The neural processes used to extract perceptual features of vocal calls, and subsequently to re-integrate those features to form a coherent auditory object, are poorly understood. In this thesis, extracellular recordings were carried out in order to investigate how the temporal envelope, pitch, timbre and spatial location of communication sounds are represented by neurons in two core and three belt areas of ferret (Mustela putorius furo) auditory cortex. Potential neural underpinnings of auditory perception were tested using neurometric analysis to relate the reliability of neural responses to the performance of ferret and human listeners on psychophysical tasks. I found that human listeners' discrimination of the temporal envelopes of vocalization sounds matched the best neurometrics calculated from the temporal spiking patterns of ferret cortical neurons. Neurometric scores based on the spike rates of cortical neurons accounted for ferrets' discrimination of the pitch of artificial vowels. I show that most auditory cortical neurons are modulated by a number of stimulus features, rather than being tuned to only one feature. Neurons in the core auditory cortical fields often respond uniquely to particular combinations of pitch and timbre features, while those in belt regions respond more linearly to feature combinations. Subtle differences in the sensitivity of neurons to pitch, timbre and azimuthal cues were found across cortical areas and depths. These results suggest that auditory cortical neurons provide widely distributed representations of vocalizations, and a single neuron can often use combinations of spike rate and temporal spiking responses to encode multiple sound features.

It is well known that machines perform far worse than humans in recognizing speech and audio, especially in noisy environments. One method of addressing this issue of robustness is to study physiological models of the human auditory system and to adopt some of its characteristics in computers. As a first step in studying the potential benefits of an elaborate computational model of the primary auditory cortex (A1) in the central auditory system, we qualitatively and quantitatively validate the model under existing speech processing recognition methodology. Next, we develop new insights and ideas on how to interpret the model, and reveal some of the advantages of its dimension-expansion that may be potentially used to improve existing speech processing and recognition methods. This is done by statistically analyzing the neural responses to various classes of speech signals and forming empirical conjectures on how cognitive information is encoded in a category-dependent manner. We also establish a theoretical framework that shows how noise and signal can be separated in the dimension-expanded cortical space. Finally, we develop new feature selection and pattern recognition methods to exploit the category-dependent encoding of noise-robust cognitive information in the cortical response. Category-dependent features are proposed as features that "specialize" in discriminating specific sets of classes, and as a natural way of incorporating them into a Bayesian decision framework, we propose methods to construct hierarchical classifiers that perform decisions in a two-stage process. Phoneme classification tasks using the TIMIT speech database are performed to quantitatively validate all developments in this work, and the results encourage future work in exploiting high-dimensional data with category(or class)-dependent features for improved classification or detection.

A novel method is presented for analyzing fMRI data, which relies on probabilistic estimates of microanatomically defined regions in individual fMRI volunteers. Postmortem structural and cytoarchitectonic information from the Julich/Dusseldorf group in Germany is aligned to the high-resolution structural MR images of functional MRI volunteers. This is achieved using nonlinear registration, which is applied only to the region of interest. The registered postmortem datasets are then combined into probability maps for microanatomically defined regions that are tailored to the anatomy of individual fMRI volunteers. These are then used as weighted spatial filters on functional MR data. In this thesis, three regions of the primary auditory cortex (located on Heschl's gyrus) have been targeted, and the analysis method is used to explore how these three areas respond to different kinds of sound. Regions Te1.0 and Te1.2 both demonstrate pitch sensitivity, consistent with published observations of the functional response of homologous regions in nonhuman primates. Area Te1.1 displayed sensitivity to both noise and pitch, consistent with the theory that it is homologous with the microanatomically similar area CM in nonhuman primates. Furthermore, the custom probability maps are much less diffuse and anatomically more precise than previous versions generated using the same postmortem data, and therefore permit a more sensitive and anatomically precise analysis of functional activity. This method could be applied to any other microanatomically defined region that has been characterized in the Julich postmortem dataset. / Thesis (Master, Computing) -- Queen's University, 2008-09-26 19:50:54.582

