Discrimination of cortical laminae using MEG.

Typically MEG source reconstruction is used to estimate the distribution of current flow on a single anatomically derived cortical surface model. In this study we use two such models representing superficial and deep cortical laminae. We establish how well we can discriminate between these two different cortical layer models based on the same MEG data in the presence of different levels of co-registration noise, Signal-to-Noise Ratio (SNR) and cortical patch size. We demonstrate that it is possible to make a distinction between superficial and deep cortical laminae for levels of co-registration noise of less than 2mm translation and 2° rotation at SNR>11dB. We also show that an incorrect estimate of cortical patch size will tend to bias layer estimates. We then use a 3D printed head-cast (Troebinger et al., 2014) to achieve comparable levels of co-registration noise, in an auditory evoked response paradigm, and show that it is possible to discriminate between these cortical layer models in real data.

Pathological substrates of cognitive decline in Alzheimer's disease

The progressive development of Alzheimer's disease (AD)-related lesions such as neurofibrillary tangles,amyloid deposits and synaptic loss within the cerebral cortex is a main event of brain aging.Recent neuropathologic studies strongly suggested that the clinical diagnosis of dementia depends more on the severity and topography of pathologic changes than on the presence of a qualitative marker. However, several methodological problems such as selection biases, case-control design,density-based measures, and masking effects of concomitant pathologies should be taken into account when interpreting these data. In last years, the use of stereologic counting permitted to define reliably the cognitive impact of AD lesions in the human brain. Unlike fibrillar amyloid deposits that are poorly or not related to the dementia severity, the use of this method documented that total neurofibrillary tangles and neuron numbers in the CA1 field are the best correlates of cognitive deterioration in brain aging. Loss of dendritic spines in neocortical but not hippocampal areas has a modest but independent contribution to dementia. In contrast, the importance of early dendritic and axonal tau-related pathologic changes such as neuropil threads remains doubtful. Despite these progresses, neuronal pathology and synaptic loss in cases with pure AD pathology cannot explain more than 50% of clinical severity. The present review discusses the complex structure/function relationships in brain aging and AD within the theoretical framework of the functional neuropathology of brain aging.

Brittle cornea syndrome: recognition, molecular diagnosis and management.

Brittle cornea syndrome (BCS) is an autosomal recessive disorder characterised by extreme corneal thinning and fragility. Corneal rupture can therefore occur either spontaneously or following minimal trauma in affected patients. Two genes, ZNF469 and PRDM5, have now been identified, in which causative pathogenic mutations collectively account for the condition in nearly all patients with BCS ascertained to date. Therefore, effective molecular diagnosis is now available for affected patients, and those at risk of being heterozygous carriers for BCS. We have previously identified mutations in ZNF469 in 14 families (in addition to 6 reported by others in the literature), and in PRDM5 in 8 families (with 1 further family now published by others). Clinical features include extreme corneal thinning with rupture, high myopia, blue sclerae, deafness of mixed aetiology with hypercompliant tympanic membranes, and variable skeletal manifestations. Corneal rupture may be the presenting feature of BCS, and it is possible that this may be incorrectly attributed to non-accidental injury. Mainstays of management include the prevention of ocular rupture by provision of protective polycarbonate spectacles, careful monitoring of visual and auditory function, and assessment for skeletal complications such as developmental dysplasia of the hip. Effective management depends upon appropriate identification of affected individuals, which may be challenging given the phenotypic overlap of BCS with other connective tissue disorders.

Learning-induced plasticity in human audition: Objects, time, and space.

The human auditory system is comprised of specialized but interacting anatomic and functional pathways encoding object, spatial, and temporal information. We review how learning-induced plasticity manifests along these pathways and to what extent there are common mechanisms subserving such plasticity. A first series of experiments establishes a temporal hierarchy along which sounds of objects are discriminated along basic to fine-grained categorical boundaries and learned representations. A widespread network of temporal and (pre)frontal brain regions contributes to object discrimination via recursive processing. Learning-induced plasticity typically manifested as repetition suppression within a common set of brain regions. A second series considered how the temporal sequence of sound sources is represented. We show that lateralized responsiveness during the initial encoding phase of pairs of auditory spatial stimuli is critical for their accurate ordered perception. Finally, we consider how spatial representations are formed and modified through training-induced learning. A population-based model of spatial processing is supported wherein temporal and parietal structures interact in the encoding of relative and absolute spatial information over the initial ∼300ms post-stimulus onset. Collectively, these data provide insights into the functional organization of human audition and open directions for new developments in targeted diagnostic and neurorehabilitation strategies.

