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Multiple sclerosis (MS) is a neurological disorder affecting the central nervous system and features extensive functional brain changes that are poorly understood but relate strongly to clinical impairments. Functional magnetic resonance imaging (fMRI) is a non-invasive, powerful technique able to map activity of brain regions and to assess how such regions interact for an efficient brain network. FMRI has been widely applied to study functional brain changes in MS, allowing to investigate functional plasticity consequent to disease-related structural injury. The first studies in MS using active fMRI tasks mainly aimed to study such plastic changes by identifying abnormal activity in salient brain regions (or systems) involved by the task. In later studies the focus shifted towards resting state (RS) functional connectivity (FC) studies, which aimed to map large-scale functional networks of the brain and to establish how MS pathology impairs functional integration, eventually leading to the hypothesized network collapse as patients clinically progress. This review provides a summary of the main findings from studies using task-based and RS fMRI and illustrates how functional brain alterations relate to clinical disability and cognitive deficits in this condition. We also give an overview of longitudinal studies that used task-based and RS fMRI to monitor disease evolution and effects of motor and cognitive rehabilitation. In addition, we discuss the results of studies using newer technologies involving time-varying FC to investigate abnormal dynamism and flexibility of network configurations in MS. Finally, we show some preliminary results from two recent topics (i.e., multimodal MRI analysis and artificial intelligence) that are receiving increasing attention. Together, these functional studies could provide new (conceptual) insights into disease stage-specific mechanisms underlying progression in MS, with recommendations for future research., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Functional MR imaging (MRI) is a valuable tool for presurgical planning and is well established in adult patients. The use of task-based fMRI is increasing in pediatric populations because it provides similar benefits for pre-surgical planning in children. This article reviews special adaptations that are required for successful applications of task-based fMRI in children, especially in the motor and language systems. The more recently introduced method of resting state fMRI is reviewed and its relative advantages and disadvantages discussed. Common pitfalls and other systems and networks that may be of interest in special circumstances also are reviewed., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Whether antagonistic brain states constitute a fundamental principle of human brain organization has been debated over the past decade. Some argue that intrinsically anti-correlated brain networks in resting-state functional connectivity are an artifact of preprocessing. Others argue that anti-correlations are biologically meaningful predictors of how the brain will respond to different stimuli. Here, we investigated the co-activation patterns across the whole brain in various tasks and test whether brain regions demonstrate anti-correlated activity similar to those observed at rest. We examined brain activity in 47 task contrasts from the Human Connectome Project (N = 680) and found robust antagonistic interactions between networks. Regions of the default network exhibited the highest degree of cortex-wide negative connectivity. The negative co-activation patterns across tasks showed good correspondence to that derived from resting-state data processed with global signal regression (GSR). Interestingly, GSR-processed resting-state data was a significantly better predictor of task-induced modulation than data processed without GSR. Finally, in a cohort of 25 patients with depression, we found that task-based anti-correlations between the dorsolateral prefrontal cortex (DLPFC) and subgenual anterior cingulate cortex were associated with clinical efficacy of transcranial magnetic stimulation therapy targeting the DLPFC. Overall, our findings indicate that anti-correlations are a biologically meaningful phenomenon and may reflect an important principle of functional brain organization. [ABSTRACT FROM AUTHOR]

• Confidence Sets (CSs) extend the idea of confidence intervals to fMRI maps. • For a Cohen's d threshold c , upper CS asserts where d > c , lower CS where d < c. • We demonstrate the CSs method on HCP subject-level Cohen's d data. • We compare the CSs with results from standard statistical voxelwise inference. • Unlike traditional cluster tests, CSs precisely quantify spatial uncertainty. Current statistical inference methods for task-fMRI suffer from two fundamental limitations. First, the focus is solely on detection of non-zero signal or signal change, a problem that is exacerbated for large scale studies (e.g. UK Biobank, N = 40 , 000 +) where the 'null hypothesis fallacy' causes even trivial effects to be determined as significant. Second, for any sample size, widely used cluster inference methods only indicate regions where a null hypothesis can be rejected, without providing any notion of spatial uncertainty about the activation. In this work, we address these issues by developing spatial Confidence Sets (CSs) on clusters found in thresholded Cohen's d effect size images. We produce an upper and lower CS to make confidence statements about brain regions where Cohen's d effect sizes have exceeded and fallen short of a non-zero threshold, respectively. The CSs convey information about the magnitude and reliability of effect sizes that is usually given separately in a t -statistic and effect estimate map. We expand the theory developed in our previous work on CSs for %BOLD change effect maps (Bowring et al., 2019) using recent results from the bootstrapping literature. By assessing the empirical coverage with 2D and 3D Monte Carlo simulations resembling fMRI data, we find our method is accurate in sample sizes as low as N = 60. We compute Cohen's d CSs for the Human Connectome Project working memory task-fMRI data, illustrating the brain regions with a reliable Cohen's d response for a given threshold. By comparing the CSs with results obtained from a traditional statistical voxelwise inference, we highlight the improvement in activation localization that can be gained with the Confidence Sets. [ABSTRACT FROM AUTHOR]

