The objectives of my PhD were to identify the spatial and the temporal dynamics of the brain areas involved in tactile change detection as well as the neural mechanisms responsible for the processing of tactile change detection. To that aim, three specific MEG studies were performed; each of them is addressing specific research aims.The first study investigated the spatiotemporal dynamics of the multilevel cortical processing of tactile change detection in human healthy subjects. This study disclosed a hierarchical organization from unimodal early tactile change detection at secondary somatosensory cortex to multi modal complex processing at bilateral temporo-parietal junctions, posterior parietal cortex and supplementary motor areas. The second study aimed at discriminating between debated neural mechanisms responsible for the genesis of the somatosensory mismatch negativity (sMMN). To do so, we manipulated the predictability of the deviant stimuli and the response to omissions in different kind of oddballs, the response to deviant stimuli paired with standards and occurring alone. We found out that mechanisms for early tactile change detection reflected by the sMMN were better explained by the predictive coding theory compared to the adaptation and adjustment theories. Finally we sought to characterize the alterations in early cortical tactile change detection in Friedreich Ataxia (FRDA); a neurological disorder characterized by somatosensory and cerebellar pathways degeneration. The aim of this work was to study the role of the cerebellum in the genesis of sMMN and its potential selectivity for somatosensory change detection compared to auditory. This study demonstrated that, in FRDA, both tactile and auditory pathways are affected at the level of primary sensory neurons and dorsal root/spiral ganglia in a genetically determined. By contrasts, early cortical sensory change detection in FRDA was impaired only in the tactile modality in line with the sMMN impairment described in patients with acquired cerebellar lesions or during cerebellar inhibition by trans cranial magnetic stimulation. These data brought novel empirical evidence supporting the contribution of spinocerebellar tracts in sMMN genesis at cSII cortex.In conclusion, this PhD contributed to identify the network responsible for tactile change detection that involves cuneocerebellar spinocerebellar tract and cSII cortex as somatosensory specific areas and TPJ, SMA & PPC as multimodal brain areas. We further provided evidence that early change detection mechanisms at SII cortex fall under the predictive coding framework and that change detection is hierarchically organized with inputs from low level areas for genesis of an adequate generative model of our environment and conscious representation of our body. / Doctorat en Sciences médicales (Médecine) / info:eu-repo/semantics/nonPublished

This work concerns the investigation of the neuronal mechanisms at the basis of language acquisition and processing, and the complex interactions of language and attention processes in the human brain. In particular, this research was motivated by two sets of existing neurophysiological data which cannot be reconciled on the basis of current psycholinguistic accounts: on the one hand, the N400, a robust index of lexico-semantic processing which emerges at around 400ms after stimulus onset in attention demanding tasks and is larger for senseless materials (meaningless pseudowords) than for matched meaningful stimuli (words); on the other, the more recent results on the Mismatch Negativity (MMN, latency 100-250ms), an early automatic brain response elicited under distraction which is larger to words than to pseudowords. We asked what the mechanisms underlying these differential neurophysiological responses may be, and whether attention and language processes could interact so as to produce the observed brain responses, having opposite magnitude and different latencies. We also asked questions about the functional nature and anatomical characteristics of the cortical representation of linguistic elements. These questions were addressed by combining neurocomputational techniques and neuroimaging (magneto-encephalography, MEG) experimental methods. Firstly, a neurobiologically realistic neural-network model composed of neuron-like elements (graded response units) was implemented, which closely replicates the neuroanatomical and connectivity features of the main areas of the left perisylvian cortex involved in spoken language processing (i.e., the areas controlling speech output – left inferior-prefrontal cortex, including Broca’s area – and the main sensory input – auditory – areas, located in the left superior-temporal lobe, including Wernicke’s area). Secondly, the model was used to simulate early word acquisition processes by means of a Hebbian correlation learning rule (which reflects known synaptic plasticity mechanisms of the neocortex). The network was “taught” to associate pairs of auditory and articulatory activation patterns, simulating activity due to perception and production of the same speech sound: as a result, neuronal word representations distributed over the different cortical areas of the model emerged. Thirdly, the network was stimulated, in its “auditory cortex”, with either one of the words it had learned, or new, unfamiliar pseudoword patterns, while the availability of attentional resources was modulated by changing the level of non-specific, global cortical inhibition. In this way, the model was able to replicate both the MMN and N400 brain responses by means of a single set of neuroscientifically grounded principles, providing the first mechanistic account, at the cortical-circuit level, for these data. Finally, in order to verify the neurophysiological validity of the model, its crucial predictions were tested in a novel MEG experiment investigating how attention processes modulate event-related brain responses to speech stimuli. Neurophysiological responses to the same words and pseudowords were recorded while the same subjects were asked to attend to the spoken input or ignore it. The experimental results confirmed the model’s predictions; in particular, profound variability of magnetic brain responses to pseudowords but relative stability of activation to words as a function of attention emerged. While the results of the simulations demonstrated that distributed cortical representations for words can spontaneously emerge in the cortex as a result of neuroanatomical structure and synaptic plasticity, the experimental results confirm the validity of the model and provide evidence in support of the existence of such memory circuits in the brain. This work is a first step towards a mechanistic account of cognition in which the basic atoms of cognitive processing (e.g., words, objects, faces) are represented in the brain as discrete and distributed action-perception networks that behave as closed, independent systems.

