Guo, Hao; Liu, Lei; Chen, Junjie; Xu, Yong; Jie, Xiang
2017-01-01
Functional magnetic resonance imaging (fMRI) is one of the most useful methods to generate functional connectivity networks of the brain. However, conventional network generation methods ignore dynamic changes of functional connectivity between brain regions. Previous studies proposed constructing high-order functional connectivity networks that consider the time-varying characteristics of functional connectivity, and a clustering method was performed to decrease computational cost. However, random selection of the initial clustering centers and the number of clusters negatively affected classification accuracy, and the network lost neurological interpretability. Here we propose a novel method that introduces the minimum spanning tree method to high-order functional connectivity networks. As an unbiased method, the minimum spanning tree simplifies high-order network structure while preserving its core framework. The dynamic characteristics of time series are not lost with this approach, and the neurological interpretation of the network is guaranteed. Simultaneously, we propose a multi-parameter optimization framework that involves extracting discriminative features from the minimum spanning tree high-order functional connectivity networks. Compared with the conventional methods, our resting-state fMRI classification method based on minimum spanning tree high-order functional connectivity networks greatly improved the diagnostic accuracy for Alzheimer's disease. PMID:29249926
Masud, Mohammad Shahed; Borisyuk, Roman; Stuart, Liz
2017-07-15
This study analyses multiple spike trains (MST) data, defines its functional connectivity and subsequently visualises an accurate diagram of connections. This is a challenging problem. For example, it is difficult to distinguish the common input and the direct functional connection of two spike trains. The new method presented in this paper is based on the traditional pairwise cross-correlation function (CCF) and a new combination of statistical techniques. First, the CCF is used to create the Advanced Correlation Grid (ACG) correlation where both the significant peak of the CCF and the corresponding time delay are used for detailed analysis of connectivity. Second, these two features of functional connectivity are used to classify connections. Finally, the visualization technique is used to represent the topology of functional connections. Examples are presented in the paper to demonstrate the new Advanced Correlation Grid method and to show how it enables discrimination between (i) influence from one spike train to another through an intermediate spike train and (ii) influence from one common spike train to another pair of analysed spike trains. The ACG method enables scientists to automatically distinguish between direct connections from spurious connections such as common source connection and indirect connection whereas existing methods require in-depth analysis to identify such connections. The ACG is a new and effective method for studying functional connectivity of multiple spike trains. This method can identify accurately all the direct connections and can distinguish common source and indirect connections automatically. Copyright © 2017 Elsevier B.V. All rights reserved.
Functional connectivity change as shared signal dynamics
Cole, Michael W.; Yang, Genevieve J.; Murray, John D.; Repovš, Grega; Anticevic, Alan
2015-01-01
Background An increasing number of neuroscientific studies gain insights by focusing on differences in functional connectivity – between groups, individuals, temporal windows, or task conditions. We found using simulations that additional insights into such differences can be gained by forgoing variance normalization, a procedure used by most functional connectivity measures. Simulations indicated that these functional connectivity measures are sensitive to increases in independent fluctuations (unshared signal) in time series, consistently reducing functional connectivity estimates (e.g., correlations) even though such changes are unrelated to corresponding fluctuations (shared signal) between those time series. This is inconsistent with the common notion of functional connectivity as the amount of inter-region interaction. New Method Simulations revealed that a version of correlation without variance normalization – covariance – was able to isolate differences in shared signal, increasing interpretability of observed functional connectivity change. Simulations also revealed cases problematic for non-normalized methods, leading to a “covariance conjunction” method combining the benefits of both normalized and non-normalized approaches. Results We found that covariance and covariance conjunction methods can detect functional connectivity changes across a variety of tasks and rest in both clinical and non-clinical functional MRI datasets. Comparison with Existing Method(s) We verified using a variety of tasks and rest in both clinical and non-clinical functional MRI datasets that it matters in practice whether correlation, covariance, or covariance conjunction methods are used. Conclusions These results demonstrate the practical and theoretical utility of isolating changes in shared signal, improving the ability to interpret observed functional connectivity change. PMID:26642966
A new class of methods for functional connectivity estimation
NASA Astrophysics Data System (ADS)
Lin, Wutu
Measuring functional connectivity from neural recordings is important in understanding processing in cortical networks. The covariance-based methods are the current golden standard for functional connectivity estimation. However, the link between the pair-wise correlations and the physiological connections inside the neural network is unclear. Therefore, the power of inferring physiological basis from functional connectivity estimation is limited. To build a stronger tie and better understand the relationship between functional connectivity and physiological neural network, we need (1) a realistic model to simulate different types of neural recordings with known ground truth for benchmarking; (2) a new functional connectivity method that produce estimations closely reflecting the physiological basis. In this thesis, (1) I tune a spiking neural network model to match with human sleep EEG data, (2) introduce a new class of methods for estimating connectivity from different kinds of neural signals and provide theory proof for its superiority, (3) apply it to simulated fMRI data as an application.
Statistical technique for analysing functional connectivity of multiple spike trains.
Masud, Mohammad Shahed; Borisyuk, Roman
2011-03-15
A new statistical technique, the Cox method, used for analysing functional connectivity of simultaneously recorded multiple spike trains is presented. This method is based on the theory of modulated renewal processes and it estimates a vector of influence strengths from multiple spike trains (called reference trains) to the selected (target) spike train. Selecting another target spike train and repeating the calculation of the influence strengths from the reference spike trains enables researchers to find all functional connections among multiple spike trains. In order to study functional connectivity an "influence function" is identified. This function recognises the specificity of neuronal interactions and reflects the dynamics of postsynaptic potential. In comparison to existing techniques, the Cox method has the following advantages: it does not use bins (binless method); it is applicable to cases where the sample size is small; it is sufficiently sensitive such that it estimates weak influences; it supports the simultaneous analysis of multiple influences; it is able to identify a correct connectivity scheme in difficult cases of "common source" or "indirect" connectivity. The Cox method has been thoroughly tested using multiple sets of data generated by the neural network model of the leaky integrate and fire neurons with a prescribed architecture of connections. The results suggest that this method is highly successful for analysing functional connectivity of simultaneously recorded multiple spike trains. Copyright © 2011 Elsevier B.V. All rights reserved.
Passaro, Antony D; Vettel, Jean M; McDaniel, Jonathan; Lawhern, Vernon; Franaszczuk, Piotr J; Gordon, Stephen M
2017-03-01
During an experimental session, behavioral performance fluctuates, yet most neuroimaging analyses of functional connectivity derive a single connectivity pattern. These conventional connectivity approaches assume that since the underlying behavior of the task remains constant, the connectivity pattern is also constant. We introduce a novel method, behavior-regressed connectivity (BRC), to directly examine behavioral fluctuations within an experimental session and capture their relationship to changes in functional connectivity. This method employs the weighted phase lag index (WPLI) applied to a window of trials with a weighting function. Using two datasets, the BRC results are compared to conventional connectivity results during two time windows: the one second before stimulus onset to identify predictive relationships, and the one second after onset to capture task-dependent relationships. In both tasks, we replicate the expected results for the conventional connectivity analysis, and extend our understanding of the brain-behavior relationship using the BRC analysis, demonstrating subject-specific BRC maps that correspond to both positive and negative relationships with behavior. Comparison with Existing Method(s): Conventional connectivity analyses assume a consistent relationship between behaviors and functional connectivity, but the BRC method examines performance variability within an experimental session to understand dynamic connectivity and transient behavior. The BRC approach examines connectivity as it covaries with behavior to complement the knowledge of underlying neural activity derived from conventional connectivity analyses. Within this framework, BRC may be implemented for the purpose of understanding performance variability both within and between participants. Published by Elsevier B.V.
Cheng, Wei; Rolls, Edmund T; Zhang, Jie; Sheng, Wenbo; Ma, Liang; Wan, Lin; Luo, Qiang; Feng, Jianfeng
2017-03-01
A powerful new method is described called Knowledge based functional connectivity Enrichment Analysis (KEA) for interpreting resting state functional connectivity, using circuits that are functionally identified using search terms with the Neurosynth database. The method derives its power by focusing on neural circuits, sets of brain regions that share a common biological function, instead of trying to interpret single functional connectivity links. This provides a novel way of investigating how task- or function-related networks have resting state functional connectivity differences in different psychiatric states, provides a new way to bridge the gap between task and resting-state functional networks, and potentially helps to identify brain networks that might be treated. The method was applied to interpreting functional connectivity differences in autism. Functional connectivity decreases at the network circuit level in 394 patients with autism compared with 473 controls were found in networks involving the orbitofrontal cortex, anterior cingulate cortex, middle temporal gyrus cortex, and the precuneus, in networks that are implicated in the sense of self, face processing, and theory of mind. The decreases were correlated with symptom severity. Copyright © 2017. Published by Elsevier Inc.
Schmithorst, Vincent J; Holland, Scott K
2007-03-01
A Bayesian method for functional connectivity analysis was adapted to investigate between-group differences. This method was applied in a large cohort of almost 300 children to investigate differences in boys and girls in the relationship between intelligence and functional connectivity for the task of narrative comprehension. For boys, a greater association was shown between intelligence and the functional connectivity linking Broca's area to auditory processing areas, including Wernicke's areas and the right posterior superior temporal gyrus. For girls, a greater association was shown between intelligence and the functional connectivity linking the left posterior superior temporal gyrus to Wernicke's areas bilaterally. A developmental effect was also seen, with girls displaying a positive correlation with age in the association between intelligence and the functional connectivity linking the right posterior superior temporal gyrus to Wernicke's areas bilaterally. Our results demonstrate a sexual dimorphism in the relationship of functional connectivity to intelligence in children and an increasing reliance on inter-hemispheric connectivity in girls with age.
Whole Brain Functional Connectivity Pattern Homogeneity Mapping.
Wang, Lijie; Xu, Jinping; Wang, Chao; Wang, Jiaojian
2018-01-01
Mounting studies have demonstrated that brain functions are determined by its external functional connectivity patterns. However, how to characterize the voxel-wise similarity of whole brain functional connectivity pattern is still largely unknown. In this study, we introduced a new method called functional connectivity homogeneity (FcHo) to delineate the voxel-wise similarity of whole brain functional connectivity patterns. FcHo was defined by measuring the whole brain functional connectivity patterns similarity of a given voxel with its nearest 26 neighbors using Kendall's coefficient concordance (KCC). The robustness of this method was tested in four independent datasets selected from a large repository of MRI. Furthermore, FcHo mapping results were further validated using the nearest 18 and six neighbors and intra-subject reproducibility with each subject scanned two times. We also compared FcHo distribution patterns with local regional homogeneity (ReHo) to identify the similarity and differences of the two methods. Finally, FcHo method was used to identify the differences of whole brain functional connectivity patterns between professional Chinese chess players and novices to test its application. FcHo mapping consistently revealed that the high FcHo was mainly distributed in association cortex including parietal lobe, frontal lobe, occipital lobe and default mode network (DMN) related areas, whereas the low FcHo was mainly found in unimodal cortex including primary visual cortex, sensorimotor cortex, paracentral lobule and supplementary motor area. These results were further supported by analyses of the nearest 18 and six neighbors and intra-subject similarity. Moreover, FcHo showed both similar and different whole brain distribution patterns compared to ReHo. Finally, we demonstrated that FcHo can effectively identify the whole brain functional connectivity pattern differences between professional Chinese chess players and novices. Our findings indicated that FcHo is a reliable method to delineate the whole brain functional connectivity pattern similarity and may provide a new way to study the functional organization and to reveal neuropathological basis for brain disorders.
Altered Whole-Brain and Network-Based Functional Connectivity in Parkinson's Disease.
de Schipper, Laura J; Hafkemeijer, Anne; van der Grond, Jeroen; Marinus, Johan; Henselmans, Johanna M L; van Hilten, Jacobus J
2018-01-01
Background: Functional imaging methods, such as resting-state functional magnetic resonance imaging, reflect changes in neural connectivity and may help to assess the widespread consequences of disease-specific network changes in Parkinson's disease. In this study we used a relatively new graph analysis approach in functional imaging: eigenvector centrality mapping. This model-free method, applied to all voxels in the brain, identifies prominent regions in the brain network hierarchy and detects localized differences between patient populations. In other neurological disorders, eigenvector centrality mapping has been linked to changes in functional connectivity in certain nodes of brain networks. Objectives: Examining changes in functional brain connectivity architecture on a whole brain and network level in patients with Parkinson's disease. Methods: Whole brain resting-state functional architecture was studied with a recently introduced graph analysis approach (eigenvector centrality mapping). Functional connectivity was further investigated in relation to eight known resting-state networks. Cross-sectional analyses included group comparison of functional connectivity measures of Parkinson's disease patients ( n = 107) with control subjects ( n = 58) and correlations with clinical data, including motor and cognitive impairment and a composite measure of predominantly non-dopaminergic symptoms. Results: Eigenvector centrality mapping revealed that frontoparietal regions were more prominent in the whole-brain network function in patients compared to control subjects, while frontal and occipital brain areas were less prominent in patients. Using standard resting-state networks, we found predominantly increased functional connectivity, namely within sensorimotor system and visual networks in patients. Regional group differences in functional connectivity of both techniques between patients and control subjects partly overlapped for highly connected posterior brain regions, in particular in the posterior cingulate cortex and precuneus. Clinico-functional imaging relations were not found. Conclusions: Changes on the level of functional brain connectivity architecture might provide a different perspective of pathological consequences of Parkinson's disease. The involvement of specific, highly connected (hub) brain regions may influence whole brain functional network architecture in Parkinson's disease.
Predicting individual brain functional connectivity using a Bayesian hierarchical model.
Dai, Tian; Guo, Ying
2017-02-15
Network-oriented analysis of functional magnetic resonance imaging (fMRI), especially resting-state fMRI, has revealed important association between abnormal connectivity and brain disorders such as schizophrenia, major depression and Alzheimer's disease. Imaging-based brain connectivity measures have become a useful tool for investigating the pathophysiology, progression and treatment response of psychiatric disorders and neurodegenerative diseases. Recent studies have started to explore the possibility of using functional neuroimaging to help predict disease progression and guide treatment selection for individual patients. These studies provide the impetus to develop statistical methodology that would help provide predictive information on disease progression-related or treatment-related changes in neural connectivity. To this end, we propose a prediction method based on Bayesian hierarchical model that uses individual's baseline fMRI scans, coupled with relevant subject characteristics, to predict the individual's future functional connectivity. A key advantage of the proposed method is that it can improve the accuracy of individualized prediction of connectivity by combining information from both group-level connectivity patterns that are common to subjects with similar characteristics as well as individual-level connectivity features that are particular to the specific subject. Furthermore, our method also offers statistical inference tools such as predictive intervals that help quantify the uncertainty or variability of the predicted outcomes. The proposed prediction method could be a useful approach to predict the changes in individual patient's brain connectivity with the progression of a disease. It can also be used to predict a patient's post-treatment brain connectivity after a specified treatment regimen. Another utility of the proposed method is that it can be applied to test-retest imaging data to develop a more reliable estimator for individual functional connectivity. We show there exists a nice connection between our proposed estimator and a recently developed shrinkage estimator of connectivity measures in the neuroimaging community. We develop an expectation-maximization (EM) algorithm for estimation of the proposed Bayesian hierarchical model. Simulations studies are performed to evaluate the accuracy of our proposed prediction methods. We illustrate the application of the methods with two data examples: the longitudinal resting-state fMRI from ADNI2 study and the test-retest fMRI data from Kirby21 study. In both the simulation studies and the fMRI data applications, we demonstrate that the proposed methods provide more accurate prediction and more reliable estimation of individual functional connectivity as compared with alternative methods. Copyright © 2017 Elsevier Inc. All rights reserved.
Guo, Hao; Qin, Mengna; Chen, Junjie; Xu, Yong; Xiang, Jie
2017-01-01
High-order functional connectivity networks are rich in time information that can reflect dynamic changes in functional connectivity between brain regions. Accordingly, such networks are widely used to classify brain diseases. However, traditional methods for processing high-order functional connectivity networks generally include the clustering method, which reduces data dimensionality. As a result, such networks cannot be effectively interpreted in the context of neurology. Additionally, due to the large scale of high-order functional connectivity networks, it can be computationally very expensive to use complex network or graph theory to calculate certain topological properties. Here, we propose a novel method of generating a high-order minimum spanning tree functional connectivity network. This method increases the neurological significance of the high-order functional connectivity network, reduces network computing consumption, and produces a network scale that is conducive to subsequent network analysis. To ensure the quality of the topological information in the network structure, we used frequent subgraph mining technology to capture the discriminative subnetworks as features and combined this with quantifiable local network features. Then we applied a multikernel learning technique to the corresponding selected features to obtain the final classification results. We evaluated our proposed method using a data set containing 38 patients with major depressive disorder and 28 healthy controls. The experimental results showed a classification accuracy of up to 97.54%.
Qin, Mengna; Chen, Junjie; Xu, Yong; Xiang, Jie
2017-01-01
High-order functional connectivity networks are rich in time information that can reflect dynamic changes in functional connectivity between brain regions. Accordingly, such networks are widely used to classify brain diseases. However, traditional methods for processing high-order functional connectivity networks generally include the clustering method, which reduces data dimensionality. As a result, such networks cannot be effectively interpreted in the context of neurology. Additionally, due to the large scale of high-order functional connectivity networks, it can be computationally very expensive to use complex network or graph theory to calculate certain topological properties. Here, we propose a novel method of generating a high-order minimum spanning tree functional connectivity network. This method increases the neurological significance of the high-order functional connectivity network, reduces network computing consumption, and produces a network scale that is conducive to subsequent network analysis. To ensure the quality of the topological information in the network structure, we used frequent subgraph mining technology to capture the discriminative subnetworks as features and combined this with quantifiable local network features. Then we applied a multikernel learning technique to the corresponding selected features to obtain the final classification results. We evaluated our proposed method using a data set containing 38 patients with major depressive disorder and 28 healthy controls. The experimental results showed a classification accuracy of up to 97.54%. PMID:29387141
Sojoudi, Alireza; Goodyear, Bradley G
2016-12-01
Spontaneous fluctuations of blood-oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI) signals are highly synchronous between brain regions that serve similar functions. This provides a means to investigate functional networks; however, most analysis techniques assume functional connections are constant over time. This may be problematic in the case of neurological disease, where functional connections may be highly variable. Recently, several methods have been proposed to determine moment-to-moment changes in the strength of functional connections over an imaging session (so called dynamic connectivity). Here a novel analysis framework based on a hierarchical observation modeling approach was proposed, to permit statistical inference of the presence of dynamic connectivity. A two-level linear model composed of overlapping sliding windows of fMRI signals, incorporating the fact that overlapping windows are not independent was described. To test this approach, datasets were synthesized whereby functional connectivity was either constant (significant or insignificant) or modulated by an external input. The method successfully determines the statistical significance of a functional connection in phase with the modulation, and it exhibits greater sensitivity and specificity in detecting regions with variable connectivity, when compared with sliding-window correlation analysis. For real data, this technique possesses greater reproducibility and provides a more discriminative estimate of dynamic connectivity than sliding-window correlation analysis. Hum Brain Mapp 37:4566-4580, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Zou, Ling; Guo, Qian; Xu, Yi; Yang, Biao; Jiao, Zhuqing; Xiang, Jianbo
2016-04-29
Functional magnetic resonance imaging (fMRI) is an important tool in neuroscience for assessing connectivity and interactions between distant areas of the brain. To find and characterize the coherent patterns of brain activity as a means of identifying brain systems for the cognitive reappraisal of the emotion task, both density-based k-means clustering and independent component analysis (ICA) methods can be applied to characterize the interactions between brain regions involved in cognitive reappraisal of emotion. Our results reveal that compared with the ICA method, the density-based k-means clustering method provides a higher sensitivity of polymerization. In addition, it is more sensitive to those relatively weak functional connection regions. Thus, the study concludes that in the process of receiving emotional stimuli, the relatively obvious activation areas are mainly distributed in the frontal lobe, cingulum and near the hypothalamus. Furthermore, density-based k-means clustering method creates a more reliable method for follow-up studies of brain functional connectivity.
Cao, Longlong; Guo, Shuixia; Xue, Zhimin; Hu, Yong; Liu, Haihong; Mwansisya, Tumbwene E; Pu, Weidan; Yang, Bo; Liu, Chang; Feng, Jianfeng; Chen, Eric Y H; Liu, Zhening
2014-02-01
Aberrant brain functional connectivity patterns have been reported in major depressive disorder (MDD). It is unknown whether they can be used in discriminant analysis for diagnosis of MDD. In the present study we examined the efficiency of discriminant analysis of MDD by individualized computer-assisted diagnosis. Based on resting-state functional magnetic resonance imaging data, a new approach was adopted to investigate functional connectivity changes in 39 MDD patients and 37 well-matched healthy controls. By using the proposed feature selection method, we identified significant altered functional connections in patients. They were subsequently applied to our analysis as discriminant features using a support vector machine classification method. Furthermore, the relative contribution of functional connectivity was estimated. After subset selection of high-dimension features, the support vector machine classifier reached up to approximately 84% with leave-one-out training during the discrimination process. Through summarizing the classification contribution of functional connectivities, we obtained four obvious contribution modules: inferior orbitofrontal module, supramarginal gyrus module, inferior parietal lobule-posterior cingulated gyrus module and middle temporal gyrus-inferior temporal gyrus module. The experimental results demonstrated that the proposed method is effective in discriminating MDD patients from healthy controls. Functional connectivities might be useful as new biomarkers to assist clinicians in computer auxiliary diagnosis of MDD. © 2013 The Authors. Psychiatry and Clinical Neurosciences © 2013 Japanese Society of Psychiatry and Neurology.
[Seeking the aetiology of autistic spectrum disorder. Part 2: Functional neuroimaging].
Bryńska, Anita
2012-01-01
Multiple functional imaging techniques help to a better understanding of the neurobiological basis of autism-spectrum disorders (ASD). The early functional imaging studies on ASD focused on task-specific methods related to core symptom domains and explored patterns of activation in response to face processing, theory of mind tasks, language processing and executive function tasks. On the other hand, fMRI research in ASD focused on the development of functional connectivity methods and has provided evidence of alterations in cortical connectivity in ASD and establish autism as a disorder of under-connectivity among the brain regions participating in cortical networks. This atypical functional connectivity in ASD results in inefficiency and poor integration of processing in network connections to achieve task performance. The goal of this review is to summarise the actual neuroimaging functional data and examine their implication for understanding of the neurobiology of ASD.
NASA Astrophysics Data System (ADS)
D'Souza, Adora M.; Abidin, Anas Zainul; Nagarajan, Mahesh B.; Wismüller, Axel
2016-03-01
We investigate the applicability of a computational framework, called mutual connectivity analysis (MCA), for directed functional connectivity analysis in both synthetic and resting-state functional MRI data. This framework comprises of first evaluating non-linear cross-predictability between every pair of time series prior to recovering the underlying network structure using community detection algorithms. We obtain the non-linear cross-prediction score between time series using Generalized Radial Basis Functions (GRBF) neural networks. These cross-prediction scores characterize the underlying functionally connected networks within the resting brain, which can be extracted using non-metric clustering approaches, such as the Louvain method. We first test our approach on synthetic models with known directional influence and network structure. Our method is able to capture the directional relationships between time series (with an area under the ROC curve = 0.92 +/- 0.037) as well as the underlying network structure (Rand index = 0.87 +/- 0.063) with high accuracy. Furthermore, we test this method for network recovery on resting-state fMRI data, where results are compared to the motor cortex network recovered from a motor stimulation sequence, resulting in a strong agreement between the two (Dice coefficient = 0.45). We conclude that our MCA approach is effective in analyzing non-linear directed functional connectivity and in revealing underlying functional network structure in complex systems.
DSouza, Adora M; Abidin, Anas Zainul; Nagarajan, Mahesh B; Wismüller, Axel
2016-03-29
We investigate the applicability of a computational framework, called mutual connectivity analysis (MCA), for directed functional connectivity analysis in both synthetic and resting-state functional MRI data. This framework comprises of first evaluating non-linear cross-predictability between every pair of time series prior to recovering the underlying network structure using community detection algorithms. We obtain the non-linear cross-prediction score between time series using Generalized Radial Basis Functions (GRBF) neural networks. These cross-prediction scores characterize the underlying functionally connected networks within the resting brain, which can be extracted using non-metric clustering approaches, such as the Louvain method. We first test our approach on synthetic models with known directional influence and network structure. Our method is able to capture the directional relationships between time series (with an area under the ROC curve = 0.92 ± 0.037) as well as the underlying network structure (Rand index = 0.87 ± 0.063) with high accuracy. Furthermore, we test this method for network recovery on resting-state fMRI data, where results are compared to the motor cortex network recovered from a motor stimulation sequence, resulting in a strong agreement between the two (Dice coefficient = 0.45). We conclude that our MCA approach is effective in analyzing non-linear directed functional connectivity and in revealing underlying functional network structure in complex systems.
Functional Brain Networks: Does the Choice of Dependency Estimator and Binarization Method Matter?
NASA Astrophysics Data System (ADS)
Jalili, Mahdi
2016-07-01
The human brain can be modelled as a complex networked structure with brain regions as individual nodes and their anatomical/functional links as edges. Functional brain networks are constructed by first extracting weighted connectivity matrices, and then binarizing them to minimize the noise level. Different methods have been used to estimate the dependency values between the nodes and to obtain a binary network from a weighted connectivity matrix. In this work we study topological properties of EEG-based functional networks in Alzheimer’s Disease (AD). To estimate the connectivity strength between two time series, we use Pearson correlation, coherence, phase order parameter and synchronization likelihood. In order to binarize the weighted connectivity matrices, we use Minimum Spanning Tree (MST), Minimum Connected Component (MCC), uniform threshold and density-preserving methods. We find that the detected AD-related abnormalities highly depend on the methods used for dependency estimation and binarization. Topological properties of networks constructed using coherence method and MCC binarization show more significant differences between AD and healthy subjects than the other methods. These results might explain contradictory results reported in the literature for network properties specific to AD symptoms. The analysis method should be seriously taken into account in the interpretation of network-based analysis of brain signals.
Ing, Alex; Schwarzbauer, Christian
2014-01-01
Functional connectivity has become an increasingly important area of research in recent years. At a typical spatial resolution, approximately 300 million connections link each voxel in the brain with every other. This pattern of connectivity is known as the functional connectome. Connectivity is often compared between experimental groups and conditions. Standard methods used to control the type 1 error rate are likely to be insensitive when comparisons are carried out across the whole connectome, due to the huge number of statistical tests involved. To address this problem, two new cluster based methods--the cluster size statistic (CSS) and cluster mass statistic (CMS)--are introduced to control the family wise error rate across all connectivity values. These methods operate within a statistical framework similar to the cluster based methods used in conventional task based fMRI. Both methods are data driven, permutation based and require minimal statistical assumptions. Here, the performance of each procedure is evaluated in a receiver operator characteristic (ROC) analysis, utilising a simulated dataset. The relative sensitivity of each method is also tested on real data: BOLD (blood oxygen level dependent) fMRI scans were carried out on twelve subjects under normal conditions and during the hypercapnic state (induced through the inhalation of 6% CO2 in 21% O2 and 73%N2). Both CSS and CMS detected significant changes in connectivity between normal and hypercapnic states. A family wise error correction carried out at the individual connection level exhibited no significant changes in connectivity.
Ing, Alex; Schwarzbauer, Christian
2014-01-01
Functional connectivity has become an increasingly important area of research in recent years. At a typical spatial resolution, approximately 300 million connections link each voxel in the brain with every other. This pattern of connectivity is known as the functional connectome. Connectivity is often compared between experimental groups and conditions. Standard methods used to control the type 1 error rate are likely to be insensitive when comparisons are carried out across the whole connectome, due to the huge number of statistical tests involved. To address this problem, two new cluster based methods – the cluster size statistic (CSS) and cluster mass statistic (CMS) – are introduced to control the family wise error rate across all connectivity values. These methods operate within a statistical framework similar to the cluster based methods used in conventional task based fMRI. Both methods are data driven, permutation based and require minimal statistical assumptions. Here, the performance of each procedure is evaluated in a receiver operator characteristic (ROC) analysis, utilising a simulated dataset. The relative sensitivity of each method is also tested on real data: BOLD (blood oxygen level dependent) fMRI scans were carried out on twelve subjects under normal conditions and during the hypercapnic state (induced through the inhalation of 6% CO2 in 21% O2 and 73%N2). Both CSS and CMS detected significant changes in connectivity between normal and hypercapnic states. A family wise error correction carried out at the individual connection level exhibited no significant changes in connectivity. PMID:24906136
Nakae, Ken; Ikegaya, Yuji; Ishikawa, Tomoe; Oba, Shigeyuki; Urakubo, Hidetoshi; Koyama, Masanori; Ishii, Shin
2014-01-01
Crosstalk between neurons and glia may constitute a significant part of information processing in the brain. We present a novel method of statistically identifying interactions in a neuron–glia network. We attempted to identify neuron–glia interactions from neuronal and glial activities via maximum-a-posteriori (MAP)-based parameter estimation by developing a generalized linear model (GLM) of a neuron–glia network. The interactions in our interest included functional connectivity and response functions. We evaluated the cross-validated likelihood of GLMs that resulted from the addition or removal of connections to confirm the existence of specific neuron-to-glia or glia-to-neuron connections. We only accepted addition or removal when the modification improved the cross-validated likelihood. We applied the method to a high-throughput, multicellular in vitro Ca2+ imaging dataset obtained from the CA3 region of a rat hippocampus, and then evaluated the reliability of connectivity estimates using a statistical test based on a surrogate method. Our findings based on the estimated connectivity were in good agreement with currently available physiological knowledge, suggesting our method can elucidate undiscovered functions of neuron–glia systems. PMID:25393874
Structure-Function Network Mapping and Its Assessment via Persistent Homology
2017-01-01
Understanding the relationship between brain structure and function is a fundamental problem in network neuroscience. This work deals with the general method of structure-function mapping at the whole-brain level. We formulate the problem as a topological mapping of structure-function connectivity via matrix function, and find a stable solution by exploiting a regularization procedure to cope with large matrices. We introduce a novel measure of network similarity based on persistent homology for assessing the quality of the network mapping, which enables a detailed comparison of network topological changes across all possible thresholds, rather than just at a single, arbitrary threshold that may not be optimal. We demonstrate that our approach can uncover the direct and indirect structural paths for predicting functional connectivity, and our network similarity measure outperforms other currently available methods. We systematically validate our approach with (1) a comparison of regularized vs. non-regularized procedures, (2) a null model of the degree-preserving random rewired structural matrix, (3) different network types (binary vs. weighted matrices), and (4) different brain parcellation schemes (low vs. high resolutions). Finally, we evaluate the scalability of our method with relatively large matrices (2514x2514) of structural and functional connectivity obtained from 12 healthy human subjects measured non-invasively while at rest. Our results reveal a nonlinear structure-function relationship, suggesting that the resting-state functional connectivity depends on direct structural connections, as well as relatively parsimonious indirect connections via polysynaptic pathways. PMID:28046127
Caffo, Brian S.; Crainiceanu, Ciprian M.; Verduzco, Guillermo; Joel, Suresh; Mostofsky, Stewart H.; Bassett, Susan Spear; Pekar, James J.
2010-01-01
Functional connectivity is the study of correlations in measured neurophysiological signals. Altered functional connectivity has been shown to be associated with a variety of cognitive and memory impairments and dysfunction, including Alzheimer’s disease. In this manuscript we use a two-stage application of the singular value decomposition to obtain data driven population-level measures of functional connectivity in functional magnetic resonance imaging (fMRI). The method is computationally simple and amenable to high dimensional fMRI data with large numbers of subjects. Simulation studies suggest the ability of the decomposition methods to recover population brain networks and their associated loadings. We further demonstrate the utility of these decompositions in a functional logistic regression model. The method is applied to a novel fMRI study of Alzheimer’s disease risk under a verbal paired associates task. We found a indication of alternative connectivity in clinically asymptomatic at-risk subjects when compared to controls, that was not significant in the light of multiple comparisons adjustment. The relevant brain network loads primarily on the temporal lobe and overlaps significantly with the olfactory areas and temporal poles. PMID:20227508
Caffo, Brian S; Crainiceanu, Ciprian M; Verduzco, Guillermo; Joel, Suresh; Mostofsky, Stewart H; Bassett, Susan Spear; Pekar, James J
2010-07-01
Functional connectivity is the study of correlations in measured neurophysiological signals. Altered functional connectivity has been shown to be associated with a variety of cognitive and memory impairments and dysfunction, including Alzheimer's disease. In this manuscript we use a two-stage application of the singular value decomposition to obtain data driven population-level measures of functional connectivity in functional magnetic resonance imaging (fMRI). The method is computationally simple and amenable to high dimensional fMRI data with large numbers of subjects. Simulation studies suggest the ability of the decomposition methods to recover population brain networks and their associated loadings. We further demonstrate the utility of these decompositions in a functional logistic regression model. The method is applied to a novel fMRI study of Alzheimer's disease risk under a verbal paired associates task. We found an indication of alternative connectivity in clinically asymptomatic at-risk subjects when compared to controls, which was not significant in the light of multiple comparisons adjustment. The relevant brain network loads primarily on the temporal lobe and overlaps significantly with the olfactory areas and temporal poles. Copyright (c) 2010 Elsevier Inc. All rights reserved.
Hirayama, Jun-ichiro; Hyvärinen, Aapo; Kiviniemi, Vesa; Kawanabe, Motoaki; Yamashita, Okito
2016-01-01
Characterizing the variability of resting-state functional brain connectivity across subjects and/or over time has recently attracted much attention. Principal component analysis (PCA) serves as a fundamental statistical technique for such analyses. However, performing PCA on high-dimensional connectivity matrices yields complicated “eigenconnectivity” patterns, for which systematic interpretation is a challenging issue. Here, we overcome this issue with a novel constrained PCA method for connectivity matrices by extending the idea of the previously proposed orthogonal connectivity factorization method. Our new method, modular connectivity factorization (MCF), explicitly introduces the modularity of brain networks as a parametric constraint on eigenconnectivity matrices. In particular, MCF analyzes the variability in both intra- and inter-module connectivities, simultaneously finding network modules in a principled, data-driven manner. The parametric constraint provides a compact module-based visualization scheme with which the result can be intuitively interpreted. We develop an optimization algorithm to solve the constrained PCA problem and validate our method in simulation studies and with a resting-state functional connectivity MRI dataset of 986 subjects. The results show that the proposed MCF method successfully reveals the underlying modular eigenconnectivity patterns in more general situations and is a promising alternative to existing methods. PMID:28002474
Integration of Network Topological and Connectivity Properties for Neuroimaging Classification
Jie, Biao; Gao, Wei; Wang, Qian; Wee, Chong-Yaw
2014-01-01
Rapid advances in neuroimaging techniques have provided an efficient and noninvasive way for exploring the structural and functional connectivity of the human brain. Quantitative measurement of abnormality of brain connectivity in patients with neurodegenerative diseases, such as mild cognitive impairment (MCI) and Alzheimer’s disease (AD), have also been widely reported, especially at a group level. Recently, machine learning techniques have been applied to the study of AD and MCI, i.e., to identify the individuals with AD/MCI from the healthy controls (HCs). However, most existing methods focus on using only a single property of a connectivity network, although multiple network properties, such as local connectivity and global topological properties, can potentially be used. In this paper, by employing multikernel based approach, we propose a novel connectivity based framework to integrate multiple properties of connectivity network for improving the classification performance. Specifically, two different types of kernels (i.e., vector-based kernel and graph kernel) are used to quantify two different yet complementary properties of the network, i.e., local connectivity and global topological properties. Then, multikernel learning (MKL) technique is adopted to fuse these heterogeneous kernels for neuroimaging classification. We test the performance of our proposed method on two different data sets. First, we test it on the functional connectivity networks of 12 MCI and 25 HC subjects. The results show that our method achieves significant performance improvement over those using only one type of network property. Specifically, our method achieves a classification accuracy of 91.9%, which is 10.8% better than those by single network-property-based methods. Then, we test our method for gender classification on a large set of functional connectivity networks with 133 infants scanned at birth, 1 year, and 2 years, also demonstrating very promising results. PMID:24108708
NASA Astrophysics Data System (ADS)
Boucharin, Alexis; Oguz, Ipek; Vachet, Clement; Shi, Yundi; Sanchez, Mar; Styner, Martin
2011-03-01
The use of regional connectivity measurements derived from diffusion imaging datasets has become of considerable interest in the neuroimaging community in order to better understand cortical and subcortical white matter connectivity. Current connectivity assessment methods are based on streamline fiber tractography, usually applied in a Monte-Carlo fashion. In this work we present a novel, graph-based method that performs a fully deterministic, efficient and stable connectivity computation. The method handles crossing fibers and deals well with multiple seed regions. The computation is based on a multi-directional graph propagation method applied to sampled orientation distribution function (ODF), which can be computed directly from the original diffusion imaging data. We show early results of our method on synthetic and real datasets. The results illustrate the potential of our method towards subjectspecific connectivity measurements that are performed in an efficient, stable and reproducible manner. Such individual connectivity measurements would be well suited for application in population studies of neuropathology, such as Autism, Huntington's Disease, Multiple Sclerosis or leukodystrophies. The proposed method is generic and could easily be applied to non-diffusion data as long as local directional data can be derived.
Cetin, Mustafa S.; Houck, Jon M.; Rashid, Barnaly; Agacoglu, Oktay; Stephen, Julia M.; Sui, Jing; Canive, Jose; Mayer, Andy; Aine, Cheryl; Bustillo, Juan R.; Calhoun, Vince D.
2016-01-01
Mental disorders like schizophrenia are currently diagnosed by physicians/psychiatrists through clinical assessment and their evaluation of patient's self-reported experiences as the illness emerges. There is great interest in identifying biological markers of prognosis at the onset of illness, rather than relying on the evolution of symptoms across time. Functional network connectivity, which indicates a subject's overall level of “synchronicity” of activity between brain regions, demonstrates promise in providing individual subject predictive power. Many previous studies reported functional connectivity changes during resting-state using only functional magnetic resonance imaging (fMRI). Nevertheless, exclusive reliance on fMRI to generate such networks may limit the inference of the underlying dysfunctional connectivity, which is hypothesized to be a factor in patient symptoms, as fMRI measures connectivity via hemodynamics. Therefore, combination of connectivity assessments using fMRI and magnetoencephalography (MEG), which more directly measures neuronal activity, may provide improved classification of schizophrenia than either modality alone. Moreover, recent evidence indicates that metrics of dynamic connectivity may also be critical for understanding pathology in schizophrenia. In this work, we propose a new framework for extraction of important disease related features and classification of patients with schizophrenia based on using both fMRI and MEG to investigate functional network components in the resting state. Results of this study show that the integration of fMRI and MEG provides important information that captures fundamental characteristics of functional network connectivity in schizophrenia and is helpful for prediction of schizophrenia patient group membership. Combined fMRI/MEG methods, using static functional network connectivity analyses, improved classification accuracy relative to use of fMRI or MEG methods alone (by 15 and 12.45%, respectively), while combined fMRI/MEG methods using dynamic functional network connectivity analyses improved classification up to 5.12% relative to use of fMRI alone and up to 17.21% relative to use of MEG alone. PMID:27807403
Functional Connectivity among Spikes in Low Dimensional Space during Working Memory Task in Rat
Tian, Xin
2014-01-01
Working memory (WM) is critically important in cognitive tasks. The functional connectivity has been a powerful tool for understanding the mechanism underlying the information processing during WM tasks. The aim of this study is to investigate how to effectively characterize the dynamic variations of the functional connectivity in low dimensional space among the principal components (PCs) which were extracted from the instantaneous firing rate series. Spikes were obtained from medial prefrontal cortex (mPFC) of rats with implanted microelectrode array and then transformed into continuous series via instantaneous firing rate method. Granger causality method is proposed to study the functional connectivity. Then three scalar metrics were applied to identify the changes of the reduced dimensionality functional network during working memory tasks: functional connectivity (GC), global efficiency (E) and casual density (CD). As a comparison, GC, E and CD were also calculated to describe the functional connectivity in the original space. The results showed that these network characteristics dynamically changed during the correct WM tasks. The measure values increased to maximum, and then decreased both in the original and in the reduced dimensionality. Besides, the feature values of the reduced dimensionality were significantly higher during the WM tasks than they were in the original space. These findings suggested that functional connectivity among the spikes varied dynamically during the WM tasks and could be described effectively in the low dimensional space. PMID:24658291
Yu, Renping; Zhang, Han; An, Le; Chen, Xiaobo; Wei, Zhihui; Shen, Dinggang
2017-01-01
Brain functional network analysis has shown great potential in understanding brain functions and also in identifying biomarkers for brain diseases, such as Alzheimer's disease (AD) and its early stage, mild cognitive impairment (MCI). In these applications, accurate construction of biologically meaningful brain network is critical. Sparse learning has been widely used for brain network construction; however, its l1-norm penalty simply penalizes each edge of a brain network equally, without considering the original connectivity strength which is one of the most important inherent linkwise characters. Besides, based on the similarity of the linkwise connectivity, brain network shows prominent group structure (i.e., a set of edges sharing similar attributes). In this article, we propose a novel brain functional network modeling framework with a “connectivity strength-weighted sparse group constraint.” In particular, the network modeling can be optimized by considering both raw connectivity strength and its group structure, without losing the merit of sparsity. Our proposed method is applied to MCI classification, a challenging task for early AD diagnosis. Experimental results based on the resting-state functional MRI, from 50 MCI patients and 49 healthy controls, show that our proposed method is more effective (i.e., achieving a significantly higher classification accuracy, 84.8%) than other competing methods (e.g., sparse representation, accuracy = 65.6%). Post hoc inspection of the informative features further shows more biologically meaningful brain functional connectivities obtained by our proposed method. PMID:28150897
Varoquaux, G; Gramfort, A; Poline, J B; Thirion, B
2012-01-01
Correlations in the signal observed via functional Magnetic Resonance Imaging (fMRI), are expected to reveal the interactions in the underlying neural populations through hemodynamic response. In particular, they highlight distributed set of mutually correlated regions that correspond to brain networks related to different cognitive functions. Yet graph-theoretical studies of neural connections give a different picture: that of a highly integrated system with small-world properties: local clustering but with short pathways across the complete structure. We examine the conditional independence properties of the fMRI signal, i.e. its Markov structure, to find realistic assumptions on the connectivity structure that are required to explain the observed functional connectivity. In particular we seek a decomposition of the Markov structure into segregated functional networks using decomposable graphs: a set of strongly-connected and partially overlapping cliques. We introduce a new method to efficiently extract such cliques on a large, strongly-connected graph. We compare methods learning different graph structures from functional connectivity by testing the goodness of fit of the model they learn on new data. We find that summarizing the structure as strongly-connected networks can give a good description only for very large and overlapping networks. These results highlight that Markov models are good tools to identify the structure of brain connectivity from fMRI signals, but for this purpose they must reflect the small-world properties of the underlying neural systems. Copyright © 2012 Elsevier Ltd. All rights reserved.
EXPLORING FUNCTIONAL CONNECTIVITY IN FMRI VIA CLUSTERING.
Venkataraman, Archana; Van Dijk, Koene R A; Buckner, Randy L; Golland, Polina
2009-04-01
In this paper we investigate the use of data driven clustering methods for functional connectivity analysis in fMRI. In particular, we consider the K-Means and Spectral Clustering algorithms as alternatives to the commonly used Seed-Based Analysis. To enable clustering of the entire brain volume, we use the Nyström Method to approximate the necessary spectral decompositions. We apply K-Means, Spectral Clustering and Seed-Based Analysis to resting-state fMRI data collected from 45 healthy young adults. Without placing any a priori constraints, both clustering methods yield partitions that are associated with brain systems previously identified via Seed-Based Analysis. Our empirical results suggest that clustering provides a valuable tool for functional connectivity analysis.
