fMRI Time Series Data Research Articles

The mesolimbic system and the loss of higher order network features in schizophrenia when learning without reward.

Schizophrenia is characterized by a loss of network features between cognition and reward sub-circuits (notably involving the mesolimbic system), and this loss may explain deficits in learning and cognition. Learning in schizophrenia has typically been studied with tasks that include reward related contingencies, but recent theoretical models have argued that a loss of network features should be seen even when learning without reward. We tested this model using a learning paradigm that required participants to learn without reward or feedback. We used a novel method for capturing higher order network features, to demonstrate that the mesolimbic system is heavily implicated in the loss of network features in schizophrenia, even when learning without reward. fMRI data (Siemens Verio 3T) were acquired in a group of schizophrenia patients and controls (n=78; 46 SCZ, 18 ≤ Age ≤ 50) while participants engaged in associative learning without reward-related contingencies. The task was divided into task-active conditions for encoding (of associations) and cued-retrieval (where the cue was to be used to retrieve the associated memoranda). No feedback was provided during retrieval. From the fMRI time series data, network features were defined as follows: First, for each condition of the task, we estimated 2nd order undirected functional connectivity for each participant (uFC, based on zero lag correlations between all pairs of regions). These conventional 2nd order features represent the task/condition evoked synchronization of activity between pairs of brain regions. Next, in each of the patient and control groups, the statistical relationship between all possible pairs of 2nd order features were computed. These higher order features represent the consistency between all possible pairs of 2nd order features in that group and embed within them the contributions of individual regions to such group structure. From the identified inter-group differences (SCZ ≠ HC) in higher order features, we quantified the respective contributions of individual brain regions. Two principal effects emerged: 1) SCZ were characterized by a massive loss of higher order features during multiple task conditions (encoding and retrieval of associations). 2) Nodes in the mesolimbic system were over-represented in the loss of higher order features in SCZ, and notably so during retrieval. Our analytical goals were linked to a recent circuit-based integrative model which argued that synergy between learning and reward circuits is lost in schizophrenia. The model's notable prediction was that such a loss would be observed even when patients learned without reward. Our results provide substantial support for these predictions where we observed a loss of network features between the brain's sub-circuits for a) learning (including the hippocampus and prefrontal cortex) and b) reward processing (specifically constituents of the mesolimbic system that included the ventral tegmental area and the nucleus accumbens. Our findings motivate a renewed appraisal of the relationship between reward and cognition in schizophrenia and we discuss their relevance for putative behavioral interventions.

Dynamicity of brain network organization & their community architecture as characterizing features for classification of common mental disorders from whole-brain connectome

The urgency of addressing common mental disorders (bipolar disorder, attention-deficit hyperactivity disorder (ADHD), and schizophrenia) arises from their significant societal impact. Developing strategies to support psychiatrists is crucial. Previous studies focused on the relationship between these disorders and changes in the resting-state functional connectome’s modularity, often using static functional connectivity (sFC) estimation. However, understanding the dynamic reconfiguration of resting-state brain networks with rich temporal structure is essential for comprehending neural activity and addressing mental health disorders. This study proposes an unsupervised approach combining spatial and temporal characterization of brain networks to classify common mental disorders using fMRI timeseries data from two cohorts (N = 408 participants). We employ the weighted stochastic block model to uncover mesoscale community architecture differences, providing insights into network organization. Our approach overcomes sFC limitations and biases in community detection algorithms by modelling the functional connectome’s temporal dynamics as a landscape, quantifying temporal stability at whole-brain and network levels. Findings reveal individuals with schizophrenia exhibit less assortative community structure and participate in multiple motif classes, indicating less specialized network organization. Patients with schizophrenia and ADHD demonstrate significantly reduced temporal stability compared to healthy controls. This study offers insights into functional connectivity (FC) patterns’ spatiotemporal organization and their alterations in common mental disorders, highlighting the potential of temporal stability as a biomarker.

