The auditory region of the arctoid carnivores.

v.29:no.3(1943)

Morphological parallelisms of the bulla and auditory ossicles in some insectivores and marsupials.

v.51:no.16(1970)

The morphology of the swim bladder and auditory bulla in the Holocentridae.

v.37:no.5(1955)

Modularity of auditory spatial representations

Abstract : Auditory spatial functions are of crucial importance in everyday life. Determining the origin of sound sources in space plays a key role in a variety of tasks including orientation of attention, disentangling of complex acoustic patterns reaching our ears in noisy environments. Following brain damage, auditory spatial processing can be disrupted, resulting in severe handicaps. Complaints of patients with sound localization deficits include the inability to locate their crying child or being over-loaded by sounds in crowded public places. Yet, the brain bears a large capacity for reorganization following damage and/or learning. This phenomenon is referred as plasticity and is believed to underlie post-lesional functional recovery as well as learning-induced improvement. The aim of this thesis was to investigate the organization and plasticity of different aspects of auditory spatial functions. Overall, we report the outcomes of three studies: In the study entitled "Learning-induced plasticity in auditory spatial representations" (Spierer et al., 2007b), we focused on the neurophysiological and behavioral changes induced by auditory spatial training in healthy subjects. We found that relatively brief auditory spatial discrimination training improves performance and modifies the cortical representation of the trained sound locations, suggesting that cortical auditory representations of space are dynamic and subject to rapid reorganization. In the same study, we tested the generalization and persistence of training effects over time, as these are two determining factors in the development of neurorehabilitative intervention. In "The path to success in auditory spatial discrimination" (Spierer et al., 2007c), we investigated the neurophysiological correlates of successful spatial discrimination and contribute to the modeling of the anatomo-functional organization of auditory spatial processing in healthy subjects. We showed that discrimination accuracy depends on superior temporal plane (STP) activity in response to the first sound of a pair of stimuli. Our data support a model wherein refinement of spatial representations occurs within the STP and that interactions with parietal structures allow for transformations into coordinate frames that are required for higher-order computations including absolute localization of sound sources. In "Extinction of auditory stimuli in hemineglect: space versus ear" (Spierer et al., 2007a), we investigated auditory attentional deficits in brain-damaged patients. This work provides insight into the auditory neglect syndrome and its relation with neglect symptoms within the visual modality. Apart from contributing to a basic understanding of the cortical mechanisms underlying auditory spatial functions, the outcomes of the studies also contribute to develop neurorehabilitation strategies, which are currently being tested in clinical populations.

Role of intracellular signaling pathways activated in fibroblasts in response to lipoproteins

