During the first year of life, infants go from perceiving speech sounds primarily based on their acoustic characteristics, to perceiving speech sounds as belonging to speech sound categories relevant in their native language(s). The transition is apparent in that very young infants typically discriminate both native and non-native speech sound contrasts, whereas older infants show better discrimination for native contrasts and worse or no discrimi­na­tion for non-native contrasts. The rate of this perceptual reorganization depends, among other things, on the salience of the relevant speech sounds within the speech signal. As such, the perceptual reorganization of vowels and lexical tone typically precedes the perceptual reorganization of consonants. Perceptual reorganizatoin of speech sounds is often demonstrated by measuring in­fants’ discrimination of specific speech sound contrasts across development. One way of measuring discriminatory ability is to use the mismatch response (MMR). This is a brain response that can be measured using external electroencephalography re­cord­ings. Pre­senting an oddball (deviant) stimulus among a series of standard stimuli elicits a response that, in adults, correlates well with behavioral discrimination. When the two stimuli are speech sounds contrastive in the listeners’ language, the response arguably reflects both acoustic and linguistic processing. In infants, the response is less studied, but has nevertheless already proven useful for studies on the perceptual reorganization of speech sounds. The present thesis documents a series of studies with the end game of investigating how amount of speech exposure influences the perceptual reorganization, and whe­ther the learning mechanisms involved in speech sound cate­gory learning is specific to speech or domain-general. In order to be able to compare MMR results across diffe­rent age groups in infancy, a non-speech control condition needed to be devised however, to account for changes in the MMR across development that are attributable to general brain matura­tion rather than language development specifically. Findings of studies incorporated in the thesis show that spectrally rotated speech can be used to approximate the acoustic part of the MMR in adults. Subtracting the acoustic part of the MMR from the full MMR thus estimates the part of the MMR that is linked to linguistic, rather than acoustic, processing. The strength of this linguistic part of the MMR in four- and eight-month-old infants is directly related to the daily amount of speech that the infants are exposed to. No evidence of distributional learning of non-speech auditory categories was demonstrated in adults, but the results together with previous research generated hypo­theses for future study. In conclusion, the research performed within the scope of this thesis highlight the need of a non-speech control condition for use in developmental speech perception studies using the MMR, demonstrates the viability of one such non-speech control condition, and points toward relevant future research within the topic of speech sound category development. / <p>At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 3: Manuscript.</p>

Transcranial direct current stimulation (tDCS) is a non-invasive form of brain stimulation which uses a very weak constant current to temporarily excite or inhibit activity in the brain area of interest via electrodes placed on the scalp, depending on the polarity and strength of the current. Presently, tDCS is being used as a tool to investigate frontal cognition in healthy controls and to improve symptoms in neurological and psychiatric patients. Relatively little research has been conducted with respect to tDCS and the auditory cortex (AC). The primary aim of this thesis was to elucidate the effects of tDCS on auditory sensory discrimination, assessed with the mismatch negativity (MMN) event-related potential (ERP). In the first pilot study, healthy participants were assessed in a randomized, double-blind, sham-controlled design, in which participants received anodal tDCS over the primary AC (2 mA for 20 minutes) in one session and ‘sham’ stimulation (i.e. no stimulation) in the other. Pitch MMN was found to be enhanced after receiving anodal tDCS, with the effects being evidenced in individuals with relatively low (vs. high) baseline amplitudes. No significant effects were seen with sham stimulation. A second study examined the separate and interacting effects of anodal and cathodal tDCS on MMN measures. MMN was assessed pre- and post-tDCS (2 mA, 20 minutes) in 2 separate sessions, one involving sham stimulation, followed by anodal stimulation, and one involving cathodal stimulation, followed by anodal stimulation. Only anodal tDCS over the AC increased pitch MMN in baseline-stratified groups, and while cathodal tDCS decreased MMN, subsequent anodal stimulation did not significantly alter MMNs. As evidence has shown that tDCS lasting effects may be dependent on N-methyl-D-aspartate (NMDA) receptor activity, a pharmacological study investigated the use of dextromethorphan (DMO), an NMDA antagonist, to assess possible modulation of tDCS’ effects on both MMN and working memory (WM) performance. The study involved four test sessions that compared pre- and post-anodal tDCS over the AC and sham stimulation with both DMO (50 mL) and placebo administration. MMN amplitude increases were only seen with anodal tDCS with placebo administration, not with sham stimulation, nor with DMO administration. In the sham condition, DMO decreased MMN amplitudes. Anodal tDCS improved WM performance in the active drug condition. Findings from this study contribute to the understanding of underlying neurobiological mechanisms mediating tDCS-sensory and memory improvements. As cognitive impairment has been proposed to be the core feature of schizophrenia disorder (Sz) and MMN is a putative biomarker of Sz, a pilot study was conducted to assess the effects of pre- and post-tDCS on MMN measures in 12 Sz patients, as well as WM performance. Temporal, frontal and sham tDCS were applied in separate sessions. Results demonstrated a trend for pitch MMNs to increase with anodal temporal tDCS, which was significant in a subgroup of Sz individuals with auditory hallucinations, who had low MMNs at baseline. Anodal frontal tDCS significantly increased WM performance, which was found to positively correlate with MMN-tDCS effects. The findings contribute to our understanding of tDCS effects for MMN-indexed sensory discrimination and WM performance in healthy participants and individuals with Sz disorder and may have implications for treatment of sensory processing deficits in neuropsychiatric illness.

