Two distinct networks containing position-tolerant representations of actions in the human brain.

Humans can recognize others' actions in the social environment. This action recognition ability is rarely hindered by the movement of people in the environment. The neural basis of this position tolerance for observed actions is not fully understood. Here, we aimed to identify brain regions capable of generalizing representations of actions across different positions and investigate the representational content of these regions. In a functional magnetic resonance imaging experiment, participants viewed point-light displays of different human actions. Stimuli were presented in either the upper or the lower visual field. Multivariate pattern analysis and a surface-based searchlight approach were employed to identify brain regions that contain position-tolerant action representation: Classifiers were trained with patterns in response to stimuli presented in one position and were tested with stimuli presented in another position. Results showed above-chance classification in the left and right lateral occipitotemporal cortices, right intraparietal sulcus, and right postcentral gyrus. Further analyses exploring the representational content of these regions showed that responses in the lateral occipitotemporal regions were more related to subjective judgments, while those in the parietal regions were more related to objective measures. These results provide evidence for two networks that contain abstract representations of human actions with distinct representational content.

Neural modulation enhancement using connectivity-based EEG neurofeedback with simultaneous fMRI for emotion regulation.

Emotion regulation plays a key role in human behavior and overall well-being. Neurofeedback is a non-invasive self-brain training technique used for emotion regulation to enhance brain function and treatment of mental disorders through behavioral changes. Previous neurofeedback research often focused on using activity from a single brain region as measured by fMRI or power from one or two EEG electrodes. In a new study, we employed connectivity-based EEG neurofeedback through recalling positive autobiographical memories and simultaneous fMRI to upregulate positive emotion. In our novel approach, the feedback was determined by the coherence of EEG electrodes rather than the power of one or two electrodes. We compared the efficiency of this connectivity-based neurofeedback to traditional activity-based neurofeedback through multiple experiments. The results showed that connectivity-based neurofeedback effectively improved BOLD signal change and connectivity in key emotion regulation regions such as the amygdala, thalamus, and insula, and increased EEG frontal asymmetry, which is a biomarker for emotion regulation and treatment of mental disorders such as PTSD, anxiety, and depression and coherence among EEG channels. The psychometric evaluations conducted both before and after the neurofeedback experiments revealed that participants demonstrated improvements in enhancing positive emotions and reducing negative emotions when utilizing connectivity-based neurofeedback, as compared to traditional activity-based and sham neurofeedback approaches. These findings suggest that connectivity-based neurofeedback may be a superior method for regulating emotions and could be a useful alternative therapy for mental disorders, providing individuals with greater control over their brain and mental functions.

Dysconnection and cognition in schizophrenia: A spectral dynamic causal modeling study.

Schizophrenia (SZ) is a severe mental disorder characterized by failure of functional integration (aka dysconnection) across the brain. Recent functional connectivity (FC) studies have adopted functional parcellations to define subnetworks of large-scale networks, and to characterize the (dys)connection between them, in normal and clinical populations. While FC examines statistical dependencies between observations, model-based effective connectivity (EC) can disclose the causal influences that underwrite the observed dependencies. In this study, we investigated resting state EC within seven large-scale networks, in 66 SZ and 74 healthy subjects from a public dataset. The results showed that a remarkable 33% of the effective connections (among subnetworks) of the cognitive control network had been pathologically modulated in SZ. Further dysconnection was identified within the visual, default mode and sensorimotor networks of SZ subjects, with 24%, 20%, and 11% aberrant couplings. Overall, the proportion of discriminative connections was remarkably larger in EC (24%) than FC (1%) analysis. Subsequently, to study the neural correlates of impaired cognition in SZ, we conducted a canonical correlation analysis between the EC parameters and the cognitive scores of the patients. As such, the self-inhibitions of supplementary motor area and paracentral lobule (in the sensorimotor network) and the excitatory connection from parahippocampal gyrus to inferior temporal gyrus (in the cognitive control network) were significantly correlated with the social cognition, reasoning/problem solving and working memory capabilities of the patients. Future research can investigate the potential of whole-brain EC as a biomarker for diagnosis of brain disorders and for neuroimaging-based cognitive assessment.

Statistical Significance Assessment of Phase Synchrony in the Presence of Background Couplings: An ECoG Study.

