Understanding the origin, nature and functional significance of complex patterns of neural activity, as recorded by diverse electrophysiological and neuroimaging techniques, is a central challenge in Neuroscience. Such patterns include collective oscillations, emerging out of neural synchronization, as well as highly-heterogeneous outbursts of activity interspersed by periods of quiescence, called "neuronal avalanches". Much debate has been generated about the possible scale-invariance or criticality of such avalanches, and its relevance for brain function. Aimed at shedding light onto this, here we analyze the large-scale collective properties of the cortex by using a mesoscopic approach, following the principle of parsimony of Landau-Ginzburg. Our model is similar to that of Wilson-Cowan for neural dynamics but, crucially, including stochasticity and space; synaptic plasticity and inhibition are considered as possible regulatory mechanisms. Detailed analyses uncover a phase diagram including down-states, synchronous, asynchronous, and up-state phases, and reveal that empirical findings for neuronal avalanches are consistently reproduced by tuning our model to the edge of synchronization. This reveals that the putative criticality of cortical dynamics does not correspond to a quiescent-to-active phase transition, as usually assumed in theoretical approaches, but to a synchronization phase transition, at which incipient oscillations and scalefree avalanches coexist. Furthermore, our model also accounts for up and down states as they occur, e.g. during deep sleep. The present approach constitutes a framework to rationalize the possible collective phases and phase transitions of cortical networks in simple terms, thus helping shed light into basic aspects of brain functioning from a very broad perspective.Cortical dynamics | Neuronal avalanches | Criticality | Synaptic plasticity T he cerebral cortex exhibits spontaneous activity even in the absence of any task or external stimuli (1-3). A salient aspect of this, so-called, resting-state dynamics, as revealed by in vivo and in vitro measurements, is that it exhibits outbursts of electrochemical activity, characterized by brief episodes of coherence -during which many neurons fire within a narrow time window-interspaced by periods of relative quiescence, giving rise to collective oscillatory rhythms (4, 5). Shedding light on the origin, nature, and functional meaning of such an intricate dynamics is a fundamental challenge in Neuroscience (6).Upon experimentally enhancing the spatio-temporal resolution of activity recordings, Beggs and Plenz made the remarkable finding that, actually, synchronized outbursts of neural activity could be decomposed into complex spatio-temporal patterns, thereon named "neuronal avalanches" (7). The sizes and durations of such avalanches were reported to be distributed as power-laws, i.e. to be organized in a scale-free way, limited only by network size (7). Furthermore, they obey finite-size scaling (8), a trademark of scale invariance...

Object-Platelet isoprostane 8-ISO-prostaglandin F2␣ (8-iso-PGF2␣), a proaggregating molecule, is believed to derive from nonenzymatic oxidation of arachidonic acid. We hypothesized that NADPH is implicated in isoprostane formation and platelet activation. Methods and Results-We studied 8-iso-PGF2␣ in platelets from 8 male patients with hereditary deficiency of gp91 phox , the catalytic subunit of NADPH oxidase, and 8 male controls. On stimulation, platelets from controls produced 8-iso-PGF2␣, which was inhibited Ϫ8% by aspirin and Ϫ58% by a specific inhibitor of gp91 phox . Platelets from patients with gp91phox hereditary deficiency had normal thromboxane A 2 formation but marked 8-iso-PGF2␣ reduction compared with controls. In normal platelets incubated with a gp91 phox inhibitor or with SQ29548, a thromboxane A 2 /isoprostane receptor inhibitor, platelet recruitment, an in vitro model of thrombus growth, was reduced by 44% and 64%, respectively; a lower effect (Ϫ17%) was seen with aspirin. Moreover, thrombus formation under shear stress (blood perfusion at the wall shear rate of 1500 s Ϫ1 ) was reduced in samples in which isoprostane formation was inhibited by NADPH oxidase inhibitors. In gp91 phox -deficient patients, agonist-induced platelet aggregation was within the normal range, whereas platelet recruitment was reduced compared with controls. Incubation of platelets from gp91 phox -deficient patients with 8-iso-PGF2␣ dose-dependently (1 to 100 pmol/L) increased platelet recruitment by mobilizing platelet Ca 2ϩ and activating gpIIb/IIIa; a further increase in platelet recruitment was detected by platelet coincubation with L-NAME, an inhibitor of NO synthase. Conclusion-This