Thérapie cognitive et comportementale pour les hallucinations auditives résistantes au traitement neuroleptique

The aim of this study is to test the feasibility and the efficacy of a cognitive and behavior therapy manual for auditory hallucinations with persons suffering from schizophrenia in a French-speaking environment and under natural clinical conditions. Eight patients met ICD-10 criteria for paranoid schizophrenia, 2 for hebephrenic schizophrenia and 1 for schizoaffective disorder. All were hearing voices daily. Patients followed the intervention for 3 to 6 months according to their individual rhythms. Participants filled up questionnaires at pre-test, post-test and three months follow-up. The instruments were the Belief About Voice Questionnaire--Revised and two seven points scales about frequency of hallucinations and attribution of the source of the voices. Results show a decrease of voices' frequency and improvement in attributing the voices rather to an internal than to an external source. Malevolent or benevolent beliefs about voices are significantly decreased at follow-up as well as efforts at coping with hallucinations. Results should be interpreted with caution because of the small number of subjects. The sample may not be representative of patients with persistent symptoms since there is an over representation of patients with benevolent voices and an under representation of patients with substance misuse

Is there a common factor for vision?

In cognition, common factors play a crucial role. For example, different types of intelligence are highly correlated, pointing to a common factor, which is often called g. One might expect that a similar common factor would also exist for vision. Surprisingly, no one in the field has addressed this issue. Here, we provide the first evidence that there is no common factor for vision. We tested 40 healthy students' performance in six basic visual paradigms: visual acuity, vernier discrimination, two visual backward masking paradigms, Gabor detection, and bisection discrimination. One might expect that performance levels on these tasks would be highly correlated because some individuals generally have better vision than others due to superior optics, better retinal or cortical processing, or enriched visual experience. However, only four out of 15 correlations were significant, two of which were nontrivial. These results cannot be explained by high intraobserver variability or ceiling effects because test-retest reliability was high and the variance in our student population is commensurate with that from other studies with well-sighted populations. Using a variety of tests (e.g., principal components analysis, Bayes theorem, test-retest reliability), we show the robustness of our null results. We suggest that neuroplasticity operates during everyday experience to generate marked individual differences. Our results apply only to the normally sighted population (i.e., restricted range sampling). For the entire population, including those with degenerate vision, we expect different results.

The behavioral relevance and top-down susceptibility of early, low level multisensory interactions in humans

