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Proceedings ArticleDOI

Assessing assumptions of multivariate linear regression framework implemented for directionality analysis of fMRI

TL;DR: Assessment of assumptions of Multivariate Autoregressive (MAR) framework which is employed for evaluating directionality among fMRI time-series recorded during a Sensory-Motor (SM) task indicates inadequacy of MAR models to find directional interactions among different task-activated regions of brain.
Abstract: Directionality analysis of time-series, recorded from task-activated regions-of-interest (ROIs) during functional Magnetic Resonance Imaging (fMRI), has helped in gaining insights of complex human behavior and human brain functioning. The most widely used standard method of Granger Causality for evaluating directionality employ linear regression modeling of temporal processes. Such a parameter-driven approach rests on various underlying assumptions about the data. The short-comings can arise when misleading conclusions are reached after exploration of data for which the assumptions are getting violated. In this study, we assess assumptions of Multivariate Autoregressive (MAR) framework which is employed for evaluating directionality among fMRI time-series recorded during a Sensory-Motor (SM) task. The fMRI time-series here is an averaged time-series from a user-defined ROI of multiple voxels. The “aim” is to establish a step-by-step procedure using statistical methods in conjunction with graphical methods to seek the validity of MAR models, specifically in the context of directionality analysis of fMRI data which has not been done previously to the best of our knowledge. Here, in our case of SM task (block design paradigm) there is violation of assumptions, indicating the inadequacy of MAR models to find directional interactions among different task-activated regions of brain.
Citations
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Journal ArticleDOI
TL;DR: Use of autoregressive hidden Markov model with missing data (AR-HMM-md) in dynamically multi-linked (DML) framework for learning EC using multiple fMRI time series overcomes the disadvantage of low-temporal resolution and improves cross-validation accuracy significantly.

14 citations

Journal ArticleDOI
TL;DR: A novel anatomically informed (AI) score that evaluates fitness of a given connectivity structure to both DTI and fMRI data simultaneously is proposed that is employed in structure learning of DBN given the data.
Abstract: Objective: Effective connectivity (EC) is the methodology for determining functional-integration among the functionally active segregated regions of the brain. By definition [1] EC is “the causal influence exerted by one neuronal group on another” which is constrained by anatomical connectivity (AC) (axonal connections). AC is necessary for EC but does not fully determine it, because synaptic communication occurs dynamically in a context-dependent fashion. Although there is a vast emerging evidence of structure–function relationship using multimodal imaging studies, till date only a few studies have done joint modeling of the two modalities: functional MRI (fMRI) and diffusion tensor imaging (DTI). We aim to propose a unified probabilistic framework that combines information from both sources to learn EC using dynamic Bayesian networks (DBNs). Method: DBNs are probabilistic graphical temporal models that learn EC in an exploratory fashion. Specifically, we propose a novel anatomically informed (AI) score that evaluates fitness of a given connectivity structure to both DTI and fMRI data simultaneously. The AI score is employed in structure learning of DBN given the data. Results: Experiments with synthetic-data demonstrate the face validity of structure learning with our AI score over anatomically uninformed counterpart. Moreover, real-data results are cross-validated by performing classification-experiments. Conclusion: EC inferred on real fMRI-DTI datasets is found to be consistent with previous literature and show promising results in light of the AC present as compared to other classically used techniques such as Granger-causality. Significance: Multimodal analyses provide a more reliable basis for differentiating brain under abnormal/diseased conditions than the single modality analysis.

13 citations


Cites background or methods from "Assessing assumptions of multivaria..."

  • ...However, the MVGC approach does not use any information about the underlying anatomical connectivity and is purely a model-based data-driven approach which makes various untenable model assumptions [13]....

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  • ...Traditional Granger Causality (GC) [12] analysis for learning EC from fMRI is a model-based approach where model assumptions make GC vulnerable to violations for fMRI data, as shown in our previous work [13]....

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Journal ArticleDOI
TL;DR: The results demonstrate that HO-DBN-DP is comparably more accurate and faster than currently used structure-learning algorithms used for identifying EC from fMRI and can be employed for reliable EC estimates from experimental fMRI data.

8 citations

Journal ArticleDOI
TL;DR: The proposed method is promising to serve as a first post-hoc explainable NN-approach for brain-connectivity analysis in clinical applications, by proposing a novel score depending on weights as a quantitative measure of connectivity, called as relative relevance score (xNN-RRS).