Integrating Multimodal Neuroimaging and Genetics: A Structurally-Linked Sparse Canonical Correlation Analysis Approach.

Neuroimaging genetics represents a multivariate approach aimed at elucidating the intricate relationships between high-dimensional genetic variations and neuroimaging data. Predominantly, existing methodologies revolve around Sparse Canonical Correlation Analysis (SCCA), a framework we expand to 1) encompass multiple imaging modalities and 2) promote the simultaneous identification of structurally linked features across imaging modalities. The structurally linked brain regions were assessed using diffusion tensor imaging, which quantifies the presence of neuronal fibers, thereby grounding our approach in biologically well-founded prior knowledge within the SCCA model. In our proposed structurally linked SCCA framework, we leverage T1-weighted MRI and functional MRI (fMRI) time series data to delineate both the structural and functional characteristics of the brain. Genetic variations, specifically single nucleotide polymorphisms (SNPs), are also incorporated as a genetic modality. Validation of our methodology was conducted using a simulated dataset and large-scale normative data from the Human Connectome Project (HCP). Our approach demonstrated superior performance compared to existing methods on simulated data and revealed interpretable gene-imaging associations in the real dataset. Thus, our methodology lays the groundwork for elucidating the genetic underpinnings of brain structure and function, thereby providing novel insights into the field of neuroscience. Our code is available at https://github.com/mungegg.

Causal functional connectivity in Alzheimer's disease computed from time series fMRI data.

Functional connectivity between brain regions is known to be altered in Alzheimer's disease and promises to be a biomarker for early diagnosis. Several approaches for functional connectivity obtain an un-directed network representing stochastic associations (correlations) between brain regions. However, association does not necessarily imply causation. In contrast, Causal Functional Connectivity (CFC) is more informative, providing a directed network representing causal relationships between brain regions. In this paper, we obtained the causal functional connectome for the whole brain from resting-state functional magnetic resonance imaging (rs-fMRI) recordings of subjects from three clinical groups: cognitively normal, mild cognitive impairment, and Alzheimer's disease. We applied the recently developed Time-aware PC (TPC) algorithm to infer the causal functional connectome for the whole brain. TPC supports model-free estimation of whole brain CFC based on directed graphical modeling in a time series setting. We compared the CFC outcome of TPC with that of other related approaches in the literature. Then, we used the CFC outcomes of TPC and performed an exploratory analysis of the difference in strengths of CFC edges between Alzheimer's and cognitively normal groups, based on edge-wise p-values obtained by Welch's t-test. The brain regions thus identified are found to be in agreement with literature on brain regions impacted by Alzheimer's disease, published by researchers from clinical/medical institutions.

MP-PCA denoising of fMRI time-series data can lead to artificial activation “spreading”

MP-PCA denoising has become the method of choice for denoising MRI data since it provides an objective threshold to separate the signal components from unwanted thermal noise components. In rodents, thermal noise in the coils is an important source of noise that can reduce the accuracy of activation mapping in fMRI. Further confounding this problem, vendor data often contains zero-filling and other post-processing steps that may violate MP-PCA assumptions. Here, we develop an approach to denoise vendor data and assess activation “spreading” caused by MP-PCA denoising in rodent task-based fMRI data. Data was obtained from N = 3 mice using conventional multislice and ultrafast fMRI acquisitions (1 s and 50 ms temporal resolution, respectively), using a visual stimulation paradigm. MP-PCA denoising produced SNR gains of 64% and 39%, and Fourier Spectral Amplitude (FSA) increases in BOLD maps of 9% and 7% for multislice and ultrafast data, respectively, when using a small [2 2] denoising window. Larger windows provided higher SNR and FSA gains with increased spatial extent of activation that may or may not represent real activation. Simulations showed that MP-PCA denoising can incur activation “spreading” with increased false positive rate and smoother functional maps due to local “bleeding” of principal components, and that the optimal denoising window for improved specificity of functional mapping, based on Dice score calculations, depends on the data's tSNR and functional CNR. This “spreading” effect applies also to another recently proposed low-rank denoising method (NORDIC), although to a lesser degree. Our results bode well for enhancing spatial and/or temporal resolution in future fMRI work, while taking into account the sensitivity/specificity trade-offs of low-rank denoising methods.