Prior research has shown a role of the medial temporal lobe, particularly the hippocampal-parahippocampal complex, in spatial cognition. Here, we developed a new paradigm, the conformational shift spatial task (CSST), which examines the ability to encode and retrieve spatial relations between unrelated items. This task is short, uses symbolic cues, incorporates two difficulty levels, and can be administered inside the scanner. A cohort of 48 healthy young adults underwent the CSST, together with a set of behavioral measures and multimodal magnetic resonance imaging (MRI). Inter-individual differences in CSST performance correlated with scores on an established spatial memory paradigm, but neither with episodic memory nor mnemonic discrimination, supporting specificity. Analyzing high-resolution structural MRI data, individuals with better spatial memory showed thicker medial and lateral temporal cortices. Functional relevance of these findings was supported by task-based functional MRI analysis in the same participants and ad hoc meta-analysis. Exploratory resting-state functional MRI analyses centered on clusters of morphological effects revealed additional modulation of intrinsic network integration, particularly between lateral and medial temporal structures. Our work presents a novel spatial memory paradigm and supports an integrated structure-function substrate in the human temporal lobe. Task paradigms are programmed in python and made open access., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Illustration of the proposed NAS-DBN framework for deriving functional brain networks and temporal responses from volumetric task-based fMRI data. (A) PSO based NAS framework. 30 particles are initialized with random position and velocity, each particle represents a sub-net of DBN with specific network architecture. Testing loss of each sub-net (fitness function of PSO algorithm) is calculated after training. Then, evaluation and updating operation is conducted according to standard PSO procedure. After iterations of PSO, the global best particle represents the optimal architecture of DBN. (B) The optimal architecture of DBN. After NAS, DBN with optimal architecture is trained on group-wise fMRI data, and hierarchical temporal responses can be generated from each hidden layer. (C) Functional brain networks (spatial maps). The weight matrix of DBN model are mapped back to the brain 3D space and visualized as FBNs, which will be further compared with GLM derived templates by overlap rate. • A novel unsupervised PSO based deep belief network model with neural architecture search (NAS-DBN) in modeling functional brain networks (FBNs) from fMRI. • The NAS-DBN acts as a hierarchical feature extractor that decompose the preprocessed fMRI data into spatial features (FBNs) and temporal features. • The data-driven deep learning model provides much more latent information of fMRI than traditional models. • We derived 260 of hierarchical FBNs and temporal features from each hidden layer of DBN, including meaningful task specific FBNs and 10 resting state networks (RSNs). It has been shown that deep neural networks are powerful and flexible models that can be applied on fMRI data with superb representation ability over traditional methods. However, a challenge of neural network architecture design has also attracted attention: due to the high dimension of fMRI volume images, the manual process of network model design is very time-consuming and not optimal. To tackle this problem, we proposed an unsupervised neural architecture search (NAS) framework on a deep belief network (DBN) that models volumetric fMRI data, named NAS-DBN. The NAS-DBN framework is based on Particle Swarm Optimization (PSO) where the swarms of neural architectures can evolve and converge to a feasible optimal solution. The experiments showed that the proposed NAS-DBN framework can quickly find a robust architecture of DBN, yielding a hierarchy organization of functional brain networks (FBNs) and temporal responses. Compared with 3 manually designed DBNs, the proposed NAS-DBN has the lowest testing loss of 0.0197, suggesting an overall performance improvement of up to 47.9 %. For each task, the NAS-DBN identified 260 FBNs, including task-specific FBNs and resting state networks (RSN), which have high overlap rates to general linear model (GLM) derived templates and independent component analysis (ICA) derived RSN templates. The average overlap rate of NAS-DBN to GLM on 20 task-specific FBNs is as high as 0.536, indicating a performance improvement of up to 63.9 % in respect of network modeling. Besides, we showed that the NAS-DBN can simultaneously generate temporal responses that resemble the task designs very well, and it was observed that widespread overlaps between FBNs from different layers of NAS-DBN model form a hierarchical organization of FBNs. Our NAS-DBN framework contributes an effective, unsupervised NAS method for modeling volumetric task fMRI data. [ABSTRACT FROM AUTHOR]

