A blind deconvolution approach to recover effective connectivity brain networks from resting state fMRI data

A great improvement to the insight on brain function that we can get from fMRI data can come from effective connectivity analysis, in which the flow of information between even remote brain regions is inferred by the parameters of a predictive dynamical model. As opposed to biologically inspired models, some techniques as Granger causality (GC) are purely data-driven and rely on statistical prediction and temporal precedence. While powerful and widely applicable, this approach could suffer from two main limitations when applied to BOLD fMRI data: confounding effect of hemodynamic response function (HRF) and conditioning to a large number of variables in presence of short time series. For task-related fMRI, neural population dynamics can be captured by modeling signal dynamics with explicit exogenous inputs; for resting-state fMRI on the other hand, the absence of explicit inputs makes this task more difficult, unless relying on some specific prior physiological hypothesis. In order to overcome these issues and to allow a more general approach, here we present a simple and novel blind-deconvolution technique for BOLD-fMRI signal. Coming to the second limitation, a fully multivariate conditioning with short and noisy data leads to computational problems due to overfitting. Furthermore, conceptual issues arise in presence of redundancy. We thus apply partial conditioning to a limited subset of variables in the framework of information theory, as recently proposed. Mixing these two improvements we compare the differences between BOLD and deconvolved BOLD level effective networks and draw some conclusions

Leave-one-out prediction error of systolic arterial pressure time series under paced breathing

In this paper we show that different physiological states and pathological conditions may be characterized in terms of predictability of time series signals from the underlying biological system. In particular we consider systolic arterial pressure time series from healthy subjects and Chronic Heart Failure patients, undergoing paced respiration. We model time series by the regularized least squares approach and quantify predictability by the leave-one-out error. We find that the entrainment mechanism connected to paced breath, that renders the arterial blood pressure signal more regular, thus more predictable, is less effective in patients, and this effect correlates with the seriousness of the heart failure. The leave-one-out error separates controls from patients and, when all orders of nonlinearity are taken into account, alive patients from patients for which cardiac death occurred

Natural clustering: the modularity approach

We show that modularity, a quantity introduced in the study of networked systems, can be generalized and used in the clustering problem as an indicator for the quality of the solution. The introduction of this measure arises very naturally in the case of clustering algorithms that are rooted in Statistical Mechanics and use the analogy with a physical system.Comment: 11 pages, 5 figure enlarged versio

Disambiguating the role of blood flow and global signal with partial information decomposition

Global signal (GS) is an ubiquitous construct in resting state functional magnetic resonance imaging (rs-fMRI), associated to nuisance, but containing by definition most of the neuronal signal. Global signal regression (GSR) effectively removes the impact of physiological noise and other artifacts, but at the same time it alters correlational patterns in unpredicted ways. Performing GSR taking into account the underlying physiology (mainly the blood arrival time) has been proven to be beneficial. From these observations we aimed to: 1) characterize the effect of GSR on network-level functional connectivity in a large dataset; 2) assess the complementary role of global signal and vessels; and 3) use the framework of partial information decomposition to further look into the joint dynamics of the global signal and vessels, and their respective influence on the dynamics of cortical areas. We observe that GSR affects intrinsic connectivity networks in the connectome in a non-uniform way. Furthermore, by estimating the predictive information of blood flow and the global signal using partial information decomposition, we observe that both signals are present in different amounts across intrinsic connectivity networks. Simulations showed that differences in blood arrival time can largely explain this phenomenon, while using hemodynamic and calcium mouse recordings we were able to confirm the presence of vascular effects, as calcium recordings lack hemodynamic information. With these results we confirm network-specific effects of GSR and the importance of taking blood flow into account for improving de-noising methods. Additionally, and beyond the mere issue of data denoising, we quantify the diverse and complementary effect of global and vessel BOLD signals on the dynamics of cortical areas

Grouping time series by pairwise measures of redundancy

A novel approach is proposed to group redundant time series in the frame of causality. It assumes that (i) the dynamics of the system can be described using just a small number of characteristic modes, and that (ii) a pairwise measure of redundancy is sufficient to elicit the presence of correlated degrees of freedom. We show the application of the proposed approach on fMRI data from a resting human brain and gene expression profiles from HeLa cell culture.Comment: 4 pages, 8 figure

Identification of network modules by optimization of ratio association

We introduce a novel method for identifying the modular structures of a network based on the maximization of an objective function: the ratio association. This cost function arises when the communities detection problem is described in the probabilistic autoencoder frame. An analogy with kernel k-means methods allows to develop an efficient optimization algorithm, based on the deterministic annealing scheme. The performance of the proposed method is shown on a real data set and on simulated networks

