Individual Brain Charting dataset extension, third release for movie watching and retinotopy data.

The Individual Brain Charting (IBC) is a multi-task functional Magnetic Resonance Imaging dataset acquired at high spatial-resolution and dedicated to the cognitive mapping of the human brain. It consists in the deep phenotyping of twelve individuals, covering a broad range of psychological domains suitable for functional-atlasing applications. Here, we present the inclusion of task data from both naturalistic stimuli and trial-based designs, to uncover structures of brain activation. We rely on the Fast Shared Response Model (FastSRM) to provide a data-driven solution for modelling naturalistic stimuli, typically containing many features. We show that data from left-out runs can be reconstructed using FastSRM, enabling the extraction of networks from the visual, auditory and language systems. We also present the topographic organization of the visual system through retinotopy. In total, six new tasks were added to IBC, wherein four trial-based retinotopic tasks contributed with a mapping of the visual field to the cortex. IBC is open access: source plus derivatives imaging data and meta-data are available in public repositories.

Subject-specific segregation of functional territories based on deep phenotyping.

Functional magnetic resonance imaging (fMRI) has opened the possibility to investigate how brain activity is modulated by behavior. Most studies so far are bound to one single task, in which functional responses to a handful of contrasts are analyzed and reported as a group average brain map. Contrariwise, recent data-collection efforts have started to target a systematic spatial representation of multiple mental functions. In this paper, we leverage the Individual Brain Charting (IBC) dataset-a high-resolution task-fMRI dataset acquired in a fixed environment-in order to study the feasibility of individual mapping. First, we verify that the IBC brain maps reproduce those obtained from previous, large-scale datasets using the same tasks. Second, we confirm that the elementary spatial components, inferred across all tasks, are consistently mapped within and, to a lesser extent, across participants. Third, we demonstrate the relevance of the topographic information of the individual contrast maps, showing that contrasts from one task can be predicted by contrasts from other tasks. At last, we showcase the benefit of contrast accumulation for the fine functional characterization of brain regions within a prespecified network. To this end, we analyze the cognitive profile of functional territories pertaining to the language network and prove that these profiles generalize across participants.

Individual Brain Charting dataset extension, second release of high-resolution fMRI data for cognitive mapping.

We present an extension of the Individual Brain Charting dataset -a high spatial-resolution, multi-task, functional Magnetic Resonance Imaging dataset, intended to support the investigation on the functional principles governing cognition in the human brain. The concomitant data acquisition from the same 12 participants, in the same environment, allows to obtain in the long run finer cognitive topographies, free from inter-subject and inter-site variability. This second release provides more data from psychological domains present in the first release, and also yields data featuring new ones. It includes tasks on e.g. mental time travel, reward, theory-of-mind, pain, numerosity, self-reference effect and speech recognition. In total, 13 tasks with 86 contrasts were added to the dataset and 63 new components were included in the cognitive description of the ensuing contrasts. As the dataset becomes larger, the collection of the corresponding topographies becomes more comprehensive, leading to better brain-atlasing frameworks. This dataset is an open-access facility; raw data and derivatives are publicly available in neuroimaging repositories.

Individual Brain Charting, a high-resolution fMRI dataset for cognitive mapping.

Functional Magnetic Resonance Imaging (fMRI) has furthered brain mapping on perceptual, motor, as well as higher-level cognitive functions. However, to date, no data collection has systematically addressed the functional mapping of cognitive mechanisms at a fine spatial scale. The Individual Brain Charting (IBC) project stands for a high-resolution multi-task fMRI dataset that intends to provide the objective basis toward a comprehensive functional atlas of the human brain. The data refer to a cohort of 12 participants performing many different tasks. The large amount of task-fMRI data on the same subjects yields a precise mapping of the underlying functions, free from both inter-subject and inter-site variability. The present article gives a detailed description of the first release of the IBC dataset. It comprises a dozen of tasks, addressing both low- and high- level cognitive functions. This openly available dataset is thus intended to become a reference for cognitive brain mapping.

Anti-aggregating effect of BAY 58-2667, an activator of soluble guanylyl cyclase.

