Disruption of transfer entropy and inter-hemispheric brain functional connectivity in patients with disorder of consciousness

Severe traumatic brain injury can lead to disorders of consciousness (DOC) characterized by deficit in conscious awareness and cognitive impairment including coma, vegetative state, minimally consciousness, and lock-in syndrome. Of crucial importance is to find objective markers that can account for the large-scale disturbances of brain function to help the diagnosis and prognosis of DOC patients and eventually the prediction of the coma outcome. Following recent studies suggesting that the functional organization of brain networks can be altered in comatose patients, this work analyzes brain functional connectivity (FC) networks obtained from resting-state functional magnetic resonance imaging (rs-fMRI). Two approaches are used to estimate the FC: the Partial Correlation (PC) and the Transfer Entropy (TE). Both the PC and the TE show significant statistical differences between the group of patients and control subjects; in brief, the inter-hemispheric PC and the intra-hemispheric TE account for such differences. Overall, these results suggest two possible rs-fMRI markers useful to design new strategies for the management and neuropsychological rehabilitation of DOC patients.Comment: 25 pages; 4 figures; 3 tables; 1 supplementary figure; 4 supplementary tables; accepted for publication in Frontiers in Neuroinformatic

New neuroimaging methods for clinical neuroscience and neurological disorders

236 p.Clinical neuroscience today makes use of state-of-the-art neuroimaging to study structural and functional brain data to improve diagnosis and prognosis in different neurological disorders.In this thesis dissertation, I focused on Magnetic Resonance Imaging (MRI), a non-invasive neuroimaging modality to study brain functional and structural data. Different new methods for brain connectivity analysis are described and applied to three pathologies: Disorder of Consciousness, Alzheimer's Disease and Traumatic Axonal Injury. This work is at the frontiers between two fields, the Biomedical Engineering of Image Processing and the Clinical Neuroscience

Information flow between resting state networks

The resting brain dynamics self-organizes into a finite number of correlated patterns known as resting state networks (RSNs). It is well known that techniques like independent component analysis can separate the brain activity at rest to provide such RSNs, but the specific pattern of interaction between RSNs is not yet fully understood. To this aim, we propose here a novel method to compute the information flow (IF) between different RSNs from resting state magnetic resonance imaging. After haemodynamic response function blind deconvolution of all voxel signals, and under the hypothesis that RSNs define regions of interest, our method first uses principal component analysis to reduce dimensionality in each RSN to next compute IF (estimated here in terms of Transfer Entropy) between the different RSNs by systematically increasing k (the number of principal components used in the calculation). When k = 1, this method is equivalent to computing IF using the average of all voxel activities in each RSN. For k greater than one our method calculates the k-multivariate IF between the different RSNs. We find that the average IF among RSNs is dimension-dependent, increasing from k =1 (i.e., the average voxels activity) up to a maximum occurring at k =5 to finally decay to zero for k greater than 10. This suggests that a small number of components (close to 5) is sufficient to describe the IF pattern between RSNs. Our method - addressing differences in IF between RSNs for any generic data - can be used for group comparison in health or disease. To illustrate this, we have calculated the interRSNs IF in a dataset of Alzheimer's Disease (AD) to find that the most significant differences between AD and controls occurred for k =2, in addition to AD showing increased IF w.r.t. controls.Comment: 47 pages, 5 figures, 4 tables, 3 supplementary figures. Accepted for publication in Brain Connectivity in its current for

Evaluation of brain functional connectivity from electroencephalographic signals under different emotional states

The identification of the emotional states corresponding to the four quadrants of the valence/arousal space has been widely analyzed in the scientific literature by means of multiple techniques. Nevertheless, most of these methods were based on the assessment of each brain region separately, without considering the possible interactions among different areas. In order to study these interconnections, this study computes for the first time the functional connectivity metric called cross-sample entropy for the analysis of the brain synchronization in four groups of emotions from electroencephalographic signals. Outcomes reported a strong synchronization in the interconnections among central, parietal and occipital areas, while the interactions between left frontal and temporal structures with the rest of brain regions presented the lowest coordination. These differences were statistically significant for the four groups of emotions. All emotions were simultaneously classified with a 95.43% of accuracy, overcoming the results reported in previous studies. Moreover, the differences between high and low levels of valence and arousal, taking into account the state of the counterpart dimension, also provided notable findings about the degree of synchronization in the brain within different emotional conditions and the possible implications of these outcomes from a psychophysiological point of view.- This publication is part of the R&D Projects Nos. PID2020-115220RB-C21, EQC2019-006063P, funded by MCIN/AEI/10.13039/501100011033/, and 2018/11744, funded by "ERDF A way to make Europe". This work was partially supported by Biomedical Research Networking Centre in Mental Health (CIBERSAM) of the Instituto de Salud Carlos III. Beatriz Garcia-Martinez holds FPU16/03740 scholarship from Spanish Ministerio de Educacion y Formacion Profesional

Mutual Information in Coupled Double Quantum Dots: A Simple Analytic Model for Potential Artificial Consciousness

The integrated information theory is thought to be a key clue towards the theoretical understanding of consciousness. In this study, we propose a simple numerical model comprising a set of coupled double quantum dots, where the disconnection of the elements is represented by the removal of Coulomb interaction between the quantum dots, for the quantitative investigation of integrated information. As a measure of integrated information, we calculate the mutual information in the model system, as the Kullback-Leibler divergence between the connected and disconnected status, through the probability distribution of the electronic states from the master transition-rate equations. We reasonably demonstrate that the increase in the strength of interaction between the quantum dots leads to higher mutual information, owing to the larger divergence in the probability distributions of the electronic states. Our model setup could be a useful basic tool for numerical analyses in the field of integrated information theory.Comment: 10 pages, 6 figure

Delirium screening in the intensive care unit using emerging QEEG techniques : A pilot study

This work was supported by an Alzheimer’s Society grant (project grant number AS-PG-14-039 to BP) and a British Journal of Anaesthesia / Royal College of Anaesthetists funded John Snow Anaesthesia iBSc Award (to AH).Peer reviewedPublisher PD

High-density EEG power topography and connectivity during confusional arousal.