Investigating context-dependent modulations of Functional Connectivity (FC) with functional magnetic resonance imaging is crucial to reveal the neurological underpinnings of cognitive processing. Most current analysis methods hypothesise sustained FC within the duration of a task, but this assumption has been shown too limiting by recent imaging studies. While several methods have been proposed to study functional dynamics during rest, task-based studies are yet to fully disentangle network modulations. Here, we propose a seed-based method to probe task-dependent modulations of brain activity by revealing Psychophysiological Interactions of Co-activation Patterns (PPI-CAPs). This point process-based approach temporally decomposes task-modulated connectivity into dynamic building blocks which cannot be captured by current methods, such as PPI or Dynamic Causal Modelling. Additionally, it identifies the occurrence of co-activation patterns at single frame resolution as opposed to window-based methods. In a naturalistic setting where participants watched a TV program, we retrieved several patterns of co-activation with a posterior cingulate cortex seed whose occurrence rates and polarity varied depending on the context; on the seed activity; or on an interaction between the two. Moreover, our method exposed the consistency in effective connectivity patterns across subjects and time, allowing us to uncover links between PPI-CAPs and specific stimuli contained in the video. Our study reveals that explicitly tracking connectivity pattern transients is paramount to advance our understanding of how different brain areas dynamically communicate when presented with a set of cues. • PPI-CAPs is a method for dynamic task-based effective connectivity. • Sparse moments of seed (de)activation show task-based changes in brain connectivity. • K-means++ clustered fMRI frames decompose Psychophysiological Interaction effects. • Moment-to-moment patterns of co-activation with a seed are linked to movie cues. [ABSTRACT FROM AUTHOR]

Resting state functional MR imaging methods can provide localization of the language system; however, presurgical functional localization of the language system with task-based functional MR imaging is the current standard of care before resection of brain tumors. These methods provide similar results and comparing them could be helpful for presurgical planning. We combine information from 3 data resources to provide quantitative information on the components of the language system. Tables and figures compare anatomic information, localization information from resting state fMR imaging, and activation patterns in different components of the language system expected from commonly used task fMR imaging experiments., Competing Interests: Disclosure No conflicts for all authors., (Copyright © 2020 Elsevier Inc. All rights reserved.)

We propose a method for estimating more reproducible functional networks that are more strongly associated with dynamic task activity by using recurrent neural networks with long short term memory (LSTMs). The LSTM model is trained in an unsupervised manner to learn to generate the functional magnetic resonance imaging (fMRI) time-series data in regions of interest. The learned functional networks can then be used for further analysis, e.g., correlation analysis to determine functional networks that are strongly associated with an fMRI task paradigm. We test our approach and compare to other methods for decomposing functional networks from fMRI activity on 2 related but separate datasets that employ a biological motion perception task. We demonstrate that the functional networks learned by the LSTM model are more strongly associated with the task activity and dynamics compared to other approaches. Furthermore, the patterns of network association are more closely replicated across subjects within the same dataset as well as across datasets. More reproducible functional networks are essential for better characterizing the neural correlates of a target task.