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.

Previous research indicates that humans develop a phonological library in infancy. As humans grow into adulthood, their phonological library becomes well established. Upon encountering phonemes from a new language, humans process these phonemes by comparison to their native phonological library. Event-related potentials (ERP), specifically the mismatch negativity, have been shown to indicate that this process of comparing non-native phonemes to our native phonological library is not improved through learning the new language as an adult. An alternative explanation may be that there is an underlying change in the neural generators as the non-native phonemes are learned, but that this change is not reflected in the ERP. The current study seeks to examine this hypothesis through the simultaneous collection of ERP and blood-oxygen-level-dependent functional MRI (fMRI) data. The findings of the ERP and fMRI data are inconclusive. The study also explores the processing of diphthongs, a category of phonemes rarely tested before, through both behavioral and neuroimaging methods. The study presents behavioral data demonstrating that non-native diphthongs are processed based upon the separate elements of the phonemes, rather than as complete units.

Hearing loss, as a result of old age, has been linked to a decline in speech perception despite the use of additional listening devices. Even though the relationship between hearing loss and decreased speech perception has been well established, research in this area has often focused on the behavioral aspects of language and not on the functionality of the brain itself. In the present study, the mismatch negativity, an event related potential, was examined in order to determine the differences in speech perception between young adult participants, geriatric normal hearing participants, and geriatric hearing-impaired participants. It was hypothesized that a significantly weaker mismatch negativity would occur in the geriatric hearing-impaired participants when compared to the young adult participants and the geriatric normal hearing participants. A passive same/different discrimination task was administered to 10 young adult controls (5 male, 5 female) and eight older adult participants with and without hearing loss (4 male, 4 female). Data from behavioral responses and event related potentials were recorded from 64 electrodes placed across the scalp. Results demonstrated that the mismatch negativity occurred at various amplitudes across all participants tested; however, an increased latency in the presence of the mismatch negativity was noted for the geriatric normal hearing and the geriatric hearing-impaired participants. Dipoles reconstructed from temporal event related potential data were located in the cortical areas known to be instrumental in auditory and language processing for the young adult participants; however, within the geriatric normal hearing and the geriatric hearing-impaired participants, dipoles were seen in multiple locations not directly associated with language and auditory processing. Although not conclusive, it appears that within the geriatric normal hearing and the geriatric hearing-impaired participants there is slower processing of the speech information, as well as some cognitive confusion which leads to fewer available resources for interpretation.