Confusional arousal is the milder expression of a family of disorders known as Disorders of Arousal (DOA) from non-REM sleep. These disorders are characterized by recurrent abnormal behaviors that occur in a state of reduced awareness for the external environment. Despite frequent amnesia for the nocturnal events, when actively probed, patients are able to report vivid hallucinatory/dream-like mental imagery. Traditional (low-density) scalp and stereo-electroencephalographic (EEG) recordings previously showed a pathological admixture of slow oscillations typical of NREM sleep and wake-like fast-mixed frequencies during these phenomena. However, our knowledge about the specific neural EEG dynamics over the entire brain is limited. We collected 2 consecutive in-laboratory sleep recordings using high-density (hd)-EEG (256 vertex-referenced geodesic system) coupled with standard video-polysomnography (v-PSG) from a 12-year-old drug-naïve and otherwise healthy child with a long-lasting history of sleepwalking. Source power topography and functional connectivity were computed during 20 selected confusional arousal episodes (from -6 to +18 sec after motor onset), and during baseline slow wave sleep preceding each episode (from - 3 to -2 min before onset). We found a widespread increase in slow wave activity (SWA) theta, alpha, beta, gamma power, associated with a parallel decrease in the sigma range during behavioral episodes compared to baseline sleep. Bilateral Broadman area 7 and right Broadman areas 39 and 40 were relatively spared by the massive increase in SWA power. Functional SWA connectivity analysis revealed a drastic increase in the number and complexity of connections from baseline sleep to full-blown episodes, that mainly involved an increased out-flow from bilateral fronto-medial prefrontal cortex and left temporal lobe to other cortical regions. These effects could be appreciated in the 6 sec window preceding behavioral onset. Overall, our results support the idea that DOA are the expression of peculiar brain states, compatible with a partial re-emergence of consciousness

Methods and models for brain connectivity assessment across levels of consciousness

The human brain is one of the most complex and fascinating systems in nature. In the last decades, two events have boosted the investigation of its functional and structural properties. Firstly, the emergence of novel noninvasive neuroimaging modalities, which helped improving the spatial and temporal resolution of the data collected from in vivo human brains. Secondly, the development of advanced mathematical tools in network science and graph theory, which has recently translated into modeling the human brain as a network, giving rise to the area of research so called Brain Connectivity or Connectomics. In brain network models, nodes correspond to gray-matter regions (based on functional or structural, atlas-based parcellations that constitute a partition), while links or edges correspond either to structural connections as modeled based on white matter fiber-tracts or to the functional coupling between brain regions by computing statistical dependencies between measured brain activity from different nodes. Indeed, the network approach for studying the brain has several advantages: 1) it eases the study of collective behaviors and interactions between regions; 2) allows to map and study quantitative properties of its anatomical pathways; 3) gives measures to quantify integration and segregation of information processes in the brain, and the flow (i.e. the interacting dynamics) between different cortical and sub-cortical regions. The main contribution of my PhD work was indeed to develop and implement new models and methods for brain connectivity assessment in the human brain, having as primary application the analysis of neuroimaging data coming from subjects at different levels of consciousness. I have here applied these methods to investigate changes in levels of consciousness, from normal wakefulness (healthy human brains) or drug-induced unconsciousness (i.e. anesthesia) to pathological (i.e. patients with disorders of consciousness)

Lagged and instantaneous dynamical influences related to brain structural connectivity

Contemporary neuroimaging methods can shed light on the basis of human neural and cognitive specializations, with important implications for neuroscience and medicine. Different MRI acquisitions provide different brain networks at the macroscale; whilst diffusion-weighted MRI (dMRI) provides a structural connectivity (SC) coincident with the bundles of parallel fibers between brain areas, functional MRI (fMRI) accounts for the variations in the blood-oxygenation-level-dependent T2* signal, providing functional connectivity (FC).Understanding the precise relation between FC and SC, that is, between brain dynamics and structure, is still a challenge for neuroscience. To investigate this problem, we acquired data at rest and built the corresponding SC (with matrix elements corresponding to the fiber number between brain areas) to be compared with FC connectivity matrices obtained by 3 different methods: directed dependencies by an exploratory version of structural equation modeling (eSEM), linear correlations (C) and partial correlations (PC). We also considered the possibility of using lagged correlations in time series; so, we compared a lagged version of eSEM and Granger causality (GC). Our results were two-fold: firstly, eSEM performance in correlating with SC was comparable to those obtained from C and PC, but eSEM (not C nor PC) provides information about directionality of the functional interactions. Second, interactions on a time scale much smaller than the sampling time, captured by instantaneous connectivity methods, are much more related to SC than slow directed influences captured by the lagged analysis. Indeed the performance in correlating with SC was much worse for GC and for the lagged version of eSEM. We expect these results to supply further insights to the interplay between SC and functional patterns, an important issue in the study of brain physiology and function.Comment: Accepted and published in Frontiers in Psychology in its current form. 27 pages, 1 table, 5 figures, 2 suppl. figure