Abstract (English)General backgroundMultisensory stimuli are easier to recognize, can improve learning and a processed faster compared to unisensory ones. As such, the ability an organism has to extract and synthesize relevant sensory inputs across multiple sensory modalities shapes his perception of and interaction with the environment. A major question in the scientific field is how the brain extracts and fuses relevant information to create a unified perceptual representation (but also how it segregates unrelated information). This fusion between the senses has been termed "multisensory integration", a notion that derives from seminal animal single-cell studies performed in the superior colliculus, a subcortical structure shown to create a multisensory output differing from the sum of its unisensory inputs. At the cortical level, integration of multisensory information is traditionally deferred to higher classical associative cortical regions within the frontal, temporal and parietal lobes, after extensive processing within the sensory-specific and segregated pathways. However, many anatomical, electrophysiological and neuroimaging findings now speak for multisensory convergence and interactions as a distributed process beginning much earlier than previously appreciated and within the initial stages of sensory processing.The work presented in this thesis is aimed at studying the neural basis and mechanisms of how the human brain combines sensory information between the senses of hearing and touch. Early latency non-linear auditory-somatosensory neural response interactions have been repeatedly observed in humans and non-human primates. Whether these early, low-level interactions are directly influencing behavioral outcomes remains an open question as they have been observed under diverse experimental circumstances such as anesthesia, passive stimulation, as well as speeded reaction time tasks. Under laboratory settings, it has been demonstrated that simple reaction times to auditory-somatosensory stimuli are facilitated over their unisensory counterparts both when delivered to the same spatial location or not, suggesting that audi- tory-somatosensory integration must occur in cerebral regions with large-scale spatial representations. However experiments that required the spatial processing of the stimuli have observed effects limited to spatially aligned conditions or varying depending on which body part was stimulated. Whether those divergences stem from task requirements and/or the need for spatial processing has not been firmly established.Hypotheses and experimental resultsIn a first study, we hypothesized that auditory-somatosensory early non-linear multisensory neural response interactions are relevant to behavior. Performing a median split according to reaction time of a subset of behavioral and electroencephalographic data, we found that the earliest non-linear multisensory interactions measured within the EEG signal (i.e. between 40-83ms post-stimulus onset) were specific to fast reaction times indicating a direct correlation of early neural response interactions and behavior.In a second study, we hypothesized that the relevance of spatial information for task performance has an impact on behavioral measures of auditory-somatosensory integration. Across two psychophysical experiments we show that facilitated detection occurs even when attending to spatial information, with no modulation according to spatial alignment of the stimuli. On the other hand, discrimination performance with probes, quantified using sensitivity (d'), is impaired following multisensory trials in general and significantly more so following misaligned multisensory trials.In a third study, we hypothesized that behavioral improvements might vary depending which body part is stimulated. Preliminary results suggest a possible dissociation between behavioral improvements andERPs. RTs to multisensory stimuli were modulated by space only in the case when somatosensory stimuli were delivered to the neck whereas multisensory ERPs were modulated by spatial alignment for both types of somatosensory stimuli.ConclusionThis thesis provides insight into the functional role played by early, low-level multisensory interac-tions. Combining psychophysics and electrical neuroimaging techniques we demonstrate the behavioral re-levance of early and low-level interactions in the normal human system. Moreover, we show that these early interactions are hermetic to top-down influences on spatial processing suggesting their occurrence within cerebral regions having access to large-scale spatial representations. We finally highlight specific interactions between auditory space and somatosensory stimulation on different body parts. Gaining an in-depth understanding of how multisensory integration normally operates is of central importance as it will ultimately permit us to consider how the impaired brain could benefit from rehabilitation with multisensory stimula-Abstract (French)Background théoriqueDes stimuli multisensoriels sont plus faciles à reconnaître, peuvent améliorer l'apprentissage et sont traités plus rapidement comparé à des stimuli unisensoriels. Ainsi, la capacité qu'un organisme possède à extraire et à synthétiser avec ses différentes modalités sensorielles des inputs sensoriels pertinents, façonne sa perception et son interaction avec l'environnement. Une question