Wang, Yikai; Kang, Jian; Kemmer, Phebe B.; Guo, Ying
2016-01-01
Currently, network-oriented analysis of fMRI data has become an important tool for understanding brain organization and brain networks. Among the range of network modeling methods, partial correlation has shown great promises in accurately detecting true brain network connections. However, the application of partial correlation in investigating brain connectivity, especially in large-scale brain networks, has been limited so far due to the technical challenges in its estimation. In this paper, we propose an efficient and reliable statistical method for estimating partial correlation in large-scale brain network modeling. Our method derives partial correlation based on the precision matrix estimated via Constrained L1-minimization Approach (CLIME), which is a recently developed statistical method that is more efficient and demonstrates better performance than the existing methods. To help select an appropriate tuning parameter for sparsity control in the network estimation, we propose a new Dens-based selection method that provides a more informative and flexible tool to allow the users to select the tuning parameter based on the desired sparsity level. Another appealing feature of the Dens-based method is that it is much faster than the existing methods, which provides an important advantage in neuroimaging applications. Simulation studies show that the Dens-based method demonstrates comparable or better performance with respect to the existing methods in network estimation. We applied the proposed partial correlation method to investigate resting state functional connectivity using rs-fMRI data from the Philadelphia Neurodevelopmental Cohort (PNC) study. Our results show that partial correlation analysis removed considerable between-module marginal connections identified by full correlation analysis, suggesting these connections were likely caused by global effects or common connection to other nodes. Based on partial correlation, we find that the most significant direct connections are between homologous brain locations in the left and right hemisphere. When comparing partial correlation derived under different sparse tuning parameters, an important finding is that the sparse regularization has more shrinkage effects on negative functional connections than on positive connections, which supports previous findings that many of the negative brain connections are due to non-neurophysiological effects. An R package “DensParcorr” can be downloaded from CRAN for implementing the proposed statistical methods. PMID:27242395
Wang, Yikai; Kang, Jian; Kemmer, Phebe B; Guo, Ying
2016-01-01
Currently, network-oriented analysis of fMRI data has become an important tool for understanding brain organization and brain networks. Among the range of network modeling methods, partial correlation has shown great promises in accurately detecting true brain network connections. However, the application of partial correlation in investigating brain connectivity, especially in large-scale brain networks, has been limited so far due to the technical challenges in its estimation. In this paper, we propose an efficient and reliable statistical method for estimating partial correlation in large-scale brain network modeling. Our method derives partial correlation based on the precision matrix estimated via Constrained L1-minimization Approach (CLIME), which is a recently developed statistical method that is more efficient and demonstrates better performance than the existing methods. To help select an appropriate tuning parameter for sparsity control in the network estimation, we propose a new Dens-based selection method that provides a more informative and flexible tool to allow the users to select the tuning parameter based on the desired sparsity level. Another appealing feature of the Dens-based method is that it is much faster than the existing methods, which provides an important advantage in neuroimaging applications. Simulation studies show that the Dens-based method demonstrates comparable or better performance with respect to the existing methods in network estimation. We applied the proposed partial correlation method to investigate resting state functional connectivity using rs-fMRI data from the Philadelphia Neurodevelopmental Cohort (PNC) study. Our results show that partial correlation analysis removed considerable between-module marginal connections identified by full correlation analysis, suggesting these connections were likely caused by global effects or common connection to other nodes. Based on partial correlation, we find that the most significant direct connections are between homologous brain locations in the left and right hemisphere. When comparing partial correlation derived under different sparse tuning parameters, an important finding is that the sparse regularization has more shrinkage effects on negative functional connections than on positive connections, which supports previous findings that many of the negative brain connections are due to non-neurophysiological effects. An R package "DensParcorr" can be downloaded from CRAN for implementing the proposed statistical methods.
Smitha, K A; Akhil Raja, K; Arun, K M; Rajesh, P G; Thomas, Bejoy; Kapilamoorthy, T R; Kesavadas, Chandrasekharan
2017-08-01
The inquisitiveness about what happens in the brain has been there since the beginning of humankind. Functional magnetic resonance imaging is a prominent tool which helps in the non-invasive examination, localisation as well as lateralisation of brain functions such as language, memory, etc. In recent years, there is an apparent shift in the focus of neuroscience research to studies dealing with a brain at 'resting state'. Here the spotlight is on the intrinsic activity within the brain, in the absence of any sensory or cognitive stimulus. The analyses of functional brain connectivity in the state of rest have revealed different resting state networks, which depict specific functions and varied spatial topology. However, different statistical methods have been introduced to study resting state functional magnetic resonance imaging connectivity, yet producing consistent results. In this article, we introduce the concept of resting state functional magnetic resonance imaging in detail, then discuss three most widely used methods for analysis, describe a few of the resting state networks featuring the brain regions, associated cognitive functions and clinical applications of resting state functional magnetic resonance imaging. This review aims to highlight the utility and importance of studying resting state functional magnetic resonance imaging connectivity, underlining its complementary nature to the task-based functional magnetic resonance imaging.
NASA Astrophysics Data System (ADS)
Ali, G.; Rinderer, M.
2016-12-01
In hydrology, several connectivity definitions exist that hinder intercomparison between different studies. Yet, consensus exists on the distinction between structural connectivity (i.e., physical adjacency of landscape elements that is thought to influence material transfer) and functional or effective connectivity (i.e., interaction or causality between spatial adjacency characteristics and temporally varying factors, leading to the connected flow of material). While hydrologists have succeeded in deriving measures of structural connectivity (SC), the quantification of functional (FC) or effective connectivity (EC) is elusive. Here we borrowed timeseries analysis methods from brain neuroscience to quantify EC and FC among groundwater (n = 34) and stream discharge (n = 1) monitoring sites in a 20-ha Swiss catchment where topography is assumed to be a major driver of connectivity. Influence maps created from elevation data were used to assess SC. FC was assessed by cross-correlation, total and partial mutual information and EC quantified via total and partial entropy, Granger causality and a phase slope index. Results show that generally, a fair percentage of structural connections were also expressed as functional or effective connections. Some FC and EC measures had clear advantages over others, for instance in terms of making a distinction between Darcian fluxes of water and pressure wave-driven processes. False-positive estimations, i.e., the detection of FC and EC despite the absence of SC, were also encountered and used to invalidate the applicability of some brain-connectivity measures in a hydrological context. While our goal was not to identify the best measure of FC or EC, our study showed that the application of brain neuroscience methods for assessing FC and EC in hydrology was possible as long as SC measures were used as constraints for (or prior beliefs about) the establishment of FC and EC.
Quantifying hydrologic connectivity with measures from the brain neurosciences - a feasibility study
NASA Astrophysics Data System (ADS)
Rinderer, Michael; Ali, Genevieve; Larsen, Laurel
2017-04-01
While the concept of connectivity is increasingly applied in hydrology and ecology, little agreement exists on its definition and quantification approaches. In contrast, the neurosciences have developed a systematic conceptualization of connectivity and methods to quantify it. In particular, neuroscientists make a clear distinction between: 1) structural connectivity, which is determined by the anatomy of the brain neural network, 2) functional connectivity, that is based on statistical dependencies between neural signals, and 3) effective connectivity, that allows to infer causal relations based on the assumption that "true" interactions occur with a certain time delay. In a similar vein, in hydrology, structural connectivity can be defined as the physical adjacency of landscape elements that are seen as a prerequisite of material transfer, while functional or process connectivity would rather describe interactions or causal relations between spatial adjacency characteristics and temporally varying factors. While hydrologists have suggested methods to derive structural connectivity (SC), the quantification of functional (FC) or effective connectivity (EC) has remained elusive. The goal of the current study was therefore to apply timeseries analysis methods from brain neuroscience to quantify EC and FC among groundwater (n = 34) and stream discharge (n = 1) monitoring sites in a 20-ha Swiss catchment where topography is assumed to be a major driver of connectivity. SC was assessed through influence maps that quantify the percentage of flow from an upslope site to a downslope site by applying a multiple flow direction algorithm. FC was assessed by cross-correlation, total and partial mutual information while EC was quantified via total and partial entropy, Granger causality and a phase slope index. Our results showed that many structural connections were also expressed as functional or effective connections, which is reasonable in a catchment with shallow perched groundwater tables. The differentiation between FC and EC measures allowed us to distinguish between hydrological connectivity (i.e., Darcian fluxes of water) and hydraulic connectivity (i.e. pressure wave-driven processes). However, some FC and EC measures also detected the presence of connectivity despite the absence of SC, which highlights the limits of applying brain connectivity measures to hydrology. We therefore conclude that brain neuroscience methods for assessing FC and EC can be powerful tools in assessing hydrological connectivity as long as they are constrained by SC measures.
Wetherill, Reagan R.; Fang, Zhuo; Jagannathan, Kanchana; Childress, Anna Rose; Rao, Hengyi; Franklin, Teresa R.
2015-01-01
Background Resting-state functional connectivity is a noninvasive, neuroimaging method for assessing neural network function. Altered functional connectivity among regions of the default-mode network have been associated with both nicotine and cannabis use; however, less is known about co-occurring cannabis and tobacco use. Methods We used posterior cingulate cortex (PCC) seed-based resting-state functional connectivity analyses to examine default mode network (DMN) connectivity strength differences between four groups: 1) individuals diagnosed with cannabis dependence who do not smoke tobacco (n=19; ages 20–50), 2) cannabis-dependent individuals who smoke tobacco (n=23, ages 21–52), 3) cannabis-naïve, nicotine-dependent individuals who smoke tobacco (n=24, ages 21–57), and 4) cannabis- and tobacco-naïve healthy controls (n=21, ages 21–50), controlling for age, sex, and alcohol use. We also explored associations between connectivity strength and measures of cannabis and tobacco use. Results PCC seed-based analyses identified the core nodes of the DMN (i.e., PCC, medial prefrontal cortex, inferior parietal cortex, and temporal cortex). In general, the cannabis-dependent, nicotine-dependent, and co-occurring use groups showed lower DMN connectivity strengths than controls, with unique group differences in connectivity strength between the PCC and the cerebellum, medial prefrontal cortex, parahippocampus, and anterior insula. In cannabis-dependent individuals, PCC-right anterior insula connectivity strength correlated with duration of cannabis use. Conclusions This study extends previous research that independently examined the differences in resting-state functional connectivity among individuals who smoke cannabis and tobacco by including an examination of co-occurring cannabis and tobacco use and provides further evidence that cannabis and tobacco exposure is associated with alterations in DMN connectivity. PMID:26094186
Examining Neuronal Connectivity and Its Role in Learning and Memory
NASA Astrophysics Data System (ADS)
Gala, Rohan
Learning and long-term memory formation are accompanied with changes in the patterns and weights of synaptic connections in the underlying neuronal network. However, the fundamental rules that drive connectivity changes, and the precise structure-function relationships within neuronal networks remain elusive. Technological improvements over the last few decades have enabled the observation of large but specific subsets of neurons and their connections in unprecedented detail. Devising robust and automated computational methods is critical to distill information from ever-increasing volumes of raw experimental data. Moreover, statistical models and theoretical frameworks are required to interpret the data and assemble evidence into understanding of brain function. In this thesis, I first describe computational methods to reconstruct connectivity based on light microscopy imaging experiments. Next, I use these methods to quantify structural changes in connectivity based on in vivo time-lapse imaging experiments. Finally, I present a theoretical model of associative learning that can explain many stereotypical features of experimentally observed connectivity.
Discriminant analysis of resting-state functional connectivity patterns on the Grassmann manifold
NASA Astrophysics Data System (ADS)
Fan, Yong; Liu, Yong; Jiang, Tianzi; Liu, Zhening; Hao, Yihui; Liu, Haihong
2010-03-01
The functional networks, extracted from fMRI images using independent component analysis, have been demonstrated informative for distinguishing brain states of cognitive functions and neurological diseases. In this paper, we propose a novel algorithm for discriminant analysis of functional networks encoded by spatial independent components. The functional networks of each individual are used as bases for a linear subspace, referred to as a functional connectivity pattern, which facilitates a comprehensive characterization of temporal signals of fMRI data. The functional connectivity patterns of different individuals are analyzed on the Grassmann manifold by adopting a principal angle based subspace distance. In conjunction with a support vector machine classifier, a forward component selection technique is proposed to select independent components for constructing the most discriminative functional connectivity pattern. The discriminant analysis method has been applied to an fMRI based schizophrenia study with 31 schizophrenia patients and 31 healthy individuals. The experimental results demonstrate that the proposed method not only achieves a promising classification performance for distinguishing schizophrenia patients from healthy controls, but also identifies discriminative functional networks that are informative for schizophrenia diagnosis.
Connectivity of streams and wetlands to downstream waters: An integrated systems framework
Leibowitz, Scott G.; Wigington, Parker J.; Schoefield, Kate A.; Alexander, Laurie C.; Vanderhoof, Melanie; Golden, Heather E.
2018-01-01
Interest in connectivity has increased in the aquatic sciences, partly because of its relevance to the Clean Water Act. This paper has two objectives: (1) provide a framework to understand hydrological, chemical, and biological connectivity, focusing on how headwater streams and wetlands connect to and contribute to rivers; and (2) briefly review methods to quantify hydrological and chemical connectivity. Streams and wetlands affect river structure and function by altering material and biological fluxes to the river; this depends on two factors: (1) functions within streams and wetlands that affect material fluxes; and (2) connectivity (or isolation) from streams and wetlands to rivers that allows (or prevents) material transport between systems. Connectivity can be described in terms of frequency, magnitude, duration, timing, and rate of change. It results from physical characteristics of a system, e.g., climate, soils, geology, topography, and the spatial distribution of aquatic components. Biological connectivity is also affected by traits and behavior of the biota. Connectivity can be altered by human impacts, often in complex ways. Because of variability in these factors, connectivity is not constant but varies over time and space. Connectivity can be quantified with field‐based methods, modeling, and remote sensing. Further studies using these methods are needed to classify and quantify connectivity of aquatic ecosystems and to understand how impacts affect connectivity.
Replicability of time-varying connectivity patterns in large resting state fMRI samples.
Abrol, Anees; Damaraju, Eswar; Miller, Robyn L; Stephen, Julia M; Claus, Eric D; Mayer, Andrew R; Calhoun, Vince D
2017-12-01
The past few years have seen an emergence of approaches that leverage temporal changes in whole-brain patterns of functional connectivity (the chronnectome). In this chronnectome study, we investigate the replicability of the human brain's inter-regional coupling dynamics during rest by evaluating two different dynamic functional network connectivity (dFNC) analysis frameworks using 7 500 functional magnetic resonance imaging (fMRI) datasets. To quantify the extent to which the emergent functional connectivity (FC) patterns are reproducible, we characterize the temporal dynamics by deriving several summary measures across multiple large, independent age-matched samples. Reproducibility was demonstrated through the existence of basic connectivity patterns (FC states) amidst an ensemble of inter-regional connections. Furthermore, application of the methods to conservatively configured (statistically stationary, linear and Gaussian) surrogate datasets revealed that some of the studied state summary measures were indeed statistically significant and also suggested that this class of null model did not explain the fMRI data fully. This extensive testing of reproducibility of similarity statistics also suggests that the estimated FC states are robust against variation in data quality, analysis, grouping, and decomposition methods. We conclude that future investigations probing the functional and neurophysiological relevance of time-varying connectivity assume critical importance. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Replicability of time-varying connectivity patterns in large resting state fMRI samples
Abrol, Anees; Damaraju, Eswar; Miller, Robyn L.; Stephen, Julia M.; Claus, Eric D.; Mayer, Andrew R.; Calhoun, Vince D.
2018-01-01
The past few years have seen an emergence of approaches that leverage temporal changes in whole-brain patterns of functional connectivity (the chronnectome). In this chronnectome study, we investigate the replicability of the human brain’s inter-regional coupling dynamics during rest by evaluating two different dynamic functional network connectivity (dFNC) analysis frameworks using 7 500 functional magnetic resonance imaging (fMRI) datasets. To quantify the extent to which the emergent functional connectivity (FC) patterns are reproducible, we characterize the temporal dynamics by deriving several summary measures across multiple large, independent age-matched samples. Reproducibility was demonstrated through the existence of basic connectivity patterns (FC states) amidst an ensemble of inter-regional connections. Furthermore, application of the methods to conservatively configured (statistically stationary, linear and Gaussian) surrogate datasets revealed that some of the studied state summary measures were indeed statistically significant and also suggested that this class of null model did not explain the fMRI data fully. This extensive testing of reproducibility of similarity statistics also suggests that the estimated FC states are robust against variation in data quality, analysis, grouping, and decomposition methods. We conclude that future investigations probing the functional and neurophysiological relevance of time-varying connectivity assume critical importance. PMID:28916181
Functional Connectivity of the Amygdala in Early-Childhood-Onset Depression
ERIC Educational Resources Information Center
Luking, Katherine R.; Repovs, Grega; Belden, Andy C.; Gaffrey, Michael S.; Botteron, Kelly N.; Luby, Joan L.; Barch, Deanna M.
2011-01-01
Objective: Adult major depressive disorder (MDD) is associated with reduced cortico-limbic functional connectivity thought to indicate decreased top-down control of emotion. However, it is unclear whether such connectivity alterations are also present in early-childhood-onset MDD. Method: A total of 51 children 7 through 11 years of age who had…
Network inference from functional experimental data (Conference Presentation)
NASA Astrophysics Data System (ADS)
Desrosiers, Patrick; Labrecque, Simon; Tremblay, Maxime; Bélanger, Mathieu; De Dorlodot, Bertrand; Côté, Daniel C.
2016-03-01
Functional connectivity maps of neuronal networks are critical tools to understand how neurons form circuits, how information is encoded and processed by neurons, how memory is shaped, and how these basic processes are altered under pathological conditions. Current light microscopy allows to observe calcium or electrical activity of thousands of neurons simultaneously, yet assessing comprehensive connectivity maps directly from such data remains a non-trivial analytical task. There exist simple statistical methods, such as cross-correlation and Granger causality, but they only detect linear interactions between neurons. Other more involved inference methods inspired by information theory, such as mutual information and transfer entropy, identify more accurately connections between neurons but also require more computational resources. We carried out a comparative study of common connectivity inference methods. The relative accuracy and computational cost of each method was determined via simulated fluorescence traces generated with realistic computational models of interacting neurons in networks of different topologies (clustered or non-clustered) and sizes (10-1000 neurons). To bridge the computational and experimental works, we observed the intracellular calcium activity of live hippocampal neuronal cultures infected with the fluorescent calcium marker GCaMP6f. The spontaneous activity of the networks, consisting of 50-100 neurons per field of view, was recorded from 20 to 50 Hz on a microscope controlled by a homemade software. We implemented all connectivity inference methods in the software, which rapidly loads calcium fluorescence movies, segments the images, extracts the fluorescence traces, and assesses the functional connections (with strengths and directions) between each pair of neurons. We used this software to assess, in real time, the functional connectivity from real calcium imaging data in basal conditions, under plasticity protocols, and epileptic conditions.
A SVM-based quantitative fMRI method for resting-state functional network detection.
Song, Xiaomu; Chen, Nan-kuei
2014-09-01
Resting-state functional magnetic resonance imaging (fMRI) aims to measure baseline neuronal connectivity independent of specific functional tasks and to capture changes in the connectivity due to neurological diseases. Most existing network detection methods rely on a fixed threshold to identify functionally connected voxels under the resting state. Due to fMRI non-stationarity, the threshold cannot adapt to variation of data characteristics across sessions and subjects, and generates unreliable mapping results. In this study, a new method is presented for resting-state fMRI data analysis. Specifically, the resting-state network mapping is formulated as an outlier detection process that is implemented using one-class support vector machine (SVM). The results are refined by using a spatial-feature domain prototype selection method and two-class SVM reclassification. The final decision on each voxel is made by comparing its probabilities of functionally connected and unconnected instead of a threshold. Multiple features for resting-state analysis were extracted and examined using an SVM-based feature selection method, and the most representative features were identified. The proposed method was evaluated using synthetic and experimental fMRI data. A comparison study was also performed with independent component analysis (ICA) and correlation analysis. The experimental results show that the proposed method can provide comparable or better network detection performance than ICA and correlation analysis. The method is potentially applicable to various resting-state quantitative fMRI studies. Copyright © 2014 Elsevier Inc. All rights reserved.
Network analysis of mesoscale optical recordings to assess regional, functional connectivity.
Lim, Diana H; LeDue, Jeffrey M; Murphy, Timothy H
2015-10-01
With modern optical imaging methods, it is possible to map structural and functional connectivity. Optical imaging studies that aim to describe large-scale neural connectivity often need to handle large and complex datasets. In order to interpret these datasets, new methods for analyzing structural and functional connectivity are being developed. Recently, network analysis, based on graph theory, has been used to describe and quantify brain connectivity in both experimental and clinical studies. We outline how to apply regional, functional network analysis to mesoscale optical imaging using voltage-sensitive-dye imaging and channelrhodopsin-2 stimulation in a mouse model. We include links to sample datasets and an analysis script. The analyses we employ can be applied to other types of fluorescence wide-field imaging, including genetically encoded calcium indicators, to assess network properties. We discuss the benefits and limitations of using network analysis for interpreting optical imaging data and define network properties that may be used to compare across preparations or other manipulations such as animal models of disease.
Yu, Renping; Zhang, Han; An, Le; Chen, Xiaobo; Wei, Zhihui; Shen, Dinggang
2017-05-01
Brain functional network analysis has shown great potential in understanding brain functions and also in identifying biomarkers for brain diseases, such as Alzheimer's disease (AD) and its early stage, mild cognitive impairment (MCI). In these applications, accurate construction of biologically meaningful brain network is critical. Sparse learning has been widely used for brain network construction; however, its l 1 -norm penalty simply penalizes each edge of a brain network equally, without considering the original connectivity strength which is one of the most important inherent linkwise characters. Besides, based on the similarity of the linkwise connectivity, brain network shows prominent group structure (i.e., a set of edges sharing similar attributes). In this article, we propose a novel brain functional network modeling framework with a "connectivity strength-weighted sparse group constraint." In particular, the network modeling can be optimized by considering both raw connectivity strength and its group structure, without losing the merit of sparsity. Our proposed method is applied to MCI classification, a challenging task for early AD diagnosis. Experimental results based on the resting-state functional MRI, from 50 MCI patients and 49 healthy controls, show that our proposed method is more effective (i.e., achieving a significantly higher classification accuracy, 84.8%) than other competing methods (e.g., sparse representation, accuracy = 65.6%). Post hoc inspection of the informative features further shows more biologically meaningful brain functional connectivities obtained by our proposed method. Hum Brain Mapp 38:2370-2383, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
Human brain mapping: A systematic comparison of parcellation methods for the human cerebral cortex.
Arslan, Salim; Ktena, Sofia Ira; Makropoulos, Antonios; Robinson, Emma C; Rueckert, Daniel; Parisot, Sarah
2018-04-15
The macro-connectome elucidates the pathways through which brain regions are structurally connected or functionally coupled to perform a specific cognitive task. It embodies the notion of representing and understanding all connections within the brain as a network, while the subdivision of the brain into interacting functional units is inherent in its architecture. As a result, the definition of network nodes is one of the most critical steps in connectivity network analysis. Although brain atlases obtained from cytoarchitecture or anatomy have long been used for this task, connectivity-driven methods have arisen only recently, aiming to delineate more homogeneous and functionally coherent regions. This study provides a systematic comparison between anatomical, connectivity-driven and random parcellation methods proposed in the thriving field of brain parcellation. Using resting-state functional MRI data from the Human Connectome Project and a plethora of quantitative evaluation techniques investigated in the literature, we evaluate 10 subject-level and 24 groupwise parcellation methods at different resolutions. We assess the accuracy of parcellations from four different aspects: (1) reproducibility across different acquisitions and groups, (2) fidelity to the underlying connectivity data, (3) agreement with fMRI task activation, myelin maps, and cytoarchitectural areas, and (4) network analysis. This extensive evaluation of different parcellations generated at the subject and group level highlights the strengths and shortcomings of the various methods and aims to provide a guideline for the choice of parcellation technique and resolution according to the task at hand. The results obtained in this study suggest that there is no optimal method able to address all the challenges faced in this endeavour simultaneously. Copyright © 2017 Elsevier Inc. All rights reserved.
Maggioni, Eleonora; Tana, Maria Gabriella; Arrigoni, Filippo; Zucca, Claudio; Bianchi, Anna Maria
2014-05-15
Functional Magnetic Resonance Imaging (fMRI) is used for exploring brain functionality, and recently it was applied for mapping the brain connection patterns. To give a meaningful neurobiological interpretation to the connectivity network, it is fundamental to properly define the network framework. In particular, the choice of the network nodes may affect the final connectivity results and the consequent interpretation. We introduce a novel method for the intra subject topological characterization of the nodes of fMRI brain networks, based on a whole brain parcellation scheme. The proposed whole brain parcellation algorithm divides the brain into clusters that are homogeneous from the anatomical and functional point of view, each of which constitutes a node. The functional parcellation described is based on the Tononi's cluster index, which measures instantaneous correlation in terms of intrinsic and extrinsic statistical dependencies. The method performance and reliability were first tested on simulated data, then on a real fMRI dataset acquired on healthy subjects during visual stimulation. Finally, the proposed algorithm was applied to epileptic patients' fMRI data recorded during seizures, to verify its usefulness as preparatory step for effective connectivity analysis. For each patient, the nodes of the network involved in ictal activity were defined according to the proposed parcellation scheme and Granger Causality Analysis (GCA) was applied to infer effective connectivity. We showed that the algorithm 1) performed well on simulated data, 2) was able to produce reliable inter subjects results and 3) led to a detailed definition of the effective connectivity pattern. Copyright © 2014 Elsevier B.V. All rights reserved.
Chu, Shu-Hsien; Parhi, Keshab K; Lenglet, Christophe
2018-03-16
A joint structural-functional brain network model is presented, which enables the discovery of function-specific brain circuits, and recovers structural connections that are under-estimated by diffusion MRI (dMRI). Incorporating information from functional MRI (fMRI) into diffusion MRI to estimate brain circuits is a challenging task. Usually, seed regions for tractography are selected from fMRI activation maps to extract the white matter pathways of interest. The proposed method jointly analyzes whole brain dMRI and fMRI data, allowing the estimation of complete function-specific structural networks instead of interactively investigating the connectivity of individual cortical/sub-cortical areas. Additionally, tractography techniques are prone to limitations, which can result in erroneous pathways. The proposed framework explicitly models the interactions between structural and functional connectivity measures thereby improving anatomical circuit estimation. Results on Human Connectome Project (HCP) data demonstrate the benefits of the approach by successfully identifying function-specific anatomical circuits, such as the language and resting-state networks. In contrast to correlation-based or independent component analysis (ICA) functional connectivity mapping, detailed anatomical connectivity patterns are revealed for each functional module. Results on a phantom (Fibercup) also indicate improvements in structural connectivity mapping by rejecting false-positive connections with insufficient support from fMRI, and enhancing under-estimated connectivity with strong functional correlation.
Scheinost, Dustin; Holmes, Sophie E; DellaGioia, Nicole; Schleifer, Charlie; Matuskey, David; Abdallah, Chadi G; Hampson, Michelle; Krystal, John H; Anticevic, Alan; Esterlis, Irina
2018-01-01
Converging evidence suggests that major depressive disorder (MDD) affects multiple large-scale brain networks. Analyses of the correlation or covariance of regional brain structure and function applied to structural and functional MRI data may provide insights into systems-level organization and structure-to-function correlations in the brain in MDD. This study applied tensor-based morphometry and intrinsic connectivity distribution to identify regions of altered volume and intrinsic functional connectivity in data from unmedicated individuals with MDD (n=17) and healthy comparison participants (HC, n=20). These regions were then used as seeds for exploratory anatomical covariance and connectivity analyses. Reduction in volume in the anterior cingulate cortex (ACC) and lower structural covariance between the ACC and the cerebellum were observed in the MDD group. Additionally, individuals with MDD had significantly lower whole-brain intrinsic functional connectivity in the medial prefrontal cortex (mPFC). This mPFC region showed altered connectivity to the ventral lateral PFC (vlPFC) and local circuitry in MDD. Global connectivity in the ACC was negatively correlated with reported depressive symptomatology. The mPFC–vlPFC connectivity was positively correlated with depressive symptoms. Finally, we observed increased structure-to-function correlation in the PFC/ACC in the MDD group. Although across all analysis methods and modalities alterations in the PFC/ACC were a common finding, each modality and method detected alterations in subregions belonging to distinct large-scale brain networks. These exploratory results support the hypothesis that MDD is a systems level disorder affecting multiple brain networks located in the PFC and provide new insights into the pathophysiology of this disorder. PMID:28944772
Scheinost, Dustin; Holmes, Sophie E; DellaGioia, Nicole; Schleifer, Charlie; Matuskey, David; Abdallah, Chadi G; Hampson, Michelle; Krystal, John H; Anticevic, Alan; Esterlis, Irina
2018-04-01
Converging evidence suggests that major depressive disorder (MDD) affects multiple large-scale brain networks. Analyses of the correlation or covariance of regional brain structure and function applied to structural and functional MRI data may provide insights into systems-level organization and structure-to-function correlations in the brain in MDD. This study applied tensor-based morphometry and intrinsic connectivity distribution to identify regions of altered volume and intrinsic functional connectivity in data from unmedicated individuals with MDD (n=17) and healthy comparison participants (HC, n=20). These regions were then used as seeds for exploratory anatomical covariance and connectivity analyses. Reduction in volume in the anterior cingulate cortex (ACC) and lower structural covariance between the ACC and the cerebellum were observed in the MDD group. Additionally, individuals with MDD had significantly lower whole-brain intrinsic functional connectivity in the medial prefrontal cortex (mPFC). This mPFC region showed altered connectivity to the ventral lateral PFC (vlPFC) and local circuitry in MDD. Global connectivity in the ACC was negatively correlated with reported depressive symptomatology. The mPFC-vlPFC connectivity was positively correlated with depressive symptoms. Finally, we observed increased structure-to-function correlation in the PFC/ACC in the MDD group. Although across all analysis methods and modalities alterations in the PFC/ACC were a common finding, each modality and method detected alterations in subregions belonging to distinct large-scale brain networks. These exploratory results support the hypothesis that MDD is a systems level disorder affecting multiple brain networks located in the PFC and provide new insights into the pathophysiology of this disorder.
Raz, Gal; Shpigelman, Lavi; Jacob, Yael; Gonen, Tal; Benjamini, Yoav; Hendler, Talma
2016-12-01
We introduce a novel method for delineating context-dependent functional brain networks whose connectivity dynamics are synchronized with the occurrence of a specific psychophysiological process of interest. In this method of context-related network dynamics analysis (CRNDA), a continuous psychophysiological index serves as a reference for clustering the whole-brain into functional networks. We applied CRNDA to fMRI data recorded during the viewing of a sadness-inducing film clip. The method reliably demarcated networks in which temporal patterns of connectivity related to the time series of reported emotional intensity. Our work successfully replicated the link between network connectivity and emotion rating in an independent sample group for seven of the networks. The demarcated networks have clear common functional denominators. Three of these networks overlap with distinct empathy-related networks, previously identified in distinct sets of studies. The other networks are related to sensorimotor processing, language, attention, and working memory. The results indicate that CRNDA, a data-driven method for network clustering that is sensitive to transient connectivity patterns, can productively and reliably demarcate networks that follow psychologically meaningful processes. Hum Brain Mapp 37:4654-4672, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Kim, Jae-Hun; Lee, Jong-Min; Jo, Hang Joon; Kim, Sook Hui; Lee, Jung Hee; Kim, Sung Tae; Seo, Sang Won; Cox, Robert W; Na, Duk L; Kim, Sun I; Saad, Ziad S
2010-02-01
Noninvasive parcellation of the human cerebral cortex is an important goal for understanding and examining brain functions. Recently, the patterns of anatomical connections using diffusion tensor imaging (DTI) have been used to parcellate brain regions. Here, we present a noninvasive parcellation approach that uses "functional fingerprints" obtained by correlation measures on resting state functional magnetic resonance imaging (fMRI) data to parcellate brain regions. In other terms, brain regions are parcellated based on the similarity of their connection--as reflected by correlation during resting state--to the whole brain. The proposed method was used to parcellate the medial frontal cortex (MFC) into supplementary motor areas (SMA) and pre-SMA subregions. In agreement with anatomical landmark-based parcellation, we find that functional fingerprint clustering of the MFC results in anterior and posterior clusters. The probabilistic maps from 12 subjects showed that the anterior cluster is mainly located rostral to the vertical commissure anterior (VCA) line, whereas the posterior cluster is mainly located caudal to VCA line, suggesting the homologues of pre-SMA and SMA. The functional connections from the putative pre-SMA cluster were connected to brain regions which are responsible for complex/cognitive motor control, whereas those from the putative SMA cluster were connected to brain regions which are related to the simple motor control. These findings demonstrate the feasibility of the functional connectivity-based parcellation of the human cerebral cortex using resting state fMRI. Copyright (c) 2009 Elsevier Inc. All rights reserved.
Advanced Connectivity Analysis (ACA): a Large Scale Functional Connectivity Data Mining Environment.
Chen, Rong; Nixon, Erika; Herskovits, Edward
2016-04-01
Using resting-state functional magnetic resonance imaging (rs-fMRI) to study functional connectivity is of great importance to understand normal development and function as well as a host of neurological and psychiatric disorders. Seed-based analysis is one of the most widely used rs-fMRI analysis methods. Here we describe a freely available large scale functional connectivity data mining software package called Advanced Connectivity Analysis (ACA). ACA enables large-scale seed-based analysis and brain-behavior analysis. It can seamlessly examine a large number of seed regions with minimal user input. ACA has a brain-behavior analysis component to delineate associations among imaging biomarkers and one or more behavioral variables. We demonstrate applications of ACA to rs-fMRI data sets from a study of autism.
Yang, Jialiang; Qiu, Jing; Wang, Kejing; Zhu, Lijuan; Fan, Jingjing; Zheng, Deyin; Meng, Xiaodi; Yang, Jiasheng; Peng, Lihong; Fu, Yu; Zhang, Dahan; Peng, Shouneng; Huang, Haiyun; Zhang, Yi
2017-01-01
Obesity is a primary risk factor for many diseases such as certain cancers. In this study, we have developed three algorithms including a random-walk based method OBNet, a shortest-path based method OBsp and a direct-overlap method OBoverlap, to reveal obesity-disease connections at protein-interaction subnetworks corresponding to thousands of biological functions and pathways. Through literature mining, we also curated an obesity-associated disease list, by which we compared the methods. As a result, OBNet outperforms other two methods. OBNet can predict whether a disease is obesity-related based on its associated genes. Meanwhile, OBNet identifies extensive connections between obesity genes and genes associated with a few diseases at various functional modules and pathways. Using breast cancer and Type 2 diabetes as two examples, OBNet identifies meaningful genes that may play key roles in connecting obesity and the two diseases. For example, TGFB1 and VEGFA are inferred to be the top two key genes mediating obesity-breast cancer connection in modules associated with brain development. Finally, the top modules identified by OBNet in breast cancer significantly overlap with modules identified from TCGA breast cancer gene expression study, revealing the power of OBNet in identifying biological processes involved in the disease. PMID:29156709
Development of the brain's functional network architecture.
Vogel, Alecia C; Power, Jonathan D; Petersen, Steven E; Schlaggar, Bradley L
2010-12-01
A full understanding of the development of the brain's functional network architecture requires not only an understanding of developmental changes in neural processing in individual brain regions but also an understanding of changes in inter-regional interactions. Resting state functional connectivity MRI (rs-fcMRI) is increasingly being used to study functional interactions between brain regions in both adults and children. We briefly review methods used to study functional interactions and networks with rs-fcMRI and how these methods have been used to define developmental changes in network functional connectivity. The developmental rs-fcMRI studies to date have found two general properties. First, regional interactions change from being predominately anatomically local in children to interactions spanning longer cortical distances in young adults. Second, this developmental change in functional connectivity occurs, in general, via mechanisms of segregation of local regions and integration of distant regions into disparate subnetworks.
Development of the Brain's Functional Network Architecture
Power, Jonathan D.; Petersen, Steven E.; Schlaggar, Bradley L.
2013-01-01
A full understanding of the development of the brain's functional network architecture requires not only an understanding of developmental changes in neural processing in individual brain regions but also an understanding of changes in inter-regional interactions. Resting state functional connectivity MRI (rs-fcMRI) is increasingly being used to study functional interactions between brain regions in both adults and children. We briefly review methods used to study functional interactions and networks with rs-fcMRI and how these methods have been used to define developmental changes in network functional connectivity. The developmental rs-fcMRI studies to date have found two general properties. First, regional interactions change from being predominately anatomically local in children to interactions spanning longer cortical distances in young adults. Second, this developmental change in functional connectivity occurs, in general, via mechanisms of segregation of local regions and integration of distant regions into disparate subnetworks. PMID:20976563
Partitioning of functional gene expression data using principal points.
Kim, Jaehee; Kim, Haseong
2017-10-12
DNA microarrays offer motivation and hope for the simultaneous study of variations in multiple genes. Gene expression is a temporal process that allows variations in expression levels with a characterized gene function over a period of time. Temporal gene expression curves can be treated as functional data since they are considered as independent realizations of a stochastic process. This process requires appropriate models to identify patterns of gene functions. The partitioning of the functional data can find homogeneous subgroups of entities for the massive genes within the inherent biological networks. Therefor it can be a useful technique for the analysis of time-course gene expression data. We propose a new self-consistent partitioning method of functional coefficients for individual expression profiles based on the orthonormal basis system. A principal points based functional partitioning method is proposed for time-course gene expression data. The method explores the relationship between genes using Legendre coefficients as principal points to extract the features of gene functions. Our proposed method provides high connectivity in connectedness after clustering for simulated data and finds a significant subsets of genes with the increased connectivity. Our approach has comparative advantages that fewer coefficients are used from the functional data and self-consistency of principal points for partitioning. As real data applications, we are able to find partitioned genes through the gene expressions found in budding yeast data and Escherichia coli data. The proposed method benefitted from the use of principal points, dimension reduction, and choice of orthogonal basis system as well as provides appropriately connected genes in the resulting subsets. We illustrate our method by applying with each set of cell-cycle-regulated time-course yeast genes and E. coli genes. The proposed method is able to identify highly connected genes and to explore the complex dynamics of biological systems in functional genomics.
Ma, Hong-Wu; Zhao, Xue-Ming; Yuan, Ying-Jin; Zeng, An-Ping
2004-08-12
Metabolic networks are organized in a modular, hierarchical manner. Methods for a rational decomposition of the metabolic network into relatively independent functional subsets are essential to better understand the modularity and organization principle of a large-scale, genome-wide network. Network decomposition is also necessary for functional analysis of metabolism by pathway analysis methods that are often hampered by the problem of combinatorial explosion due to the complexity of metabolic network. Decomposition methods proposed in literature are mainly based on the connection degree of metabolites. To obtain a more reasonable decomposition, the global connectivity structure of metabolic networks should be taken into account. In this work, we use a reaction graph representation of a metabolic network for the identification of its global connectivity structure and for decomposition. A bow-tie connectivity structure similar to that previously discovered for metabolite graph is found also to exist in the reaction graph. Based on this bow-tie structure, a new decomposition method is proposed, which uses a distance definition derived from the path length between two reactions. An hierarchical classification tree is first constructed from the distance matrix among the reactions in the giant strong component of the bow-tie structure. These reactions are then grouped into different subsets based on the hierarchical tree. Reactions in the IN and OUT subsets of the bow-tie structure are subsequently placed in the corresponding subsets according to a 'majority rule'. Compared with the decomposition methods proposed in literature, ours is based on combined properties of the global network structure and local reaction connectivity rather than, primarily, on the connection degree of metabolites. The method is applied to decompose the metabolic network of Escherichia coli. Eleven subsets are obtained. More detailed investigations of the subsets show that reactions in the same subset are really functionally related. The rational decomposition of metabolic networks, and subsequent studies of the subsets, make it more amenable to understand the inherent organization and functionality of metabolic networks at the modular level. http://genome.gbf.de/bioinformatics/
Dynamic Connectivity Patterns in Conscious and Unconscious Brain
Ma, Yuncong; Hamilton, Christina
2017-01-01
Abstract Brain functional connectivity undergoes dynamic changes from the awake to unconscious states. However, how the dynamics of functional connectivity patterns are linked to consciousness at the behavioral level remains elusive. In this study, we acquired resting-state functional magnetic resonance imaging data during wakefulness and graded levels of consciousness in rats. Data were analyzed using a dynamic approach combining the sliding window method and k-means clustering. Our results demonstrate that whole-brain networks contained several quasi-stable patterns that dynamically recurred from the awake state into anesthetized states. Remarkably, two brain connectivity states with distinct spatial similarity to the structure of anatomical connectivity were strongly biased toward high and low consciousness levels, respectively. These results provide compelling neuroimaging evidence linking the dynamics of whole-brain functional connectivity patterns and states of consciousness at the behavioral level. PMID:27846731
Johnston, Jennifer A. Y.; Wang, Fei; Liu, Jie; Blond, Benjamin N.; Wallace, Amanda; Liu, Jiacheng; Spencer, Linda; Cox Lippard, Elizabeth T.; Purves, Kirstin L.; Landeros-Weisenberger, Angeli; Hermes, Eric; Pittman, Brian; Zhang, Sheng; King, Robert; Martin, Andrés; Oquendo, Maria A.; Blumberg, Hilary P.