Statistical inference for persistent homology applied to simulated fMRI time series data

<p style='text-indent:20px;'>Time-series data are amongst the most widely-used in biomedical sciences, including domains such as functional Magnetic Resonance Imaging (fMRI). Structure within time series data can be captured by the tools of topological data analysis (TDA). Persistent homology is the mostly commonly used data-analytic tool in TDA, and can effectively summarize complex high-dimensional data into an interpretable 2-dimensional representation called a <i>persistence diagram</i>. Existing methods for statistical inference for persistent homology of data depend on an independence assumption being satisfied. While persistent homology can be computed for each time index in a time-series, time-series data often fail to satisfy the independence assumption. This paper develops a statistical test that obviates the independence assumption by implementing a multi-level block sampled Monte Carlo test with sets of persistence diagrams. Its efficacy for detecting task-dependent topological organization is then demonstrated on simulated fMRI data. This new statistical test is therefore suitable for analyzing persistent homology of fMRI data, and of non-independent data in general.</p>

The topology, stability, and instability of learning-induced brain network repertoires in schizophrenia.

There is a paucity of graph theoretic methods applied to task-based data in schizophrenia (SCZ). Tasks are useful for modulating brain network dynamics, and topology. Understanding how changes in task conditions impact inter-group differences in topology can elucidate unstable network characteristics in SCZ. Here, in a group of patients and healthy controls (n = 59 total, 32 SCZ), we used an associative learning task with four distinct conditions (Memory Formation, Post-Encoding Consolidation, Memory Retrieval, and Post-Retrieval Consolidation) to induce network dynamics. From the acquired fMRI time series data, betweenness centrality (BC), a metric of a node's integrative value was used to summarize network topology in each condition. Patients showed (a) differences in BC across multiple nodes and conditions; (b) decreased BC in more integrative nodes, but increased BC in less integrative nodes; (c) discordant node ranks in each of the conditions; and (d) complex patterns of stability and instability of node ranks across conditions. These analyses reveal that task conditions induce highly variegated patterns of network dys-organization in SCZ. We suggest that the dys-connection syndrome that is schizophrenia, is a contextually evoked process, and that the tools of network neuroscience should be oriented toward elucidating the limits of this dys-connection.

Improving the accuracy of single-trial fMRI response estimates using GLMsingle.

Advances in artificial intelligence have inspired a paradigm shift in human neuroscience, yielding large-scale functional magnetic resonance imaging (fMRI) datasets that provide high-resolution brain responses to thousands of naturalistic visual stimuli. Because such experiments necessarily involve brief stimulus durations and few repetitions of each stimulus, achieving sufficient signal-to-noise ratio can be a major challenge. We address this challenge by introducing GLMsingle, a scalable, user-friendly toolbox available in MATLAB and Python that enables accurate estimation of single-trial fMRI responses (glmsingle.org). Requiring only fMRI time-series data and a design matrix as inputs, GLMsingle integrates three techniques for improving the accuracy of trial-wise general linear model (GLM) beta estimates. First, for each voxel, a custom hemodynamic response function (HRF) is identified from a library of candidate functions. Second, cross-validation is used to derive a set of noise regressors from voxels unrelated to the experiment. Third, to improve the stability of beta estimates for closely spaced trials, betas are regularized on a voxel-wise basis using ridge regression. Applying GLMsingle to the Natural Scenes Dataset and BOLD5000, we find that GLMsingle substantially improves the reliability of beta estimates across visually-responsive cortex in all subjects. Comparable improvements in reliability are also observed in a smaller-scale auditory dataset from the StudyForrest experiment. These improvements translate into tangible benefits for higher-level analyses relevant to systems and cognitive neuroscience. We demonstrate that GLMsingle: (i) helps decorrelate response estimates between trials nearby in time; (ii) enhances representational similarity between subjects within and across datasets; and (iii) boosts one-versus-many decoding of visual stimuli. GLMsingle is a publicly available tool that can significantly improve the quality of past, present, and future neuroimaging datasets sampling brain activity across many experimental conditions.