3 citations

Posted ContentDOI
27 Jan 2020-bioRxiv
TL;DR: A robust point-process Granger causality technique that is robust with respect to the two most common exogenous modulations observed in real neuronal responses: within-trial temporal variations in spiking rate and between-trial variability in their magnitudes is proposed.
Abstract: Assessing directional influences between neurons is instrumental to understand how brain circuits process information. To this end, Granger causality, a technique originally developed for time-continuous signals, has been extended to discrete spike trains. A fundamental assumption of this technique is that the temporal evolution of neuronal responses must be due only to endogenous interactions between recorded units, including self-interactions. This assumption is however rarely met in neurophysiological studies, where the response of each neuron is modulated by other exogenous causes such as, for example, other unobserved units or slow adaptation processes. Here, we propose a novel point-process Granger causality technique that is robust with respect to the two most common exogenous modulations observed in real neuronal responses: within-trial temporal variations in spiking rate and between-trial variability in their magnitudes. This novel method works by explicitly including both types of modulations into the generalized linear model of the neuronal conditional intensity function (CIF). We then assess the causal influence of neuron i onto neuron j by measuring the relative reduction of neuron j’s point process likelihood obtained considering or removing neuron i. CIF’s hyper-parameters are set on a per-neuron basis by minimizing Akaike’s information criterion. In simulated data, the proposed method recovered with high accuracy the underlying ground-truth connectivity pattern. Application of presently available point-process Granger causality techniques produced instead a significant number of false positive connections. In real spiking responses recorded from neurons in the monkey pre-motor cortex (area F5), our method revealed many causal relationships between neurons as well as the temporal structure of their interactions. Given its robustness our method can be effectively applied to real neuronal data. Furthermore, its explicit estimate of the effects of unobserved causes on the recorded neuronal firing patterns can help decomposing their temporal variations into endogenous and exogenous components. Author summary Modern techniques in Neuroscience allow to investigate the brain at the network level by studying the flow of information between neurons. To this end, Granger causality has been extended to point process spike trains. A fundamental assumption of this technique is that there should be no unobserved causes of temporal variability in the recorded spike trains. This, however, greatly limits its applicability to real neuronal recordings as very often not all the sources of variability in neuronal responses can be concurrently recorded. We present here a robust point-process Granger causality technique that overcome this problem by explicitly incorporating unobserved sources of variability into the model of neuronal spiking responses. In synthetic data sets, our new technique correctly recovered the underlying ground-truth functional connectivity between simulated units with a great degree of accuracy. Furthermore, its application to real neuronal recordings revealed many causal relationships between neurons as well as the temporal structure of their interactions. Our results suggest that our novel Granger causality method is robust and it can be used to study the flow of information in the spiking patterns of simultaneously recorded neurons even in presence of unobserved causes of temporal variability.

3 citations


Cites background from "Assessing assumptions of multivaria..."

  • ...At the practical level, the results of our Montecarlo simulations stress the 286 importance of carefully checking that the data set under scrutiny meets the assumptions 287 of Granger causality [19]....

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References
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Journal ArticleDOI
TL;DR: In this article, the limit distributions of the estimator of p and of the regression t test are derived under the assumption that p = ± 1, where p is a fixed constant and t is a sequence of independent normal random variables.
Abstract: Let n observations Y 1, Y 2, ···, Y n be generated by the model Y t = pY t−1 + e t , where Y 0 is a fixed constant and {e t } t-1 n is a sequence of independent normal random variables with mean 0 and variance σ2. Properties of the regression estimator of p are obtained under the assumption that p = ±1. Representations for the limit distributions of the estimator of p and of the regression t test are derived. The estimator of p and the regression t test furnish methods of testing the hypothesis that p = 1.

23,509 citations

Journal ArticleDOI
TL;DR: In this article, the cross spectrum between two variables can be decomposed into two parts, each relating to a single causal arm of a feedback situation, and measures of causal lag and causal strength can then be constructed.
Abstract: There occurs on some occasions a difficulty in deciding the direction of causality between two related variables and also whether or not feedback is occurring. Testable definitions of causality and feedback are proposed and illustrated by use of simple two-variable models. The important problem of apparent instantaneous causality is discussed and it is suggested that the problem often arises due to slowness in recording information or because a sufficiently wide class of possible causal variables has not been used. It can be shown that the cross spectrum between two variables can be decomposed into two parts, each relating to a single causal arm of a feedback situation. Measures of causal lag and causal strength can then be constructed. A generalisation of this result with the partial cross spectrum is suggested.

16,349 citations

Journal ArticleDOI
TL;DR: In this paper, the authors present a test of independence that can be applied to the estimated residuals of any time series model, which can be transformed into a model driven by independent and identically distributed errors.
Abstract: This paper presents a test of independence that can be applied to the estimated residuals of any time series model that can be transformed into a model driven by independent and identically distributed errors. The first order asymptotic distribution of the test statistic is independent of estimation error provided that the parameters of the model under test can be estimated -consistently. Because of this, our method can be used as a model selection tool and as a specification test. Widely used software1 written by Dechert and LeBaron can be used to implement the test. Also, this software is fast enough that the null distribution of our test statistic can be estimated with bootstrap methods. Our method can be viewed as a nonlinear analog of the Box-Pierce Q statistic used in ARIMA analysis.

2,723 citations

Journal ArticleDOI
TL;DR: This article presents one approach that has been used in functional imaging and shows how the integration within and between functionally specialized areas is mediated by functional or effective connectivity.
Abstract: The brain appears to adhere to two principles of functional organization; junctional segregation and functional intryration. The integration within and between functionally specialized areas is mediated by functional or ejectiue connectioity. The characterization of this sort of connectivity is an important theme in many areas of neuroscience. This article presents one approach that has been used in functional imaging. This article reviews the basic distinction between functional and effective connectivity (as the terms are used in neuroimaging) and their role in addressing several aspects of functional organization (e.g. the topography of distributed systems, integration between cortical areas, time-dependent changes in connectivity and nonlinear interactions). Emphasis is placed on the points of contact between the apparently diverse applications of these concepts and in particular the central role of eigenimages or spatial modes. Although the framework that has been developed is inherently linear, it has been extended to assess nonlinear interactions among cortical areas.

2,270 citations

Journal ArticleDOI
TL;DR: In this paper, the authors define measures of linear dependence and feedback for multiple time series, and a readily usable theory of inference for all of these measures and their decompositions is described; the computations involved are modest.
Abstract: Measures of linear dependence and feedback for multiple time series are defined. The measure of linear dependence is the sum of the measure of linear feedback from the first series to the second, linear feedback from the second to the first, and instantaneous linear feedback. The measures are nonnegative, and zero only when feedback (causality) of the relevant type is absent. The measures of linear feedback from one series to another can be additively decomposed by frequency. A readily usable theory of inference for all of these measures and their decompositions is described; the computations involved are modest.

1,874 citations