysiologic Responses and Discrimination Deficits in Children with Learning Problems , 1996, Science.

[58]  Gregory A. Miller,et al.  M50 sensory gating predicts negative symptoms in schizophrenia , 2005, Schizophrenia Research.

[59]  S. Jones The internal auditory clock: what can evoked potentials reveal about the analysis of temporal sound patterns, and abnormal states of consciousness? , 2002, Neurophysiologie Clinique/Clinical Neurophysiology.

[60]  Hagai Attias,et al.  A probabilistic algorithm integrating source localization and noise suppression for MEG and EEG data , 2006, NeuroImage.

[61]  M. Merzenich,et al.  Brain plasticity and functional losses in the aged: scientific bases for a novel intervention. , 2006, Progress in brain research.

[62]  J. Stein,et al.  To see but not to read; the magnocellular theory of dyslexia , 1997, Trends in Neurosciences.

[63]  Mingxiong Huang,et al.  Distinct M50 and M100 auditory gating deficits in schizophrenia. , 2005, Psychophysiology.

[64]  P Tallal,et al.  Developmental aphasia: rate of auditory processing and selective impairment of consonant perception. , 1974, Neuropsychologia.

[65]  P Tallal,et al.  Cortical plasticity underlying perceptual, motor, and cognitive skill development: implications for neurorehabilitation. , 1996, Cold Spring Harbor symposia on quantitative biology.

[66]  Sophia Vinogradov,et al.  Using neuroplasticity-based auditory training to improve verbal memory in schizophrenia. , 2009, The American journal of psychiatry.

[67]  S. Sponheim,et al.  An auditory processing abnormality specific to liability for schizophrenia , 2008, Schizophrenia Research.

[68]  D. Javitt,et al.  Early-stage visual processing and cortical amplification deficits in schizophrenia. , 2005, Archives of general psychiatry.

[69]  H. Yabe,et al.  Deviant Matters: Duration, Frequency, and Intensity Deviants Reveal Different Patterns of Mismatch Negativity Reduction in Early and Late Schizophrenia , 2008, Biological Psychiatry.

[70]  F. Boers,et al.  Optimized mismatch negativity paradigm reflects deficits in schizophrenia patients A combined EEG and MEG study , 2008, Biological Psychology.

[71]  Wouter A. Dreschler,et al.  ICRA Noises: Artificial Noise Signals with Speech-like Spectral and Temporal Properties for Hearing Instrument Assessment: Ruidos ICRA: Señates de ruido artificial con espectro similar al habla y propiedades temporales para pruebas de instrumentos auditivos , 2001 .

[72]  C. Gallistel,et al.  Toward a neurobiology of temporal cognition: advances and challenges , 1997, Current Opinion in Neurobiology.

[73]  A. A. Fife,et al.  The Use of a Squid Third Order Spatial Gradiometer to Measure Magnetic Fields of the Brain a , 1984, Annals of the New York Academy of Sciences.

[74]  M Steinschneider,et al.  Temporal encoding of the voice onset time phonetic parameter by field potentials recorded directly from human auditory cortex. , 1999, Journal of neurophysiology.

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