majeure dans le domaine scientifique est comment le cerveau parvient à extraire et à fusionner des stimuli pour créer une représentation percep- tuelle cohérente (mais aussi comment il isole les stimuli sans rapport). Cette fusion entre les sens est appelée "intégration multisensorielle", une notion qui provient de travaux effectués dans le colliculus supérieur chez l'animal, une structure sous-corticale possédant des neurones produisant une sortie multisensorielle différant de la somme des entrées unisensorielles. Traditionnellement, l'intégration d'informations multisen- sorielles au niveau cortical est considérée comme se produisant tardivement dans les aires associatives supérieures dans les lobes frontaux, temporaux et pariétaux, suite à un traitement extensif au sein de régions unisensorielles primaires. Cependant, plusieurs découvertes anatomiques, électrophysiologiques et de neuroimageries remettent en question ce postulat, suggérant l'existence d'une convergence et d'interactions multisensorielles précoces.Les travaux présentés dans cette thèse sont destinés à mieux comprendre les bases neuronales et les mécanismes impliqués dans la combinaison d'informations sensorielles entre les sens de l'audition et du toucher chez l'homme. Des interactions neuronales non-linéaires précoces audio-somatosensorielles ont été observées à maintes reprises chez l'homme et le singe dans des circonstances aussi variées que sous anes- thésie, avec stimulation passive, et lors de tâches nécessitant un comportement (une détection simple de stimuli, par exemple). Ainsi, le rôle fonctionnel joué par ces interactions à une étape du traitement de l'information si précoce demeure une question ouverte. Il a également été démontré que les temps de réaction en réponse à des stimuli audio-somatosensoriels sont facilités par rapport à leurs homologues unisensoriels indépendamment de leur position spatiale. Ce résultat suggère que l'intégration audio- somatosensorielle se produit dans des régions cérébrales possédant des représentations spatiales à large échelle. Cependant, des expériences qui ont exigé un traitement spatial des stimuli ont produits des effets limités à des conditions où les stimuli multisensoriels étaient, alignés dans l'espace ou encore comme pouvant varier selon la partie de corps stimulée. Il n'a pas été établi à ce jour si ces divergences pourraient être dues aux contraintes liées à la tâche et/ou à la nécessité d'un traitement de l'information spatiale.Hypothèse et résultats expérimentauxDans une première étude, nous avons émis l'hypothèse que les interactions audio- somatosensorielles précoces sont pertinentes pour le comportement. En effectuant un partage des temps de réaction par rapport à la médiane d'un sous-ensemble de données comportementales et électroencépha- lographiques, nous avons constaté que les interactions multisensorielles qui se produisent à des latences précoces (entre 40-83ms) sont spécifique aux temps de réaction rapides indiquant une corrélation directe entre ces interactions neuronales précoces et le comportement.Dans une deuxième étude, nous avons émis l'hypothèse que si l'information spatiale devient perti-nente pour la tâche, elle pourrait exercer une influence sur des mesures comportementales de l'intégration audio-somatosensorielles. Dans deux expériences psychophysiques, nous montrons que même si les participants prêtent attention à l'information spatiale, une facilitation de la détection se produit et ce toujours indépendamment de la configuration spatiale des stimuli. Cependant, la performance de discrimination, quantifiée à l'aide d'un index de sensibilité (d') est altérée suite aux essais multisensoriels en général et de manière plus significative pour les essais multisensoriels non-alignés dans l'espace.Dans une troisième étude, nous avons émis l'hypothèse que des améliorations comportementales pourraient différer selon la partie du corps qui est stimulée (la main vs. la nuque). Des résultats préliminaires suggèrent une dissociation possible entre une facilitation comportementale et les potentiels évoqués. Les temps de réactions étaient influencés par la configuration spatiale uniquement dans le cas ou les stimuli somatosensoriels étaient sur la nuque alors que les potentiels évoqués étaient modulés par l'alignement spatial pour les deux types de stimuli somatosensorielles.ConclusionCette thèse apporte des éléments nouveaux concernant le rôle fonctionnel joué par les interactions multisensorielles précoces de bas niveau. En combinant la psychophysique et la neuroimagerie électrique, nous démontrons la pertinence comportementale des ces interactions dans le système humain normal. Par ailleurs, nous montrons que ces interactions précoces sont hermétiques aux influences dites «top-down» sur le traitement spatial suggérant leur occurrence dans des régions cérébrales ayant accès à des représentations spatiales de grande échelle. Nous soulignons enfin des interactions spécifiques entre l'espace auditif et la stimulation somatosensorielle sur différentes parties du corps. Approfondir la connaissance concernant les bases neuronales et les mécanismes impliqués dans l'intégration multisensorielle dans le système normale est d'une importance centrale car elle permettra d'examiner et de mieux comprendre comment le cerveau déficient pourrait bénéficier d'une réhabilitation avec la stimulation multisensorielle.