A simplicial analysis of the fMRI data from human brain dynamics under functional cognitive tasks.

The topological analysis of fMRI time series data has recently been used to characterize the identification of patterns of brain activity seen during specific tasks carried out under experimentally controlled conditions. This study uses the methods of algebraic topology to characterize time series networks constructed from fMRI data measured for adult and children populations carrying out differentiated reading tasks. Our pilot study shows that our methods turn out to be capable of identifying distinct differences between the activity of adult and children populations carrying out identical reading tasks. We also see differences between activity patterns seen when subjects recognize word and nonword patterns. The results generalize across different populations, different languages and different active and inactive brain regions.

Sustained attention induces altered effective connectivity of the ascending thalamo-cortical relay in obsessive-compulsive disorder.

Abnormal function of the thalamo-cortical relay is considered a hallmark of obsessive-compulsive disorder (OCD) and aberrant network interactions may underpin many of the clinical and cognitive symptoms that characterize the disorder. Several statistical approaches have been applied to in vivo fMRI data to support the general loss of thalamo-cortical connectivity in OCD. However, (a) few studies have assessed the contextual constraints under which abnormal network interactions arise or (b) have used methods of effective connectivity to understand abnormal network interactions. Effective connectivity is a particularly valuable method as it describes the putative causal influences that brain regions exert over each other, as opposed to the largely statistical consistencies captured in functional connectivity techniques. Here, using dynamic causal modeling (DCM), we evaluated how attention demand induced inter-group differences (HC ≠ OCD) in effective connectivity within a motivated thalamo-cortical network. Of interest was whether these effects were observed on the ascending thalamo-cortical relay, essential for the sensory innervation of the cortex. fMRI time series data from sixty-two participants (OCD, 30; HC, 32) collected using an established sustained attention task were submitted to a space of 162 competing models. Across the space, models distinguished between competing hypotheses of thalamo-cortical interactions. Bayesian model selection (BMS) identified marginally differing likely generative model architectures in OCD and HC groups. Bayesian model averaging (BMA), was used to weight connectivity parameter estimates across all models, with each parameter weighted by each model’s posterior probability, thus providing more stable estimates of effective connectivity. Inferential statistical analyses of estimated parameters revealed two principal results: (1) Significantly reduced intrinsic connectivity of the V1 → SPC pathway in OCD, suggested connective weakness in the early constituents of the dorsal visual pathway; (2) More pertinent with the discovery possibilities afforded by DCM, sustained attention in OCD patients induced significantly reduced contextual modulation of the ascending relay from the thalamus to the prefrontal cortex. These results form an important complement to our understanding of the contextual bases of thalamo-cortical network deficits in OCD, emphasizing vulnerability of the ascending relay.

Alzheimer's Disease Diagnosis and Biomarker Analysis Using Resting-State Functional MRI Functional Brain Network With Multi-Measures Features and Hippocampal Subfield and Amygdala Volume of Structural MRI.

