Resting-state connectivity and functional specialization in human medial parieto-occipital cortex

According to recent models of visuo-spatial processing, the medial parieto-occipital cortex is a crucial node of the dorsal visual stream. Evidence from neurophysiological studies in monkeys has indicated that the parieto-occipital sulcus (POS) contains three functionally and cytoarchitectonically distinct areas: the visual area V6 in the fundus of the POS, and the visuo-motor areas V6Av and V6Ad in a progressively dorsal and anterior location with respect to V6. Besides different topographical organization, cytoarchitectonics, and functional properties, these three monkey areas can also be distinguished based on their patterns of cortico-cortical connections. Thanks to wide-field retinotopic mapping, areas V6 and V6Av have been also mapped in the human brain. Here, using a combined approach of resting-state functional connectivity and task-evoked activity by fMRI, we identified a new region in the anterior POS showing a pattern of functional properties and cortical connections that suggests a homology with the monkey area V6Ad. In addition, we observed distinct patterns of cortical connections associated with the human V6 and V6Av which are remarkably consistent with those showed by the anatomical tracing studies in the corresponding monkey areas. Consistent with recent models on visuo-spatial processing, our findings demonstrate a gradient of functional specialization and cortical connections within the human POS, with more posterior regions primarily dedicated to the analysis of visual attributes useful for spatial navigation and more anterior regions primarily dedicated to analyses of spatial information relevant for goal-directed action

Eye position modulates retinotopic responses in early visual areas: a bias for the straight-ahead direction

Even though the eyes constantly change position, the location of a stimulus can be accurately represented by a population of neurons with retinotopic receptive fields modulated by eye position gain fields. Recent electrophysiological studies, however, indicate that eye position gain fields may serve an additional function since they have a non-uniform spatial distribution that increases the neural response to stimuli in the straight-ahead direction. We used functional magnetic resonance imaging and a wide-field stimulus display to determine whether gaze modulations in early human visual cortex enhance the blood-oxygenation-level dependent (BOLD) response to stimuli that are straight-ahead. Subjects viewed rotating polar angle wedge stimuli centered straight-ahead or vertically displaced by ±20° eccentricity. Gaze position did not affect the topography of polar phase-angle maps, confirming that coding was retinotopic, but did affect the amplitude of the BOLD response, consistent with a gain field. In agreement with recent electrophysiological studies, BOLD responses in V1 and V2 to a wedge stimulus at a fixed retinal locus decreased when the wedge location in head-centered coordinates was farther from the straight-ahead direction. We conclude that stimulus-evoked BOLD signals are modulated by a systematic, non-uniform distribution of eye-position gain fields

A common neural substrate for processing scenes and egomotion-compatible visual motion

Neuroimaging studies have revealed two separate classes of category-selective regions specialized in optic flow (egomotion-compatible) processing and in scene/place perception. Despite the importance of both optic flow and scene/place recognition to estimate changes in position and orientation within the environment during self-motion, the possible functional link between egomotion- and scene-selective regions has not yet been established. Here we reanalyzed functional magnetic resonance images from a large sample of participants performing two well-known “localizer” fMRI experiments, consisting in passive viewing of navigationally relevant stimuli such as buildings and places (scene/place stimulus) and coherently moving fields of dots simulating the visual stimulation during self-motion (flow fields). After interrogating the egomotion-selective areas with respect to the scene/place stimulus and the scene-selective areas with respect to flow fields, we found that the egomotion-selective areas V6+ and pIPS/V3A responded bilaterally more to scenes/places compared to faces, and all the scene-selective areas (parahippocampal place area or PPA, retrosplenial complex or RSC, and occipital place area or OPA) responded more to egomotion-compatible optic flow compared to random motion. The conjunction analysis between scene/place and flow field stimuli revealed that the most important focus of common activation was found in the dorsolateral parieto-occipital cortex, spanning the scene-selective OPA and the egomotion-selective pIPS/V3A. Individual inspection of the relative locations of these two regions revealed a partial overlap and a similar response profile to an independent low-level visual motion stimulus, suggesting that OPA and pIPS/V3A may be part of a unique motion-selective complex specialized in encoding both egomotion- and scene-relevant information, likely for the control of navigation in a structured environment

The Human Homologue of Macaque Area V6A

In macaque monkeys, V6A is a visuomotor area located in the anterior bank of the POs, dorsal and anterior to retinotopically-organized extrastriate area V6 (Galletti et al 1996). Unlike V6, V6A represents both contra- and ipsilateral visual fields and is broadly retinotopically organized (Galletti et al 1999b). The contralateral lower visual field is over-represented in V6A. The central 20°-30° of the visual field are mainly represented dorsally (V6Ad) and the periphery ventrally (V6Av), at the border with V6. Both sectors of area V6A contain arm movement-related cells, active during spatially-directed reaching movements (Gamberini et al., 2011). In humans, we previously mapped the retinotopic organization of area V6 (Pitzalis et al., 2006). Here, using phase-encoded fMRI, cortical surface-based analysis and wide-field retinotopic mapping, we define a new cortical region that borders V6 anteriorly and shows a clear over-representation of the contralateral lower visual field and of the periphery. As with macaque V6A, the eccentricity increases moving ventrally within the area. The new region contains a non-mirror-image representation of the visual field. Functional mapping reveals that, as in macaque V6A, the new region, but not the nearby area V6, responds during finger pointing and reaching movements. Based on similarity in position, retinotopic properties, functional organization and relationship with the neighbouring extrastriate visual areas, we propose that the new cortical region is the human homologue of macaque area V6A