Statistical significance testing is a necessary step in connectivity analysis. Several statistical test methods have been employed to assess the significance of functional connectivity, but the performance of these methods has not been thoroughly evaluated. In addition, the effects of the intrinsic brain connectivity and background couplings on performance of statistical test methods in task-based studies have not been investigated yet. The background couplings may exist independent of cognitive state and can be observed on both pre- and post-stimulus time intervals. The background couplings may be falsely detected by a statistical test as task-related connections, which can mislead interpretations of the task-related functional networks. The aim of this study was to investigate the relative performance of four commonly used non-parametric statistical test methods-surrogate, demeaned surrogate, bootstrap resampling, and Monte Carlo permutation methods-in the presence of background couplings and noise, with different signal-to-noise ratios (SNRs). Using simulated electrocorticographic (ECoG) datasets and phase locking value (PLV) as a measure of functional connectivity, we evaluated the performances of the statistical test methods utilizing sensitivity, specificity, accuracy, and receiver operating curve (ROC) analysis. Furthermore, we calculated optimal p values for each statistical test method using the ROC analysis, and found that the optimal p values were increased by decreasing the SNR. We also found that the optimal p value of the bootstrap resampling was greater than that of other methods. Our results from the simulation datasets and a real ECoG dataset, as an illustrative case report, revealed that the bootstrap resampling is the most efficient non-parametric statistical test for identifying the significant PLV of ECoG data, especially in the presence of background couplings.

Nonlinear effective connectivity measure based on adaptive Neuro Fuzzy Inference System and Granger Causality.

Exploring brain networks is an essential step towards understanding functional organization of the brain, which needs characterization of linear and nonlinear connections based on measurements like EEG or MEG. Conventional measures of connectivity are mostly linear and bivariate. This paper proposes an effective connectivity measure called Adaptive Neuro-Fuzzy Inference System Granger Causality (ANFISGC). The proposed measure is based on the symplectic geometry embedding dimension, Adaptive Neuro-Fuzzy Inference System (ANFIS) predictor, and Granger Causality (GC). It is a powerful predictor that detects both linear and nonlinear causal information flow. It is not bivariate and thus can distinguish between direct and indirect connections. The performance of the proposed method is evaluated and compared with those of the Linear Granger Causality (LGC), Kernel Granger Causality (KGC), combination of Pairwise Granger Causality and Conditional Granger Causality (PwGC + CGC), Transfer Entropy (TE), and Phase Transfer Entropy (PTE) methods using simulated and experimental MEG data. Simulation results show that ANFISGC outperforms the other methods in detecting both linear and nonlinear connections and, by increasing the coupling strength between nodes, the value of ANFISGC increases. In the analysis of the time series of the brain sources of epilepsy patients obtained from the MEG inverse problem, the regions found by ANFISGC were more similar to the clinical findings than those found by the other methods.

Long-Range Reduced Predictive Information Transfers of Autistic Youths in EEG Sensor-Space During Face Processing.

The majority of previous functional/effective connectivity studies conducted on the autistic patients converged to the underconnectivity theory of ASD: "long-range underconnectivity and sometimes short-rang overconnectivity". However, to the best of our knowledge the total (linear and nonlinear) predictive information transfers (PITs) of autistic patients have not been investigated yet. Also, EEG data have rarely been used for exploring the information processing deficits in autistic subjects. This study is aimed at comparing the total (linear and nonlinear) PITs of autistic and typically developing healthy youths during human face processing by using EEG data. The ERPs of 12 autistic youths and 19 age-matched healthy control (HC) subjects were recorded while they were watching upright and inverted human face images. The PITs among EEG channels were quantified using two measures separately: transfer entropy with self-prediction optimality (TESPO), and modified transfer entropy with self-prediction optimality (MTESPO). Afterwards, the directed differential connectivity graphs (dDCGs) were constructed to characterize the significant changes in the estimated PITs of autistic subjects compared with HC ones. By using both TESPO and MTESPO, long-range reduction of PITs of ASD group during face processing was revealed (particularly from frontal channels to right temporal channels). Also, it seemed the orientation of face images (upright or upside down) did not modulate the binary pattern of PIT-based dDCGs, significantly. Moreover, compared with TESPO, the results of MTESPO were more compatible with the underconnectivity theory of ASD in the sense that MTESPO showed no long-range increase in PIT. It is also noteworthy that to the best of our knowledge it is the first time that a version of MTE is applied for patients (here ASD) and it is also its first use for EEG data analysis.

