Dataset Information

Effects of metabotropic glutamate receptor 3 genotype on phonetic mismatch negativity.

ABSTRACT: BACKGROUND: The genetic and molecular basis of glutamatergic dysfunction is one key to understand schizophrenia, with the identification of an intermediate phenotype being an essential step. Mismatch negativity (MMN) or its magnetic counterpart, magnetic mismatch field (MMF) is an index of preattentive change detection processes in the auditory cortex and is generated through glutamatergic neurotransmission. We have previously shown that MMN/MMF in response to phoneme change is markedly reduced in schizophrenia. Variations in metabotropic glutamate receptor (GRM3) may be associated with schizophrenia, and has been shown to affect cortical function. Here we investigated the effect of GRM3 genotypes on phonetic MMF in healthy men. METHODS: MMF in response to phoneme change was recorded using magnetoencephalography in 41 right-handed healthy Japanese men. Based on previous genetic association studies in schizophrenia, 4 candidate SNPs (rs6465084, rs2299225, rs1468412, rs274622) were genotyped. RESULTS: GRM3 rs274622 genotype variations significantly predicted MMF strengths (p?=?0.009), with C carriers exhibiting significantly larger MMF strengths in both hemispheres compared to the TT subjects. CONCLUSIONS: These results suggest that variations in GRM3 genotype modulate the auditory cortical response to phoneme change in humans. MMN/MMF, particularly those in response to speech sounds, may be a promising and sensitive intermediate phenotype for clarifying glutamatergic dysfunction in schizophrenia.

SUBMITTER: Kawakubo Y

PROVIDER: S-EPMC3191133 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Effects of metabotropic glutamate receptor 3 genotype on phonetic mismatch negativity.

Kawakubo Yuki Y Suga Motomu M Tochigi Mamoru M Yumoto Masato M Itoh Kenji K Sasaki Tsukasa T Kano Yukiko Y Kasai Kiyoto K

PloS one 20111011 10

<h4>Background</h4>The genetic and molecular basis of glutamatergic dysfunction is one key to understand schizophrenia, with the identification of an intermediate phenotype being an essential step. Mismatch negativity (MMN) or its magnetic counterpart, magnetic mismatch field (MMF) is an index of preattentive change detection processes in the auditory cortex and is generated through glutamatergic neurotransmission. We have previously shown that MMN/MMF in response to phoneme change is markedly r ...[more]

PMID: 22022368

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Project description:How speech sounds are represented in the brain is not fully understood. The mismatch negativity (MMN) has proven to be a powerful tool in this regard. The MMN event-related potential is elicited by a deviant stimulus embedded within a series of repeating standard stimuli. Listeners construct auditory memory representations of these standards despite acoustic variability. In most designs that test speech sounds, however, this variation is typically intra-category: All standards belong to the same phonetic category. In the current paper, inter-category variation is presented in the standards. These standards vary in manner of articulation but share a common phonetic feature. In the standard retroflex experimental block, Mandarin Chinese speaking participants are presented with a series of "standard" consonants that share the feature [retroflex], interrupted by infrequent non-retroflex deviants. In the non-retroflex standard experimental block, non-retroflex standards are interrupted by infrequent retroflex deviants. The within-block MMN was calculated, as was the identity MMN (iMMN) to account for intrinsic differences in responses to the stimuli. We only observed a within-block MMN to the non-retroflex deviant embedded in the standard retroflex block. This suggests that listeners extract [retroflex] despite significant inter-category variation. In the non-retroflex standard block, because there is little on which to base a coherent auditory memory representation, no within-block MMN was observed. The iMMN to the retroflex was observed in a late time-window at centro-parieto-occipital electrode sites instead of fronto-central electrodes, where the MMN is typically observed, potentially reflecting the increased difficulty posed by the added variation in the standards. In short, participants can construct auditory memory representations despite significant acoustic and inter-category phonological variation so long as a shared phonetic feature binds them together.

Dataset Information

Effects of metabotropic glutamate receptor 3 genotype on phonetic mismatch negativity.

Publications

Effects of metabotropic glutamate receptor 3 genotype on phonetic mismatch negativity.

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