Lagged and instantaneous dynamical influences related to brain structural connectivity

Contemporary neuroimaging methods can shed light on the basis of human neural and cognitive specializations, with important implications for neuroscience and medicine. Different MRI acquisitions provide different brain networks at the macroscale; whilst diffusion-weighted MRI (dMRI) provides a structural connectivity (SC) coincident with the bundles of parallel fibers between brain areas, functional MRI (fMRI) accounts for the variations in the blood-oxygenation-level-dependent T2* signal, providing functional connectivity (FC).Understanding the precise relation between FC and SC, that is, between brain dynamics and structure, is still a challenge for neuroscience. To investigate this problem, we acquired data at rest and built the corresponding SC (with matrix elements corresponding to the fiber number between brain areas) to be compared with FC connectivity matrices obtained by 3 different methods: directed dependencies by an exploratory version of structural equation modeling (eSEM), linear correlations (C) and partial correlations (PC). We also considered the possibility of using lagged correlations in time series; so, we compared a lagged version of eSEM and Granger causality (GC). Our results were two-fold: firstly, eSEM performance in correlating with SC was comparable to those obtained from C and PC, but eSEM (not C nor PC) provides information about directionality of the functional interactions. Second, interactions on a time scale much smaller than the sampling time, captured by instantaneous connectivity methods, are much more related to SC than slow directed influences captured by the lagged analysis. Indeed the performance in correlating with SC was much worse for GC and for the lagged version of eSEM. We expect these results to supply further insights to the interplay between SC and functional patterns, an important issue in the study of brain physiology and function.Comment: Accepted and published in Frontiers in Psychology in its current form. 27 pages, 1 table, 5 figures, 2 suppl. figure

The effect of neural adaptation of population coding accuracy

Most neurons in the primary visual cortex initially respond vigorously when a preferred stimulus is presented, but adapt as stimulation continues. The functional consequences of adaptation are unclear. Typically a reduction of firing rate would reduce single neuron accuracy as less spikes are available for decoding, but it has been suggested that on the population level, adaptation increases coding accuracy. This question requires careful analysis as adaptation not only changes the firing rates of neurons, but also the neural variability and correlations between neurons, which affect coding accuracy as well. We calculate the coding accuracy using a computational model that implements two forms of adaptation: spike frequency adaptation and synaptic adaptation in the form of short-term synaptic plasticity. We find that the net effect of adaptation is subtle and heterogeneous. Depending on adaptation mechanism and test stimulus, adaptation can either increase or decrease coding accuracy. We discuss the neurophysiological and psychophysical implications of the findings and relate it to published experimental data.Comment: 35 pages, 8 figure

Parameterized hemodynamic response function data of healthy individuals obtained from resting-state functional MRI in a 7T MRI scanner

Functional magnetic resonance imaging (fMRI), being an indirect measure of brain activity, is mathematically defined as a convolution of the unmeasured latent neural signal and the hemodynamic response function (HRF). The HRF is known to vary across the brain and across individuals, and it is modulated by neural as well as non-neural factors. Three parameters characterize the shape of the HRF, which is obtained by performing deconvolution on resting-state fMRI data: response height, time-to-peak and full-width at half-max. The data provided here, obtained from 47 healthy adults, contains these three HRF parameters at every voxel in the brain, as well as HRF parameters from the default-mode network (DMN). In addition, we have provided functional connectivity (FC) data from the same DMN regions, obtained for two cases: data with deconvolution (HRF variability minimized) and data with no deconvolution (HRF variability corrupted). This would enable researchers to compare regional changes in HRF with corresponding FC differences, to assess the impact of HRF variability on FC. Importantly, the data was obtained in a 7T MRI scanner. While most fMRI studies are conducted at lower field strengths, like 3T, ours is the first study to report HRF data obtained at 7T. FMRI data at ultra-high fields contains larger contributions from small vessels, consequently HRF variability is lower for small vessels at higher field strengths. This implies that findings made from this data would be more conservative than from data acquired at lower fields, such as 3T. Results obtained with this data and further interpretations are available in our recent research study (Rangaprakash et al., in press) [1]. This is a valuable dataset for studying HRF variability in conjunction with FC, and for developing the HRF profile in healthy individuals, which would have direct implications for fMRI data analysis, especially resting-state connectivity modeling. This is the first public HRF data at 7T