Human brain state dynamics are highly reproducible and associated with neural and behavioral features.

Neural activity and behavior vary within an individual (states) and between individuals (traits). However, the mapping of state-trait neural variation to behavior is not well understood. To address this gap, we quantify moment-to-moment changes in brain-wide co-activation patterns derived from resting-state functional magnetic resonance imaging. In healthy young adults, we identify reproducible spatiotemporal features of co-activation patterns at the single-subject level. We demonstrate that a joint analysis of state-trait neural variations and feature reduction reveal general motifs of individual differences, encompassing state-specific and general neural features that exhibit day-to-day variability. The principal neural variations co-vary with the principal variations of behavioral phenotypes, highlighting cognitive function, emotion regulation, alcohol and substance use. Person-specific probability of occupying a particular co-activation pattern is reproducible and associated with neural and behavioral features. This combined analysis of state-trait variations holds promise for developing reproducible neuroimaging markers of individual life functional outcome.

An altered balance of integrated and segregated brain activity is a marker of cognitive deficits following sleep deprivation.

Sleep deprivation (SD) leads to impairments in cognitive function. Here, we tested the hypothesis that cognitive changes in the sleep-deprived brain can be explained by information processing within and between large-scale cortical networks. We acquired functional magnetic resonance imaging (fMRI) scans of 20 healthy volunteers during attention and executive tasks following a regular night of sleep, a night of SD, and a recovery nap containing nonrapid eye movement (NREM) sleep. Overall, SD was associated with increased cortex-wide functional integration, driven by a rise of integration within cortical networks. The ratio of within versus between network integration in the cortex increased further in the recovery nap, suggesting that prolonged wakefulness drives the cortex towards a state resembling sleep. This balance of integration and segregation in the sleep-deprived state was tightly associated with deficits in cognitive performance. This was a distinct and better marker of cognitive impairment than conventional indicators of homeostatic sleep pressure, as well as the pronounced thalamocortical connectivity changes that occurs towards falling asleep. Importantly, restoration of the balance between segregation and integration of cortical activity was also related to performance recovery after the nap, demonstrating a bidirectional effect. These results demonstrate that intra- and interindividual differences in cortical network integration and segregation during task performance may play a critical role in vulnerability to cognitive impairment in the sleep-deprived state.

Arousal impacts distributed hubs modulating the integration of brain functional connectivity.

Even when subjects are at rest, it is thought that brain activity is organized into distinct brain states during which reproducible patterns are observable. Yet, it is unclear how to define or distinguish different brain states. A potential source of brain state variation is arousal, which may play a role in modulating functional interactions between brain regions. Here, we use simultaneous resting state functional magnetic resonance imaging (fMRI) and pupillometry to study the impact of arousal levels indexed by pupil area on the integration of large-scale brain networks. We employ a novel sparse dictionary learning-based method to identify hub regions participating in between-network integration stratified by arousal, by measuring k-hubness, the number (k) of functionally overlapping networks in each brain region. We show evidence of a brain-wide decrease in between-network integration and inter-subject variability at low relative to high arousal, with differences emerging across regions of the frontoparietal, default mode, motor, limbic, and cerebellum networks. State-dependent changes in k-hubness relate to the actual patterns of network integration within these hubs, suggesting a brain state transition from high to low arousal characterized by global synchronization and reduced network overlaps. We demonstrate that arousal is not limited to specific brain areas known to be directly associated with arousal regulation, but instead has a brain-wide impact that involves high-level between-network communications. Lastly, we show a systematic change in pairwise fMRI signal correlation structures in the arousal state-stratified data, and demonstrate that the choice of global signal regression could result in different conclusions in conventional graph theoretical analysis and in the analysis of k-hubness when studying arousal modulations. Together, our results suggest the presence of global and local effects of pupil-linked arousal modulations on resting state brain functional connectivity.

SPARK: Sparsity-based analysis of reliable k-hubness and overlapping network structure in brain functional connectivity.