Accurate diagnosis of the initial phase of Alzheimer’s disease (AD) is essential and crucial. The objective of this research was to employ efficient biomarkers for the diagnostic analysis and classification of AD based on combining structural MRI (sMRI) and resting-state functional MRI (rs-fMRI). So far, several anatomical MRI imaging markers for AD diagnosis have been identified. The use of cortical and subcortical volumes, the hippocampus, and amygdala volume, as well as genetic patterns, has proven to be beneficial in distinguishing patients with AD from the healthy population. The fMRI time series data have the potential for specific numerical information as well as dynamic temporal information. Voxel and graphical analyses have gained popularity for analyzing neurodegenerative diseases, such as Alzheimer’s and its prodromal phase, mild cognitive impairment (MCI). So far, these approaches have been utilized separately for the diagnosis of AD. In recent studies, the classification of cases of MCI into those that are not converted for a certain period as stable MCI (MCIs) and those that converted to AD as MCIc has been less commonly reported with inconsistent results. In this study, we verified and validated the potency of a proposed diagnostic framework to identify AD and differentiate MCIs from MCIc by utilizing the efficient biomarkers obtained from sMRI, along with functional brain networks of the frequency range .01–.027 at the resting state and the voxel-based features. The latter mainly included default mode networks (amplitude of low-frequency fluctuation [ALFF], fractional ALFF [ALFF], and regional homogeneity [ReHo]), degree centrality (DC), and salience networks (SN). Pearson’s correlation coefficient for measuring fMRI functional networks has proven to be an efficient means for disease diagnosis. We applied the graph theory to calculate nodal features (nodal degree [ND], nodal path length [NL], and between centrality [BC]) as a graphical feature and analyzed the connectivity link between different brain regions. We extracted three-dimensional (3D) patterns to calculate regional coherence and then implement a univariate statistical t-test to access a 3D mask that preserves voxels showing significant changes. Similarly, from sMRI, we calculated the hippocampal subfield and amygdala nuclei volume using Freesurfer (version 6). Finally, we implemented and compared the different feature selection algorithms to integrate the structural features, brain networks, and voxel features to optimize the diagnostic identifications of AD using support vector machine (SVM) classifiers. We also compared the performance of SVM with Random Forest (RF) classifiers. The obtained results demonstrated the potency of our framework, wherein a combination of the hippocampal subfield, the amygdala volume, and brain networks with multiple measures of rs-fMRI could significantly enhance the accuracy of other approaches in diagnosing AD. The accuracy obtained by the proposed method was reported for binary classification. More importantly, the classification results of the less commonly reported MCIs vs. MCIc improved significantly. However, this research involved only the AD Neuroimaging Initiative (ADNI) cohort to focus on the diagnosis of AD advancement by integrating sMRI and fMRI. Hence, the study’s primary disadvantage is its small sample size. In this case, the dataset we utilized did not fully reflect the whole population. As a result, we cannot guarantee that our findings will be applicable to other populations.

Biclustering fMRI time series: a comparative study

BackgroundThe effectiveness of biclustering, simultaneous clustering of rows and columns in a data matrix, was shown in gene expression data analysis. Several researchers recognize its potentialities in other research areas. Nevertheless, the last two decades have witnessed the development of a significant number of biclustering algorithms targeting gene expression data analysis and a lack of consistent studies exploring the capacities of biclustering outside this traditional application domain.ResultsThis work evaluates the potential use of biclustering in fMRI time series data, targeting the Region × Time dimensions by comparing seven state-in-the-art biclustering and three traditional clustering algorithms on artificial and real data. It further proposes a methodology for biclustering evaluation beyond gene expression data analysis. The results discuss the use of different search strategies in both artificial and real fMRI time series showed the superiority of exhaustive biclustering approaches, obtaining the most homogeneous biclusters. However, their high computational costs are a challenge, and further work is needed for the efficient use of biclustering in fMRI data analysis.ConclusionsThis work pinpoints avenues for the use of biclustering in spatio-temporal data analysis, in particular neurosciences applications. The proposed evaluation methodology showed evidence of the effectiveness of biclustering in finding local patterns in fMRI time series data. Further work is needed regarding scalability to promote the application in real scenarios.

