Distant heterotopic callosal connections to premotor cortex in non-human primates

Cortico-cortical connectivity has become a major focus of neuroscience in the last decade but most of the connectivity studies focused on intrahemispheric circuits. Little has been reported about information acquired and processed in the premotor cortex and its functional connection with its homotopic counterpart in the opposite hemisphere via the corpus callosum. In non-human primates (macaques) lateralization is not well documented and its exact role is still unknown. The present study confirms in two macaques the existence of homotopic contralateral projections and completes the picture by further exploring heterotopic (non-motor) callosal projections. This was tested by injecting retrograde tracers in the premotor cortical areas PMv and PMd (targets). Our method consisted of identifying the connections with all the homo- and heterotopic cortical areas located in the contralateral hemisphere. The results showed that PMd and PMv receive multiple low-density labeled inputs from the opposite heterotopic prefrontal, parietal, motor, insular and temporal regions. Such unexpected collection of transcallosal inputs from heterotopic areas suggests that the premotor areas communicate with other modalities through long distance low-density networks which could have important implications in the understanding of sensorimotor and multimodal integration

Développement d'un modèle expérimental d'implant cochléaire incorporant des propriétés d'adaptation neuronale

Les travaux de recherche rapportés dans la présente thèse s’intéressent à la fonction auditive qu’elle aborde sous l’angle de la réhabilitation à l’aide d’une prothèse implantée dans la cochlée : l’implant cochléaire. Ce type de prothèse est utilisé depuis une vingtaine d’années et fournit d’ores et déjà à de nombreux patients des conditions d’écoute satisfaisantes, exceptées dans des ambiances bruyantes. Dans l’optique d’améliorer les performances de ces appareils dans le bruit, nous avons mis au point un modèle expérimental chez le rat adulte qui permet d’identifier les fonctions importantes perdues avec les systèmes électriques actuels. Grâce à une comparaison entre les réponses produites par une stimulation naturelle de l’oreille (acoustique) et celles issues de stimulations artificielles (électriques), nous avons montré que les phénomènes d’adaptation neuronale communs à tous les systèmes sensoriels et qui se manifestent par une diminution de l’activité neuronale pendant une stimulation ne sont peu ou pas reproduits lorsque la cochlée est stimulée électriquement. Une nouvelle stratégie de stimulation électrique a donc été développée et est présentée dans ce travail. Sa validation définitive est en cours sur un second modèle expérimental, le singe adulte. Les résultats préliminaires laissent prévoir sur le plan clinique une amélioration significative de la compréhension de la parole en conditions d’écoute difficile chez les patients implantés.The research projects reported in the present thesis deal with the auditory function and more specifically the topic dedicated to auditory rehabilitation with a prosthesis implanted into the cochlea: the cochlear implant (CI). Such prosthesis was used for about twenty years and already provides to numerous patients satisfactory conditions, excepted in noisy environment. From the point of view to improve the performance of these devices in noise, we developed an experimental model in the adult rat in order to identify normal hearing functions that are lost in electro-auditory hearing with present CI. Based on the comparison between responses obtained by natural stimulation of the ear (acoustic) and those obtained by artificial stimulation (electric), we demonstrated that neuronal adaptation phenomena common to all sensory systems and represented by a decrease of neuronal activity during the stimulation are little or none reproduced when the cochlea is electrically stimulated. Therefore, a new strategy of electrical stimulation has been developed and is described in details in the present work. The final validation is under process in a second experimental model, the adult monkey. From a clinical point of view, preliminary results suggest that a significant improvement in speech intelligibility in noise may be achieved for cochlear implanted patients

Direct comparison between properties of adaptation of the auditory nerve and the ventral cochlear nucleus in response to repetitive clicks

The present study was designed to complete two previous reports [Loquet, G., Rouiller, E.M., 2002. Neural adaptation to pulsatile acoustical stimulation in the cochlear nucleus of the rat. Hear. Res. 171, 72–81; Loquet, G., Meyer, K., Rouiller, E.M., 2003. Effects of intensity of repetitive acoustic stimuli on neural adaptation in the ventral cochlear nucleus of the rat. Exp. Brain Res. 153, 436–442] on neural adaptation properties in the auditory system of the rat. Again, auditory near-field evoked potentials (ANEPs) were recorded in response to 250-ms trains of clicks from an electrode chronically implanted in the ventral cochlear nucleus (VCN). Up to now, our interest had focused on the adaptive behavior of the first one (N₁) of the two negative ANEP components. A re-examination of our data for the second negative component (N₂) was now undertaken. Results show that the adaptation time course observed for N₂ displayed the same three-stage pattern previously reported for N₁. Similarly, adaptation became more pronounced and occurred faster as stimulus intensity and/or repetition rate were increased. Based on latency data which suggest N₁ and N₂ to be mainly due to the activity of auditory-nerve (AN) fibers and cochlear nucleus neurons, respectively, it was concluded that neural adaptation assessed by gross-potentials was similar in the AN and VCN. This finding is meaningful in the context of our search to restore normal adaptation phenomena via electro-auditory hearing with an auditory brainstem implant on the same lines as our work in cochlear implants

Multisensory integration in non-human primates during a sensory-motor task

Daily our central nervous system receives inputs via several sensory modalities, processes them and integrates information in order to produce a suitable behavior. The amazing part is that such a multisensory integration brings all information into a unified percept. An approach to start investigating this property is to show that perception is better and faster when multimodal stimuli are used as compared to unimodal stimuli. This forms the first part of the present study conducted in a non-human primate’s model (n = 2) engaged in a detection sensory-motor task where visual and auditory stimuli were displayed individually or simultaneously. The measured parameters were the reaction time (RT) between stimulus and onset of arm movement, successes and errors percentages, as well as the evolution as a function of time of these parameters with training. As expected, RTs were shorter when the subjects were exposed to combined stimuli. The gains for both subjects were around 20 and 40 ms, as compared with the auditory and visual stimulus alone, respectively. Moreover the number of correct responses increased in response to bimodal stimuli. We interpreted such multisensory advantage through redundant signal effect which decreases perceptual ambiguity, increases speed of stimulus detection, and improves performance accuracy. The second part of the study presents single-unit recordings derived from the premotor cortex (PM) of the same subjects during the sensory-motor task. Response patterns to sensory/multisensory stimulation are documented and specific type proportions are reported. Characterization of bimodal neurons indicates a mechanism of audio-visual integration possibly through a decrease of inhibition. Nevertheless the neural processing leading to faster motor response from PM as a polysensory association cortical area remains still unclear