Automated iterative reclustering framework for determining hierarchical functional networks in resting state fMRI.

To spatially cluster resting state-functional magnetic resonance imaging (rs-fMRI) data into potential networks, there are only a few general approaches that determine the number of networks/clusters, despite a wide variety of techniques proposed for clustering. For individual subjects, extraction of a large number of spatially disjoint clusters results in multiple small networks that are spatio-temporally homogeneous but irreproducible across subjects. Alternatively, extraction of a small number of clusters creates spatially large networks that are temporally heterogeneous but spatially reproducible across subjects. We propose a fully automatic, iterative reclustering framework in which a small number of spatially large, heterogeneous networks are initially extracted to maximize spatial reproducibility. Subsequently, the large networks are iteratively subdivided to create spatially reproducible subnetworks until the overall within-network homogeneity does not increase substantially. The proposed approach discovers a rich network hierarchy in the brain while simultaneously optimizing spatial reproducibility of networks across subjects and individual network homogeneity. We also propose a novel metric to measure the connectivity of brain regions, and in a simulation study show that our connectivity metric and framework perform well in the face of low signal to noise and initial segmentation errors. Experimental results generated using real fMRI data show that the proposed metric improves stability of network clusters across subjects, and generates a meaningful pattern for spatially hierarchical structure of the brain.

The normalization model predicts responses in the human visual cortex during object-based attention.

Divisive normalization of the neural responses by the activity of the neighboring neurons has been proposed as a fundamental operation in the nervous system based on its success in predicting neural responses recorded in primate electrophysiology studies. Nevertheless, experimental evidence for the existence of this operation in the human brain is still scant. Here, using functional MRI, we examined the role of normalization across the visual hierarchy in the human visual cortex. Using stimuli form the two categories of human bodies and houses, we presented objects in isolation or in clutter and asked participants to attend or ignore the stimuli. Focusing on the primary visual area V1, the object-selective regions LO and pFs, the body-selective region EBA, and the scene-selective region PPA, we first modeled single-voxel responses using a weighted sum, a weighted average, and a normalization model and demonstrated that although the weighted sum and weighted average models also made acceptable predictions in some conditions, the response to multiple stimuli could generally be better described by a model that takes normalization into account. We then determined the observed effects of attention on cortical responses and demonstrated that these effects were predicted by the normalization model, but not by the weighted sum or the weighted average models. Our results thus provide evidence that the normalization model can predict responses to objects across shifts of visual attention, suggesting the role of normalization as a fundamental operation in the human brain.

Disturbance of information in superior parietal lobe during dual-task interference in a simulated driving task.

Performing a secondary task while driving causes a decline in driving performance. This phenomenon, called dual-task interference, can have lethal consequences. Previous fMRI studies have looked at the changes in the average brain activity to uncover the neural correlates of dual-task interference. From these results, it is unclear whether the overall modulations in brain activity result from general effects such as task difficulty, attentional modulations, and mental effort or whether it is caused by a change in the responses specific to each condition due to dual-task interference. To overcome this limitation, here, we used multi-voxel pattern analysis (MVPA) to interrogate the change in the information content in multiple brain regions during dual-task interference in simulated driving. Participants performed a lane-change task in a simulated driving environment, along with a tone discrimination task with either short or long onset time difference (Stimulus Onset Asynchrony, SOA) between the two tasks. Behavioral results indicated a robust dual-task effect on lane-change reaction time (RT). MVPA revealed regions that carry information about the driving lane-change direction (shift right/shift left), including the superior parietal lobe (SPL), visual, and motor regions. Comparison of decoding accuracies across SOA conditions in the SPL region revealed lower accuracy in the short compared to the long SOA condition. This change in accuracy was not observed in the visual and motor regions. These findings suggest that the dual-task interference in driving may be related to the disturbance of information processing in the SPL region.

Attention Modulates Human Visual Responses to Objects by Tuning Sharpening.