In the field of neuroimaging and cognitive neuroscience, functional Magnetic Resonance Imaging (fMRI) has been widely used to study the functional localization and connectivity of the brain. However, the inherently low signal-to-noise ratio (SNR) of the fMRI signals greatly limits the accuracy and resolution of current studies. In addressing this fundamental challenge in fMRI analytics, in this work we develop and implement a denoising method for task fMRI (tfMRI) data in order to delineate the high-resolution spatial pattern of the brain activation and functional connectivity via dictionary learning and sparse coding (DLSC). In addition to the traditional unsupervised dictionary learning model which has shown success in image denoising, we further utilize the prior knowledge of task paradigm to learn a dictionary consisting of both data-driven and model-driven terms for a more stable sparse representation of the data. The proposed method is applied to preprocess the motor tfMRI dataset from Human Connectome Project (HCP) for the purpose of brain activation detection and functional connectivity estimation. Comparison between the results from original and denoised fMRI data shows that the disruptive brain activation and functional connectivity patterns can be recovered, and the prominence of such patterns is improved through denoising. The proposed method is then compared with the temporal non-local means (tNLM)-based denoising method and shows consistently superior performance in various experimental settings. The promising results show that the proposed DLSC-based fMRI denoising method can effectively reduce the noise level of the fMRI signals and increase the interpretability of the inferred results, therefore constituting a crucial part of the preprocessing pipeline and provide the foundation for further high-resolution functional analysis.

Color is continuous, yet we group colors into discrete categories associated with color names (e.g., yellow, blue). Color categorization is a case in point in the debate on how language shapes human cognition. Evidence suggests that color categorization depends on top-down input from the language system to the visual cortex. We directly tested this hypothesis by assessing color categorization in a stroke patient, RDS, with a rare, selective deficit in naming visually presented chromatic colors, and relatively preserved achromatic color naming. Multimodal MRI revealed a left occipito-temporal lesion that directly damaged left color-biased regions, and functionally disconnected their right-hemisphere homologs from the language system. The lesion had a greater effect on RDS's chromatic color naming than on color categorization, which was relatively preserved on a nonverbal task. Color categorization and naming can thus be independent in the human brain, challenging the mandatory involvement of language in adult human cognition. • Are color categories an example of linguistic impact on non-verbal human cognition? • Patient RDS shows impairment in naming colors after a left-hemisphere stroke • The lesion disconnects color-biased visual regions from the language system • Relative sparing of color categorization shows its independence from color naming Color categories (e.g., red, yellow) may result from the top-down impact of language on perception. Siuda-Krzywicka et al. describe a patient with impaired color naming, after a stroke disconnects color perception from language. The patient still categorizes colors they could not name, showing robustness of color categorization against impaired linguistic processing. [ABSTRACT FROM AUTHOR]

The mainstream method used for the analysis of task functional Magnetic Resonance Imaging (fMRI) data, is to obtain task-related active brain regions based on generalized linear models. Machine learning as a data-driven technical method is increasingly used in fMRI data analysis. The language task data, including math task and story task, of the Human Connectome Project (HCP) was used in this work. We chose a linear support vector machine as a classifier to classify math and story tasks and compared them with the activated brain regions of a SPM statistical analysis. As a result, 13 of the 25 regions used for classification in SVM were activated regions, and 12 were non-activated regions. In particular, the right Paracentral Lobule and right Rolandic Operculum which belong to non-activated regions, contributed most to the classification. Therefore, the differences found in machine learning can provide a new understanding of the physiological mechanisms of brain regions under different tasks.

Objective: Patients with major depressive disorder (MDD) may experience a series of emotional and mental problems accompanied by characteristic clinical symptoms. Depressive patients often have emotional recognition disorders, but the reasons remain unclear. Though a great many functional abnormalities have been observed in the brains of depressed patients, such abnormalities are not often related to clinical symptoms. Currently in Traditional Chinese Medicine (TCM), syndrome differentiation for the MDD mainly consists of excess pattern (EP), and deficiency pattern (DP). EP and DP emphasize balance-regulation thought processes, and are widely used in diagnosis of diseases including depression, anxiety, insomnia, and other emotional disorders. We hope that syndrome differentiation in TCM can combine clinical symptoms and brain function more effectively. The present study investigated altered patterns and different association of brain activation in MDD patients with EP and DP during a facial emotion discrimination task with fMRI., Methods: A total of 45 patients (20 with EP and 25 with DP) and 18 normal controls participated in this study. Whole-brain functional scans were collected for each subject. Different patterns of brain activation and association during the facial emotion discrimination task were analyzed statistically., Results: Comparing all the MDD patients with the normal controls, there were no significant differences for sad vs. neutral condition or for happy vs. neutral condition (corrected p >  0.05). One-way ANCOVA showed significant differences in the left inferior frontal gyrus, the left insula, and the left caudate for sad vs. neutral condition across the DP, EP and NC groups (corrected p <  0.05). The whole brain activation comparison for sad vs. neutral condition between the EP MDD subtype and the DP MDD subtype further verified these differences in the left insula and left inferior frontal gyrus, discovering that these regions showed increased activation in EP MDD subtype compared with the DP MDD subtype (corrected p <  0.05). There were no significant differences in brain activation between each MDD subtype and the normal controls., Conclusion: Disparities in sad face processing exist between MDD patients with different TCM syndrome types, suggesting that TCM syndrome differentiation may provide a biological basis for negativity bias in depression, and may determine both symptom formation and social dysfunction., (Copyright © 2018. Published by Elsevier Ltd.)