The purpose of the present study was to determine whether an activator of soluble guanylyl cyclase (sGC), BAY 58-2667, inhibits platelet aggregation and to clarify its mechanism of action. Blood was collected from anesthetized WKY rats. The aggregation of washed platelet was measured and the production of cAMP and cGMP was determined. BAY 58-2667 produced a partial inhibition of the ADP- and collagen-induced platelet aggregation, but did not significantly affect thrombin-induced aggregation. In ADP-induced platelet aggregation, the inhibitory effects of BAY 58-2667 were associated with an increased level of both cGMP and cAMP while that of the prostacyclin analogue, beraprost, was correlated only with an increase in cAMP. The inhibitor of sGC, ODQ, enhanced the effects of BAY 58-2667. The presence of L-nitroarginine, an inhibitor of NO-synthase, hydroxocobalamin, a scavenger of NO, or that of three different NO-donors did not affect the anti-aggregating effect of BAY 58-2667. However, the anti-aggregating effects of beraprost were potentiated by BAY 58-2667. Therefore, the platelet inhibitory effects of BAY 58-2667 are associated with the generation of cGMP and a secondary increase in cAMP, both being totally NO-independent. When the sGC is oxidized, BAY 58-2667 becomes a relevant anti-aggregating agent, which synergizes with the cAMP-dependent pathway.

The anti-aggregating effect of BAY 41-2272, a stimulator of soluble guanylyl cyclase, requires the presence of nitric oxide.

BACKGROUND AND PURPOSE: The purpose of the present study was to determine whether a stimulator of soluble guanylyl cyclase, BAY 41-2272, inhibits platelet aggregation and to clarify its interaction with nitric oxide (NO). EXPERIMENTAL APPROACH: Blood was collected from anaesthetized Wistar Kyoto rats. The aggregation of washed platelets was measured and the production of cAMP and cGMP was determined. KEY RESULTS: In adenosine 5'-diphosphate (ADP)-induced platelet aggregation, the anti-aggregating effects of BAY 41-2272, nitroglycerin, sodium nitroprusside and DEA-NONOate were associated with increased levels of cGMP while that of beraprost, a prostacyclin analogue, was correlated with an increase in cAMP. 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) prevented the effects of BAY 41-2272 and that of nitroglycerin and sodium nitroprusside, but only inhibited the increase in cGMP produced by of DEA-NONOate. Hydroxocobalamin, an NO scavenger, inhibited the effects of the three NO donors and BAY 41-2272 but did not affect those of beraprost. ADP-induced aggregation and the effects of BAY 41-2272 were not affected by L-nitroarginine. A positive interaction was observed between BAY 41-2272 and the three NO donors. BAY 41-2272 potentiated also the anti-aggregating effects of beraprost, and again this potentiation was inhibited by hydroxocobalamin. CONCLUSIONS AND IMPLICATIONS: Inhibition of platelet aggregation by BAY 41-2272 requires the reduced form of soluble guanylyl cyclase and the presence of NO. The positive interaction observed between BAY 41-2272 and various NO donors is qualitatively similar whatever the mechanism involved in NO release. Furthermore, a potent synergism is observed between BAY 41-2272 and a prostacyclin analogue, but only in the presence of NO.

Aging and prostacyclin responses in aorta and platelets from WKY and SHR rats.

In spontaneously hypertensive rat (SHR) aorta, prostacyclin is an endothelium-derived contracting factor contributing to the endothelial dysfunction. This study was designed to determine whether the impairment of the prostacyclin response is influenced by aging and whether such a dysfunction is observed in platelets. Isometric tension was measured in aortic rings, and aggregation was studied in platelet-rich plasma taken from 3-, 6-, and 15-mo-old Wistar-Kyoto rats (WKY) and SHR. In aorta from 3- and 6-mo-old WKY, prostacyclin and beraprost [prostacyclin receptor (IP) agonists] produced relaxations that were enhanced by Triplion (thromboxane-prostanoid receptor antagonist). In 15-mo-old WKY, the relaxations to beraprost were maintained, but not those to prostacyclin. In SHR aorta, prostacyclin or beraprost produced no or minor relaxations, which, in younger SHR, were enhanced by Triplion. In both strains, the relaxations were inhibited by CAY-10441 (IP receptor antagonist). The relaxations to forskolin and isoproterenol were reduced with aging. When compared with those of WKY, the relaxations to isoproterenol were reduced in 3- but not in 6- or 15-mo-old SHR, whereas those to forskolin were consistently diminished at any given age. Whatever the age, prostacyclin and beraprost produced CAY-10441-sensitive inhibitions of ADP-induced platelet aggregation. Both agonists were more potent in SHR than in WKY. Therefore, in platelets from WKY and SHR, the IP receptor-dependent antiaggregant response is functional and maintained during aging. In aorta from WKY those responses are reduced by aging and, in SHR, are already compromised at 3 mo. This dysfunction of the IP receptor is only partially explained by a general dysfunction of the adenylate cyclase pathway.

Protease-activating receptor-4 induces full platelet spreading on a fibrinogen matrix: involvement of ERK2 and p38 and Ca2+ mobilization.

