Laminar Origin of Corticostriatal Projections to the Motor Putamen in the Macaque Brain

In the macaque brain, projections from distant, interconnected cortical areas converge in specific zones of the striatum. For example, specific zones of the motor putamen are targets of projections from frontal motor, inferior parietal, and ventrolateral prefrontal hand-related areas and thus are integral part of the so-called "lateral grasping network." In the present study, we analyzed the laminar distribution of corticostriatal neurons projecting to different parts of the motor putamen. Retrograde neural tracers were injected in different parts of the putamen in 3 Macaca mulatta (one male) and the laminar distribution of the labeled corticostriatal neurons was analyzed quantitatively. In frontal motor areas and frontal operculum, where most labeled cells were located, almost everywhere the proportion of corticostriatal labeled neurons in layers III and/or VI was comparable or even stronger than in layer V. Furthermore, within these regions, the laminar distribution pattern of corticostriatal labeled neurons largely varied independently from their density and from the projecting area/sector, but likely according to the target striatal zone. Accordingly, the present data show that cortical areas may project in different ways to different striatal zones, which can be targets of specific combinations of signals originating from the various cortical layers of the areas of a given network. These observations extend current models of corticostriatal interactions, suggesting more complex modes of information processing in the basal ganglia for different motor and nonmotor functions and opening new questions on the architecture of the corticostriatal circuitry

The complex hodological architecture of the macaque dorsal intraparietal areas as emerging from neural tracers and DW-MRI tractography

In macaque monkeys, dorsal intraparietal areas are involved in several daily visuo-motor actions. However, their border and sources of cortical afferents remain loosely defined. Combining retrograde histological tracing and MRI diffusion-based tractography we found a complex hodology of the dorsal bank of the IPS, which can be subdivided into a rostral area PEip, projecting to the spinal cord, and a caudal area MIP lacking such projections. Both include a rostral and a caudal sector, emerging from their ipsilateral, gradient-like connectivity profiles. As tractography estimations, we used the cross-sectional volume of the white matter bundles connecting each area with other parietal and frontal regions, after selecting ROIs corresponding to the injection sites of neural tracers. For most connections, we found a significant correlation between the proportions of cells projecting to all sectors of PEip and MIP along the continuum of the dorsal bank of the IPS and tractography. The latter also revealed “false positive” but plausible streamlines awaiting histological validation

Anterior Intraparietal Area: a Hub in the Observed Manipulative Action Network.

Current knowledge regarding the processing of observed manipulative actions (OMAs) (e.g., grasping, dragging, or dropping) is limited to grasping and underlying neural circuitry remains controversial. Here, we addressed these issues by combining chronic neuronal recordings along the anteroposterior extent of monkeys\u2019 anterior intraparietal (AIP) area with tracer injections into the recorded sites. We found robust neural selectivity for 7 distinct OMAs, particularly in the posterior part of AIP (pAIP), where it was associated with motor coding of grip type and own-hand visual feedback. This cluster of functional properties appears to be specifically grounded in stronger direct connections of pAIP with the temporal regions of the ventral visual stream and the prefrontal cortex, as connections with skeletomotor related areas and regions of the dorsal visual stream exhibited opposite or no rostrocaudal gradients. Temporal and prefrontal areas may provide visual and contextual information relevant for manipulative action processing. These results revise existing models of the action observation network, suggesting that pAIP constitutes a parietal hub for routing information about OMA identity to the other nodes of the network

Occupational Exposure to Solar UV Radiation of a Group of Fishermen Working in the Italian North Adriatic Sea

Occupational solar radiation exposure is a relevant heath risk in the fishing sector. Our aim was to provide a detailed evaluation of individual UV exposure in three different fishing activities in Italy, with personal UV dosimeters and a simple formula to calculate the fraction of ambient erythemal UV dose received by the workers. The potential individual UV exposure of the fishermen was between 65 and 542 Joules/m2. The percentages of the ambient exposure were estimated between 2.5% and 65.3%. Workers\u2019 UV exposure was mainly influenced by the characteristics of the work activity, the postures adopted, and the type of boats. Overall, our data showed that 43% of the daily measurements could result largely above the occupational limits of 1\u20131.3 standard erythemal dose (i.e., 100 Joules/m2) per day, in case of exposure of uncovered skin areas. Measurements of individual UV exposure are important not only to assess the risk but also to increase workers\u2019 perception and stimulate the adoption of preventive measures to reduce solar UV risk. Furthermore, the simple method proposed, linking ambient erythemal UV dose to the workers\u2019 exposure, can be a promising tool for a reliable assessment of the UV risk, as time series of environmental UV dose are widely availabl

Cortical Connections to Area TE in Monkey: Hybrid Modular and Distributed Organization