Neural Activation in the Ventromedial Prefrontal Cortex Precedes Conscious Experience of Being in or out of a Transient Hallucinatory State.

Auditory verbal hallucinations (AVHs) is not only a common symptom in schizophrenia but also observed in individuals in the general population. Despite extensive research, AVHs are poorly understood, especially their underlying neuronal architecture. Neuroimaging methods have been used to identify brain areas and networks that are activated during hallucinations. A characteristic feature of AVHs is, however, that they fluctuate over time, with varying frequencies of starts and stops. An unanswered question is, therefore, what neuronal events co-occur with the initiation and inhibition of an AVH episode. We investigated brain activation with fMRI in 66 individuals who experienced multiple AVH-episodes while in the scanner. We extracted time-series fMRI-data and monitored changes second-by-second from 10 s before to 15 s after participants indicated the start and stop of an episode, respectively, by pressing a hand-held response-button. We found a region in the ventromedial prefrontal cortex (VMPFC) which showed a significant increase in activation initiated a few seconds before participants indicated the start of an episode, and a corresponding decrease in activation initiated a few seconds before the end of an episode. The consistent increase and decrease in activation in this area in advance of the consciously experienced presence or absence of the "voice" imply that this region may act as a switch in turning episodes on and off. The activation is unlikely to be confounded by motor responses. The findings could have clinical implications for brain stimulation treatments, like transcranial magnetic stimulation.

Data augmentation with Mixup: Enhancing performance of a functional neuroimaging-based prognostic deep learning classifier in recent onset psychosis

Although deep learning holds great promise as a prognostic tool in psychiatry, a limitation of the method is that it requires large training sample sizes to achieve replicable accuracy. This is problematic for fMRI datasets as they are typically small due to the considerable time, cost, and resources necessary to obtain them. A recently developed self-supervised learning method called Mixup may help overcome this challenge. In Mixup, the learner combines pairs of training instances to produce a virtual third instance that is a linear combination of the two instances and their labels. This procedure is also well-suited to the coregistered images typically found in fMRI datasets. Here we compared performance of a task fMRI-based deep learner with Mixup vs without Mixup on predicting response to treatment in recent onset psychosis. Whole brain fMRI time series data were extracted from a cognitive control task in 82 patients with recent onset psychosis and used to predict “Improver” (n = 47) vs “Non-Improver” (n = 35) status, with Improver defined as showing a 20 % reduction in total Brief Psychiatric Rating Scale score after 1 year of treatment. Mixup significantly improved performance (accuracy without Mixup: 76.5 % [95 % CI: 75.9–77.1 %]; accuracy with Mixup: 80.1 % [95 % CI: 79.4–80.8 %]). Ablation showed the improvement was due to improvement in both Improvers and Non-Improvers. These results suggest that using Mixup may significantly improve performance and reduce overfitting of fMRI-based prognostic deep learners and may also help overcome the small sample size challenge inherent to many neuroimaging datasets.

Dynamic effective connectivity network based on change points detection

Human brain networks can be modeled as a system of interconnected brain regions which are recorded by time-dependent observations with functional magnetic resonance imaging (fMRI). In order to spot trends, detect anomalies, and interpret the temporal dynamics, it is essential to understand the connections among distinct brain regions, and how these connections evolve over time. However, the change points of dynamic reorganization in brain connectivity are unknown, which may occur frequently during the scanning session. In this paper, we introduce a fused lasso regression approach to detect the number and position of rapid connectivity changes of subject and subsequently estimate the brain effective connectivity networks within each state phase lying between consecutive change points by conditional Granger causality method from fMRI time series data. The performance of the method is verified via numerical simulations and the obtained classification accuracy with support vector machine (SVM) was 86.24% in 140 subjects from Alzheimer's Disease Neuroimaging Initiative (ADNI). Compared with static EC model and conventional dynamic EC model based on sliding window technique, the experimental results show that the fused lasso achieved better classification effect, which probably due to better dynamic description. The result shows that the dynamic effective connectivity based on change points detected by fused lasso method is a better feature for classification.