Functional hubs are defined as the specific brain regions with dense connections to other regions in a functional brain network. Among them, connector hubs are of great interests, as they are assumed to promote global and hierarchical communications between functionally specialized networks. Damage to connector hubs may have a more crucial effect on the system than does damage to other hubs. Hubs in graph theory are often identified from a correlation matrix, and classified as connector hubs when the hubs are more connected to regions in other networks than within the networks to which they belong. However, the identification of hubs from functional data is more complex than that from structural data, notably because of the inherent problem of multicollinearity between temporal dynamics within a functional network. In this context, we developed and validated a method to reliably identify connectors and corresponding overlapping network structure from resting-state fMRI. This new method is actually handling the multicollinearity issue, since it does not rely on counting the number of connections from a thresholded correlation matrix. The novelty of the proposed method is that besides counting the number of networks involved in each voxel, it allows us to identify which networks are actually involved in each voxel, using a data-driven sparse general linear model in order to identify brain regions involved in more than one network. Moreover, we added a bootstrap resampling strategy to assess statistically the reproducibility of our results at the single subject level. The unified framework is called SPARK, i.e. SParsity-based Analysis of Reliable k-hubness, where k-hubness denotes the number of networks overlapping in each voxel. The accuracy and robustness of SPARK were evaluated using two dimensional box simulations and realistic simulations that examined detection of artificial hubs generated on real data. Then, test/retest reliability of the method was assessed using the 1000 Functional Connectome Project database, which includes data obtained from 25 healthy subjects at three different occasions with long and short intervals between sessions. We demonstrated that SPARK provides an accurate and reliable estimation of k-hubness, suggesting a promising tool for understanding hub organization in resting-state fMRI.

Sparse SPM: Group Sparse-dictionary learning in SPM framework for resting-state functional connectivity MRI analysis.

Recent studies of functional connectivity MR imaging have revealed that the default-mode network activity is disrupted in diseases such as Alzheimer's disease (AD). However, there is not yet a consensus on the preferred method for resting-state analysis. Because the brain is reported to have complex interconnected networks according to graph theoretical analysis, the independency assumption, as in the popular independent component analysis (ICA) approach, often does not hold. Here, rather than using the independency assumption, we present a new statistical parameter mapping (SPM)-type analysis method based on a sparse graph model where temporal dynamics at each voxel position are described as a sparse combination of global brain dynamics. In particular, a new concept of a spatially adaptive design matrix has been proposed to represent local connectivity that shares the same temporal dynamics. If we further assume that local network structures within a group are similar, the estimation problem of global and local dynamics can be solved using sparse dictionary learning for the concatenated temporal data across subjects. Moreover, under the homoscedasticity variance assumption across subjects and groups that is often used in SPM analysis, the aforementioned individual and group analyses using sparse dictionary learning can be accurately modeled by a mixed-effect model, which also facilitates a standard SPM-type group-level inference using summary statistics. Using an extensive resting fMRI data set obtained from normal, mild cognitive impairment (MCI), and Alzheimer's disease patient groups, we demonstrated that the changes in the default mode network extracted by the proposed method are more closely correlated with the progression of Alzheimer's disease.

NREM sleep brain networks modulate cognitive recovery from sleep deprivation.

Decrease in cognitive performance after sleep deprivation followed by recovery after sleep suggests its key role, and especially non-rapid eye movement (NREM) sleep, in the maintenance of cognition. It remains unknown whether brain network reorganization in NREM sleep stages N2 and N3 can uniquely be mapped onto individual differences in cognitive performance after a recovery nap following sleep deprivation. Using resting state functional magnetic resonance imaging (fMRI), we quantified the integration and segregation of brain networks during NREM sleep stages N2 and N3 while participants took a 1-hour nap following 24-hour sleep deprivation, compared to well-rested wakefulness. Here, we advance a new analytic framework called the hierarchical segregation index (HSI) to quantify network segregation across spatial scales, from whole-brain to the voxel level, by identifying spatio-temporally overlapping large-scale networks and the corresponding voxel-to-region hierarchy. Our results show that network segregation increased in the default mode, dorsal attention and somatomotor networks during NREM sleep compared to wakefulness. Segregation within the visual, limbic, and executive control networks exhibited N2 versus N3 sleep-specific voxel-level patterns. More segregation during N3 was associated with worse recovery of working memory, executive attention, and psychomotor vigilance after the nap. The level of spatial resolution of network segregation varied among brain regions and was associated with the recovery of performance in distinct cognitive tasks. We demonstrated the sensitivity and reliability of voxel-level HSI to provide key insights into within-region variation, suggesting a mechanistic understanding of how NREM sleep replenishes cognition after sleep deprivation.

