Physiologically informed dynamic causal modeling of fMRI data

AbstractThe functional MRI (fMRI) signal is an indirect measure of neuronal activity. In order to deconvolve the neuronal activity from the experimental fMRI data, biophysical generative models have been proposed describing the link between neuronal activity and the cerebral blood flow (the neurovascular coupling), and further the hemodynamic response and the BOLD signal equation. These generative models have been employed both for single brain area deconvolution and to infer effective connectivity in networks of multiple brain areas. In the current paper, we introduce a new fMRI model inspired by experimental observations about the physiological underpinnings of the BOLD signal and compare it with the generative models currently used in dynamic causal modeling (DCM), a widely used framework to study effective connectivity in the brain. We consider three fundamental aspects of such generative models for fMRI: (i) an adaptive two-state neuronal model that accounts for a wide repertoire of neuronal responses during and after stimulation; (ii) feedforward neurovascular coupling that links neuronal activity to blood flow; and (iii) a balloon model that can account for vascular uncoupling between the blood flow and the blood volume. Finally, we adjust the parameterization of the BOLD signal equation for different magnetic field strengths. This paper focuses on the form, motivation and phenomenology of DCMs for fMRI and the characteristics of the various models are demonstrated using simulations. These simulations emphasize a more accurate modeling of the transient BOLD responses — such as adaptive decreases to sustained inputs during stimulation and the post-stimulus undershoot. In addition, we demonstrate using experimental data that it is necessary to take into account both neuronal and vascular transients to accurately model the signal dynamics of fMRI data. By refining the models of the transient responses, we provide a more informed perspective on the underlying neuronal process and offer new ways of inferring changes in local neuronal activity and effective connectivity from fMRI

Increasing robustness of pairwise methods for effective connectivity in Magnetic Resonance Imaging by using fractional moment series of BOLD signal distributions

Estimating causal interactions in the brain from functional magnetic resonance imaging (fMRI) data remains a challenging task. Multiple studies have demonstrated that all current approaches to determine direction of connectivity perform poorly even when applied to synthetic fMRI datasets. Recent advances in this field include methods for pairwise inference, which involve creating a sparse connectome in the first step, and then using a classifier in order to determine the directionality of connection between of every pair of nodes in the second step. In this work, we introduce an advance to the second step of this procedure, by building a classifier based on fractional moments of the BOLD distribution combined into cumulants. The classifier is trained on datasets generated under the Dynamic Causal Modeling (DCM) generative model. The directionality is inferred based upon statistical dependencies between the two node time series, e.g. assigning a causal link from time series of low variance to time series of high variance. Our approach outperforms or performs as well as other methods for effective connectivity when applied to the benchmark datasets. Crucially, it is also more resilient to confounding effects such as differential noise level across different areas of the connectome.Comment: 41 pages, 12 figure

Interregional compensatory mechanisms of motor functioning in progressing preclinical neurodegeneration.

Understanding brain reserve in preclinical stages of neurodegenerative disorders allows determination of which brain regions contribute to normal functioning despite accelerated neuronal loss. Besides the recruitment of additional regions, a reorganisation and shift of relevance between normally engaged regions are a suggested key mechanism. Thus, network analysis methods seem critical for investigation of changes in directed causal interactions between such candidate brain regions. To identify core compensatory regions, fifteen preclinical patients carrying the genetic mutation leading to Huntington's disease and twelve controls underwent fMRI scanning. They accomplished an auditory paced finger sequence tapping task, which challenged cognitive as well as executive aspects of motor functioning by varying speed and complexity of movements. To investigate causal interactions among brain regions a single Dynamic Causal Model (DCM) was constructed and fitted to the data from each subject. The DCM parameters were analysed using statistical methods to assess group differences in connectivity, and the relationship between connectivity patterns and predicted years to clinical onset was assessed in gene carriers. In preclinical patients, we found indications for neural reserve mechanisms predominantly driven by bilateral dorsal premotor cortex, which increasingly activated superior parietal cortices the closer individuals were to estimated clinical onset. This compensatory mechanism was restricted to complex movements characterised by high cognitive demand. Additionally, we identified task-induced connectivity changes in both groups of subjects towards pre- and caudal supplementary motor areas, which were linked to either faster or more complex task conditions. Interestingly, coupling of dorsal premotor cortex and supplementary motor area was more negative in controls compared to gene mutation carriers. Furthermore, changes in the connectivity pattern of gene carriers allowed prediction of the years to estimated disease onset in individuals. Our study characterises the connectivity pattern of core cortical regions maintaining motor function in relation to varying task demand. We identified connections of bilateral dorsal premotor cortex as critical for compensation as well as task-dependent recruitment of pre- and caudal supplementary motor area. The latter finding nicely mirrors a previously published general linear model-based analysis of the same data. Such knowledge about disease specific inter-regional effective connectivity may help identify foci for interventions based on transcranial magnetic stimulation designed to stimulate functioning and also to predict their impact on other regions in motor-associated networks

Exploiting Magnetic Resonance Angiography Imaging Improves Model Estimation of BOLD Signal

