The time scales of irreversibility in spontaneous brain activity are altered in obsessive compulsive disorder.

We study how obsessive-compulsive disorder (OCD) affects the complexity and time-reversal symmetry-breaking (irreversibility) of the brain resting-state activity as measured by magnetoencephalography (MEG). Comparing MEG recordings from OCD patients and age/sex matched control subjects, we find that irreversibility is more concentrated at faster time scales and more uniformly distributed across different channels of the same hemisphere in OCD patients than in control subjects. Furthermore, the interhemispheric asymmetry between homologous areas of OCD patients and controls is also markedly different. Some of these differences were reduced by 1-year of Kundalini Yoga meditation treatment. Taken together, these results suggest that OCD alters the dynamic attractor of the brain's resting state and hint at a possible novel neurophysiological characterization of this psychiatric disorder and how this therapy can possibly modulate brain function.

Micro-CT-derived ventilation biomarkers for the longitudinal assessment of pathology and response to therapy in a mouse model of lung fibrosis.

Experimental in-vivo animal models are key tools to investigate the pathogenesis of lung disease and to discover new therapeutics. Histopathological and biochemical investigations of explanted lung tissue are currently considered the gold standard, but they provide space-localized information and are not amenable to longitudinal studies in individual animals. Here, we present an imaging procedure that uses micro-CT to extract morpho-functional indicators of lung pathology in a murine model of lung fibrosis. We quantified the decrease of lung ventilation and measured the antifibrotic effect of Nintedanib. A robust structure-function relationship was revealed by cumulative data correlating micro-CT with histomorphometric endpoints. The results highlight the potential of in-vivo micro-CT biomarkers as novel tools to monitor the progression of inflammatory and fibrotic lung disease and to shed light on the mechanism of action of candidate drugs. Our platform is also expected to streamline translation from preclinical studies to human patients.

The importance of routine quality control for reproducible pulmonary measurements by in vivo micro-CT.

Micro-computed tomography (CT) imaging provides densitometric and functional assessment of lung diseases in animal models, playing a key role either in understanding disease progression or in drug discovery studies. The generation of reliable and reproducible experimental data is strictly dependent on a system's stability. Quality controls (QC) are essential to monitor micro-CT performance but, although QC procedures are standardized and routinely employed in clinical practice, detailed guidelines for preclinical imaging are lacking. In this work, we propose a routine QC protocol for in vivo micro-CT, based on three commercial phantoms. To investigate the impact of a detected scanner drift on image post-processing, a retrospective analysis using twenty-two healthy mice was performed and lung density histograms used to compare the area under curve (AUC), the skewness and the kurtosis before and after the drift. As expected, statistically significant differences were found for all the selected parameters [AUC 532 ± 31 vs. 420 ± 38 (p < 0.001); skewness 2.3 ± 0.1 vs. 2.5 ± 0.1 (p < 0.001) and kurtosis 4.2 ± 0.3 vs. 5.1 ± 0.5 (p < 0.001)], confirming the importance of the designed QC procedure to obtain a reliable longitudinal quantification of disease progression and drug efficacy evaluation.

Run with the Brownian Hare, Hunt with the Deterministic Hounds.

We present analytic results for mean capture time and energy expended by a pack of deterministic hounds actively chasing a randomly diffusing prey. Depending on the number of chasers, the mean capture time as a function of the prey's diffusion coefficient can be monotonically increasing, decreasing, or attain a minimum at a finite value. Optimal speed and number of chasing hounds exist and depend on each chaser's baseline power consumption. The model can serve as an analytically tractable basis for further studies with bearing on the growing field of smart microswimmers and autonomous robots.

Critical current for giant Fano factor in neural models with bistable firing dynamics and implications for signal transmission.

Bistability in the firing rate is a prominent feature in different types of neurons as well as in neural networks. We show that for a constant input below a critical value, such bistability can lead to a giant spike-count diffusion. We study the transmission of a periodic signal and demonstrate that close to the critical bias current, the signal-to-noise ratio suffers a sharp increase, an effect that can be traced back to the giant diffusion and large Fano factor.

A network model of the barrel cortex combined with a differentiator detector reproduces features of the behavioral response to single-neuron stimulation.

The stimulation of a single neuron in the rat somatosensory cortex can elicit a behavioral response. The probability of a behavioral response does not depend appreciably on the duration or intensity of a constant stimulation, whereas the response probability increases significantly upon injection of an irregular current. Biological mechanisms that can potentially suppress a constant input signal are present in the dynamics of both neurons and synapses and seem ideal candidates to explain these experimental findings. Here, we study a large network of integrate-and-fire neurons with several salient features of neuronal populations in the rat barrel cortex. The model includes cellular spike-frequency adaptation, experimentally constrained numbers and types of chemical synapses endowed with short-term plasticity, and gap junctions. Numerical simulations of this model indicate that cellular and synaptic adaptation mechanisms alone may not suffice to account for the experimental results if the local network activity is read out by an integrator. However, a circuit that approximates a differentiator can detect the single-cell stimulation with a reliability that barely depends on the length or intensity of the stimulus, but that increases when an irregular signal is used. This finding is in accordance with the experimental results obtained for the stimulation of a regularly-spiking excitatory cell.