2018-01-01
Objective Bipolar disorder is associated with high risk for suicide behavior that often develops in adolescence/young adulthood. Elucidation of involved neural systems is critical for prevention. This study of adolescents/young adults with bipolar disorder with and without history of suicide attempts combines structural, diffusion tensor and functional magnetic resonance imaging methods to investigate implicated abnormalities in structural and functional connectivity within fronto-limbic systems. Method Participants with bipolar disorder included 26 with a prior suicide attempt and 42 without attempts. Regional gray matter volume, white matter integrity and functional connectivity during processing of emotional stimuli were compared between groups and differences were explored for relationships between imaging modalities and associations with suicide-related symptoms and behaviors. Results Compared to the non-attempter group, the attempter group showed reductions in gray matter volume in orbitofrontal cortex, hippocampus and cerebellum; white matter integrity in uncinate fasciculus, ventral frontal and right cerebellum regions; and amygdala functional connectivity to left ventral and right rostral prefrontal cortex (p<0.05, corrected). In exploratory analyses, among attempters, right rostral prefrontal connectivity was negatively correlated with suicidal ideation (p<0.05), and left ventral prefrontal connectivity was negatively correlated with attempt lethality (p<0.05). Conclusions Adolescent/young adult suicide attempters with bipolar disorder demonstrate less gray matter volume and decreased structural and functional connectivity in a ventral fronto-limbic neural system subserving emotion regulation. Among suicide attempters, reductions in amygdala-prefrontal functional connectivity may be associated with severity of suicide ideation and attempt lethality. PMID:28135845
Peeters, Sanne C. T.; van de Ven, Vincent; Gronenschild, Ed H. B. M; Patel, Ameera X.; Habets, Petra; Goebel, Rainer; van Os, Jim; Marcelis, Machteld
2015-01-01
Background Research suggests that altered interregional connectivity in specific networks, such as the default mode network (DMN), is associated with cognitive and psychotic symptoms in schizophrenia. In addition, frontal and limbic connectivity alterations have been associated with trauma, drug use and urban upbringing, though these environmental exposures have never been examined in relation to DMN functional connectivity in psychotic disorder. Methods Resting-state functional MRI scans were obtained from 73 patients with psychotic disorder, 83 non-psychotic siblings of patients with psychotic disorder and 72 healthy controls. Posterior cingulate cortex (PCC) seed-based correlation analysis was used to estimate functional connectivity within the DMN. DMN functional connectivity was examined in relation to group (familial risk), group × environmental exposure (to cannabis, developmental trauma and urbanicity) and symptomatology. Results There was a significant association between group and PCC connectivity with the inferior parietal lobule (IPL), the precuneus (PCu) and the medial prefrontal cortex (MPFC). Compared to controls, patients and siblings had increased PCC connectivity with the IPL, PCu and MPFC. In the IPL and PCu, the functional connectivity of siblings was intermediate to that of controls and patients. No significant associations were found between DMN connectivity and (subclinical) psychotic/cognitive symptoms. In addition, there were no significant interactions between group and environmental exposures in the model of PCC functional connectivity. Discussion Increased functional connectivity in individuals with (increased risk for) psychotic disorder may reflect trait-related network alterations. The within-network “connectivity at rest” intermediate phenotype was not associated with (subclinical) psychotic or cognitive symptoms. The association between familial risk and DMN connectivity was not conditional on environmental exposure. PMID:25790002
Sensation-to-Cognition Cortical Streams in Attention-Deficit/Hyperactivity Disorder
Carmona, Susana; Hoekzema, Elseline; Castellanos, Francisco X.; García-García, David; Lage-Castellanos, Agustín; Dijk, Koene R.A.Van; Navas-Sánchez, Francisco J.; Martínez, Kenia; Desco, Manuel; Sepulcre, Jorge
2015-01-01
We sought to determine whether functional connectivity streams that link sensory, attentional, and higher-order cognitive circuits are atypical in attention-deficit/hyperactivity disorder (ADHD). We applied a graph-theory method to the resting-state functional magnetic resonance imaging data of 120 children with ADHD and 120 age-matched typically developing children (TDC). Starting in unimodal primary cortex—visual, auditory, and somatosensory—we used stepwise functional connectivity to calculate functional connectivity paths at discrete numbers of relay stations (or link-step distances). First, we characterized the functional connectivity streams that link sensory, attentional, and higher-order cognitive circuits in TDC and found that systems do not reach the level of integration achieved by adults. Second, we searched for stepwise functional connectivity differences between children with ADHD and TDC. We found that, at the initial steps of sensory functional connectivity streams, patients display significant enhancements of connectivity degree within neighboring areas of primary cortex, while connectivity to attention-regulatory areas is reduced. Third, at subsequent link-step distances from primary sensory cortex, children with ADHD show decreased connectivity to executive processing areas and increased degree of connections to default mode regions. Fourth, in examining medication histories in children with ADHD, we found that children medicated with psychostimulants present functional connectivity streams with higher degree of connectivity to regions subserving attentional and executive processes compared to medication-naïve children. We conclude that predominance of local sensory processing and lesser influx of information to attentional and executive regions may reduce the ability to organize and control the balance between external and internal sources of information in ADHD. PMID:25821110
NASA Astrophysics Data System (ADS)
Zhang, Lei; Sun, Jinyan; Sun, Bailei; Luo, Qingming; Gong, Hui
2014-05-01
Near-infrared spectroscopy (NIRS) is a developing and promising functional brain imaging technology. Developing data analysis methods to effectively extract meaningful information from collected data is the major bottleneck in popularizing this technology. In this study, we measured hemodynamic activity of the prefrontal cortex (PFC) during a color-word matching Stroop task using NIRS. Hemispheric lateralization was examined by employing traditional activation and novel NIRS-based connectivity analyses simultaneously. Wavelet transform coherence was used to assess intrahemispheric functional connectivity. Spearman correlation analysis was used to examine the relationship between behavioral performance and activation/functional connectivity, respectively. In agreement with activation analysis, functional connectivity analysis revealed leftward lateralization for the Stroop effect and correlation with behavioral performance. However, functional connectivity was more sensitive than activation for identifying hemispheric lateralization. Granger causality was used to evaluate the effective connectivity between hemispheres. The results showed increased information flow from the left to the right hemispheres for the incongruent versus the neutral task, indicating a leading role of the left PFC. This study demonstrates that the NIRS-based connectivity can reveal the functional architecture of the brain more comprehensively than traditional activation, helping to better utilize the advantages of NIRS.
Neonatal brain resting-state functional connectivity imaging modalities.
Mohammadi-Nejad, Ali-Reza; Mahmoudzadeh, Mahdi; Hassanpour, Mahlegha S; Wallois, Fabrice; Muzik, Otto; Papadelis, Christos; Hansen, Anne; Soltanian-Zadeh, Hamid; Gelovani, Juri; Nasiriavanaki, Mohammadreza
2018-06-01
Infancy is the most critical period in human brain development. Studies demonstrate that subtle brain abnormalities during this state of life may greatly affect the developmental processes of the newborn infants. One of the rapidly developing methods for early characterization of abnormal brain development is functional connectivity of the brain at rest. While the majority of resting-state studies have been conducted using magnetic resonance imaging (MRI), there is clear evidence that resting-state functional connectivity (rs-FC) can also be evaluated using other imaging modalities. The aim of this review is to compare the advantages and limitations of different modalities used for the mapping of infants' brain functional connectivity at rest. In addition, we introduce photoacoustic tomography, a novel functional neuroimaging modality, as a complementary modality for functional mapping of infants' brain.
Maturing Thalamocortical Functional Connectivity Across Development
Fair, Damien A.; Bathula, Deepti; Mills, Kathryn L.; Dias, Taciana G. Costa; Blythe, Michael S.; Zhang, Dongyang; Snyder, Abraham Z.; Raichle, Marcus E.; Stevens, Alexander A.; Nigg, Joel T.; Nagel, Bonnie J.
2010-01-01
Recent years have witnessed a surge of investigations examining functional brain organization using resting-state functional connectivity MRI (rs-fcMRI). To date, this method has been used to examine systems organization in typical and atypical developing populations. While the majority of these investigations have focused on cortical–cortical interactions, cortical–subcortical interactions also mature into adulthood. Innovative work by Zhang et al. (2008) in adults have identified methods that utilize rs-fcMRI and known thalamo-cortical topographic segregation to identify functional boundaries in the thalamus that are remarkably similar to known thalamic nuclear grouping. However, despite thalamic nuclei being well formed early in development, the developmental trajectory of functional thalamo-cortical relations remains unexplored. Thalamic maps generated by rs-fcMRI are based on functional relationships, and should modify with the dynamic thalamo-cortical changes that occur throughout maturation. To examine this possibility, we employed a strategy as previously described by Zhang et al. to a sample of healthy children, adolescents, and adults. We found strengthening functional connectivity of the cortex with dorsal/anterior subdivisions of the thalamus, with greater connectivity observed in adults versus children. Temporal lobe connectivity with ventral/midline/posterior subdivisions of the thalamus weakened with age. Changes in sensory and motor thalamo-cortical interactions were also identified but were limited. These findings are consistent with known anatomical and physiological cortical–subcortical changes over development. The methods and developmental context provided here will be important for understanding how cortical–subcortical interactions relate to models of typically developing behavior and developmental neuropsychiatric disorders. PMID:20514143
Zhou, Yunyi; Tao, Chenyang; Lu, Wenlian; Feng, Jianfeng
2018-04-20
Functional connectivity is among the most important tools to study brain. The correlation coefficient, between time series of different brain areas, is the most popular method to quantify functional connectivity. Correlation coefficient in practical use assumes the data to be temporally independent. However, the time series data of brain can manifest significant temporal auto-correlation. A widely applicable method is proposed for correcting temporal auto-correlation. We considered two types of time series models: (1) auto-regressive-moving-average model, (2) nonlinear dynamical system model with noisy fluctuations, and derived their respective asymptotic distributions of correlation coefficient. These two types of models are most commonly used in neuroscience studies. We show the respective asymptotic distributions share a unified expression. We have verified the validity of our method, and shown our method exhibited sufficient statistical power for detecting true correlation on numerical experiments. Employing our method on real dataset yields more robust functional network and higher classification accuracy than conventional methods. Our method robustly controls the type I error while maintaining sufficient statistical power for detecting true correlation in numerical experiments, where existing methods measuring association (linear and nonlinear) fail. In this work, we proposed a widely applicable approach for correcting the effect of temporal auto-correlation on functional connectivity. Empirical results favor the use of our method in functional network analysis. Copyright © 2018. Published by Elsevier B.V.
Langs, Georg; Sweet, Andrew; Lashkari, Danial; Tie, Yanmei; Rigolo, Laura; Golby, Alexandra J; Golland, Polina
2014-12-01
In this paper we construct an atlas that summarizes functional connectivity characteristics of a cognitive process from a population of individuals. The atlas encodes functional connectivity structure in a low-dimensional embedding space that is derived from a diffusion process on a graph that represents correlations of fMRI time courses. The functional atlas is decoupled from the anatomical space, and thus can represent functional networks with variable spatial distribution in a population. In practice the atlas is represented by a common prior distribution for the embedded fMRI signals of all subjects. We derive an algorithm for fitting this generative model to the observed data in a population. Our results in a language fMRI study demonstrate that the method identifies coherent and functionally equivalent regions across subjects. The method also successfully maps functional networks from a healthy population used as a training set to individuals whose language networks are affected by tumors. Copyright © 2014. Published by Elsevier Inc.
Lin, Tiger W.; Das, Anup; Krishnan, Giri P.; Bazhenov, Maxim; Sejnowski, Terrence J.
2017-01-01
With our ability to record more neurons simultaneously, making sense of these data is a challenge. Functional connectivity is one popular way to study the relationship of multiple neural signals. Correlation-based methods are a set of currently well-used techniques for functional connectivity estimation. However, due to explaining away and unobserved common inputs (Stevenson, Rebesco, Miller, & Körding, 2008), they produce spurious connections. The general linear model (GLM), which models spike trains as Poisson processes (Okatan, Wilson, & Brown, 2005; Truccolo, Eden, Fellows, Donoghue, & Brown, 2005; Pillow et al., 2008), avoids these confounds. We develop here a new class of methods by using differential signals based on simulated intracellular voltage recordings. It is equivalent to a regularized AR(2) model. We also expand the method to simulated local field potential recordings and calcium imaging. In all of our simulated data, the differential covariance-based methods achieved performance better than or similar to the GLM method and required fewer data samples. This new class of methods provides alternative ways to analyze neural signals. PMID:28777719
Lin, Tiger W; Das, Anup; Krishnan, Giri P; Bazhenov, Maxim; Sejnowski, Terrence J
2017-10-01
With our ability to record more neurons simultaneously, making sense of these data is a challenge. Functional connectivity is one popular way to study the relationship of multiple neural signals. Correlation-based methods are a set of currently well-used techniques for functional connectivity estimation. However, due to explaining away and unobserved common inputs (Stevenson, Rebesco, Miller, & Körding, 2008 ), they produce spurious connections. The general linear model (GLM), which models spike trains as Poisson processes (Okatan, Wilson, & Brown, 2005 ; Truccolo, Eden, Fellows, Donoghue, & Brown, 2005 ; Pillow et al., 2008 ), avoids these confounds. We develop here a new class of methods by using differential signals based on simulated intracellular voltage recordings. It is equivalent to a regularized AR(2) model. We also expand the method to simulated local field potential recordings and calcium imaging. In all of our simulated data, the differential covariance-based methods achieved performance better than or similar to the GLM method and required fewer data samples. This new class of methods provides alternative ways to analyze neural signals.
Dimitriadis, S I; Sun, Yu; Kwok, K; Laskaris, N A; Bezerianos, A
2013-01-01
The association of functional connectivity patterns with particular cognitive tasks has long been a topic of interest in neuroscience, e.g., studies of functional connectivity have demonstrated its potential use for decoding various brain states. However, the high-dimensionality of the pairwise functional connectivity limits its usefulness in some real-time applications. In the present study, the methodology of tensor subspace analysis (TSA) is used to reduce the initial high-dimensionality of the pairwise coupling in the original functional connectivity network to a space of condensed descriptive power, which would significantly decrease the computational cost and facilitate the differentiation of brain states. We assess the feasibility of the proposed method on EEG recordings when the subject was performing mental arithmetic task which differ only in the difficulty level (easy: 1-digit addition v.s. 3-digit additions). Two different cortical connective networks were detected, and by comparing the functional connectivity networks in different work states, it was found that the task-difficulty is best reflected in the connectivity structure of sub-graphs extending over parietooccipital sites. Incorporating this data-driven information within original TSA methodology, we succeeded in predicting the difficulty level from connectivity patterns in an efficient way that can be implemented so as to work in real-time.
Khan, Amanda J.; Nair, Aarti; Keown, Christopher L.; Datko, Michael C.; Lincoln, Alan J.; Müller, Ralph-Axel
2017-01-01
Background The cerebellum plays important roles in both sensorimotor and supramodal cognitive functions. Cellular, volumetric, and functional abnormalities of the cerebellum have been found in autism spectrum disorders (ASD), but no comprehensive investigation of cerebro-cerebellar connectivity in ASD is available. Methods We used resting-state functional connectivity MRI in 56 children and adolescents (28 ASD, 28 typically developing [TD]) aged 8–17 years. Partial and total correlation analyses were performed for unilateral regions of interest (ROIs), distinguished in two broad domains as sensorimotor (premotor/primary motor, somatosensory, superior temporal, occipital) and supramodal (prefrontal, posterior parietal, and inferior and middle temporal). Results There were three main findings: (i) Total correlation analyses showed predominant cerebro-cerebellar functional overconnectivity in the ASD group; (ii) partial correlation analyses that emphasized domain-specificity (sensorimotor vs. supramodal) indicated a pattern of robustly increased connectivity in the ASD group (compared to the TD group) for sensorimotor ROIs, but predominantly reduced connectivity for supramodal ROIs; (iii) this atypical pattern of connectivity was supported by significantly increased non-canonical connections (between sensorimotor cerebral and supramodal cerebellar ROIs, and vice versa) in the ASD group. Conclusions Our findings indicate that sensorimotor intrinsic functional connectivity is atypically increased in ASD, at the expense of connectivity supporting cerebellar participation in supramodal cognition. PMID:25959247
Mapping functional connectivity
Peter Vogt; Joseph R. Ferrari; Todd R. Lookingbill; Robert H. Gardner; Kurt H. Riitters; Katarzyna Ostapowicz
2009-01-01
An objective and reliable assessment of wildlife movement is important in theoretical and applied ecology. The identification and mapping of landscape elements that may enhance functional connectivity is usually a subjective process based on visual interpretations of species movement patterns. New methods based on mathematical morphology provide a generic, flexible,...
Complete affine connection in the causal boundary: static, spherically symmetric spacetimes
NASA Astrophysics Data System (ADS)
Harris, Steven (Stacey) G.
2017-02-01
The boundary at I^+, future null infinity, for a standard static, spherically symmetric spactime is examined for possible linear connections. Two independent methods are employed, one for treating I^+ as the future causal boundary, and one for treating it as a conformal boundary (the latter is subsumed in the former, which is of greater generality). Both methods provide the same result: a constellation of various possible connections, depending on an arbitrary choice of a certain function, a sort of gauge freedom in obtaining a natural connection on I^+; choosing that function to be constant (for instance) results in a complete connection. Treating I^+ as part of the future causal boundary, the method is to impute affine connections on null hypersurfaces going out to I^+, in terms of a transverse vector field on each null hypersurface (there is much gauge freedom on choice of the transverse vector fields). Treating I^+ as part of a conformal boundary, the method is to make a choice of conformal factor that makes the boundary totally geodesic in the enveloping manifold (there is much gauge freedom in choice of that conformal factor). Similar examination is made of other boundaries, such as timelike infinity and timelike and spacelike singularities. These are much simpler, as they admit a unique connection from a similar limiting process (i.e., no gauge freedom); and that connection is complete.
Harris, N.G.; Verley, D.R.; Gutman, B.A.; Thompson, P.M.; Yeh, H.J.; Brown, J.A.
2016-01-01
While past neuroimaging methods have contributed greatly to our understanding of brain function after traumatic brain injury (TBI), resting state functional MRI (rsfMRI) connectivity methods have more recently provided a far more unbiased approach with which to monitor brain circuitry compared to task-based approaches. However, current knowledge on the physiologic underpinnings of the correlated blood oxygen level dependent signal, and how changes in functional connectivity relate to reorganizational processes that occur following injury is limited. The degree and extent of this relationship remain to be determined in order that rsfMRI methods can be fully adapted for determining the optimal timing and type of rehabilitative interventions that can be used post-TBI to achieve the best outcome. Very few rsfMRI studies exist after experimental TBI and therefore we chose to acquire rsfMRI data before and at 7, 14 and 28 days after experimental TBI using a well-known, clinically-relevant, unilateral controlled cortical impact injury (CCI) adult rat model of TBI. This model was chosen since it has widespread axonal injury, a well-defined time-course of reorganization including spine, dendrite, axonal and cortical map changes, as well as spontaneous recovery of sensorimotor function by 28 d post-injury from which to interpret alterations in functional connectivity. Data were co-registered to a parcellated rat template to generate adjacency matrices for network analysis by graph theory. Making no assumptions about direction of change, we used two-tailed statistical analysis over multiple brain regions in a data-driven approach to access global and regional changes in network topology in order to assess brain connectivity in an unbiased way. Our main hypothesis was that deficits in functional connectivity would become apparent in regions known to be structurally altered or deficient in axonal connectivity in this model. The data show the loss of functional connectivity predicted by the structural deficits, not only within the primary sensorimotor injury site and pericontused regions, but the normally connected homotopic cortex, as well as subcortical regions, all of which persisted chronically. Especially novel in this study is the unanticipated finding of widespread increases in connection strength that dwarf both the degree and extent of the functional disconnections, and which persist chronically in some sensorimotor and subcortically connected regions. Exploratory global network analysis showed changes in network parameters indicative of possible acutely increased random connectivity and temporary reductions in modularity that were matched by local increases in connectedness and increased efficiency among more weakly connected regions. The global network parameters: shortest path-length, clustering coefficient and modularity that were most affected by trauma also scaled with the severity of injury, so that the corresponding regional measures were correlated to the injury severity most notably at 7 and 14 days and especially within, but not limited to, the contralateral cortex. These changes in functional network parameters are discussed in relation to the known time-course of physiologic and anatomic data that underlie structural and functional reorganization in this experiment model of TBI. PMID:26730520
Harris, N G; Verley, D R; Gutman, B A; Thompson, P M; Yeh, H J; Brown, J A
2016-03-01
While past neuroimaging methods have contributed greatly to our understanding of brain function after traumatic brain injury (TBI), resting state functional MRI (rsfMRI) connectivity methods have more recently provided a far more unbiased approach with which to monitor brain circuitry compared to task-based approaches. However, current knowledge on the physiologic underpinnings of the correlated blood oxygen level dependent signal, and how changes in functional connectivity relate to reorganizational processes that occur following injury is limited. The degree and extent of this relationship remain to be determined in order that rsfMRI methods can be fully adapted for determining the optimal timing and type of rehabilitative interventions that can be used post-TBI to achieve the best outcome. Very few rsfMRI studies exist after experimental TBI and therefore we chose to acquire rsfMRI data before and at 7, 14 and 28 days after experimental TBI using a well-known, clinically-relevant, unilateral controlled cortical impact injury (CCI) adult rat model of TBI. This model was chosen since it has widespread axonal injury, a well-defined time-course of reorganization including spine, dendrite, axonal and cortical map changes, as well as spontaneous recovery of sensorimotor function by 28 d post-injury from which to interpret alterations in functional connectivity. Data were co-registered to a parcellated rat template to generate adjacency matrices for network analysis by graph theory. Making no assumptions about direction of change, we used two-tailed statistical analysis over multiple brain regions in a data-driven approach to access global and regional changes in network topology in order to assess brain connectivity in an unbiased way. Our main hypothesis was that deficits in functional connectivity would become apparent in regions known to be structurally altered or deficient in axonal connectivity in this model. The data show the loss of functional connectivity predicted by the structural deficits, not only within the primary sensorimotor injury site and pericontused regions, but the normally connected homotopic cortex, as well as subcortical regions, all of which persisted chronically. Especially novel in this study is the unanticipated finding of widespread increases in connection strength that dwarf both the degree and extent of the functional disconnections, and which persist chronically in some sensorimotor and subcortically connected regions. Exploratory global network analysis showed changes in network parameters indicative of possible acutely increased random connectivity and temporary reductions in modularity that were matched by local increases in connectedness and increased efficiency among more weakly connected regions. The global network parameters: shortest path-length, clustering coefficient and modularity that were most affected by trauma also scaled with the severity of injury, so that the corresponding regional measures were correlated to the injury severity most notably at 7 and 14 days and especially within, but not limited to, the contralateral cortex. These changes in functional network parameters are discussed in relation to the known time-course of physiologic and anatomic data that underlie structural and functional reorganization in this experiment model of TBI. Copyright © 2015 Elsevier Inc. All rights reserved.
Jaspers, Ellen; Balsters, Joshua H; Kassraian Fard, Pegah; Mantini, Dante; Wenderoth, Nicole
2017-03-01
Over the last decade, structure-function relationships have begun to encompass networks of brain areas rather than individual structures. For example, corticostriatal circuits have been associated with sensorimotor, limbic, and cognitive information processing, and damage to these circuits has been shown to produce unique behavioral outcomes in Autism, Parkinson's Disease, Schizophrenia and healthy ageing. However, it remains an open question how abnormal or absent connectivity can be detected at the individual level. Here, we provide a method for clustering gross morphological structures into subregions with unique functional connectivity fingerprints, and generate network probability maps usable as a baseline to compare individual cases against. We used connectivity metrics derived from resting-state fMRI (N = 100), in conjunction with hierarchical clustering methods, to parcellate the striatum into functionally distinct clusters. We identified three highly reproducible striatal subregions, across both hemispheres and in an independent replication dataset (N = 100) (dice-similarity values 0.40-1.00). Each striatal seed region resulted in a highly reproducible distinct connectivity fingerprint: the putamen showed predominant connectivity with cortical and cerebellar sensorimotor and language processing areas; the ventromedial striatum cluster had a distinct limbic connectivity pattern; the caudate showed predominant connectivity with the thalamus, frontal and occipital areas, and the cerebellum. Our corticostriatal probability maps agree with existing connectivity data in humans and non-human primates, and showed a high degree of replication. We believe that these maps offer an efficient tool to further advance hypothesis driven research and provide important guidance when investigating deviant connectivity in neurological patient populations suffering from e.g., stroke or cerebral palsy. Hum Brain Mapp 38:1478-1491, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
An information theory framework for dynamic functional domain connectivity.
Vergara, Victor M; Miller, Robyn; Calhoun, Vince
2017-06-01
Dynamic functional network connectivity (dFNC) analyzes time evolution of coherent activity in the brain. In this technique dynamic changes are considered for the whole brain. This paper proposes an information theory framework to measure information flowing among subsets of functional networks call functional domains. Our method aims at estimating bits of information contained and shared among domains. The succession of dynamic functional states is estimated at the domain level. Information quantity is based on the probabilities of observing each dynamic state. Mutual information measurement is then obtained from probabilities across domains. Thus, we named this value the cross domain mutual information (CDMI). Strong CDMIs were observed in relation to the subcortical domain. Domains related to sensorial input, motor control and cerebellum form another CDMI cluster. Information flow among other domains was seldom found. Other methods of dynamic connectivity focus on whole brain dFNC matrices. In the current framework, information theory is applied to states estimated from pairs of multi-network functional domains. In this context, we apply information theory to measure information flow across functional domains. Identified CDMI clusters point to known information pathways in the basal ganglia and also among areas of sensorial input, patterns found in static functional connectivity. In contrast, CDMI across brain areas of higher level cognitive processing follow a different pattern that indicates scarce information sharing. These findings show that employing information theory to formally measured information flow through brain domains reveals additional features of functional connectivity. Copyright © 2017 Elsevier B.V. All rights reserved.
Franco, Alexandre R; Ling, Josef; Caprihan, Arvind; Calhoun, Vince D; Jung, Rex E; Heileman, Gregory L; Mayer, Andrew R
2008-12-01
The human brain functions as an efficient system where signals arising from gray matter are transported via white matter tracts to other regions of the brain to facilitate human behavior. However, with a few exceptions, functional and structural neuroimaging data are typically optimized to maximize the quantification of signals arising from a single source. For example, functional magnetic resonance imaging (FMRI) is typically used as an index of gray matter functioning whereas diffusion tensor imaging (DTI) is typically used to determine white matter properties. While it is likely that these signals arising from different tissue sources contain complementary information, the signal processing algorithms necessary for the fusion of neuroimaging data across imaging modalities are still in a nascent stage. In the current paper we present a data-driven method for combining measures of functional connectivity arising from gray matter sources (FMRI resting state data) with different measures of white matter connectivity (DTI). Specifically, a joint independent component analysis (J-ICA) was used to combine these measures of functional connectivity following intensive signal processing and feature extraction within each of the individual modalities. Our results indicate that one of the most predominantly used measures of functional connectivity (activity in the default mode network) is highly dependent on the integrity of white matter connections between the two hemispheres (corpus callosum) and within the cingulate bundles. Importantly, the discovery of this complex relationship of connectivity was entirely facilitated by the signal processing and fusion techniques presented herein and could not have been revealed through separate analyses of both data types as is typically performed in the majority of neuroimaging experiments. We conclude by discussing future applications of this technique to other areas of neuroimaging and examining potential limitations of the methods.
Hinkley, Leighton B.N.; Vinogradov, Sophia; Guggisberg, Adrian G.; Fisher, Melissa; Findlay, Anne M.; Nagarajan, Srikantan S.
2011-01-01
Background Schizophrenia is associated with functional decoupling between cortical regions, but we do not know whether and where this occurs in low-frequency electromagnetic oscillations. The goal of this study was to use magnetoencephalography (MEG) to identify brain regions that exhibit abnormal resting-state connectivity in the alpha frequency range in patients with schizophrenia and investigate associations between functional connectivity and clinical symptoms in stable outpatient participants. Method Thirty patients with schizophrenia and fifteen healthy comparison participants were scanned in resting-state MEG (eyes closed). Functional connectivity MEGI (fcMEGI) data were reconstructed globally in the alpha range, quantified by the mean imaginary coherence between a voxel and the rest of the brain. Results In patients, decreased connectivity was observed in left pre-frontal cortex (PFC) and right superior temporal cortex while increased connectivity was observed in left extrastriate cortex and the right inferior PFC. Functional connectivity of left inferior parietal cortex was negatively related to positive symptoms. Low left PFC connectivity was associated with negative symptoms. Functional connectivity of midline PFC was negatively correlated with depressed symptoms. Functional connectivity of right PFC was associated with other (cognitive) symptoms. Conclusions This study demonstrates direct functional disconnection in schizophrenia between specific cortical fields within low-frequency resting-state oscillations. Impaired alpha coupling in frontal, parietal, and temporal regions is associated with clinical symptoms in these stable outpatients. Our findings indicate that this level of functional disconnection between cortical regions is an important treatment target in schizophrenia. PMID:21861988
Differential reward network functional connectivity in cannabis dependent and non-dependent users☆
Filbey, Francesca M.; Dunlop, Joseph
2015-01-01
Background Emergent studies show that similar to other substances of abuse, cue-reactivity to cannabis is also associated with neural response in the brain’s reward pathway (Filbey et al., 2009). However, the inter-relatedness of brain regions during cue-reactivity in cannabis users remains unknown. Methods In this study, we conducted a series of investigations to determine functional connectivity during cue-reactivity in 71 cannabis users. First, we used psychophysiological interaction (PPI) analysis to examine coherent neural response to cannabis cues. Second, we evaluated whether these patterns of network functional connectivity differentiated dependent and non-dependent users. Finally, as an exploratory analysis, we determined the directionality of these connections via Granger connectivity analyses. Results PPI analyses showed reward network functional connectivity with the nucleus accumbens (NAc) seed region during cue exposure. Between-group contrasts found differential effects of dependence status. Dependent users (N = 31) had greater functional connectivity with amygdala and anterior cingulate gyrus (ACG) seeds while the non-dependent users (N = 24) had greater functional connectivity with the NAc, orbitofrontal cortex (OFC) and hippocampus seeds. Granger analyses showed that hippocampal and ACG activation preceded neural response in reward areas. Conclusions Both PPI and Granger analyses demonstrated strong functional coherence in reward regions during exposure to cannabis cues in current cannabis users. Functional connectivity (but not regional activation) in the reward network differentiated dependent from non-dependent cannabis users. Our findings suggest that repeated cannabis exposure causes observable changes in functional connectivity in the reward network and should be considered in intervention strategies. PMID:24838032
From Connectivity Models to Region Labels: Identifying Foci of a Neurological Disorder
Venkataraman, Archana; Kubicki, Marek; Golland, Polina
2014-01-01
We propose a novel approach to identify the foci of a neurological disorder based on anatomical and functional connectivity information. Specifically, we formulate a generative model that characterizes the network of abnormal functional connectivity emanating from the affected foci. This allows us to aggregate pairwise connectivity changes into a region-based representation of the disease. We employ the variational expectation-maximization algorithm to fit the model and subsequently identify both the afflicted regions and the differences in connectivity induced by the disorder. We demonstrate our method on a population study of schizophrenia. PMID:23864168
Göttlich, Martin; Heldmann, Marcus; Göbel, Anna; Dirk, Anna-Luise; Brabant, Georg; Münte, Thomas F
2015-06-01
Adult onset hyperthyroidism may impact on different cognitive domains, including attention and concentration, memory, perceptual function, language and executive function. Previous PET studies implicated changed functionality of limbic regions, the temporal and frontal lobes in hyperthyroidism, whereas it is unknown whether cognitive effects of hyperthyroidism may be due to changed brain connectivity. This study aimed to investigate the effect of experimentally induced short-term hyperthyroidism thyrotoxicosis on resting-state functional connectivity using functional magnetic resonance imaging. Twenty-nine healthy male right-handed subjects were examined twice, once prior and once after 8 weeks of oral administration of 250 μg levothyroxine per day. Resting-state fMRI was subjected to graph-theory based analysis methods to investigate whole-brain intrinsic functional connectivity. Despite a lack of subjective changes noticed by the subjects significant thyrotoxicosis was confirmed in all subjects. This induced a significant increase in resting-state functional connectivity specifically in the rostral temporal lobes (0.05 FDR corrected at the cluster level), which is caused by an increased connectivity to the cognitive control network. The increased connectivity between temporal poles and the cognitive control network shown here under experimental conditions supports an important function of thyroid hormones in the regulation of paralimbic structures. Copyright © 2015 Elsevier Ltd. All rights reserved.
Decreased Functional Brain Connectivity in Adolescents with Internet Addiction
Hong, Soon-Beom; Zalesky, Andrew; Cocchi, Luca; Fornito, Alex; Choi, Eun-Jung; Kim, Ho-Hyun; Suh, Jeong-Eun; Kim, Chang-Dai; Kim, Jae-Won; Yi, Soon-Hyung
2013-01-01
Background Internet addiction has become increasingly recognized as a mental disorder, though its neurobiological basis is unknown. This study used functional neuroimaging to investigate whole-brain functional connectivity in adolescents diagnosed with internet addiction. Based on neurobiological changes seen in other addiction related disorders, it was predicted that connectivity disruptions in adolescents with internet addiction would be most prominent in cortico-striatal circuitry. Methods Participants were 12 adolescents diagnosed with internet addiction and 11 healthy comparison subjects. Resting-state functional magnetic resonance images were acquired, and group differences in brain functional connectivity were analyzed using the network-based statistic. We also analyzed network topology, testing for between-group differences in key graph-based network measures. Results Adolescents with internet addiction showed reduced functional connectivity spanning a distributed network. The majority of impaired connections involved cortico-subcortical circuits (∼24% with prefrontal and ∼27% with parietal cortex). Bilateral putamen was the most extensively involved subcortical brain region. No between-group difference was observed in network topological measures, including the clustering coefficient, characteristic path length, or the small-worldness ratio. Conclusions Internet addiction is associated with a widespread and significant decrease of functional connectivity in cortico-striatal circuits, in the absence of global changes in brain functional network topology. PMID:23451272
Functional connectivity analysis of resting-state fMRI networks in nicotine dependent patients
NASA Astrophysics Data System (ADS)
Smith, Aria; Ehtemami, Anahid; Fratte, Daniel; Meyer-Baese, Anke; Zavala-Romero, Olmo; Goudriaan, Anna E.; Schmaal, Lianne; Schulte, Mieke H. J.
2016-03-01
Brain imaging studies identified brain networks that play a key role in nicotine dependence-related behavior. Functional connectivity of the brain is dynamic; it changes over time due to different causes such as learning, or quitting a habit. Functional connectivity analysis is useful in discovering and comparing patterns between functional magnetic resonance imaging (fMRI) scans of patients' brains. In the resting state, the patient is asked to remain calm and not do any task to minimize the contribution of external stimuli. The study of resting-state fMRI networks have shown functionally connected brain regions that have a high level of activity during this state. In this project, we are interested in the relationship between these functionally connected brain regions to identify nicotine dependent patients, who underwent a smoking cessation treatment. Our approach is on the comparison of the set of connections between the fMRI scans before and after treatment. We applied support vector machines, a machine learning technique, to classify patients based on receiving the treatment or the placebo. Using the functional connectivity (CONN) toolbox, we were able to form a correlation matrix based on the functional connectivity between different regions of the brain. The experimental results show that there is inadequate predictive information to classify nicotine dependent patients using the SVM classifier. We propose other classification methods be explored to better classify the nicotine dependent patients.
Sensation-to-cognition cortical streams in attention-deficit/hyperactivity disorder.
Carmona, Susana; Hoekzema, Elseline; Castellanos, Francisco X; García-García, David; Lage-Castellanos, Agustín; Van Dijk, Koene R A; Navas-Sánchez, Francisco J; Martínez, Kenia; Desco, Manuel; Sepulcre, Jorge
2015-07-01
We sought to determine whether functional connectivity streams that link sensory, attentional, and higher-order cognitive circuits are atypical in attention-deficit/hyperactivity disorder (ADHD). We applied a graph-theory method to the resting-state functional magnetic resonance imaging data of 120 children with ADHD and 120 age-matched typically developing children (TDC). Starting in unimodal primary cortex-visual, auditory, and somatosensory-we used stepwise functional connectivity to calculate functional connectivity paths at discrete numbers of relay stations (or link-step distances). First, we characterized the functional connectivity streams that link sensory, attentional, and higher-order cognitive circuits in TDC and found that systems do not reach the level of integration achieved by adults. Second, we searched for stepwise functional connectivity differences between children with ADHD and TDC. We found that, at the initial steps of sensory functional connectivity streams, patients display significant enhancements of connectivity degree within neighboring areas of primary cortex, while connectivity to attention-regulatory areas is reduced. Third, at subsequent link-step distances from primary sensory cortex, children with ADHD show decreased connectivity to executive processing areas and increased degree of connections to default mode regions. Fourth, in examining medication histories in children with ADHD, we found that children medicated with psychostimulants present functional connectivity streams with higher degree of connectivity to regions subserving attentional and executive processes compared to medication-naïve children. We conclude that predominance of local sensory processing and lesser influx of information to attentional and executive regions may reduce the ability to organize and control the balance between external and internal sources of information in ADHD. © 2015 Wiley Periodicals, Inc.
Smith, Jason F.; Chen, Kewei; Pillai, Ajay S.; Horwitz, Barry
2013-01-01
The number and variety of connectivity estimation methods is likely to continue to grow over the coming decade. Comparisons between methods are necessary to prune this growth to only the most accurate and robust methods. However, the nature of connectivity is elusive with different methods potentially attempting to identify different aspects of connectivity. Commonalities of connectivity definitions across methods upon which base direct comparisons can be difficult to derive. Here, we explicitly define “effective connectivity” using a common set of observation and state equations that are appropriate for three connectivity methods: dynamic causal modeling (DCM), multivariate autoregressive modeling (MAR), and switching linear dynamic systems for fMRI (sLDSf). In addition while deriving this set, we show how many other popular functional and effective connectivity methods are actually simplifications of these equations. We discuss implications of these connections for the practice of using one method to simulate data for another method. After mathematically connecting the three effective connectivity methods, simulated fMRI data with varying numbers of regions and task conditions is generated from the common equation. This simulated data explicitly contains the type of the connectivity that the three models were intended to identify. Each method is applied to the simulated data sets and the accuracy of parameter identification is analyzed. All methods perform above chance levels at identifying correct connectivity parameters. The sLDSf method was superior in parameter estimation accuracy to both DCM and MAR for all types of comparisons. PMID:23717258
Bai, Feng; Zhang, Zhijun; Watson, David R; Yu, Hui; Shi, Yongmei; Yuan, Yonggui; Zang, Yufeng; Zhu, Chaozhe; Qian, Yun
2009-06-01
Functional connectivity magnetic resonance imaging technique has revealed the importance of distributed network structures in higher cognitive processes in the human brain. The hippocampus has a key role in a distributed network supporting memory encoding and retrieval. Hippocampal dysfunction is a recurrent finding in memory disorders of aging such as amnestic mild cognitive impairment (aMCI) in which learning- and memory-related cognitive abilities are the predominant impairment. The functional connectivity method provides a novel approach in our attempts to better understand the changes occurring in this structure in aMCI patients. Functional connectivity analysis was used to examine episodic memory retrieval networks in vivo in twenty 28 aMCI patients and 23 well-matched control subjects, specifically between the hippocampal structures and other brain regions. Compared with control subjects, aMCI patients showed significantly lower hippocampus functional connectivity in a network involving prefrontal lobe, temporal lobe, parietal lobe, and cerebellum, and higher functional connectivity to more diffuse areas of the brain than normal aging control subjects. In addition, those regions associated with increased functional connectivity with the hippocampus demonstrated a significantly negative correlation to episodic memory performance. aMCI patients displayed altered patterns of functional connectivity during memory retrieval. The degree of this disturbance appears to be related to level of impairment of processes involved in memory function. Because aMCI is a putative prodromal syndrome to Alzheimer's disease (AD), these early changes in functional connectivity involving the hippocampus may yield important new data to predict whether a patient will eventually develop AD.
Joos, Kathleen; De Ridder, Dirk; Boey, Ronny A.; Vanneste, Sven
2014-01-01
Introduction: Stuttering is defined as speech characterized by verbal dysfluencies, but should not be seen as an isolated speech disorder, but as a generalized sensorimotor timing deficit due to impaired communication between speech related brain areas. Therefore we focused on resting state brain activity and functional connectivity. Method: We included 11 patients with developmental stuttering and 11 age matched controls. To objectify stuttering severity and the impact on quality of life (QoL), we used the Dutch validated Test for Stuttering Severity-Readers (TSS-R) and the Overall Assessment of the Speaker’s Experience of Stuttering (OASES), respectively. Furthermore, we used standardized low resolution brain electromagnetic tomography (sLORETA) analyses to look at resting state activity and functional connectivity differences and their correlations with the TSS-R and OASES. Results: No significant results could be obtained when looking at neural activity, however significant alterations in resting state functional connectivity could be demonstrated between persons who stutter (PWS) and fluently speaking controls, predominantly interhemispheric, i.e., a decreased functional connectivity for high frequency oscillations (beta and gamma) between motor speech areas (BA44 and 45) and the contralateral premotor (BA6) and motor (BA4) areas. Moreover, a positive correlation was found between functional connectivity at low frequency oscillations (theta and alpha) and stuttering severity, while a mixed increased and decreased functional connectivity at low and high frequency oscillations correlated with QoL. Discussion: PWS are characterized by decreased high frequency interhemispheric functional connectivity between motor speech, premotor and motor areas in the resting state, while higher functional connectivity in the low frequency bands indicates more severe speech disturbances, suggesting that increased interhemispheric and right sided functional connectivity is maladaptive. PMID:25352797
Recursive feature elimination for biomarker discovery in resting-state functional connectivity.
Ravishankar, Hariharan; Madhavan, Radhika; Mullick, Rakesh; Shetty, Teena; Marinelli, Luca; Joel, Suresh E
2016-08-01
Biomarker discovery involves finding correlations between features and clinical symptoms to aid clinical decision. This task is especially difficult in resting state functional magnetic resonance imaging (rs-fMRI) data due to low SNR, high-dimensionality of images, inter-subject and intra-subject variability and small numbers of subjects compared to the number of derived features. Traditional univariate analysis suffers from the problem of multiple comparisons. Here, we adopt an alternative data-driven method for identifying population differences in functional connectivity. We propose a machine-learning approach to down-select functional connectivity features associated with symptom severity in mild traumatic brain injury (mTBI). Using this approach, we identified functional regions with altered connectivity in mTBI. including the executive control, visual and precuneus networks. We compared functional connections at multiple resolutions to determine which scale would be more sensitive to changes related to patient recovery. These modular network-level features can be used as diagnostic tools for predicting disease severity and recovery profiles.
Knösche, Thomas R; Tittgemeyer, Marc
2011-01-01
This review focuses on the role of long-range connectivity as one element of brain structure that is of key importance for the functional-anatomical organization of the cortex. In this context, we discuss the putative guiding principles for mapping brain function and structure onto the cortical surface. Such mappings reveal a high degree of functional-anatomical segregation. Given that brain regions frequently maintain characteristic connectivity profiles and the functional repertoire of a cortical area is closely related to its anatomical connections, long-range connectivity may be used to define segregated cortical areas. This methodology is called connectivity-based parcellation. Within this framework, we investigate different techniques to estimate connectivity profiles with emphasis given to non-invasive methods based on diffusion magnetic resonance imaging (dMRI) and diffusion tractography. Cortical parcellation is then defined based on similarity between diffusion tractograms, and different clustering approaches are discussed. We conclude that the use of non-invasively acquired connectivity estimates to characterize the functional-anatomical organization of the brain is a valid, relevant, and necessary endeavor. Current and future developments in dMRI technology, tractography algorithms, and models of the similarity structure hold great potential for a substantial improvement and enrichment of the results of the technique.
Inter-hemispheric functional connectivity disruption in children with prenatal alcohol exposure
Wozniak, Jeffrey R.; Mueller, Bryon A.; Muetzel, Ryan L.; Bell, Christopher J.; Hoecker, Heather L.; Nelson, Miranda L.; Chang, Pi-Nian; Lim, Kelvin O.
2010-01-01
Background MRI studies, including recent diffusion tensor imaging (DTI) studies, have shown corpus callosum abnormalities in children prenatally exposed to alcohol, especially in the posterior regions. These abnormalities appear across the range of Fetal Alcohol Spectrum Disorders (FASD). Several studies have demonstrated cognitive correlates of callosal abnormalities in FASD including deficits in visual-motor skill, verbal learning, and executive functioning. The goal of this study was to determine if inter-hemispheric structural connectivity abnormalities in FASD are associated with disrupted inter-hemispheric functional connectivity and disrupted cognition. Methods Twenty-one children with FASD and 23 matched controls underwent a six minute resting-state functional MRI scan as well as anatomical imaging and DTI. Using a semiautomated method, we parsed the corpus callosum and delineated seven inter-hemispheric white matter tracts with DTI tractography. Cortical regions of interest (ROIs) at the distal ends of these tracts were identified. Right-left correlations in resting fMRI signal were computed for these sets of ROIs and group comparisons were done. Correlations with facial dysmorphology, cognition, and DTI measures were computed. Results A significant group difference in inter-hemispheric functional connectivity was seen in a posterior set of ROIs, the para-central region. Children with FASD had functional connectivity that was 12% lower than controls in this region. Sub-group analyses were not possible due to small sample size, but the data suggest that there were effects across the FASD spectrum. No significant association with facial dysmorphology was found. Para-central functional connectivity was significantly correlated with DTI mean diffusivity, a measure of microstructural integrity, in posterior callosal tracts in controls but not in FASD. Significant correlations were seen between these structural and functional measures and Wechsler perceptual reasoning ability. Conclusions Inter-hemispheric functional connectivity disturbances were observed in children with FASD relative to controls. The disruption was measured in medial parietal regions (para-central) that are connected by posterior callosal fiber projections. We have previously shown microstructural abnormalities in these same posterior callosal regions and the current study suggests a possible relationship between the two. These measures have clinical relevance as they are associated with cognitive functioning. PMID:21303384
Davey, Christopher G.; Yücel, Murat; Allen, Nicholas B.; Harrison, Ben J.
