Functional connectivity in relation to motor performance and recovery after stroke.

Plasticity after stroke has traditionally been studied by observing changes only in the spatial distribution and laterality of focal brain activation during affected limb movement. However, neural reorganization is multifaceted and our understanding may be enhanced by examining dynamics of activity within large-scale networks involved in sensorimotor control of the limbs. Here, we review functional connectivity as a promising means of assessing the consequences of a stroke lesion on the transfer of activity within large-scale neural networks. We first provide a brief overview of techniques used to assess functional connectivity in subjects with stroke. Next, we review task-related and resting-state functional connectivity studies that demonstrate a lesion-induced disruption of neural networks, the relationship of the extent of this disruption with motor performance, and the potential for network reorganization in the presence of a stroke lesion. We conclude with suggestions for future research and theories that may enhance the interpretation of changing functional connectivity. Overall findings suggest that a network level assessment provides a useful framework to examine brain reorganization and to potentially better predict behavioral outcomes following stroke

Decoupling of brain function from structure reveals regional behavioral specialization in humans

The brain is an assembly of neuronal populations interconnected by structural pathways. Brain activity is expressed on and constrained by this substrate. Therefore, statistical dependencies between functional signals in directly connected areas can be expected higher. However, the degree to which brain function is bound by the underlying wiring diagram remains a complex question that has been only partially answered. Here, we introduce the structural-decoupling index to quantify the coupling strength between structure and function, and we reveal a macroscale gradient from brain regions more strongly coupled, to regions more strongly decoupled, than expected by realistic surrogate data. This gradient spans behavioral domains from lower-level sensory function to high-level cognitive ones and shows for the first time that the strength of structure-function coupling is spatially varying in line with evidence derived from other modalities, such as functional connectivity, gene expression, microstructural properties and temporal hierarchy

Genetic and Neuroanatomical Support for Functional Brain Network Dynamics in Epilepsy

Focal epilepsy is a devastating neurological disorder that affects an overwhelming number of patients worldwide, many of whom prove resistant to medication. The efficacy of current innovative technologies for the treatment of these patients has been stalled by the lack of accurate and effective methods to fuse multimodal neuroimaging data to map anatomical targets driving seizure dynamics. Here we propose a parsimonious model that explains how large-scale anatomical networks and shared genetic constraints shape inter-regional communication in focal epilepsy. In extensive ECoG recordings acquired from a group of patients with medically refractory focal-onset epilepsy, we find that ictal and preictal functional brain network dynamics can be accurately predicted from features of brain anatomy and geometry, patterns of white matter connectivity, and constraints complicit in patterns of gene coexpression, all of which are conserved across healthy adult populations. Moreover, we uncover evidence that markers of non-conserved architecture, potentially driven by idiosyncratic pathology of single subjects, are most prevalent in high frequency ictal dynamics and low frequency preictal dynamics. Finally, we find that ictal dynamics are better predicted by white matter features and more poorly predicted by geometry and genetic constraints than preictal dynamics, suggesting that the functional brain network dynamics manifest in seizures rely on - and may directly propagate along - underlying white matter structure that is largely conserved across humans. Broadly, our work offers insights into the generic architectural principles of the human brain that impact seizure dynamics, and could be extended to further our understanding, models, and predictions of subject-level pathology and response to intervention

Centralized and distributed cognitive task processing in the human connectome

A key question in modern neuroscience is how cognitive changes in a human brain can be quantified and captured by functional connectomes (FC) . A systematic approach to measure pairwise functional distance at different brain states is lacking. This would provide a straight-forward way to quantify differences in cognitive processing across tasks; also, it would help in relating these differences in task-based FCs to the underlying structural network. Here we propose a framework, based on the concept of Jensen-Shannon divergence, to map the task-rest connectivity distance between tasks and resting-state FC. We show how this information theoretical measure allows for quantifying connectivity changes in distributed and centralized processing in functional networks. We study resting-state and seven tasks from the Human Connectome Project dataset to obtain the most distant links across tasks. We investigate how these changes are associated to different functional brain networks, and use the proposed measure to infer changes in the information processing regimes. Furthermore, we show how the FC distance from resting state is shaped by structural connectivity, and to what extent this relationship depends on the task. This framework provides a well grounded mathematical quantification of connectivity changes associated to cognitive processing in large-scale brain networks.Comment: 22 pages main, 6 pages supplementary, 6 figures, 5 supplementary figures, 1 table, 1 supplementary table. arXiv admin note: text overlap with arXiv:1710.0219

Model-free reconstruction of neuronal network connectivity from calcium imaging signals

