The Open-Access European Prevention of Alzheimer's Dementia (EPAD) MRI dataset and processing workflow.

The European Prevention of Alzheimer Dementia (EPAD) is a multi-center study that aims to characterize the preclinical and prodromal stages of Alzheimer's Disease. The EPAD imaging dataset includes core (3D T1w, 3D FLAIR) and advanced (ASL, diffusion MRI, and resting-state fMRI) MRI sequences. Here, we give an overview of the semi-automatic multimodal and multisite pipeline that we developed to curate, preprocess, quality control (QC), and compute image-derived phenotypes (IDPs) from the EPAD MRI dataset. This pipeline harmonizes DICOM data structure across sites and performs standardized MRI preprocessing steps. A semi-automated MRI QC procedure was implemented to visualize and flag MRI images next to site-specific distributions of QC features - i.e. metrics that represent image quality. The value of each of these QC features was evaluated through comparison with visual assessment and step-wise parameter selection based on logistic regression. IDPs were computed from 5 different MRI modalities and their sanity and potential clinical relevance were ascertained by assessing their relationship with biological markers of aging and dementia. The EPAD v1500.0 data release encompassed core structural scans from 1356 participants 842 fMRI, 831 dMRI, and 858 ASL scans. From 1356 3D T1w images, we identified 17 images with poor quality and 61 with moderate quality. Five QC features - Signal to Noise Ratio (SNR), Contrast to Noise Ratio (CNR), Coefficient of Joint Variation (CJV), Foreground-Background energy Ratio (FBER), and Image Quality Rate (IQR) - were selected as the most informative on image quality by comparison with visual assessment. The multimodal IDPs showed greater impairment in associations with age and dementia biomarkers, demonstrating the potential of the dataset for future clinical analyses.

Application of the ATN classification scheme in a population without dementia: Findings from the EPAD cohort.

BACKGROUND: We classified non-demented European Prevention of Alzheimer's Dementia (EPAD) participants through the amyloid/tau/neurodegeneration (ATN) scheme and assessed their neuropsychological and imaging profiles. MATERIALS AND METHODS: From 1500 EPAD participants, 312 were excluded. Cerebrospinal fluid cut-offs of 1000 pg/mL for amyloid beta (Aß)1-42 and 27 pg/mL for p-tau181 were validated using Gaussian mixture models. Given strong correlation of p-tau and t-tau (R2  = 0.98, P < 0.001), neurodegeneration was defined by age-adjusted hippocampal volume. Multinomial regressions were used to test whether neuropsychological tests and regional brain volumes could distinguish ATN stages. RESULTS: Age was 65 ± 7 years, with 58% females and 38% apolipoprotein E (APOE) ε4 carriers; 57.1% were A-T-N-, 32.5% were in the Alzheimer's disease (AD) continuum, and 10.4% suspected non-Alzheimer's pathology. Age and cerebrovascular burden progressed with biomarker positivity (P < 0.001). Cognitive dysfunction appeared with T+. Paradoxically higher regional gray matter volumes were observed in A+T-N- compared to A-T-N- (P < 0.001). DISCUSSION: In non-demented individuals along the AD continuum, p-tau drives cognitive dysfunction. Memory and language domains are affected in the earliest stages.

Diagnostic quality assessment of IR-prepared 3D magnetic resonance neuroimaging accelerated using compressed sensing and k-space sampling order optimization.

PURPOSE: To evaluate the clinical diagnostic efficacy of accelerated 3D magnetic resonance (MR) neuroimaging by radiological assessment for image quality and artefacts. STUDY TYPE: Prospective healthy volunteer study. SUBJECTS: Eight healthy subjects. FIELD STRENGTH/SEQUENCE: Inversion Recovery (IR) prepared 3D Gradient Echo (GRE) sequence on a 1.5 T GE Signa HDx scanner. ASSESSMENT: Independent radiological diagnostic quality assessments of accelerated 3D MR brain datasets were carried out by four experienced neuro-radiologists who were blinded to the acceleration factor and to the subject. The radiological grading was based on a previously reported radiological scoring key that was used for image quality assessment of human brains. STATISTICAL TESTS: Bland-Altman analysis. RESULTS: Optimization of the k-space sampling order was important for preserving contrast in accelerated scans. Despite having lower scores than fully sampled datasets, the majority of the compressed sensing (CS) accelerated brain datasets with k-space sampling order optimization (19/24 datasets by Radiologist 1, 24/24 datasets by Radiologist 2 and 16/24 datasets by Radiologist 3) were graded to be fully diagnostic indicating that there was adequate confidence for performing gross structural assessment of the brain. CONCLUSION: Optimization of k-space acquisition order improves the clinical utility of CS accelerated 3D neuroimaging. This method may be appropriate for routine radiological assessment of the brain.