The present thesis employed event-related potentials, the minute responses of the brain, to examine the differences in processing of increases and decreases in auditory intensity. The manner in which intensity was manipulated (i.e., whether it represented physical or psychological change) varied across the studies of the thesis. Study 1 investigated the processing of physical intensity change during wakefulness and natural sleep. An oddball paradigm (80 dB standard, 90 dB increment, 60 dB decrement) was presented to subjects during the waking state and during sleep. The increment elicited a larger deviant-related negativity and P3a than the decrement in the waking state. During sleep, only the increment deviant continued to elicit ERPs related to the detection of change. The waking and sleeping findings support the notion that increases in intensity are more salient to an observer. Studies 2 and 3 of this thesis determined the degree to which this differential salience could be attributed to the fact that intensity increments result in increased activation of the change and transient detection systems while intensity decrements result in greater activation of only the change detection system. In order to address this question, an alternating intensity pattern was employed (HLHLHLHL) with deviants created by the repetition of a tone in the sequence (HLHLHHHL) that violated the expectancy for a higher (psychological decrements) or lower intensity tone (psychological increments). Because deviant stimuli were physically identical to preceding standards, this manipulation should not have led to increased output of the transient detection system (N1 enhancement), permitting isolation of the output of the change detection system (Mismatch Negativity, MMN). The findings of these studies indicated that psychological increments resulted in shorter latency and larger amplitude MMNs than psychological decrements and that these differences could not be explained by the physical differences between deviant stimuli or temporal integration. This thesis provides convincing evidence that stimuli representing increments in intensity result in faster and more robust change detection. Further, the increased salience of increment stimuli cannot be solely explained by the contribution of transient detector activation, as it persists even when deviance-related processing is isolated to the change detection system.

Short-term memory (STM) has demonstrated to be affected by serial order, involving the use of rhythm and entrainment to stimuli. However, less is known of the extent of this relationship and language learning, and the literature focuses on words rather than sentences. Moreover, the literature lacks an exploration of whether this relationship has a correlation with MMN responses. We had 30 participants (21 female) complete two sentence repetition tasks, a temporal rhythm accuracy task, and two temporal order judgment tasks. We also recorded the electroencephalograms (EEG) from 24 of the participants (17 female) while they listened to syllables differing by time of presentation and differing by consonant and vowel. We then correlated performance on these tasks to performance on a foreign-word learning (FWL) task. We hypothesized that the STM tasks would predict performance in the FWL task, and we explored whether temporal accuracy and word learning correlated with MMN responses to early stimuli. We found that only the foreign sentence repetition task significantly predicted performance in the FWL task. We also did not find any significant correlations with MMN responses and temporal accuracy and word learning abilities. Findings show that with previous exposure to a novel language, the prosodic pattern of the foreign language is stored temporarily in STM, which enhances learning of the foreign words. Further exploration is needed to understand the relationship of temporal order and language learning with cortical responses. / Thesis / Master of Science (MSc) / Spoken language is driven by rhythm and keeping track of this rhythm allows us to keep track of the order in which sounds in language are presented. Remembering the order of items requires the use of short-term memory. The better one is at repeating back the order of items, the better they are at learning new words. This thesis investigates the relationship between various short-term memory tasks (English nonword sentence repetition task, foreign sentence repetition task, temporal rhythm accuracy task, auditory judgment task, visual judgment task) and foreign-word learning. This thesis also explores whether there is a correlation between one’s brain responses to differing stimuli and a person’s ability to track the timing and order of items, as well as a person’s ability to learn new words. The results reveal that only the foreign sentence repetition task, using the same foreign language as the word learning task, significantly predicts one’s ability to accurately learn foreign words. The results did not show any significant interaction between one’s neural responses and rhythm or word learning. These results suggest that the ability to maintain the order of items in memory aids word learning, but further exploration is required with regards to non-verbal stimuli and neural responses. It is important to investigate individual differences in repetition tasks that require short-term memory, as this will aid in understanding normal language development and language acquisition.