Summary The best described physiological function of low-density lipoproteins (LDL) is to transport cholesterol to target tissues. LDL deliver their cholesterol cargo to cells following their interaction with the LDL receptor. LDL, when their vascular concentrations increase, have also been implicated in pathologies such as atherosclerosis. Among the cell types that are found in blood vessels, endothelial and smooth muscle cells have dominated cellular research on atherosclerotic mechanisms and LDL activation of signaling pathways, while very little is known about adventitial fibroblast activation caused by elevated lipoprotein levels. Since fibroblasts participate in wound repair and since it has recently been recognized that fibroblasts may play pivotal roles in vascular remodeling and repair of injury, we assessed whether lipoproteins affect fibroblast function. We have found that LDL specifically mediate the activation of a class of mitogen-activated protein kinases (MAPKs): the p38 MAPKs. The activation of this pathway in turn modulates cell shape by promoting lamellipodia formation and extensive cell spreading. This is of particular interest because it provides a mechanism by which LDL can promote wound healing or vessel wall remodeling as observed during the development of atherosclerosis. In order to understand the molecular mechanisms by which LDL induce p38 activation we searched for the component in the LDL particle responsible for the induction of this pathway. We found that cholesterol is the major component of lipoprotein particles that mediates their ability to stimulate the p38 MAPK pathway. Furthermore, we investigated the cellular mechanisms underlying the ability of LDL to induce cell shape changes and whether this could participate in wound repair. Our recent data demonstrates that the capacity of LDL to induce fibroblast spreading relies on their ability to stimulate IL-8 secretion, which in turn leads to accelerated wound healing. LDL-induced IL-8 production and subsequent wound closure are impaired upon inhibition of the p38 MAPK pathway indicating that the LDL-induced spreading and accelerated wound sealing rely on the ability of LDL to stimulate IL-8 secretion in a p38 MAPK-dependent manner. Therefore, regulation of fibroblast shape and migration by lipoproteins may be relevant to atherosclerosis that is characterized by increased LDL-cholesterol levels, IL-8 production and extensive remodeling of the vessel wall. Résumé: La fonction physiologique des lipoprotéines à faible densité (LDL) la mieux décrite est celle du transport du cholestérol aux tissus cibles. Les LDL livrent leur cargaison de cholestérol aux cellules après leur interaction avec le récepteur au LDL. Une concentration vasculaire des LDL augmenté est également impliquée dans le développement de l'athérosclérose. Parmi les types de cellule présents dans les vaisseaux sanguins, les cellules endothéliales et les cellules du muscle lisse ont dominé la recherche cellulaire sur les mécanismes athérosclérotiques et sur l'activation par les LDL des voies de signalisation intracellulaire. A l'inverse peu de choses sont connues sur l'activation des fibroblastes de l'adventice par les lipoprotéines. Puisqu'il a été récemment reconnu que les fibroblastes peuvent jouer un rôle central dans la remodélisation vasculaire et la réparation tissulaire, nous avons étudié si les lipoprotéines affectent la fonction des fibroblastes. Nous avons constaté que les LDL activent spécifiquement une classe de protéines kinases: les p38 MAPK (mitogen-activated protein kinases). L'activation de cette voie module à son tour la forme de la cellule en favorisant la formation de lamellipodes et l'agrandissement des cellules. Cela a un intérêt particulier car il fournit un mécanisme par lequel les LDL peuvent promouvoir la cicatrisation ou la remodélisation des parois vasculaires comme observés lors du développement de l'athérosclérose. Pour comprendre les mécanismes moléculaires par lesquels les LDL provoquent l'activation des p38 MAPK, nous avons cherché à identifier les composants dans la particule de LDL responsables de l'induction de cette voie. Nous avons constaté que le cholestérol est l'élément principal des particules de lipoprotéine qui contrôle leur capacité à stimuler la voie des p38 MAPK. En outre, nous avons examiné les mécanismes cellulaires responsables de la capacité des LDL à induire des changements dans la forme des cellules. Nos données récentes démontrent que la capacité des LDL à induire l'agrandissement des cellules, ainsi que leur aptitude à favoriser la cicatrisation, reposant sur leur capacité à stimuler la sécrétiond'IL-8. La production d'IL-8 induite par les LDL est bloquée par l'inhibition de la voie p38 MAPK, ce qui indique que l'étalement des cellules induit par les LDL ainsi que l'accélération de la cicatrisation sont liés à la capacité des LDL à stimuler la sécrétion d'IL8 via l'activation des p38 MAPK. La régulation de la forme et de la migration des fibroblastes par les lipoprotéines peuvent donc participer au développement de l'athérosclérose qui est caractérisée par l'augmentation des niveaux de production de LDL-cholestérol et d'IL-8 ainsi que par une remodélisation augmentée de la paroi du vaisseau.

Auditory spatial deficits following hemispheric lesions : dissociation of explicit and implicit processing

Les déficits auditifs spatiaux se produisent fréquemment après une lésion hémisphérique ; un précédent case report suggérait que la capacité explicite à reconnaître des positions sonores, comme dans la localisation des sons, peut être atteinte alors que l'utilisation implicite d'indices sonores pour la reconnaissance d'objets sonores dans un environnement bruyant reste préservée. En testant systématiquement des patients avec lésion hémisphérique inaugurale, nous avons montré que (1) l'utilisation explicite et/ou implicite des indices sonores peut être perturbée ; (2) la dissociation entre l'atteinte de l'utilisation explicite des indices sonores versus une préservation de l'utilisation implicite de ces indices est assez fréquente ; et (3) différents types de déficits dans la localisation des sons peuvent être associés avec une utilisation implicite préservée de ces indices sonores. Conceptuellement, la dissociation entre l'utilisation explicite et implicite de ces indices sonores peut illustrer la dichotomie des deux voies du système auditif. Nos résultats parlent en faveur d'une évaluation systématique des fonctions auditives spatiales dans un contexte clinique, surtout quand l'adaptation à un environnement sonore est en jeu. De plus, des études systématiques sont nécessaires afin de mettre en lien les troubles de l'utilisation explicite versus implicite de ces indices sonores avec les difficultés à effectuer les activités de la vie quotidienne, afin d'élaborer des stratégies de réhabilitation appropriées et afin de s'assurer jusqu'à quel point l'utilisation explicite et implicite des indices spatiaux peut être rééduquée à la suite d'un dommage cérébral.

