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Feedback connections play a major role in many theories of brain function. Previous studies of feedback connections to early visual areas have mainly concentrated on the representation of central visual fields. Here, injections of tracers at different eccentricities in areas V1 and V2 revealed retinotopically organized feedback. Peripheral injections revealed projections from 15 areas that are not labeled by central injections. Connection strengths for the majority of projections vary significantly with eccentricity in a systematic fashion with respect to distance and origin; whereas projections to central and upper visual fields are significantly stronger from ventral stream areas, peripheral and lower field projections are stronger from the dorsal stream. Non-invasive functional connectivity suggests a similar anatomical organization in humans. These features are discussed with respect to the cognitive and perceptual roles of these feedback pathways.

Parkinson’s disease (PD) evolves over an extended and variable period in humans; several years prior to the onset of classical motor symptoms, cognitive deficits as well as sleep and biological rhythm disorders develop and worsen with disease progression, significantly impacting the quality of life of patients. The gold standard MPTP macaque model of PD recapitulates the progression of motor and non-motor symptoms over contracted periods of time.Here, this multidisciplinary and multiparametric study follows, in five animals, the steady progression of motor and non-motor symptoms and describes their reversal following bilateral grafts of neural precursors in diverse functional domains of the basal ganglia.Results show unprecedented recovery from cognitive symptoms in addition to a strong clinical motor recuperation. Both motor and cognitive recovery and partial circadian rhythm recovery correlate with the degree of graft integration into the host environment as well as with in-vivo levels of striatal dopaminergic innervation and function.Given inter-individuality of disease progression and recovery the present study underlines the importance of longitudinal multidisciplinary assessments in view of clinical translation and provides empirical evidence that integration of neural precursors following transplantation efficiently restores function at multiple levels in parkinsonian non-human primates.One Sentence SummaryEmpirical evidence that cell therapy efficiently reverts cognitive and clinical motor symptoms in the non-human primate model of Parkinson’s disease.

Cognitive deficits as well as disorders of sleep and biological rhythms constitute non-motor symptoms that significantly impact quality of life in Parkinson’s disease patients. Few studies have evaluated the impact of cell replacement therapy on such non-motor symptoms. Here we used a multidisciplinary approach to assess the therapeutic potential of bilateral grafts of neural stem cells in a macaque model of Parkinson’s disease on both motor and non-motor markers of functional recovery. Grafts led to varying degrees of functional recovery while sham experiments did not. We show unprecedented recovery from cognitive symptoms in addition to a clear clinical motor recuperation. Motor and cognitive recovery but not circadian rhythm recovery correlated with the degree of graft integration into the host environment and with in-vivo levels of striatal dopaminergic transporters and function. This study provides empirical evidence that neural stem cells transplantation efficiently restore function at multiple levels in Parkinsonian non-human primates. We demonstrate the promising potential of multiple-sites neural stem cells grafts for Parkinson’s disease but furthermore underline the crucial importance of such multidisciplinary approaches for an effective clinical translation.

The laminar location of the cell bodies and terminals of interareal connections determines the hierarchical structural organization of the cortex and has been intensively studied. However, we still have only a rudimentary understanding of the connectional principles of feedforward (FF) and feedback (FB) pathways. Quantitative analysis of retrograde tracers was used to extend the notion that the laminar distribution of neurons interconnecting visual areas provides an index of hierarchical distance (percentage of supragranular labeled neurons [SLN]). We show that: 1) SLN values constrain models of cortical hierarchy, revealing previously unsuspected areal relations; 2) SLN reflects the operation of a combinatorial distance rule acting differentially on sets of connections between areas; 3) Supragranular layers contain highly segregated bottom-up and top-down streams, both of which exhibit point-to-point connectivity. This contrasts with the infragranular layers, which contain diffuse bottom-up and top-down streams; 4) Cell filling of the parent neurons of FF and FB pathways provides further evidence of compartmentalization; 5) FF pathways have higher weights, cross fewer hierarchical levels, and are less numerous than FB pathways. Taken together, the present results suggest that cortical hierarchies are built from supra- and infragranular counterstreams. This compartmentalized dual counterstream organization allows point-to-point connectivity in both bottom-up and top-down directions.

SummaryRecent advances in neuroscience have engendered interest in large-scale brain networks. Using a consistent database of cortico-cortical connectivity, generated from hemisphere-wide, retrograde tracing experiments in the macaque, we analyzed interareal weights and distances to reveal an important organizational principle of brain connectivity. Using appropriate graph theoretical measures, we show that although very dense (66%), the interareal network has strong structural specificity. Connection weights exhibit a heavy-tailed lognormal distribution spanning five orders of magnitude and conform to a distance rule reflecting exponential decay with interareal separation. A single-parameter random graph model based on this rule predicts numerous features of the cortical network: (1) the existence of a network core and the distribution of cliques, (2) global and local binary properties, (3) global and local weight-based communication efficiencies modeled as network conductance, and (4) overall wire-length minimization. These findings underscore the importance of distance and weight-based heterogeneity in cortical architecture and processing.