Fear assessment in pigs exposed to a novel object test

The experiment aimed to study approach and locomotive behaviour as indicators of fear in a novel object test carried out in pigs. Thirty post-weaning (30 kg) and 30 finishing (90 kg) pigs were exposed to visual, auditory and olfactory novel stimuli during 2 different experiments. The facilities consisted of a test pen in which a trough was located. The trough contained chopped apples. Once the animals were trained to enter the test pen individually they were subjected to 3 different fear stimuli. These stimuli were applied in the test pen and next to the trough. The variables studied were feeding behaviour, approach behaviour (the distance and position of the animal with respect to the trough) and locomotive behaviour (general activity, reluctance to move, turning back and retreat attempts). Two groups were studied: saline and midazolam treated group. Twenty minutes before the start of the sessions, 15 post-weaning and finishing pigs received an intramuscular injection of 0.20 and 0.15 mg/kg, respectively, midazolam (Dormicum1). The saline pigs (15 animals per group) were injected with saline. The administration of midazolam increased the feeding behaviour and approaching behaviour, and reduced the locomotive behaviour. In front of the visual and olfactory stimuli post-weaning pigs showed a higher general activity than finishing pigs, but the contrary was found when the auditory stimulus was applied. The olfactory stimulus was more related to the turning back behaviour, whereas the visual stimulus was more related to retreat attempts. Although it could be concluded that reluctant to move was the most common response to the different fear stimuli applied in our study regardless of the age of animals, the combination of reluctant to move and turning back would be a good criterion to assess fear in domestic pigs. The use of midazolam as anxiolytic for studies of fear in commercial conditions in pigs is recommended.

Looming signals reveal synergistic principles of multisensory integration.

Multisensory interactions are a fundamental feature of brain organization. Principles governing multisensory processing have been established by varying stimulus location, timing and efficacy independently. Determining whether and how such principles operate when stimuli vary dynamically in their perceived distance (as when looming/receding) provides an assay for synergy among the above principles and also means for linking multisensory interactions between rudimentary stimuli with higher-order signals used for communication and motor planning. Human participants indicated movement of looming or receding versus static stimuli that were visual, auditory, or multisensory combinations while 160-channel EEG was recorded. Multivariate EEG analyses and distributed source estimations were performed. Nonlinear interactions between looming signals were observed at early poststimulus latencies (∼75 ms) in analyses of voltage waveforms, global field power, and source estimations. These looming-specific interactions positively correlated with reaction time facilitation, providing direct links between neural and performance metrics of multisensory integration. Statistical analyses of source estimations identified looming-specific interactions within the right claustrum/insula extending inferiorly into the amygdala and also within the bilateral cuneus extending into the inferior and lateral occipital cortices. Multisensory effects common to all conditions, regardless of perceived distance and congruity, followed (∼115 ms) and manifested as faster transition between temporally stable brain networks (vs summed responses to unisensory conditions). We demonstrate the early-latency, synergistic interplay between existing principles of multisensory interactions. Such findings change the manner in which to model multisensory interactions at neural and behavioral/perceptual levels. We also provide neurophysiologic backing for the notion that looming signals receive preferential treatment during perception.

Robust discrimination between EEG responses to categories of environmental sounds in early coma.

Humans can recognize categories of environmental sounds, including vocalizations produced by humans and animals and the sounds of man-made objects. Most neuroimaging investigations of environmental sound discrimination have studied subjects while consciously perceiving and often explicitly recognizing the stimuli. Consequently, it remains unclear to what extent auditory object processing occurs independently of task demands and consciousness. Studies in animal models have shown that environmental sound discrimination at a neural level persists even in anesthetized preparations, whereas data from anesthetized humans has thus far provided null results. Here, we studied comatose patients as a model of environmental sound discrimination capacities during unconsciousness. We included 19 comatose patients treated with therapeutic hypothermia (TH) during the first 2 days of coma, while recording nineteen-channel electroencephalography (EEG). At the level of each individual patient, we applied a decoding algorithm to quantify the differential EEG responses to human vs. animal vocalizations as well as to sounds of living vocalizations vs. man-made objects. Discrimination between vocalization types was accurate in 11 patients and discrimination between sounds from living and man-made sources in 10 patients. At the group level, the results were significant only for the comparison between vocalization types. These results lay the groundwork for disentangling truly preferential activations in response to auditory categories, and the contribution of awareness to auditory category discrimination.

