Pain-Evoked Reorganization in Functional Brain Networks.

Recent studies indicate that a significant reorganization of cerebral networks may occur in patients with chronic pain, but how immediate pain experience influences the organization of large-scale functional networks is not yet well characterized. To investigate this question, we used functional magnetic resonance imaging in 106 participants experiencing both noxious and innocuous heat. Painful stimulation caused network-level reorganization of cerebral connectivity that differed substantially from organization during innocuous stimulation and standard resting-state networks. Noxious stimuli increased somatosensory network connectivity with (a) frontoparietal networks involved in context representation, (b) "ventral attention network" regions involved in motivated action selection, and (c) basal ganglia and brainstem regions. This resulted in reduced "small-worldness," modularity (fewer networks), and global network efficiency and in the emergence of an integrated "pain supersystem" (PS) whose activity predicted individual differences in pain sensitivity across 5 participant cohorts. Network hubs were reorganized ("hub disruption") so that more hubs were localized in PS, and there was a shift from "connector" hubs linking disparate networks to "provincial" hubs connecting regions within PS. Our findings suggest that pain reorganizes the network structure of large-scale brain systems. These changes may prioritize responses to painful events and provide nociceptive systems privileged access to central control of cognition and action during pain.

Functional hub disruption emphasizes consciousness recovery in severe traumatic brain injury.

Severe traumatic brain injury can lead to transient or even chronic disorder of consciousness. To increase diagnosis and prognosis accuracy of disorder of consciousness, functional neuroimaging is recommended 1 month post-injury. Here, we investigated brain networks remodelling on longitudinal data between 1 and 3 months post severe traumatic brain injury related to change of consciousness. Thirty-four severe traumatic brain-injured patients were included in a cross-sectional and longitudinal clinical study, and their MRI data were compared to those of 20 healthy subjects. Long duration resting-state functional MRI were acquired in minimally conscious and conscious patients at two time points after their brain injury. The first time corresponds to the exit from intensive care unit and the second one to the discharge from post-intensive care rehabilitation ward. Brain networks data were extracted using graph analysis and metrics at each node quantifying local (clustering) and global (degree) connectivity characteristics. Comparison with brain networks of healthy subjects revealed patterns of hyper- and hypo-connectivity that characterize brain networks reorganization through the hub disruption index, a value quantifying the functional disruption in each individual severe traumatic brain injury graph. At discharge from intensive care unit, 24 patients' graphs (9 minimally conscious and 15 conscious) were fully analysed and demonstrated significant network disruption. Clustering and degree nodal metrics, respectively, related to segregation and integration properties of the network, were relevant to distinguish minimally conscious and conscious groups. At discharge from post-intensive care rehabilitation unit, 15 patients' graphs (2 minimally conscious, 13 conscious) were fully analysed. The conscious group still presented a significant difference with healthy subjects. Using mixed effects models, we showed that consciousness state, rather than time, explained the hub disruption index differences between minimally conscious and conscious groups. While severe traumatic brain-injured patients recovered full consciousness, regional functional connectivity evolved towards a healthy pattern. More specifically, the restoration of a healthy brain functional segregation could be necessary for consciousness recovery after severe traumatic brain injury. For the first time, extracting the hub disruption index directly from each patient's graph, we were able to track the clinical alteration and subsequent recovery of consciousness during the first 3 months following a severe traumatic brain injury.

A covariate-constraint method to map brain feature space into lower dimensional manifolds.

Human brain connectome studies aim to both explore healthy brains, and extract and analyze relevant features associated with pathologies of interest. Usually this consists of modeling the brain connectome as a graph and using graph metrics as features. A fine brain description requires graph metrics computation at the node level. Given the relatively reduced number of patients in standard cohorts, such data analysis problems fall in the high-dimension, low-sample-size framework. In this context, our goal is to provide a machine learning technique that exhibits flexibility, gives the investigator an understanding of the features and covariates, allows visualization and exploration, and yields insight into the data and the biological phenomena at stake. The retained approach is dimension reduction in a manifold learning methodology; the originality is that the investigator chooses one (or several) reduced variables. The proposed method is illustrated in two studies. The first one addresses comatose patients; the second one compares young and elderly populations. The method sheds light on the differences between brain connectivity graphs using graph metrics and potential clinical interpretations of these differences.

Topological Modification of Brain Networks Organization in Children With High Intelligence Quotient: A Resting-State fMRI Study.