2012-01-01
Background: Major depressive disorder is associated with functional alterations in activity and resting-state connectivity of the extended medial frontal network. In this study we aimed to examine how task-related medial network activity and connectivity were affected in depression. Methods: 18 patients with major depressive disorder, aged 15- to 24-years-old, were matched with 19 healthy control participants. We characterized task-related activations and deactivations while participants engaged with an executive-control task (the multi-source interference task, MSIT). We used a psycho-physiological interactions approach to examine functional connectivity changes with subgenual anterior cingulate cortex. Voxel-wise statistical maps for each analysis were compared between the patient and control groups. Results: There were no differences between groups in their behavioral performances on the MSIT task, and nor in patterns of activation and deactivation. Assessment of functional connectivity with the subgenual cingulate showed that depressed patients did not demonstrate the same reduction in functional connectivity with the ventral striatum during task performance, but that they showed greater reduction in functional connectivity with adjacent ventromedial frontal cortex. The magnitude of this latter connectivity change predicted the relative activation of task-relevant executive-control regions in depressed patients. Conclusion: The study reinforces the importance of the subgenual cingulate cortex for depression, and demonstrates how dysfunctional connectivity with ventral brain regions might influence executive–attentional processes. PMID:22403553
NASA Astrophysics Data System (ADS)
Bauer, Adam Q.; Kraft, Andrew; Baxter, Grant A.; Bruchas, Michael; Lee, Jin-Moo; Culver, Joseph P.
2017-02-01
Functional magnetic resonance imaging (fMRI) has transformed our understanding of the brain's functional organization. However, mapping subunits of a functional network using hemoglobin alone presents several disadvantages. Evoked and spontaneous hemodynamic fluctuations reflect ensemble activity from several populations of neurons making it difficult to discern excitatory vs inhibitory network activity. Still, blood-based methods of brain mapping remain powerful because hemoglobin provides endogenous contrast in all mammalian brains. To add greater specificity to hemoglobin assays, we integrated optical intrinsic signal(OIS) imaging with optogenetic stimulation to create an Opto-OIS mapping tool that combines the cell-specificity of optogenetics with label-free, hemoglobin imaging. Before mapping, titrated photostimuli determined which stimulus parameters elicited linear hemodynamic responses in the cortex. Optimized stimuli were then scanned over the left hemisphere to create a set of optogenetically-defined effective connectivity (Opto-EC) maps. For many sites investigated, Opto-EC maps exhibited higher spatial specificity than those determined using spontaneous hemodynamic fluctuations. For example, resting-state functional connectivity (RS-FC) patterns exhibited widespread ipsilateral connectivity while Opto-EC maps contained distinct short- and long-range constellations of ipsilateral connectivity. Further, RS-FC maps were usually symmetric about midline while Opto-EC maps displayed more heterogeneous contralateral homotopic connectivity. Both Opto-EC and RS-FC patterns were compared to mouse connectivity data from the Allen Institute. Unlike RS-FC maps, Thy1-based maps collected in awake, behaving mice closely recapitulated the connectivity structure derived using ex vivo anatomical tracer methods. Opto-OIS mapping could be a powerful tool for understanding cellular and molecular contributions to network dynamics and processing in the mouse brain.
Differences in functional connectivity between alcohol dependence and internet gaming disorder
Han, Ji Won; Han, Doug Hyun; Bolo, Nicolas; Kim, BoAh; Kim, Boong Nyun; Renshaw, Perry F.
2017-01-01
Introduction Internet gaming disorder (IGD) and alcohol dependence (AD) have been reported to share clinical characteristics including craving and over-engagement despite negative consequences. However, there are also clinical factors that differ between individuals with IGD and those with AD in terms of chemical intoxication, prevalence age, and visual and auditory stimulation. Methods We assessed brain functional connectivity within the prefrontal, striatum, and temporal lobe in 15 patients with IGD and in 16 patients with AD. Symptoms of depression, anxiety, and the attention deficit hyperactivity disorder were assessed in patients with IGD and in patients with AD. Results Both AD and IGD subjects have positive functional connectivity between the dorsolateral prefrontal cortex (DLPFC), cingulate, and cerebellum. In addition, both groups have negative functional connectivity between the DLPFC and the orbitofrontal cortex. However, the AD subjects have positive functional connectivity between the DLPFC, temporal lobe and striatal areas while IGD subjects have negative functional connectivity between the DLPFC, temporal lobe and striatal areas. Conclusions AD and IGD subjects may share deficits in executive function, including problems with self-control and adaptive responding. However, the negative connectivity between the DLPFC and the striatal areas in IGD subjects, different from the connectivity observed in AD subjects, may be due to the earlier prevalence age, different comorbid diseases as well as visual and auditory stimulation. PMID:25282597
Flexible modulation of network connectivity related to cognition in Alzheimer's disease.
McLaren, Donald G; Sperling, Reisa A; Atri, Alireza
2014-10-15
Functional neuroimaging tools, such as fMRI methods, may elucidate the neural correlates of clinical, behavioral, and cognitive performance. Most functional imaging studies focus on regional task-related activity or resting state connectivity rather than how changes in functional connectivity across conditions and tasks are related to cognitive and behavioral performance. To investigate the promise of characterizing context-dependent connectivity-behavior relationships, this study applies the method of generalized psychophysiological interactions (gPPI) to assess the patterns of associative-memory-related fMRI hippocampal functional connectivity in Alzheimer's disease (AD) associated with performance on memory and other cognitively demanding neuropsychological tests and clinical measures. Twenty-four subjects with mild AD dementia (ages 54-82, nine females) participated in a face-name paired-associate encoding memory study. Generalized PPI analysis was used to estimate the connectivity between the hippocampus and the whole brain during encoding. The difference in hippocampal-whole brain connectivity between encoding novel and encoding repeated face-name pairs was used in multiple-regression analyses as an independent predictor for 10 behavioral, neuropsychological and clinical tests. The analysis revealed connectivity-behavior relationships that were distributed, dynamically overlapping, and task-specific within and across intrinsic networks; hippocampal-whole brain connectivity-behavior relationships were not isolated to single networks, but spanned multiple brain networks. Importantly, these spatially distributed performance patterns were unique for each measure. In general, out-of-network behavioral associations with encoding novel greater than repeated face-name pairs hippocampal-connectivity were observed in the default-mode network, while correlations with encoding repeated greater than novel face-name pairs hippocampal-connectivity were observed in the executive control network (p<0.05, cluster corrected). Psychophysiological interactions revealed significantly more extensive and robust associations between paired-associate encoding task-dependent hippocampal-whole brain connectivity and performance on memory and behavioral/clinical measures than previously revealed by standard activity-behavior analysis. Compared to resting state and task-activation methods, gPPI analyses may be more sensitive to reveal additional complementary information regarding subtle within- and between-network relations. The patterns of robust correlations between hippocampal-whole brain connectivity and behavioral measures identified here suggest that there are 'coordinated states' in the brain; that the dynamic range of these states is related to behavior and cognition; and that these states can be observed and quantified, even in individuals with mild AD. Copyright © 2014 Elsevier Inc. All rights reserved.
Ihme, Matthias; Marsden, Alison L; Pitsch, Heinz
2008-02-01
A pattern search optimization method is applied to the generation of optimal artificial neural networks (ANNs). Optimization is performed using a mixed variable extension to the generalized pattern search method. This method offers the advantage that categorical variables, such as neural transfer functions and nodal connectivities, can be used as parameters in optimization. When used together with a surrogate, the resulting algorithm is highly efficient for expensive objective functions. Results demonstrate the effectiveness of this method in optimizing an ANN for the number of neurons, the type of transfer function, and the connectivity among neurons. The optimization method is applied to a chemistry approximation of practical relevance. In this application, temperature and a chemical source term are approximated as functions of two independent parameters using optimal ANNs. Comparison of the performance of optimal ANNs with conventional tabulation methods demonstrates equivalent accuracy by considerable savings in memory storage. The architecture of the optimal ANN for the approximation of the chemical source term consists of a fully connected feedforward network having four nonlinear hidden layers and 117 synaptic weights. An equivalent representation of the chemical source term using tabulation techniques would require a 500 x 500 grid point discretization of the parameter space.
Malekpour, Sheida; Li, Zhimin; Cheung, Bing Leung Patrick; Castillo, Eduardo M.; Papanicolaou, Andrew C.; Kramer, Larry A.; Fletcher, Jack M.
2012-01-01
Abstract The impact of the posterior callosal anomalies associated with spina bifida on interhemispheric cortical connectivity is studied using a method for estimating cortical multivariable autoregressive models from scalp magnetoencephalography data. Interhemispheric effective and functional connectivity, measured using conditional Granger causality and coherence, respectively, is determined for the anterior and posterior cortical regions in a population of five spina bifida and five control subjects during a resting eyes-closed state. The estimated connectivity is shown to be consistent over the randomly selected subsets of the data for each subject. The posterior interhemispheric effective and functional connectivity and cortical power are significantly lower in the spina bifida group, a result that is consistent with posterior callosal anomalies. The anterior interhemispheric effective and functional connectivity are elevated in the spina bifida group, a result that may reflect compensatory mechanisms. In contrast, the intrahemispheric effective connectivity is comparable in the two groups. The differences between the spina bifida and control groups are most significant in the θ and α bands. PMID:22571349
Comparison of continuously acquired resting state and extracted analogues from active tasks.
Ganger, Sebastian; Hahn, Andreas; Küblböck, Martin; Kranz, Georg S; Spies, Marie; Vanicek, Thomas; Seiger, René; Sladky, Ronald; Windischberger, Christian; Kasper, Siegfried; Lanzenberger, Rupert
2015-10-01
Functional connectivity analysis of brain networks has become an important tool for investigation of human brain function. Although functional connectivity computations are usually based on resting-state data, the application to task-specific fMRI has received growing attention. Three major methods for extraction of resting-state data from task-related signal have been proposed (1) usage of unmanipulated task data for functional connectivity; (2) regression against task effects, subsequently using the residuals; and (3) concatenation of baseline blocks located in-between task blocks. Despite widespread application in current research, consensus on which method best resembles resting-state seems to be missing. We, therefore, evaluated these techniques in a sample of 26 healthy controls measured at 7 Tesla. In addition to continuous resting-state, two different task paradigms were assessed (emotion discrimination and right finger-tapping) and five well-described networks were analyzed (default mode, thalamus, cuneus, sensorimotor, and auditory). Investigating the similarity to continuous resting-state (Dice, Intraclass correlation coefficient (ICC), R(2) ) showed that regression against task effects yields functional connectivity networks most alike to resting-state. However, all methods exhibited significant differences when compared to continuous resting-state and similarity metrics were lower than test-retest of two resting-state scans. Omitting global signal regression did not change these findings. Visually, the networks are highly similar, but through further investigation marked differences can be found. Therefore, our data does not support referring to resting-state when extracting signals from task designs, although functional connectivity computed from task-specific data may indeed yield interesting information. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.
Comparison of continuously acquired resting state and extracted analogues from active tasks
Ganger, Sebastian; Hahn, Andreas; Küblböck, Martin; Kranz, Georg S.; Spies, Marie; Vanicek, Thomas; Seiger, René; Sladky, Ronald; Windischberger, Christian; Kasper, Siegfried
2015-01-01
Abstract Functional connectivity analysis of brain networks has become an important tool for investigation of human brain function. Although functional connectivity computations are usually based on resting‐state data, the application to task‐specific fMRI has received growing attention. Three major methods for extraction of resting‐state data from task‐related signal have been proposed (1) usage of unmanipulated task data for functional connectivity; (2) regression against task effects, subsequently using the residuals; and (3) concatenation of baseline blocks located in‐between task blocks. Despite widespread application in current research, consensus on which method best resembles resting‐state seems to be missing. We, therefore, evaluated these techniques in a sample of 26 healthy controls measured at 7 Tesla. In addition to continuous resting‐state, two different task paradigms were assessed (emotion discrimination and right finger‐tapping) and five well‐described networks were analyzed (default mode, thalamus, cuneus, sensorimotor, and auditory). Investigating the similarity to continuous resting‐state (Dice, Intraclass correlation coefficient (ICC), R 2) showed that regression against task effects yields functional connectivity networks most alike to resting‐state. However, all methods exhibited significant differences when compared to continuous resting‐state and similarity metrics were lower than test‐retest of two resting‐state scans. Omitting global signal regression did not change these findings. Visually, the networks are highly similar, but through further investigation marked differences can be found. Therefore, our data does not support referring to resting‐state when extracting signals from task designs, although functional connectivity computed from task‐specific data may indeed yield interesting information. Hum Brain Mapp 36:4053–4063, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:26178250
Desjardins, Marie-Ève; Carrier, Julie; Lina, Jean-Marc; Fortin, Maxime; Gosselin, Nadia; Montplaisir, Jacques
2017-01-01
Abstract Study Objectives: Although sleepwalking (somnambulism) affects up to 4% of adults, its pathophysiology remains poorly understood. Sleepwalking can be preceded by fluctuations in slow-wave sleep EEG signals, but the significance of these pre-episode changes remains unknown and methods based on EEG functional connectivity have yet to be used to better comprehend the disorder. Methods: We investigated the sleep EEG of 27 adult sleepwalkers (mean age: 29 ± 7.6 years) who experienced a somnambulistic episode during slow-wave sleep. The 20-second segment of sleep EEG immediately preceding each patient’s episode was compared with the 20-second segment occurring 2 minutes prior to episode onset. Results: Results from spectral analyses revealed increased delta and theta spectral power in the 20 seconds preceding the episodes’ onset as compared to the 20 seconds occurring 2 minutes before the episodes. The imaginary part of the coherence immediately prior to episode onset revealed (1) decreased delta EEG functional connectivity in parietal and occipital regions, (2) increased alpha connectivity over a fronto-parietal network, and (3) increased beta connectivity involving symmetric inter-hemispheric networks implicating frontotemporal, parietal and occipital areas. Conclusions: Taken together, these modifications in EEG functional connectivity suggest that somnambulistic episodes are preceded by brain processes characterized by the co-existence of arousal and deep sleep. PMID:28204773
NASA Astrophysics Data System (ADS)
Medvedev, Andrei V.; Kainerstorfer, Jana M.; Borisov, Sergey V.; Vanmeter, John
2011-01-01
Near-infrared spectroscopy (NIRS) is a developing technology for low-cost noninvasive functional brain imaging. With multichannel optical instruments, it becomes possible to measure not only local changes in hemoglobin concentrations but also temporal correlations of those changes in different brain regions which gives an optical analog of functional connectivity traditionally measured by fMRI. We recorded hemodynamic activity during the Go-NoGo task from 11 right-handed subjects with probes placed bilaterally over prefrontal areas. Subjects were detecting animals as targets in natural scenes pressing a mouse button. Data were low-pass filtered <1 Hz and cardiac/respiration/superficial layers artifacts were removed using Independent Component Analysis. Fisher's transformed correlations of poststimulus responses (30 s) were averaged over groups of channels unilaterally in each hemisphere (intrahemispheric connectivity) and the corresponding channels between hemispheres (interhemispheric connectivity). The hemodynamic response showed task-related activation (an increase/decrease in oxygenated/deoxygenated hemoglobin, respectively) greater in the right versus left hemisphere. Intra- and interhemispheric functional connectivity was also significantly stronger during the task compared to baseline. Functional connectivity between the inferior and the middle frontal regions was significantly stronger in the right hemisphere. Our results demonstrate that optical methods can be used to detect transient changes in functional connectivity during rapid cognitive processes.
Sinha, Rajita; Lacadie, Cheryl M.; Scheinost, Dustin; Jastreboff, Ania M.; Constable, R. Todd; Potenza, Marc N.
2016-01-01
Introduction: Tobacco-use disorder is a complex condition involving multiple brain networks and presenting with multiple behavioral correlates including changes in diet and stress. In a previous functional magnetic resonance imaging (fMRI) study of neural responses to favorite-food, stress, and neutral-relaxing imagery, smokers versus nonsmokers demonstrated blunted corticostriatal-limbic responses to favorite-food cues. Based on other recent reports of alterations in functional brain networks in smokers, the current study examined functional connectivity during exposure to favorite-food, stress, and neutral-relaxing imagery in smokers and nonsmokers, using the same dataset. Methods: The intrinsic connectivity distribution was measured to identify brain regions that differed in degree of functional connectivity between groups during each imagery condition. Resulting clusters were evaluated for seed-to-voxel connectivity to identify the specific connections that differed between groups during each imagery condition. Results: During exposure to favorite-food imagery, smokers versus nonsmokers showed lower connectivity in the supramarginal gyrus, and differences in connectivity between the supramarginal gyrus and the corticostriatal-limbic system. During exposure to neutral-relaxing imagery, smokers versus nonsmokers showed greater connectivity in the precuneus, and greater connectivity between the precuneus and the posterior insula and rolandic operculum. During exposure to stress imagery, smokers versus nonsmokers showed lower connectivity in the cerebellum. Conclusions: These findings provide data-driven insights into smoking-related alterations in brain functional connectivity patterns related to appetitive, relaxing, and stressful states. Implications: This study uses a data-driven approach to demonstrate that smokers and nonsmokers show differential patterns of functional connectivity during guided imagery related to personalized favorite-food, stress, and neutral-relaxing cues, in brain regions implicated in attention, reward-related, emotional, and motivational processes. For smokers, these differences in connectivity may impact appetite, stress, and relaxation, and may interfere with smoking cessation. PMID:26995796
Langen, Carolyn D; White, Tonya; Ikram, M Arfan; Vernooij, Meike W; Niessen, Wiro J
2015-01-01
Structural and functional brain connectivity are increasingly used to identify and analyze group differences in studies of brain disease. This study presents methods to analyze uni- and bi-modal brain connectivity and evaluate their ability to identify differences. Novel visualizations of significantly different connections comparing multiple metrics are presented. On the global level, "bi-modal comparison plots" show the distribution of uni- and bi-modal group differences and the relationship between structure and function. Differences between brain lobes are visualized using "worm plots". Group differences in connections are examined with an existing visualization, the "connectogram". These visualizations were evaluated in two proof-of-concept studies: (1) middle-aged versus elderly subjects; and (2) patients with schizophrenia versus controls. Each included two measures derived from diffusion weighted images and two from functional magnetic resonance images. The structural measures were minimum cost path between two anatomical regions according to the "Statistical Analysis of Minimum cost path based Structural Connectivity" method and the average fractional anisotropy along the fiber. The functional measures were Pearson's correlation and partial correlation of mean regional time series. The relationship between structure and function was similar in both studies. Uni-modal group differences varied greatly between connectivity types. Group differences were identified in both studies globally, within brain lobes and between regions. In the aging study, minimum cost path was highly effective in identifying group differences on all levels; fractional anisotropy and mean correlation showed smaller differences on the brain lobe and regional levels. In the schizophrenia study, minimum cost path and fractional anisotropy showed differences on the global level and within brain lobes; mean correlation showed small differences on the lobe level. Only fractional anisotropy and mean correlation showed regional differences. The presented visualizations were helpful in comparing and evaluating connectivity measures on multiple levels in both studies.
Varikuti, Deepthi P; Hoffstaedter, Felix; Genon, Sarah; Schwender, Holger; Reid, Andrew T; Eickhoff, Simon B
2017-04-01
Resting-state functional connectivity analysis has become a widely used method for the investigation of human brain connectivity and pathology. The measurement of neuronal activity by functional MRI, however, is impeded by various nuisance signals that reduce the stability of functional connectivity. Several methods exist to address this predicament, but little consensus has yet been reached on the most appropriate approach. Given the crucial importance of reliability for the development of clinical applications, we here investigated the effect of various confound removal approaches on the test-retest reliability of functional-connectivity estimates in two previously defined functional brain networks. Our results showed that gray matter masking improved the reliability of connectivity estimates, whereas denoising based on principal components analysis reduced it. We additionally observed that refraining from using any correction for global signals provided the best test-retest reliability, but failed to reproduce anti-correlations between what have been previously described as antagonistic networks. This suggests that improved reliability can come at the expense of potentially poorer biological validity. Consistent with this, we observed that reliability was proportional to the retained variance, which presumably included structured noise, such as reliable nuisance signals (for instance, noise induced by cardiac processes). We conclude that compromises are necessary between maximizing test-retest reliability and removing variance that may be attributable to non-neuronal sources.
Varikuti, Deepthi P.; Hoffstaedter, Felix; Genon, Sarah; Schwender, Holger; Reid, Andrew T.; Eickhoff, Simon B.
2016-01-01
Resting-state functional connectivity analysis has become a widely used method for the investigation of human brain connectivity and pathology. The measurement of neuronal activity by functional MRI, however, is impeded by various nuisance signals that reduce the stability of functional connectivity. Several methods exist to address this predicament, but little consensus has yet been reached on the most appropriate approach. Given the crucial importance of reliability for the development of clinical applications, we here investigated the effect of various confound removal approaches on the test-retest reliability of functional-connectivity estimates in two previously defined functional brain networks. Our results showed that grey matter masking improved the reliability of connectivity estimates, whereas de-noising based on principal components analysis reduced it. We additionally observed that refraining from using any correction for global signals provided the best test-retest reliability, but failed to reproduce anti-correlations between what have been previously described as antagonistic networks. This suggests that improved reliability can come at the expense of potentially poorer biological validity. Consistent with this, we observed that reliability was proportional to the retained variance, which presumably included structured noise, such as reliable nuisance signals (for instance, noise induced by cardiac processes). We conclude that compromises are necessary between maximizing test-retest reliability and removing variance that may be attributable to non-neuronal sources. PMID:27550015
Liu, Chunyan; Wang, Jiaojian; Hou, Yue; Qi, Zhigang; Wang, Li; Zhan, Shuqin; Wang, Rong; Wang, Yuping
2018-05-01
The hubs of the brain network play a key role in integrating and transferring information between different functional modules. However, whether the changed pattern in functional network hubs contributes to the onset of leg discomfort symptoms in restless legs syndrome (RLS) patients remains unclear. Using resting-state functional magnetic resonance imaging (rs-fMRI) and graph theory methods, we investigated whether alterations of hubs can be detected in RLS. First, we constructed the whole-brain voxelwise functional connectivity and calculated a functional connectivity strength (FCS) map in each of 16 drug-naive idiopathic RLS patients and 26 gender- and age-matched healthy control (HC) subjects. Next, a two-sample t test was applied to compare the FCS maps between HC and RLS patients, and to identify significant changes in FCS in RLS patients. To further elucidate the corresponding changes in the functional connectivity patterns of the aberrant hubs in RLS patients, whole-brain resting-state functional connectivity analyses for the hub areas were performed. The hub analysis revealed decreased FCS in the cuneus, fusiform gyrus, paracentral lobe, and precuneus, and increased FCS in the superior frontal gyrus and thalamus in idiopathic drug-naive RLS patients. Subsequent functional connectivity analyses revealed decreased functional connectivity in sensorimotor and visual processing networks and increased functional connectivity in the affective cognitive network and cerebellar-thalamic circuit. Furthermore, the mean FCS value in the superior frontal gyrus was significantly correlated with Hamilton Anxiety Rating Scale scores in RLS patients, and the mean FCS value in the fusiform gyrus was significantly correlated with Hamilton Depression Rating Scale scores. These findings may provide novel insight into the pathophysiology of RLS. Copyright © 2018 Elsevier B.V. All rights reserved.
van Rooij, Daan; Hartman, Catharina A.; Mennes, Maarten; Oosterlaan, Jaap; Franke, Barbara; Rommelse, Nanda; Heslenfeld, Dirk; Faraone, Stephen V.; Buitelaar, Jan K.; Hoekstra, Pieter J.
2015-01-01
Introduction Response inhibition is one of the executive functions impaired in attention-deficit/hyperactivity disorder (ADHD). Increasing evidence indicates that altered functional and structural neural connectivity are part of the neurobiological basis of ADHD. Here, we investigated if adolescents with ADHD show altered functional connectivity during response inhibition compared to their unaffected siblings and healthy controls. Methods Response inhibition was assessed using the stop signal paradigm. Functional connectivity was assessed using psycho-physiological interaction analyses applied to BOLD time courses from seed regions within inferior- and superior frontal nodes of the response inhibition network. Resulting networks were compared between adolescents with ADHD (N = 185), their unaffected siblings (N = 111), and controls (N = 125). Results Control subjects showed stronger functional connectivity than the other two groups within the response inhibition network, while subjects with ADHD showed relatively stronger connectivity between default mode network (DMN) nodes. Stronger connectivity within the response inhibition network was correlated with lower ADHD severity, while stronger connectivity with the DMN was correlated with increased ADHD severity. Siblings showed connectivity patterns similar to controls during successful inhibition and to ADHD subjects during failed inhibition. Additionally, siblings showed decreased connectivity with the primary motor areas as compared to both participants with ADHD and controls. Discussion Subjects with ADHD fail to integrate activation within the response inhibition network and to inhibit connectivity with task-irrelevant regions. Unaffected siblings show similar alterations only during failed stop trials, as well as unique suppression of motor areas, suggesting compensatory strategies. These findings support the role of altered functional connectivity in understanding the neurobiology and familial transmission of ADHD. PMID:25610797
Jafri, Madiha J; Pearlson, Godfrey D; Stevens, Michael; Calhoun, Vince D
2008-02-15
Functional connectivity of the brain has been studied by analyzing correlation differences in time courses among seed voxels or regions with other voxels of the brain in healthy individuals as well as in patients with brain disorders. The spatial extent of strongly temporally coherent brain regions co-activated during rest has also been examined using independent component analysis (ICA). However, the weaker temporal relationships among ICA component time courses, which we operationally define as a measure of functional network connectivity (FNC), have not yet been studied. In this study, we propose an approach for evaluating FNC and apply it to functional magnetic resonance imaging (fMRI) data collected from persons with schizophrenia and healthy controls. We examined the connectivity and latency among ICA component time courses to test the hypothesis that patients with schizophrenia would show increased functional connectivity and increased lag among resting state networks compared to controls. Resting state fMRI data were collected and the inter-relationships among seven selected resting state networks (identified using group ICA) were evaluated by correlating each subject's ICA time courses with one another. Patients showed higher correlation than controls among most of the dominant resting state networks. Patients also had slightly more variability in functional connectivity than controls. We present a novel approach for quantifying functional connectivity among brain networks identified with spatial ICA. Significant differences between patient and control connectivity in different networks were revealed possibly reflecting deficiencies in cortical processing in patients.
Jafri, Madiha J; Pearlson, Godfrey D; Stevens, Michael; Calhoun, Vince D
2011-01-01
Functional connectivity of the brain has been studied by analyzing correlation differences in time courses among seed voxels or regions with other voxels of the brain in patients versus controls. The spatial extent of strongly temporally coherent brain regions co-activated during rest has also been examined using independent component analysis (ICA). However, the weaker temporal relationships among ICA component time courses, which we operationally define as a measure of functional network connectivity (FNC), have not yet been studied. In this study, we propose an approach for evaluating FNC and apply it to functional magnetic resonance imaging (fMRI) data collected from persons with schizophrenia and healthy controls. We examined the connectivity and latency among ICA component time courses to test the hypothesis that patients with schizophrenia would show increased functional connectivity and increased lag among resting state networks compared to controls. Resting state fMRI data were collected and the inter-relationships among seven selected resting state networks (identified using group ICA) were evaluated by correlating each subject’s ICA time courses with one another. Patients showed higher correlation than controls among most of the dominant resting state networks. Patients also had slightly more variability in functional connectivity than controls. We present a novel approach for quantifying functional connectivity among brain networks identified with spatial ICA. Significant differences between patient and control connectivity in different networks were revealed possibly reflecting deficiencies in cortical processing in patients. PMID:18082428
Osmanski, Bruno-Félix; Pezet, Sophie; Ricobaraza, Ana; Lenkei, Zsolt; Tanter, Mickael
2014-01-01
Long-range coherences in spontaneous brain activity reflect functional connectivity. Here we propose a novel, highly resolved connectivity mapping approach, using ultrafast functional ultrasound (fUS), which enables imaging of cerebral microvascular haemodynamics deep in the anaesthetized rodent brain, through a large thinned-skull cranial window, with pixel dimensions of 100 μm × 100 μm in-plane. The millisecond-range temporal resolution allows unambiguous cancellation of low-frequency cardio-respiratory noise. Both seed-based and singular value decomposition analysis of spatial coherences in the low-frequency (<0.1 Hz) spontaneous fUS signal fluctuations reproducibly report, at different coronal planes, overlapping high-contrast, intrinsic functional connectivity patterns. These patterns are similar to major functional networks described in humans by resting-state fMRI, such as the lateral task-dependent network putatively anticorrelated with the midline default-mode network. These results introduce fUS as a powerful novel neuroimaging method, which could be extended to portable systems for three-dimensional functional connectivity imaging in awake and freely moving rodents. PMID:25277668
Coveleskie, K.; Kilpatrick, L. A.; Gupta, A.; Stains, J.; Connolly, L.; Labus, J. S.; Sanmiguel, C.
2017-01-01
Summary Objective The differential effect of GLP‐1 agonist Exenatide on functional connectivity of the nucleus tractus solitaries (NTS), a key region associated with homeostasis, and on appetite‐related behaviours was investigated in women with normal weight compared with women with obesity. Methods Following an 8‐h fast, 19 female subjects (11 lean, 8 obese) participated in a 2‐d double blind crossover study. Subjects underwent functional magnetic resonance imaging at fast and 30‐min post subcutaneous injection of 5 μg of Exenatide or placebo. Functional connectivity was examined with the NTS. Drug‐induced functional connectivity changes within and between groups and correlations with appetite measures were examined in a region of interest approach focusing on the thalamus and hypothalamus. Results Women with obesity reported less hunger after drug injection. Exenatide administration increased functional connectivity of the left NTS with the left thalamus and hypothalamus in the obese group only and increased the correlation between NTS functional connectivity and hunger scores in all subjects, but more so in the obese. Conclusions Obesity can impact the effects of Exenatide on brain connectivity, specifically in the NTS and is linked to changes in appetite control. This has implications for the use of GLP‐1 analogues in therapeutic interventions. PMID:29259802
Stoeckel, Luke E.; Chai, Xiaoqian J.; Zhang, Jiahe; Whitfield-Gabrieli, Susan; Evins, A. Eden
2015-01-01
Rationale While nicotine addiction is characterized by both structural and functional abnormalities in brain networks involved in salience and cognitive control, few studies have integrated these data to understand how these abnormalities may support addiction. Objectives (1) To evaluate grey matter density and functional connectivity of the anterior insula in cigarette smokers and never-smokers and (2) characterize how differences in these measures related to smoking behavior. Methods We compared structural MRI (grey matter density via voxel-based morphometry) and seed-based functional connectivity MRI data in 16 minimally deprived smokers and 16 matched never-smokers. Results Compared to controls, smokers had lower grey matter density in left anterior insula extending into inferior frontal and temporal cortex. Grey matter density in this region was inversely correlated with cigarettes smoked per day. Smokers exhibited negative functional connectivity (anti-correlation) between the anterior insula and regions involved in cognitive control (left lateral prefrontal cortex) and semantic processing / emotion regulation (lateral temporal cortex), whereas controls exhibited positive connectivity between these regions. Conclusions There were differences in the anterior insula, a central region in the brain’s salience network, when comparing both volumetric and functional connectivity data between cigarette smokers and never smokers. Volumetric data, but not the functional connectivity data, was also associated with an aspect of smoking behavior (daily cigarettes smoked). PMID:25990865
2013-01-01
Background The dimensional approach to autism spectrum disorder (ASD) considers ASD as the extreme of a dimension traversing through the entire population. We explored the potential utility of electroencephalography (EEG) functional connectivity as a biomarker. We hypothesized that individual differences in autistic traits of typical subjects would involve a long-range connectivity diminution within the delta band. Methods Resting-state EEG functional connectivity was measured for 74 neurotypical subjects. All participants also provided a questionnaire (Social Responsiveness Scale, SRS) that was completed by an informant who knows the participant in social settings. We conducted multivariate regression between the SRS score and functional connectivity in all EEG frequency bands. We explored modulations of network graph metrics characterizing the optimality of a network using the SRS score. Results Our results show a decay in functional connectivity mainly within the delta and theta bands (the lower part of the EEG spectrum) associated with an increasing number of autistic traits. When inspecting the impact of autistic traits on the global organization of the functional network, we found that the optimal properties of the network are inversely related to the number of autistic traits, suggesting that the autistic dimension, throughout the entire population, modulates the efficiency of functional brain networks. Conclusions EEG functional connectivity at low frequencies and its associated network properties may be associated with some autistic traits in the general population. PMID:23806204
Neural Signatures of Autism Spectrum Disorders: Insights into Brain Network Dynamics
Hernandez, Leanna M; Rudie, Jeffrey D; Green, Shulamite A; Bookheimer, Susan; Dapretto, Mirella
2015-01-01
Neuroimaging investigations of autism spectrum disorders (ASDs) have advanced our understanding of atypical brain function and structure, and have recently converged on a model of altered network-level connectivity. Traditional task-based functional magnetic resonance imaging (MRI) and volume-based structural MRI studies have identified widespread atypicalities in brain regions involved in social behavior and other core ASD-related behavioral deficits. More recent advances in MR-neuroimaging methods allow for quantification of brain connectivity using diffusion tensor imaging, functional connectivity, and graph theoretic methods. These newer techniques have moved the field toward a systems-level understanding of ASD etiology, integrating functional and structural measures across distal brain regions. Neuroimaging findings in ASD as a whole have been mixed and at times contradictory, likely due to the vast genetic and phenotypic heterogeneity characteristic of the disorder. Future longitudinal studies of brain development will be crucial to yield insights into mechanisms of disease etiology in ASD sub-populations. Advances in neuroimaging methods and large-scale collaborations will also allow for an integrated approach linking neuroimaging, genetics, and phenotypic data. PMID:25011468
Whole brain resting-state analysis reveals decreased functional connectivity in major depression.
Veer, Ilya M; Beckmann, Christian F; van Tol, Marie-José; Ferrarini, Luca; Milles, Julien; Veltman, Dick J; Aleman, André; van Buchem, Mark A; van der Wee, Nic J; Rombouts, Serge A R B
2010-01-01
Recently, both increases and decreases in resting-state functional connectivity have been found in major depression. However, these studies only assessed functional connectivity within a specific network or between a few regions of interest, while comorbidity and use of medication was not always controlled for. Therefore, the aim of the current study was to investigate whole-brain functional connectivity, unbiased by a priori definition of regions or networks of interest, in medication-free depressive patients without comorbidity. We analyzed resting-state fMRI data of 19 medication-free patients with a recent diagnosis of major depression (within 6 months before inclusion) and no comorbidity, and 19 age- and gender-matched controls. Independent component analysis was employed on the concatenated data sets of all participants. Thirteen functionally relevant networks were identified, describing the entire study sample. Next, individual representations of the networks were created using a dual regression method. Statistical inference was subsequently done on these spatial maps using voxel-wise permutation tests. Abnormal functional connectivity was found within three resting-state networks in depression: (1) decreased bilateral amygdala and left anterior insula connectivity in an affective network, (2) reduced connectivity of the left frontal pole in a network associated with attention and working memory, and (3) decreased bilateral lingual gyrus connectivity within ventromedial visual regions. None of these effects were associated with symptom severity or gray matter density. We found abnormal resting-state functional connectivity not previously associated with major depression, which might relate to abnormal affect regulation and mild cognitive deficits, both associated with the symptomatology of the disorder.
Whole Brain Resting-State Analysis Reveals Decreased Functional Connectivity in Major Depression
Veer, Ilya M.; Beckmann, Christian F.; van Tol, Marie-José; Ferrarini, Luca; Milles, Julien; Veltman, Dick J.; Aleman, André; van Buchem, Mark A.; van der Wee, Nic J.; Rombouts, Serge A.R.B.
2010-01-01
Recently, both increases and decreases in resting-state functional connectivity have been found in major depression. However, these studies only assessed functional connectivity within a specific network or between a few regions of interest, while comorbidity and use of medication was not always controlled for. Therefore, the aim of the current study was to investigate whole-brain functional connectivity, unbiased by a priori definition of regions or networks of interest, in medication-free depressive patients without comorbidity. We analyzed resting-state fMRI data of 19 medication-free patients with a recent diagnosis of major depression (within 6 months before inclusion) and no comorbidity, and 19 age- and gender-matched controls. Independent component analysis was employed on the concatenated data sets of all participants. Thirteen functionally relevant networks were identified, describing the entire study sample. Next, individual representations of the networks were created using a dual regression method. Statistical inference was subsequently done on these spatial maps using voxel-wise permutation tests. Abnormal functional connectivity was found within three resting-state networks in depression: (1) decreased bilateral amygdala and left anterior insula connectivity in an affective network, (2) reduced connectivity of the left frontal pole in a network associated with attention and working memory, and (3) decreased bilateral lingual gyrus connectivity within ventromedial visual regions. None of these effects were associated with symptom severity or gray matter density. We found abnormal resting-state functional connectivity not previously associated with major depression, which might relate to abnormal affect regulation and mild cognitive deficits, both associated with the symptomatology of the disorder. PMID:20941370
Rodriguez-Sabate, Clara; Morales, Ingrid; Sanchez, Alberto; Rodriguez, Manuel
2017-01-01
The complexity of basal ganglia (BG) interactions is often condensed into simple models mainly based on animal data and that present BG in closed-loop cortico-subcortical circuits of excitatory/inhibitory pathways which analyze the incoming cortical data and return the processed information to the cortex. This study was aimed at identifying functional relationships in the BG motor-loop of 24 healthy-subjects who provided written, informed consent and whose BOLD-activity was recorded by MRI methods. The analysis of the functional interaction between these centers by correlation techniques and multiple linear regression showed non-linear relationships which cannot be suitably addressed with these methods. The multiple correspondence analysis (MCA), an unsupervised multivariable procedure which can identify non-linear interactions, was used to study the functional connectivity of BG when subjects were at rest. Linear methods showed different functional interactions expected according to current BG models. MCA showed additional functional interactions which were not evident when using lineal methods. Seven functional configurations of BG were identified with MCA, two involving the primary motor and somatosensory cortex, one involving the deepest BG (external-internal globus pallidum, subthalamic nucleus and substantia nigral), one with the input-output BG centers (putamen and motor thalamus), two linking the input-output centers with other BG (external pallidum and subthalamic nucleus), and one linking the external pallidum and the substantia nigral. The results provide evidence that the non-linear MCA and linear methods are complementary and should be best used in conjunction to more fully understand the nature of functional connectivity of brain centers.
Altered resting-state amygdala functional connectivity in men with posttraumatic stress disorder
Sripada, Rebecca K.; King, Anthony P.; Garfinkel, Sarah N.; Wang, Xin; Sripada, Chandra S.; Welsh, Robert C.; Liberzon, Israel
2012-01-01
Background Converging neuroimaging research suggests altered emotion neurocircuitry in individuals with posttraumatic stress disorder (PTSD). Emotion activation studies in these individuals have shown hyperactivation in emotion-related regions, including the amygdala and insula, and hypoactivation in emotion-regulation regions, including the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC). However, few studies have examined patterns of connectivity at rest in individuals with PTSD, a potentially powerful method for illuminating brain network structure. Methods Using the amygdala as a seed region, we measured resting-state brain connectivity using 3 T functional magnetic resonance imaging in returning male veterans with PTSD and combat controls without PTSD. Results Fifteen veterans with PTSD and 14 combat controls enrolled in our study. Compared with controls, veterans with PTSD showed greater positive connectivity between the amygdala and insula, reduced positive connectivity between the amygdala and hippocampus, and reduced anticorrelation between the amygdala and dorsal ACC and rostral ACC. Limitations Only male veterans with combat exposure were tested, thus our findings cannot be generalized to women or to individuals with non–combat related PTSD. Conclusion These results demonstrate that studies of functional connectivity during resting state can discern aberrant patterns of coupling within emotion circuits and suggest a possible brain basis for emotion-processing and emotion-regulation deficits in individuals with PTSD. PMID:22313617
Model-Free Reconstruction of Excitatory Neuronal Connectivity from Calcium Imaging Signals
Stetter, Olav; Battaglia, Demian; Soriano, Jordi; Geisel, Theo
2012-01-01
A systematic assessment of global neural network connectivity through direct electrophysiological assays has remained technically infeasible, even in simpler systems like dissociated neuronal cultures. We introduce an improved algorithmic approach based on Transfer Entropy to reconstruct structural connectivity from network activity monitored through calcium imaging. We focus in this study on the inference of excitatory synaptic links. Based on information theory, our method requires no prior assumptions on the statistics of neuronal firing and neuronal connections. The performance of our algorithm is benchmarked on surrogate time series of calcium fluorescence generated by the simulated dynamics of a network with known ground-truth topology. We find that the functional network topology revealed by Transfer Entropy depends qualitatively on the time-dependent dynamic state of the network (bursting or non-bursting). Thus by conditioning with respect to the global mean activity, we improve the performance of our method. This allows us to focus the analysis to specific dynamical regimes of the network in which the inferred functional connectivity is shaped by monosynaptic excitatory connections, rather than by collective synchrony. Our method can discriminate between actual causal influences between neurons and spurious non-causal correlations due to light scattering artifacts, which inherently affect the quality of fluorescence imaging. Compared to other reconstruction strategies such as cross-correlation or Granger Causality methods, our method based on improved Transfer Entropy is remarkably more accurate. In particular, it provides a good estimation of the excitatory network clustering coefficient, allowing for discrimination between weakly and strongly clustered topologies. Finally, we demonstrate the applicability of our method to analyses of real recordings of in vitro disinhibited cortical cultures where we suggest that excitatory connections are characterized by an elevated level of clustering compared to a random graph (although not extreme) and can be markedly non-local. PMID:22927808
On characterizing population commonalities and subject variations in brain networks.
Ghanbari, Yasser; Bloy, Luke; Tunc, Birkan; Shankar, Varsha; Roberts, Timothy P L; Edgar, J Christopher; Schultz, Robert T; Verma, Ragini
2017-05-01
Brain networks based on resting state connectivity as well as inter-regional anatomical pathways obtained using diffusion imaging have provided insight into pathology and development. Such work has underscored the need for methods that can extract sub-networks that can accurately capture the connectivity patterns of the underlying population while simultaneously describing the variation of sub-networks at the subject level. We have designed a multi-layer graph clustering method that extracts clusters of nodes, called 'network hubs', which display higher levels of connectivity within the cluster than to the rest of the brain. The method determines an atlas of network hubs that describes the population, as well as weights that characterize subject-wise variation in terms of within- and between-hub connectivity. This lowers the dimensionality of brain networks, thereby providing a representation amenable to statistical analyses. The applicability of the proposed technique is demonstrated by extracting an atlas of network hubs for a population of typically developing controls (TDCs) as well as children with autism spectrum disorder (ASD), and using the structural and functional networks of a population to determine the subject-level variation of these hubs and their inter-connectivity. These hubs are then used to compare ASD and TDCs. Our method is generalizable to any population whose connectivity (structural or functional) can be captured via non-negative network graphs. Copyright © 2015 Elsevier B.V. All rights reserved.
Reduced Global Functional Connectivity of the Medial Prefrontal Cortex in Major Depressive Disorder
Murrough, James W.; Abdallah, Chadi G.; Anticevic, Alan; Collins, Katherine A.; Geha, Paul; Averill, Lynnette A.; Schwartz, Jaclyn; DeWilde, Kaitlin E.; Averill, Christopher; Yang, Genevieve Jia-wei; Wong, Edmund; Tang, Cheuk Y.; Krystal, John H.; Iosifescu, Dan V.; Charney, Dennis S.