The change of BOLD signal relies heavily upon the resting blood volume fraction () associated with regional vasculature. However, existing hemodynamic data assimilation studies pretermit such concern. They simply assign the value in a physiologically plausible range to get over ill-conditioning of the assimilation problem and fail to explore actual . Such performance might lead to unreliable model estimation. In this work, we present the first exploration of the influence of on fMRI data assimilation, where actual within a given cortical area was calibrated by an MR angiography experiment and then was augmented into the assimilation scheme. We have investigated the impact of on single-region data assimilation and multi-region data assimilation (dynamic cause modeling, DCM) in a classical flashing checkerboard experiment. Results show that the employment of an assumed in fMRI data assimilation is only suitable for fMRI signal reconstruction and activation detection grounded on this signal, and not suitable for estimation of unobserved states and effective connectivity study. We thereby argue that introducing physically realistic in the assimilation process may provide more reliable estimation of physiological information, which contributes to a better understanding of the underlying hemodynamic processes. Such an effort is valuable and should be well appreciated

Physiological Gaussian Process Priors for the Hemodynamics in fMRI Analysis

Background: Inference from fMRI data faces the challenge that the hemodynamic system that relates neural activity to the observed BOLD fMRI signal is unknown. New Method: We propose a new Bayesian model for task fMRI data with the following features: (i) joint estimation of brain activity and the underlying hemodynamics, (ii) the hemodynamics is modeled nonparametrically with a Gaussian process (GP) prior guided by physiological information and (iii) the predicted BOLD is not necessarily generated by a linear time-invariant (LTI) system. We place a GP prior directly on the predicted BOLD response, rather than on the hemodynamic response function as in previous literature. This allows us to incorporate physiological information via the GP prior mean in a flexible way, and simultaneously gives us the nonparametric flexibility of the GP. Results: Results on simulated data show that the proposed model is able to discriminate between active and non-active voxels also when the GP prior deviates from the true hemodynamics. Our model finds time varying dynamics when applied to real fMRI data. Comparison with Existing Method(s): The proposed model is better at detecting activity in simulated data than standard models, without inflating the false positive rate. When applied to real fMRI data, our GP model in several cases finds brain activity where previously proposed LTI models does not. Conclusions: We have proposed a new non-linear model for the hemodynamics in task fMRI, that is able to detect active voxels, and gives the opportunity to ask new kinds of questions related to hemodynamics.Comment: 18 pages, 14 figure

Brain information processing capacity modeling

Neurophysiological measurements suggest that human information processing is evinced by neuronal activity. However, the quantitative relationship between the activity of a brain region and its information processing capacity remains unclear. We introduce and validate a mathematical model of the information processing capacity of a brain region in terms of neuronal activity, input storage capacity, and the arrival rate of afferent information. We applied the model to fMRI data obtained from a flanker paradigm in young and old subjects. Our analysis showed that-for a given cognitive task and subject-higher information processing capacity leads to lower neuronal activity and faster responses. Crucially, processing capacity-as estimated from fMRI data-predicted task and age-related differences in reaction times, speaking to the model's predictive validity. This model offers a framework for modelling of brain dynamics in terms of information processing capacity, and may be exploited for studies of predictive coding and Bayes-optimal decision-making

Combining optogenetic stimulation and fMRI to validate a multivariate dynamical systems model for estimating causal brain interactions

State-space multivariate dynamical systems (MDS) (Ryali et al., 2011) and other causal estimation models are being increasingly used to identify directed functional interactions between brain regions. However, the validity and accuracy of such methods is poorly understood. Performance evaluation based on computer simulations of small artificial causal networks can address this problem to some extent, but they often involve simplifying assumptions that reduce biological validity of the resulting data. Here, we use a novel approach taking advantage of recently developed optogenetic fMRI (ofMRI) techniques to selectively stimulate brain regions while simultaneously recording high-resolution whole-brain fMRI data. ofMRI allows for a more direct investigation of causal influences from the stimulated site to brain regions activated downstream and is therefore ideal for evaluating causal estimation methods in vivo. We used ofMRI to investigate whether MDS models for fMRI can accurately estimate causal functional interactions between brain regions. Two cohorts of ofMRI data were acquired, one at Stanford University and the University of California Los Angeles (Cohort 1) and the other at the University of North Carolina Chapel Hill (Cohort 2). In each cohort optical stimulation was delivered to the right primary motor cortex (M1). General linear model analysis revealed prominent downstream thalamic activation in Cohort 1, and caudate-putamen (CPu) activation in Cohort 2. MDS accurately estimated causal interactions from M1 to thalamus and from M1 to CPu in Cohort 1 and Cohort 2, respectively. As predicted, no causal influences were found in the reverse direction. Additional control analyses demonstrated the specificity of causal interactions between stimulated and target sites. Our findings suggest that MDS state-space models can accurately and reliably estimate causal interactions in ofMRI data and further validate their use for estimating causal interactions in fMRI. More generally, our study demonstrates that the combined use of optogenetics and fMRI provides a powerful new tool for evaluating computational methods designed to estimate causal interactions between distributed brain regions

Multimodal imaging of human brain activity: rational, biophysical aspects and modes of integration

Until relatively recently the vast majority of imaging and electrophysiological studies of human brain activity have relied on single-modality measurements usually correlated with readily observable or experimentally modified behavioural or brain state patterns. Multi-modal imaging is the concept of bringing together observations or measurements from different instruments. We discuss the aims of multi-modal imaging and the ways in which it can be accomplished using representative applications. Given the importance of haemodynamic and electrophysiological signals in current multi-modal imaging applications, we also review some of the basic physiology relevant to understanding their relationship