The idea that intelligence is embedded not only in a single brain network, but instead in a complex, well-optimized system of complementary networks, has led to the development of whole brain network analysis. Using graph theory to analyze resting-state functional MRI data, we investigated the brain graph networks (or brain networks) of high intelligence quotient (HIQ) children. To this end, we computed the "hub disruption index κ," an index sensitive to graph network modifications. We found significant topological differences in the integration and segregation properties of brain networks in HIQ compared to standard IQ children, not only for the whole brain graph, but also for each hemispheric graph, and for the homotopic connectivity. Moreover, two profiles of HIQ children, homogenous and heterogeneous, based on the differences between the two main IQ subscales [verbal comprehension index (VCI) and perceptual reasoning index (PRI)], were compared. Brain network changes were more pronounced in the heterogeneous than in the homogeneous HIQ subgroups. Finally, we found significant correlations between the graph networks' changes and the full-scale IQ (FSIQ), as well as the subscales VCI and PRI. Specifically, the higher the FSIQ the greater was the brain organization modification in the whole brain, the left hemisphere, and the homotopic connectivity. These results shed new light on the relation between functional connectivity topology and high intelligence, as well as on different intelligence profiles.

Corrigendum: Topological Modification of Brain Networks Organization in Children With High Intelligence Quotient: A Resting-State fMRI Study.

[This corrects the article DOI: 10.3389/fnhum.2019.00241.].

Classification and characterisation of brain network changes in chronic back pain: A multicenter study.

Background. Chronic pain is a common, often disabling condition thought to involve a combination of peripheral and central neurobiological factors. However, the extent and nature of changes in the brain is poorly understood. Methods. We investigated brain network architecture using resting-state fMRI data in chronic back pain patients in the UK and Japan (41 patients, 56 controls), as well as open data from USA. We applied machine learning and deep learning (conditional variational autoencoder architecture) methods to explore classification of patients/controls based on network connectivity. We then studied the network topology of the data, and developed a multislice modularity method to look for consensus evidence of modular reorganisation in chronic back pain. Results. Machine learning and deep learning allowed reliable classification of patients in a third, independent open data set with an accuracy of 63%, with 68% in cross validation of all data. We identified robust evidence of network hub disruption in chronic pain, most consistently with respect to clustering coefficient and betweenness centrality. We found a consensus pattern of modular reorganisation involving extensive, bilateral regions of sensorimotor cortex, and characterised primarily by negative reorganisation - a tendency for sensorimotor cortex nodes to be less inclined to form pairwise modular links with other brain nodes. Furthermore, these regions were found to display increased connectivity with the pregenual anterior cingulate cortex, a region known to be involved in endogenous pain control. In contrast, intraparietal sulcus displayed a propensity towards positive modular reorganisation, suggesting that it might have a role in forming modules associated with the chronic pain state. Conclusion. The results provide evidence of consistent and characteristic brain network changes in chronic pain, characterised primarily by extensive reorganisation of the network architecture of the sensorimotor cortex.

The "Hub Disruption Index," a Reliable Index Sensitive to the Brain Networks Reorganization. A Study of the Contralesional Hemisphere in Stroke.

Stroke, resulting in focal structural damage, induces changes in brain function at both local and global levels. Following stroke, cerebral networks present structural, and functional reorganization to compensate for the dysfunctioning provoked by the lesion itself and its remote effects. As some recent studies underlined the role of the contralesional hemisphere during recovery, we studied its role in the reorganization of brain function of stroke patients using resting state fMRI and graph theory. We explored this reorganization using the "hub disruption index" (κ), a global index sensitive to the reorganization of nodes within the graph. For a given graph metric, κ of a subject corresponds to the slope of the linear regression model between the mean local network measures of a reference group, and the difference between that reference and the subject under study. In order to translate the use of κ in clinical context, a prerequisite to achieve meaningful results is to investigate the reliability of this index. In a preliminary part, we studied the reliability of κ by computing the intraclass correlation coefficient in a cohort of 100 subjects from the Human Connectome Project. Then, we measured intra-hemispheric κ index in the contralesional hemisphere of 20 subacute stroke patients compared to 20 age-matched healthy controls. Finally, due to the small number of patients, we tested the robustness of our results repeating the experiment 1000 times by bootstrapping on the Human Connectome Project database. Statistical analysis showed a significant reduction of κ for the contralesional hemisphere of right stroke patients compared to healthy controls. Similar results were observed for the right contralesional hemisphere of left stroke patients. We showed that κ, is more reliable than global graph metrics and more sensitive to detect differences between groups of patients as compared to healthy controls. Using new graph metrics as κ allows us to show that stroke induces a network-wide pattern of reorganization in the contralesional hemisphere whatever the side of the lesion. Graph modeling combined with measure of reorganization at the level of large-scale networks can become a useful tool in clinic.