Dataset Information

Involvement of the Serotonin Transporter Gene in Accurate Subcortical Speech Encoding.

ABSTRACT: A flourishing line of evidence has highlighted the encoding of speech sounds in the subcortical auditory system as being shaped by acoustic, linguistic, and musical experience and training. And while the heritability of auditory speech as well as nonspeech processing has been suggested, the genetic determinants of subcortical speech processing have not yet been uncovered. Here, we postulated that the serotonin transporter-linked polymorphic region (5-HTTLPR), a common functional polymorphism located in the promoter region of the serotonin transporter gene (SLC6A4), is implicated in speech encoding in the human subcortical auditory pathway. Serotonin has been shown as essential for modulating the brain response to sound both cortically and subcortically, yet the genetic factors regulating this modulation regarding speech sounds have not been disclosed. We recorded the frequency following response, a biomarker of the neural tracking of speech sounds in the subcortical auditory pathway, and cortical evoked potentials in 58 participants elicited to the syllable /ba/, which was presented >2000 times. Participants with low serotonin transporter expression had higher signal-to-noise ratios as well as a higher pitch strength representation of the periodic part of the syllable than participants with medium to high expression, possibly by tuning synaptic activity to the stimulus features and hence a more efficient suppression of noise. These results imply the 5-HTTLPR in subcortical auditory speech encoding and add an important, genetically determined layer to the factors shaping the human subcortical response to speech sounds.

Significance statement

The accurate encoding of speech sounds in the subcortical auditory nervous system is of paramount relevance for human communication, and it has been shown to be altered in different disorders of speech and auditory processing. Importantly, this encoding is plastic and can therefore be enhanced by language and music experience. Whether genetic factors play a role in speech encoding at the subcortical level remains unresolved. Here we show that a common polymorphism in the serotonin transporter gene relates to an accurate and robust neural tracking of speech stimuli in the subcortical auditory pathway. This indicates that serotonin transporter expression, eventually in combination with other polymorphisms, delimits the extent to which lifetime experience shapes the subcortical encoding of speech.

SUBMITTER: Selinger L

PROVIDER: S-EPMC6601888 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Publications

Involvement of the Serotonin Transporter Gene in Accurate Subcortical Speech Encoding.

Selinger Lenka L Zarnowiec Katarzyna K Via Marc M Clemente Immaculada C IC Escera Carles C

The Journal of neuroscience : the official journal of the Society for Neuroscience 20161001 42

A flourishing line of evidence has highlighted the encoding of speech sounds in the subcortical auditory system as being shaped by acoustic, linguistic, and musical experience and training. And while the heritability of auditory speech as well as nonspeech processing has been suggested, the genetic determinants of subcortical speech processing have not yet been uncovered. Here, we postulated that the serotonin transporter-linked polymorphic region (5-HTTLPR), a common functional polymorphism loc ...[more]

PMID: 27798133

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Project description:BackgroundWe explored the relationship of genetic variants of the serotonin transporter gene SLC6A4, a key regulator of the serotonergic neurotransmission, with both depressive symptoms and plasma interleukin-6 (IL-6) levels.Methods and resultsWe genotyped 20 polymorphisms in 360 male twins (mean age, 54 years) from the Vietnam Era Twin Registry. Current depressive symptoms were measured with the Beck Depression Inventory II. IL-6 was assessed using a commercially available ELISA kit. Genotype associations were analyzed using generalized estimating equations. To study how SLC6A4 genetic vulnerability influences the relationship between depressive symptoms and IL-6, bivariate models were constructed using structural equation modeling. Of the 20 polymorphisms examined, the effective number of independent tests was 6, and the threshold of significance after Bonferroni correction was 0.008. There were 6 single-nucleotide polymorphisms significantly associated with Beck Depression Inventory (P< or =0.008), including rs8071667, rs2020936, rs25528, rs6354, rs11080122, and rs8076005, and 1 single-nucleotide polymorphism was borderline associated (rs12150214, P=0.017). Of these 7 single-nucleotide polymorphisms, 3 were also significantly associated with IL-6 (P<0.008), including rs25528, rs6354, and rs8076005, and the other 4 were borderline associated (P=0.009 to 0.025). The subjects with 1 copy of the minor allele of these 7 single-nucleotide polymorphisms had higher Beck Depression Inventory scores and IL-6 levels. Further bivariate modeling revealed that approximately 10% of the correlation between Beck Depression Inventory and IL-6 could be explained by the SLC6A4 gene.ConclusionsGenetic vulnerability involving the SLC6A4 gene is significantly associated with both increased depressive symptoms and elevated IL-6 plasma levels. Common pathophysiological processes may link depression and inflammation, and implicate the serotonin pathway in neural-immune interactions.

Project description:Auditory masking-the interference of the encoding and processing of an acoustic stimulus imposed by one or more competing stimuli-is nearly omnipresent in daily life, and presents a critical barrier to many listeners, including people with hearing loss, users of hearing aids and cochlear implants, and people with auditory processing disorders. The perceptual aspects of masking have been actively studied for several decades, and particular emphasis has been placed on masking of speech by other speech sounds. The neural effects of such masking, especially at the subcortical level, have been much less studied, in large part due to the technical limitations of making such measurements. Recent work has allowed estimation of the auditory brainstem response (ABR), whose characteristic waves are linked to specific subcortical areas, to naturalistic speech. In this study, we used those techniques to measure the encoding of speech stimuli that were masked by one or more simultaneous other speech stimuli. We presented listeners with simultaneous speech from one, two, three, or five simultaneous talkers, corresponding to a range of signal-to-noise ratios ( SNR ; Clean, 0, -3, and -6 dB), and derived the ABR to each talker in the mixture. Each talker in a mixture was treated in turn as a target sound masked by other talkers, making the response quicker to acquire. We found consistently across listeners that ABR wave V amplitudes decreased and latencies increased as the number of competing talkers increased.Significance statementTrying to listen to someone speak in a noisy setting is a common challenge for most people, due to auditory masking. Masking has been studied extensively at the behavioral level, and more recently in the cortex using EEG and other neurophysiological methods. Much less is known, however, about how masking affects speech encoding in the subcortical auditory system. Here we presented listeners with mixtures of simultaneous speech streams ranging from one to five talkers. We used recently developed tools for measuring subcortical speech encoding to determine how the encoding of each speech stream was impacted by the masker speech. We show that the subcortical response to masked speech becomes smaller and increasingly delayed as the masking becomes more severe.

Dataset Information

Involvement of the Serotonin Transporter Gene in Accurate Subcortical Speech Encoding.

Significance statement

Publications

Involvement of the Serotonin Transporter Gene in Accurate Subcortical Speech Encoding.

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