2016-01-01
Background Major depressive disorder is a disabling neuropsychiatric condition that is associated with disrupted functional connectivity across brain networks. The precise nature of altered connectivity, however, remains incompletely understood. The current study was designed to examine the coherence of large-scale connectivity in depression using a recently developed technique termed global brain connectivity. Methods A total of 82 subjects, including medication-free patients with major depression (n=57) and healthy volunteers (n=25) underwent functional magnetic resonance imaging with resting data acquisition for functional connectivity analysis. Global brain connectivity was computed as the mean of each voxel’s time series correlation with every other voxel and compared between study groups. Relationships between global connectivity and depressive symptom severity measured using the Montgomery-Åsberg Depression Rating Scale were examined by means of linear correlation. Results Relative to the healthy group, patients with depression evidenced reduced global connectivity bilaterally within multiple regions of medial and lateral prefrontal cortex. The largest between-group difference was observed within the right subgenual anterior cingulate cortex, extending into ventromedial prefrontal cortex bilaterally (Hedges’ g = −1.48, p<0.000001). Within the depressed group, patients with the lowest connectivity evidenced the highest symptom severity within ventromedial prefrontal cortex (r = −0.47, p=0.0005). Conclusions Patients with major depressive evidenced abnormal large-scale functional coherence in the brain that was centered within the subgenual cingulate cortex, and medial prefrontal cortex more broadly. These data extend prior studies of connectivity in depression and demonstrate that functional disconnection of the medial prefrontal cortex is a key pathological feature of the disorder. PMID:27144347
Dawson, Neil; Thompson, Rhiannon J.; McVie, Allan; Thomson, David M.; Morris, Brian J.; Pratt, Judith A.
2012-01-01
Objective: In the present study, we employ mathematical modeling (partial least squares regression, PLSR) to elucidate the functional connectivity signatures of discrete brain regions in order to identify the functional networks subserving PCP-induced disruption of distinct cognitive functions and their restoration by the procognitive drug modafinil. Methods: We examine the functional connectivity signatures of discrete brain regions that show overt alterations in metabolism, as measured by semiquantitative 2-deoxyglucose autoradiography, in an animal model (subchronic phencyclidine [PCP] treatment), which shows cognitive inflexibility with relevance to the cognitive deficits seen in schizophrenia. Results: We identify the specific components of functional connectivity that contribute to the rescue of this cognitive inflexibility and to the restoration of overt cerebral metabolism by modafinil. We demonstrate that modafinil reversed both the PCP-induced deficit in the ability to switch attentional set and the PCP-induced hypometabolism in the prefrontal (anterior prelimbic) and retrosplenial cortices. Furthermore, modafinil selectively enhanced metabolism in the medial prelimbic cortex. The functional connectivity signatures of these regions identified a unifying functional subsystem underlying the influence of modafinil on cerebral metabolism and cognitive flexibility that included the nucleus accumbens core and locus coeruleus. In addition, these functional connectivity signatures identified coupling events specific to each brain region, which relate to known anatomical connectivity. Conclusions: These data support clinical evidence that modafinil may alleviate cognitive deficits in schizophrenia and also demonstrate the benefit of applying PLSR modeling to characterize functional brain networks in translational models relevant to central nervous system dysfunction. PMID:20810469
Extraversion modulates functional connectivity hubs of resting-state brain networks.
Pang, Yajing; Cui, Qian; Duan, Xujun; Chen, Heng; Zeng, Ling; Zhang, Zhiqiang; Lu, Guangming; Chen, Huafu
2017-09-01
Personality dimension extraversion describes individual differences in social behaviour and socio-emotional functioning. The intrinsic functional connectivity patterns of the brain are reportedly associated with extraversion. However, whether or not extraversion is associated with functional hubs warrants clarification. Functional hubs are involved in the rapid integration of neural processing, and their dysfunction contributes to the development of neuropsychiatric disorders. In this study, we employed the functional connectivity density (FCD) method for the first time to distinguish the energy-efficient hubs associated with extraversion. The resting-state functional magnetic resonance imaging data of 71 healthy subjects were used in the analysis. Short-range FCD was positively correlated with extraversion in the left cuneus, revealing a link between the local functional activity of this region and extraversion in risk-taking. Long-range FCD was negatively correlated with extraversion in the right superior frontal gyrus and the inferior frontal gyrus. Seed-based resting-state functional connectivity (RSFC) analyses revealed that a decreased long-range FCD in individuals with high extraversion scores showed a low long-range functional connectivity pattern between the medial and dorsolateral prefrontal cortex, middle temporal gyrus, and anterior cingulate cortex. This result suggests that decreased RSFC patterns are responsible for self-esteem, self-evaluation, and inhibitory behaviour system that account for the modulation and shaping of extraversion. Overall, our results emphasize specific brain hubs, and reveal long-range functional connections in relation to extraversion, thereby providing a neurobiological basis of extraversion. © 2015 The British Psychological Society.
Integrated segmentation and recognition of connected Ottoman script
NASA Astrophysics Data System (ADS)
Yalniz, Ismet Zeki; Altingovde, Ismail Sengor; Güdükbay, Uğur; Ulusoy, Özgür
2009-11-01
We propose a novel context-sensitive segmentation and recognition method for connected letters in Ottoman script. This method first extracts a set of segments from a connected script and determines the candidate letters to which extracted segments are most similar. Next, a function is defined for scoring each different syntactically correct sequence of these candidate letters. To find the candidate letter sequence that maximizes the score function, a directed acyclic graph is constructed. The letters are finally recognized by computing the longest path in this graph. Experiments using a collection of printed Ottoman documents reveal that the proposed method provides >90% precision and recall figures in terms of character recognition. In a further set of experiments, we also demonstrate that the framework can be used as a building block for an information retrieval system for digital Ottoman archives.
Disruption of functional networks in dyslexia: A whole-brain, data-driven analysis of connectivity
Finn, Emily S.; Shen, Xilin; Holahan, John M.; Scheinost, Dustin; Lacadie, Cheryl; Papademetris, Xenophon; Shaywitz, Sally E.; Shaywitz, Bennett A.; Constable, R. Todd
2013-01-01
Background Functional connectivity analyses of fMRI data are a powerful tool for characterizing brain networks and how they are disrupted in neural disorders. However, many such analyses examine only one or a small number of a priori seed regions. Studies that consider the whole brain frequently rely on anatomic atlases to define network nodes, which may result in mixing distinct activation timecourses within a single node. Here, we improve upon previous methods by using a data-driven brain parcellation to compare connectivity profiles of dyslexic (DYS) versus non-impaired (NI) readers in the first whole-brain functional connectivity analysis of dyslexia. Methods Whole-brain connectivity was assessed in children (n = 75; 43 NI, 32 DYS) and adult (n = 104; 64 NI, 40 DYS) readers. Results Compared to NI readers, DYS readers showed divergent connectivity within the visual pathway and between visual association areas and prefrontal attention areas; increased right-hemisphere connectivity; reduced connectivity in the visual word-form area (part of the left fusiform gyrus specialized for printed words); and persistent connectivity to anterior language regions around the inferior frontal gyrus. Conclusions Together, findings suggest that NI readers are better able to integrate visual information and modulate their attention to visual stimuli, allowing them to recognize words based on their visual properties, while DYS readers recruit altered reading circuits and rely on laborious phonology-based “sounding out” strategies into adulthood. These results deepen our understanding of the neural basis of dyslexia and highlight the importance of synchrony between diverse brain regions for successful reading. PMID:24124929
Colclough, Giles L; Woolrich, Mark W; Harrison, Samuel J; Rojas López, Pedro A; Valdes-Sosa, Pedro A; Smith, Stephen M
2018-05-07
A Bayesian model for sparse, hierarchical, inver-covariance estimation is presented, and applied to multi-subject functional connectivity estimation in the human brain. It enables simultaneous inference of the strength of connectivity between brain regions at both subject and population level, and is applicable to fMRI, MEG and EEG data. Two versions of the model can encourage sparse connectivity, either using continuous priors to suppress irrelevant connections, or using an explicit description of the network structure to estimate the connection probability between each pair of regions. A large evaluation of this model, and thirteen methods that represent the state of the art of inverse covariance modelling, is conducted using both simulated and resting-state functional imaging datasets. Our novel Bayesian approach has similar performance to the best extant alternative, Ng et al.'s Sparse Group Gaussian Graphical Model algorithm, which also is based on a hierarchical structure. Using data from the Human Connectome Project, we show that these hierarchical models are able to reduce the measurement error in MEG beta-band functional networks by 10%, producing concomitant increases in estimates of the genetic influence on functional connectivity. Copyright © 2018. Published by Elsevier Inc.
Marcos-Vidal, Luis; Martínez-García, Magdalena; Pretus, Clara; Garcia-Garcia, David; Martínez, Kenia; Janssen, Joost; Vilarroya, Oscar; Castellanos, Francisco X; Desco, Manuel; Sepulcre, Jorge; Carmona, Susanna
2018-06-01
Previous studies have associated Attention-Deficit/Hyperactivity Disorder (ADHD) with a maturational lag of brain functional networks. Functional connectivity of the human brain changes from primarily local to more distant connectivity patterns during typical development. Under the maturational lag hypothesis, we expect children with ADHD to exhibit increased local connectivity and decreased distant connectivity compared with neurotypically developing (ND) children. We applied a graph-theory method to compute local and distant connectivity levels and cross-sectionally compared them in a sample of 120 children with ADHD and 120 age-matched ND children (age range = 7-17 years). In addition, we measured if potential group differences in local and distant connectivity were stable across the age range considered. Finally, we assessed the clinical relevance of observed group differences by correlating the connectivity levels and ADHD symptoms severity separately for each group. Children with ADHD exhibited more local connectivity than age-matched ND children in multiple brain regions, mainly overlapping with default mode, fronto-parietal and ventral attentional functional networks (p < .05- threshold free-cluster enhancement-family-wise error). We detected an atypical developmental pattern of local connectivity in somatomotor regions, that is, decreases with age in ND children, and increases with age in children with ADHD. Furthermore, local connectivity within somatomotor areas correlated positively with clinical severity of ADHD symptoms, both in ADHD and ND children. Results suggest an immature functional state of multiple brain networks in children with ADHD. Whereas the ADHD diagnosis is associated with the integrity of the system comprising the fronto-parietal, default mode and ventral attentional networks, the severity of clinical symptoms is related to atypical functional connectivity within somatomotor areas. Additionally, our findings are in line with the view of ADHD as a disorder of deviated maturational trajectories, mainly affecting somatomotor areas, rather than delays that normalize with age. © 2018 Wiley Periodicals, Inc.
The heritability of the functional connectome is robust to common nonlinear registration methods
NASA Astrophysics Data System (ADS)
Hafzalla, George W.; Prasad, Gautam; Baboyan, Vatche G.; Faskowitz, Joshua; Jahanshad, Neda; McMahon, Katie L.; de Zubicaray, Greig I.; Wright, Margaret J.; Braskie, Meredith N.; Thompson, Paul M.
2016-03-01
Nonlinear registration algorithms are routinely used in brain imaging, to align data for inter-subject and group comparisons, and for voxelwise statistical analyses. To understand how the choice of registration method affects maps of functional brain connectivity in a sample of 611 twins, we evaluated three popular nonlinear registration methods: Advanced Normalization Tools (ANTs), Automatic Registration Toolbox (ART), and FMRIB's Nonlinear Image Registration Tool (FNIRT). Using both structural and functional MRI, we used each of the three methods to align the MNI152 brain template, and 80 regions of interest (ROIs), to each subject's T1-weighted (T1w) anatomical image. We then transformed each subject's ROIs onto the associated resting state functional MRI (rs-fMRI) scans and computed a connectivity network or functional connectome for each subject. Given the different degrees of genetic similarity between pairs of monozygotic (MZ) and same-sex dizygotic (DZ) twins, we used structural equation modeling to estimate the additive genetic influences on the elements of the function networks, or their heritability. The functional connectome and derived statistics were relatively robust to nonlinear registration effects.
Dynamic connectivity regression: Determining state-related changes in brain connectivity
Cribben, Ivor; Haraldsdottir, Ragnheidur; Atlas, Lauren Y.; Wager, Tor D.; Lindquist, Martin A.
2014-01-01
Most statistical analyses of fMRI data assume that the nature, timing and duration of the psychological processes being studied are known. However, often it is hard to specify this information a priori. In this work we introduce a data-driven technique for partitioning the experimental time course into distinct temporal intervals with different multivariate functional connectivity patterns between a set of regions of interest (ROIs). The technique, called Dynamic Connectivity Regression (DCR), detects temporal change points in functional connectivity and estimates a graph, or set of relationships between ROIs, for data in the temporal partition that falls between pairs of change points. Hence, DCR allows for estimation of both the time of change in connectivity and the connectivity graph for each partition, without requiring prior knowledge of the nature of the experimental design. Permutation and bootstrapping methods are used to perform inference on the change points. The method is applied to various simulated data sets as well as to an fMRI data set from a study (N=26) of a state anxiety induction using a socially evaluative threat challenge. The results illustrate the method’s ability to observe how the networks between different brain regions changed with subjects’ emotional state. PMID:22484408
On temporal connectivity of PFC via Gauss-Markov modeling of fNIRS signals.
Aydöre, Sergül; Mihçak, M Kivanç; Ciftçi, Koray; Akin, Ata
2010-03-01
Functional near-infrared spectroscopy (fNIRS) is an optical imaging method, which monitors the brain activation by measuring the successive changes in the concentration of oxy- and deoxyhemoglobin in real time. In this study, we present a method to investigate the functional connectivity of prefrontal cortex (PFC) Sby applying a Gauss-Markov model to fNIRS signals. The hemodynamic changes on PFC during the performance of cognitive paradigm are measured by fNIRS for 17 healthy adults. The color-word matching Stroop task is performed to activate 16 different regions of PFC. There are three different types of stimuli in this task, which can be listed as incongruent stimulus (IS), congruent stimulus (CS), and neutral stimulus (NS), respectively. We introduce a new measure, called "information transfer metric" (ITM) for each time sample. The behavior of ITMs during IS are significantly different from the ITMs during CS and NS, which is consistent with the outcome of the previous research, which concentrated on fNIRS signal analysis via color-word matching Stroop task. Our analysis shows that the functional connectivity of PFC is highly relevant with the cognitive load, i.e., functional connectivity increases with the increasing cognitive load.
Effect of sensory and motor connectivity on hand function in pediatric hemiplegia.
Gupta, Disha; Barachant, Alexandre; Gordon, Andrew M; Ferre, Claudio; Kuo, Hsing-Ching; Carmel, Jason B; Friel, Kathleen M
2017-11-01
We tested the hypothesis that somatosensory system injury would more strongly affect movement than motor system injury in children with unilateral cerebral palsy (USCP). This hypothesis was based on how somatosensory and corticospinal circuits adapt to injury during development; whereas the motor system can maintain connections to the impaired hand from the uninjured hemisphere, this does not occur in the somatosensory system. As a corollary, cortical injury strongly impairs sensory function, so we hypothesized that cortical lesions would impair hand function more than subcortical lesions. Twenty-four children with unilateral cerebral palsy had physiological and anatomical measures of the motor and somatosensory systems and lesion classification. Motor physiology was performed with transcranial magnetic stimulation and somatosensory physiology with vibration-evoked electroencephalographic potentials. Tractography of the corticospinal tract and the medial lemniscus was performed with diffusion tensor imaging, and lesions were classified by magnetic resonance imaging. Anatomical and physiological results were correlated with measures of hand function using 2 independent statistical methods. Children with disruptions in the somatosensory connectivity and cortical lesions had the most severe upper extremity impairments, particularly somatosensory function. Motor system connectivity was significantly correlated with bimanual function, but not unimanual function or somatosensory function. Both sensory and motor connectivity impact hand function in children with USCP. Somatosensory connectivity could be an important target for recovery of hand function in children with USCP. Ann Neurol 2017;82:766-780. © 2017 American Neurological Association.
Park, Ji Eun; Park, Bumwoo; Kim, Ho Sung; Choi, Choong Gon; Jung, Seung Chai; Oh, Joo Young; Lee, Jae-Hong; Roh, Jee Hoon; Shim, Woo Hyun
2017-01-01
Objective To identify potential imaging biomarkers of Alzheimer's disease by combining brain cortical thickness (CThk) and functional connectivity and to validate this model's diagnostic accuracy in a validation set. Materials and Methods Data from 98 subjects was retrospectively reviewed, including a study set (n = 63) and a validation set from the Alzheimer's Disease Neuroimaging Initiative (n = 35). From each subject, data for CThk and functional connectivity of the default mode network was extracted from structural T1-weighted and resting-state functional magnetic resonance imaging. Cortical regions with significant differences between patients and healthy controls in the correlation of CThk and functional connectivity were identified in the study set. The diagnostic accuracy of functional connectivity measures combined with CThk in the identified regions was evaluated against that in the medial temporal lobes using the validation set and application of a support vector machine. Results Group-wise differences in the correlation of CThk and default mode network functional connectivity were identified in the superior temporal (p < 0.001) and supramarginal gyrus (p = 0.007) of the left cerebral hemisphere. Default mode network functional connectivity combined with the CThk of those two regions were more accurate than that combined with the CThk of both medial temporal lobes (91.7% vs. 75%). Conclusion Combining functional information with CThk of the superior temporal and supramarginal gyri in the left cerebral hemisphere improves diagnostic accuracy, making it a potential imaging biomarker for Alzheimer's disease. PMID:29089831
Large-scale DCMs for resting-state fMRI.
Razi, Adeel; Seghier, Mohamed L; Zhou, Yuan; McColgan, Peter; Zeidman, Peter; Park, Hae-Jeong; Sporns, Olaf; Rees, Geraint; Friston, Karl J
2017-01-01
This paper considers the identification of large directed graphs for resting-state brain networks based on biophysical models of distributed neuronal activity, that is, effective connectivity . This identification can be contrasted with functional connectivity methods based on symmetric correlations that are ubiquitous in resting-state functional MRI (fMRI). We use spectral dynamic causal modeling (DCM) to invert large graphs comprising dozens of nodes or regions. The ensuing graphs are directed and weighted, hence providing a neurobiologically plausible characterization of connectivity in terms of excitatory and inhibitory coupling. Furthermore, we show that the use of to discover the most likely sparse graph (or model) from a parent (e.g., fully connected) graph eschews the arbitrary thresholding often applied to large symmetric (functional connectivity) graphs. Using empirical fMRI data, we show that spectral DCM furnishes connectivity estimates on large graphs that correlate strongly with the estimates provided by stochastic DCM. Furthermore, we increase the efficiency of model inversion using functional connectivity modes to place prior constraints on effective connectivity. In other words, we use a small number of modes to finesse the potentially redundant parameterization of large DCMs. We show that spectral DCM-with functional connectivity priors-is ideally suited for directed graph theoretic analyses of resting-state fMRI. We envision that directed graphs will prove useful in understanding the psychopathology and pathophysiology of neurodegenerative and neurodevelopmental disorders. We will demonstrate the utility of large directed graphs in clinical populations in subsequent reports, using the procedures described in this paper.
Discriminative analysis of non-linear brain connectivity for leukoaraiosis with resting-state fMRI
NASA Astrophysics Data System (ADS)
Lai, Youzhi; Xu, Lele; Yao, Li; Wu, Xia
2015-03-01
Leukoaraiosis (LA) describes diffuse white matter abnormalities on CT or MR brain scans, often seen in the normal elderly and in association with vascular risk factors such as hypertension, or in the context of cognitive impairment. The mechanism of cognitive dysfunction is still unclear. The recent clinical studies have revealed that the severity of LA was not corresponding to the cognitive level, and functional connectivity analysis is an appropriate method to detect the relation between LA and cognitive decline. However, existing functional connectivity analyses of LA have been mostly limited to linear associations. In this investigation, a novel measure utilizing the extended maximal information coefficient (eMIC) was applied to construct non-linear functional connectivity in 44 LA subjects (9 dementia, 25 mild cognitive impairment (MCI) and 10 cognitively normal (CN)). The strength of non-linear functional connections for the first 1% of discriminative power increased in MCI compared with CN and dementia, which was opposed to its linear counterpart. Further functional network analysis revealed that the changes of the non-linear and linear connectivity have similar but not completely the same spatial distribution in human brain. In the multivariate pattern analysis with multiple classifiers, the non-linear functional connectivity mostly identified dementia, MCI and CN from LA with a relatively higher accuracy rate than the linear measure. Our findings revealed the non-linear functional connectivity provided useful discriminative power in classification of LA, and the spatial distributed changes between the non-linear and linear measure may indicate the underlying mechanism of cognitive dysfunction in LA.
Bernas, Antoine; Barendse, Evelien M; Aldenkamp, Albert P; Backes, Walter H; Hofman, Paul A M; Hendriks, Marc P H; Kessels, Roy P C; Willems, Frans M J; de With, Peter H N; Zinger, Svitlana; Jansen, Jacobus F A
2018-02-01
Autism spectrum disorder (ASD) is mainly characterized by functional and communication impairments as well as restrictive and repetitive behavior. The leading hypothesis for the neural basis of autism postulates globally abnormal brain connectivity, which can be assessed using functional magnetic resonance imaging (fMRI). Even in the absence of a task, the brain exhibits a high degree of functional connectivity, known as intrinsic, or resting-state, connectivity. Global default connectivity in individuals with autism versus controls is not well characterized, especially for a high-functioning young population. The aim of this study is to test whether high-functioning adolescents with ASD (HFA) have an abnormal resting-state functional connectivity. We performed spatial and temporal analyses on resting-state networks (RSNs) in 13 HFA adolescents and 13 IQ- and age-matched controls. For the spatial analysis, we used probabilistic independent component analysis (ICA) and a permutation statistical method to reveal the RSN differences between the groups. For the temporal analysis, we applied Granger causality to find differences in temporal neurodynamics. Controls and HFA display very similar patterns and strengths of resting-state connectivity. We do not find any significant differences between HFA adolescents and controls in the spatial resting-state connectivity. However, in the temporal dynamics of this connectivity, we did find differences in the causal effect properties of RSNs originating in temporal and prefrontal cortices. The results show a difference between HFA and controls in the temporal neurodynamics from the ventral attention network to the salience-executive network: a pathway involving cognitive, executive, and emotion-related cortices. We hypothesized that this weaker dynamic pathway is due to a subtle trigger challenging the cognitive state prior to the resting state.
Robinson, Lucy F; Atlas, Lauren Y; Wager, Tor D
2015-03-01
We present a new method, State-based Dynamic Community Structure, that detects time-dependent community structure in networks of brain regions. Most analyses of functional connectivity assume that network behavior is static in time, or differs between task conditions with known timing. Our goal is to determine whether brain network topology remains stationary over time, or if changes in network organization occur at unknown time points. Changes in network organization may be related to shifts in neurological state, such as those associated with learning, drug uptake or experimental conditions. Using a hidden Markov stochastic blockmodel, we define a time-dependent community structure. We apply this approach to data from a functional magnetic resonance imaging experiment examining how contextual factors influence drug-induced analgesia. Results reveal that networks involved in pain, working memory, and emotion show distinct profiles of time-varying connectivity. Copyright © 2014 Elsevier Inc. All rights reserved.
Alderson-Day, Ben; McCarthy-Jones, Simon; Fernyhough, Charles
2018-01-01
Resting state networks (RSNs) are thought to reflect the intrinsic functional connectivity of brain regions. Alterations to RSNs have been proposed to underpin various kinds of psychopathology, including the occurrence of auditory verbal hallucinations (AVH). This review outlines the main hypotheses linking AVH and the resting state, and assesses the evidence for alterations to intrinsic connectivity provided by studies of resting fMRI in AVH. The influence of hallucinations during data acquisition, medication confounds, and movement are also considered. Despite a large variety of analytic methods and designs being deployed, it is possible to conclude that resting connectivity in the left temporal lobe in general and left superior temporal gyrus in particular are disrupted in AVH. There is also preliminary evidence of atypical connectivity in the default mode network and its interaction with other RSNs. Recommendations for future research include the adoption of a common analysis protocol to allow for more overlapping datasets and replication of intrinsic functional connectivity alterations. PMID:25956256
Resting bold fMRI differentiates dementia with Lewy bodies vs Alzheimer disease
Price, J.L.; Yan, Z.; Morris, J.C.; Sheline, Y.I.
2011-01-01
Objective: Clinicopathologic phenotypes of dementia with Lewy bodies (DLB) and Alzheimer disease (AD) often overlap, making discrimination difficult. We performed resting state blood oxygen level–dependent (BOLD) functional connectivity MRI (fcMRI) to determine whether there were differences between AD and DLB. Methods: Participants (n = 88) enrolled in a longitudinal study of memory and aging underwent 3-T fcMRI. Clinical diagnoses of probable DLB (n = 15) were made according to published criteria. Cognitively normal control participants (n = 38) were selected for the absence of cerebral amyloid burden as imaged with Pittsburgh compound B (PiB). Probable AD cases (n = 35) met published criteria and had appreciable amyloid deposits with PiB imaging. Functional images were collected using a gradient spin-echo sequence sensitive to BOLD contrast (T2* weighting). Correlation maps selected a seed region in the combined bilateral precuneus. Results: Participants with DLB had a functional connectivity pattern for the precuneus seed region that was distinct from AD; both the DLB and AD groups had functional connectivity patterns that differed from the cognitively normal group. In the DLB group, we found increased connectivity between the precuneus and regions in the dorsal attention network and the putamen. In contrast, we found decreased connectivity between the precuneus and other task-negative default regions and visual cortices. There was also a reversal of connectivity in the right hippocampus. Conclusions: Changes in functional connectivity in DLB indicate patterns of activation that are distinct from those seen in AD and may improve discrimination of DLB from AD and cognitively normal individuals. Since patterns of connectivity differ between AD and DLB groups, measurements of BOLD functional connectivity can shed further light on neuroanatomic connections that distinguish DLB from AD. PMID:21525427
Chen, Xue; Wang, Yao; Zhou, Yan; Sun, Yawen; Ding, Weina; Zhuang, Zhiguo; Xu, Jianrong; Du, Yasong
2014-01-01
This study investigated changes in resting-state functional connectivity (rsFC) of posterior cingulate cortex (PCC) in smokers and nonsmokers with Internet gaming addiction (IGA). Twenty-nine smokers with IGA, 22 nonsmokers with IGA, and 30 healthy controls (HC group) underwent a resting-state fMRI scan. PCC connectivity was determined in all subjects by investigating synchronized low-frequency fMRI signal fluctuations using a temporal correlation method. Compared with the nonsmokers with IGA, the smokers with IGA exhibited decreased rsFC with PCC in the right rectus gyrus. Left middle frontal gyrus exhibited increased rsFC. The PCC connectivity with the right rectus gyrus was found to be negatively correlated with the CIAS scores in the smokers with IGA before correction. Our results suggested that smokers with IGA had functional changes in brain areas related to motivation and executive function compared with the nonsmokers with IGA. PMID:25506057
Sun, Junfeng; Li, Zhijun; Tong, Shanbao
2012-01-01
Functional neural connectivity is drawing increasing attention in neuroscience research. To infer functional connectivity from observed neural signals, various methods have been proposed. Among them, phase synchronization analysis is an important and effective one which examines the relationship of instantaneous phase between neural signals but neglecting the influence of their amplitudes. In this paper, we review the advances in methodologies of phase synchronization analysis. In particular, we discuss the definitions of instantaneous phase, the indexes of phase synchronization and their significance test, the issues that may affect the detection of phase synchronization and the extensions of phase synchronization analysis. In practice, phase synchronization analysis may be affected by observational noise, insufficient samples of the signals, volume conduction, and reference in recording neural signals. We make comments and suggestions on these issues so as to better apply phase synchronization analysis to inferring functional connectivity from neural signals. PMID:22577470
Decoding Lifespan Changes of the Human Brain Using Resting-State Functional Connectivity MRI
Wang, Lubin; Su, Longfei; Shen, Hui; Hu, Dewen
2012-01-01
The development of large-scale functional brain networks is a complex, lifelong process that can be investigated using resting-state functional connectivity MRI (rs-fcMRI). In this study, we aimed to decode the developmental dynamics of the whole-brain functional network in seven decades (8–79 years) of the human lifespan. We first used parametric curve fitting to examine linear and nonlinear age effect on the resting human brain, and then combined manifold learning and support vector machine methods to predict individuals' “brain ages” from rs-fcMRI data. We found that age-related changes in interregional functional connectivity exhibited spatially and temporally specific patterns. During brain development from childhood to senescence, functional connections tended to linearly increase in the emotion system and decrease in the sensorimotor system; while quadratic trajectories were observed in functional connections related to higher-order cognitive functions. The complex patterns of age effect on the whole-brain functional network could be effectively represented by a low-dimensional, nonlinear manifold embedded in the functional connectivity space, which uncovered the inherent structure of brain maturation and aging. Regression of manifold coordinates with age further showed that the manifold representation extracted sufficient information from rs-fcMRI data to make prediction about individual brains' functional development levels. Our study not only gives insights into the neural substrates that underlie behavioral and cognitive changes over age, but also provides a possible way to quantitatively describe the typical and atypical developmental progression of human brain function using rs-fcMRI. PMID:22952990
Decoding lifespan changes of the human brain using resting-state functional connectivity MRI.
Wang, Lubin; Su, Longfei; Shen, Hui; Hu, Dewen
2012-01-01
The development of large-scale functional brain networks is a complex, lifelong process that can be investigated using resting-state functional connectivity MRI (rs-fcMRI). In this study, we aimed to decode the developmental dynamics of the whole-brain functional network in seven decades (8-79 years) of the human lifespan. We first used parametric curve fitting to examine linear and nonlinear age effect on the resting human brain, and then combined manifold learning and support vector machine methods to predict individuals' "brain ages" from rs-fcMRI data. We found that age-related changes in interregional functional connectivity exhibited spatially and temporally specific patterns. During brain development from childhood to senescence, functional connections tended to linearly increase in the emotion system and decrease in the sensorimotor system; while quadratic trajectories were observed in functional connections related to higher-order cognitive functions. The complex patterns of age effect on the whole-brain functional network could be effectively represented by a low-dimensional, nonlinear manifold embedded in the functional connectivity space, which uncovered the inherent structure of brain maturation and aging. Regression of manifold coordinates with age further showed that the manifold representation extracted sufficient information from rs-fcMRI data to make prediction about individual brains' functional development levels. Our study not only gives insights into the neural substrates that underlie behavioral and cognitive changes over age, but also provides a possible way to quantitatively describe the typical and atypical developmental progression of human brain function using rs-fcMRI.
Eack, Shaun M.; Newhill, Christina E.; Keshavan, Matcheri S.
2016-01-01
Objective Cognitive remediation is emerging as an effective psychosocial intervention for addressing untreated cognitive and functional impairments in persons with schizophrenia, and might achieve its benefits through neuroplastic changes in brain connectivity. This study seeks to examine the effects of cognitive enhancement therapy (CET) on fronto-temporal brain connectivity in a randomized controlled trial with individuals in the early course of schizophrenia. Method Stabilized, early course outpatients with schizophrenia or schizoaffective disorder (N = 41) were randomly assigned to CET (n = 25) or an active enriched supportive therapy (EST) control (n = 16) and treated for 2 years. Functional MRI data were collected annually, and pseudo resting-state functional connectivity analysis was used to examine differential changes in fronto-temporal connectivity between those treated with CET compared with EST. Results Individuals receiving CET evidenced significantly less functional connectivity loss between the resting-state network and the left dorsolateral prefrontal cortex as well as significantly increased connectivity with the right insular cortex compared to EST (all corrected p < .01). These neural networks are involved in emotion processing and problem-solving. Increased connectivity with the right insula significantly mediated CET effects on improved emotion perception (z′ = −1.96, p = .021), and increased connectivity with the left dorsolateral prefrontal cortex mediated CET-related improvements in emotion regulation (z′ = −1.71, p = .052). Conclusions These findings provide preliminary evidence that CET, a psychosocial cognitive remediation intervention, may enhance connectivity between frontal and temporal brain regions implicated in problem-solving and emotion processing in service of cognitive enhancement in schizophrenia. PMID:27713804
Aberrant patterns of local and long-range functional connectivity densities in schizophrenia
Tian, Hongjun; Li, Jie; Qu, Hongru; Cheng, Langlang; Zhu, Jingjing; Zhuo, Chuanjun
2017-01-01
Schizophrenia is a disorder of brain dysconnectivity, and both the connection strength and connection number are disrupted in patients with schizophrenia. The functional connectivity density (FCD) can reflect alterations in the connection number. Alterations in the global FCD (gFCD) in schizophrenia were previously demonstrated; however, alterations in two other indices of the pathological characteristics of the brain, local FCD (lFCD) and long-range FCD (lrFCD), have not been revealed. To investigate lFCD and lrFCD alterations in patients with schizophrenia, 95 patients and 93 matched healthy controls were examined using structural and resting-state functional magnetic resonance imaging scanning. lFCD and lrFCD were measured using FCD mapping, and differences were identified using a two-sample t-test in a voxel-wise manner, with age and gender considered to increase variability. Multiple comparisons were performed using a false discovery rate method with a corrected threshold of P<0.05. Our analysis showed that lFCD was primarily decreased in the postcentral gyrus, right calcarine sulcus, and inferior occipital gyrus lobule, but increased in the bilateral subcortical regions. The differences in lFCD were more pronounced and complicated than those in lrFCD. In summary, in contrast with previous studies that focused on the connection strength, our findings, from the perspective of connection number, indicate that schizophrenia is a disorder of brain dysconnectivity, particularly affecting the local functional connectivity network, and support the hypothesis that schizophrenia is associated with a widespread cortical functional connectivity/activity deficit, with hyper- and/or hypo-connectivity/activity coexisting in some cortical or subcortical regions. PMID:28654893
Aberrant patterns of local and long-range functional connectivity densities in schizophrenia.
Liu, Chuanxin; Zhang, Wei; Chen, Guangdong; Tian, Hongjun; Li, Jie; Qu, Hongru; Cheng, Langlang; Zhu, Jingjing; Zhuo, Chuanjun
2017-07-18
Schizophrenia is a disorder of brain dysconnectivity, and both the connection strength and connection number are disrupted in patients with schizophrenia. The functional connectivity density (FCD) can reflect alterations in the connection number. Alterations in the global FCD (gFCD) in schizophrenia were previously demonstrated; however, alterations in two other indices of the pathological characteristics of the brain, local FCD (lFCD) and long-range FCD (lrFCD), have not been revealed. To investigate lFCD and lrFCD alterations in patients with schizophrenia, 95 patients and 93 matched healthy controls were examined using structural and resting-state functional magnetic resonance imaging scanning. lFCD and lrFCD were measured using FCD mapping, and differences were identified using a two-sample t-test in a voxel-wise manner, with age and gender considered to increase variability. Multiple comparisons were performed using a false discovery rate method with a corrected threshold of P<0.05. Our analysis showed that lFCD was primarily decreased in the postcentral gyrus, right calcarine sulcus, and inferior occipital gyrus lobule, but increased in the bilateral subcortical regions. The differences in lFCD were more pronounced and complicated than those in lrFCD. In summary, in contrast with previous studies that focused on the connection strength, our findings, from the perspective of connection number, indicate that schizophrenia is a disorder of brain dysconnectivity, particularly affecting the local functional connectivity network, and support the hypothesis that schizophrenia is associated with a widespread cortical functional connectivity/activity deficit, with hyper- and/or hypo-connectivity/activity coexisting in some cortical or subcortical regions.
What We Know About the Brain Structure-Function Relationship.
Batista-García-Ramó, Karla; Fernández-Verdecia, Caridad Ivette
2018-04-18
How the human brain works is still a question, as is its implication with brain architecture: the non-trivial structure–function relationship. The main hypothesis is that the anatomic architecture conditions, but does not determine, the neural network dynamic. The functional connectivity cannot be explained only considering the anatomical substrate. This involves complex and controversial aspects of the neuroscience field and that the methods and methodologies to obtain structural and functional connectivity are not always rigorously applied. The goal of the present article is to discuss about the progress made to elucidate the structure–function relationship of the Central Nervous System, particularly at the brain level, based on results from human and animal studies. The current novel systems and neuroimaging techniques with high resolutive physio-structural capacity have brought about the development of an integral framework of different structural and morphometric tools such as image processing, computational modeling and graph theory. Different laboratories have contributed with in vivo, in vitro and computational/mathematical models to study the intrinsic neural activity patterns based on anatomical connections. We conclude that multi-modal techniques of neuroimaging are required such as an improvement on methodologies for obtaining structural and functional connectivity. Even though simulations of the intrinsic neural activity based on anatomical connectivity can reproduce much of the observed patterns of empirical functional connectivity, future models should be multifactorial to elucidate multi-scale relationships and to infer disorder mechanisms.
Epicenters of dynamic connectivity in the adaptation of the ventral visual system.
Prčkovska, Vesna; Huijbers, Willem; Schultz, Aaron; Ortiz-Teran, Laura; Peña-Gomez, Cleofe; Villoslada, Pablo; Johnson, Keith; Sperling, Reisa; Sepulcre, Jorge
2017-04-01
Neuronal responses adapt to familiar and repeated sensory stimuli. Enhanced synchrony across wide brain systems has been postulated as a potential mechanism for this adaptation phenomenon. Here, we used recently developed graph theory methods to investigate hidden connectivity features of dynamic synchrony changes during a visual repetition paradigm. Particularly, we focused on strength connectivity changes occurring at local and distant brain neighborhoods. We found that connectivity reorganization in visual modal cortex-such as local suppressed connectivity in primary visual areas and distant suppressed connectivity in fusiform areas-is accompanied by enhanced local and distant connectivity in higher cognitive processing areas in multimodal and association cortex. Moreover, we found a shift of the dynamic functional connections from primary-visual-fusiform to primary-multimodal/association cortex. These findings suggest that repetition-suppression is made possible by reorganization of functional connectivity that enables communication between low- and high-order areas. Hum Brain Mapp 38:1965-1976, 2017. © 2017 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Probabilistic drug connectivity mapping
2014-01-01
Background The aim of connectivity mapping is to match drugs using drug-treatment gene expression profiles from multiple cell lines. This can be viewed as an information retrieval task, with the goal of finding the most relevant profiles for a given query drug. We infer the relevance for retrieval by data-driven probabilistic modeling of the drug responses, resulting in probabilistic connectivity mapping, and further consider the available cell lines as different data sources. We use a special type of probabilistic model to separate what is shared and specific between the sources, in contrast to earlier connectivity mapping methods that have intentionally aggregated all available data, neglecting information about the differences between the cell lines. Results We show that the probabilistic multi-source connectivity mapping method is superior to alternatives in finding functionally and chemically similar drugs from the Connectivity Map data set. We also demonstrate that an extension of the method is capable of retrieving combinations of drugs that match different relevant parts of the query drug response profile. Conclusions The probabilistic modeling-based connectivity mapping method provides a promising alternative to earlier methods. Principled integration of data from different cell lines helps to identify relevant responses for specific drug repositioning applications. PMID:24742351
Hyperconnectivity is a fundamental response to neurological disruption.
Hillary, Frank G; Roman, Cristina A; Venkatesan, Umesh; Rajtmajer, Sarah M; Bajo, Ricardo; Castellanos, Nazareth D
2015-01-01
In the cognitive and clinical neurosciences, the past decade has been marked by dramatic growth in a literature examining brain "connectivity" using noninvasive methods. We offer a critical review of the blood oxygen level dependent functional MRI (BOLD fMRI) literature examining neural connectivity changes in neurological disorders with focus on brain injury and dementia. The goal is to demonstrate that there are identifiable shifts in local and large-scale network connectivity that can be predicted by the degree of pathology. We anticipate that the most common network response to neurological insult is hyperconnectivity but that this response depends upon demand and resource availability. To examine this hypothesis, we initially reviewed the results from 1,426 studies examining functional brain connectivity in individuals diagnosed with multiple sclerosis, traumatic brain injury, mild cognitive impairment, and Alzheimer's disease. Based upon inclusionary criteria, 126 studies were included for detailed analysis. RESULTS from 126 studies examining local and whole brain connectivity demonstrated increased connectivity in traumatic brain injury and multiple sclerosis. This finding is juxtaposed with findings in mild cognitive impairment and Alzheimer's disease where there is a shift to diminished connectivity as degeneration progresses. This summary of the functional imaging literature using fMRI methods reveals that hyperconnectivity is a common response to neurological disruption and that it may be differentially observable across brain regions. We discuss the factors contributing to both hyper- and hypoconnectivity results after neurological disruption and the implications these findings have for network plasticity. PsycINFO Database Record (c) 2015 APA, all rights reserved.
Erdoğan, Sinem B; Tong, Yunjie; Hocke, Lia M; Lindsey, Kimberly P; deB Frederick, Blaise
2016-01-01
Resting state functional connectivity analysis is a widely used method for mapping intrinsic functional organization of the brain. Global signal regression (GSR) is commonly employed for removing systemic global variance from resting state BOLD-fMRI data; however, recent studies have demonstrated that GSR may introduce spurious negative correlations within and between functional networks, calling into question the meaning of anticorrelations reported between some networks. In the present study, we propose that global signal from resting state fMRI is composed primarily of systemic low frequency oscillations (sLFOs) that propagate with cerebral blood circulation throughout the brain. We introduce a novel systemic noise removal strategy for resting state fMRI data, "dynamic global signal regression" (dGSR), which applies a voxel-specific optimal time delay to the global signal prior to regression from voxel-wise time series. We test our hypothesis on two functional systems that are suggested to be intrinsically organized into anticorrelated networks: the default mode network (DMN) and task positive network (TPN). We evaluate the efficacy of dGSR and compare its performance with the conventional "static" global regression (sGSR) method in terms of (i) explaining systemic variance in the data and (ii) enhancing specificity and sensitivity of functional connectivity measures. dGSR increases the amount of BOLD signal variance being modeled and removed relative to sGSR while reducing spurious negative correlations introduced in reference regions by sGSR, and attenuating inflated positive connectivity measures. We conclude that incorporating time delay information for sLFOs into global noise removal strategies is of crucial importance for optimal noise removal from resting state functional connectivity maps.
Dynamics of the human brain network revealed by time-frequency effective connectivity in fNIRS
Vergotte, Grégoire; Torre, Kjerstin; Chirumamilla, Venkata Chaitanya; Anwar, Abdul Rauf; Groppa, Sergiu; Perrey, Stéphane; Muthuraman, Muthuraman
2017-01-01
Functional near infrared spectroscopy (fNIRS) is a promising neuroimaging method for investigating networks of cortical regions over time. We propose a directed effective connectivity method (TPDC) allowing the capture of both time and frequency evolution of the brain’s networks using fNIRS data acquired from healthy subjects performing a continuous finger-tapping task. Using this method we show the directed connectivity patterns among cortical motor regions involved in the task and their significant variations in the strength of information flow exchanges. Intra and inter-hemispheric connections during the motor task with their temporal evolution are also provided. Characterisation of the fluctuations in brain connectivity opens up a new way to assess the organisation of the brain to adapt to changing task constraints, or under pathological conditions. PMID:29188123
Feng, Jun-Tao; Liu, Han-Qiu; Hua, Xu-Yun; Gu, Yu-Dong; Xu, Jian-Guang; Xu, Wen-Dong
2016-12-01
Brachial plexus injury (BPI) is a type of severe peripheral nerve trauma that leads to central remodeling in the brain, as revealed by functional MRI analysis. However, previously reported remodeling is mostly restricted to sensorimotor areas of the brain. Whether this disturbance in the sensorimotor network leads to larger-scale functional remodeling remains unknown. We sought to explore the higher-level brain functional abnormality pattern of BPI patients from a large-scale network function connectivity dimension in 15 right-handed BPI patients. Resting-state functional MRI data were collected and analyzed using independent component analysis methods. Five components of interest were recognized and compared between patients and healthy subjects. Patients showed significantly altered brain local functional activities in the bilateral fronto-parietal network (FPN), sensorimotor network (SMN), and executive-control network (ECN) compared with healthy subjects. Moreover, functional connectivity between SMN and ECN were significantly less in patients compared with healthy subjects, and connectivity strength between ECN and SMN was negatively correlated with patients' residual function of the affected limb. Functional connectivity between SMN and right FPN were also significantly less than in controls, although connectivity between ECN and default mode network (DMN) was greater than in controls. These data suggested that brain functional disturbance in BPI patients extends beyond the sensorimotor network and cascades serial remodeling in the brain, which significantly correlates with residual hand function of the paralyzed limb. Furthermore, functional remodeling in these higher-level functional networks may lead to cognitive alterations in complex tasks.
Connectivity Predicts Deep Brain Stimulation Outcome in Parkinson Disease
Horn, Andreas; Reich, Martin; Vorwerk, Johannes; Li, Ningfei; Wenzel, Gregor; Fang, Qianqian; Schmitz-Hübsch, Tanja; Nickl, Robert; Kupsch, Andreas; Volkmann, Jens; Kühn, Andrea A.; Fox, Michael D.