The infrequent occurrence of a transient feature (deviance; e.g., frequency modulation, FM) in one of the regular occurring sinusoidal tones (standards) elicits the deviance related mismatch negativity (MMN) component of the event-related brain potential. Based on a memory-based comparison, MMN reflects the mismatch between the representations of incoming and standard sounds. The present study investigated to what extent the infrequent exclusion of an FM is detected by the MMN system. For that purpose we measured MMN to deviances that either consisted of the exclusion or inclusion of an FM at an early or late position within the sound that was present or absent, respectively, in the standard. According to the information-content hypothesis, deviance detection relies on the difference in informational content of the deviant relative to that of the standard. As this difference between deviants with FM and standards without FM is the same as in the reversed case, comparable MMNs should be elicited to FM inclusions and exclusions. According to the feature-detector hypothesis, however, the deviance detection depends on the increased activation of feature detectors to additional sound features. Thus, rare exclusions of the FM should elicit no or smaller MMN than FM inclusions. In passive listening condition, MMN was obtained only for the early inclusion, but not for the exclusions nor for the late inclusion of an FM. This asymmetry in automatic deviance detection seems to partly reflect the contribution of feature detectors even though it cannot fully account for the missing MMN to late FM inclusions. Importantly, the behavioral deviance detection performance in the active listening condition did not reveal such an asymmetry, suggesting that the intentional detection of the deviants is based on the difference in informational content. On a more general level, the results partly support the “fresh-afferent” account or an extended memory-comparison based account of MMN.

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.

Comprendre les mécanismes neurophysiologiques et les bases neurales de la conscience est un défi médico-scientifique majeur. A cette fin, il faut opérer une distinction entre les mécanismes neuraux des états de conscience, et ceux qui sous-tendent l'accès conscient à un contenu mental particulier (ou la prise de conscience). Les données expérimentales ayant contrasté état conscient/ état non conscient (coma, sommeil, sédation) d'une part, et perception consciente/inconsciente d'un même stimulus d'autre part, sont en faveur de l'implication d'un réseau d'aires cérébrales fronto-pariétales à la fois dans l'état et dans l'accès conscient à une information donnée. La comparaison état conscient/ état non conscient est malheureusement limitée par les différences de vigilance existant entre ces états. Nous avons cherché à contourner ce problème en nous focalisant sur deux populations de malades présentant un niveau de vigilance proche mais différant sous l'angle de l'état de conscience : patients éveillés, non conscients (état végétatif) versus patients éveillés et minimalement conscients (état de conscience minimale). Nos résultats, obtenus en utilisant les potentiels évoqués auditifs cognitifs à haute densité spatiale, sont en faveur de l'implication du même réseau d'aires cérébrales fronto-pariétales que celui mentionné ci-dessus, à la fois dans l'état et l'accès conscient. L'activation de ce réseau est contemporaine de l'apparition d'une P300b en potentiels évoqués qui semble constituer un marqueur très spécifique de conscience. Notre travail nous a permis également d'identifier un possible nouveau marqueur de la conscience qu'est la variation contingente négative (CNV). / Understanding the neurophysiological mechanisms and neural bases of consciousness is a major scientific and medical challenge. To do this, one has to distinguish neural mechanisms of conscious state from those subserving conscious access to a given mental state (that is awareness). Experimental data having contrasted conscious / non conscious state (coma, sleep, sedation) on the one hand, and conscious/ unconscious processing of a very same stimulus on the other hand are in favour of the implication of a network of lateral and medial frontal and parietal areas in both conscious state and conscious access. The comparison of conscious/ non conscious state is unfortunately limited by arousal difference between these two states. So, we endeavoured to overcome this problem by exploring two categories of patients with a same level of arousal but a different state of awareness: unaware awaked patients (vegetative state) versus awaked and minimally conscious patients (minimally conscious state). Our results obtained by using high-density auditory event related potentials argue in favour of the implication of the very same network of frontal and parietal areas than the one described above in both conscious state and conscious access to a given information. This network activation is associated with the emergence of a P300b wave, on event related potentials, which seems to be a very specific marker of consciousness. Our work also give us the opportunity to discover a potential new marker of consciousness, namely the contingent negative variation (CNV).