Visible-Light-Induced DDQ-Catalyzed Fluorocarbamoylation Using CF3SO2Na and Oxygen.

The synthesis of carbamoyl fluorides via visible-light induced DDQ catalysis of secondary amines is described. This protocol employs sodium trifluorosulfinate and molecular oxygen for the in situ generation of carbonyl difluoride, which is reacted with amines to afford the corresponding carbamoyl fluorides efficiently. Moreover, carbamoyl fluorides are easily transformed to synthetically useful carbonyl compounds under mild reaction conditions.

Human brain state dynamics reflect individual neuro-phenotypes.

Neural activity and behavior manifest state and trait dynamics, as well as variation within and between individuals. However, the mapping of state-trait neural variation to behavior is not well understood. To address this gap, we quantify moment-to-moment changes in brain-wide co-activation patterns derived from resting-state functional magnetic resonance imaging. In healthy young adults, we identify reproducible spatio-temporal features of co-activation patterns at the single subject level. We demonstrate that a joint analysis of state-trait neural variations and feature reduction reveal general motifs of individual differences, encompassing state-specific and general neural features that exhibit day-to-day variability. The principal neural variations co-vary with the principal variations of behavioral phenotypes, highlighting cognitive function, emotion regulation, alcohol and substance use. Person-specific probability of occupying a particular co-activation pattern is reproducible and associated with neural and behavioral features. This combined analysis of state-trait variations holds promise for developing reproducible neuroimaging markers of individual life functional outcome.

A common symptom geometry of mood improvement under sertraline and placebo associated with distinct neural patterns.

Importance: Understanding the mechanisms of major depressive disorder (MDD) improvement is a key challenge to determine effective personalized treatments. Objective: To perform a secondary analysis quantifying neural-to-symptom relationships in MDD as a function of antidepressant treatment. Design: Double blind randomized controlled trial. Setting: Multicenter. Participants: Patients with early onset recurrent depression from the public Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study. Interventions: Either sertraline or placebo during 8 weeks (stage 1), and according to response a second line of treatment for 8 additional weeks (stage 2). Main Outcomes and Measures: To identify a data-driven pattern of symptom variations during these two stages, we performed a Principal Component Analysis (PCA) on the variations of individual items of four clinical scales measuring depression, anxiety, suicidal ideas and manic-like symptoms, resulting in a univariate measure of clinical improvement. We then investigated how initial clinical and neural factors predicted this measure during stage 1. To do so, we extracted resting-state global brain connectivity (GBC) at baseline at the individual level using a whole-brain functional network parcellation. In turn, we computed a linear model for each brain parcel with individual data-driven clinical improvement scores during stage 1 for each group. Results: 192 patients (127 women), age 37.7 years old (standard deviation: 13.5), were included. The first PC (PC1) capturing 20% of clinical variation was similar across treatment groups at stage 1 and stage 2, suggesting a reproducible pattern of symptom improvement. PC1 patients' scores significantly differed according to treatment during stage 1, whereas no difference of response was evidenced between groups with the Clinical Global Impressions (CGI). Baseline GBC correlated to stage 1 PC1 scores in the sertraline, but not in the placebo group. Conclusions and Relevance: Using data-driven reduction of symptoms scales, we identified a common profile of symptom improvement across placebo and sertraline. However, the neural patterns of baseline that mapped onto symptom improvement distinguished between treatment and placebo. Our results underscore that mapping from data-driven symptom improvement onto neural circuits is vital to detect treatment-responsive neural profiles that may aid in optimal patient selection for future trials.