Comparison of two osteoporotic fracture management pathways: experience at 1 year

Introduction: Osteoporosis presenting as low-impact fractures to traumatology units is often undiagnosed and under-treated. Results from the Osteocare study in Lausanne (a nurse based intervention, passive pathway) showed that only 19% of patients received management for osteoporosis, and in the literature [1], the rate is between 10-25%. We have evaluated a different management concept, based on the systematic assessment of patients with osteoporotic fractures during and after hospitalization (active pathway). Methods: Inpatients admitted to the Department of Musculoskeletal Medicine for a fragility fracture were identified by a nurse according to a predefined questionnaire and were then clinically evaluated by a doctor. Based on the results, a management plan was proposed to the patients. Patients could choose between follow up either by their GP or by the Centre of Bone Disease of the CHUV. For patients who chose follow-up in our Centre, we assessed their adherence to medical follow-up 1 year inclusion. The results of patients who had been evaluated in our cohort between the 1 November 2008 and the 1 December 2009 were analysed. Results: 573 inpatients received specific management of their osteoporotic fracture over 18 months. The mean age was 77 y (31-99), 81% were women (203 hip fractures, 40 pelvis fractures, 101 arm fractures, 57 vertebral fractures, 63 ankle fractures, and 25 others sites). During the study period, 303 patients received a proposition of a specific treatment. 39 (13%) chose a follow up with the GP, 19 (6%) dead and 245 (81%) preferred a follow up in our Centre. After 1 year, 166 (67%) patients are under follow up in our outpatient clinic. Conclusion: With an active clinical pathway that starts during the hospitalization, consisting on a nursing evaluation followed by a medical consultation by an expert in osteoporosis, the adherence increased from 19% to 67% in terms of follow up. These results lead us to propose a consultation with a doctor experienced in osteoporosis after all osteoporotic fractures.

Multimeric complexes of the PML-retinoic acid receptor alpha fusion protein in acute promyelocytic leukemia cells and interference with retinoid and peroxisome-proliferator signaling pathways.

The t(15;17) chromosomal translocation, specific for acute promyelocytic leukemia (APL), fuses the PML gene to the retinoic acid receptor alpha (RAR alpha) gene, resulting in expression of a PML-RAR alpha hybrid protein. In this report, we analyzed the nature of PML-RAR alpha-containing complexes in nuclear protein extracts of t(15;17)-positive cells. We show that endogenous PML-RAR alpha can bind to DNA as a homodimer, in contrast to RAR alpha that requires the retinoid X receptor (RXR) dimerization partner. In addition, these cells contain oligomeric complexes of PML-RAR alpha and endogenous RXR. Treatment with retinoic acid results in a decrease of PML-RAR alpha protein levels and, as a consequence, of DNA binding by the different complexes. Using responsive elements from various hormone signaling pathways, we show that PML-RAR alpha homodimers have altered DNA-binding characteristics when compared to RAR alpha-RXR alpha heterodimers. In transfected Drosophila SL-3 cells that are devoid of endogenous retinoid receptors PML-RAR alpha inhibits transactivation by RAR alpha-RXR alpha heterodimers in a dominant fashion. In addition, we show that both normal retinoid receptors and the PML-RAR alpha hybrid bind and activate the peroxisome proliferator-activated receptor responsive element from the Acyl-CoA oxidase gene, indicating that retinoids and peroxisome proliferator receptors may share common target genes. These properties of PML-RAR alpha may contribute to the transformed phenotype of APL cells.

Hemispheric competence for auditory spatial representation.

Sound localization relies on the analysis of interaural time and intensity differences, as well as attenuation patterns by the outer ear. We investigated the relative contributions of interaural time and intensity difference cues to sound localization by testing 60 healthy subjects: 25 with focal left and 25 with focal right hemispheric brain damage. Group and single-case behavioural analyses, as well as anatomo-clinical correlations, confirmed that deficits were more frequent and much more severe after right than left hemispheric lesions and for the processing of interaural time than intensity difference cues. For spatial processing based on interaural time difference cues, different error types were evident in the individual data. Deficits in discriminating between neighbouring positions occurred in both hemispaces after focal right hemispheric brain damage, but were restricted to the contralesional hemispace after focal left hemispheric brain damage. Alloacusis (perceptual shifts across the midline) occurred only after focal right hemispheric brain damage and was associated with minor or severe deficits in position discrimination. During spatial processing based on interaural intensity cues, deficits were less severe in the right hemispheric brain damage than left hemispheric brain damage group and no alloacusis occurred. These results, matched to anatomical data, suggest the existence of a binaural sound localization system predominantly based on interaural time difference cues and primarily supported by the right hemisphere. More generally, our data suggest that two distinct mechanisms contribute to: (i) the precise computation of spatial coordinates allowing spatial comparison within the contralateral hemispace for the left hemisphere and the whole space for the right hemisphere; and (ii) the building up of global auditory spatial representations in right temporo-parietal cortices.