<p>Dendritic spines are mushroom-shaped appendages on the dendritic branches of neurons. They are invaluable to the function of the brain as they form the major site for excitatory signal transmission in the mammalian brain. These ubiquitous structures have several invaluable and unique characteristics – namely that their morphological and functional characteristics are activity-dependent and undergo remodeling as the spine experiences stimulation. This activity-dependent regulation then in turn modulates the excitatory postsynaptic potential that propagates into the adjacent parent dendrite, and which ultimately reaches the somatic compartment. The mediation of this modulatory effect on the postsynaptic signal by dendritic spines renders them invaluable to the brain’s ability to change neuronal circuits as it learns. The relationship between the structural and functional change in dendritic spines as plasticity is induced remains poorly understood; while efforts have been made to examine the morphology of dendritic spines during plasticity as well as the change to receptor insertion on the postsynaptic density, a comprehensive methodology to interrogate the concomitant changes to several aspects of dendritic spine structure and function as plasticity occurs has not been established. In this study, such a methodology was developed in order to facilitate future study of how a dendritic spine’s diffusional neck resistance, head volume, calcium-sensitive channels (on the postsynaptic density), and excitatory postsynaptic potential amplitude change concurrently as the spine undergoes activity-dependent regulation. This activity-dependent regulation also occurs in groups of spines called “clusters” <em>in vivo</em>, and the structural and functional dynamics of spines as these groups are formed also remains unknown. In order to to facilitate future <em>in vivo</em> studies on how clustered dendritic spines may change dynamically in both structure and function, a methodology for surgically accessing and recording calcium-based activity from the primary auditory cortex was developed, as the frequency-specific tuning of dendritic spines in this cortical area forms a compelling environment in which to study the relationship between spine form and function. </p>

The critical bandwidth (CBW) is an auditory phenomenon that has been used to study various aspects of auditory processing, including auditory masking, complex tone processing, and loudness perception. Although the psychoacoustic aspects of the CBW have been well studied, the underlying neurophysiology of the CBW has not been as thoroughly examined. The current study examined the neurophysiology of the CBW in young adults, as well as loudness perception in response to the CBW. Auditory stimuli consisting of complex tones of varying bandwidths were presented to 12 individuals (6 male and 6 female, ages 18-26 years). Complex tones were presented around center frequencies (CFs) of 250, 500, 1000, and 3000 Hz at bandwidths of 2, 5, 8, 10, 20, 50, 100, 200, 500, 1000, and 2000 Hz. Participants made loudness perception judgments while electroencephalography measured and recorded components of the event related potentials (ERPs) in response to the acoustic stimuli. Reaction time (RT) was recorded for each behavioral response, and the latencies of the N1, P2, C3, and C4 components of the ERPs were obtained. The results showed that RT increased with increasing bandwidth followed by a decrease in RT corresponding approximately with the CBW. This indicated that participants perceived a change in loudness at bandwidths greater than the CBW. Significant differences, p < .05, in RT were observed in bandwidths of 5 Hz and greater, although there was not complete consistency in this observation across all CFs and bandwidths. No significant critical band-like behavior amongst ERP latencies was observed. The results indicated that responses to acoustic stimuli originating in the superior temporal gyrus progressed to areas of higher neural function in the mid-temporal lobe. It was observed that each response must be processed temporally and independently to determine if a frequency difference is present for each stimulus. This observation is significant because this type of processing had not been identified prior to the current study.