Zero Energy Heating of Solvent with Network-Structured Solar-Thermal Material: Eco-Friendly Palladium Catalysis of the Suzuki Reaction.

Solar-thermal materials absorb sunlight and convert it into heat, which is released into the surrounding medium. Utilization of solar energy for solvent heating can be a potential method of eco-friendly organic reactions. However, to date, significant heating of the entire volume of a solvent by 1 sun illumination has not been reported. In the present work, a network structure of solar-thermal materials has been proposed for zero energy heating of a solvent under 1 sun illumination. A network-structured solar-thermal material with an additional catalytic function was fabricated by sputtering palladium into a melamine sponge. The nanocrystalline palladium-decorated melamine sponge (Pd-sponge) has excellent sunlight absorption properties in the entire wavelength range that enable efficient solar-thermal conversion. The Pd-sponge can reduce heat loss to the surroundings by effectively blocking thermal radiation from the heated solvent. The temperature of the reaction solution with the ethanol-water mixture filled in the Pd-sponge increased from 23 to 59 °C under 1 sun illumination. The elevated temperature of the reaction solutions by solar-thermal conversion successfully accelerated the heterogeneous Pd-catalyzed Suzuki coupling reactions with high conversions. Easy and low-energy-consuming multicycle use of the solar-thermal and catalytic properties of the Pd-sponge has also been demonstrated.

A protocol for working with open-source neuroimaging datasets.

Large, publicly available neuroimaging datasets are becoming increasingly common, but their use presents challenges because of insufficient knowledge of the tool options for data processing and proper data organization. Here, we describe a protocol to lessen these barriers. We describe the steps for the search and download of the open-source dataset. We detail the steps for proper data management and practical guidelines for data analysis. Finally, we give instructions for data and result sharing on public repositories and preprint services. For complete details on the use and execution of this profile, please refer to Horien et al. (2021).

A hitchhiker's guide to working with large, open-source neuroimaging datasets.

Large datasets that enable researchers to perform investigations with unprecedented rigor are growing increasingly common in neuroimaging. Due to the simultaneous increasing popularity of open science, these state-of-the-art datasets are more accessible than ever to researchers around the world. While analysis of these samples has pushed the field forward, they pose a new set of challenges that might cause difficulties for novice users. Here we offer practical tips for working with large datasets from the end-user's perspective. We cover all aspects of the data lifecycle: from what to consider when downloading and storing the data to tips on how to become acquainted with a dataset one did not collect and what to share when communicating results. This manuscript serves as a practical guide one can use when working with large neuroimaging datasets, thus dissolving barriers to scientific discovery.

Low-motion fMRI data can be obtained in pediatric participants undergoing a 60-minute scan protocol.

Performing functional magnetic resonance imaging (fMRI) scans of children can be a difficult task, as participants tend to move while being scanned. Head motion represents a significant confound in fMRI connectivity analyses. One approach to limit motion has been to use shorter MRI protocols, though this reduces the reliability of results. Hence, there is a need to implement methods to achieve high-quality, low-motion data while not sacrificing data quantity. Here we show that by using a mock scan protocol prior to a scan, in conjunction with other in-scan steps (weighted blanket and incentive system), it is possible to achieve low-motion fMRI data in pediatric participants (age range: 7-17 years old) undergoing a 60 min MRI session. We also observe that motion is low during the MRI protocol in a separate replication group of participants, including some with autism spectrum disorder. Collectively, the results indicate it is possible to conduct long scan protocols in difficult-to-scan populations and still achieve high-quality data, thus potentially allowing more reliable fMRI findings.

Automatic classification and removal of structured physiological noise for resting state functional connectivity MRI analysis.