Developmental critical period in gentic redox dysregulation: animal and human studies in schizophrenia

Converging evidence favors an abnormal susceptibility to oxidative stress in schizophrenia. Decreased levels of glutathione (GSH), the major cellular antioxidant and redox regulator, was observed in cerebrospinal-fluid and prefrontal cortex of patients. Importantly, abnormal GSH synthesis of genetic origin was observed: Two case-control studies showed an association with a GAG trinucleotide repeat (TNR) polymorphism in the GSH key synthesizing enzyme glutamate-cysteine-ligase (GCL) catalytic subunit (GCLC) gene. The most common TNR genotype 7/7 was more frequent in controls, whereas the rarest TNR genotype 8/8 was three times more frequent in patients. The disease associated genotypes (35% of patients) correlated with decreased GCLC protein, GCL activity and GSH content. Similar GSH system anomalies were observed in early psychosis patients. Such redox dysregulation combined with environmental stressors at specific developmental stages could underlie structural and functional connectivity anomalies. In pharmacological and knock-out (KO) models, GSH deficit induces anomalies analogous to those reported in patients. (a) morphology: spine density and GABA-parvalbumine immunoreactivity (PV-I) were decreased in anterior cingulate cortex. KO mice showed delayed cortical PV-I at PD10. This effect is exacerbated in mice with increased DA from PD5-10. KO mice exhibit cortical impairment in myelin and perineuronal net known to modulate PV connectivity. (b) physiology: In cultured neurons, NMDA response are depressed by D2 activation. In hippocampus, NMDA-dependent synaptic plasticity is impaired and kainate induced g-oscillations are reduced in parallel to PV-I. (c) cognition: low GSH models show increased sensitivity to stress, hyperactivity, abnormal object recognition, olfactory integration and social behavior. In a clinical study, GSH precursor N-acetyl cysteine (NAC) as add on therapy, improves the negative symptoms and decreases the side effects of antipsychotics. In an auditory oddball paradigm, NAC improves the mismatched negativity, an evoked potential related to pre-attention and to NMDA receptors function. In summary, clinical and experimental evidence converge to demonstrate that a genetically induced dysregulation of GSH synthesis combined with environmental insults in early development represent a major risk factor contributing to the development of schizophrenia Conclusion Based on these data, we proposed a model for PSIP1 promoter activity involving a complex interplay between yet undefined regulatory elements to modulate gene expression.

The role of multisensory memories in unisensory object discrimination.

Past multisensory experiences can influence current unisensory processing and memory performance. Repeated images are better discriminated if initially presented as auditory-visual pairs, rather than only visually. An experience's context thus plays a role in how well repetitions of certain aspects are later recognized. Here, we investigated factors during the initial multisensory experience that are essential for generating improved memory performance. Subjects discriminated repeated versus initial image presentations intermixed within a continuous recognition task. Half of initial presentations were multisensory, and all repetitions were only visual. Experiment 1 examined whether purely episodic multisensory information suffices for enhancing later discrimination performance by pairing visual objects with either tones or vibrations. We could therefore also assess whether effects can be elicited with different sensory pairings. Experiment 2 examined semantic context by manipulating the congruence between auditory and visual object stimuli within blocks of trials. Relative to images only encountered visually, accuracy in discriminating image repetitions was significantly impaired by auditory-visual, yet unaffected by somatosensory-visual multisensory memory traces. By contrast, this accuracy was selectively enhanced for visual stimuli with semantically congruent multisensory pasts and unchanged for those with semantically incongruent multisensory pasts. The collective results reveal opposing effects of purely episodic versus semantic information from auditory-visual multisensory events. Nonetheless, both types of multisensory memory traces are accessible for processing incoming stimuli and indeed result in distinct visual object processing, leading to either impaired or enhanced performance relative to unisensory memory traces. We discuss these results as supporting a model of object-based multisensory interactions.

Discharge properties of single neurons in the dorsal nucleus of the lateral lemniscus of the rat.