Neurophysiological Correlates of a Single Session of Prefrontal tDCS in Patients with Prolonged Disorders of Consciousness: A Pilot Double-Blind Randomized Controlled Study.

Background. Transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (lDLPFC) was reported to promote the recovery of signs of consciousness in some patients in a minimally conscious state (MCS), but its electrophysiological effects on brain activity remain poorly understood. Objective. We aimed to assess behavioral (using the Coma Recovery Scale-Revised; CRS-R) and neurophysiological effects (using high density electroencephalography; hdEEG) of lDLPFC-tDCS in patients with prolonged disorders of consciousness (DOC). Methods. In a double-blind, sham-controlled, crossover design, one active and one sham tDCS (2 mA, 20 min) were delivered in a randomized order. Directly before and after tDCS, 10 min of hdEEG were recorded and the CRS-R was administered. Results. Thirteen patients with severe brain injury were enrolled in the study. We found higher relative power at the group level after the active tDCS session in the alpha band in central regions and in the theta band over the frontal and posterior regions (uncorrected results). Higher weighted symbolic mutual information (wSMI) connectivity was found between left and right parietal regions, and higher fronto-parietal weighted phase lag index (wPLI) connectivity was found, both in the alpha band (uncorrected results). At the group level, no significant treatment effect was observed. Three patients showed behavioral improvement after the active session and one patient improved after the sham. Conclusion. We provide preliminary indications that neurophysiological changes can be observed after a single session of tDCS in patients with prolonged DOC, although they are not necessarily paralleled with significant behavioral improvements.

Resting-state functional connectivity and cortical thickness characterization of a patient with Charles Bonnet syndrome.

Charles Bonnet syndrome (CBS) is a rare condition characterized by visual impairment associated with complex visual hallucinations in elderly people. Although studies suggested that visual hallucinations may be caused by brain damage in the visual system in CBS patients, alterations in specific brain regions in the occipital cortex have not been studied. Functional connectivity during resting-state functional magnetic resonance imaging (rs-fMRI; without hallucinations) in CBS patients, has never been explored. We aimed to investigate brain structural and functional changes in a patient with CBS, as compared with late blind (LB) and normally sighted subjects. We employed voxel-based morphometry and cortical thickness analyses to investigate alterations in grey matter characteristics, and rs-fMRI to study changes in functional brain connectivity. Decreased grey matter volume was observed in the middle occipital gyrus and in the cuneus in the CBS patient, and in the middle occipital gyrus and in the lingual gyrus within LB subjects, compared to their respective control groups. Reductions in cortical thickness in associative and multimodal cortices were observed in the CBS patient when comparing with LB subjects. The precuneus exhibited increased functional connectivity with the secondary visual cortex in the CBS patient compared to the controls. In contrast, LB patients showed decreased functional connectivity compared to sighted controls between the DMN and the temporo-occipital fusiform gyrus, a region known to support hallucinations. Our findings suggest a reorganization of the functional connectivity between regions involved in self-awareness and in visual and salience processing in CBS that may contribute to the appearance of visual hallucinations.

Measures of CNS-Autonomic Interaction and Responsiveness in Disorder of Consciousness.

Neuroimaging studies have demonstrated functional interactions between autonomic (ANS) and brain (CNS) structures involved in higher brain functions, including attention and conscious processes. These interactions have been described by the Central Autonomic Network (CAN), a concept model based on the brain-heart two-way integrated interaction. Heart rate variability (HRV) measures proved reliable as non-invasive descriptors of the ANS-CNS function setup and are thought to reflect higher brain functions. Autonomic function, ANS-mediated responsiveness and the ANS-CNS interaction qualify as possible independent indicators for clinical functional assessment and prognosis in Disorders of Consciousness (DoC). HRV has proved helpful to investigate residual responsiveness in DoC and predict clinical recovery. Variability due to internal (e.g., homeostatic and circadian processes) and environmental factors remains a key independent variable and systematic research with this regard is warranted. The interest in bidirectional ANS-CNS interactions in a variety of physiopathological conditions is growing, however, these interactions have not been extensively investigated in DoC. In this brief review we illustrate the potentiality of brain-heart investigation by means of HRV analysis in assessing patients with DoC. The authors' opinion is that this easy, inexpensive and non-invasive approach may provide useful information in the clinical assessment of this challenging patient population.