Resting state functional magnetic resonance imaging is used to study how brain regions are functionally connected by measuring temporal correlation of the fMRI signals, when a subject is at rest. Sparse dictionary learning is used to estimate a dictionary of resting state networks by decomposing the whole brain signals into several temporal features (atoms), each being shared by a set of voxels associated to a network. Recently, we proposed and validated a new method entitled Sparsity-based Analysis of Reliable K-hubness (SPARK), suggesting that connector hubs of brain networks participating in inter-network communication can be identified by counting the number of atoms involved in each voxel (sparse number k). However, such hub analysis can be corrupted by the presence of noise-related atoms, where physiological fluctuations in cardiorespiratory processes may remain even after band-pass filtering and regression of confound signals from the white matter and cerebrospinal fluid. Handling this issue might require manual classification of noisy atoms, which is a time-consuming and subjective task. Motivated by the fact that the physiological fluctuations are often localized in tissues close to large vasculatures, i.e. sagittal sinus, we propose an automatic classification of physiological noise-related atoms for SPARK using spatial priors and a stepwise regression procedure. We measured the degree to which the noise-characteristic time-courses within the mask are explained by each atom, and classified noise-related atoms using a subject-specific threshold estimated using a bootstrap resampling based strategy. Using real data from healthy subjects (N = 25), manual classification of the atoms by two independent reviewers showed the presence of sagittal sinus related noise in 65% of the runs. Applying the same manual classification after the proposed automatic removal method reduced this rate to 19%. A 10-fold cross-validation on real data showed good specificity and accuracy of the proposed automated method in classifying the target noise (area under the ROC curve= 0.89), when compared to the manual classification considered as the reference. We demonstrated decrease in k-hubness values in the voxels involved in the sagittal sinus at both individual and group levels, suggesting a significant improvement of SPARK, which is particularly important when considering clinical applications.

Disruption, emergence and lateralization of brain network hubs in mesial temporal lobe epilepsy.

Hubs of brain networks are brain regions exhibiting denser connections than others, promoting long-range communication. Studies suggested the reorganization of hubs in epilepsy. The patterns of connector hub abnormalities specific to mesial temporal lobe epilepsy (mTLE) are unclear. We wish to quantify connector hub abnormalities in mTLE and identify epilepsy-related resting state networks involving abnormal connector hubs. A recently developed sparsity-based analysis of reliable k-hubness (SPARK) allowed us to address this question by using resting state functional MRI in 20 mTLE patients and 17 healthy controls. Handling the multicollinearity of functional networks, SPARK measures a new metric of hubness by counting the number (k) of networks involved in each voxel, and identifies which networks are actually associated to each connector hub. This measure provides new information about the network architecture involving connector hubs and a realistic range of k-hubness. We quantified the disruption and emergence of connector hubs in individual epileptic subjects and assessed the lateralization of networks involving connector hubs. In mTLE, we found pathological disruptions of normal connector hubs in the mTL and within the default mode network. Right mTLE had remarkably higher emergence of new connector hubs in the mTL than left mTLE. Different patterns of lateralization of the salience network involving the abnormal hippocampus were found in right versus left mTLE. The temporal, cerebellar, default mode, subcortical and motor networks also contributed to the lateralization of hippocampal networks. We finally observed an asymmetrical connector hub reorganization and overall regularization of epilepsy-related resting state networks in mTLE, characterized by the disruption of distant connections and the emergence of local connections.

Detection of abnormal resting-state networks in individual patients suffering from focal epilepsy: an initial step toward individual connectivity assessment.