La voix est un stimulus auditif omniprésent dans notre environnement sonore. Elle permet non seulement la parole, mais serait aussi l’équivalent d’un visage auditif transmettant notamment des informations identitaires et affectives importantes. Notre capacité à discriminer et reconnaître des voix est socialement et biologiquement importante et elle figure parmi les fonctions les plus importantes du système auditif humain. La présente thèse s’intéressait à l’ontogénèse et à la spécificité de la réponse corticale à la voix humaine et avait pour but trois objectifs : (1) mettre sur pied un protocole électrophysiologique permettant de mesurer objectivement le traitement de la familiarité de la voix chez le sujet adulte; (2) déterminer si ce même protocole pouvait aussi objectiver chez le nouveau-né de 24 heures un traitement préférentiel d’une voix familière, notamment la voix de la mère; et (3) mettre à l’épreuve la robustesse d’une mesure électrophysiologique, notamment la Fronto-Temporal Positivity to Voices, s’intéressant à la discrimination pré-attentionnelle entre des stimuli vocaux et non-vocaux. Les résultats découlant des trois études expérimentales qui composent cette thèse ont permis (1) d’identifier des composantes électrophysiologiques (Mismatch Negativity et P3a) sensibles au traitement de la familiarité d’une voix; (2) de mettre en lumière un patron d’activation corticale singulier à la voix de la mère chez le nouveau-né, fournissant le premier indice neurophysiologique de l’acquisition du langage, processus particulièrement lié à l’interaction mère-enfant; et (3) de confirmer l’aspect pré-attentionnel de la distinction entre une voix et un stimulus non-vocal tout en accentuant la sélectivité et la sensibilité de la réponse corticale réservée au traitement de la voix. / Voice is a very prominent auditory stimulus in our acoustic environment. It is not only the carrier of speech, but would also be an auditory face that conveys important affective and identity information. Our ability to discriminate and recognize voices is socially and biologically important as it is amongst the most important functions of the human auditory system. This thesis was interested in the ontogenesis and specificity of the cortical response to human voice and had three objectives: (1) to develop an electrophysiological protocol to objectively measure the processing of voice familiarity in adult subjects; (2) to assess whether the same electrophysiological protocol could also objectify preferential processing of a familiar voice in 24-hour-old newborns, in particular the mother’s voice; and (3) to test the robustness of an electrophysiological measure, more specifically the Fronto-Temporal Positivity to Voices, interested in pre-attentional discrimination between vocal and non-vocal stimuli. Results from these three experimental designs have enabled (1) to identify electrophysiological components (Mismatch Negativity and P3a) sensitive to the processing of voice familiarity; (2) to highlight a singular pattern of cortical activation to the mother’s voice in newborns, providing the first neurophysiological evidence of language acquisition, a process especially related to the mother-child interaction; and (3) to confirm that vocal/non-vocal discrimination is a pre-attentional process, while enhancing the selectivity and the specificity of voice processing cortical response.