Receiver operating characteristic curves for a simple stochastic process that carries a static signal.

The detection of a weak signal in the presence of noise is an important problem that is often studied in terms of the receiver operating characteristic (ROC) curve, in which the probability of correct detection is plotted against the probability for a false positive. This kind of analysis is typically applied to the situation in which signal and noise are stochastic variables; the detection problem emerges, however, also often in a context in which both signal and noise are stochastic processes and the (correct or false) detection is said to take place when the process crosses a threshold in a given time window. Here we consider the problem for a combination of a static signal which has to be detected against a dynamic noise process, the well-known Ornstein-Uhlenbeck process. We give exact (but difficult to evaluate) quadrature expressions for the detection rates for false positives and correct detections, investigate systematically a simple sampling approximation suggested earlier, compare to an approximation by Stratonovich for the limit of high threshold, and briefly explore the case of multiplicative signal; all theoretical results are compared to extensive numerical simulations of the corresponding Langevin equation. Our results demonstrate that the sampling approximation provides a reasonable description of the ROC curve for this system, and it clarifies limit cases for the ROC curve.

Detecting single-cell stimulation in a large network of integrate-and-fire neurons.

Several experiments have shown that the stimulation of a single neuron in the cortex can influence the local network activity and even the behavior of an animal. From the theoretical point of view, it is not clear how stimulating a single cell in a cortical network can evoke a statistically significant change in the activity of a large population. Our previous study considered a random network of integrate-and-fire neurons and proposed a way of detecting the stimulation of a single neuron in the activity of a local network: a threshold detector biased toward a specific subset of neurons. Here, we revisit this model and extend it by introducing a second network acting as a readout. In the simplest scenario, the readout consists of a collection of integrate-and-fire neurons with no recurrent connections. In this case, the ability to detect the stimulus does not improve. However, a readout network with both feed-forward and local recurrent inhibition permits detection with a very small bias, if compared to the readout scheme introduced previously. The crucial role of inhibition is to reduce global input cross correlations, the main factor limiting detectability. Finally, we show that this result is robust if recurrent excitatory connections are included or if a different kind of readout bias (in the synaptic amplitudes instead of connection probability) is used.

Self-Consistent Scheme for Spike-Train Power Spectra in Heterogeneous Sparse Networks.

Recurrent networks of spiking neurons can be in an asynchronous state characterized by low or absent cross-correlations and spike statistics which resemble those of cortical neurons. Although spatial correlations are negligible in this state, neurons can show pronounced temporal correlations in their spike trains that can be quantified by the autocorrelation function or the spike-train power spectrum. Depending on cellular and network parameters, correlations display diverse patterns (ranging from simple refractory-period effects and stochastic oscillations to slow fluctuations) and it is generally not well-understood how these dependencies come about. Previous work has explored how the single-cell correlations in a homogeneous network (excitatory and inhibitory integrate-and-fire neurons with nearly balanced mean recurrent input) can be determined numerically from an iterative single-neuron simulation. Such a scheme is based on the fact that every neuron is driven by the network noise (i.e., the input currents from all its presynaptic partners) but also contributes to the network noise, leading to a self-consistency condition for the input and output spectra. Here we first extend this scheme to homogeneous networks with strong recurrent inhibition and a synaptic filter, in which instabilities of the previous scheme are avoided by an averaging procedure. We then extend the scheme to heterogeneous networks in which (i) different neural subpopulations (e.g., excitatory and inhibitory neurons) have different cellular or connectivity parameters; (ii) the number and strength of the input connections are random (Erdos-Rényi topology) and thus different among neurons. In all heterogeneous cases, neurons are lumped in different classes each of which is represented by a single neuron in the iterative scheme; in addition, we make a Gaussian approximation of the input current to the neuron. These approximations seem to be justified over a broad range of parameters as indicated by comparison with simulation results of large recurrent networks. Our method can help to elucidate how network heterogeneity shapes the asynchronous state in recurrent neural networks.

Optimal Detection of a Localized Perturbation in Random Networks of Integrate-and-Fire Neurons.

Experimental and theoretical studies suggest that cortical networks are chaotic and coding relies on averages over large populations. However, there is evidence that rats can respond to the short stimulation of a single cortical cell, a theoretically unexplained fact. We study effects of single-cell stimulation on a large recurrent network of integrate-and-fire neurons and propose a simple way to detect the perturbation. Detection rates obtained from simulations and analytical estimates are similar to experimental response rates if the readout is slightly biased towards specific neurons. Near-optimal detection is attained for a broad range of intermediate values of the mean coupling between neurons.

Slow fluctuations in recurrent networks of spiking neurons.