The spatial coherence of spontaneous slow fluctuations in the blood-oxygen-level dependent (BOLD) signal at rest is routinely used to characterize the underlying resting-state networks (RSNs). Studies have demonstrated that these patterns are organized in space and highly reproducible from subject to subject. Moreover, RSNs reorganizations have been suggested in pathological conditions. Comparisons of RSNs organization have been performed between groups of subjects but have rarely been applied at the individual level, a step required for clinical application. Defining the notion of modularity as the organization of brain activity in stable networks, we propose Detection of Abnormal Networks in Individuals (DANI) to identify modularity changes at the individual level. The stability of each RSN was estimated using a spatial clustering method: Bootstrap Analysis of Stable Clusters (BASC) (Bellec et al., 2010). Our contributions consisted in (i) providing functional maps of the most stable cores of each networks and (ii) in detecting "abnormal" individual changes in networks organization when compared to a population of healthy controls. DANI was first evaluated using realistic simulated data, showing that focussing on a conservative core size (50% most stable regions) improved the sensitivity to detect modularity changes. DANI was then applied to resting state fMRI data of six patients with focal epilepsy who underwent multimodal assessment using simultaneous EEG/fMRI acquisition followed by surgery. Only patient with a seizure free outcome were selected and the resected area was identified using a post-operative MRI. DANI automatically detected abnormal changes in 5 out of 6 patients, with excellent sensitivity, showing for each of them at least one "abnormal" lateralized network closely related to the epileptic focus. For each patient, we also detected some distant networks as abnormal, suggesting some remote reorganization in the epileptic brain.

A data-driven sparse GLM for fMRI analysis using sparse dictionary learning with MDL criterion.

We propose a novel statistical analysis method for functional magnetic resonance imaging (fMRI) to overcome the drawbacks of conventional data-driven methods such as the independent component analysis (ICA). Although ICA has been broadly applied to fMRI due to its capacity to separate spatially or temporally independent components, the assumption of independence has been challenged by recent studies showing that ICA does not guarantee independence of simultaneously occurring distinct activity patterns in the brain. Instead, sparsity of the signal has been shown to be more promising. This coincides with biological findings such as sparse coding in V1 simple cells, electrophysiological experiment results in the human medial temporal lobe, etc. The main contribution of this paper is, therefore, a new data driven fMRI analysis that is derived solely based upon the sparsity of the signals. A compressed sensing based data-driven sparse generalized linear model is proposed that enables estimation of spatially adaptive design matrix as well as sparse signal components that represent synchronous, functionally organized and integrated neural hemodynamics. Furthermore, a minimum description length (MDL)-based model order selection rule is shown to be essential in selecting unknown sparsity level for sparse dictionary learning. Using simulation and real fMRI experiments, we show that the proposed method can adapt individual variation better compared to the conventional ICA methods.

Quantification of CMRO(2) without hypercapnia using simultaneous near-infrared spectroscopy and fMRI measurements.

Estimation of the cerebral metabolic rate of oxygen (CMRO(2)) and cerebral blood flow (CBF) is important to investigate the neurovascular coupling and physiological components in blood oxygenation level-dependent (BOLD) signals quantitatively. Although there are methods that can determine CMRO(2) changes using functional MRI (fMRI) or near-infrared spectroscopy (NIRS), current approaches require a separate hypercapnia calibration process and have the potential to incur bias in many assumed model parameters. In this paper, a novel method to estimate CMRO(2) without hypercapnia is described using simultaneous measurements of NIRS and fMRI. Specifically, an optimization framework is proposed that minimizes the differences between the two forms of the relative CMRO(2)-CBF coupling ratio from BOLD and NIRS biophysical models, from which hypercapnia calibration and model parameters are readily estimated. Based on the new methods, we found that group average CBF, CMRO(2), cerebral blood volume (CBV), and BOLD changes within activation of the primary motor cortex during a finger tapping task increased by 39.5 +/- 21.4%, 18.4 +/- 8.7%, 12.9 +/- 6.7%, and 0.5 +/- 0.2%, respectively. The group average estimated flow-metabolism coupling ratio was 2.38 +/- 0.65 and the hypercapnia parameter was 7.7 +/- 1.7%. These values are within the range of values reported from other literatures. Furthermore, the activation maps from CBF and CMRO(2) were well localized on the primary motor cortex, which is the main target region of the finger tapping task.