Mon thème de recherche est d’étudier l’influence de l’apprentissage de la musique sur le traitement acoustique et phonologique de la syllabe chez des enfants normolecteurs et dyslexiques. Dans ce but, j’ai conduit plusieurs expériences basées sur l’utilisation conjointe des méthodes issues de la psychologie expérimentale (Temps de Réaction, TRs, et pourcentage d’erreurs, %err) et de l’électrophysiologie chez l’homme (Potentiels Evoqués, PEs). En comparant des enfants musiciens et non-musiciens de 9 ans, j’ai d’abord testé les effets de l’expertise musicale sur les traitements attentif (TRs et %err) et pré-attentif (en utilisant la Mismatch Negativity, MMN) de paramètres acoustiques, fréquence et durée des syllabes, et d’un paramètre phonologique, le Voice Onset Time (VOT; Expérience I). Les résultats montrent que l'expertise musicale améliore les traitements pré-attentif et attentif de la durée et du VOT dans les syllabes et le traitement attentif des variations de fréquence. Dans une seconde étude, j’ai utilisé la MMN pour comparer le traitement de ces mêmes paramètres chez des enfants dyslexiques et normolecteurs. Les enfants dyslexiques montrent un déficit du traitement de la durée des syllabes et du VOT comparés aux enfants normolecteurs. Enfin, dans les deux dernières études, j’ai utilisé la méthode longitudinale pour tester l’influence de l’apprentissage de la musique sur le traitement pré-attentif (MMN) de ces mêmes paramètres chez des enfants normolecteurs (Expérience III) et dyslexiques (Expérience IV). Les résultats de l’Expérience III montrent que 12 mois d’apprentissage de la musique améliorent le traitement pré-attentif de la durée et du VOT chez les enfants normolecteurs. En reproduisant les effets trouvés dans l’Expérience I, ces résultats soulignent que l’avantage mis en évidence chez les enfants musiciens ne résulterait pas uniquement de prédispositions génétiques pour la musique mais serait causalement lié à l’apprentissage musical. Enfin, les résultats de l’Expérience IV montrent que 6 mois d’apprentissage de la musique améliorent le traitement pré-attentif du VOT chez les enfants dyslexiques, suggérant que l’apprentissage musical pourrait être utilisé comme une aide à la remédiation de la dyslexie.Pris dans leur ensemble, ces résultats démontrent une relation forte entre traitements acoustique et phonologique. L’apprentissage de la musique, en améliorant la sensibilité des enfants aux paramètres acoustiques dans la musique et dans le langage (processus communs), augmenterait également leur sensibilité aux paramètres phonologiques associés et permettrait ainsi la construction de représentations phonologiques plus robustes (transfert d’apprentissage de la musique vers le langage). / My research is aimed at studying the influence of musical training on the acoustic and phonological processing of syllables in children with dyslexia and in normal-reading children. To this aim, I conducted several experiments by using methods issued from experimental psychology (Reaction Times, RTs, and error rates, %err) and from human electrophysiology (Event-Related brain Potentials, ERPs)By comparing 9-year-old musician and non-musician children, I first tested for the effects of musical expertise on attentive (RTs and %err) and preattentive processing (by using the Mismatch Negativity, MMN) of the acoustical parameters, frequency and duration, of syllables and of a phonological parameter, the Voice Onset Time (VOT; Experiment I). Results showed enhanced preattentive and attentive processing of syllables’ duration and VOT in musicians compared to nonmusician children. Secondly, I compared the processing of these same parameters in dyslexic and normal-reading children (Experiment II) by using the MMN. Results revealed that children with dyslexia showed deficits for the processing of duration and VOT in syllables compared to normal-readers. Finally, in the last two studies, I used the longitudinal method to test for the influence of musical training on the processing of the same acoustic and phonological parameters of syllables, in normal-reading children (Experiment III) and in children with dyslexia (Experiment IV). Results of Experiment III showed that 12 months of musical training enhanced duration and VOT processing in syllables, thereby demonstrating that the effects of musical expertise shown in Experiment I are not likely to only result from specific genetic predispositions for music but are causally linked to musical training. Finally, results of Experiment IV revealed that 6 months of musical training in children with dyslexia enhanced their sensitivity to VOT processing, suggesting that musical training could be an aid for the remediation of dyslexia.These results highlight the relationship between acoustical and phonological processing. Musical training, by refining the acoustical network responsible for the acoustic processing in music and speech sounds (common processing) also enhances sensitivity to phonological associated features and, consequently, the building-up of more robust phonological representations (transfer of training effect from music to language processing).