2018-01-01
Objective The benefit of deep brain stimulation (DBS) for Parkinson disease (PD) may depend on connectivity between the stimulation site and other brain regions, but which regions and whether connectivity can predict outcome in patients remain unknown. Here, we identify the structural and functional connectivity profile of effective DBS to the subthalamic nucleus (STN) and test its ability to predict outcome in an independent cohort. Methods A training dataset of 51 PD patients with STN DBS was combined with publicly available human connectome data (diffusion tractography and resting state functional connectivity) to identify connections reliably associated with clinical improvement (motor score of the Unified Parkinson Disease Rating Scale [UPDRS]). This connectivity profile was then used to predict outcome in an independent cohort of 44 patients from a different center. Results In the training dataset, connectivity between the DBS electrode and a distributed network of brain regions correlated with clinical response including structural connectivity to supplementary motor area and functional anticorrelation to primary motor cortex (p<0.001). This same connectivity profile predicted response in an independent patient cohort (p<0.01). Structural and functional connectivity were independent predictors of clinical improvement (p<0.001) and estimated response in individual patients with an average error of 15% UPDRS improvement. Results were similar using connectome data from normal subjects or a connectome age, sex, and disease matched to our DBS patients. Interpretation Effective STN DBS for PD is associated with a specific connectivity profile that can predict clinical outcome across independent cohorts. This prediction does not require specialized imaging in PD patients themselves. PMID:28586141
Yang, Chuan-Chih; Barrós-Loscertales, Alfonso; Pinazo, Daniel; Ventura-Campos, Noelia; Borchardt, Viola; Bustamante, Juan-Carlos; Rodríguez-Pujadas, Aina; Fuentes-Claramonte, Paola; Balaguer, Raúl; Ávila, César; Walter, Martin
2016-01-01
The topic of investigating how mindfulness meditation training can have antidepressant effects via plastic changes in both resting state and meditation state brain activity is important in the rapidly emerging field of neuroplasticity. In the present study, we used a longitudinal design investigating resting state fMRI both before and after 40 days of meditation training in 13 novices. After training, we compared differences in network connectivity between rest and meditation using common resting state functional connectivity methods. Interregional methods were paired with local measures such as Regional Homogeneity. As expected, significant differences in functional connectivity both between states (rest versus meditation) and between time points (before versus after training) were observed. During meditation, the internal consistency in the precuneus and the temporoparietal junction increased, while the internal consistency of frontal brain regions decreased. A follow-up analysis of regional connectivity of the dorsal anterior cingulate cortex further revealed reduced connectivity with anterior insula during meditation. After meditation training, reduced resting state functional connectivity between the pregenual anterior cingulate and dorsal medical prefrontal cortex was observed. Most importantly, significantly reduced depression/anxiety scores were observed after training. Hence, these findings suggest that mindfulness meditation might be of therapeutic use by inducing plasticity related network changes altering the neuronal basis of affective disorders such as depression.
Yang, Chuan-Chih; Barrós-Loscertales, Alfonso; Pinazo, Daniel; Ventura-Campos, Noelia; Borchardt, Viola; Bustamante, Juan-Carlos; Rodríguez-Pujadas, Aina; Fuentes-Claramonte, Paola; Balaguer, Raúl; Ávila, César; Walter, Martin
2016-01-01
The topic of investigating how mindfulness meditation training can have antidepressant effects via plastic changes in both resting state and meditation state brain activity is important in the rapidly emerging field of neuroplasticity. In the present study, we used a longitudinal design investigating resting state fMRI both before and after 40 days of meditation training in 13 novices. After training, we compared differences in network connectivity between rest and meditation using common resting state functional connectivity methods. Interregional methods were paired with local measures such as Regional Homogeneity. As expected, significant differences in functional connectivity both between states (rest versus meditation) and between time points (before versus after training) were observed. During meditation, the internal consistency in the precuneus and the temporoparietal junction increased, while the internal consistency of frontal brain regions decreased. A follow-up analysis of regional connectivity of the dorsal anterior cingulate cortex further revealed reduced connectivity with anterior insula during meditation. After meditation training, reduced resting state functional connectivity between the pregenual anterior cingulate and dorsal medical prefrontal cortex was observed. Most importantly, significantly reduced depression/anxiety scores were observed after training. Hence, these findings suggest that mindfulness meditation might be of therapeutic use by inducing plasticity related network changes altering the neuronal basis of affective disorders such as depression. PMID:26998365
Thalamocortical dysconnectivity in schizophrenia
Woodward, Neil D.; Karbasforoushan, Haleh; Heckers, Stephan
2013-01-01
Objective The thalamus and cerebral cortex are connected via topographically organized, reciprocal connections. Previous studies revealed thalamic abnormalities in schizophrenia; however, it is not known if thalamocortical networks are differentially affected in the disorder. To explore this possibility, we examined functional connectivity in intrinsic low frequency blood-oxygen-level-dependent (BOLD) signal fluctuations between major divisions of the cortex and thalamus using resting-state functional magnetic resonance imaging. Method 77 healthy subjects and 62 patients with schizophrenia underwent resting-state fMRI. To identify functional subdivisions of the thalamus, we parceled the cortex into six regions-of-interest; prefrontal, motor, somatosensory, temporal, posterior parietal, and occipital cortex. Mean BOLD time-series was extracted from each of the regions-of-interest and entered into a seed-based functional connectivity analysis. Results Consistent with prior reports, activity in distinct cortical areas correlated with specific, largely non-overlapping regions of the thalamus in both healthy subjects and schizophrenia patients. Direct comparison between groups revealed reduced prefrontal-thalamic connectivity and increased motor/somatosensory-thalamic connectivity in schizophrenia. The changes in connectivity were unrelated to local grey matter content within the thalamus and antipsychotic medication dosage. No differences were observed in temporal, posterior parietal, and occipital cortex connectivity with the thalamus. Conclusions This study establishes differential abnormalities of thalamocortical networks in schizophrenia. The etiology of schizophrenia may disrupt the development of prefrontal-thalamic connectivity and refinement of somatomotor connectivity with the thalamus that occurs during brain maturation. PMID:23032387
Havlicek, Martin; Jan, Jiri; Brazdil, Milan; Calhoun, Vince D.
2015-01-01
Increasing interest in understanding dynamic interactions of brain neural networks leads to formulation of sophisticated connectivity analysis methods. Recent studies have applied Granger causality based on standard multivariate autoregressive (MAR) modeling to assess the brain connectivity. Nevertheless, one important flaw of this commonly proposed method is that it requires the analyzed time series to be stationary, whereas such assumption is mostly violated due to the weakly nonstationary nature of functional magnetic resonance imaging (fMRI) time series. Therefore, we propose an approach to dynamic Granger causality in the frequency domain for evaluating functional network connectivity in fMRI data. The effectiveness and robustness of the dynamic approach was significantly improved by combining a forward and backward Kalman filter that improved estimates compared to the standard time-invariant MAR modeling. In our method, the functional networks were first detected by independent component analysis (ICA), a computational method for separating a multivariate signal into maximally independent components. Then the measure of Granger causality was evaluated using generalized partial directed coherence that is suitable for bivariate as well as multivariate data. Moreover, this metric provides identification of causal relation in frequency domain, which allows one to distinguish the frequency components related to the experimental paradigm. The procedure of evaluating Granger causality via dynamic MAR was demonstrated on simulated time series as well as on two sets of group fMRI data collected during an auditory sensorimotor (SM) or auditory oddball discrimination (AOD) tasks. Finally, a comparison with the results obtained from a standard time-invariant MAR model was provided. PMID:20561919
Thompson, Deanne K.; Chen, Jian; Beare, Richard; Adamson, Christopher L.; Ellis, Rachel; Ahmadzai, Zohra M.; Kelly, Claire E.; Lee, Katherine J.; Zalesky, Andrew; Yang, Joseph Y.M.; Hunt, Rodney W.; Cheong, Jeanie L.Y.; Inder, Terrie E.; Doyle, Lex W.; Seal, Marc L.; Anderson, Peter J.
2016-01-01
Objective To use structural connectivity to (1) compare brain networks between typically and atypically developing (very preterm) children, (2) explore associations between potential perinatal developmental disturbances and brain networks, and (3) describe associations between brain networks and functional impairments in very preterm children. Methods 26 full-term and 107 very preterm 7-year-old children (born <30 weeks’ gestational age and/or <1250 g) underwent T1- and diffusion-weighted imaging. Global white matter fiber networks were produced using 80 cortical and subcortical nodes, and edges created using constrained spherical deconvolution-based tractography. Global graph theory metrics were analysed, and regional networks were identified using network-based statistics. Cognitive and motor function were assessed at 7 years of age. Results Compared with full-term children, very preterm children had reduced density, lower global efficiency and higher local efficiency. Those with lower gestational age at birth, infection or higher neonatal brain abnormality score had reduced connectivity. Reduced connectivity within a widespread network was predictive of impaired IQ, while reduced connectivity within the right parietal and temporal lobes was associated with motor impairment in very preterm children. Conclusions This study utilized an innovative structural connectivity pipeline to reveal that children born very preterm have less connected and less complex brain networks compared with typically developing term-born children. Adverse perinatal factors led to disturbances in white matter connectivity, which in turn are associated with impaired functional outcomes, highlighting novel structure-function relationships. PMID:27046108
Resting-state functional connectivity imaging of the mouse brain using photoacoustic tomography
NASA Astrophysics Data System (ADS)
Nasiriavanaki, Mohammadreza; Xia, Jun; Wan, Hanlin; Bauer, Adam Q.; Culver, Joseph P.; Wang, Lihong V.
2014-03-01
Resting-state functional connectivity (RSFC) imaging is an emerging neuroimaging approach that aims to identify spontaneous cerebral hemodynamic fluctuations and their associated functional connections. Clinical studies have demonstrated that RSFC is altered in brain disorders such as stroke, Alzheimer's, autism, and epilepsy. However, conventional neuroimaging modalities cannot easily be applied to mice, the most widely used model species for human brain disease studies. For instance, functional magnetic resonance imaging (fMRI) of mice requires a very high magnetic field to obtain a sufficient signal-to-noise ratio and spatial resolution. Functional connectivity mapping with optical intrinsic signal imaging (fcOIS) is an alternative method. Due to the diffusion of light in tissue, the spatial resolution of fcOIS is limited, and experiments have been performed using an exposed skull preparation. In this study, we show for the first time, the use of photoacoustic computed tomography (PACT) to noninvasively image resting-state functional connectivity in the mouse brain, with a large field of view and a high spatial resolution. Bilateral correlations were observed in eight regions, as well as several subregions. These findings agreed well with the Paxinos mouse brain atlas. This study showed that PACT is a promising, non-invasive modality for small-animal functional brain imaging.
Identifying disease-related subnetwork connectome biomarkers by sparse hypergraph learning.
Zu, Chen; Gao, Yue; Munsell, Brent; Kim, Minjeong; Peng, Ziwen; Cohen, Jessica R; Zhang, Daoqiang; Wu, Guorong
2018-06-14
The functional brain network has gained increased attention in the neuroscience community because of its ability to reveal the underlying architecture of human brain. In general, majority work of functional network connectivity is built based on the correlations between discrete-time-series signals that link only two different brain regions. However, these simple region-to-region connectivity models do not capture complex connectivity patterns between three or more brain regions that form a connectivity subnetwork, or subnetwork for short. To overcome this current limitation, a hypergraph learning-based method is proposed to identify subnetwork differences between two different cohorts. To achieve our goal, a hypergraph is constructed, where each vertex represents a subject and also a hyperedge encodes a subnetwork with similar functional connectivity patterns between different subjects. Unlike previous learning-based methods, our approach is designed to jointly optimize the weights for all hyperedges such that the learned representation is in consensus with the distribution of phenotype data, i.e. clinical labels. In order to suppress the spurious subnetwork biomarkers, we further enforce a sparsity constraint on the hyperedge weights, where a larger hyperedge weight indicates the subnetwork with the capability of identifying the disorder condition. We apply our hypergraph learning-based method to identify subnetwork biomarkers in Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD). A comprehensive quantitative and qualitative analysis is performed, and the results show that our approach can correctly classify ASD and ADHD subjects from normal controls with 87.65 and 65.08% accuracies, respectively.
A human brain network derived from coma-causing brainstem lesions
Boes, Aaron D.; Demertzi, Athena; Evrard, Henry C.; Laureys, Steven; Edlow, Brian L.; Liu, Hesheng; Saper, Clifford B.; Pascual-Leone, Alvaro; Geerling, Joel C.
2016-01-01
Objective: To characterize a brainstem location specific to coma-causing lesions, and its functional connectivity network. Methods: We compared 12 coma-causing brainstem lesions to 24 control brainstem lesions using voxel-based lesion-symptom mapping in a case-control design to identify a site significantly associated with coma. We next used resting-state functional connectivity from a healthy cohort to identify a network of regions functionally connected to this brainstem site. We further investigated the cortical regions of this network by comparing their spatial topography to that of known networks and by evaluating their functional connectivity in patients with disorders of consciousness. Results: A small region in the rostral dorsolateral pontine tegmentum was significantly associated with coma-causing lesions. In healthy adults, this brainstem site was functionally connected to the ventral anterior insula (AI) and pregenual anterior cingulate cortex (pACC). These cortical areas aligned poorly with previously defined resting-state networks, better matching the distribution of von Economo neurons. Finally, connectivity between the AI and pACC was disrupted in patients with disorders of consciousness, and to a greater degree than other brain networks. Conclusions: Injury to a small region in the pontine tegmentum is significantly associated with coma. This brainstem site is functionally connected to 2 cortical regions, the AI and pACC, which become disconnected in disorders of consciousness. This network of brain regions may have a role in the maintenance of human consciousness. PMID:27815400
Chen, Xingui; Tao, Longxiang; Li, Jingjing; Wu, Jiaonan; Zhu, Chunyan; Yu, Fengqiong; Zhang, Lei; Zhang, Jingjie; Qiu, Bensheng; Yu, Yongqiang; He, Xiaoxuan
2017-01-01
Abstract Background: Tamoxifen is the most widely used drug for treating patients with estrogen receptor-sensitive breast cancer. There is evidence that breast cancer patients treated with tamoxifen exhibit cognitive dysfunction. However, the underlying neural mechanism remains unclear. The present study aimed to investigate the neural mechanisms underlying working memory deficits in combination with functional connectivity changes in premenopausal women with breast cancer who received long-term tamoxifen treatment. Methods: A total of 31 premenopausal women with breast cancer who received tamoxifen and 32 matched healthy control participants were included. The participants completed n-back tasks and underwent resting-state functional magnetic resonance imaging, which measure working memory performance and brain functional connectivity, respectively. A seed-based functional connectivity analysis within the whole brain was conducted, for which the dorsolateral prefrontal cortex was chosen as the seed region. Results: Our results indicated that the tamoxifen group had significant deficits in working memory and general executive function performance and significantly lower functional connectivity of the right dorsolateral prefrontal cortex with the right hippocampus compared with the healthy controls. There were no significant changes in functional connectivity in the left dorsolateral prefrontal cortex within the whole brain between the tamoxifen group and healthy controls. Moreover, significant correlations were found in the tamoxifen group between the functional connectivity strength of the dorsolateral prefrontal cortex with the right hippocampus and decreased working memory performance. Conclusion: This study demonstrates that the prefrontal cortex and hippocampus may be affected by tamoxifen treatment, supporting an antagonistic role of tamoxifen in the long-term treatment of breast cancer patients. PMID:28177081
Wei, Pengxu; Zhang, Zuting; Lv, Zeping; Jing, Bin
2017-01-01
The mechanism underlying brain region organization for motor control in humans remains poorly understood. In this functional magnetic resonance imaging (fMRI) study, right-handed volunteers were tasked to maintain unilateral foot movements on the right and left sides as consistently as possible. We aimed to identify the similarities and differences between brain motor networks of the two conditions. We recruited 18 right-handed healthy volunteers aged 25 ± 2.3 years and used a whole-body 3T system for magnetic resonance (MR) scanning. Image analysis was performed using SPM8, Conn toolbox and Brain Connectivity Toolbox. We determined a craniocaudally distributed, mirror-symmetrical modular structure. The functional connectivity between homotopic brain areas was generally stronger than the intrahemispheric connections, and such strong connectivity led to the abovementioned modular structure. Our findings indicated that the interhemispheric functional interaction between homotopic brain areas is more intensive than the interaction along the conventional top-down and bottom-up pathways within the brain during unilateral limb movement. The detected strong interhemispheric horizontal functional interaction is an important aspect of motor control but often neglected or underestimated. The strong interhemispheric connectivity may explain the physiological phenomena and effects of promising therapeutic approaches. Further accurate and effective therapeutic methods may be developed on the basis of our findings.
Connectopic mapping with resting-state fMRI.
Haak, Koen V; Marquand, Andre F; Beckmann, Christian F
2018-04-15
Brain regions are often topographically connected: nearby locations within one brain area connect with nearby locations in another area. Mapping these connection topographies, or 'connectopies' in short, is crucial for understanding how information is processed in the brain. Here, we propose principled, fully data-driven methods for mapping connectopies using functional magnetic resonance imaging (fMRI) data acquired at rest by combining spectral embedding of voxel-wise connectivity 'fingerprints' with a novel approach to spatial statistical inference. We apply the approach in human primary motor and visual cortex, and show that it can trace biologically plausible, overlapping connectopies in individual subjects that follow these regions' somatotopic and retinotopic maps. As a generic mechanism to perform inference over connectopies, the new spatial statistics approach enables rigorous statistical testing of hypotheses regarding the fine-grained spatial profile of functional connectivity and whether that profile is different between subjects or between experimental conditions. The combined framework offers a fundamental alternative to existing approaches to investigating functional connectivity in the brain, from voxel- or seed-pair wise characterizations of functional association, towards a full, multivariate characterization of spatial topography. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Mechanism to support generic collective communication across a variety of programming models
Almasi, Gheorghe [Ardsley, NY; Dozsa, Gabor [Ardsley, NY; Kumar, Sameer [White Plains, NY
2011-07-19
A system and method for supporting collective communications on a plurality of processors that use different parallel programming paradigms, in one aspect, may comprise a schedule defining one or more tasks in a collective operation, an executor that executes the task, a multisend module to perform one or more data transfer functions associated with the tasks, and a connection manager that controls one or more connections and identifies an available connection. The multisend module uses the available connection in performing the one or more data transfer functions. A plurality of processors that use different parallel programming paradigms can use a common implementation of the schedule module, the executor module, the connection manager and the multisend module via a language adaptor specific to a parallel programming paradigm implemented on a processor.
Lohse, Christian; Bassett, Danielle S; Lim, Kelvin O; Carlson, Jean M
2014-10-01
Human brain anatomy and function display a combination of modular and hierarchical organization, suggesting the importance of both cohesive structures and variable resolutions in the facilitation of healthy cognitive processes. However, tools to simultaneously probe these features of brain architecture require further development. We propose and apply a set of methods to extract cohesive structures in network representations of brain connectivity using multi-resolution techniques. We employ a combination of soft thresholding, windowed thresholding, and resolution in community detection, that enable us to identify and isolate structures associated with different weights. One such mesoscale structure is bipartivity, which quantifies the extent to which the brain is divided into two partitions with high connectivity between partitions and low connectivity within partitions. A second, complementary mesoscale structure is modularity, which quantifies the extent to which the brain is divided into multiple communities with strong connectivity within each community and weak connectivity between communities. Our methods lead to multi-resolution curves of these network diagnostics over a range of spatial, geometric, and structural scales. For statistical comparison, we contrast our results with those obtained for several benchmark null models. Our work demonstrates that multi-resolution diagnostic curves capture complex organizational profiles in weighted graphs. We apply these methods to the identification of resolution-specific characteristics of healthy weighted graph architecture and altered connectivity profiles in psychiatric disease.
Detecting nonlinear dynamics of functional connectivity
NASA Astrophysics Data System (ADS)
LaConte, Stephen M.; Peltier, Scott J.; Kadah, Yasser; Ngan, Shing-Chung; Deshpande, Gopikrishna; Hu, Xiaoping
2004-04-01
Functional magnetic resonance imaging (fMRI) is a technique that is sensitive to correlates of neuronal activity. The application of fMRI to measure functional connectivity of related brain regions across hemispheres (e.g. left and right motor cortices) has great potential for revealing fundamental physiological brain processes. Primarily, functional connectivity has been characterized by linear correlations in resting-state data, which may not provide a complete description of its temporal properties. In this work, we broaden the measure of functional connectivity to study not only linear correlations, but also those arising from deterministic, non-linear dynamics. Here the delta-epsilon approach is extended and applied to fMRI time series. The method of delays is used to reconstruct the joint system defined by a reference pixel and a candidate pixel. The crux of this technique relies on determining whether the candidate pixel provides additional information concerning the time evolution of the reference. As in many correlation-based connectivity studies, we fix the reference pixel. Every brain location is then used as a candidate pixel to estimate the spatial pattern of deterministic coupling with the reference. Our results indicate that measured connectivity is often emphasized in the motor cortex contra-lateral to the reference pixel, demonstrating the suitability of this approach for functional connectivity studies. In addition, discrepancies with traditional correlation analysis provide initial evidence for non-linear dynamical properties of resting-state fMRI data. Consequently, the non-linear characterization provided from our approach may provide a more complete description of the underlying physiology and brain function measured by this type of data.
Johnston, Jennifer A Y; Wang, Fei; Liu, Jie; Blond, Benjamin N; Wallace, Amanda; Liu, Jiacheng; Spencer, Linda; Cox Lippard, Elizabeth T; Purves, Kirstin L; Landeros-Weisenberger, Angeli; Hermes, Eric; Pittman, Brian; Zhang, Sheng; King, Robert; Martin, Andrés; Oquendo, Maria A; Blumberg, Hilary P
2017-07-01
Bipolar disorder is associated with high risk for suicidal behavior that often develops in adolescence and young adulthood. Elucidation of involved neural systems is critical for prevention. This study of adolescents and young adults with bipolar disorder with and without a history of suicide attempts combines structural, diffusion tensor, and functional MR imaging methods to investigate implicated abnormalities in the morphology and structural and functional connectivity within frontolimbic systems. The study had 26 participants with bipolar disorder who had a prior suicide attempt (the attempter group) and 42 participants with bipolar disorder without a suicide attempt (the nonattempter group). Regional gray matter volume, white matter integrity, and functional connectivity during processing of emotional stimuli were compared between groups, and differences were explored for relationships between imaging modalities and associations with suicide-related symptoms and behaviors. Compared with the nonattempter group, the attempter group showed significant reductions in gray matter volume in the orbitofrontal cortex, hippocampus, and cerebellum; white matter integrity in the uncinate fasciculus, ventral frontal, and right cerebellum regions; and amygdala functional connectivity to the left ventral and right rostral prefrontal cortex. In exploratory analyses, among attempters, there was a significant negative correlation between right rostral prefrontal connectivity and suicidal ideation and between left ventral prefrontal connectivity and attempt lethality. Adolescent and young adult suicide attempters with bipolar disorder demonstrate less gray matter volume and decreased structural and functional connectivity in a ventral frontolimbic neural system subserving emotion regulation. Among attempters, reductions in amygdala-prefrontal functional connectivity may be associated with severity of suicidal ideation and attempt lethality.
Korponay, Cole; Pujara, Maia; Deming, Philip; Philippi, Carissa; Decety, Jean; Kosson, David S.; Kiehl, Kent A.; Koenigs, Michael
2016-01-01
Background Psychopathy is a mental health disorder characterized by callous and impulsive antisocial behavior, and is associated with a high incidence of violent crime, substance abuse, and recidivism. Recent studies suggest that the striatum may be a key component of the neurobiological basis for the disorder, though structural findings have been mixed and functional connectivity of the striatum in psychopathy has yet to be fully examined. Methods We performed a multimodal neuroimaging study of striatum volume and functional connectivity in psychopathy, using a large sample of adult male prison inmates (N=124). We conducted volumetric analyses in striatal subnuclei, and subsequently assessed resting-state functional connectivity in areas where volume was related to psychopathy severity. Results Total PCL-R and Factor 2 scores (which index the impulsive/antisocial traits of psychopathy) were associated with larger striatal subnuclei volumes and increased volume in focal areas throughout the striatum, particularly in the nucleus accumbens and putamen bilaterally. Furthermore, at many of the striatal areas where volume was positively associated with Factor 2 scores, psychopathy severity was also associated with abnormal functional connectivity with other brain regions, including dorsolateral prefrontal cortex, ventral midbrain and other areas of the striatum. The results were not attributable to age, race, IQ, substance use history, or intracranial volume. Conclusion These findings associate the impulsive/antisocial dimension of psychopathy with enlarged striatal subnuclei and aberrant functional connectivity between the striatum and other brain regions. Furthermore, the co-localization of volumetric and functional connectivity findings suggests that these neural abnormalities may be pathophysiologically linked. PMID:28367514
Zheng, Yu; Wang, Yuying; Lan, Yujun; Qu, Xiaodong; Lin, Kelin; Zhang, Jiping; Qu, Shanshan; Wang, Yanjie; Tang, Chunzhi; Huang, Yong
2016-01-01
This Study observed the relevant brain areas activated by acupuncture at the Taichong acupoint (LR3) and analyzed the functional connectivity among brain areas using resting state functional magnetic resonance imaging (fMRI) to explore the acupoint specificity of the Taichong acupoint. A total of 45 healthy subjects were randomly divided into the Taichong (LR3) group, sham acupuncture group and sham acupoint group. Subjects received resting state fMRI before acupuncture, after true (sham) acupuncture in each group. Analysis of changes in connectivity among the brain areas was performed using the brain functional connectivity method. The right cerebrum temporal lobe was selected as the seed point to analyze the functional connectivity. It had a functional connectivity with right cerebrum superior frontal gyrus, limbic lobe cingulate gyrus and left cerebrum inferior temporal gyrus (BA 37), inferior parietal lobule compared by before vs. after acupuncture at LR3, and right cerebrum sub-lobar insula and left cerebrum middle frontal gyrus, medial frontal gyrus compared by true vs. sham acupuncture at LR3, and right cerebrum occipital lobe cuneus, occipital lobe sub-gyral, parietal lobe precuneus and left cerebellum anterior lobe culmen by acupuncture at LR3 vs. sham acupoint. Acupuncture at LR3 mainly specifically activated the brain functional network that participates in visual function, associative function, and emotion cognition, which are similar to the features on LR3 in tradition Chinese medicine. These brain areas constituted a neural network structure with specific functions that had specific reference values for the interpretation of the acupoint specificity of the Taichong acupoint.
Lopes, Renaud; Moeller, Friederike; Besson, Pierre; Ogez, François; Szurhaj, William; Leclerc, Xavier; Siniatchkin, Michael; Chipaux, Mathilde; Derambure, Philippe; Tyvaert, Louise
2014-01-01
Rationale: Simultaneous recording of electroencephalogram and functional MRI (EEG–fMRI) is a powerful tool for localizing epileptic networks via the detection of hemodynamic changes correlated with interictal epileptic discharges (IEDs). fMRI can be used to study the long-lasting effect of epileptic activity by assessing stationary functional connectivity during the resting-state period [especially, the connectivity of the default mode network (DMN)]. Temporal lobe epilepsy (TLE) and idiopathic generalized epilepsy (IGE) are associated with low responsiveness and disruption of DMN activity. A dynamic functional connectivity approach might enable us to determine the effect of IEDs on DMN connectivity and to better understand the correlation between DMN connectivity changes and altered consciousness. Method: We studied dynamic changes in DMN intrinsic connectivity and their relation to IEDs. Six IGE patients (with generalized spike and slow-waves) and 6 TLE patients (with unilateral left temporal spikes) were included. Functional connectivity before, during, and after IEDs was estimated using a sliding window approach and compared with the baseline period. Results: No dependence on window size was observed. The baseline DMN connectivity was decreased in the left hemisphere (ipsilateral to the epileptic focus) in TLEs and was less strong but remained bilateral in IGEs. We observed an overall increase in DMN intrinsic connectivity prior to the onset of IEDs in both IGEs and TLEs. After IEDs in TLEs, we found that DMN connectivity increased before it returned to baseline values. Most of the DMN regions with increased connectivity before and after IEDs were lateralized to the left hemisphere in TLE (i.e., ipsilateral to the epileptic focus). Conclusion: Results suggest that DMN connectivity may facilitate IED generation and may be affected at the time of the IED. However, these results need to be confirmed in a larger independent cohort. PMID:25346721
Kyeong, Sunghyon; Park, Seonjeong; Cheon, Keun-Ah; Kim, Jae-Jin; Song, Dong-Ho; Kim, Eunjoo
2015-01-01
Attention-deficit/hyperactivity disorder (ADHD) is currently diagnosed by a diagnostic interview, mainly based on subjective reports from parents or teachers. It is necessary to develop methods that rely on objectively measureable neurobiological data to assess brain-behavior relationship in patients with ADHD. We investigated the application of a topological data analysis tool, Mapper, to analyze the brain functional connectivity data from ADHD patients. To quantify the disease severity using the neuroimaging data, the decomposition of individual functional networks into normal and disease components by the healthy state model (HSM) was performed, and the magnitude of the disease component (MDC) was computed. Topological data analysis using Mapper was performed to distinguish children with ADHD (n = 196) from typically developing controls (TDC) (n = 214). In the topological data analysis, the partial clustering results of patients with ADHD and normal subjects were shown in a chain-like graph. In the correlation analysis, the MDC showed a significant increase with lower intelligence scores in TDC. We also found that the rates of comorbidity in ADHD significantly increased when the deviation of the functional connectivity from HSM was large. In addition, a significant correlation between ADHD symptom severity and MDC was found in part of the dataset. The application of HSM and topological data analysis methods in assessing the brain functional connectivity seem to be promising tools to quantify ADHD symptom severity and to reveal the hidden relationship between clinical phenotypic variables and brain connectivity.
Disrupted Brain Functional Organization in Epilepsy Revealed by Graph Theory Analysis.
Song, Jie; Nair, Veena A; Gaggl, Wolfgang; Prabhakaran, Vivek
2015-06-01
The human brain is a complex and dynamic system that can be modeled as a large-scale brain network to better understand the reorganizational changes secondary to epilepsy. In this study, we developed a brain functional network model using graph theory methods applied to resting-state fMRI data acquired from a group of epilepsy patients and age- and gender-matched healthy controls. A brain functional network model was constructed based on resting-state functional connectivity. A minimum spanning tree combined with proportional thresholding approach was used to obtain sparse connectivity matrices for each subject, which formed the basis of brain networks. We examined the brain reorganizational changes in epilepsy thoroughly at the level of the whole brain, the functional network, and individual brain regions. At the whole-brain level, local efficiency was significantly decreased in epilepsy patients compared with the healthy controls. However, global efficiency was significantly increased in epilepsy due to increased number of functional connections between networks (although weakly connected). At the functional network level, there were significant proportions of newly formed connections between the default mode network and other networks and between the subcortical network and other networks. There was a significant proportion of decreasing connections between the cingulo-opercular task control network and other networks. Individual brain regions from different functional networks, however, showed a distinct pattern of reorganizational changes in epilepsy. These findings suggest that epilepsy alters brain efficiency in a consistent pattern at the whole-brain level, yet alters brain functional networks and individual brain regions differently.
Longitudinal Changes of Resting-State Functional Connectivity during Motor Recovery after Stroke
Park, Chang-hyun; Chang, Won Hyuk; Ohn, Suk Hoon; Kim, Sung Tae; Bang, Oh Young; Pascual-Leone, Alvaro; Kim, Yun-Hee
2013-01-01
Background and Purpose Functional magnetic resonance imaging (fMRI) studies could provide crucial information on the neural mechanisms of motor recovery in stroke patients. Resting-state fMRI is applicable to stroke patients who are not capable of proper performance of the motor task. In this study, we explored neural correlates of motor recovery in stroke patients by investigating longitudinal changes in resting-state functional connectivity of the ipsilesional primary motor cortex (M1). Methods A longitudinal observational study using repeated fMRI experiments was conducted in 12 patients with stroke. Resting-state fMRI data were acquired four times over a period of 6 months. Patients participated in the first session of fMRI shortly after onset, and thereafter in subsequent sessions at 1, 3, and 6 months after onset. Resting-state functional connectivity of the ipsilesional M1 was assessed and compared with that of healthy subjects. Results Compared with healthy subjects, patients demonstrated higher functional connectivity with the ipsilesional frontal and parietal cortices, bilateral thalamus, and cerebellum. Instead, functional connectivity with the contralesional M1 and occipital cortex were decreased in stroke patients. Functional connectivity between the ipsilesional and contralesional M1 showed the most asymmetry at 1 month after onset to the ipsilesional side. Functional connectivity of the ipsilesional M1 with the contralesional thalamus, supplementary motor area, and middle frontal gyrus at onset was positively correlated with motor recovery at 6 months after stroke. Conclusions Resting-state fMRI elicited distinctive but comparable results with previous task-based fMRI, presenting complementary and practical values for use in the study of stroke patients. PMID:21441147
Intensity-based masking: A tool to improve functional connectivity results of resting-state fMRI.
Peer, Michael; Abboud, Sami; Hertz, Uri; Amedi, Amir; Arzy, Shahar
2016-07-01
Seed-based functional connectivity (FC) of resting-state functional MRI data is a widely used methodology, enabling the identification of functional brain networks in health and disease. Based on signal correlations across the brain, FC measures are highly sensitive to noise. A somewhat neglected source of noise is the fMRI signal attenuation found in cortical regions in close vicinity to sinuses and air cavities, mainly in the orbitofrontal, anterior frontal and inferior temporal cortices. BOLD signal recorded at these regions suffers from dropout due to susceptibility artifacts, resulting in an attenuated signal with reduced signal-to-noise ratio in as many as 10% of cortical voxels. Nevertheless, signal attenuation is largely overlooked during FC analysis. Here we first demonstrate that signal attenuation can significantly influence FC measures by introducing false functional correlations and diminishing existing correlations between brain regions. We then propose a method for the detection and removal of the attenuated signal ("intensity-based masking") by fitting a Gaussian-based model to the signal intensity distribution and calculating an intensity threshold tailored per subject. Finally, we apply our method on real-world data, showing that it diminishes false correlations caused by signal dropout, and significantly improves the ability to detect functional networks in single subjects. Furthermore, we show that our method increases inter-subject similarity in FC, enabling reliable distinction of different functional networks. We propose to include the intensity-based masking method as a common practice in the pre-processing of seed-based functional connectivity analysis, and provide software tools for the computation of intensity-based masks on fMRI data. Hum Brain Mapp 37:2407-2418, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
The Effects of rTMS Combined with Motor Training on Functional Connectivity in Alpha Frequency Band.
Jin, Jing-Na; Wang, Xin; Li, Ying; Jin, Fang; Liu, Zhi-Peng; Yin, Tao
2017-01-01
It has recently been reported that repetitive transcranial magnetic stimulation combined with motor training (rTMS-MT) could improve motor function in post-stroke patients. However, the effects of rTMS-MT on cortical function using functional connectivity and graph theoretical analysis remain unclear. Ten healthy subjects were recruited to receive rTMS immediately before application of MT. Low frequency rTMS was delivered to the dominant hemisphere and non-dominant hand performed MT over 14 days. The reaction time of Nine-Hole Peg Test and electroencephalography (EEG) in resting condition with eyes closed were recorded before and after rTMS-MT. Functional connectivity was assessed by phase synchronization index (PSI), and subsequently thresholded to construct undirected graphs in alpha frequency band (8-13 Hz). We found a significant decrease in reaction time after rTMS-MT. The functional connectivity between the parietal and frontal cortex, and the graph theory statistics of node degree and efficiency in the parietal cortex increased. Besides the functional connectivity between premotor and frontal cortex, the degree and efficiency of premotor cortex showed opposite results. In addition, the number of connections significantly increased within inter-hemispheres and inter-regions. In conclusion, this study could be helpful in our understanding of how rTMS-MT modulates brain activity. The methods and results in this study could be taken as reference in future studies of the effects of rTMS-MT in stroke patients.
A brain-region-based meta-analysis method utilizing the Apriori algorithm.
Niu, Zhendong; Nie, Yaoxin; Zhou, Qian; Zhu, Linlin; Wei, Jieyao
2016-05-18
Brain network connectivity modeling is a crucial method for studying the brain's cognitive functions. Meta-analyses can unearth reliable results from individual studies. Meta-analytic connectivity modeling is a connectivity analysis method based on regions of interest (ROIs) which showed that meta-analyses could be used to discover brain network connectivity. In this paper, we propose a new meta-analysis method that can be used to find network connectivity models based on the Apriori algorithm, which has the potential to derive brain network connectivity models from activation information in the literature, without requiring ROIs. This method first extracts activation information from experimental studies that use cognitive tasks of the same category, and then maps the activation information to corresponding brain areas by using the automatic anatomical label atlas, after which the activation rate of these brain areas is calculated. Finally, using these brain areas, a potential brain network connectivity model is calculated based on the Apriori algorithm. The present study used this method to conduct a mining analysis on the citations in a language review article by Price (Neuroimage 62(2):816-847, 2012). The results showed that the obtained network connectivity model was consistent with that reported by Price. The proposed method is helpful to find brain network connectivity by mining the co-activation relationships among brain regions. Furthermore, results of the co-activation relationship analysis can be used as a priori knowledge for the corresponding dynamic causal modeling analysis, possibly achieving a significant dimension-reducing effect, thus increasing the efficiency of the dynamic causal modeling analysis.
SDN solutions for switching dedicated long-haul connections: Measurements and comparative analysis
Rao, Nageswara S. V.
2016-01-01
We consider a scenario of two sites connected over a dedicated, long-haul connection that must quickly fail-over in response to degradations in host-to-host application performance. The traditional layer-2/3 hot stand-by fail-over solutions do not adequately address the variety of application degradations, and more recent single controller Software Defined Networks (SDN) solutions are not effective for long-haul connections. We present two methods for such a path fail-over using OpenFlow enabled switches: (a) a light-weight method that utilizes host scripts to monitor application performance and dpctl API for switching, and (b) a generic method that uses two OpenDaylight (ODL) controllers and RESTmore » interfaces. For both methods, the restoration dynamics of applications contain significant statistical variations due to the complexities of controllers, north bound interfaces and switches; they, together with the wide variety of vendor implementations, complicate the choice among such solutions. We develop the impulse-response method based on regression functions of performance parameters to provide a rigorous and objective comparison of different solutions. We describe testing results of the two proposed methods, using TCP throughput and connection rtt as main parameters, over a testbed consisting of HP and Cisco switches connected over longhaul connections emulated in hardware by ANUE devices. Lastly, the combination of analytical and experimental results demonstrate that the dpctl method responds seconds faster than the ODL method on average, even though both methods eventually restore original TCP throughput.« less
Estimation of effective connectivity via data-driven neural modeling
Freestone, Dean R.; Karoly, Philippa J.; Nešić, Dragan; Aram, Parham; Cook, Mark J.; Grayden, David B.
2014-01-01
This research introduces a new method for functional brain imaging via a process of model inversion. By estimating parameters of a computational model, we are able to track effective connectivity and mean membrane potential dynamics that cannot be directly measured using electrophysiological measurements alone. The ability to track the hidden aspects of neurophysiology will have a profound impact on the way we understand and treat epilepsy. For example, under the assumption the model captures the key features of the cortical circuits of interest, the framework will provide insights into seizure initiation and termination on a patient-specific basis. It will enable investigation into the effect a particular drug has on specific neural populations and connectivity structures using minimally invasive measurements. The method is based on approximating brain networks using an interconnected neural population model. The neural population model is based on a neural mass model that describes the functional activity of the brain, capturing the mesoscopic biophysics and anatomical structure. The model is made subject-specific by estimating the strength of intra-cortical connections within a region and inter-cortical connections between regions using a novel Kalman filtering method. We demonstrate through simulation how the framework can be used to track the mechanisms involved in seizure initiation and termination. PMID:25506315
Kerr, Deborah L.; Nitschke, Jack B.
2013-01-01
Abstract Granger causality analysis of functional magnetic resonance imaging (fMRI) blood-oxygen-level-dependent signal data allows one to infer the direction and magnitude of influence that brain regions exert on one another. We employed a method for upsampling the time resolution of fMRI data that does not require additional interpolation beyond the interpolation that is regularly used for slice-timing correction. The mathematics for this new method are provided, and simulations demonstrate its viability. Using fMRI, 17 snake phobics and 19 healthy controls viewed snake, disgust, and neutral fish video clips preceded by anticipatory cues. Multivariate Granger causality models at the native 2-sec resolution and at the upsampled 400-ms resolution assessed directional associations of fMRI data among 13 anatomical regions of interest identified in prior research on anxiety and emotion. Superior sensitivity was observed for the 400-ms model, both for connectivity within each group and for group differences in connectivity. Context-dependent analyses for the 400-ms multivariate Granger causality model revealed the specific trial types showing group differences in connectivity. This is the first demonstration of effective connectivity of fMRI data using a method for achieving 400-ms resolution without sacrificing accuracy available at 2-sec resolution. PMID:23134194
NASA Astrophysics Data System (ADS)
Wang, Jiang; Yang, Chen; Wang, Ruofan; Yu, Haitao; Cao, Yibin; Liu, Jing
2016-10-01
In this paper, EEG series are applied to construct functional connections with the correlation between different regions in order to investigate the nonlinear characteristic and the cognitive function of the brain with Alzheimer's disease (AD). First, limited penetrable visibility graph (LPVG) and phase space method map single EEG series into networks, and investigate the underlying chaotic system dynamics of AD brain. Topological properties of the networks are extracted, such as average path length and clustering coefficient. It is found that the network topology of AD in several local brain regions are different from that of the control group with no statistically significant difference existing all over the brain. Furthermore, in order to detect the abnormality of AD brain as a whole, functional connections among different brain regions are reconstructed based on similarity of clustering coefficient sequence (CCSS) of EEG series in the four frequency bands (delta, theta, alpha, and beta), which exhibit obvious small-world properties. Graph analysis demonstrates that for both methodologies, the functional connections between regions of AD brain decrease, particularly in the alpha frequency band. AD causes the graph index complexity of the functional network decreased, the small-world properties weakened, and the vulnerability increased. The obtained results show that the brain functional network constructed by LPVG and phase space method might be more effective to distinguish AD from the normal control than the analysis of single series, which is helpful for revealing the underlying pathological mechanism of the disease.