The aim of the present study was to characterize the discharge properties of single neurons in the dorsal nucleus of the lateral lemniscus (DNLL) of the rat. In the absence of acoustic stimulation, two types of spontaneous discharge patterns were observed: units tended to fire in a bursting or in a nonbursting mode. The distribution of units in the DNLL based on spontaneous firing rate followed a rostrocaudal gradient: units with high spontaneous rates were most commonly located in the rostral part of the DNLL, whereas in the caudal part units had lower spontaneous discharge rates. The most common response pattern of DNLL units to 200 ms binaural noise bursts contained a prominent onset response followed by a lower but steady-state response and an inhibitory response in the early-off period. Thresholds of response to noise bursts were on average higher for DNLL units than for units recorded in the inferior colliculus under the same experimental conditions. The DNLL units were arranged according to a mediolateral sensitivity gradient with the lowest threshold units in the most lateral part of the nucleus. In the rat, as in other mammals, the most common DNLL binaural input type was an excitatory response to contralateral ear stimulation and inhibitory response to ipsilateral ear stimulation (EI type). Pure tone bursts were in general a more effective stimulus compared to noise bursts. Best frequency (BF) was established for 97 DNLL units and plotted according to their spatial location. The DNLL exhibits a loose tonotopic organization, where there is a concentric pattern with high BF units located in the most dorsal and ventral parts of the DNLL and lower BF units in the middle part of the nucleus.

The spatio-temporal brain dynamics of processing and integrating sound localization cues in humans.

Interaural intensity and time differences (IID and ITD) are two binaural auditory cues for localizing sounds in space. This study investigated the spatio-temporal brain mechanisms for processing and integrating IID and ITD cues in humans. Auditory-evoked potentials were recorded, while subjects passively listened to noise bursts lateralized with IID, ITD or both cues simultaneously, as well as a more frequent centrally presented noise. In a separate psychophysical experiment, subjects actively discriminated lateralized from centrally presented stimuli. IID and ITD cues elicited different electric field topographies starting at approximately 75 ms post-stimulus onset, indicative of the engagement of distinct cortical networks. By contrast, no performance differences were observed between IID and ITD cues during the psychophysical experiment. Subjects did, however, respond significantly faster and more accurately when both cues were presented simultaneously. This performance facilitation exceeded predictions from probability summation, suggestive of interactions in neural processing of IID and ITD cues. Supra-additive neural response interactions as well as topographic modulations were indeed observed approximately 200 ms post-stimulus for the comparison of responses to the simultaneous presentation of both cues with the mean of those to separate IID and ITD cues. Source estimations revealed differential processing of IID and ITD cues initially within superior temporal cortices and also at later stages within temporo-parietal and inferior frontal cortices. Differences were principally in terms of hemispheric lateralization. The collective psychophysical and electrophysiological results support the hypothesis that IID and ITD cues are processed by distinct, but interacting, cortical networks that can in turn facilitate auditory localization.

Distinct subcellular localization of beta-tubulin epitopes in the adult mouse brain.

A panel of monoclonal antibodies specific of alpha-tubulin (TU-01, TU-09) and beta-tubulin (TU-06, TU-13) subunits was used to study the location of N-terminal structural domains of tubulin in adult mouse brain. The specificity of antibodies was confirmed b immunoblotting experiments. Immunohistochemical staining of vibratome sections from cerebral cortex, cerebellum, hippocampus, and corpus callosum showed that antibodies TU-01, TU-09, and TU-13 reacted with neuronal and glial cells and their processes, whereas the TU-06 antibody stained only the perikarya. Dendrites and axons were either unstained or their staining was very weak. As the TU-06 epitope is located on the N-terminal structural domain of beta-tubulin, the observed staining pattern cannot be interpreted as evidence of a distinct subcellular localization of beta-tubulin isotypes or known post-translational modifications. The limited distribution of the epitope could, rather, reflect differences between the conformations of tubulin molecules in microtubules of somata and neurites or, alternatively, a specific masking of the corresponding region on the N-terminal domain of beta-tubulin by interacting protein(s) in dendrites and axons.