Circadian Rhythms and Measures of CNS/Autonomic Interaction.

The physiological role and relevance of the mechanisms sustaining circadian rhythms have been acknowledged. Abnormalities of the circadian and/or sleep-wakefulness cycles can result in major metabolic disorders or behavioral/professional inadequacies and stand as independent risk factors for metabolic, psychiatric, and cerebrovascular disorders and early markers of disease. Neuroimaging and clinical evidence have documented functional interactions between autonomic (ANS) and CNS structures that are described by a concept model (Central Autonomic Network) based on the brain-heart two-way interplay. The circadian rhythms of autonomic function, ANS-mediated processes, and ANS/CNS interaction appear to be sources of variability adding to a variety of environmental factors, and may become crucial when considering the ANS major role in internal environment constancy and adaptation that are fundamental to homeostasis. The CNS/ANS interaction has not yet obtained full attention and systematic investigation remains overdue.

Modulation of the spontaneous hemodynamic response function across levels of consciousness.

Functional imaging research has already contributed with several results to the study of neural correlates of consciousness. Apart from task-related activation derived in fMRI, PET based glucose metabolism rate or cerebral blood flow account for a considerable proportion of the study of brain activity under different levels of consciousness. Resting state functional connectivity MRI is playing a crucial role to explore the consciousness related functional integration, successfully complementing PET, another widely used neuroimaging technique. Here, spontaneous hemodynamic response is introduced to characterize resting state brain activity giving information on the local metabolism (neurovascular coupling), and useful to improve the time-resolved activity and connectivity measures based on BOLD fMRI. This voxel-wise measure is then used to investigate the loss of consciousness under Propofol anesthesia and unresponsive wakefulness syndrome. Changes in the hemodynamic response in precuneus and posterior cingulate are found to be a common principle underlying loss of consciousness in both conditions. The thalamus appears to be less obviously modulated by Propofol, compared with frontoparietal regions. However, a significant increase in spontaneous thalamic hemodynamic response was found in patients in unresponsive wakefulness syndrome compared with healthy controls. Our results ultimately show that anesthesia- or pathology-induced neurovascular coupling could be tracked by modulated spontaneous hemodynamic response derived from resting state fMRI.

Changes in Whole Brain Dynamics and Connectivity Patterns during Sevoflurane- and Propofol-induced Unconsciousness Identified by Functional Magnetic Resonance Imaging.

BACKGROUND: A key feature of the human brain is its capability to adapt flexibly to changing external stimuli. This capability can be eliminated by general anesthesia, a state characterized by unresponsiveness, amnesia, and (most likely) unconsciousness. Previous studies demonstrated decreased connectivity within the thalamus, frontoparietal, and default mode networks during general anesthesia. We hypothesized that these alterations within specific brain networks lead to a change of communication between networks and their temporal dynamics. METHODS: We conducted a pooled spatial independent component analysis of resting-state functional magnetic resonance imaging data obtained from 16 volunteers during propofol and 14 volunteers during sevoflurane general anesthesia that have been previously published. Similar to previous studies, mean z-scores of the resulting spatial maps served as a measure of the activity within a network. Additionally, correlations of associated time courses served as a measure of the connectivity between networks. To analyze the temporal dynamics of between-network connectivity, we computed the correlation matrices during sliding windows of 1 min and applied k-means clustering to the matrices during both general anesthesia and wakefulness. RESULTS: Within-network activity was decreased in the default mode, attentional, and salience networks during general anesthesia (P < 0.001, range of median changes: -0.34, -0.13). Average between-network connectivity was reduced during general anesthesia (P < 0.001, median change: -0.031). Distinct between-network connectivity patterns for both wakefulness and general anesthesia were observed irrespective of the anesthetic agent (P < 0.001), and there were fewer transitions in between-network connectivity patterns during general anesthesia (P < 0.001, median number of transitions during wakefulness: 4 and during general anesthesia: 0). CONCLUSIONS: These results suggest that (1) higher-order brain regions play a crucial role in the generation of specific between-network connectivity patterns and their dynamics, and (2) the capability to interact with external stimuli is represented by complex between-network connectivity patterns.