Visual stimuli compete with each other for cortical processing and attention biases this competition in favor of the attended stimulus. How does the relationship between the stimuli affect the strength of this attentional bias? Here, we used functional MRI to explore the effect of target-distractor similarity in neural representation on attentional modulation in the human visual cortex using univariate and multivariate pattern analyses. Using stimuli from four object categories (human bodies, cats, cars and houses), we investigated attentional effects in the primary visual area V1, the object-selective regions LO and pFs, the body-selective region EBA, and the scene-selective region PPA. We demonstrated that the strength of the attentional bias towards the target is not fixed but decreases with increasing distractor-target similarity. Simulations provided evidence that this result pattern is explained by tuning sharpening rather than an increase in gain. Our findings provide a mechanistic explanation for behavioral effects of target-distractor similarity on attentional biases and suggest tuning sharpening as the underlying mechanism in object-based attention.

EEG-based classification of individuals with neuropsychiatric disorders using deep neural networks: A systematic review of current status and future directions.

The use of deep neural networks for electroencephalogram (EEG) classification has rapidly progressed and gained popularity in recent years, but automatic feature extraction from EEG signals remains a challenging task. The classification of neuropsychiatric disorders demands the extraction of neuro-markers for use in automated EEG classification. Numerous advanced deep learning algorithms can be used for this purpose. In this article, we present a comprehensive review of the main factors and parameters that affect the performance of deep neural networks in classifying different neuropsychiatric disorders using EEG signals. We also analyze the EEG features used for improving classification performance. Our analysis includes 82 scientific journal papers that applied deep neural networks for subject-wise classification based on EEG signals. We extracted information on the EEG dataset and types of disorders, deep neural network structures, performance, and hyperparameters. The results show that most studies have focused on clinical classification, achieving an average accuracy of 91.83 ± 7.34, with convolutional neural networks (CNNs) being the most frequently used network architecture and resting-state EEG signals being the most commonly used data type. Additionally, the review reveals that depression (N = 18), Alzheimer's (N = 11), and schizophrenia (N = 11) were studied more frequently than other types of neuropsychiatric disorders. Our review provides insight into the performance of deep neural networks in EEG classification and highlights the importance of EEG feature extraction in improving classification accuracy. By identifying the main factors and parameters that affect deep neural network performance in EEG classification, our review can guide future research in this area. We hope that our findings will encourage further exploration of deep learning methods for EEG classification and contribute to the development of more accurate and effective methods for diagnosing and monitoring neuropsychiatric disorders using EEG signals.

Subspace-based Identification Algorithm for characterizing causal networks in resting brain.

The resting brain has been extensively investigated for low frequency synchrony between brain regions, namely Functional Connectivity (FC). However the other main stream of brain connectivity analysis that seeks causal interactions between brain regions, Effective Connectivity (EC), has been little explored. Inherent complexity of brain activities in resting-state, as observed in BOLD (Blood Oxygenation-Level Dependant) fluctuations, calls for exploratory methods for characterizing these causal networks. On the other hand, the inevitable effects that hemodynamic system imposes on causal inferences in fMRI data, lead us toward the methods in which causal inferences can take place in latent neuronal level, rather than observed BOLD time-series. To simultaneously satisfy these two concerns, in this paper, we introduce a novel state-space system identification approach for studying causal interactions among brain regions in the absence of explicit cognitive task. This algorithm is a geometrically inspired method for identification of stochastic systems, purely based on output observations. Using extensive simulations, three aspects of our proposed method are investigated: ability in discriminating existent interactions from non-existent ones, the effect of observation noise, and downsampling on algorithm performance. Our simulations demonstrate that Subspace-based Identification Algorithm (SIA) is sufficiently robust against above-mentioned factors, and can reliably uncover the underlying causal interactions of resting-state fMRI. Furthermore, in contrast to previously established state-space approaches in Effective Connectivity studies, this method is able to characterize causal networks with large number of brain regions. In addition, we utilized the proposed algorithm for identification of causal relationships underlying anti-correlation of default-mode and Dorsal Attention Networks during the rest, using fMRI. We observed that Default-Mode Network places in a higher order in hierarchical structure of brain functional networks compared to Dorsal Attention Networks.