La voix est un stimulus auditif omniprésent dans notre environnement sonore. Elle permet non seulement la parole, mais serait aussi l’équivalent d’un visage auditif transmettant notamment des informations identitaires et affectives importantes. Notre capacité à discriminer et reconnaître des voix est socialement et biologiquement importante et elle figure parmi les fonctions les plus importantes du système auditif humain. La présente thèse s’intéressait à l’ontogénèse et à la spécificité de la réponse corticale à la voix humaine et avait pour but trois objectifs : (1) mettre sur pied un protocole électrophysiologique permettant de mesurer objectivement le traitement de la familiarité de la voix chez le sujet adulte; (2) déterminer si ce même protocole pouvait aussi objectiver chez le nouveau-né de 24 heures un traitement préférentiel d’une voix familière, notamment la voix de la mère; et (3) mettre à l’épreuve la robustesse d’une mesure électrophysiologique, notamment la Fronto-Temporal Positivity to Voices, s’intéressant à la discrimination pré-attentionnelle entre des stimuli vocaux et non-vocaux. Les résultats découlant des trois études expérimentales qui composent cette thèse ont permis (1) d’identifier des composantes électrophysiologiques (Mismatch Negativity et P3a) sensibles au traitement de la familiarité d’une voix; (2) de mettre en lumière un patron d’activation corticale singulier à la voix de la mère chez le nouveau-né, fournissant le premier indice neurophysiologique de l’acquisition du langage, processus particulièrement lié à l’interaction mère-enfant; et (3) de confirmer l’aspect pré-attentionnel de la distinction entre une voix et un stimulus non-vocal tout en accentuant la sélectivité et la sensibilité de la réponse corticale réservée au traitement de la voix. / Voice is a very prominent auditory stimulus in our acoustic environment. It is not only the carrier of speech, but would also be an auditory face that conveys important affective and identity information. Our ability to discriminate and recognize voices is socially and biologically important as it is amongst the most important functions of the human auditory system. This thesis was interested in the ontogenesis and specificity of the cortical response to human voice and had three objectives: (1) to develop an electrophysiological protocol to objectively measure the processing of voice familiarity in adult subjects; (2) to assess whether the same electrophysiological protocol could also objectify preferential processing of a familiar voice in 24-hour-old newborns, in particular the mother’s voice; and (3) to test the robustness of an electrophysiological measure, more specifically the Fronto-Temporal Positivity to Voices, interested in pre-attentional discrimination between vocal and non-vocal stimuli. Results from these three experimental designs have enabled (1) to identify electrophysiological components (Mismatch Negativity and P3a) sensitive to the processing of voice familiarity; (2) to highlight a singular pattern of cortical activation to the mother’s voice in newborns, providing the first neurophysiological evidence of language acquisition, a process especially related to the mother-child interaction; and (3) to confirm that vocal/non-vocal discrimination is a pre-attentional process, while enhancing the selectivity and the specificity of voice processing cortical response.

A neuropatia motora multifocal (NMM) é uma doença rara, que compromete as fibras nervosas motoras e que pode levar a incapacidades de gravidade variável, provavelmente na dependência do seu diagnóstico e tratamento precoces. O uso de imunoglobulina humana por via endovenosa em altas doses é considerado o tratamento mais eficaz para NMM. A objetivação das incapacidades funcionais que a NMM provoca e da sua reversão parcial ou completa em decorrência do tratamento ou de sua evolução não tem sido uniforme. Tais dificuldades se devem ao fato de que os instrumentos utilizados para a mensuração das incapacidades têm sido variados e não uniformes. A escala global de avaliação das incapacidades na neuropatia motora multifocal construída pelo método Rasch (GIR - MNN) ou Multifocal Motor Neuropathy - Rasch-built Overal Disability Scale (MMN-RODS©) foi desenvolvida especificamente para a avaliação das incapacidades funcionais dos pacientes com NMM. Em recente estudo, multicêntrico, foi verificado que a MMN-RODS©, originalmente desenvolvida em inglês, preenche as expectativas do modelo de Rasch. Para aplicação no Brasil, o presente trabalho realizou a tradução, a adaptação transcultural, conforme metodologia descrita na literatura, e a aplicação da escala em pacientes com Neuropatia Motora Multifocal / Multifocal Motor Neuropathy (MMN) is a rare disease that involves the motor nerve fibers. A better prognosis for MMN is probably linked to early diagnoses and treatment. Even so, MMN can lead to severe incapacities. The use of intravenous high doses of human immunoglobulin (IgIV) is considered efficacious to treat MMN. The objectification of the incapacities provoked by MNN, their evolution, and partial or complete deficits reversion due to the treatment has not been standardized. This lack of uniformity is due to the variety of tools used for the measurement of the deficits in MMN. The multifocal motor neuropathy - Raschbuilt overall disability scale (MMN-RODS©) was developed specifically for evaluation of the functional incapacities in MNN patients. In a recent multicentric study, it was verified that MMN-RODS© fulfill the expectations of the Rasch method. The present work realized the translation, transcultural adaptation and validation of the scale to the Brazilian Portuguese context aiming to use this tool to evaluate MMN patients living in Brazil