Estimating Effective Connectivity by Recurrent Generative Adversarial Networks.

Estimating effective connectivity from functional magnetic resonance imaging (fMRI) time series data has become a very hot topic in neuroinformatics and brain informatics. However, it is hard for the current methods to accurately estimate the effective connectivity due to the high noise and small sample size of fMRI data. In this paper, we propose a novel framework for estimating effective connectivity based on recurrent generative adversarial networks, called EC-RGAN. The proposed framework employs the generator that consists of a set of effective connectivity generators based on recurrent neural networks to generate the fMRI time series of each brain region, and uses the discriminator to distinguish between the joint distributions of the real and generated fMRI time series. When the model is well-trained and generated fMRI data is similar to real fMRI data, EC-RGAN outputs the effective connectivity by means of the causal parameters of the effective connectivity generators. Experimental results on both simulated and real-world fMRI time series data demonstrate the efficacy of our proposed framework.

Evidence supporting a time-limited hippocampal role in retrieving autobiographical memories

The necessity of the human hippocampus for remote autobiographical recall remains fiercely debated. The standard model of consolidation predicts a time-limited role for the hippocampus, but the competing multiple trace/trace transformation theories posit indefinite involvement. Lesion evidence remains inconclusive, and the inferences one can draw from functional MRI (fMRI) have been limited by reliance on covert (silent) recall, which obscures dynamic, moment-to-moment content of retrieved memories. Here, we capitalized on advances in fMRI denoising to employ overtly spoken recall. Forty participants retrieved recent and remote memories, describing each for approximately 2 min. Details associated with each memory were identified and modeled in the fMRI time-series data using a variant of the Autobiographical Interview procedure, and activity associated with the recall of recent and remote memories was then compared. Posterior hippocampal regions exhibited temporally graded activity patterns (recent events > remote events), as did several regions of frontal and parietal cortex. Consistent with predictions of the standard model, recall-related hippocampal activity differed from a non-autobiographical control task only for recent, and not remote, events. Task-based connectivity between posterior hippocampal regions and others associated with mental scene construction also exhibited a temporal gradient, with greater connectivity accompanying the recall of recent events. These findings support predictions of the standard model of consolidation and demonstrate the potential benefits of overt recall in neuroimaging experiments.

Multi-Scale Time-Series Kernel-Based Learning Method for Brain Disease Diagnosis.

The functional magnetic resonance imaging (fMRI) is a noninvasive technique for studying brain activity, such as brain network analysis, neural disease automated diagnosis and so on. However, many existing methods have some drawbacks, such as limitations of graph theory, lack of global topology characteristic, local sensitivity of functional connectivity, and absence of temporal or context information. In addition to many numerical features, fMRI time series data also cover specific contextual knowledge and global fluctuation information. Here, we propose multi-scale time-series kernel-based learning model for brain disease diagnosis, based on Jensen-Shannon divergence. First, we calculate correlation value within and between brain regions over time. In addition, we extract multi-scale synergy expression probability distribution (interactional relation) between brain regions. Also, we produce state transition probability distribution (sequential relation) on single brain regions. Then, we build time-series kernel-based learning model based on Jensen-Shannon divergence to measure similarity of brain functional connectivity. Finally, we provide an efficient system to deal with brain network analysis and neural disease automated diagnosis. On Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, our proposed method achieves accuracy of 0.8994 and AUC of 0.8623. On Major Depressive Disorder (MDD) dataset, our proposed method achieves accuracy of 0.9166 and AUC of 0.9263. Experiments show that our proposed method outperforms other existing excellent neural disease automated diagnosis approaches. It shows that our novel prediction method performs great accurate for identification of brain diseases as well as existing outstanding prediction tools.