Enhancing reproducibility of fMRI statistical maps using generalized canonical correlation analysis in NPAIRS framework.

Common fMRI data processing techniques usually minimize a temporal cost function or fit a temporal model to extract an activity map. Here, we focus on extracting a highly, spatially reproducible statistical parametric map (SPM) from fMRI data using a cost function that does not depend on a model of the subjects' temporal response. Based on a generalized version of canonical correlation analysis (gCCA), we propose a method to extract a highly reproducible map by maximizing the sum of pair-wise correlations between some maps. In a group analysis, each map is calculated from a linear combination of fMRI scans of a subset of subjects under study. The proposed method is applied to BOLD fMRI datasets without any spatial smoothing from 10 subjects performing a simple reaction time (RT) task. Using the NPAIRS split-half resampling framework with a reproducibility measure based on SPM correlations, we compare the proposed approach with canonical variate analysis (CVA) and a simple general linear model (GLM). gCCA provides statistical parametric maps with higher reproducibility than CVA and GLM with correlation reproducibilities across independent split-half SPMs of 0.78, 0.46, and 0.41, respectively. Our results show that gCCA is an efficient approach for extracting the default mode network, assessing brain connectivity, and processing event-related and resting-state datasets in which the temporal BOLD signal varies from subject to subject.

Probing fMRI brain connectivity and activity changes during emotion regulation by EEG neurofeedback.

Despite the existence of several emotion regulation studies using neurofeedback, interactions among a small number of regions were evaluated, and therefore, further investigation is needed to understand the interactions of the brain regions involved in emotion regulation. We implemented electroencephalography (EEG) neurofeedback with simultaneous functional magnetic resonance imaging (fMRI) using a modified happiness-inducing task through autobiographical memories to upregulate positive emotion. Then, an explorative analysis of whole brain regions was done to understand the effect of neurofeedback on brain activity and the interaction of whole brain regions involved in emotion regulation. The participants in the control and experimental groups were asked to do emotion regulation while viewing positive images of autobiographical memories and getting sham or real (based on alpha asymmetry) EEG neurofeedback, respectively. The proposed multimodal approach quantified the effects of EEG neurofeedback in changing EEG alpha power, fMRI blood oxygenation level-dependent (BOLD) activity of prefrontal, occipital, parietal, and limbic regions (up to 1.9% increase), and functional connectivity in/between prefrontal, parietal, limbic system, and insula in the experimental group. New connectivity links were identified by comparing the brain functional connectivity between experimental conditions (Upregulation and View blocks) and also by comparing the brain connectivity of the experimental and control groups. Psychometric assessments confirmed significant changes in positive and negative mood states in the experimental group by neurofeedback. Based on the exploratory analysis of activity and connectivity among all brain regions involved in emotion regions, we found significant BOLD and functional connectivity increases due to EEG neurofeedback in the experimental group, but no learning effect was observed in the control group. The results reveal several new connections among brain regions as a result of EEG neurofeedback which can be justified according to emotion regulation models and the role of those regions in emotion regulation and recalling positive autobiographical memories.

Dynamic functional connectivity estimation for neurofeedback emotion regulation paradigm with simultaneous EEG-fMRI analysis.

Joint Analysis of EEG and fMRI datasets can bring new insight into brain mechanisms. In this paper, we employed the recently introduced Correlated Coupled Tensor Matrix Factorization (CCMTF) method for analysis of the emotion regulation paradigm based on EEG frontal asymmetry neurofeedback in the alpha frequency band with simultaneous fMRI. CCMTF method assumes that the co-variations of the common dimension (temporal dimension) between EEG and fMRI are correlated and not necessarily identical. The results of the CCMTF method suggested that EEG and fMRI had similar covariations during the transition of brain activities from resting states to task (view and upregulation) states and these covariations followed an increasing trend. The fMRI shared spatial component showed activations in the limbic system, DLPFC, OFC, and VLPC regions, which were consistent with the previous studies and were linked to EEG frequency patterns in the range of 1-15 Hz with a correlation value close to 0.75. The estimated regions from the CCMTF method were then used as the candidate nodes for dynamic functional connectivity (dFC) analysis, in which the changes in connectivity from view to upregulation states were examined. The results of the dFC analysis were compared with a Normalized Mutual information (NMI) based approach in two different frequency ranges (1-15 and 15-40 Hz) as the NMI method was applied to the vectors of dFC nodes of EEG and fMRI data. The results of the two methods illustrated that the relation between EEG and fMRI datasets was mostly in the frequency range of 1-15 Hz. These relations were both in the brain activations and the dFCs between the two modalities. This paper suggests that the CCMTF method is a capable approach for extracting the shared information between EEG and fMRI data and can reveal new information about brain functions and their connectivity without solving the EEG inverse problem or analyzing different frequency bands.