Although the involvement of protease-activating receptor PAR1 and PAR4 is well established in platelet aggregation, their role in platelet adhesion and spreading has yet to be characterized. We investigated platelet adhesion and spreading on a fibrinogen matrix after PAR1 and PAR4 stimulation in correlation with the activation of two MAPKs, ERK2 and p38. Of the two PAR-activating peptides (PAR-APs), PAR1-AP and PAR4-AP, which both induce adhesion, only PAR4-AP induced full platelet spreading. Although both PAR1-AP and PAR4-AP induced ADP secretion, which is required for platelet spreading, only PAR4-AP induced sustained Ca(2+) mobilization. In these conditions of PAR4 induction, ERK2 and p38 activation were involved in platelet spreading but not in platelet adhesion. p38 phosphorylation was dependent on ADP signaling through P2Y12, its receptor. ERK2 phosphorylation was triggered through integrin alphaIIbbeta3 outside-in signaling and was dependent on the Rho pathway. ERK2 and p38 activation induced phosphorylation of the myosin light chain and actin polymerization, respectively, necessary for cytoskeleton reorganization. These findings provide the first evidence that thrombin requires PAR4 for the full spreading response. ERK2 and p38 and sustained Ca(2+) mobilization, involved in PAR4-induced platelet spreading, contribute to the stabilization of platelet thrombi at sites of high thrombin production.

Differential Involvement of ERK2 and p38 in platelet adhesion to collagen.

We investigated the role of two MAP kinases, ERK2 and p38, in platelet adhesion and spreading over collagen matrix in static and blood flow conditions. P38 was involved in collagen-induced platelet adhesion and spreading in static adhesion conditions, whereas ERK2 was not. In blood flow conditions, with shear rates of 300 or 1500 s(-1), ERK2 and p38 displayed differential involvement in platelet adhesion, depending on the presence or absence of the von Willebrand factor (vWF). Low collagen coverage densities (0.04 microg/cm2) did not support vWF binding. During perfusions over this surface, platelet adhesion was not affected by the inhibition of ERK2 phosphorylation by PD 98059. However, abolishing p38 activation by SB 203580 treatment reduced platelet adhesion by 67 +/- 9% at 300 s(-1) and 56 +/- 2% at 1500 s(-1). In these conditions, the p38 activity required for platelet adhesion depends on the alpha2beta1 collagen receptor. At higher collagen coverage densities (0.8 microg/cm2) supporting vWF binding, the inhibition of ERK2 activity by PD 98059 decreased adhesion by 47 +/- 6% at 300 s(-1) and 72 +/- 3% at 1500 s(-1), whereas p38 inhibition had only a small effect. The ERK2 activity required for platelet adhesion was dependent on the interaction of vWF with GPIb. In conclusion, ERK2 and p38 have complementary effects in the control of platelet adhesion to collagen in a shear stress-dependent manner.

Costimulation of the Gi-coupled ADP receptor and the Gq-coupled TXA2 receptor is required for ERK2 activation in collagen-induced platelet aggregation.

The stimulation of platelets by low doses of collagen induces extracellular signal-regulated kinase 2 (ERK2) activation. In this report, we demonstrate that collagen-induced ERK2 activation depends on thromboxane A(2) (TXA(2)) formation and ADP release. The collagen-induced ERK2 activation was inhibited by indomethacin (88%) and by AR-C69931MX (70%), a specific antagonist of P2Y12, a Gi-coupled ADP receptor. AR-C69931MX (10 microM) inhibition was overcome by epinephrine (1 microM), an agonist of the Gi-coupled alpha(2A)-adrenergic receptor, suggesting that the Gi-coupled receptor was necessary for ERK2 activation by collagen. By contrast, MRS 2179 (10 microM), a specific antagonist of P2Y1, a Gq-coupled ADP receptor, did not affect collagen-induced ERK2 activation. Little or no ERK2 activation was observed with ADP alone (10 microM). By contrast, U46619 (10 microM), a stable analog of TXA(2), induced ERK2 activation in an ADP-dependent manner, via the P2Y12 receptor. These results suggest that the Gi-dependent signaling pathway, stimulated by ADP or epinephrine, was not the only pathway required for ERK2 activation by collagen. Costimulation of the specific G(12/13)-coupled TXA(2) receptor with a low dose of U46619 (10 nM) and of Gi- and Gq-coupled ADP receptor (10 microM) induced very low levels of ERK2 activation, similar to those observed with ADP alone, suggesting that G(12/13) is not involved or not sufficient to induce the additional pathway necessary for ERK2 activation. The Gq-coupled TXA(2) receptor was required for ERK2 activation by U46619 (10 microM) and low doses of collagen, clearly showing that a coordinated pathway through both Gq from TXA(2) and Gi from ADP was necessary for ERK2 activation. Finally, we demonstrate that ERK2 activation is involved in collagen-induced aggregation and secretion.