We can hold conversations with people in environments where typically there are additional simultaneous talkers in background acoustic space or noise like vehicles on the street or music playing at a café on the sidewalk. This seemingly trivial everyday task is difficult for people with hearing deficits and is extremely hard to model in machines. This dissertation focuses on exploring the neural mechanisms of how the human brain encodes such complex acoustic environments and how cognitive processes like attention shapes processing of the attended speech. My initial experiments explore the representation of acoustic features that help us localize single sound sources in the environment- features like direction and spectrotemporal content of the sounds, and the interaction of these representations with each other. I play natural American English sentences coming from five azimuthal directions in space. Using intracranial electrocorticography (ECoG) recordings from the human auditory cortex of the listener, I show that the direction of sound and the spectrotemporal content are encoded in two distinct aspects of neural response, the direction modulates the mean of the response and the spectrotemporal features contributes to the modulation of neural response around its mean. Furthermore, I show that these features are orthogonal to each other and do not interact. This representation enables successful decoding of both spatial and phonetic information. These findings contribute to defining the functional organization of responses in the human auditory cortex, with implications for more accurate neurophysiological models of spatial speech processing. I take a step further to investigate the role of attention in encoding the direction and phonetic features of speech. I play a mixture of male and female spatialized talkers eg. male at left side to the listener and female at right side (talker’s locations switch randomly after each sentence). I ask the listener to follow a given talker e.g. follow male talker as they switch their location after each uttered sentence. While the listener performs this experiment, I collect intracranial EEG data from their auditory cortex. I investigate the bottom-up stimulus dependent and attention independent encoding of such a cocktail party speech and the top-down attention driven role in the encoding of location and speech features. I find a bottom-up stimulus driven contralateral preference in encoding of the mixed speech i.e. Left brain hemisphere automatically and predominantly encodes speech coming from right direction and vice-versa. On top of this bottom-up representation, I find that attended talker’s direction modulates the baseline of the neural response and attended talker’s voice modulates the spectrotemporal tuning of the neural response. Moreover, the modulation to attended talker’s location is present throughout the auditory cortex but the modulation to attended talker’s voice is present only at higher order auditory cortex areas. My findings provide crucially needed evidence to determine how bottom-up and top-down signals interact in the auditory cortex in crowded and complex acoustic scenes to enable robust speech perception. Furthermore, they shed light on the hierarchical encoding of attended speech that have implications on bettering the auditory attention decoding models. Finally, I talk about a clinical case study where we show that electrical stimulation to specific sites in planum temporale (PT) of an epilepsy patient implanted with intracranial electrode leads to enhancement in speech in noise perception. When noisy speech is played with such an electrical stimulation, the patient perceives that the noise disappears, and that the speech is similar to clean speech that they hear without any noise. We performed series of analysis to determine functional organization of the three main sub regions of the human auditory cortex- planum temporale (PT), Heschl’s gyrus (HG) and superior temporal gyrus (STG). Using Cortico-Cortical Evoked Potentials (CCEPs), we modeled the PT sites to be located between the sites in HG and STG. Furthermore, we find that the discriminability of speech from nonspeech sounds increased in population neural responses from HG to the PT to the STG sites. These findings causally implicate the PT in background noise suppression and may point to a novel potential neuroprosthetic solution to assist in the challenging task of speech perception in noise. Together, this dissertation shows new evidence for the neural encoding of spatial speech; interaction of stimulus driven, and attention driven neural processes in spatial multi-talker speech perception and enhancement of speech in noise perception by electrical brain stimulation.