Neuroimaging research made rapid advances in the study of the functional architecture of the brain during the past decade. Many proposals endorsed the relevance of large-scale brain networks, defined as ensembles of brain regions that exhibit highly correlated signal fluctuations. However, analysis methods need further elaboration to define the functional and anatomical extent of specialized subsystems within classical networks with a high reliability. We present a novel approach to characterize and examine the functional proprieties of brain networks. This approach, labeled as brain network profiling (BNP), considers similarities in task-evoked activity and resting-state functional connectivity across biologically relevant brain subregions. To combine task-driven activity and functional connectivity features, principal components were extracted separately for task-related beta values and resting-state functional connectivity z-values (data available from the Human Connectome Project), from 360 brain parcels. Multiple clustering procedures were employed to assess if different clustering methods (Gaussian mixtures; k-means) and/or data structures (task and rest data; only rest data) led to improvements in the replication of the brain architecture. The results indicated that combining information from resting-state functional connectivity and task-evoked activity and using Gaussian mixtures models for clustering produces more reliable results (99% replication across data sets). Moreover, the findings revealed a high-resolution partition of the cerebral cortex in 16 networks with unique functional connectivity and/or task-evoked activity profiles. BNP potentially offers new approaches to advance the investigation of the brain functional architecture., (© 2018 Wiley Periodicals, Inc.)

It is being hypothesised that the developing adolescent brain is increasingly enlisting long-range connectivity, allowing improved communication between spatially distant brain regions. The developmental trajectories of such maturational changes remain elusive. Here, we aim to study how the brain engages in multiple tasks (working memory, reward processing, and inhibition) at the network-level and evaluate how effects of age across these tasks are related to each other. We characterise how the brain departs from its functional baseline architecture towards task-induced functional connectivity modulations using a novel measure called task potency, allowing direct comparison between tasks by defining sensitivity to one or multiple tasks. By applying this method in a sample of healthy participants (N = 218) aged 8-30 years, we demonstrate maturational changes in task-dependent functional co-activation over and above baseline connectivity maturation. Our results provide evidence for task-specific maturational windows with different cognitive systems probed by different tasks displaying specific age-range dependencies of strongest developmental change. Our results highlight the use of task potency for modelling developmental trajectories and the impact of differential maturation across tasks. This enables better characterisation of cognitive processes disrupted in neurodevelopmental disorders and may explain the increased level of heterogeneity observed in adolescent population studies., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Preterm birth engenders an increased risk of conditions like cerebral palsy and therefore this time may be crucial for the brain's developing sensori-motor system. However, little is known about how cortical sensori-motor function matures at this time, whether development is influenced by experience, and about its role in spontaneous motor behavior. We aimed to systematically characterize spatial and temporal maturation of sensori-motor functional brain activity across this period using functional MRI and a custom-made robotic stimulation device. We studied 57 infants aged from 30 + 2 to 43 + 2 weeks postmenstrual age. Following both induced and spontaneous right wrist movements, we saw consistent positive blood oxygen level-dependent functional responses in the contralateral (left) primary somatosensory and motor cortices. In addition, we saw a maturational trend toward faster, higher amplitude, and more spatially dispersed functional responses; and increasing integration of the ipsilateral hemisphere and sensori-motor associative areas. We also found that interhemispheric functional connectivity was significantly related to ex-utero exposure, suggesting the influence of experience-dependent mechanisms. At term equivalent age, we saw a decrease in both response amplitude and interhemispheric functional connectivity, and an increase in spatial specificity, culminating in the establishment of a sensori-motor functional response similar to that seen in adults., (© The Author 2015. Published by Oxford University Press.)