Li, Lei; Xu, Jian-rong
2013-01-01
Purpose Excessive use of the Internet has been linked to a variety of negative psychosocial consequences. This study used resting-state functional magnetic resonance imaging (fMRI) to investigate whether functional connectivity is altered in adolescents with Internet gaming addiction (IGA). Methods Seventeen adolescents with IGA and 24 normal control adolescents underwent a 7.3 minute resting-state fMRI scan. Posterior cingulate cortex (PCC) connectivity was determined in all subjects by investigating synchronized low-frequency fMRI signal fluctuations using a temporal correlation method. To assess the relationship between IGA symptom severity and PCC connectivity, contrast images representing areas correlated with PCC connectivity were correlated with the scores of the 17 subjects with IGA on the Chen Internet Addiction Scale (CIAS) and Barratt Impulsiveness Scale-11 (BIS-11) and their hours of Internet use per week. Results There were no significant differences in the distributions of the age, gender, and years of education between the two groups. The subjects with IGA showed longer Internet use per week (hours) (p<0.0001) and higher CIAS (p<0.0001) and BIS-11 (p = 0.01) scores than the controls. Compared with the control group, subjects with IGA exhibited increased functional connectivity in the bilateral cerebellum posterior lobe and middle temporal gyrus. The bilateral inferior parietal lobule and right inferior temporal gyrus exhibited decreased connectivity. Connectivity with the PCC was positively correlated with CIAS scores in the right precuneus, posterior cingulate gyrus, thalamus, caudate, nucleus accumbens, supplementary motor area, and lingual gyrus. It was negatively correlated with the right cerebellum anterior lobe and left superior parietal lobule. Conclusion Our results suggest that adolescents with IGA exhibit different resting-state patterns of brain activity. As these alterations are partially consistent with those in patients with substance addiction, they support the hypothesis that IGA as a behavioral addiction that may share similar neurobiological abnormalities with other addictive disorders. PMID:23555827
Mapping thalamocortical functional connectivity in chronic and early stages of psychotic disorders
Woodward, Neil D.; Heckers, Stephan
2015-01-01
Objective There is considerable evidence that the thalamus is abnormal in psychotic disorders. Resting-state fMRI (RS-fMRI) has revealed an intriguing pattern of thalamic dysconnectivity in psychosis characterized by reduced prefrontal cortex (PFC) connectivity and increased somatomotor-thalamic connectivity. However, critical knowledge gaps remain with respect to the onset, anatomical specificity, and clinical correlates of thalamic dysconnectivity in psychosis. Method RS-fMRI was collected on 105 healthy subjects and 148 individuals with psychosis, including 53 early stage psychosis patients. Using all 253 subjects, the thalamus was parceled into functional regions-of-interest (ROIs) on the basis of connectivity with six a-priori defined cortical ROIs covering most of the cortical mantle. Functional connectivity between each cortical ROI and its corresponding thalamic ROI was quantified and compared across groups. Significant differences in the ROI-to-ROI analysis were followed up with voxel-wise seed-based analyses to further localize thalamic dysconnectivity. Results ROI analysis revealed reduced PFC-thalamic connectivity and increased somatomotor-thalamic connectivity in both chronic and early stages psychosis patients. PFC hypo-connectivity and motor cortex hyper-connectivity correlated in patients suggesting they result from a common pathophysiological mechanism. Seed-based analyses revealed thalamic hypo-connectivity in psychosis localized to dorsolateral PFC, medial PFC, and cerebellar areas of the well-described ‘executive control’ network. Across all subjects, thalamic connectivity with areas of the fronto-parietal network correlated with cognitive functioning, including verbal learning and memory. Conclusions Thalamocortical dysconnectivity is present in both chronic and early stages of psychosis, includes reduced thalamic connectivity with the executive control network, and is related to cognitive impairment. PMID:26248537
de Marco, G; Menuel, C; Guillevin, R; Vallée, J-N; Lehmann, P; Fall, S; Quaglino, V; Bourdin, B; Devauchelle, B; Chiras, J
2008-07-01
After having provided a brief reminder of the principle of the blood oxygen level-dependent (BOLD) contrast effect, the physiological bases of brain activity and the concepts of functional integration and effective connectivity, we describe the most recent approaches, which permit to explore brain activity and putative networks of interconnected active areas in order to examine the normal brain physiology and its dysfunctions. We present various methods and studies of brain activity analysis clinically applicable, and we detail the concepts of functional and effective connectivity, which allow to study the cerebral plasticity which occurs at the child's during the maturation (e.g., dyslexia), at the adult during the ageing (e.g., Alzheimer disease), or still in schizophrenia or Parkinson disease. The study of specific circuits in networks has to allow defining in a more realistic way the dynamic of the central nervous system, which underlies various cerebral functions, both in physiological and pathological conditions. This connectivity approach should improve the diagnostic and facilitate the development of new therapeutic strategies.
Chemical wiring and soldering toward all-molecule electronic circuitry.
Okawa, Yuji; Mandal, Swapan K; Hu, Chunping; Tateyama, Yoshitaka; Goedecker, Stefan; Tsukamoto, Shigeru; Hasegawa, Tsuyoshi; Gimzewski, James K; Aono, Masakazu
2011-06-01
Key to single-molecule electronics is connecting functional molecules to each other using conductive nanowires. This involves two issues: how to create conductive nanowires at designated positions, and how to ensure chemical bonding between the nanowires and functional molecules. Here, we present a novel method that solves both issues. Relevant functional molecules are placed on a self-assembled monolayer of diacetylene compound. A probe tip of a scanning tunneling microscope is then positioned on the molecular row of the diacetylene compound to which the functional molecule is adsorbed, and a conductive polydiacetylene nanowire is fabricated by initiating chain polymerization by stimulation with the tip. Since the front edge of chain polymerization necessarily has a reactive chemical species, the created polymer nanowire forms chemical bonding with an encountered molecular element. We name this spontaneous reaction "chemical soldering". First-principles theoretical calculations are used to investigate the structures and electronic properties of the connection. We demonstrate that two conductive polymer nanowires are connected to a single phthalocyanine molecule. A resonant tunneling diode formed by this method is discussed. © 2011 American Chemical Society
Wu, Huawang; Sun, Hui; Xu, Jinping; Wu, Yan; Wang, Chao; Xiao, Jing; She, Shenglin; Huang, Jianwei; Zou, Wenjin; Peng, Hongjun; Lu, Xiaobing; Huang, Guimao; Jiang, Tianzi; Ning, Yuping; Wang, Jiaojian
2016-01-01
Major depressive disorder (MDD) is one of the most prevalent mental disorders. In the brain, the hubs of the brain network play a key role in integrating and transferring information between different functional modules. However, whether the changed pattern in functional network hubs contributes to the onset of MDD remains unclear. Using resting-state functional magnetic resonance imaging (rs-fMRI) and graph theory methods, we investigated whether alterations of hubs can be detected in MDD. First, we constructed the whole-brain voxel-wise functional networks and calculated a functional connectivity strength (FCS) map in each subject in 34 MDD patients and 34 gender-, age- and education level-matched healthy controls (HCs). Next, the two-sample t-test was applied to compare the FCS maps between HC and MDD patients and identified significant decrease of FCS in subgenual anterior cingulate cortex (sgACC) in MDD patients. Subsequent functional connectivity analyses of sgACC showed disruptions in functional connectivity with posterior insula, middle and inferior temporal gyrus, lingual gyrus and cerebellum in MDD patients. Furthermore, the changed FCS of sgACC and functional connections to sgACC were significantly correlated with the Hamilton Depression Rating Scale (HDRS) scores in MDD patients. The results of the present study revealed the abnormal hub of sgACC and its corresponding disrupted frontal-limbic-visual cognitive-cerebellum functional networks in MDD. These findings may provide a new insight for the diagnosis and treatment of MDD. PMID:28018183
Liu, Chao; Abu-Jamous, Basel; Brattico, Elvira; Nandi, Asoke K
2017-03-01
In the past decades, neuroimaging of humans has gained a position of status within neuroscience, and data-driven approaches and functional connectivity analyses of functional magnetic resonance imaging (fMRI) data are increasingly favored to depict the complex architecture of human brains. However, the reliability of these findings is jeopardized by too many analysis methods and sometimes too few samples used, which leads to discord among researchers. We propose a tunable consensus clustering paradigm that aims at overcoming the clustering methods selection problem as well as reliability issues in neuroimaging by means of first applying several analysis methods (three in this study) on multiple datasets and then integrating the clustering results. To validate the method, we applied it to a complex fMRI experiment involving affective processing of hundreds of music clips. We found that brain structures related to visual, reward, and auditory processing have intrinsic spatial patterns of coherent neuroactivity during affective processing. The comparisons between the results obtained from our method and those from each individual clustering algorithm demonstrate that our paradigm has notable advantages over traditional single clustering algorithms in being able to evidence robust connectivity patterns even with complex neuroimaging data involving a variety of stimuli and affective evaluations of them. The consensus clustering method is implemented in the R package "UNCLES" available on http://cran.r-project.org/web/packages/UNCLES/index.html .
Rajabioun, Mehdi; Nasrabadi, Ali Motie; Shamsollahi, Mohammad Bagher
2017-09-01
Effective connectivity is one of the most important considerations in brain functional mapping via EEG. It demonstrates the effects of a particular active brain region on others. In this paper, a new method is proposed which is based on dual Kalman filter. In this method, firstly by using a brain active localization method (standardized low resolution brain electromagnetic tomography) and applying it to EEG signal, active regions are extracted, and appropriate time model (multivariate autoregressive model) is fitted to extracted brain active sources for evaluating the activity and time dependence between sources. Then, dual Kalman filter is used to estimate model parameters or effective connectivity between active regions. The advantage of this method is the estimation of different brain parts activity simultaneously with the calculation of effective connectivity between active regions. By combining dual Kalman filter with brain source localization methods, in addition to the connectivity estimation between parts, source activity is updated during the time. The proposed method performance has been evaluated firstly by applying it to simulated EEG signals with interacting connectivity simulation between active parts. Noisy simulated signals with different signal to noise ratios are used for evaluating method sensitivity to noise and comparing proposed method performance with other methods. Then the method is applied to real signals and the estimation error during a sweeping window is calculated. By comparing proposed method results in different simulation (simulated and real signals), proposed method gives acceptable results with least mean square error in noisy or real conditions.
Default Mode Network Mechanisms of Transcranial Magnetic Stimulation in Depression
Liston, Conor; Chen, Ashley C.; Zebley, Benjamin D.; Drysdale, Andrew T.; Gordon, Rebecca; Leuchter, Bruce; Voss, Henning U.; Casey, B.J.; Etkin, Amit; Dubin, Marc J.
2014-01-01
Background Repetitive transcranial magnetic stimulation (TMS) of the dorsolateral prefrontal cortex (DLPFC) is an established treatment for depression, but its underlying mechanism of action remains unknown. Abnormalities in two large-scale neuronal networks—the frontoparietal central executive network (CEN) and the medial prefrontal-medial parietal default mode network (DMN)—are consistent findings in depression and potential therapeutic targets for TMS. Here, we assessed the impact of TMS on activity in these networks and their relation to treatment response. Methods We used resting state functional magnetic resonance imaging (rs-fMRI) to measure functional connectivity within and between the DMN and CEN in 17 depressed patients, before and after a five-week course of TMS. Motivated by prior reports, we focused on connectivity seeded from the DLPFC and the subgenual cingulate, a key region closely aligned with the DMN in depression. Connectivity was also compared to a cohort of 35 healthy controls. Results Prior to treatment, functional connectivity in depressed patients was abnormally elevated within the DMN and diminished within the CEN, and connectivity between these two networks was altered. TMS normalized depression-related subgenual hyperconnectivity in the DMN but did not alter connectivity in the CEN. TMS also induced anticorrelated connectivity between the DLPFC and medial prefrontal DMN nodes. Baseline subgenual connectivity predicted subsequent clinical improvement. Conclusions TMS selectively modulates functional connectivity both within and between the CEN and DMN, and modulation of subgenual cingulate connectivity may play an important mechanistic role in alleviating depression. The results also highlight potential neuroimaging biomarkers for predicting treatment response. PMID:24629537
van Dellen, E.; de Witt Hamer, P.C.; Douw, L.; Klein, M.; Heimans, J.J.; Stam, C.J.; Reijneveld, J.C.; Hillebrand, A.
2012-01-01
Purpose Low-grade glioma (LGG) patients often have cognitive deficits. Several disease- and treatment related factors affect cognitive processing. Cognitive outcome of resective surgery is unpredictable, both for improvement and deterioration, especially for complex domains such as attention and executive functioning. MEG analysis of resting-state networks (RSNs) is a good candidate for presurgical prediction of cognitive outcome. In this study, we explore the relation between alterations in connectivity of RSNs and changes in cognitive processing after resective surgery, as a stepping stone to ultimately predict postsurgical cognitive outcome. Methods Ten patients with LGG were included, who had no adjuvant therapy. MEG recording and neuropsychological assessment were obtained before and after resective surgery. MEG data were recorded during a no-task eyes-closed condition, and projected to the anatomical space of the AAL atlas. Alterations in functional connectivity, as characterized by the phase lag index (PLI), within the default mode network (DMN), executive control network (ECN), and left- and right-sided frontoparietal networks (FPN) were compared to cognitive changes. Results Lower alpha band DMN connectivity was increased after surgery, and this increase was related to improved verbal memory functioning. Similarly, right FPN connectivity was increased after resection in the upper alpha band, which correlated with improved attention, working memory and executive functioning. Discussion Increased alpha band RSN functional connectivity in MEG recordings correlates with improved cognitive outcome after resective surgery. The mechanisms resulting in functional connectivity alterations after resection remain to be elucidated. Importantly, our findings indicate that connectivity of MEG RSNs may be used for presurgical prediction of cognitive outcome in future studies. PMID:24179752
Piantoni, Giovanni; Cheung, Bing Leung P.; Van Veen, Barry D.; Romeijn, Nico; Riedner, Brady A.; Tononi, Giulio; Van Der Werf, Ysbrand D.; Van Someren, Eus J.W.
2013-01-01
The cingulate cortex is regarded as the backbone of structural and functional connectivity of the brain. While its functional connectivity has been intensively studied, little is known about its effective connectivity, its modulation by behavioral states, and its involvement in cognitive performance. Given their previously reported effects on cingulate functional connectivity, we investigated how eye-closure and sleep deprivation changed cingulate effective connectivity, estimated from resting-state high-density electroencephalography (EEG) using a novel method to calculate Granger Causality directly in source space. Effective connectivity along the cingulate cortex was dominant in the forward direction. Eyes-open connectivity in the forward direction was greater compared to eyes-closed, in well-rested participants. The difference between eyes-open and eyes-closed connectivity was attenuated and no longer significant after sleep deprivation. Individual variability in the forward connectivity after sleep deprivation predicted subsequent task performance, such that those subjects who showed a greater increase in forward connectivity between the eyes-open and the eyes-closed periods also performed better on a sustained attention task. Effective connectivity in the opposite, backward, direction was not affected by whether the eyes were open or closed or by sleep deprivation. These findings indicate that the effective connectivity from posterior to anterior cingulate regions is enhanced when a well-rested subject has his eyes open compared to when they are closed. Sleep deprivation impairs this directed information flow, proportional to its deleterious effect on vigilance. Therefore, sleep may play a role in the maintenance of waking effective connectivity. PMID:23643925
Abnormal functional connectivity density in children with anisometropic amblyopia at resting-state.
Wang, Tianyue; Li, Qian; Guo, Mingxia; Peng, Yanmin; Li, Qingji; Qin, Wen; Yu, Chunshui
2014-05-14
Amblyopia is a developmental disorder resulting from anomalous binocular visual input in early life. Task-based neuroimaging studies have widely investigated cortical functional impairments in amblyopia, but changes in spontaneous neuronal functional activities in amblyopia remain largely unknown. In the present study, functional connectivity density (FCD) mapping, an ultrafast data-driven method based on fMRI, was applied for the first time to investigate changes in cortical functional connectivities in amblyopia during the resting-state. We quantified and compared both short- and long-range FCD in both the brains of children with anisometropic amblyopia (AAC) and normal sighted children (NSC). In contrast to the NSC, the AAC showed significantly decreased short-range FCD in the inferior temporal/fusiform gyri, parieto-occipital and rostrolateral prefrontal cortices, as well as decreased long-range FCD in the premotor cortex, dorsal inferior parietal lobule, frontal-insular and dorsal prefrontal cortices. Furthermore, most regions with reduced long-range FCD in the AAC showed decreased functional connectivity with occipital and posterior parietal cortices in the AAC. The results suggest that chronically poor visual input in amblyopia not only impairs the brain's short-range functional connections in visual pathways and in the frontal cortex, which is important for cognitive control, but also affects long-range functional connections among the visual areas, posterior parietal and frontal cortices that subserve visuomotor and visual-guided actions, visuospatial attention modulation and the integration of salient information. This study provides evidence for abnormal spontaneous brain activities in amblyopia. Copyright © 2014 Elsevier B.V. All rights reserved.
Postoperative seizure freedom does not normalize altered connectivity in temporal lobe epilepsy.
Maccotta, Luigi; Lopez, Mayra A; Adeyemo, Babatunde; Ances, Beau M; Day, Brian K; Eisenman, Lawrence N; Dowling, Joshua L; Leuthardt, Eric C; Schlaggar, Bradley L; Hogan, Robert Edward
2017-11-01
Specific changes in the functional connectivity of brain networks occur in patients with epilepsy. Yet whether such changes reflect a stable disease effect or one that is a function of active seizure burden remains unclear. Here, we longitudinally assessed the connectivity of canonical cognitive functional networks in patients with intractable temporal lobe epilepsy (TLE), both before and after patients underwent epilepsy surgery and achieved seizure freedom. Seventeen patients with intractable TLE who underwent epilepsy surgery with Engel class I outcome and 17 matched healthy controls took part in the study. The functional connectivity of a set of cognitive functional networks derived from typical cognitive tasks was assessed in patients, preoperatively and postoperatively, as well as in controls, using stringent methods of artifact reduction. Preoperatively, functional networks in TLE patients differed significantly from healthy controls, with differences that largely, but not exclusively, involved the default mode and temporal/auditory subnetworks. However, undergoing epilepsy surgery and achieving seizure freedom did not lead to significant changes in network connectivity, with postoperative functional network abnormalities closely mirroring the preoperative state. This result argues for a stable chronic effect of the disease on brain connectivity, with changes that are largely "burned in" by the time a patient with intractable TLE undergoes epilepsy surgery, which typically occurs years after the initial diagnosis. The result has potential implications for the treatment of intractable epilepsy, suggesting that delaying surgical intervention that may achieve seizure freedom may lead to functional network changes that are no longer reversible by the time of epilepsy surgery. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.
Zador, Anthony M.; Dubnau, Joshua; Oyibo, Hassana K.; Zhan, Huiqing; Cao, Gang; Peikon, Ian D.
2012-01-01
Connectivity determines the function of neural circuits. Historically, circuit mapping has usually been viewed as a problem of microscopy, but no current method can achieve high-throughput mapping of entire circuits with single neuron precision. Here we describe a novel approach to determining connectivity. We propose BOINC (“barcoding of individual neuronal connections”), a method for converting the problem of connectivity into a form that can be read out by high-throughput DNA sequencing. The appeal of using sequencing is that its scale—sequencing billions of nucleotides per day is now routine—is a natural match to the complexity of neural circuits. An inexpensive high-throughput technique for establishing circuit connectivity at single neuron resolution could transform neuroscience research. PMID:23109909
Default Mode Network Subsystems are Differentially Disrupted in Posttraumatic Stress Disorder
Miller, Danielle R.; Hayes, Scott M.; Hayes, Jasmeet P.; Spielberg, Jeffrey M.; Lafleche, Ginette; Verfaellie, Mieke
2017-01-01
Background Posttraumatic stress disorder (PTSD) is a psychiatric disorder characterized by debilitating re-experiencing, avoidance, and hyperarousal symptoms following trauma exposure. Recent evidence suggests that individuals with PTSD show disrupted functional connectivity in the default mode network, an intrinsic network that consists of a midline core, a medial temporal lobe (MTL) subsystem, and a dorsomedial prefrontal cortex (dMPFC) subsystem. The present study examined whether functional connectivity in these subsystems is differentially disrupted in PTSD. Methods Sixty-nine returning war Veterans with PTSD and 44 trauma-exposed Veterans without PTSD underwent resting state functional MRI (rs-fMRI). To examine functional connectivity, seeds were placed in the core hubs of the default mode network, namely the posterior cingulate cortex (PCC) and anterior medial PFC (aMPFC), and in each subsystem. Results Compared to controls, individuals with PTSD had reduced functional connectivity between the PCC and the hippocampus, a region of the MTL subsystem. Groups did not differ in connectivity between the PCC and dMPFC subsystem or between the aMPFC and any region within either subsystem. In the PTSD group, connectivity between the PCC and hippocampus was negatively associated with avoidance/numbing symptoms. Examination of the MTL and dMPFC subsystems revealed reduced anticorrelation between the ventromedial PFC (vMPFC) seed of the MTL subsystem and the dorsal anterior cingulate cortex in the PTSD group. Conclusions Our results suggest that selective alterations in functional connectivity in the MTL subsystem of the default mode network in PTSD may be an important factor in PTSD pathology and symptomatology. PMID:28435932
On the Reliability of Individual Brain Activity Networks.
Cassidy, Ben; Bowman, F DuBois; Rae, Caroline; Solo, Victor
2018-02-01
There is intense interest in fMRI research on whole-brain functional connectivity, and however, two fundamental issues are still unresolved: the impact of spatiotemporal data resolution (spatial parcellation and temporal sampling) and the impact of the network construction method on the reliability of functional brain networks. In particular, the impact of spatiotemporal data resolution on the resulting connectivity findings has not been sufficiently investigated. In fact, a number of studies have already observed that functional networks often give different conclusions across different parcellation scales. If the interpretations from functional networks are inconsistent across spatiotemporal scales, then the whole validity of the functional network paradigm is called into question. This paper investigates the consistency of resting state network structure when using different temporal sampling or spatial parcellation, or different methods for constructing the networks. To pursue this, we develop a novel network comparison framework based on persistent homology from a topological data analysis. We use the new network comparison tools to characterize the spatial and temporal scales under which consistent functional networks can be constructed. The methods are illustrated on Human Connectome Project data, showing that the DISCOH 2 network construction method outperforms other approaches at most data spatiotemporal resolutions.
Prenatal stress alters amygdala functional connectivity in preterm neonates.
Scheinost, Dustin; Kwon, Soo Hyun; Lacadie, Cheryl; Sze, Gordon; Sinha, Rajita; Constable, R Todd; Ment, Laura R
2016-01-01
Exposure to prenatal and early-life stress results in alterations in neural connectivity and an increased risk for neuropsychiatric disorders. In particular, alterations in amygdala connectivity have emerged as a common effect across several recent studies. However, the impact of prenatal stress exposure on the functional organization of the amygdala has yet to be explored in the prematurely-born, a population at high risk for neuropsychiatric disorders. We test the hypothesis that preterm birth and prenatal exposure to maternal stress alter functional connectivity of the amygdala using two independent cohorts. The first cohort is used to establish the effects of preterm birth and consists of 12 very preterm neonates and 25 term controls, all without prenatal stress exposure. The second is analyzed to establish the effects of prenatal stress exposure and consists of 16 extremely preterm neonates with prenatal stress exposure and 10 extremely preterm neonates with no known prenatal stress exposure. Standard resting-state functional magnetic resonance imaging and seed connectivity methods are used. When compared to term controls, very preterm neonates show significantly reduced connectivity between the amygdala and the thalamus, the hypothalamus, the brainstem, and the insula (p < 0.05). Similarly, when compared to extremely preterm neonates without exposure to prenatal stress, extremely preterm neonates with exposure to prenatal stress show significantly less connectivity between the left amygdala and the thalamus, the hypothalamus, and the peristriate cortex (p < 0.05). Exploratory analysis of the combined cohorts suggests additive effects of prenatal stress on alterations in amygdala connectivity associated with preterm birth. Functional connectivity from the amygdala to other subcortical regions is decreased in preterm neonates compared to term controls. In addition, these data, for the first time, suggest that prenatal stress exposure amplifies these decreases.
Joint brain connectivity estimation from diffusion and functional MRI data
NASA Astrophysics Data System (ADS)
Chu, Shu-Hsien; Lenglet, Christophe; Parhi, Keshab K.
2015-03-01
Estimating brain wiring patterns is critical to better understand the brain organization and function. Anatomical brain connectivity models axonal pathways, while the functional brain connectivity characterizes the statistical dependencies and correlation between the activities of various brain regions. The synchronization of brain activity can be inferred through the variation of blood-oxygen-level dependent (BOLD) signal from functional MRI (fMRI) and the neural connections can be estimated using tractography from diffusion MRI (dMRI). Functional connections between brain regions are supported by anatomical connections, and the synchronization of brain activities arises through sharing of information in the form of electro-chemical signals on axon pathways. Jointly modeling fMRI and dMRI data may improve the accuracy in constructing anatomical connectivity as well as functional connectivity. Such an approach may lead to novel multimodal biomarkers potentially able to better capture functional and anatomical connectivity variations. We present a novel brain network model which jointly models the dMRI and fMRI data to improve the anatomical connectivity estimation and extract the anatomical subnetworks associated with specific functional modes by constraining the anatomical connections as structural supports to the functional connections. The key idea is similar to a multi-commodity flow optimization problem that minimizes the cost or maximizes the efficiency for flow configuration and simultaneously fulfills the supply-demand constraint for each commodity. In the proposed network, the nodes represent the grey matter (GM) regions providing brain functionality, and the links represent white matter (WM) fiber bundles connecting those regions and delivering information. The commodities can be thought of as the information corresponding to brain activity patterns as obtained for instance by independent component analysis (ICA) of fMRI data. The concept of information flow is introduced and used to model the propagation of information between GM areas through WM fiber bundles. The link capacity, i.e., ability to transfer information, is characterized by the relative strength of fiber bundles, e.g., fiber count gathered from the tractography of dMRI data. The node information demand is considered to be proportional to the correlation between neural activity at various cortical areas involved in a particular functional mode (e.g. visual, motor, etc.). These two properties lead to the link capacity and node demand constraints in the proposed model. Moreover, the information flow of a link cannot exceed the demand from either end node. This is captured by the feasibility constraints. Two different cost functions are considered in the optimization formulation in this paper. The first cost function, the reciprocal of fiber strength represents the unit cost for information passing through the link. In the second cost function, a min-max (minimizing the maximal link load) approach is used to balance the usage of each link. Optimizing the first cost function selects the pathway with strongest fiber strength for information propagation. In the second case, the optimization procedure finds all the possible propagation pathways and allocates the flow proportionally to their strength. Additionally, a penalty term is incorporated with both the cost functions to capture the possible missing and weak anatomical connections. With this set of constraints and the proposed cost functions, solving the network optimization problem recovers missing and weak anatomical connections supported by the functional information and provides the functional-associated anatomical subnetworks. Feasibility is demonstrated using realistic diffusion and functional MRI phantom data. It is shown that the proposed model recovers the maximum number of true connections, with fewest number of false connections when compared with the connectivity derived from a joint probabilistic model using the expectation-maximization (EM) algorithm presented in a prior work. We also apply the proposed method to data provided by the Human Connectome Project (HCP).
Ortiz, Andrés; Munilla, Jorge; Álvarez-Illán, Ignacio; Górriz, Juan M; Ramírez, Javier
2015-01-01
Alzheimer's Disease (AD) is the most common neurodegenerative disease in elderly people. Its development has been shown to be closely related to changes in the brain connectivity network and in the brain activation patterns along with structural changes caused by the neurodegenerative process. Methods to infer dependence between brain regions are usually derived from the analysis of covariance between activation levels in the different areas. However, these covariance-based methods are not able to estimate conditional independence between variables to factor out the influence of other regions. Conversely, models based on the inverse covariance, or precision matrix, such as Sparse Gaussian Graphical Models allow revealing conditional independence between regions by estimating the covariance between two variables given the rest as constant. This paper uses Sparse Inverse Covariance Estimation (SICE) methods to learn undirected graphs in order to derive functional and structural connectivity patterns from Fludeoxyglucose (18F-FDG) Position Emission Tomography (PET) data and segmented Magnetic Resonance images (MRI), drawn from the ADNI database, for Control, MCI (Mild Cognitive Impairment Subjects), and AD subjects. Sparse computation fits perfectly here as brain regions usually only interact with a few other areas. The models clearly show different metabolic covariation patters between subject groups, revealing the loss of strong connections in AD and MCI subjects when compared to Controls. Similarly, the variance between GM (Gray Matter) densities of different regions reveals different structural covariation patterns between the different groups. Thus, the different connectivity patterns for controls and AD are used in this paper to select regions of interest in PET and GM images with discriminative power for early AD diagnosis. Finally, functional an structural models are combined to leverage the classification accuracy. The results obtained in this work show the usefulness of the Sparse Gaussian Graphical models to reveal functional and structural connectivity patterns. This information provided by the sparse inverse covariance matrices is not only used in an exploratory way but we also propose a method to use it in a discriminative way. Regression coefficients are used to compute reconstruction errors for the different classes that are then introduced in a SVM for classification. Classification experiments performed using 68 Controls, 70 AD, and 111 MCI images and assessed by cross-validation show the effectiveness of the proposed method.
Bayesian Inference for Functional Dynamics Exploring in fMRI Data.
Guo, Xuan; Liu, Bing; Chen, Le; Chen, Guantao; Pan, Yi; Zhang, Jing
2016-01-01
This paper aims to review state-of-the-art Bayesian-inference-based methods applied to functional magnetic resonance imaging (fMRI) data. Particularly, we focus on one specific long-standing challenge in the computational modeling of fMRI datasets: how to effectively explore typical functional interactions from fMRI time series and the corresponding boundaries of temporal segments. Bayesian inference is a method of statistical inference which has been shown to be a powerful tool to encode dependence relationships among the variables with uncertainty. Here we provide an introduction to a group of Bayesian-inference-based methods for fMRI data analysis, which were designed to detect magnitude or functional connectivity change points and to infer their functional interaction patterns based on corresponding temporal boundaries. We also provide a comparison of three popular Bayesian models, that is, Bayesian Magnitude Change Point Model (BMCPM), Bayesian Connectivity Change Point Model (BCCPM), and Dynamic Bayesian Variable Partition Model (DBVPM), and give a summary of their applications. We envision that more delicate Bayesian inference models will be emerging and play increasingly important roles in modeling brain functions in the years to come.
Template based rotation: A method for functional connectivity analysis with a priori templates☆
Schultz, Aaron P.; Chhatwal, Jasmeer P.; Huijbers, Willem; Hedden, Trey; van Dijk, Koene R.A.; McLaren, Donald G.; Ward, Andrew M.; Wigman, Sarah; Sperling, Reisa A.
2014-01-01
Functional connectivity magnetic resonance imaging (fcMRI) is a powerful tool for understanding the network level organization of the brain in research settings and is increasingly being used to study large-scale neuronal network degeneration in clinical trial settings. Presently, a variety of techniques, including seed-based correlation analysis and group independent components analysis (with either dual regression or back projection) are commonly employed to compute functional connectivity metrics. In the present report, we introduce template based rotation,1 a novel analytic approach optimized for use with a priori network parcellations, which may be particularly useful in clinical trial settings. Template based rotation was designed to leverage the stable spatial patterns of intrinsic connectivity derived from out-of-sample datasets by mapping data from novel sessions onto the previously defined a priori templates. We first demonstrate the feasibility of using previously defined a priori templates in connectivity analyses, and then compare the performance of template based rotation to seed based and dual regression methods by applying these analytic approaches to an fMRI dataset of normal young and elderly subjects. We observed that template based rotation and dual regression are approximately equivalent in detecting fcMRI differences between young and old subjects, demonstrating similar effect sizes for group differences and similar reliability metrics across 12 cortical networks. Both template based rotation and dual-regression demonstrated larger effect sizes and comparable reliabilities as compared to seed based correlation analysis, though all three methods yielded similar patterns of network differences. When performing inter-network and sub-network connectivity analyses, we observed that template based rotation offered greater flexibility, larger group differences, and more stable connectivity estimates as compared to dual regression and seed based analyses. This flexibility owes to the reduced spatial and temporal orthogonality constraints of template based rotation as compared to dual regression. These results suggest that template based rotation can provide a useful alternative to existing fcMRI analytic methods, particularly in clinical trial settings where predefined outcome measures and conserved network descriptions across groups are at a premium. PMID:25150630
Noble, Stephanie; Spann, Marisa N; Tokoglu, Fuyuze; Shen, Xilin; Constable, R Todd; Scheinost, Dustin
2017-11-01
Best practices are currently being developed for the acquisition and processing of resting-state magnetic resonance imaging data used to estimate brain functional organization-or "functional connectivity." Standards have been proposed based on test-retest reliability, but open questions remain. These include how amount of data per subject influences whole-brain reliability, the influence of increasing runs versus sessions, the spatial distribution of reliability, the reliability of multivariate methods, and, crucially, how reliability maps onto prediction of behavior. We collected a dataset of 12 extensively sampled individuals (144 min data each across 2 identically configured scanners) to assess test-retest reliability of whole-brain connectivity within the generalizability theory framework. We used Human Connectome Project data to replicate these analyses and relate reliability to behavioral prediction. Overall, the historical 5-min scan produced poor reliability averaged across connections. Increasing the number of sessions was more beneficial than increasing runs. Reliability was lowest for subcortical connections and highest for within-network cortical connections. Multivariate reliability was greater than univariate. Finally, reliability could not be used to improve prediction; these findings are among the first to underscore this distinction for functional connectivity. A comprehensive understanding of test-retest reliability, including its limitations, supports the development of best practices in the field. © The Author 2017. Published by Oxford University Press.
Cai, Suping; Huang, Liyu; Zou, Jia; Jing, Longlong; Zhai, Buzhong; Ji, Gongjun; von Deneen, Karen M.; Ren, Junchan; Ren, Aifeng
2015-01-01
We used resting-state functional magnetic resonance imaging (fMRI) to investigate changes in the thalamus functional connectivity in early and late stages of amnestic mild cognitive impairment. Data of 25 late stages of amnestic mild cognitive impairment (LMCI) patients, 30 early stages of amnestic mild cognitive impairment (EMCI) patients and 30 well-matched healthy controls (HC) were analyzed from the Alzheimer’s disease Neuroimaging Initiative (ADNI). We focused on the correlation between low frequency fMRI signal fluctuations in the thalamus and those in all other brain regions. Compared to healthy controls, we found functional connectivity between the left/right thalamus and a set of brain areas was decreased in LMCI and/or EMCI including right fusiform gyrus (FG), left and right superior temporal gyrus, left medial frontal gyrus extending into supplementary motor area, right insula, left middle temporal gyrus (MTG) extending into middle occipital gyrus (MOG). We also observed increased functional connectivity between the left/right thalamus and several regions in LMCI and/or EMCI including left FG, right MOG, left and right precuneus, right MTG and left inferior temporal gyrus. In the direct comparison between the LMCI and EMCI groups, we obtained several brain regions showed thalamus-seeded functional connectivity differences such as the precentral gyrus, hippocampus, FG and MTG. Briefly, these brain regions mentioned above were mainly located in the thalamo-related networks including thalamo-hippocampus, thalamo-temporal, thalamo-visual, and thalamo-default mode network. The decreased functional connectivity of the thalamus might suggest reduced functional integrity of thalamo-related networks and increased functional connectivity indicated that aMCI patients could use additional brain resources to compensate for the loss of cognitive function. Our study provided a new sight to understand the two important states of aMCI and revealed resting-state fMRI is an appropriate method for exploring pathophysiological changes in aMCI. PMID:25679386
Cai, Suping; Huang, Liyu; Zou, Jia; Jing, Longlong; Zhai, Buzhong; Ji, Gongjun; von Deneen, Karen M; Ren, Junchan; Ren, Aifeng
2015-01-01
We used resting-state functional magnetic resonance imaging (fMRI) to investigate changes in the thalamus functional connectivity in early and late stages of amnestic mild cognitive impairment. Data of 25 late stages of amnestic mild cognitive impairment (LMCI) patients, 30 early stages of amnestic mild cognitive impairment (EMCI) patients and 30 well-matched healthy controls (HC) were analyzed from the Alzheimer's disease Neuroimaging Initiative (ADNI). We focused on the correlation between low frequency fMRI signal fluctuations in the thalamus and those in all other brain regions. Compared to healthy controls, we found functional connectivity between the left/right thalamus and a set of brain areas was decreased in LMCI and/or EMCI including right fusiform gyrus (FG), left and right superior temporal gyrus, left medial frontal gyrus extending into supplementary motor area, right insula, left middle temporal gyrus (MTG) extending into middle occipital gyrus (MOG). We also observed increased functional connectivity between the left/right thalamus and several regions in LMCI and/or EMCI including left FG, right MOG, left and right precuneus, right MTG and left inferior temporal gyrus. In the direct comparison between the LMCI and EMCI groups, we obtained several brain regions showed thalamus-seeded functional connectivity differences such as the precentral gyrus, hippocampus, FG and MTG. Briefly, these brain regions mentioned above were mainly located in the thalamo-related networks including thalamo-hippocampus, thalamo-temporal, thalamo-visual, and thalamo-default mode network. The decreased functional connectivity of the thalamus might suggest reduced functional integrity of thalamo-related networks and increased functional connectivity indicated that aMCI patients could use additional brain resources to compensate for the loss of cognitive function. Our study provided a new sight to understand the two important states of aMCI and revealed resting-state fMRI is an appropriate method for exploring pathophysiological changes in aMCI.
2017-01-01
Objective The purpose of this study was to investigate the resting-state interhemispheric functional connectivity in early blindness by using voxel-mirrored homotopic connectivity (VMHC). Materials and Methods Sixteen early blind patients (EB group) and sixteen age- and gender-matched sighted control volunteers (SC group) were recruited in this study. We used VMHC to identify brain areas with significant differences in functional connectivity between different groups and used voxel-based morphometry (VBM) to calculate the individual gray matter volume (GMV). Results VMHC analysis showed a significantly lower connectivity in primary visual cortex, visual association cortex, and somatosensory association cortex in EB group compared to sighted controls. Additionally, VBM analysis revealed that GMV was reduced in the left lateral calcarine cortices in EB group compared to sighted controls, while it was increased in the left lateral middle occipital gyri. Statistical analysis showed the duration of blindness negatively correlated with VMHC in the bilateral middle frontal gyri, middle temporal gyri, and inferior temporal gyri. Conclusions Our findings help elucidate the pathophysiological mechanisms of EB. The interhemispheric functional connectivity was impaired in EB patients. Additionally, the middle frontal gyri, middle temporal gyri, and inferior temporal gyri may be potential target regions for rehabilitation. PMID:28656145
Iyer, Swathi; Shafran, Izhak; Grayson, David; Gates, Kathleen; Nigg, Joel; Fair, Damien
2013-01-01
Resting state functional connectivity MRI (rs-fcMRI) is a popular technique used to gauge the functional relatedness between regions in the brain for typical and special populations. Most of the work to date determines this relationship by using Pearson's correlation on BOLD fMRI timeseries. However, it has been recognized that there are at least two key limitations to this method. First, it is not possible to resolve the direct and indirect connections/influences. Second, the direction of information flow between the regions cannot be differentiated. In the current paper, we follow-up on recent work by Smith et al (2011), and apply a Bayesian approach called the PC algorithm to both simulated data and empirical data to determine whether these two factors can be discerned with group average, as opposed to single subject, functional connectivity data. When applied on simulated individual subjects, the algorithm performs well determining indirect and direct connection but fails in determining directionality. However, when applied at group level, PC algorithm gives strong results for both indirect and direct connections and the direction of information flow. Applying the algorithm on empirical data, using a diffusion-weighted imaging (DWI) structural connectivity matrix as the baseline, the PC algorithm outperformed the direct correlations. We conclude that, under certain conditions, the PC algorithm leads to an improved estimate of brain network structure compared to the traditional connectivity analysis based on correlations. PMID:23501054
Altered topography of intrinsic functional connectivity in childhood risk for social anxiety
Taber-Thomas, Bradley C.; Morales, Santiago; Hillary, Frank G.; Pérez-Edgar, Koraly E.
2016-01-01
Background Extreme shyness in childhood arising from behavioral inhibition (BI) is among the strongest risk factors for developing social anxiety. Although no imaging studies of intrinsic brain networks in BI children have been reported, adults with a history of BI exhibit altered functioning of frontolimbic circuits and enhanced processing of salient, personally-relevant information. BI in childhood may be marked by increased coupling of salience (insula) and default (ventromedial prefrontal cortex) network hubs. Methods We tested this potential relation in 42 children ages 9 to 12, oversampled for high-BI. Participants provided resting-state functional magnetic resonance imaging. A novel topographical pattern analysis of salience network intrinsic functional connectivity was conducted, and the impact of salience-default coupling on the relation between BI and social anxiety symptoms was assessed via moderation analysis. Results High-BI children exhibit altered salience network topography, marked by reduced insula connectivity to dorsal anterior cingulate and increased insula connectivity to ventromedial prefrontal cortex. Whole-brain analyses revealed increased connectivity of salience, executive, and sensory networks with default network hubs in children higher in BI. Finally, the relation between insula-ventromedial prefrontal connectivity and social anxiety symptoms was strongest among the highest BI children. Conclusions BI is associated with an increase in connectivity to default network hubs that may bias processing toward personally-relevant information during development. These altered patterns of connectivity point to potential biomarkers of the neural profile of risk for anxiety in childhood. PMID:27093074
Disruptions in Functional Network Connectivity during Alcohol Intoxicated Driving
Rzepecki-Smith, Catherine I.; Meda, Shashwath A.; Calhoun, Vince D.; Stevens, Michael C.; Jafri, Madiha J.; Astur, Robert S.; Pearlson, Godfrey D.
2009-01-01
Background: Driving while under the influence of alcohol is a major public health problem whose neural basis is not well understood. In a recently published fMRI study (Meda et al, 2009), our group identified five, independent critical driving-associated brain circuits whose inter-regional connectivity was disrupted by alcohol intoxication. However, the functional connectivity between these circuits has not yet been explored in order to determine how these networks communicate with each other during sober and alcohol-intoxicated states. Methods: In the current study, we explored such differences in connections between the above brain circuits and driving behavior, under the influence of alcohol versus placebo. Forty social drinkers who drove regularly underwent fMRI scans during virtual reality driving simulations following two alcohol doses, placebo and an individualized dose producing blood alcohol concentrations (BACs) of 0.10%. Results: At the active dose, we found specific disruptions of functional network connectivity between the frontal-temporal-basal ganglia and the cerebellar circuits. The temporal connectivity between these two circuits was found to be less correlated (p <0.05) when driving under the influence of alcohol. This disconnection was also associated with an abnormal driving behavior (unstable motor vehicle steering). Conclusions: Connections between frontal-temporal-basal ganglia and cerebellum have recently been explored; these may be responsible in part for maintaining normal motor behavior by integrating their overlapping motor control functions. These connections appear to be disrupted by alcohol intoxication, in turn associated with an explicit type of impaired driving behavior. PMID:20028354
New Computer Simulations of Macular Neural Functioning
NASA Technical Reports Server (NTRS)
Ross, Muriel D.; Doshay, D.; Linton, S.; Parnas, B.; Montgomery, K.; Chimento, T.
1994-01-01
We use high performance graphics workstations and supercomputers to study the functional significance of the three-dimensional (3-D) organization of gravity sensors. These sensors have a prototypic architecture foreshadowing more complex systems. Scaled-down simulations run on a Silicon Graphics workstation and scaled-up, 3-D versions run on a Cray Y-MP supercomputer. A semi-automated method of reconstruction of neural tissue from serial sections studied in a transmission electron microscope has been developed to eliminate tedious conventional photography. The reconstructions use a mesh as a step in generating a neural surface for visualization. Two meshes are required to model calyx surfaces. The meshes are connected and the resulting prisms represent the cytoplasm and the bounding membranes. A finite volume analysis method is employed to simulate voltage changes along the calyx in response to synapse activation on the calyx or on calyceal processes. The finite volume method insures that charge is conserved at the calyx-process junction. These and other models indicate that efferent processes act as voltage followers, and that the morphology of some afferent processes affects their functioning. In a final application, morphological information is symbolically represented in three dimensions in a computer. The possible functioning of the connectivities is tested using mathematical interpretations of physiological parameters taken from the literature. Symbolic, 3-D simulations are in progress to probe the functional significance of the connectivities. This research is expected to advance computer-based studies of macular functioning and of synaptic plasticity.
fMRI during natural sleep as a method to study brain function during early childhood.
Redcay, Elizabeth; Kennedy, Daniel P; Courchesne, Eric
2007-12-01
Many techniques to study early functional brain development lack the whole-brain spatial resolution that is available with fMRI. We utilized a relatively novel method in which fMRI data were collected from children during natural sleep. Stimulus-evoked responses to auditory and visual stimuli as well as stimulus-independent functional networks were examined in typically developing 2-4-year-old children. Reliable fMRI data were collected from 13 children during presentation of auditory stimuli (tones, vocal sounds, and nonvocal sounds) in a block design. Twelve children were presented with visual flashing lights at 2.5 Hz. When analyses combined all three types of auditory stimulus conditions as compared to rest, activation included bilateral superior temporal gyri/sulci (STG/S) and right cerebellum. Direct comparisons between conditions revealed significantly greater responses to nonvocal sounds and tones than to vocal sounds in a number of brain regions including superior temporal gyrus/sulcus, medial frontal cortex and right lateral cerebellum. The response to visual stimuli was localized to occipital cortex. Furthermore, stimulus-independent functional connectivity MRI analyses (fcMRI) revealed functional connectivity between STG and other temporal regions (including contralateral STG) and medial and lateral prefrontal regions. Functional connectivity with an occipital seed was localized to occipital and parietal cortex. In sum, 2-4 year olds showed a differential fMRI response both between stimulus modalities and between stimuli in the auditory modality. Furthermore, superior temporal regions showed functional connectivity with numerous higher-order regions during sleep. We conclude that the use of sleep fMRI may be a valuable tool for examining functional brain organization in young children.