Networks of fast nonlinear elements may display slow fluctuations if interactions are strong. We find a transition in the long-term variability of a sparse recurrent network of perfect integrate-and-fire neurons at which the Fano factor switches from zero to infinity and the correlation time is minimized. This corresponds to a bifurcation in a linear map arising from the self-consistency of temporal input and output statistics. More realistic neural dynamics with a leak current and refractory period lead to smoothed transitions and modified critical couplings that can be theoretically predicted.

Helicobacter pylori in celiac disease and in duodenal intraepithelial lymphocytosis: Active protagonist or innocent bystander?

BACKGROUND AND OBJECTIVE: Helicobacter pylori (H. pylori) infection influences duodenal inflammation. Consequently, in celiac disease and in duodenal intraepithelial lymphocytosis, the bacterium could affect the clinical-histological manifestations. The aim of this work was to evaluate the prevalence and the potential role of H. pylori infection in celiac disease and duodenal intraepithelial lymphocytosis. METHODS: H. pylori status was reviewed in 154 patients with celiac disease or duodenal intraepithelial lymphocytosis and in a control population. This retrospective study was performed at Molinette hospital, university of Torino, Italy. RESULTS: H. pylori prevalence was 36% in celiac disease patients, 19% in case of duodenal intraepithelial lymphocytosis and 41% in controls (P<0.05 vs. duodenal intraepithelial lymphocytosis). H. pylori prevalence was not significantly different between celiac disease patients with or without iron deficiency anemia (22% vs. 39%) and it was higher in patients with milder duodenal lesions: 50% in Marsh-Oberhuber classification type 1-2 vs. 33% in type 3. Celiac disease patients had a mean intraepithelial lymphocytes count greater than that of duodenal intraepithelial lymphocytosis patients (52 vs. 44 intraepithelial lymphocytes per 100 epithelial cells). Both in celiac disease and in duodenal intraepithelial lymphocytosis patients, H. pylori infection was associated with an increase in intraepithelial lymphocytes count, but this difference was not significant. CONCLUSION: H. pylori prevalence was similar in celiac disease patients and in controls and higher in patients with milder duodenal lesions. There was no association between H. pylori infection and duodenal intraepithelial lymphocytosis.

A frequency-resolved mutual information rate and its application to neural systems.

The encoding and processing of time-dependent signals into sequences of action potentials of sensory neurons is still a challenging theoretical problem. Although, with some effort, it is possible to quantify the flow of information in the model-free framework of Shannon's information theory, this yields just a single number, the mutual information rate. This rate does not indicate which aspects of the stimulus are encoded. Several studies have identified mechanisms at the cellular and network level leading to low- or high-pass filtering of information, i.e., the selective coding of slow or fast stimulus components. However, these findings rely on an approximation, specifically, on the qualitative behavior of the coherence function, an approximate frequency-resolved measure of information flow, whose quality is generally unknown. Here, we develop an assumption-free method to measure a frequency-resolved information rate about a time-dependent Gaussian stimulus. We demonstrate its application for three paradigmatic descriptions of neural firing: an inhomogeneous Poisson process that carries a signal in its instantaneous firing rate; an integrator neuron (stochastic integrate-and-fire model) driven by a time-dependent stimulus; and the synchronous spikes fired by two commonly driven integrator neurons. In agreement with previous coherence-based estimates, we find that Poisson and integrate-and-fire neurons are broadband and low-pass filters of information, respectively. The band-pass information filtering observed in the coherence of synchronous spikes is confirmed by our frequency-resolved information measure in some but not all parameter configurations. Our results also explicitly show how the response-response coherence can fail as an upper bound on the information rate.

Prevalence and incidence of rheumatoid arthritis in Italy.

Aim of the study was to estimate the prevalence and incidence of rheumatoid arthritis (RA) from an administrative cohort consisting of 2,268,514 males and 2,446,769 females, aged ≥ 18 years, from 32 Italian Health Districts. The diagnosis of RA was certified by a qualified specialist and confirmed by ≥3 prescriptions of "specific drugs" (corticosteroids, DMARDs or "biological" agents) during 2011. Patients on "specific drugs" qualified as "active RA"; those who never had more than 4 prescriptions in the past were classified as "unlikely RA," and those previously on chronic treatment but who discontinued therapy for >1 year were classified as "remission RA." The patients with a diagnosis of RA were 22,801 (0.48 %) with a prevalence of "active RA," "remission RA" and "confirmed RA" (Active + Remission RA) of 0.32, 0.09 and 0.41 % (95 % CI 0.38-0.44), respectively. The classification criteria tested in a fifth of the study population by direct analysis yielded >90 % accuracy and precision. The yearly incidence of "active RA" per 100,000 subjects was 48 (95 % CI 40-57) and 20 (95 % CI 10-30) for women and men, respectively. The peak for both prevalence and incidence was around the eighth decade of life. The female/male ratios for both prevalence and incidence were ca. 2.6 before the fifth decade of life, but approached unity in the ninth decade of life. The overall prevalence and incidence of RA in a large sample of the Italian population is only marginally lower than that reported from a similar administrative database of Sweden. With advancing age, the female/male ratio declines to about one.