A Heartbeat Away From Consciousness: Heart Rate Variability Entropy Can Discriminate Disorders of Consciousness and Is Correlated With Resting-State fMRI Brain Connectivity of the Central Autonomic Network.

Background: Disorders of consciousness are challenging to diagnose, with inconsistent behavioral responses, motor and cognitive disabilities, leading to approximately 40% misdiagnoses. Heart rate variability (HRV) reflects the complexity of the heart-brain two-way dynamic interactions. HRV entropy analysis quantifies the unpredictability and complexity of the heart rate beats intervals. We here investigate the complexity index (CI), a score of HRV complexity by aggregating the non-linear multi-scale entropies over a range of time scales, and its discriminative power in chronic patients with unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), and its relation to brain functional connectivity. Methods: We investigated the CI in short (CIs) and long (CIl) time scales in 14 UWS and 16 MCS sedated. CI for MCS and UWS groups were compared using a Mann-Whitney exact test. Spearman's correlation tests were conducted between the Coma Recovery Scale-revised (CRS-R) and both CI. Discriminative power of both CI was assessed with One-R machine learning model. Correlation between CI and brain connectivity (detected with functional magnetic resonance imagery using seed-based and hypothesis-free intrinsic connectivity) was investigated using a linear regression in a subgroup of 10 UWS and 11 MCS patients with sufficient image quality. Results: Higher CIs and CIl values were observed in MCS compared to UWS. Positive correlations were found between CRS-R and both CI. The One-R classifier selected CIl as the best discriminator between UWS and MCS with 90% accuracy, 7% false positive and 13% false negative rates after a 10-fold cross-validation test. Positive correlations were observed between both CI and the recovery of functional connectivity of brain areas belonging to the central autonomic networks (CAN). Conclusion: CI of MCS compared to UWS patients has high discriminative power and low false negative rate at one third of the estimated human assessors' misdiagnosis, providing an easy, inexpensive and non-invasive diagnostic tool. CI reflects functional connectivity changes in the CAN, suggesting that CI can provide an indirect way to screen and monitor connectivity changes in this neural system. Future studies should assess the extent of CI's predictive power in a larger cohort of patients and prognostic power in acute patients.

Clinical subcategorization of minimally conscious state according to resting functional connectivity.

Patients in minimally conscious state (MCS) have been subcategorized in MCS plus and MCS minus, based on command-following, intelligible verbalization or intentional communication. We here aimed to better characterize the functional neuroanatomy of MCS based on this clinical subcategorization by means of resting state functional magnetic resonance imaging (fMRI). Resting state fMRI was acquired in 292 MCS patients and a seed-based analysis was conducted on a convenience sample of 10 MCS plus patients, 9 MCS minus patients and 35 healthy subjects. We investigated the left and right frontoparietal networks (FPN), auditory network, default mode network (DMN), thalamocortical connectivity and DMN between-network anticorrelations. We also employed an analysis based on regions of interest (ROI) to examine interhemispheric connectivity and investigated intergroup differences in gray/white matter volume by means of voxel-based morphometry. We found a higher connectivity in MCS plus as compared to MCS minus in the left FPN, specifically between the left dorso-lateral prefrontal cortex and left temporo-occipital fusiform cortex. No differences between patient groups were observed in the auditory network, right FPN, DMN, thalamocortical and interhemispheric connectivity, between-network anticorrelations and gray/white matter volume. Our preliminary group-level results suggest that the clinical subcategorization of MCS may involve functional connectivity differences in a language-related executive control network. MCS plus and minus patients are seemingly not differentiated by networks associated to auditory processing, perception of surroundings and internal awareness/self-mentation, nor by interhemispheric integration and structural brain damage.

Regional brain volumetry and brain function in severely brain-injured patients.