Les processus d'apprentissage et de mémoire sont contrôlés par des circuits et éléments neuronaux spécifiques. De nombreuses études ont récemment mis en évidence que les circuits corticaux jouent un rôle important dans la régulation des comportements de peur, cependant, leurs caractéristiques anatomiques et fonctionnelles restent encore largement inconnues. Au cours de ma thèse, en utilisant des enregistrements unitaires et des approches optogénétiques chez la souris libre de se comporter, nous avons pu montrer que les interneurones inhibiteurs du cortex auditif et du cortex préfrontal médian forment un microcircuit désinhibiteur permettant respectivement l'acquisition et l'expression de la mémoire de peur conditionnée. Dans les deux cas, les interneurones parvalbuminergiques constituent l'élément central du circuit et sont inhibés de façon phasique. D’un point de vue fonctionnel, nous avons démontré que cette inhibition était associée à la désinhibition des neurones pyramidaux par un mécanisme de réduction de l'inhibition continue exercée par les interneurones parvalbuminergiques. Ainsi, les interneurones parvalbuminergiques peuvent contrôler temporellement l'excitabilité des neurones pyramidaux. En particulier, nous avons montré que l'acquisition de la mémoire de peur conditionnée dépend du recrutement d'un microcircuit désinhibiteur localisé dans le cortex auditif. En effet, au cours du conditionnement de peur, la présentation du choc électrique induit l'inhibition des interneurones parvalbuminergiques, ce qui a pour conséquence de désinhiber les neurones pyramidaux du cortex auditif et de permettre l’apprentissage du conditionnement de peur. Dans leur ensemble, ces données suggèrent que la désinhibition est un mécanisme important dans l'apprentissage et le traitement de l'information dans les circuits corticaux. Dans un second temps, nous avons montré que l'expression de la peur conditionnée requière l'inhibition phasique des interneurones parvalbuminergiques du cortex préfrontal médian. En effet, leur inhibition désinhibe les cellules pyramidales préfrontales et synchronise leur activité en réinitialisant les oscillations thêta locales. Ces résultats mettent en évidence deux mécanismes neuronaux complémentaires induits par les interneurones parvalbuminergiques qui coordonnent et organisent avec précision l’activité neuronale des neurones pyramidaux du cortex préfrontal pour contrôler l'expression de la peur conditionnée. Ensemble, nos données montrent que la désinhibition joue un rôle important dans les comportements de peur en permettant l’association entre des informations comportementalement pertinentes, en sélectionnant les éléments spécifiques du circuit et en orchestrant l'activité neuronale des cellules pyramidales. / Learning and memory processes are controlled by specific neuronal circuits and elements. Numerous recent reports highlighted the important role of cortical circuits in the regulation of fear behaviour, however, the anatomical and functional characteristics of their neuronal components remain largely unknown. During my thesis, we used single unit recordings and optogenetic manipulations of specific neuronal elements in behaving mice, to show that both the auditory cortex and the medial prefrontal cortex contain a disinhibitory microcircuit required respectively for the acquisition and the expression of conditioned fear memory. In both cases, parvalbumin-expressing interneurons constitute the central element of the circuit and are phasically inhibited during the presentation of the conditioned tone. From a functional point of view, we demonstrated that this inhibition induced the disinhibition of cortical pyramidal neurons by releasing the ongoing perisomatic inhibition mediated by parvalbumin-expressing interneurons onto pyramidal neurons. Thereby, this disinhibition allows the precise temporal regulation of pyramidal neurons excitability. In particular, we showed that the acquisition of associative fear memories depend on the recruitment of a disinhibitory microcircuit in the auditory cortex. Fear-conditioning-associated disinhibition in auditory cortex is driven by foot-shock-mediated inhibition of parvalbumin-expressing interneurons. Importantly, pharmacological or optogenetic blockade of pyramidal neuron disinhibition abolishes fear learning. Together, these data suggest that disinhibition is an important mechanism underlying learning and information processing in cortical circuits. Secondly, in the medial prefrontal cortex, we demonstrated that expression of fear behaviour is causally related to the phasic inhibition of prefrontal parvalbumin-expressing interneurons. Inhibition of parvalbumin-expressing interneuron activity disinhibits prefrontal pyramidal neurons and synchronizes their firing by resetting local theta oscillations, leading to fear expression. These results identify two complementary neuronal mechanisms both mediated by prefrontal parvalbumin-expressing interneurons that precisely coordinate and enhance the neuronal efficiency of prefrontal pyramidal neurons to drive fear expression. Together these data highlighted the important role played by neuronal disinhibition in fear behaviour by binding behavioural relevant information, selecting specific circuit elements and orchestrating pyramidal neurons activity.