Neurological evidence indicates that instrumental musicians experience changes in the auditory system following skill acquisition and sensory training; yet, little is known about auditory neural plasticity in formally trained vocal musicians. Furthermore, auditory pitch discrimination and laryngeal control are recognized as essential skills for vocal musicians; however, the relationship between physiological variables, perceptual abilities, and vocal production is unclear. Electrophysiologic and psychoacoustic measures were used to examine pitch production accuracy as well as pre-attentive and active pitch discrimination between nonmusicians and two classes of musicians. Participants included 40 formally trained musicians (19 vocalists/21 instrumentalists) and 21 nonmusician controls. All were right-handed young adult females with normal hearing. Stimuli were harmonic tone complexes approximating the physical characteristics of piano tones and represented the mid-frequency range of the untrained female vocal register extending from C4 to G4 (F0 = 261.63-392 Hz). Vocal pitch recordings were spectrally analyzed to determine pitch production accuracy. Difference limens for frequency (DLFs) were obtained by an adaptive psychophysical paradigm. Pre-attentive auditory discrimination was assessed by auditory evoked potentials (AEPs), including the mismatch negativity (MMN). A standard tone (G4 = 392 Hz) and three deviants differing in frequency (1.5%, 3%, and 6% below) were presented in a multi-deviant paradigm. All musicians demonstrated superior pitch perception and vocal production compared to nonmusicians. Pitch perception and production accuracy did not significantly differ between vocalists and instrumentalists; however, pitch production accuracy was most consistent within the vocalist group. Music training appears to facilitate both auditory perception and vocal production regardless of music specialty. Pitch perception and production were correlated skills only for instrumental musicians. Vocalists demonstrated minimal variability for both skills so that perception and production were not correlated. These two skills may be independent abilities between which a relationship develops with training. AEP analysis revealed an influence of musical expertise on neural responses as early as 50 ms after onset of musically relevant stimuli. MMN responses indicate that vocal musicians as well as instrumental musicians have superior sensory memory representations for acoustic parameters of harmonic stimuli and imply that auditory neural sensitivity is developed by intense music training.

The human central auditory system can automatically extract abstract regularities from a variant auditory input. To this end, temporarily separated events need to be related. This study tested whether the timing between events, falling either within or outside the temporal window of integration (~350 ms), impacts the extraction of abstract feature relations. We utilized tone pairs for which tones within but not across pairs revealed a constant pitch relation (e.g., pitch of second tone of a pair higher than pitch of first tone, while absolute pitch values varied across pairs). We measured the mismatch negativity (MMN; the brain’s error signal to auditory regularity violations) to second tones that rarely violated the pitch relation (e.g., pitch of second tone lower). A Short condition in which tone duration (90 ms) and stimulus onset asynchrony between the tones of a pair were short (110 ms) was compared to two conditions, where this onset asynchrony was long (510 ms). In the Long Gap condition, the tone durations were identical to Short (90 ms), but the silent interval was prolonged by 400 ms. In Long Tone, the duration of the first tone was prolonged by 400 ms, while the silent interval was comparable to Short (20 ms). Results show a frontocentral MMN of comparable amplitude in all conditions. Thus, abstract pitch relations can be extracted even when the within-pair timing exceeds the integration period. Source analyses indicate MMN generators in the supratemporal cortex. Interestingly, they were located more anterior in Long Gap than in Short and Long Tone. Moreover, frontal generator activity was found for Long Gap and Long Tone. Thus, the way in which the system automatically registers irregular abstract pitch relations depends on the timing of the events to be linked. Pending that the current MMN data mirror established abstract rule representations coding the regular pitch relation, neural processes building these templates vary with timing.

The human brain is highly responsive to (deviant) sounds violating an auditory regularity. Respective brain responses are usually investigated in situations when the sounds were produced by the experimenter. Acknowledging that humans also actively produce sounds, the present event-related potential study tested for differences in the brain responses to deviants that were produced by the listeners by pressing one of two buttons. In one condition, deviants were unpredictable with respect to the button-sound association. In another condition, deviants were predictable with high validity yielding correctly predicted deviants and incorrectly predicted (mispredicted) deviants. Temporal principal component analysis revealed deviant-specific N1 enhancement, mismatch negativity (MMN) and P3a. N1 enhancements were highly similar for each deviant type, indicating that the underlying neural mechanism is not affected by intention-based expectation about the self-produced forthcoming sound. The MMN was abolished for predictable deviants, suggesting that the intention-based prediction for a deviant can overwrite the prediction derived from the auditory regularity (predicting a standard). The P3a was present for each deviant type but was largest for mispredicted deviants. It is argued that the processes underlying P3a not only evaluate the deviant with respect to the fact that it violates an auditory regularity but also with respect to the intended sensorial effect of an action. Overall, our results specify current theories of auditory predictive processing, as they reveal that intention-based predictions exert different effects on different deviance-specific brain responses.