Human Primary Auditory Cortex Follows the Shape of Heschl's Gyrus.

The primary auditory cortex (PAC) is central to human auditory abilities, yet its location in the brain remains unclear. We measured the two largest tonotopic subfields of PAC (hA1 and hR) using high-resolution functional MRI at 7 T relative to the underlying anatomy of Heschl's gyrus (HG) in 10 individual human subjects. The data reveals a clear anatomical-functional relationship that, for the first time, indicates the location of PAC across the range of common morphological variants of HG (single gyri, partial duplications, and complete duplications). In 20/20 individual hemispheres, two primary mirror-symmetric tonotopic maps were clearly observed with gradients perpendicular to HG. PAC spanned both divisions of HG in cases of partial and complete duplications (11/20 hemispheres), not only the anterior division as commonly assumed. Specifically, the central union of the two primary maps (the hA1-R border) was consistently centered on the full Heschl's structure: on the gyral crown of single HGs and within the sulcal divide of duplicated HGs. The anatomical-functional variants of PAC appear to be part of a continuum, rather than distinct subtypes. These findings significantly revise HG as a marker for human PAC and suggest that tonotopic maps may have shaped HG during human evolution. Tonotopic mappings were based on only 16 min of fMRI data acquisition, so these methods can be used as an initial mapping step in future experiments designed to probe the function of specific auditory fields.

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.

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.

Bihippocampal damage with emotional dysfunction: impaired auditory recognition of fear.

A right-handed man developed a sudden transient, amnestic syndrome associated with bilateral hemorrhage of the hippocampi, probably due to Urbach-Wiethe disease. In the 3rd month, despite significant hippocampal structural damage on imaging, only a milder degree of retrograde and anterograde amnesia persisted on detailed neuropsychological examination. On systematic testing of recognition of facial and vocal expression of emotion, we found an impairment of the vocal perception of fear, but not that of other emotions, such as joy, sadness and anger. Such selective impairment of fear perception was not present in the recognition of facial expression of emotion. Thus emotional perception varies according to the different aspects of emotions and the different modality of presentation (faces versus voices). This is consistent with the idea that there may be multiple emotion systems. The study of emotional perception in this unique case of bilateral involvement of hippocampus suggests that this structure may play a critical role in the recognition of fear in vocal expression, possibly dissociated from that of other emotions and from that of fear in facial expression. In regard of recent data suggesting that the amygdala is playing a role in the recognition of fear in the auditory as well as in the visual modality this could suggest that the hippocampus may be part of the auditory pathway of fear recognition.

Transport pathways in the malaria-infected erythrocyte: characterization and their use as potential targets for chemotherapy

The intraerythrocytic malarial parasite is involved in an extremely intensive anabolic activity while it resides in its metabolically quiescent host cell. The necessary fast uptake of nutrients and the discharge of waste product, are guaranteed by parasite-induced alterations of the constitutive transporters of the host cell and the production of new parallel pathways. The membrane of the host cell thus becomes permeable to phospholipids, purine bases and nucleosides, small non-electrolytes, anions and cations. When the new pathways are quantitatively unimportant, classical inhibitors of native transporters can be used to inhibit parasite growth. Several compounds were found to effectively inhibit the new pathways and consequently, parasite growth. The pathways have also been used to introduce cytotoxic agents. The parasitophorous membrane consists of channels which are highly permeable to small solutes and display no ion selectivity. Transport of some cations and anions across the parasite membrane is rapid and insensitive to classical inhibitors, and in some cases it is mediated by specific antiporters which respond to their respective inhibitors. Macromolecules have been shown to reach the parasitophorous space through a duct contiguous with the host cell membrane, and subsequently to be endocytosed at the parasite membrane. The simultaneous presence of the parasitophorous membrane channels and the duct, however, is incompatible with experimental evidences. No specific inhibitors were found as yet that would efficiently inhibit transport through the channels or the duct.