Estudamos os efeitos da estimulação elétrica no nucleus basalis magnocelular (Meynert), núcleo colinégico que projeta aferências para o córtex cerebral e tem sido associado a mecanismos de aprendizagem e memória. Verificamos os efeitos eletrofisiológicos induzidos pela estimulação elétrica do núcleo basalis pareado com apresentação de um tom puro. Caracterizamos a dinâmica da atividade elétrica neural do cortex auditivo primário e de núcleos subcorticais relacionados à circuitaria da aprendizagem e memória, durante o condicionamento auditivo nos momentos de aquisição e de revocação além correlacioná-las a dinâmica de freqüência cardiaca, variável que pode exprimir a relevância de um estímulo / Acetilcholine is related to learning and memory and is related to cortical activation. We studied the effects electrically stimulating the basal forebrain - the main cholinergic afferent to the cortex, while presenting paired and unpaired pure tones. Mathematical techniques were used to analyze electrophysiological data. The dynamics from primary auditory cortex and related subcortical nuclei were correlated to the auditory conditioning. We also correlated brain activity to the heart dynamics, considered a reliable measure of learning and conditioning, an interesting approach that uncovers the relevance of stimulus that is not detectable through other behavioral variables

Onze pacientes com diagnóstico de esquizofrenia pelo DSM-IV-TR e alucinações auditivas mesmo em uso de clozapina foram distribuídos aleatoriamente para receber estimulação magnética transcraniana de repetição (EMTr) ativa (n=6) ou inativa (n=5) no córtex têmporo-parietal esquerdo. Um total de 160 minutos de EMTr a 1 Hz foi administrada ao longo de 10 dias, 90% do limiar motor, com desenho paralelo, com pacientes e avaliadores cegos, em desenho controlado com grupo inativo. Houve um efeito de grupo significativo nos escores da escala de alucinações (realidade e influência: p=0,0360 e p=0,0493 respectivamente) e no subitem sintomas positivos da PANSS. A EMTr ativa em associação com clozapina pode ser administrada com segurança para tratar as alucinações auditivas. Embora a amostra consistia de pacientes extremamente refratários, estes resultados sugerem haver alguns efeitos da EMTr a 1 Hz no córtex têmporo-parietal esquerdo. / Eleven schizophrenics patients according to DSM-IV-TR criteria and experiencing auditory hallucinations in spite of treatment with clozapine were randomly allocated to receive repetitive transcranial magnetic stimulation (rTMS) (n=6) or sham stimulation (n=5) over left temporo-parietal cortex. A total of 160 minutes of 1 Hz rTMS was administered over 10 days at 90% motor threshold, with patients and raters blind to treatment modality, using a sham-controlled, parallel design. There was a significant group effect for the Auditory Hallucinations Rating Scale scores (reality and attencional salience: p=0.0360 and p=0.0493 respectively) and the sub item positive symptoms of PANSS. Active rTMS in association with clozapine can be administered safely to treat auditory hallucinations. Although the sample consisted of extremely refractory patients, the results suggest some effects of 1 Hz rTMS over Left temporoparietal.