OBJECTIVE: The relationship between residual brain tissue in patients with disorders of consciousness (DOC) and the clinical condition is unclear. This observational study aimed to quantify gray (GM) and white matter (WM) atrophy in states of (altered) consciousness. METHODS: Structural T1-weighted magnetic resonance images were processed for 102 severely brain-injured and 52 healthy subjects. Regional brain volume was quantified for 158 (sub)cortical regions using Freesurfer. The relationship between regional brain volume and clinical characteristics of patients with DOC and conscious brain-injured patients was assessed using a linear mixed-effects model. Classification of patients with unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS) using regional volumetric information was performed and compared to classification using cerebral glucose uptake from fluorodeoxyglucose positron emission tomography. For validation, the T1-based classifier was tested on independent datasets. RESULTS: Patients were characterized by smaller regional brain volumes than healthy subjects. Atrophy occurred faster in UWS compared to MCS (GM) and conscious (GM and WM) patients. Classification was successful (misclassification with leave-one-out cross-validation between 2% and 13%) and generalized to the independent data set with an area under the receiver operator curve of 79% (95% confidence interval [CI; 67-91.5]) for GM and 70% (95% CI [55.6-85.4]) for WM. INTERPRETATION: Brain volumetry at the single-subject level reveals that regions in the default mode network and subcortical gray matter regions, as well as white matter regions involved in long range connectivity, are most important to distinguish levels of consciousness. Our findings suggest that changes of brain structure provide information in addition to the assessment of functional neuroimaging and thus should be evaluated as well. Ann Neurol 2018;83:842-853.

Use of brain diffusion tensor imaging for the prediction of long-term neurological outcomes in patients after cardiac arrest: a multicentre, international, prospective, observational, cohort study.

BACKGROUND: Prediction of neurological outcome after cardiac arrest is a major challenge. The aim of this study was to assess whether quantitative whole-brain white matter fractional anisotropy (WWM-FA) measured by diffusion tensor imaging between day 7 and day 28 after cardiac arrest can predict long-term neurological outcome. METHODS: This prospective, observational, cohort study (part of the MRI-COMA study) was done in 14 centres in France, Italy, and Belgium. We enrolled patients aged 18 years or older who had been unconscious for at least 7 days after cardiac arrest into the derivation cohort. The following year, we recruited the validation cohort on the same basis. We also recruited a minimum of five healthy volunteers at each centre for the normalisation procedure. WWM-FA values were compared with standard criteria for unfavourable outcome, conventional MRI sequences (fluid-attenuated inversion recovery and diffusion-weighted imaging), and proton magnetic resonance spectroscopy. The primary outcome was the best achieved Glasgow-Pittsburgh Cerebral Performance Categories (CPC) at 6 months, dichotomised as favourable (CPC 1-2) and unfavourable outcome (CPC 3-5). Prognostication performance was assessed by the area under the receiver operating characteristic (ROC) curves and compared between groups. This study was registered with ClinicalTrials.gov, number NCT00577954. FINDINGS: Between Oct 1, 2006, and June 30, 2014, 185 patients were enrolled in the derivation cohort, of whom 150 had an interpretable multimodal MRI and were included in the analysis. 33 (22%) patients had a favourable neurological outcome at 6 months. Prognostic accuracy, as quantified by the area under the ROC curve, was significantly higher with the normalised WWM-FA value (area under the ROC curve 0·95, 95% CI 0·91-0·98) than with the standard criteria for unfavourable outcome or other MRI sequences. In a subsequent validation cohort of 50 patients (enrolled between April 1, 2015, and March 31, 2016), a normalised WWM-FA value lower than 0·91, set from the derivation cohort, had a negative predictive value of 71·4% (95% CI 41·9-91·6) and a positive predictive value of 100% (90·0-100), with 89·7% sensitivity (75·8-97·1) and 100% specificity (69·1-100) for the prediction of unfavourable outcome. INTERPRETATION: In patients who are unconscious 7 days after cardiac arrest, the normalised WWM-FA value, measured by diffusion tensor imaging, could be used to accurately predict neurological outcome at 6 months. This evidence requires confirmation from future large-scale trials with a strict protocol of withdrawal or limitation-of-care decisions and time window for MRI. FUNDING: French Ministry of Health, French National Agency for Research, Italian Ministry of Health, and Regione Lombardia.

Segmentation of white matter hyperintensities using convolutional neural networks with global spatial information in routine clinical brain MRI with none or mild vascular pathology.