No abstract

In patients undergoing elective percutaneous coronary intervention, impaired microcirculatory reperfusion is improved by vitamin C infusion suggesting that oxidative stress is implicated in such a phenomenon.

Avalanches of electrochemical activity in brain networks have been empirically reported to obey scale-invariant behavior -characterized by power-law distributions up to some upper cut-off-both in vitro and in vivo. Elucidating whether such scaling laws stem from the underlying neural dynamics operating at the edge of a phase transition is a fascinating possibility, as systems poised at criticality have been argued to exhibit a number of important functional advantages. Here we employ a well-known model for neural dynamics with synaptic plasticity, to elucidate an alternative scenario in which neuronal avalanches can coexist, overlapping in time, but still remaining scale-free. Remarkably their scale-invariance does not stem from underlying criticality nor self-organization at the edge of a continuous phase transition. Instead, it emerges from the fact that perturbations to the system exhibit a neutral drift -guided by demographic fluctuations-with respect to endogenous spontaneous activity. Such a neutral dynamics -similar to the one in neutral theories of population genetics-implies marginal propagation of activity, characterized by power-law distributed causal avalanches. Importantly, our results underline the importance of considering causal information -on which neuron triggers the firing of which-to properly estimate the statistics of avalanches of neural activity. We discuss the implications of these findings both in modeling and to elucidate experimental observations, as well as its possible consequences for actual neural dynamics and information processing in actual neural networks.

Self-organized criticality elucidates the conditions under which physical and biological systems tune themselves to the edge of a second-order phase transition, with scale invariance. Motivated by the empirical observation of bimodal distributions of activity in neuroscience and other fields, we propose and analyze a theory for the self-organization to the point of phase coexistence in systems exhibiting a first-order phase transition. It explains the emergence of regular avalanches with attributes of scale invariance that coexist with huge anomalous ones, with realizations in many fields.

No abstract

Epidemiological studies indicate a J-shaped relationship linking coffee consumption and cardiovascular risk, suggesting that moderate coffee consumption can be beneficial. Platelet aggregation is of critical importance in thrombotic events, and platelets play a major role in the aetiology of several CVD. The aim of this study was to evaluate the effect of coffee drinking on platelet aggregation ex vivo, using caffeine as control. A crossover study was performed on ten healthy subjects. In two different sessions, subjects drank 200 ml coffee, containing 180 mg caffeine, or a capsule of caffeine (180 mg) with 200 ml water. Platelets were separated from plasma at baseline and 30 and 60 min after coffee drinking. Platelet aggregation was induced with three different agonists: collagen, arachidonic acid and ADP. Coffee drinking inhibited collagen (P, 0·05 from baseline at time 30 min) and arachidonic acid (P,0·05 from baseline at time 60 min) induced platelet aggregation. Caffeine intake did not affect platelet aggregation induced by the three agonists. Coffee consumption induced a significant increase of platelet phenolic acids (likely present as glucuronate and sulphate derivatives), caffeic acid, the principal phenolic acid in coffee, raising from 0·3 (SEM 0·1) to 2·4 (SEM 0·6) ng/mg (P, 0·01). Caffeine was not detectable in platelets. Coffee drinking decreases platelet aggregation, and induces a significant increase in phenolic acid platelet concentration. The antiplatelet effect of coffee is independent from caffeine and could be a result of the interaction of coffee phenolic acids with the intracellular signalling network leading to platelet aggregation.