Introdução: Plasticidade auditiva refere-se a mudanças que ocorrem no sistema sensorial responsável pela transmissão da informação acústica. A plasticidade do sistema nervoso auditivo central está relacionada a capacidade de adaptação através da reintrodução de estímulos por meio de aparelhos de amplificação sonora ou implante coclear. Essas mudanças são observadas a partir do desempenho de pacientes com o uso do aparelho de amplificação sonora, e podem ser verificadas por meio dos potenciais evocados auditivos de longa latência. Objetivo: caracterizar os Potenciais Evocados Auditivos de Longa Latência (PEALL) em adultos e idosos com perda auditiva neurossensorial, verificando os efeitos da estimulação auditiva por meio da comparação destes potenciais pré e pós adaptação do Aparelho de Amplificação Sonora Individual (AASI). Metodologia: Participaram deste estudo 15 indivíduos adultos e idosos, de ambos os gêneros, de 55 a 85 anos de idade, com perda auditiva neurossensorial de grau leve a moderado com simetria entre as orelhas, sem experiência prévia com qualquer tipo de dispositivo de amplificação sonora. Os indivíduos foram encaminhados pelas empresas de aparelho auditivo WIDEX, Audibel e o Espaço Reouvir, tratando-se de novos usuários de AASI. Os PEALL foram realizados nas condições com e sem AASI, a 60 e 75 dBnNA em campo sonoro, em dois momentos: primeira avaliação realizada até uma semana após a adaptação do AASI e a segunda avaliação realizada após 6 meses da adaptação do AASI. Resultados: Na comparação da primeira avaliação com a segunda avaliação, na condição sem AASI a 60 dBnNA, observou-se diferença estatisticamente significante na latência do componente P1 (p-valor= 0,034). Na condição sem AASI a 75 dBnNA, observou-se diferença estatisticamente significante para a latência do componente P300 (p-valor 0,031) e para a amplitude P2N2 (p-valor 0,024), com diminuição da latência e aumento da amplitude na segunda avaliação. Por sua vez, na comparação da primeira avaliação com a segunda avaliação, na condição com AASI a 75 dBnNA, obteve-se uma diferença estatisticamente significante na latência do componente N2 (p-valor 0,009) e na amplitude P2N2 (p-valor 0,024), com aumento da amplitude na segunda avaliação. Evidenciou-se, também, diferença significante na amplitude P1N1 (p-valor 0,024) na condição com AASI a 60 dBnNA. Conclusão: Os PEALL com estímulo de fala demonstraram ser um importante procedimento para ser utilizado na prática clínica, visando monitorar a plasticidade neuronal do Sistema Nervoso Auditivo Central frente à estimulação auditiva (uso de AASI), em adultos e idosos com perda auditiva neurossensorial de grau leve a moderado / Introduction: Auditory plasticity refers to changes that occur in the sensory system responsible for the transmission of acoustic information. The plasticity of the central auditory nervous system is related to the capacity of adaptation through the reintroduction of stimuli of sound amplification devices or cochlear implants. These changes are observed from the performance of patients with the use of the sound amplification apparatus, and can be verified by long-latency auditory evoked potentials. Purpose: To characterize long latency auditory evoked potentials (LLAEP) in adults with sensorineural hearing loss, verifying the effects of auditory stimulation by comparing these before and after adaptation potentials of the Individual Sound Amplification (AASI). Methodology: Fifteen adult and elderly individuals of both genders, aged 55 to 85 years, with mild to moderate sensorineural hearing loss with symmetry between the ears, without prior experience with any type of sound amplification device. The subjects were referred by hearing aid companies WIDEX, Audibel and Espaço Reouvir, in the case of new hearing aids users. The LLAEP were performed in the conditions with and without AASI, at 60 and 75 dBnNA in sound field, in two moments: first evaluation performed up to one week after AASI adaptation and the second evaluation performed after 6 months of AASI adaptation. Results: In the comparison of the first evaluation with the second evaluation, in the condition without AASI at 60 dBnNA, a statistically significant difference was observed in the latency of the P1 component (p-value = 0.034). In the condition without AASI at 75 dBnNA, a statistically significant difference was observed for the latency of the P300 component (p-value 0.031) and for the P2N2 amplitude (p-value 0.024), with latency decrease and amplitude increase in the second evaluation. In the comparison of the first evaluation with the second evaluation, in the condition with AASI at 75 dBnNA, there was a statistically significant difference in the latency of the N2 component (p-value 0.009) and in the P2N2 amplitude (p-value 0.024) , With amplitude increase in the second evaluation. There was also a significant difference in P1N1 amplitude (p-value 0.024) in the condition with AASI at 60 dBnNA. Conclusion: The LLAEP was an important procedure to be used in clinical practice, aiming to monitor the neural plasticity of the Central Auditory Nervous System in front of auditory stimulation (hearing aids use) in adults and elderly patients with mild to moderate sensorineural hearing loss of amplification and the importance of neural plasticity of the Central Auditory Nervous System