A mutual information-based metric for evaluation of fMRI data-processing approaches.

We propose a novel approach for evaluating the performance of activation detection in real (experimental) datasets using a new mutual information (MI)-based metric and compare its sensitivity to several existing performance metrics in both simulated and real datasets. The proposed approach is based on measuring the approximate MI between the fMRI time-series of a validation dataset and a calculated activation map (thresholded label map or continuous map) from an independent training dataset. The MI metric is used to measure the amount of information preserved during the extraction of an activation map from experimentally related fMRI time-series. The processing method that preserves maximal information between the maps and related time-series is proposed to be superior. The results on simulation datasets for multiple analysis models are consistent with the results of ROC curves, but are shown to have lower information content than for real datasets, limiting their generalizability. In real datasets for group analyses using the general linear model (GLM; FSL4 and SPM5), we show that MI values are (1) larger for groups of 15 versus 10 subjects and (2) more sensitive measures than reproducibility (for continuous maps) or Jaccard overlap metrics (for thresholded maps). We also show that (1) for an increasing fraction of nominally active voxels, both MI and false discovery rate (FDR) increase, and (2) at a fixed FDR, GLM using FSL4 tends to extract more voxels and more information than SPM5 using the default processing techniques in each package.

Neuroscience20 (BRAIN20, SPINE20, and MENTAL20) Health Initiative: A Global Consortium Addressing the Human and Economic Burden of Brain, Spine, and Mental Disorders Through Neurotech Innovations and Policies.

Neurological disorders significantly impact the world's economy due to their often chronic and life-threatening nature afflicting individuals which, in turn, creates a global disease burden. The Group of Twenty (G20) member nations, which represent the largest economies globally, should come together to formulate a plan on how to overcome this burden. The Neuroscience-20 (N20) initiative of the Society for Brain Mapping and Therapeutics (SBMT) is at the vanguard of this global collaboration to comprehensively raise awareness about brain, spine, and mental disorders worldwide. This paper aims to provide a comprehensive review of the various brain initiatives worldwide and highlight the need for cooperation and recommend ways to bring down costs associated with the discovery and treatment of neurological disorders. Our systematic search revealed that the cost of neurological and psychiatric disorders to the world economy by 2030 is roughly $16T. The cost to the economy of the United States is $1.5T annually and growing given the impact of COVID-19. We also discovered there is a shortfall of effective collaboration between nations and a lack of resources in developing countries. Current statistical analyses on the cost of neurological disorders to the world economy strongly suggest that there is a great need for investment in neurotechnology and innovation or fast-tracking therapeutics and diagnostics to curb these costs. During the current COVID-19 pandemic, SBMT, through this paper, intends to showcase the importance of worldwide collaborations to reduce the population's economic and health burden, specifically regarding neurological/brain, spine, and mental disorders.

Dual-Task Interference in a Simulated Driving Environment: Serial or Parallel Processing?

When humans are required to perform two or more tasks concurrently, their performance declines as the tasks get closer together in time. Here, we investigated the mechanisms of this cognitive performance decline using a dual-task paradigm in a simulated driving environment, and using drift-diffusion modeling, examined if the two tasks are processed in a serial or a parallel manner. Participants performed a lane change task, along with an image discrimination task. We systematically varied the time difference between the onset of the two tasks (Stimulus Onset Asynchrony, SOA) and measured its effect on the amount of dual-task interference. Results showed that the reaction times (RTs) of the two tasks in the dual-task condition were higher than those in the single-task condition. SOA influenced the RTs of both tasks when they were presented second and the RTs of the image discrimination task when it was presented first. Results of drift-diffusion modeling indicated that dual-task performance affects both the rate of evidence accumulation and the delays outside the evidence accumulation period. These results suggest that a hybrid model containing features of both parallel and serial processing best accounts for the results. Next, manipulating the predictability of the order of the two tasks, we showed that in unpredictable conditions, the order of the response to the two tasks changes, causing attenuation in the effect of SOA. Together, our findings suggest higher-level executive functions are involved in managing the resources and controlling the processing of the tasks during dual-task performance in naturalistic settings.

