Brain imaging of locomotion in neurological conditions

Impaired locomotion is a frequent and major source of disability in patients with neurological conditions. Different neuroimaging methods have been used to understand the brain substrates of locomotion in various neurological diseases (mainly in Parkinson's disease) during actual walking, and while resting (using mental imagery of gait, or brain-behavior correlation analyses). These studies, using structural (i.e., MRI) or functional (i.e., functional MRI or functional near infra-red spectroscopy) brain imaging, electrophysiology (i.e., EEG), non-invasive brain stimulation (i.e., transcranial magnetic stimulation, or transcranial direct current stimulation) or molecular imaging methods (i.e., PET, or SPECT) reveal extended brain networks involving both grey and white matters in key cortical (i.e., prefrontal cortex) and subcortical (basal ganglia and cerebellum) regions associated with locomotion. However, the specific roles of the various pathophysiological mechanisms encountered in each neurological condition on the phenotype of gait disorders still remains unclear. After reviewing the results of individual brain imaging techniques across the common neurological conditions, such as Parkinson's disease, dementia, stroke, or multiple sclerosis, we will discuss how the development of new imaging techniques and computational analyses that integrate multivariate correlations in "large enough datasets" might help to understand how individual pathophysiological mechanisms express clinically as an abnormal gait. Finally, we will explore how these new analytic methods could drive our rehabilitative strategies. (C) 2018 Elsevier Masson SAS. All rights reserved.

Dynamic brain networks explored by structure-revealing methods

Nora Leonardi

The human brain is a complex system able to continuously adapt. How and where brain activity is modulated by behavior can be studied with functional magnetic resonance imaging (fMRI), a non-invasive neuroimaging technique with excellent spatial resolution and whole-brain coverage. FMRI scans of healthy adults completing a variety of behavioral tasks have greatly contributed to our understanding of the functional role of individual brain regions. However, by statistically analyzing each region independently, these studies ignore that brain regions act in concert rather than in unison. Thus, many studies since have instead examined how brain regions interact. Surprisingly, structured interactions between distinct brain regions not only occur during behavioral tasks but also while a subject rests quietly in the MRI scanner. Multiple groups of regions interact very strongly with each other and not only do these groups bear a striking resemblance to the sets of regions co-activated in tasks, but many of these interactions are also progressively disrupted in neurological diseases. This suggests that spontaneous fluctuations in activity can provide novel insights into fundamental organizing principles of the human brain in health and disease. Many techniques to date have segregated regions into spatially distinct networks, which ignores that any brain region can take part in multiple networks across time. A more natural view is to estimate dynamic brain networks that allow flexible functional interactions (or connectivity) over time. The estimation and analysis of such dynamic functional interactions is the subject of this dissertation. We take the perspective that dynamic brain networks evolve in a low-dimensional space and can be described by a small number of characteristic spatiotemporal patterns. Our proposed approaches are based on well-established statistical methods, such as principal component analysis (PCA), sparse matrix decompositions, temporal clustering, as well as a multiscale analysis by novel graph wavelet designs. We adapt and extend these methods to the analysis of dynamic brain networks. We show that PCA and its higher-order equivalent can identify co-varying functional interactions, which reveal disturbed dynamic properties in multiple sclerosis and which are related to the timing of stimuli for task studies, respectively. Further we show that sparse matrix decompositions provide a valid alternative approach to PCA and improve interpretability of the identified patterns. Finally, assuming an even simpler low-dimensional space and the exclusive temporal expression of individual patterns, we show that specific transient interactions of the medial prefrontal cortex are disturbed in aging and relate to impaired memory.

EPFL2014

Dynamic brain networks explored by structure-revealing methods

Nora Leonardi

EPFL2014