Weak proactive cognitive/motor brain control accounts for poor children's behavioral performance in speeded discrimination tasks

Background: Motor and inhibitory control rely on frontal cortex activity, which is known to reach full maturation only in late adolescence. The development of inhibitory control has been studied using event-related potentials (ERP), focusing on reactive processing (i.e. the N2 and the P3 components). Scarce information exists concerning pre-stimulus activity as that represented by the Bereinshafstpotential (BP) and by the prefrontal negativity (pN). Further, no literature exists concerning the post-stimulus components originating within the anterior insula (pN1, pP1, pP2). This study aims at associating children performance with these motor-cognitive processing in frontal brain areas. Methods: High-resolution EEG recordings were employed to measure ERPs from 18 children (12 years old) and 18 adults (28 years old) during a visuo-motor discriminative response task. Response time (RT), commission (CE) and omission errors, and RT variability were compared between groups. At brain level, two pre-stimulus (BP and pN) and seven post-stimulus (P1; pN1; N1; pP1; N2; pP2; P3) ERP components were compared between groups. Results: Children showed slower and more variable RTs and poorer inhibition (higher CEs) than adults. At electrophysiological level, children presented smaller BP and pN. After stimulus onset, children showed lower amplitude of N1, pP1, P3, and pP2 components. The P1, pP1, N2 and P3 were delayed compared to adults. Conclusions: Our results demonstrate that children are characterized by less intense task-related proactive activities in frontal cortex, which may account for subsequent poor and delayed reactive processing and, thus, for inaccurate and slow performance

Hepatocyte Growth Factor Receptor c-Met Instructs T Cell Cardiotropism and Promotes T Cell Migration to the Heart via Autocrine Chemokine Release

© 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)This study was funded by the British Heart Foundation (RG/09/002/2642 to F.M.M.-B.) and the Medical Research Council of the UK (G0901084 to F.M.M.-B.). ImageStream X was funded by the Wellcome Trust (101604/Z/13/Z). This work forms part of the research themes contributing to the translational research portfolio of Barts and the London Cardiovascular Biomedical Research Unit, which is supported and funded by the National Institute of Health Research

The role of lymphoid tissue SPARC in the pathogenesis and response to treatment of multiple myeloma.

BACKGROUND: Despite the significant progress in the treatment of multiple myeloma (MM), the disease remains untreatable and its cure is still an unmet clinical need. Neoplastic transformation in MM is initiated in the germinal centers (GCs) of secondary lymphoid tissue (SLT) where B cells experience extensive somatic hypermutation induced by follicular dendritic cells (FDCs) and T-cell signals. OBJECTIVE: We reason that secreted protein acidic and rich in cysteine (SPARC), a common stromal motif expressed by FDCs at the origin (SLTs) and the destination (BM) of MM, plays a role in the pathogenesis of MM, and, here, we sought to investigate this role. METHODS: There were 107 BM biopsies from 57 MM patients (taken at different time points) together with 13 control specimens assessed for SPARC gene and protein expression and compared with tonsillar tissues. In addition, regulation of myeloma-promoting genes by SPARC-secreting FDCs was assessed in in vitro GC reactions (GCRs). RESULTS: SPARC gene expression was confirmed in both human primary (BM) and secondary (tonsils) lymphoid tissues, and the expression was significantly higher in the BM. Sparc was detectable in the BM and tonsillar lysates, co-localized with the FDC markers in both tissues, and stimulation of FDCs in vitro induced significantly higher levels of SPARC expression than unstimulated controls. In addition, SPARC inversely correlated with BM PC infiltration, ISS staging, and ECOG performance of the MM patients, and in vitro addition of FDCs to lymphocytes inhibited the expression of several oncogenes associated with malignant transformation of PCs. CONCLUSION: FDC-SPARC inhibits several myelomagenic gene expression and inversely correlates with PC infiltration and MM progression. Therapeutic induction of SPARC expression through combinations of the current MM drugs, repositioning of non-MM drugs, or novel drug discovery could pave the way to better control MM in clinically severe and drug-resistant patients

Increased immunocompetence and network centrality of allogroomer workers suggest a link between individual and social immunity in honeybees.

The significant risk of disease transmission has selected for effective immune-defense strategies in insect societies. Division of labour, with individuals specialized in immunity-related tasks, strongly contributes to prevent the spread of diseases. A trade-off, however, may exist between phenotypic specialization to increase task efficiency and maintenance of plasticity to cope with variable colony demands. We investigated the extent of phenotypic specialization associated with a specific task by using allogrooming in the honeybee, Apis mellifera, where worker behaviour might lower ectoparasites load. We adopted an integrated approach to characterize the behavioural and physiological phenotype of allogroomers, by analyzing their behavior (both at individual and social network level), their immunocompetence (bacterial clearance tests) and their chemosensory specialization (proteomics of olfactory organs). We found that allogroomers have higher immune capacity compared to control bees, while they do not differ in chemosensory proteomic profiles. Behaviourally, they do not show differences in the tasks performed (other than allogrooming), while they clearly differ in connectivity within the colonial social network, having a higher centrality than control bees. This demonstrates the presence of an immune-specific physiological and social behavioural specialization in individuals involved in a social immunity related task, thus linking individual to social immunity, and it shows how phenotypes may be specialized in the task performed while maintaining an overall plasticity