Identifying Dynamic Functional Connectivity Changes in Dementia with Lewy Bodies Based on Product Hidden Markov Models.

Exploring time-varying connectivity networks in neurodegenerative disorders is a recent field of research in functional MRI. Dementia with Lewy bodies (DLB) represents 20% of the neurodegenerative forms of dementia. Fluctuations of cognition and vigilance are the key symptoms of DLB. To date, no dynamic functional connectivity (DFC) investigations of this disorder have been performed. In this paper, we refer to the concept of connectivity state as a piecewise stationary configuration of functional connectivity between brain networks. From this concept, we propose a new method for group-level as well as for subject-level studies to compare and characterize connectivity state changes between a set of resting-state networks (RSNs). Dynamic Bayesian networks, statistical and graph theory-based models, enable one to learn dependencies between interacting state-based processes. Product hidden Markov models (PHMM), an instance of dynamic Bayesian networks, are introduced here to capture both statistical and temporal aspects of DFC of a set of RSNs. This analysis was based on sliding-window cross-correlations between seven RSNs extracted from a group independent component analysis performed on 20 healthy elderly subjects and 16 patients with DLB. Statistical models of DFC differed in patients compared to healthy subjects for the occipito-parieto-frontal network, the medial occipital network and the right fronto-parietal network. In addition, pairwise comparisons of DFC of RSNs revealed a decrease of dependency between these two visual networks (occipito-parieto-frontal and medial occipital networks) and the right fronto-parietal control network. The analysis of DFC state changes thus pointed out networks related to the cognitive functions that are known to be impaired in DLB: visual processing as well as attentional and executive functions. Besides this context, product HMM applied to RSNs cross-correlations offers a promising new approach to investigate structural and temporal aspects of brain DFC.

A multi-level parcellation approach for brain functional connectivity analysis.

Most brain functional connectivity methods in fMRI require a brain parcellation into functionally homogeneous regions. In this work we propose a novel parcellation approach based on a spatial hierarchical clustering, that provides clusters within a multi-level framework. The method has the advantage of producing several brain parcellations rather than a single one from a fixed size-homogeneity criterion. Results obtained on real data demonstrate the relevance of the approach. Finally, a connectivity study shows the benefit of a prior multi-level parcellation of the brain.

Hidden Markov event sequence models: toward unsupervised functional MRI brain mapping.

RATIONALE AND OBJECTIVES: Most methods used in functional MRI (fMRI) brain mapping require restrictive assumptions about the shape and timing of the fMRI signal in activated voxels. Consequently, fMRI data may be partially and misleadingly characterized, leading to suboptimal or invalid inference. To limit these assumptions and to capture the broad range of possible activation patterns, a novel statistical fMRI brain mapping method is proposed. It relies on hidden semi-Markov event sequence models (HSMESMs), a special class of hidden Markov models (HMMs) dedicated to the modeling and analysis of event-based random processes. MATERIALS AND METHODS: Activation detection is formulated in terms of time coupling between (1) the observed sequence of hemodynamic response onset (HRO) events detected in the voxel's fMRI signal and (2) the "hidden" sequence of task-induced neural activation onset (NAO) events underlying the HROs. Both event sequences are modeled within a single HSMESM. The resulting brain activation model is trained to automatically detect neural activity embedded in the input fMRI data set under analysis. The data sets considered in this article are threefold: synthetic epoch-related, real epoch-related (auditory lexical processing task), and real event-related (oddball detection task) fMRI data sets. RESULTS: Synthetic data: Activation detection results demonstrate the superiority of the HSMESM mapping method with respect to a standard implementation of the statistical parametric mapping (SPM) approach. They are also very close, sometimes equivalent, to those obtained with an "ideal" implementation of SPM in which the activation patterns synthesized are reused for analysis. The HSMESM method appears clearly insensitive to timing variations of the hemodynamic response and exhibits low sensitivity to fluctuations of its shape (unsustained activation during task). Real epoch-related data: HSMESM activation detection results compete with those obtained with SPM, without requiring any prior definition of the expected activation patterns thanks to the unsupervised character of the HSMESM mapping approach. Along with activation maps, the method offers a wide range of additional fMRI analysis functionalities, including activation lag mapping, activation mode visualization, and hemodynamic response function analysis. Real event-related data: Activation detection results confirm and validate the overall strategy that consists in focusing the analysis on the transients, time-localized events that are the HROs. CONCLUSION: All the experiments performed on synthetic and real fMRI data demonstrate the relevance of HSMESMs in fMRI brain mapping. In particular, the statistical character of these models, along with their learning and generalizing abilities are of particular interest when dealing with strong variabilities of the active fMRI signal across time, space, experiments, and subjects.

Unsupervised learning and mapping of active brain functional MRI signals based on hidden semi-Markov event sequence models.

In this paper, a novel functional magnetic resonance imaging (fMRI) brain mapping method is presented within the statistical modeling framework of hidden semi-Markov event sequence models (HSMESMs). Neural activation detection is formulated at the voxel level in terms of time coupling between the sequence of hemodynamic response onsets (HROs) observed in the fMRI signal, and an HSMESM of the hidden sequence of task-induced neural activations. The sequence of HRO events is derived from a continuous wavelet transform (CWT) of the fMRI signal. The brain activation HSMESM is built from the timing information of the input stimulation protocol. The rich mathematical framework of HSMESMs makes these models an effective and versatile approach for fMRI data analysis. Solving for the HSMESM Evaluation and Learning problems enables the model to automatically detect neural activation embedded in a given set of fMRI signals, without requiring any template basis function or prior shape assumption for the fMRI response. Solving for the HSMESM Decoding problem allows to enrich brain mapping with activation lag mapping, activation mode visualizing, and hemodynamic response function analysis. Activation detection results obtained on synthetic and real epoch-related fMRI data demonstrate the superiority of the HSMESM mapping method with respect to a real application case of the statistical parametric mapping (SPM) approach. In addition, the HSMESM mapping method appears clearly insensitive to timing variations of the hemodynamic response, and exhibits low sensitivity to fluctuations of its shape.