Retrograde tracer injections in 29 of the 91 areas of the macaque cerebral cortex revealed 1,615 interareal pathways, a third of which have not previously been reported. A weight index (extrinsic fraction of labeled neurons [FLNe]) was determined for each area-to-area pathway. Newly found projections were weaker on average compared with the known projections; nevertheless, the 2 sets of pathways had extensively overlapping weight distributions. Repeat injections across individuals revealed modest FLNe variability given the range of FLNe values (standard deviation

We investigated the influence of interareal distance on connectivity patterns in a database obtained from the injection of retrograde tracers in 29 areas distributed over six regions (occipital, temporal, parietal, frontal, prefrontal, and limbic). One-third of the 1,615 pathways projecting to the 29 target areas were reported only recently and deemed new-found projections (NFPs). NFPs are predominantly long-range, low-weight connections. A minimum dominating set analysis (a graph theoretic measure) shows that NFPs play a major role in globalizing input to small groups of areas. Randomization tests show that ( i ) NFPs make important contributions to the specificity of the connectivity profile of individual cortical areas, and ( ii ) NFPs share key properties with known connections at the same distance. We developed a similarity index, which shows that intraregion similarity is high, whereas the interregion similarity declines with distance. For area pairs, there is a steep decline with distance in the similarity and probability of being connected. Nevertheless, the present findings reveal an unexpected binary specificity despite the high density (66%) of the cortical graph. This specificity is made possible because connections are largely concentrated over short distances. These findings emphasize the importance of long-distance connections in the connectivity profile of an area. We demonstrate that long-distance connections are particularly prevalent for prefrontal areas, where they may play a prominent role in large-scale communication and information integration.

Introduction Une analyse qualitative des donnees terrains a permis d’observer une augmentation du nombre d’interventions (SSTI, Carsat, ARACT) dans le secteur sanitaire et social sur les themes du maintien dans l’emploi, de la prevention des RPS et des TMS. Le croisement de ces constats avec des donnees regionales de sinistralite et de grandes enquetes a mis en evidence des contraintes physiques et organisationnelles importantes, des expositions aux agents biologiques et chimiques ainsi que des atteintes a la sante telles que les troubles neuropsychiques et osteo-articulaires. L’emergence de ces multiples problematiques a ete a l’origine de la genese d’un groupe de travail constitue de SSTI de la region centre Val-de-Loire, de l’ARACT et de la CARSAT centre Val-de-Loire. Objectifs La demarche MESOCAP a pour objectif de soutenir les etablissements dans l’acquisition d’une politique de prevention a l’aide d’un outil d’autodiagnostic, specifique et adapte aux risques du secteur medico-social, et de sensibiliser les structures dirigeantes ainsi que les organisations operationnelles. L’identification, le plus en amont possible, des problematiques rencontrees dans l’organisation du travail des etablissements de ce secteur constitue une entree privilegiee pour l’evaluation des risques professionnels. Methodologie Un outil d’autodiagnostic en 7 dimensions ( process /prise en compte de la charge de travail et des aleas/reconnaissance, management et relations de travail/sante et securite/gestion des ressources humaines/sens du travail et prise en compte des valeurs et attentes des salaries/contexte et relations exterieures) permet d’identifier les situations de travail pouvant etre des facteurs de risques, a l’aide d’un graphique en forme de « radar » automatise sur Excel genere selon les niveaux des reponses renseignes par les structures. A chaque dimension, sont rattachees des fiches (definitions, impact sur la sante, exemples de leviers d’action). Resultats Une phase d’experimentation en 3 etapes a permis, a travers un accompagnement individuel, collectif ou mixte du groupe de travail avec les etablissements volontaires, de reajuster certains points methodologiques et pratiques. Le deploiement de l’outil dans la region est en cours. Discussion/conclusion L’outil permet de photographier l’existant, questionner les pratiques de facon concertee, comparer et debattre des points de vue du travail entre structures et construire collectivement des axes de progres. Cet outil pourrait permettre a long terme aux SSTI et autres preventeurs de dessiner des strategies par secteur d’activite et/ou metier afin de mettre en place des actions de prevention adaptees aux plus pres des besoins des entreprises.

The operation of real world networks is largely determined by their weighted and spatial characteristics. Surprisingly little is known about these features in cortex. We generated in macaque, a consistent database of inter-areal connections comprising projection densities (link weights) and physical lengths. Contrary to previous assumptions, the cortical connection matrix is dense (66%) and therefore, not a small-world graph. Link weights are both highly specific and heterogeneous and we show that it is these properties that characterize the network. The embedding of this weighted network is governed by a distance rule that predicts both its binary features as well as the global and local communication efficiencies. Analysis of the efficiency of this weighted network suggests that small changes in global communication efficiency are offset by large changes in local efficiency. These findings indicate a weight-based hierarchical layering in cortical architecture and processing.