Applications of dynamical inference to the analysis of noisy biological time series with hidden dynamical variables.

We present a Bayesian framework for parameter inference in noisy, non-stationary, nonlinear, dynamical systems. The technique is implemented in two distinct ways: (i) Lightweight implementation: to be used for on-line analysis, allowing multiple parameter estimation, optimal compensation for dynamical noise, and reconstruction by integration of the hidden dynamical variables, but with some limitations on how the noise appears in the dynamics; (ii) Full scale implementation: of the technique with extensive numerical simulations (MCMC), allowing for more sophisticated reconstruction of hidden dynamical trajectories and dealing better with sources of noise external to the dynamics (measurements noise)

Time-resolved connectome of the five-factor model of personality

Abstract: The human brain is characterized by highly dynamic patterns of functional connectivity. However, it is unknown whether this time-variant ‘connectome’ is related to the individual differences in the behavioural and cognitive traits described in the five-factor model of personality. To answer this question, inter-network time-variant connectivity was computed in n = 818 healthy people via a dynamical conditional correlation model. Next, network dynamicity was quantified throughout an ad-hoc measure (T-index) and the generalizability of the multi-variate associations between personality traits and network dynamicity was assessed using a train/test split approach. Conscientiousness, reflecting enhanced cognitive and emotional control, was the sole trait linked to stationary connectivity across several circuits such as the default mode and prefronto-parietal network. The stationarity in the ‘communication’ across large-scale networks offers a mechanistic description of the capacity of conscientious people to ‘protect’ non-immediate goals against interference over-time. This study informs future research aiming at developing more realistic models of the brain dynamics mediating personality differences

VAESim: A probabilistic approach for self-supervised prototype discovery

In medical image datasets, discrete labels are often used to describe a continuous spectrum of conditions, making unsupervised image stratification a challenging task. In this work, we propose VAESim, an architecture for image stratification based on a conditional variational autoencoder. VAESim learns a set of prototypical vectors during training, each associated with a cluster in a continuous latent space. We perform a soft assignment of each data sample to the clusters and reconstruct the sample based on a similarity measure between the sample embedding and the prototypical vectors. to update the prototypical embeddings, we use an exponential moving average of the most similar representations between actual prototypes and samples in the batch size. We test our approach on the MNIST handwritten digit dataset and the pneumoniaMNIST medical benchmark dataset, where we show that our method outperforms baselines in terms of kNN accuracy (up to +15% improvement in performance) and performs at par with classification models trained in a fully supervised way. our model also outperforms current end-to-end models for unsupervised stratification

The central autonomic network at rest: Uncovering functional MRI correlates of time-varying autonomic outflow.

Peripheral measures of autonomic nervous system (ANS) activity at rest have been extensively employed as putative biomarkers of autonomic cardiac control. However, a comprehensive characterization of the brain-based central autonomic network (CAN) sustaining cardiovascular oscillations at rest is missing, limiting the interpretability of these ANS measures as biomarkers of cardiac control. We evaluated combined cardiac and fMRI data from 34 healthy subjects from the Human Connectome Project to detect brain areas functionally linked to cardiovagal modulation at rest. Specifically, we combined voxel-wise fMRI analysis with instantaneous heartbeat and spectral estimates obtained from inhomogeneous linear point-process models. We found exclusively negative associations between cardiac parasympathetic activity at rest and a widespread network including bilateral anterior insulae, right dorsal middle and left posterior insula, right parietal operculum, bilateral medial dorsal and ventrolateral posterior thalamic nuclei, anterior and posterior mid-cingulate cortex, medial frontal gyrus/pre-supplementary motor area. Conversely, we found only positive associations between instantaneous heart rate and brain activity in areas including frontopolar cortex, dorsomedial prefrontal cortex, anterior, middle and posterior cingulate cortices, superior frontal gyrus, and precuneus. Taken together, our data suggests a much wider involvement of diverse brain areas in the CAN at rest than previously thought, which could reflect a differential (both spatially and directionally) CAN activation according to the underlying task. Our insight into CAN activity at rest also allows the investigation of its impairment in clinical populations in which task-based fMRI is difficult to obtain (e.g., comatose patients or infants).This work was supported by the US National Institutes for Health (NIH), Office of the Director (OT2-OD023867 to VN); National Center for Complementary and Integrative Health (NCCIH), NIH (P01-AT009965, R61-AT009306, R33-AT009306, R01-AT007550 to VN); the National Institute for Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH (R01-AR064367 to VN); the Medical Research Council (MRC), UK (MR/P01271X/1 to LP); the American Heart Association (16GRNT26420084 to RB)

