Distinct Patterns of Connectivity between Brain Regions Underlie the Intra-Modal and Cross-Modal Value-Driven Modulations of the Visual Cortex.

Past reward associations may be signaled from different sensory modalities; however, it remains unclear how different types of reward-associated stimuli modulate sensory perception. In this human fMRI study (female and male participants), a visual target was simultaneously presented with either an intra- (visual) or a cross-modal (auditory) cue that was previously associated with rewards. We hypothesized that, depending on the sensory modality of the cues, distinct neural mechanisms underlie the value-driven modulation of visual processing. Using a multivariate approach, we confirmed that reward-associated cues enhanced the target representation in early visual areas and identified the brain valuation regions. Then, using an effective connectivity analysis, we tested three possible patterns of connectivity that could underlie the modulation of the visual cortex: a direct pathway from the frontal valuation areas to the visual areas, a mediated pathway through the attention-related areas, and a mediated pathway that additionally involved sensory association areas. We found evidence for the third model demonstrating that the reward-related information in both sensory modalities is communicated across the valuation and attention-related brain regions. Additionally, the superior temporal areas were recruited when reward was cued cross-modally. The strongest dissociation between the intra- and cross-modal reward-driven effects was observed at the level of the feedforward and feedback connections of the visual cortex estimated from the winning model. These results suggest that, in the presence of previously rewarded stimuli from different sensory modalities, a combination of domain-general and domain-specific mechanisms are recruited across the brain to adjust the visual perception.SIGNIFICANCE STATEMENT Reward has a profound effect on perception, but it is not known whether shared or disparate mechanisms underlie the reward-driven effects across sensory modalities. In this human fMRI study, we examined the reward-driven modulation of the visual cortex by visual (intra-modal) and auditory (cross-modal) reward-associated cues. Using a model-based approach to identify the most plausible pattern of inter-regional effective connectivity, we found that higher-order areas involved in the valuation and attentional processing were recruited by both types of rewards. However, the pattern of connectivity between these areas and the early visual cortex was distinct between the intra- and cross-modal rewards. This evidence suggests that, to effectively adapt to the environment, reward signals may recruit both domain-general and domain-specific mechanisms.

Novel relative relevance score for estimating brain connectivity from fMRI data using an explainable neural network approach.

BACKGROUND: Functional integration or connectivity in brain is directional, non-linear as well as variable in time-lagged dependence. Deep neural networks (DNN) have become an indispensable tool everywhere, by learning higher levels of abstract and complex patterns from raw data. However, in neuroscientific community they generally work as black-boxes, leading to the explanation of results difficult and less intuitive. We aim to propose a brain-connectivity measure based on an explainable NN (xNN) approach. NEW METHOD: We build a NN-based predictor for regression problem. Since we aim to determine the contribution/relevance of past data-point from one region i in the prediction of current data-point from another region j, i.e. the higher-order connectivity between two brain-regions, we employ layer-wise relevance propagation (Bach et al., 2015) (LRP, a method for explaining DNN predictions), which has not been done before to the best of our knowledge. Specifically, we propose a novel score depending on weights as a quantitative measure of connectivity, called as relative relevance score (xNN-RRS). The RRS is an intuitive and transparent score. We provide an interpretation of the trained NN weights with-respect-to the brain-connectivity. RESULTS: Face validity of our approach is demonstrated with experiments on simulated data, over existing methods. We also demonstrate construct validity of xNN-RRS in a resting-state fMRI experiment. COMPARISON: Our approach shows superior performance, in terms of accuracy and computational complexity, over existing state-of-the-art methods for brain-connectivity estimation. CONCLUSION: The proposed method is promising to serve as a first post-hoc explainable NN-approach for brain-connectivity analysis in clinical applications.

Tractography-Based Score for Learning Effective Connectivity From Multimodal Imaging Data Using Dynamic Bayesian Networks.

OBJECTIVE: Effective connectivity (EC) is the methodology for determining functional-integration among the functionally active segregated regions of the brain. By definition 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.

The dynamic programming high-order Dynamic Bayesian Networks learning for identifying effective connectivity in human brain from fMRI.

BACKGROUND: Determination of effective connectivity (EC) among brain regions using fMRI is helpful in understanding the underlying neural mechanisms. Dynamic Bayesian Networks (DBNs) are an appropriate class of probabilistic graphical temporal-models that have been used in past to model EC from fMRI, specifically order-one. NEW-METHOD: High-order DBNs (HO-DBNs) have still not been explored for fMRI data. A fundamental problem faced in the structure-learning of HO-DBN is high computational-burden and low accuracy by the existing heuristic search techniques used for EC detection from fMRI. In this paper, we propose using dynamic programming (DP) principle along with integration of properties of scoring-function in a way to reduce search space for structure-learning of HO-DBNs and finally, for identifying EC from fMRI which has not been done yet to the best of our knowledge. The proposed exact search-&-score learning approach HO-DBN-DP is an extension of the technique which was originally devised for learning a BN's structure from static data (Singh and Moore, 2005). RESULTS: The effectiveness in structure-learning is shown on synthetic fMRI dataset. The algorithm reaches globally-optimal solution in appreciably reduced time-complexity than the static counterpart due to integration of properties. The proof of optimality is provided. COMPARISON: 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. The real data EC from HO-DBN-DP shows consistency with previous literature than the classical Granger Causality method. CONCLUSION: Hence, the DP algorithm can be employed for reliable EC estimates from experimental fMRI data.

Learning effective connectivity from fMRI using autoregressive hidden Markov model with missing data.

BACKGROUND: Effective connectivity (EC) analysis of neuronal groups using fMRI delivers insights about functional-integration. However, fMRI signal has low-temporal resolution due to down-sampling and indirectly measures underlying neuronal activity. NEW METHOD: The aim is to address above issues for more reliable EC estimates. This paper proposes 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. In our recent work (Dang et al., 2016), we have shown how AR-HMM-md for modelling single fMRI time series outperforms the existing methods. AR-HMM-md models unobserved neuronal activity and lost data over time as variables and estimates their values by joint optimization given fMRI observation sequence. RESULTS: The effectiveness in learning EC is shown using simulated experiments. Also the effects of sampling and noise are studied on EC. Moreover, classification-experiments are performed for Attention-Deficit/Hyperactivity Disorder subjects and age-matched controls for performance evaluation of real data. Using Bayesian model selection, we see that the proposed model converged to higher log-likelihood and demonstrated that group-classification can be performed with higher cross-validation accuracy of above 94% using distinctive network EC which characterizes patients vs. CONTROLS: The full data EC obtained from DML-AR-HMM-md is more consistent with previous literature than the classical multivariate Granger causality method. COMPARISON: The proposed architecture leads to reliable estimates of EC than the existing latent models. CONCLUSIONS: This framework overcomes the disadvantage of low-temporal resolution and improves cross-validation accuracy significantly due to presence of missing data variables and autoregressive process.

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

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.