To investigate the fine anatomical organization of cortical inputs to visual association area TE, 2–3 small injections of retrograde tracers were made in macaque monkeys. Injections were made as a terminal procedure, after optical imaging and electrophysiological recording, and targeted to patches physiologically identified as object-selective. Retrogradely labeled neurons occurred in several unimodal visual areas, the superior temporal sulcus, intraparietal sulcus (IPS), and prefrontal cortex (PFC), consistent with previous studies. Despite the small injection size (<0.5 mm wide), the projection foci in visual areas, but not in IPS or PFC, were spatially widespread (4–6 mm in extent), and predominantly consisted of neurons labeled by only one of the injections. This can be seen as a quasi-modular organization. In addition, within each projection focus, there were scattered neurons projecting to one of the other injections, together with some double-labeled (DL) neurons, in a more distributed pattern. Finally, projection foci included smaller “hotspots,” consisting of intermixed neurons, single-labeled by the different injections, and DL neurons. DL neurons are likely the result of axons having extended, spatially separated terminal arbors, as demonstrated by anterograde experiments. These results suggest a complex, hybrid connectivity architecture, with both modular and distributed components

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Cortical connections of the macaque anterior intraparietal (AIP) area

E’ noto che l’area anteriore intraparietale (AIP) svolge un ruolo cruciale nella trasformazione visuomotoria per i movimenti di afferramento con la mano (grasping). In questo lavoro, abbiamo tracciato le connessioni corticali di AIP. AIP intraprende connessioni principali con 1) le aree della convessità del lobulo parietale inferiore, la porzione rostrale dell’area laterale intraparietale (LIP) e la regione di SII; 2) le aree della via visiva ventrale del banco inferiore del solco temporale superiore e del giro temporale medio; 3) l’area premotoria F5 e le aree prefrontali 46 e 12. Abbiamo inoltre osservato ulteriori connessioni con l’area caudale intraparietale (CIP) e la porzione ventrale del frontal eye field (FEF). I risultati di questo studio suggeriscono che in AIP la trasformazione visuomotoria per la guida delle azioni di interazione con oggetti si basa non solo sulla processazione di informazioni provenienti dalla via visiva dorsale, riguardo le proprietà fisiche dell’oggetto, ma anche su informazioni provenienti dalla via visiva ventrale, riguardo l’identità dell’oggetto. La connessione diretta con la corteccia inferotemporale suggerisce che AIP abbia anche un ruolo unico nel connettere il sistema parietofrontale, costituito da aree coinvolte nella trasformazione sensorimotoria per il grasping, con aree coinvolte nel riconoscimento di oggetti. Di conseguenza, AIP può rappresentare un nodo cruciale in un circuito neuronale in cui i segnali sensoriali e motori della mano hanno accesso alla rappresentazione degli oggetti per il loro riconoscimento su base tattile.We traced the cortical connections of the anterior intraparietal (AIP) area, which is known to play a crucial role in visuomotor transformations for grasping. AIP displayed major connections with 1) areas of the inferior parietal lobule convexity, the rostral part of the lateral intraparietal area and the SII region; 2) ventral visual stream areas of the lower bank of the superior temporal sulcus and the middle temporal gyrus; and 3) the premotor area F5 and prefrontal areas 46 and 12. Additional connections were observed with the caudal intraparietal area and the ventral part of the frontal eye field. This study suggests that visuomotor transformations for object-oriented actions, processed in AIP, rely not only on dorsal visual stream information related to the object's physical properties but also on ventral visual stream information related to object identity. The identification of direct anatomical connections with the inferotemporal cortex suggests that AIP also has a unique role in linking the parietofrontal network of areas involved in sensorimotor transformations for grasping with areas involved in object recognition. Thus, AIP could represent a crucial node in a cortical circuit in which hand-related sensory and motor signals gain access to representations of object identity for tactile object recognition

Comparative anatomy of the macaque and the human frontal oculomotor domain

In non-human primates, at the junction of the prefrontal with the premotor cortex, there is a sector designated as frontal eye field (FEF), involved in controlling oculomotor behavior and spatial attention. Evidence for at least two FEFs in humans is at the basis of the still open issue of the possible homologies between the macaque and the human frontal oculomotor system. In this review article we address this issue suggesting a new view solidly grounded on evidence from the last decade showing that, in macaques, the FEF is at the core of an oculomotor domain in which several distinct areas, including areas 45A and 45B, provide the substrate for parallel processing of different aspects of oculomotor behavior. Based on comparative considerations, we will propose a correspondence between some of the macaque and the human oculomotor fields, thus suggesting sharing of neural substrate for oculomotor control, gaze processing, and orienting attention in space. Accordingly, this article could contribute to settle some aspects of the so-called "enigma" of the human FEF anatomy