Causal influence of brainstem response to transcutaneous vagus nerve stimulation on cardiovagal outflow

background: the autonomic response to transcutaneous auricular vagus nerve stimulation (taVNS) has been linked to the engagement of brainstem circuitry modulating autonomic outflow. However, the physiological mechanisms supporting such efferent vagal responses are not well understood, particularly in humans. hypothesis: we present a paradigm for estimating directional brain-heart interactions in response to taVNS. We propose that our approach is able to identify causal links between the activity of brainstem nuclei involved in autonomic control and cardiovagal outflow. methods: we adopt an approach based on a recent reformulation of granger causality that includes permutation-based, nonparametric statistics. The method is applied to ultrahigh field (7T) functional magnetic resonance imaging (fMRI) data collected on healthy subjects during taVNS. results: our framework identified taVNS-evoked functional brainstem responses with superior sensitivity compared to prior conventional approaches, confirming causal links between taVNS stimulation and fMRI response in the nucleus tractus solitarii (NTS). furthermore, our causal approach elucidated potential mechanisms by which information is relayed between brainstem nuclei and cardiovagal, i.e., high-frequency heart rate variability, in response to taVNS. Our findings revealed that key brainstem nuclei, known from animal models to be involved in cardiovascular control, exert a causal influence on taVNS-induced cardiovagal outflow in humans. conclusion: our causal approach allowed us to noninvasively evaluate directional interactions between fMRI BOLD signals from brainstem nuclei and cardiovagal outflow

Multivariate Granger causality unveils directed parietal to prefrontal cortex connectivity during task-free MRI

While a large body of research has focused on the study of functional brain "connectivity", few investigators have focused on directionality of brain-brain interactions which, in spite of the mostly bidirectional anatomical substrates, cannot be assumed to be symmetrical. We employ a multivariate Granger Causality-based approach to estimating directed in-network interactions and quantify its advantages using extensive realistic synthetic BOLD data simulations to match Human Connectome Project (HCP) data specification. We then apply our framework to resting state functional MRI (rs-fMRI) data provided by the HCP to estimate the directed connectome of the human brain. We show that the functional interactions between parietal and prefrontal cortices commonly observed in rs-fMRI studies are not symmetrical, but consists of directional connectivity from parietal areas to prefrontal cortices rather than vice versa. These effects are localized within the same hemisphere and do not generalize to cross-hemispheric functional interactions. Our data are consistent with neurophysiological evidence that posterior parietal cortices involved in processing and integration of multi-sensory information modulate the function of more anterior prefrontal regions implicated in action control and goal-directed behaviour. The directionality of functional connectivity can provide an additional layer of information in interpreting rs-fMRI studies both in health and disease

Echo state network models for nonlinear Granger causality

While Granger causality (GC) has been often employed in network neuroscience, most GC applications are based on linear multivariate autoregressive (MVAR) models. However, real-life systems like biological networks exhibit notable nonlinear behaviour, hence undermining the validity of MVAR-based GC (MVAR-GC). Most nonlinear GC estimators only cater for additive nonlinearities or, alternatively, are based on recurrent neural networks or long short-term memory networks, which present considerable training difficulties and tailoring needs. We reformulate the GC framework in terms of echo-state networks-based models for arbitrarily complex networks, and characterize its ability to capture nonlinear causal relations in a network of noisy Duffing oscillators, showing a net advantage of echo state GC (ES-GC) in detecting nonlinear, causal links. We then explore the structure of ES-GC networks in the human brain employing functional MRI data from 1003 healthy subjects drawn from the human connectome project, demonstrating the existence of previously unknown directed within-brain interactions. In addition, we examine joint brain-heart signals in 15 subjects where we explore directed interaction between brain networks and central vagal cardiac control in order to investigate the so-called central autonomic network in a causal manner. This article is part of the theme issue 'Advanced computation in cardiovascular physiology: new challenges and opportunities'

A novel multi-branch architecture for state of the art robust detection of pathological phonocardiograms

Heart auscultation is an inexpensive and fundamental technique to effectively diagnose cardiovascular disease. However, due to relatively high human error rates even when auscultation is performed by an experienced physician, and due to the not universal availability of qualified personnel, e.g. in developing countries, many efforts are made worldwide to propose computational tools for detecting abnormalities in heart sounds. The large heterogeneity of achievable data quality and devices, the variety of possible heart pathologies, and a generally poor signal-to-noise ratio make this problem very challenging. We present an accurate classification strategy for diagnosing heart sounds based on (1) automatic heart phase segmentation, (2) state-of-the art filters drawn from the field of speech synthesis (mel-frequency cepstral representation) and (3) an ad hoc multi-branch, multi-instance artificial neural network based on convolutional layers and fully connected neuronal ensembles which separately learns from each heart phase hence implicitly leveraging their different physiological significance. We demonstrate that it is possible to train our architecture to reach very high performances, e.g. an area under the curve of 0.87 or a sensitivity of 0.97. Our machine-learning-based tool could be employed for heartsound classification, especially as a screening tool in a variety of situations including telemedicine applications. This article is part of the theme issue 'Advanced computation in cardiovascular physiology: new challenges and opportunities'