We propose an adaptation of a convolutional neural network (CNN) scheme proposed for segmenting brain lesions with considerable mass-effect, to segment white matter hyperintensities (WMH) characteristic of brains with none or mild vascular pathology in routine clinical brain magnetic resonance images (MRI). This is a rather difficult segmentation problem because of the small area (i.e., volume) of the WMH and their similarity to non-pathological brain tissue. We investigate the effectiveness of the 2D CNN scheme by comparing its performance against those obtained from another deep learning approach: Deep Boltzmann Machine (DBM), two conventional machine learning approaches: Support Vector Machine (SVM) and Random Forest (RF), and a public toolbox: Lesion Segmentation Tool (LST), all reported to be useful for segmenting WMH in MRI. We also introduce a way to incorporate spatial information in convolution level of CNN for WMH segmentation named global spatial information (GSI). Analysis of covariance corroborated known associations between WMH progression, as assessed by all methods evaluated, and demographic and clinical data. Deep learning algorithms outperform conventional machine learning algorithms by excluding MRI artefacts and pathologies that appear similar to WMH. Our proposed approach of incorporating GSI also successfully helped CNN to achieve better automatic WMH segmentation regardless of network's settings tested. The mean Dice Similarity Coefficient (DSC) values for LST-LGA, SVM, RF, DBM, CNN and CNN-GSI were 0.2963, 0.1194, 0.1633, 0.3264, 0.5359 and 5389 respectively.

Multifaceted brain networks reconfiguration in disorders of consciousness uncovered by co-activation patterns.

INTRODUCTION: Given that recent research has shown that functional connectivity is not a static phenomenon, we aim to investigate the dynamic properties of the default mode network's (DMN) connectivity in patients with disorders of consciousness. METHODS: Resting-state fMRI volumes of a convenience sample of 17 patients in unresponsive wakefulness syndrome (UWS) and controls were reduced to a spatiotemporal point process by selecting critical time points in the posterior cingulate cortex (PCC). Spatial clustering was performed on the extracted PCC time frames to obtain 8 different co-activation patterns (CAPs). We investigated spatial connectivity patterns positively and negatively correlated with PCC using both CAPs and standard stationary method. We calculated CAPs occurrences and the total number of frames. RESULTS: Compared to controls, patients showed (i) decreased within-network positive correlations and between-network negative correlations, (ii) emergence of "pathological" within-network negative correlations and between-network positive correlations (better defined with CAPs), and (iii) "pathological" increases in within-network positive correlations and between-network negative correlations (only detectable using CAPs). Patients showed decreased occurrence of DMN-like CAPs (1-2) compared to controls. No between-group differences were observed in the total number of frames CONCLUSION: CAPs reveal at a more fine-grained level the multifaceted spatial connectivity reconfiguration following the DMN disruption in UWS patients, which is more complex than previously thought and suggests alternative anatomical substrates for consciousness. BOLD fluctuations do not seem to differ between patients and controls, suggesting that BOLD response represents an intrinsic feature of the signal, and therefore that spatial configuration is more important for consciousness than BOLD activation itself. Hum Brain Mapp 39:89-103, 2018. © 2017 Wiley Periodicals, Inc.

Early Functional Connectome Integrity and 1-Year Recovery in Comatose Survivors of Cardiac Arrest.

Purpose To assess whether early brain functional connectivity is associated with functional recovery 1 year after cardiac arrest (CA). Materials and Methods Enrolled in this prospective multicenter cohort were 46 patients who were comatose after CA. Principal outcome was cerebral performance category at 12 months, with favorable outcome (FO) defined as cerebral performance category 1 or 2. All participants underwent multiparametric structural and functional magnetic resonance (MR) imaging less than 4 weeks after CA. Within- and between-network connectivity was measured in dorsal attention network (DAN), default-mode network (DMN), salience network (SN), and executive control network (ECN) by using seed-based analysis of resting-state functional MR imaging data. Structural changes identified with fluid-attenuated inversion recovery and diffusion-weighted imaging sequences were analyzed by using validated morphologic scales. The association between connectivity measures, structural changes, and the principal outcome was explored with multivariable modeling. Results Patients underwent MR imaging a mean 12.6 days ± 5.6 (standard deviation) after CA. At 12 months, 11 patients had an FO. Patients with FO had higher within-DMN connectivity and greater anticorrelation between SN and DMN and between SN and ECN compared with patients with unfavorable outcome, an effect that was maintained after multivariable adjustment. Anticorrelation of SN-DMN predicted outcomes with higher accuracy than fluid-attenuated inversion recovery or diffusion-weighted imaging scores (area under the receiver operating characteristic curves, respectively, 0.88, 0.74, and 0.71). Conclusion MR imaging-based measures of cerebral functional network connectivity obtained in the acute phase of CA were independently associated with FO at 1 year, warranting validation as early markers of long-term recovery potential in patients with anoxic-ischemic encephalopathy. © RSNA, 2017.

A method for independent component graph analysis of resting-state fMRI.