The Profiles of Non-stationarity and Non-linearity in the Time Series of Resting-State Brain Networks.

The linearity and stationarity of fMRI time series need to be understood due to their important roles in the choice of approach for brain network analysis. In this paper, we investigated the stationarity and linearity of resting-state fMRI (rs-fMRI) time-series data from the Midnight Scan Club datasets. The degree of stationarity (DS) and the degree of non-linearity (DN) were, respectively, estimated for the time series of all gray matter voxels. The similarity and difference between the DS and DN were assessed in terms of voxels and intrinsic brain networks, including the visual network, somatomotor network, dorsal attention network, ventral attention network, limbic network, frontoparietal network, and default-mode network. The test-retest scans were utilized to quantify the reliability of DS and DN. We found that DS and DN maps had overlapping spatial distribution. Meanwhile, the probability density estimate function of DS had a long tail, and that of DN had a more normal distribution. Specifically, stronger DS was present in the somatomotor, limbic, and ventral attention networks compared to other networks, and stronger DN was found in the somatomotor, visual, limbic, ventral attention, and default-mode networks. The percentage of overlapping voxels between DS and DN in different networks demonstrated a decreasing trend in the order default mode, ventral attention, somatomotor, frontoparietal, dorsal attention, visual, and limbic. Furthermore, the ICC values of DS were higher than those of DN. Our results suggest that different functional networks have distinct properties of non-stationarity and non-linearity owing to the complexity of rs-fMRI time series. Thus, caution should be taken when analyzing fMRI data (both resting-state and task-activation) using simplified models.

Directional Interactions Between Constituents of the Human Large-Scale Thermoregulatory Network

In humans, dynamic thermoregulation is (presumably) underpinned by a complex hierarchy of functional interactions between constituents of the human thermoregulatory large-scale network. However, these interactions have not been quantified from in vivo fMRI signals acquired during the experimental delivery of whole-body thermal stress. Here, we used directed functional connectivity (dFC) analysis (based on multi-variate autoregressive models) to recover directed interactions within a single thermoregulatory network during an experimental paradigm that involved controlled exposure to whole-body cooling and warming. MRI studies were performed in 30 young adults (15M/15F, mean age 25.1 ± 3.4years). Gradient echo EPI fMRI data were acquired on a 3T Siemens Verio system. The thermoregulatory challenge was applied using a specialized whole-body garment covering the entire body. Tubes lining the innards of the suit were infused with cold (2-4°C) or neutral (31-34°C) water to induce whole-body Cooling or Warming while fMRI data were contemporaneously acquired. dFC was estimated within and between the hierarchically organized homeostatic (midbrain, pons), interoceptive (insula) and executive (anterior cingulate, orbitofrontal and superior parietal cortices) sub-networks using multi-variate autoregressive models applied to the fMRI time series data. Estimates of directed interactions (akin to Granger Causality) between nodes were analyzed to recover ascending (homeostatic sub-network "upward"), descending (executive sub-network "downward"), and lateral (within sub-network) directional ("causal") effects. Both Cooling and Warming induced complex hierarchical interactions in the thermoregulatory large-scale network. Cooling induced ascending interactions from the homeostatic (midbrain) to both the executive (OFC) and interoceptive (insula) sub-networks, particularly to the superior parietal, ACC and the anterior and posterior insulae. In comparison, descending interactions were induced from the posterior insula. Warming induced ascending interactions from the homeostatic sub-network to notably the OFC (executive) and the insulae (interoceptive). Descending interactions were induced from the ACC and the OFC. Sparser effects appear from the executive to the interoceptive sub-network during warming. Our study demonstrates a hierarchical organization of thermoregulatory function between homeostatic, interoceptive and executive sub-networks. The observed information flow between/within these is consistent with a reentrant property of the hierarchical regulatory structure, characterized by the ongoing bi-directional exchange of signals along reciprocal axonal fibers linking the various nodes.