A systematic assessment of global neural network connectivity through direct electrophysiological assays has remained technically unfeasible even in dissociated neuronal cultures. We introduce an improved algorithmic approach based on Transfer Entropy to reconstruct approximations to network structural connectivities from network activity monitored through calcium fluorescence imaging. Based on information theory, our method requires no prior assumptions on the statistics of neuronal firing and neuronal connections. The performance of our algorithm is benchmarked on surrogate time-series of calcium fluorescence generated by the simulated dynamics of a network with known ground-truth topology. We find that the effective network topology revealed by Transfer Entropy depends qualitatively on the time-dependent dynamic state of the network (e.g., bursting or non-bursting). We thus demonstrate how conditioning with respect to the global mean activity improves the performance of our method. [...] Compared to other reconstruction strategies such as cross-correlation or Granger Causality methods, our method based on improved Transfer Entropy is remarkably more accurate. In particular, it provides a good reconstruction of the network clustering coefficient, allowing to discriminate between weakly or strongly clustered topologies, whereas on the other hand an approach based on cross-correlations would invariantly detect artificially high levels of clustering. Finally, we present the applicability of our method to real recordings of in vitro cortical cultures. We demonstrate that these networks are characterized by an elevated level of clustering compared to a random graph (although not extreme) and by a markedly non-local connectivity.Comment: 54 pages, 8 figures (+9 supplementary figures), 1 table; submitted for publicatio

Dynamic fluctuations coincide with periods of high and low modularity in resting-state functional brain networks

We investigate the relationship of resting-state fMRI functional connectivity estimated over long periods of time with time-varying functional connectivity estimated over shorter time intervals. We show that using Pearson's correlation to estimate functional connectivity implies that the range of fluctuations of functional connections over short time scales is subject to statistical constraints imposed by their connectivity strength over longer scales. We present a method for estimating time-varying functional connectivity that is designed to mitigate this issue and allows us to identify episodes where functional connections are unexpectedly strong or weak. We apply this method to data recorded from $N=80$ participants, and show that the number of unexpectedly strong/weak connections fluctuates over time, and that these variations coincide with intermittent periods of high and low modularity in time-varying functional connectivity. We also find that during periods of relative quiescence regions associated with default mode network tend to join communities with attentional, control, and primary sensory systems. In contrast, during periods where many connections are unexpectedly strong/weak, default mode regions dissociate and form distinct modules. Finally, we go on to show that, while all functional connections can at times manifest stronger (more positively correlated) or weaker (more negatively correlated) than expected, a small number of connections, mostly within the visual and somatomotor networks, do so a disproportional number of times. Our statistical approach allows the detection of functional connections that fluctuate more or less than expected based on their long-time averages and may be of use in future studies characterizing the spatio-temporal patterns of time-varying functional connectivityComment: 47 Pages, 8 Figures, 4 Supplementary Figure

Functional connectivity changes and their relationship with clinical disability and white matter integrity in patients with relapsing-remitting multiple sclerosis

Background and objective: To define the pathological substrate underlying disability in multiple sclerosis by evaluating the relationship of resting-state functional connectivity with microstructural brain damage, as assessed by diffusion tensor maging, and clinical impairments. Methods: Thirty relapsing–remitting patients and 24 controls underwent 3T-MRI; motor abilities were evaluated by using measures of walking speed, hand dexterity and balance capability, while information processing speed was evaluated by a paced auditory serial addiction task. Independent component analysis and tract-based spatial statistics were applied to RS-fMRI and diffusion tensor imaging data using FSL software. Group differences, after dual regression, and clinical correlations were modelled with GeneralLinear-Model and corrected for multiple comparisons. Results: Patients showed decreased functional connectivity in 5 of 11 resting-state-networks (cerebellar, executive-control, medial-visual, basal ganglia and sensorimotor), changes in inter-network correlations and widespread white matter microstructural damage. In multiple sclerosis, corpus callosum microstructural damage positively correlated with functional connectivity in cerebellar and auditory networks. Moreover, functional connectivity within the medial-visual network inversely correlated with information processing speed. White matter widespread microstructural damage inversely correlated with both the paced auditory serial addiction task and hand dexterity. Conclusions: Despite the within-network functional connectivity decrease and the widespread microstructural damage, the inter-network functional connectivity changes suggest a global brain functional rearrangement in multiple sclerosis. The correlation between functional connectivity alterations and callosal damage uncovers a link between functional and structural connectivity. Finally, functional connectivity abnormalities affect information processing speed rather than motor abilities

Learning and comparing functional connectomes across subjects

Functional connectomes capture brain interactions via synchronized fluctuations in the functional magnetic resonance imaging signal. If measured during rest, they map the intrinsic functional architecture of the brain. With task-driven experiments they represent integration mechanisms between specialized brain areas. Analyzing their variability across subjects and conditions can reveal markers of brain pathologies and mechanisms underlying cognition. Methods of estimating functional connectomes from the imaging signal have undergone rapid developments and the literature is full of diverse strategies for comparing them. This review aims to clarify links across functional-connectivity methods as well as to expose different steps to perform a group study of functional connectomes