INTRODUCTION: Independent component analysis (ICA) has been extensively used for reducing task-free BOLD fMRI recordings into spatial maps and their associated time-courses. The spatially identified independent components can be considered as intrinsic connectivity networks (ICNs) of non-contiguous regions. To date, the spatial patterns of the networks have been analyzed with techniques developed for volumetric data. OBJECTIVE: Here, we detail a graph building technique that allows these ICNs to be analyzed with graph theory. METHODS: First, ICA was performed at the single-subject level in 15 healthy volunteers using a 3T MRI scanner. The identification of nine networks was performed by a multiple-template matching procedure and a subsequent component classification based on the network "neuronal" properties. Second, for each of the identified networks, the nodes were defined as 1,015 anatomically parcellated regions. Third, between-node functional connectivity was established by building edge weights for each networks. Group-level graph analysis was finally performed for each network and compared to the classical network. RESULTS: Network graph comparison between the classically constructed network and the nine networks showed significant differences in the auditory and visual medial networks with regard to the average degree and the number of edges, while the visual lateral network showed a significant difference in the small-worldness. CONCLUSIONS: This novel approach permits us to take advantage of the well-recognized power of ICA in BOLD signal decomposition and, at the same time, to make use of well-established graph measures to evaluate connectivity differences. Moreover, by providing a graph for each separate network, it can offer the possibility to extract graph measures in a specific way for each network. This increased specificity could be relevant for studying pathological brain activity or altered states of consciousness as induced by anesthesia or sleep, where specific networks are known to be altered in different strength.

Brain plasticity after implanted peroneal nerve electrical stimulation to improve gait in chronic stroke patients: Two case reports.

BACKGROUND: Recent studies have shown that stimulation of the peroneal nerve using an implantable 4-channel peroneal nerve stimulator could improve gait in stroke patients. OBJECTIVES: To assess structural cortical and regional cerebral metabolism changes associated with an implanted peroneal nerve electrical stimulator to correct foot drop related to a central nervous system lesion. METHODS: Two stroke patients presenting a foot drop related to a central nervous system lesion were implanted with an implanted peroneal nerve electrical stimulator. Both patients underwent clinical evaluations before implantation and one year after the activation of the stimulator. Structural magnetic resonance imaging (MRI) and [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) were acquired before and one year after the activation of the stimulator. RESULTS: Foot drop was corrected for both patients after the implantation of the stimulator. After one year of treatment, patient 1 improved in three major clinical tests, while patient 2 only improved in one test. Prior to treatment, FDG-PET showed a significant hypometabolism in premotor, primary and supplementary motor areas in both patients as compared to controls, with patient 2 presenting more widespread hypometabolism. One year after the activation of the stimulator, both patients showed significantly less hypometabolism in the damaged motor cortex. No difference was observed on the structural MRI. CONCLUSION: Clinical improvement of gait under peroneal nerve electrical stimulation in chronic stroke patients presenting foot drop was paralleled to metabolic changes in the damaged motor cortex.

Mapping the functional connectome traits of levels of consciousness.

Examining task-free functional connectivity (FC) in the human brain offers insights on how spontaneous integration and segregation of information relate to human cognition, and how this organization may be altered in different conditions, and neurological disorders. This is particularly relevant for patients in disorders of consciousness (DOC) following severe acquired brain damage and coma, one of the most devastating conditions in modern medical care. We present a novel data-driven methodology, connICA, which implements Independent Component Analysis (ICA) for the extraction of robust independent FC patterns (FC-traits) from a set of individual functional connectomes, without imposing any a priori data stratification into groups. We here apply connICA to investigate associations between network traits derived from task-free FC and cognitive/clinical features that define levels of consciousness. Three main independent FC-traits were identified and linked to consciousness-related clinical features. The first one represents the functional configuration of a "resting" human brain, and it is associated to a sedative (sevoflurane), the overall effect of the pathology and the level of arousal. The second FC-trait reflects the disconnection of the visual and sensory-motor connectivity patterns. It also relates to the time since the insult and to the ability of communicating with the external environment. The third FC-trait isolates the connectivity pattern encompassing the fronto-parietal and the default-mode network areas as well as the interaction between left and right hemispheres, which are also associated to the awareness of the self and its surroundings. Each FC-trait represents a distinct functional process with a role in the degradation of conscious states of functional brain networks, shedding further light on the functional sub-circuits that get disrupted in severe brain-damage.