Deep Temporal Organization of fMRI Phase Synchrony Modes Promotes Large-Scale Disconnection in Schizophrenia.

Itinerant dynamics of the brain generates transient and recurrent spatiotemporal patterns in neuroimaging data. Characterizing metastable functional connectivity (FC) - particularly at rest and using functional magnetic resonance imaging (fMRI) - has shaped the field of dynamic functional connectivity (DFC). Mainstream DFC research relies on (sliding window) correlations to identify recurrent FC patterns. Recently, functional relevance of the instantaneous phase synchrony (IPS) of fMRI signals has been revealed using imaging studies and computational models. In the present paper, we identify the repertoire of whole-brain inter-network IPS states at rest. Moreover, we uncover a hierarchy in the temporal organization of IPS modes. We hypothesize that connectivity disorder in schizophrenia (SZ) is related to the (deep) temporal arrangement of large-scale IPS modes. Hence, we analyze resting-state fMRI data from 68 healthy controls (HC) and 51 SZ patients. Seven resting-state networks (and their sub-components) are identified using spatial independent component analysis. IPS is computed between subject-specific network time courses, using analytic signals. The resultant phase coupling patterns, across time and subjects, are clustered into eight IPS states. Statistical tests show that the relative expression and mean lifetime of certain IPS states have been altered in SZ. Namely, patients spend (45%) less time in a globally coherent state and a subcortical-centered state, and (40%) more time in states reflecting anticoupling within the cognitive control network, compared to the HC. Moreover, the transition profile (between states) reveals a deep temporal structure, shaping two metastates with distinct phase synchrony profiles. A metastate is a collection of states such that within-metastate transitions are more probable than across. Remarkably, metastate occupation balance is altered in SZ, in favor of the less synchronous metastate that promotes disconnection across networks. Furthermore, the trajectory of IPS patterns is less efficient, less smooth, and more restricted in SZ subjects, compared to the HC. Finally, a regression analysis confirms the diagnostic value of the defined IPS measures for SZ identification, highlighting the distinctive role of metastate proportion. Our results suggest that the proposed IPS features may be used for classification studies and for characterizing phase synchrony modes in other (clinical) populations.

Global Data-Driven Analysis of Brain Connectivity During Emotion Regulation by Electroencephalography Neurofeedback.

Background: Emotion regulation by neurofeedback involves interactions among multiple brain regions, including prefrontal cortex and subcortical regions. Previous studies focused on connections of specific brain regions such as amygdala with other brain regions. New method: Electroencephalography (EEG) neurofeedback is used to upregulate positive emotion by retrieving positive autobiographical memories and functional magnetic resonance imaging (fMRI) data acquired simultaneously. A global data-driven approach, group independent component analysis, is applied to the fMRI data and functional network connectivity (FNC) estimated. Results: The proposed approach identified all functional networks engaged in positive autobiographical memories and evaluated effects of neurofeedback. The results revealed two pairs of networks with significantly different functional connectivity among emotion regulation blocks (relative to other blocks of the experiment) and between experimental and control groups (false discovery rate corrected for multiple comparisons, q = 0.05). FNC distribution showed significant connectivity differences between neurofeedback blocks and other blocks, revealing more synchronized brain networks during neurofeedback. Comparison with Existing Methods: Although the results are consistent with those of previous model-based studies, some of the connections found in this study were not found previously. These connections are between (a) occipital and other regions including limbic system/sublobar, prefrontal/frontal cortex, inferior parietal, and middle temporal gyrus and (b) posterior cingulate cortex and hippocampus. Conclusions: This study provided a global insight into brain connectivity for emotion regulation. The brain network interactions may be used to develop connectivity-based neurofeedback methods and alternative therapeutic approaches, which may be more effective than the traditional activity-based neurofeedback methods.