Douw, Linda; Stam, Cornelis J.; Tewarie, Prejaas; Hillebrand, Arjan
2017-01-01
Abstract Introduction Studies using functional connectivity and network analyses based on magnetoencephalography (MEG) with source localization are rapidly emerging in neuroscientific literature. However, these analyses currently depend on the availability of costly and sometimes burdensome individual MR scans for co‐registration. We evaluated the consistency of these measures when using a template MRI, instead of native MRI, for the analysis of functional connectivity and network topology. Methods Seventeen healthy participants underwent resting‐state eyes‐closed MEG and anatomical MRI. These data were projected into source space using an atlas‐based peak voxel and a centroid beamforming approach either using (1) participants’ native MRIs or (2) the Montreal Neurological Institute's template. For both methods, time series were reconstructed from 78 cortical atlas regions. Relative power was determined in six classical frequency bands per region and globally averaged. Functional connectivity (phase lag index) between each pair of regions was calculated. The adjacency matrices were then used to reconstruct functional networks, of which regional and global metrics were determined. Intraclass correlation coefficients were calculated and Bland–Altman plots were made to quantify the consistency and potential bias of the use of template versus native MRI. Results Co‐registration with the template yielded largely consistent relative power, connectivity, and network estimates compared to native MRI. Discussion These findings indicate that there is no (systematic) bias or inconsistency between template and native MRI co‐registration of MEG. They open up possibilities for retrospective and prospective analyses to MEG datasets in the general population that have no native MRIs available. Hum Brain Mapp, 2017. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. Hum Brain Mapp 39:104–119, 2018. © 2017 Wiley Periodicals, Inc. PMID:28990264
Dottori, Martin; Sedeño, Lucas; Martorell Caro, Miguel; Alifano, Florencia; Hesse, Eugenia; Mikulan, Ezequiel; García, Adolfo M; Ruiz-Tagle, Amparo; Lillo, Patricia; Slachevsky, Andrea; Serrano, Cecilia; Fraiman, Daniel; Ibanez, Agustin
2017-06-19
Developing effective and affordable biomarkers for dementias is critical given the difficulty to achieve early diagnosis. In this sense, electroencephalographic (EEG) methods offer promising alternatives due to their low cost, portability, and growing robustness. Here, we relied on EEG signals and a novel information-sharing method to study resting-state connectivity in patients with behavioral variant frontotemporal dementia (bvFTD) and controls. To evaluate the specificity of our results, we also tested Alzheimer's disease (AD) patients. The classification power of the ensuing connectivity patterns was evaluated through a supervised classification algorithm (support vector machine). In addition, we compared the classification power yielded by (i) functional connectivity, (ii) relevant neuropsychological tests, and (iii) a combination of both. BvFTD patients exhibited a specific pattern of hypoconnectivity in mid-range frontotemporal links, which showed no alterations in AD patients. These functional connectivity alterations in bvFTD were replicated with a low-density EEG setting (20 electrodes). Moreover, while neuropsychological tests yielded acceptable discrimination between bvFTD and controls, the addition of connectivity results improved classification power. Finally, classification between bvFTD and AD patients was better when based on connectivity than on neuropsychological measures. Taken together, such findings underscore the relevance of EEG measures as potential biomarker signatures for clinical settings.
Wavelet-based clustering of resting state MRI data in the rat.
Medda, Alessio; Hoffmann, Lukas; Magnuson, Matthew; Thompson, Garth; Pan, Wen-Ju; Keilholz, Shella
2016-01-01
While functional connectivity has typically been calculated over the entire length of the scan (5-10min), interest has been growing in dynamic analysis methods that can detect changes in connectivity on the order of cognitive processes (seconds). Previous work with sliding window correlation has shown that changes in functional connectivity can be observed on these time scales in the awake human and in anesthetized animals. This exciting advance creates a need for improved approaches to characterize dynamic functional networks in the brain. Previous studies were performed using sliding window analysis on regions of interest defined based on anatomy or obtained from traditional steady-state analysis methods. The parcellation of the brain may therefore be suboptimal, and the characteristics of the time-varying connectivity between regions are dependent upon the length of the sliding window chosen. This manuscript describes an algorithm based on wavelet decomposition that allows data-driven clustering of voxels into functional regions based on temporal and spectral properties. Previous work has shown that different networks have characteristic frequency fingerprints, and the use of wavelets ensures that both the frequency and the timing of the BOLD fluctuations are considered during the clustering process. The method was applied to resting state data acquired from anesthetized rats, and the resulting clusters agreed well with known anatomical areas. Clusters were highly reproducible across subjects. Wavelet cross-correlation values between clusters from a single scan were significantly higher than the values from randomly matched clusters that shared no temporal information, indicating that wavelet-based analysis is sensitive to the relationship between areas. Copyright © 2015 Elsevier Inc. All rights reserved.
Potential function of element measurement for form-finding of wide sense tensegrity
NASA Astrophysics Data System (ADS)
Soe, C. K.; Obiya, H.; Koga, D.; Nizam, Z. M.; Ijima, K.
2018-04-01
Tensegrity is a unique morphological structure in which disconnected compression members and connected tension members make the whole structure in self-equilibrium. Many researches have been done on tensegrity structure because of its mysteriousness in form-finding analysis. This study is proposed to investigate the trends and to group into some patterns of the shape that a tensegrity structure can have under the same connectivity and support condition. In this study, tangent stiffness method adopts two different functions, namely power function and logarithm function to element measurement. Numerical examples are based on a simplex initial shape with statically determinate support condition to examine the pure effectiveness of two proposed methods. The tangent stiffness method that can evaluate strict rigid body displacement of elements has a superiority to define various measure potentials and to allow the use of virtual element stiffness freely. From the results of numerical examples, the finding of the dominant trends and patterns of the equilibrium solutions is achieved although it has many related solutions under the same circumstances.
Disrupted inter-hemispheric functional and structural coupling in Internet addiction adolescents.
Bi, Yanzhi; Yuan, Kai; Feng, Dan; Xing, Lihong; Li, Yangding; Wang, Hongmei; Yu, Dahua; Xue, Ting; Jin, Chenwang; Qin, Wei; Tian, Jie
2015-11-30
Rapid progress had been made towards the effect of Internet addiction (IA) on the adolescents brain, relatively little is known about the alterations in inter-hemispheric resting state functional connectivity (RSFC) changes. In the current study, voxel-mirrored homotopic connectivity (VMHC) was used to examine inter-hemispheric RSFC in IA adolescents (n=21) and controls (n=21). The integrity of the fibers connecting the regions, which showed aberrant inter-hemispheric functional connectivity, was assessed by fiber tractography analysis. In addition, the coupling of inter-hemispheric functional and structural connectivity was investigated. Relative to controls, IA adolescents showed decreased VMHC of dorsolateral prefrontal cortex (DLPFC) and reduced fractional anisotropy (FA) values in the genu of corpus callosum (CC). The decreased VMHC of DLPFC was significantly negative correlated with the duration of IA. Moreover, the VMHC of DLPFC showed significant correlations with the FA of CC in healthy controls, which was disrupted in IA. Our findings provided more scientific evidence for the involvement of DLPFC in IA. It is hoped that multimodal imaging methods can provide deeper insights into the IA effects on the brain. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Calamante, Fernando; Masterton, Richard A J; Tournier, Jacques-Donald; Smith, Robert E; Willats, Lisa; Raffelt, David; Connelly, Alan
2013-04-15
MRI provides a powerful tool for studying the functional and structural connections in the brain non-invasively. The technique of functional connectivity (FC) exploits the intrinsic temporal correlations of slow spontaneous signal fluctuations to characterise brain functional networks. In addition, diffusion MRI fibre-tracking can be used to study the white matter structural connections. In recent years, there has been considerable interest in combining these two techniques to provide an overall structural-functional description of the brain. In this work we applied the recently proposed super-resolution track-weighted imaging (TWI) methodology to demonstrate how whole-brain fibre-tracking data can be combined with FC data to generate a track-weighted (TW) FC map of FC networks. The method was applied to data from 8 healthy volunteers, and illustrated with (i) FC networks obtained using a seeded connectivity-based analysis (seeding in the precuneus/posterior cingulate cortex, PCC, known to be part of the default mode network), and (ii) with FC networks generated using independent component analysis (in particular, the default mode, attention, visual, and sensory-motor networks). TW-FC maps showed high intensity in white matter structures connecting the nodes of the FC networks. For example, the cingulum bundles show the strongest TW-FC values in the PCC seeded-based analysis, due to their major role in the connection between medial frontal cortex and precuneus/posterior cingulate cortex; similarly the superior longitudinal fasciculus was well represented in the attention network, the optic radiations in the visual network, and the corticospinal tract and corpus callosum in the sensory-motor network. The TW-FC maps highlight the white matter connections associated with a given FC network, and their intensity in a given voxel reflects the functional connectivity of the part of the nodes of the network linked by the structural connections traversing that voxel. They therefore contain a different (and novel) image contrast from that of the images used to generate them. The results shown in this study illustrate the potential of the TW-FC approach for the fusion of structural and functional data into a single quantitative image. This technique could therefore have important applications in neuroscience and neurology, such as for voxel-based comparison studies. Copyright © 2012 Elsevier Inc. All rights reserved.
Migraine classification using magnetic resonance imaging resting-state functional connectivity data.
Chong, Catherine D; Gaw, Nathan; Fu, Yinlin; Li, Jing; Wu, Teresa; Schwedt, Todd J
2017-08-01
Background This study used machine-learning techniques to develop discriminative brain-connectivity biomarkers from resting-state functional magnetic resonance neuroimaging ( rs-fMRI) data that distinguish between individual migraine patients and healthy controls. Methods This study included 58 migraine patients (mean age = 36.3 years; SD = 11.5) and 50 healthy controls (mean age = 35.9 years; SD = 11.0). The functional connections of 33 seeded pain-related regions were used as input for a brain classification algorithm that tested the accuracy of determining whether an individual brain MRI belongs to someone with migraine or to a healthy control. Results The best classification accuracy using a 10-fold cross-validation method was 86.1%. Resting functional connectivity of the right middle temporal, posterior insula, middle cingulate, left ventromedial prefrontal and bilateral amygdala regions best discriminated the migraine brain from that of a healthy control. Migraineurs with longer disease durations were classified more accurately (>14 years; 96.7% accuracy) compared to migraineurs with shorter disease durations (≤14 years; 82.1% accuracy). Conclusions Classification of migraine using rs-fMRI provides insights into pain circuits that are altered in migraine and could potentially contribute to the development of a new, noninvasive migraine biomarker. Migraineurs with longer disease burden were classified more accurately than migraineurs with shorter disease burden, potentially indicating that disease duration leads to reorganization of brain circuitry.
Structural Brain Connectivity Constrains within-a-Day Variability of Direct Functional Connectivity
Park, Bumhee; Eo, Jinseok; Park, Hae-Jeong
2017-01-01
The idea that structural white matter connectivity constrains functional connectivity (interactions among brain regions) has widely been explored in studies of brain networks; studies have mostly focused on the “average” strength of functional connectivity. The question of how structural connectivity constrains the “variability” of functional connectivity remains unresolved. In this study, we investigated the variability of resting state functional connectivity that was acquired every 3 h within a single day from 12 participants (eight time sessions within a 24-h period, 165 scans per session). Three different types of functional connectivity (functional connectivity based on Pearson correlation, direct functional connectivity based on partial correlation, and the pseudo functional connectivity produced by their difference) were estimated from resting state functional magnetic resonance imaging data along with structural connectivity defined using fiber tractography of diffusion tensor imaging. Those types of functional connectivity were evaluated with regard to properties of structural connectivity (fiber streamline counts and lengths) and types of structural connectivity such as intra-/inter-hemispheric edges and topological edge types in the rich club organization. We observed that the structural connectivity constrained the variability of direct functional connectivity more than pseudo-functional connectivity and that the constraints depended strongly on structural connectivity types. The structural constraints were greater for intra-hemispheric and heterologous inter-hemispheric edges than homologous inter-hemispheric edges, and feeder and local edges than rich club edges in the rich club architecture. While each edge was highly variable, the multivariate patterns of edge involvement, especially the direct functional connectivity patterns among the rich club brain regions, showed low variability over time. This study suggests that structural connectivity not only constrains the strength of functional connectivity, but also the within-a-day variability of functional connectivity and connectivity patterns, particularly the direct functional connectivity among brain regions. PMID:28848416
Resting-state functional magnetic resonance imaging: the impact of regression analysis.
Yeh, Chia-Jung; Tseng, Yu-Sheng; Lin, Yi-Ru; Tsai, Shang-Yueh; Huang, Teng-Yi
2015-01-01
To investigate the impact of regression methods on resting-state functional magnetic resonance imaging (rsfMRI). During rsfMRI preprocessing, regression analysis is considered effective for reducing the interference of physiological noise on the signal time course. However, it is unclear whether the regression method benefits rsfMRI analysis. Twenty volunteers (10 men and 10 women; aged 23.4 ± 1.5 years) participated in the experiments. We used node analysis and functional connectivity mapping to assess the brain default mode network by using five combinations of regression methods. The results show that regressing the global mean plays a major role in the preprocessing steps. When a global regression method is applied, the values of functional connectivity are significantly lower (P ≤ .01) than those calculated without a global regression. This step increases inter-subject variation and produces anticorrelated brain areas. rsfMRI data processed using regression should be interpreted carefully. The significance of the anticorrelated brain areas produced by global signal removal is unclear. Copyright © 2014 by the American Society of Neuroimaging.
Wang, Jia; Fu, Kuang; Chen, Lei; Duan, Xujun; Guo, Xiaonan; Chen, Heng; Wu, Qiong; Xia, Wei; Wu, Lijie; Chen, Huafu
2017-01-01
Autism spectrum disorder (ASD) has been widely recognized as a complex neurodevelopmental disorder. A large number of neuroimaging studies suggest abnormalities in brain structure and function of patients with ASD, but there is still no consistent conclusion. We sought to investigate both of the structural and functional brain changes in 3-7-year-old children with ASD compared with typically developing controls (TDs), and to assess whether these alterations are associated with autistic behavioral symptoms. Firstly, we applied an optimized method of voxel-based morphometry (VBM) analysis on structural magnetic resonance imaging (sMRI) data to assess the differences of gray matter volume (GMV) between 31 autistic boys aged 3-7 and 31 age- and handness-matched male TDs. Secondly, we used clusters with between-group differences as seed regions to generate intrinsic functional connectivity maps based on resting-state functional connectivity magnetic resonance imaging (rs-fcMRI) in order to evaluate the functional impairments induced by structural alterations. Brain-behavior correlations were assessed among GMV, functional connectivity and symptom severity in children with ASD. VBM analyses revealed increased GMV in left superior temporal gyrus (STG) and left postcentral gyrus (PCG) in ASD children, comparing with TDs. Using left PCG as a seed region, ASD children displayed significantly higher positive connectivity with right angular gyrus (AG) and greater negative connectivity with right superior parietal gyrus (SPG) and right superior occipital gyrus (SOG), which were associated with the severity of symptoms in social interaction, communication and self-care ability. We suggest that stronger functional connectivity between left PCG and right AG, SPG, and SOG detected in young boys with ASD may serve as important indicators of disease severity. Our study provided preliminary functional evidence that may underlie impaired higher-order multisensory integration in ASD children.
Mild cognitive impairment and fMRI studies of brain functional connectivity: the state of the art
Farràs-Permanyer, Laia; Guàrdia-Olmos, Joan; Peró-Cebollero, Maribel
2015-01-01
In the last 15 years, many articles have studied brain connectivity in Mild Cognitive Impairment patients with fMRI techniques, seemingly using different connectivity statistical models in each investigation to identify complex connectivity structures so as to recognize typical behavior in this type of patient. This diversity in statistical approaches may cause problems in results comparison. This paper seeks to describe how researchers approached the study of brain connectivity in MCI patients using fMRI techniques from 2002 to 2014. The focus is on the statistical analysis proposed by each research group in reference to the limitations and possibilities of those techniques to identify some recommendations to improve the study of functional connectivity. The included articles came from a search of Web of Science and PsycINFO using the following keywords: f MRI, MCI, and functional connectivity. Eighty-one papers were found, but two of them were discarded because of the lack of statistical analysis. Accordingly, 79 articles were included in this review. We summarized some parts of the articles, including the goal of every investigation, the cognitive paradigm and methods used, brain regions involved, use of ROI analysis and statistical analysis, emphasizing on the connectivity estimation model used in each investigation. The present analysis allowed us to confirm the remarkable variability of the statistical analysis methods found. Additionally, the study of brain connectivity in this type of population is not providing, at the moment, any significant information or results related to clinical aspects relevant for prediction and treatment. We propose to follow guidelines for publishing fMRI data that would be a good solution to the problem of study replication. The latter aspect could be important for future publications because a higher homogeneity would benefit the comparison between publications and the generalization of results. PMID:26300802
From Structure to Circuits: The Contribution of MEG Connectivity Studies to Functional Neurosurgery.
Pang, Elizabeth W; Snead Iii, O C
2016-01-01
New advances in structural neuroimaging have revealed the intricate and extensive connections within the brain, data which have informed a number of ambitious projects such as the mapping of the human connectome. Elucidation of the structural connections of the brain, at both the macro and micro levels, promises new perspectives on brain structure and function that could translate into improved outcomes in functional neurosurgery. The understanding of neuronal structural connectivity afforded by these data now offers a vista on the brain, in both healthy and diseased states, that could not be seen with traditional neuroimaging. Concurrent with these developments in structural imaging, a complementary modality called magnetoencephalography (MEG) has been garnering great attention because it too holds promise for being able to shed light on the intricacies of functional brain connectivity. MEG is based upon the elemental principle of physics that an electrical current generates a magnetic field. Hence, MEG uses highly sensitive biomagnetometers to measure extracranial magnetic fields produced by intracellular neuronal currents. Put simply then, MEG is a measure of neurophysiological activity, which captures the magnetic fields generated by synchronized intraneuronal electrical activity. As such, MEG recordings offer exquisite resolution in the time and oscillatory domain and, as well, when co-registered with magnetic resonance imaging (MRI), offer excellent resolution in the spatial domain. Recent advances in MEG computational and graph theoretical methods have led to studies of connectivity in the time-frequency domain. As such, MEG can elucidate a neurophysiological-based functional circuitry that may enhance what is seen with MRI connectivity studies. In particular, MEG may offer additional insight not possible by MRI when used to study complex eloquent function, where the precise timing and coordination of brain areas is critical. This article will review the traditional use of MEG for functional neurosurgery, describe recent advances in MEG connectivity analyses, and consider the additional benefits that could be gained with the inclusion of MEG connectivity studies. Since MEG has been most widely applied to the study of epilepsy, we will frame this article within the context of epilepsy surgery and functional neurosurgery for epilepsy.
Causal effect of disconnection lesions on interhemispheric functional connectivity in rhesus monkeys
O’Reilly, Jill X.; Croxson, Paula L.; Jbabdi, Saad; Sallet, Jerome; Noonan, MaryAnn P.; Mars, Rogier B.; Browning, Philip G.F.; Wilson, Charles R. E.; Mitchell, Anna S.; Miller, Karla L.; Rushworth, Matthew F. S.; Baxter, Mark G.
2013-01-01
In the absence of external stimuli or task demands, correlations in spontaneous brain activity (functional connectivity) reflect patterns of anatomical connectivity. Hence, resting-state functional connectivity has been used as a proxy measure for structural connectivity and as a biomarker for brain changes in disease. To relate changes in functional connectivity to physiological changes in the brain, it is important to understand how correlations in functional connectivity depend on the physical integrity of brain tissue. The causal nature of this relationship has been called into question by patient data suggesting that decreased structural connectivity does not necessarily lead to decreased functional connectivity. Here we provide evidence for a causal but complex relationship between structural connectivity and functional connectivity: we tested interhemispheric functional connectivity before and after corpus callosum section in rhesus monkeys. We found that forebrain commissurotomy severely reduced interhemispheric functional connectivity, but surprisingly, this effect was greatly mitigated if the anterior commissure was left intact. Furthermore, intact structural connections increased their functional connectivity in line with the hypothesis that the inputs to each node are normalized. We conclude that functional connectivity is likely driven by corticocortical white matter connections but with complex network interactions such that a near-normal pattern of functional connectivity can be maintained by just a few indirect structural connections. These surprising results highlight the importance of network-level interactions in functional connectivity and may cast light on various paradoxical findings concerning changes in functional connectivity in disease states. PMID:23924609
Cai, Rong-Lin; Shen, Guo-Ming; Wang, Hao; Guan, Yuan-Yuan
2018-01-01
Functional magnetic resonance imaging (fMRI) is a novel method for studying the changes of brain networks due to acupuncture treatment. In recent years, more and more studies have focused on the brain functional connectivity network of acupuncture stimulation. To offer an overview of the different influences of acupuncture on the brain functional connectivity network from studies using resting-state fMRI. The authors performed a systematic search according to PRISMA guidelines. The database PubMed was searched from January 1, 2006 to December 31, 2016 with restriction to human studies in English language. Electronic searches were conducted in PubMed using the keywords "acupuncture" and "neuroimaging" or "resting-state fMRI" or "functional connectivity". Selection of included articles, data extraction and methodological quality assessments were respectively conducted by two review authors. Forty-four resting-state fMRI studies were included in this systematic review according to inclusion criteria. Thirteen studies applied manual acupuncture vs. sham, four studies applied electro-acupuncture vs. sham, two studies also compared transcutaneous electrical acupoint stimulation vs. sham, and nine applied sham acupoint as control. Nineteen studies with a total number of 574 healthy subjects selected to perform fMRI only considered healthy adult volunteers. The brain functional connectivity of the patients had varying degrees of change. Compared with sham acupuncture, verum acupuncture could increase default mode network and sensorimotor network connectivity with pain-, affective- and memory-related brain areas. It has significantly greater connectivity of genuine acupuncture between the periaqueductal gray, anterior cingulate cortex, left posterior cingulate cortex, right anterior insula, limbic/paralimbic and precuneus compared with sham acupuncture. Some research had also shown that acupuncture could adjust the limbic-paralimbic-neocortical network, brainstem, cerebellum, subcortical and hippocampus brain areas. It can be presumed that the functional connectivity network is closely related to the mechanism of acupuncture, and central integration plays a critical role in the acupuncture mechanism. Copyright © 2017 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.
Neural system prediction and identification challenge.
Vlachos, Ioannis; Zaytsev, Yury V; Spreizer, Sebastian; Aertsen, Ad; Kumar, Arvind
2013-01-01
Can we infer the function of a biological neural network (BNN) if we know the connectivity and activity of all its constituent neurons?This question is at the core of neuroscience and, accordingly, various methods have been developed to record the activity and connectivity of as many neurons as possible. Surprisingly, there is no theoretical or computational demonstration that neuronal activity and connectivity are indeed sufficient to infer the function of a BNN. Therefore, we pose the Neural Systems Identification and Prediction Challenge (nuSPIC). We provide the connectivity and activity of all neurons and invite participants (1) to infer the functions implemented (hard-wired) in spiking neural networks (SNNs) by stimulating and recording the activity of neurons and, (2) to implement predefined mathematical/biological functions using SNNs. The nuSPICs can be accessed via a web-interface to the NEST simulator and the user is not required to know any specific programming language. Furthermore, the nuSPICs can be used as a teaching tool. Finally, nuSPICs use the crowd-sourcing model to address scientific issues. With this computational approach we aim to identify which functions can be inferred by systematic recordings of neuronal activity and connectivity. In addition, nuSPICs will help the design and application of new experimental paradigms based on the structure of the SNN and the presumed function which is to be discovered.
Neural system prediction and identification challenge
Vlachos, Ioannis; Zaytsev, Yury V.; Spreizer, Sebastian; Aertsen, Ad; Kumar, Arvind
2013-01-01
Can we infer the function of a biological neural network (BNN) if we know the connectivity and activity of all its constituent neurons?This question is at the core of neuroscience and, accordingly, various methods have been developed to record the activity and connectivity of as many neurons as possible. Surprisingly, there is no theoretical or computational demonstration that neuronal activity and connectivity are indeed sufficient to infer the function of a BNN. Therefore, we pose the Neural Systems Identification and Prediction Challenge (nuSPIC). We provide the connectivity and activity of all neurons and invite participants (1) to infer the functions implemented (hard-wired) in spiking neural networks (SNNs) by stimulating and recording the activity of neurons and, (2) to implement predefined mathematical/biological functions using SNNs. The nuSPICs can be accessed via a web-interface to the NEST simulator and the user is not required to know any specific programming language. Furthermore, the nuSPICs can be used as a teaching tool. Finally, nuSPICs use the crowd-sourcing model to address scientific issues. With this computational approach we aim to identify which functions can be inferred by systematic recordings of neuronal activity and connectivity. In addition, nuSPICs will help the design and application of new experimental paradigms based on the structure of the SNN and the presumed function which is to be discovered. PMID:24399966
MDMA (Ecstasy) association with impaired fMRI BOLD thalamic coherence and functional connectivity*
Salomon, Ronald M.; Karageorgiou, John; Dietrich, Mary S.; McLellan, Jessica Y.; Charboneau, Evonne J.; Blackford, Jennifer U.; Cowan, Ronald L.
2011-01-01
Background MDMA exposure is associated with chronic serotonergic dysfunction in preclinical and clinical studies. A recent functional magnetic resonance imaging (fMRI) comparison of past MDMA users to non-MDMA-using controls revealed increased spatial extent and amplitude of activation in the supplementary motor area during motor tasks (Karageorgiou et al., 2009). Blood oxygenation level dependent (BOLD) data from that study were reanalyzed for intraregional coherence and for inter-regional temporal correlations between time series, as functional connectivity. Methods Fourteen MDMA users and ten controls reporting similar non-MDMA abuse performed finger taps during fMRI. Fourteen motor pathway regions plus a pontine raphé region were examined. Coherence was expressed as percent of voxels positively correlated with an intraregional index voxel. Functional connectivity was determined using wavelet correlations. Results Intraregional thalamic coherence was significantly diminished at low frequencies in MDMA users compared to controls (p=0.009). Inter-regional functional connectivity was significantly weaker for right thalamo - left caudate (p=0.002), right thalamo - left thalamus (p=0.007), right caudate - right postcentral (p=0.007) and right supplementary motor area - right precentral gyrus (p=0.011) region pairs compared to controls. When stratified by lifetime exposure, significant negative associations were observed between cumulative MDMA use and functional connectivity in seven other region-pairs, while only one region-pair showed a positive association. Conclusions Reported prior MDMA use was associated with deficits in BOLD intraregional coherence and inter-regional functional connectivity, even among functionally robust pathways involving motor regions. This suggests that MDMA use is associated with long-lasting effects on brain neurophysiology beyond the cognitive domain. PMID:21807471
Bajo, R; Pusil, S; López, M E; Canuet, L; Pereda, E; Osipova, D; Maestú, F; Pekkonen, E
2015-07-01
Scopolamine administration may be considered as a psychopharmacological model of Alzheimer's disease (AD). Here, we studied a group of healthy elderly under scopolamine to test whether it elicits similar changes in brain connectivity as those observed in AD, thereby verifying a possible model of AD impairment. We did it by testing healthy elderly subjects in two experimental conditions: glycopyrrolate (placebo) and scopolamine administration. We then analyzed magnetoencephalographic (MEG) data corresponding to both conditions in resting-state with eyes closed. This analysis was performed in source space by combining a nonlinear frequency band-specific measure of functional connectivity (phase locking value, PLV) with network analysis methods. Under scopolamine, functional connectivity between several brain areas was significantly reduced as compared to placebo, in most frequency bands analyzed. Besides, regarding the two complex network indices studied (clustering and shortest path length), clustering significantly decreased in the alpha band while shortest path length significantly increased also in alpha band both after scopolamine administration. Overall our findings indicate that both PLV and graph analysis are suitable tools to measure brain connectivity changes induced by scopolamine, which causes alterations in brain connectivity apparently similar to those reported in AD.
Controlled chain polymerisation and chemical soldering for single-molecule electronics.
Okawa, Yuji; Akai-Kasaya, Megumi; Kuwahara, Yuji; Mandal, Swapan K; Aono, Masakazu
2012-05-21
Single functional molecules offer great potential for the development of novel nanoelectronic devices with capabilities beyond today's silicon-based devices. To realise single-molecule electronics, the development of a viable method for connecting functional molecules to each other using single conductive polymer chains is required. The method of initiating chain polymerisation using the tip of a scanning tunnelling microscope (STM) is very useful for fabricating single conductive polymer chains at designated positions and thereby wiring single molecules. In this feature article, developments in the controlled chain polymerisation of diacetylene compounds and the properties of polydiacetylene chains are summarised. Recent studies of "chemical soldering", a technique enabling the covalent connection of single polydiacetylene chains to single functional molecules, are also introduced. This represents a key step in advancing the development of single-molecule electronics.
Sengupta, Arkajyoti; Ramabhadran, Raghunath O; Raghavachari, Krishnan
2014-08-14
In this study we have used the connectivity-based hierarchy (CBH) method to derive accurate heats of formation of a range of biomolecules, 18 amino acids and 10 barbituric acid/uracil derivatives. The hierarchy is based on the connectivity of the different atoms in a large molecule. It results in error-cancellation reaction schemes that are automated, general, and can be readily used for a broad range of organic molecules and biomolecules. Herein, we first locate stable conformational and tautomeric forms of these biomolecules using an accurate level of theory (viz. CCSD(T)/6-311++G(3df,2p)). Subsequently, the heats of formation of the amino acids are evaluated using the CBH-1 and CBH-2 schemes and routinely employed density functionals or wave function-based methods. The calculated heats of formation obtained herein using modest levels of theory and are in very good agreement with those obtained using more expensive W1-F12 and W2-F12 methods on amino acids and G3 results on barbituric acid derivatives. Overall, the present study (a) highlights the small effect of including multiple conformers in determining the heats of formation of biomolecules and (b) in concurrence with previous CBH studies, proves that use of the more effective error-cancelling isoatomic scheme (CBH-2) results in more accurate heats of formation with modestly sized basis sets along with common density functionals or wave function-based methods.
Pedersen, Mangor; Curwood, Evan K; Archer, John S; Abbott, David F; Jackson, Graeme D
2015-11-01
Lennox-Gastaut syndrome, and the similar but less tightly defined Lennox-Gastaut phenotype, describe patients with severe epilepsy, generalized epileptic discharges, and variable intellectual disability. Our previous functional neuroimaging studies suggest that abnormal diffuse association network activity underlies the epileptic discharges of this clinical phenotype. Herein we use a data-driven multivariate approach to determine the spatial changes in local and global networks of patients with severe epilepsy of the Lennox-Gastaut phenotype. We studied 9 adult patients and 14 controls. In 20 min of task-free blood oxygen level-dependent functional magnetic resonance imaging data, two metrics of functional connectivity were studied: Regional homogeneity or local connectivity, a measure of concordance between each voxel to a focal cluster of adjacent voxels; and eigenvector centrality, a global connectivity estimate designed to detect important neural hubs. Multivariate pattern analysis of these data in a machine-learning framework was used to identify spatial features that classified disease subjects. Multivariate pattern analysis was 95.7% accurate in classifying subjects for both local and global connectivity measures (22/23 subjects correctly classified). Maximal discriminating features were the following: increased local connectivity in frontoinsular and intraparietal areas; increased global connectivity in posterior association areas; decreased local connectivity in sensory (visual and auditory) and medial frontal cortices; and decreased global connectivity in the cingulate cortex, striatum, hippocampus, and pons. Using a data-driven analysis method in task-free functional magnetic resonance imaging, we show increased connectivity in critical areas of association cortex and decreased connectivity in primary cortex. This supports previous findings of a critical role for these association cortical regions as a final common pathway in generating the Lennox-Gastaut phenotype. Abnormal function of these areas is likely to be important in explaining the intellectual problems characteristic of this disorder. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.
deepNF: Deep network fusion for protein function prediction.
Gligorijevic, Vladimir; Barot, Meet; Bonneau, Richard
2018-06-01
The prevalence of high-throughput experimental methods has resulted in an abundance of large-scale molecular and functional interaction networks. The connectivity of these networks provides a rich source of information for inferring functional annotations for genes and proteins. An important challenge has been to develop methods for combining these heterogeneous networks to extract useful protein feature representations for function prediction. Most of the existing approaches for network integration use shallow models that encounter difficulty in capturing complex and highly-nonlinear network structures. Thus, we propose deepNF, a network fusion method based on Multimodal Deep Autoencoders to extract high-level features of proteins from multiple heterogeneous interaction networks. We apply this method to combine STRING networks to construct a common low-dimensional representation containing high-level protein features. We use separate layers for different network types in the early stages of the multimodal autoencoder, later connecting all the layers into a single bottleneck layer from which we extract features to predict protein function. We compare the cross-validation and temporal holdout predictive performance of our method with state-of-the-art methods, including the recently proposed method Mashup. Our results show that our method outperforms previous methods for both human and yeast STRING networks. We also show substantial improvement in the performance of our method in predicting GO terms of varying type and specificity. deepNF is freely available at: https://github.com/VGligorijevic/deepNF. vgligorijevic@flatironinstitute.org, rb133@nyu.edu. Supplementary data are available at Bioinformatics online.
Chen, Zhiye; Chen, Xiaoyan; Liu, Mengqi; Dong, Zhao; Ma, Lin; Yu, Shengyuan
2017-12-01
Functional connectivity density (FCD) could identify the abnormal intrinsic and spontaneous activity over the whole brain, and a seed-based resting-state functional connectivity (RSFC) could further reveal the altered functional network with the identified brain regions. This may be an effective assessment strategy for headache research. This study is to investigate the RSFC architecture changes of the brain in the patients with medication overuse headache (MOH) using FCD and RSFC methods. 3D structure images and resting-state functional MRI data were obtained from 37 MOH patients, 18 episodic migraine (EM) patients and 32 normal controls (NCs). FCD was calculated to detect the brain regions with abnormal functional activity over the whole brain, and the seed-based RSFC was performed to explore the functional network changes in MOH and EM. The decreased FCD located in right parahippocampal gyrus, and the increased FCD located in left inferior parietal gyrus and right supramarginal gyrus in MOH compared with NC, and in right caudate and left insula in MOH compared with EM. RSFC revealed that decreased functional connectivity of the brain regions with decreased FCD anchored in the right dorsal-lateral prefrontal cortex, right frontopolar cortex in MOH, and in left temporopolar cortex and bilateral visual cortices in EM compared with NC, and in frontal-temporal-parietal pattern in MOH compared with EM. These results provided evidence that MOH and EM suffered from altered intrinsic functional connectivity architecture, and the current study presented a new perspective for understanding the neuromechanism of MOH and EM pathogenesis.
Pujol, Jesus; Blanco-Hinojo, Laura; Esteba-Castillo, Susanna; Caixàs, Assumpta; Harrison, Ben J.; Bueno, Marta; Deus, Joan; Rigla, Mercedes; Macià, Dídac; Llorente-Onaindia, Jone; Novell-Alsina, Ramón
2016-01-01
Background Prader Willi syndrome is a genetic disorder with a behavioural expression characterized by the presence of obsessive–compulsive phenomena ranging from elaborate obsessive eating behaviour to repetitive skin picking. Obsessive–compulsive disorder (OCD) has been recently associated with abnormal functional coupling between the frontal cortex and basal ganglia. We have tested the potential association of functional connectivity anomalies in basal ganglia circuits with obsessive–compulsive behaviour in patients with Prader Willi syndrome. Methods We analyzed resting-state functional MRI in adult patients and healthy controls. Whole-brain functional connectivity maps were generated for the dorsal and ventral aspects of the caudate nucleus and putamen. A selected obsessive–compulsive behaviour assessment included typical OCD compulsions, self picking and obsessive eating behaviour. Results We included 24 adults with Prader Willi syndrome and 29 controls in our study. Patients with Prader Willi syndrome showed abnormal functional connectivity between the prefrontal cortex and basal ganglia and within subcortical structures that correlated with the presence and severity of obsessive–compulsive behaviours. In addition, abnormally heightened functional connectivity was identified in the primary sensorimotor cortex–putamen loop, which was strongly associated with self picking. Finally, obsessive eating behaviour correlated with abnormal functional connectivity both within the basal ganglia loops and between the striatum and the hypothalamus and the amygdala. Limitations Limitations of the study include the difficulty in evaluating the nature of content of obsessions in patients with Prader Willi Syndrome and the risk of excessive head motion artifact on brain imaging. Conclusion Patients with Prader Willi syndrome showed broad functional connectivity anomalies combining prefrontal loop alterations characteristic of OCD with 1) enhanced coupling in the primary sensorimotor loop that correlated with the most impulsive aspects of the behaviour and 2) reduced coupling of the ventral striatum with limbic structures for basic internal homeostasis that correlated with the obsession to eat. PMID:26645739
Starck, Tuomo; Nikkinen, Juha; Rahko, Jukka; Remes, Jukka; Hurtig, Tuula; Haapsamo, Helena; Jussila, Katja; Kuusikko-Gauffin, Sanna; Mattila, Marja-Leena; Jansson-Verkasalo, Eira; Pauls, David L; Ebeling, Hanna; Moilanen, Irma; Tervonen, Osmo; Kiviniemi, Vesa J
2013-01-01
In resting state functional magnetic resonance imaging (fMRI) studies of autism spectrum disorders (ASDs) decreased frontal-posterior functional connectivity is a persistent finding. However, the picture of the default mode network (DMN) hypoconnectivity remains incomplete. In addition, the functional connectivity analyses have been shown to be susceptible even to subtle motion. DMN hypoconnectivity in ASD has been specifically called for re-evaluation with stringent motion correction, which we aimed to conduct by so-called scrubbing. A rich set of default mode subnetworks can be obtained with high dimensional group independent component analysis (ICA) which can potentially provide more detailed view of the connectivity alterations. We compared the DMN connectivity in high-functioning adolescents with ASDs to typically developing controls using ICA dual-regression with decompositions from typical to high dimensionality. Dual-regression analysis within DMN subnetworks did not reveal alterations but connectivity between anterior and posterior DMN subnetworks was decreased in ASD. The results were very similar with and without motion scrubbing thus indicating the efficacy of the conventional motion correction methods combined with ICA dual-regression. Specific dissociation between DMN subnetworks was revealed on high ICA dimensionality, where networks centered at the medial prefrontal cortex and retrosplenial cortex showed weakened coupling in adolescents with ASDs compared to typically developing control participants. Generally the results speak for disruption in the anterior-posterior DMN interplay on the network level whereas local functional connectivity in DMN seems relatively unaltered.
Gay, Charles W; Robinson, Michael E; Lai, Song; O'Shea, Andrew; Craggs, Jason G; Price, Donald D; Staud, Roland
2016-02-01
Although altered resting-state functional connectivity (FC) is a characteristic of many chronic pain conditions, it has not yet been evaluated in patients with chronic fatigue. Our objective was to investigate the association between fatigue and altered resting-state FC in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Thirty-six female subjects, 19 ME/CFS and 17 healthy controls, completed a fatigue inventory before undergoing functional magnetic resonance imaging. Two methods, (1) data driven and (2) model based, were used to estimate and compare the intraregional FC between both groups during the resting state (RS). The first approach using independent component analysis was applied to investigate five RS networks: the default mode network, salience network (SN), left frontoparietal networks (LFPN) and right frontoparietal networks, and the sensory motor network (SMN). The second approach used a priori selected seed regions demonstrating abnormal regional cerebral blood flow (rCBF) in ME/CFS patients at rest. In ME/CFS patients, Method-1 identified decreased intrinsic connectivity among regions within the LFPN. Furthermore, the FC of the left anterior midcingulate with the SMN and the connectivity of the left posterior cingulate cortex with the SN were significantly decreased. For Method-2, five distinct clusters within the right parahippocampus and occipital lobes, demonstrating significant rCBF reductions in ME/CFS patients, were used as seeds. The parahippocampal seed and three occipital lobe seeds showed altered FC with other brain regions. The degree of abnormal connectivity correlated with the level of self-reported fatigue. Our results confirm altered RS FC in patients with ME/CFS, which was significantly correlated with the severity of their chronic fatigue.
Gay, Charles W.; Robinson, Michael E.; Lai, Song; O'Shea, Andrew; Craggs, Jason G.; Price, Donald D.
2016-01-01
Abstract Although altered resting-state functional connectivity (FC) is a characteristic of many chronic pain conditions, it has not yet been evaluated in patients with chronic fatigue. Our objective was to investigate the association between fatigue and altered resting-state FC in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Thirty-six female subjects, 19 ME/CFS and 17 healthy controls, completed a fatigue inventory before undergoing functional magnetic resonance imaging. Two methods, (1) data driven and (2) model based, were used to estimate and compare the intraregional FC between both groups during the resting state (RS). The first approach using independent component analysis was applied to investigate five RS networks: the default mode network, salience network (SN), left frontoparietal networks (LFPN) and right frontoparietal networks, and the sensory motor network (SMN). The second approach used a priori selected seed regions demonstrating abnormal regional cerebral blood flow (rCBF) in ME/CFS patients at rest. In ME/CFS patients, Method-1 identified decreased intrinsic connectivity among regions within the LFPN. Furthermore, the FC of the left anterior midcingulate with the SMN and the connectivity of the left posterior cingulate cortex with the SN were significantly decreased. For Method-2, five distinct clusters within the right parahippocampus and occipital lobes, demonstrating significant rCBF reductions in ME/CFS patients, were used as seeds. The parahippocampal seed and three occipital lobe seeds showed altered FC with other brain regions. The degree of abnormal connectivity correlated with the level of self-reported fatigue. Our results confirm altered RS FC in patients with ME/CFS, which was significantly correlated with the severity of their chronic fatigue. PMID:26449441
On the Inference of Functional Circadian Networks Using Granger Causality
Pourzanjani, Arya; Herzog, Erik D.; Petzold, Linda R.
2015-01-01
Being able to infer one way direct connections in an oscillatory network such as the suprachiastmatic nucleus (SCN) of the mammalian brain using time series data is difficult but crucial to understanding network dynamics. Although techniques have been developed for inferring networks from time series data, there have been no attempts to adapt these techniques to infer directional connections in oscillatory time series, while accurately distinguishing between direct and indirect connections. In this paper an adaptation of Granger Causality is proposed that allows for inference of circadian networks and oscillatory networks in general called Adaptive Frequency Granger Causality (AFGC). Additionally, an extension of this method is proposed to infer networks with large numbers of cells called LASSO AFGC. The method was validated using simulated data from several different networks. For the smaller networks the method was able to identify all one way direct connections without identifying connections that were not present. For larger networks of up to twenty cells the method shows excellent performance in identifying true and false connections; this is quantified by an area-under-the-curve (AUC) 96.88%. We note that this method like other Granger Causality-based methods, is based on the detection of high frequency signals propagating between cell traces. Thus it requires a relatively high sampling rate and a network that can propagate high frequency signals. PMID:26413748
Connecting Formal and Informal Learning Experiences
ERIC Educational Resources Information Center
O'Mahony, Timothy Kieran
2010-01-01
The learning study reports on part of a larger project being lead by the author. In this dissertation I explore one goal of this project--to understand effects on student learning outcomes as a function of using different methods for connecting out-of-school experiential learning with formal school-based instruction. There is a long history of…
Fair, Damien A.; Schlaggar, Bradley L.; Cohen B.A., Alexander L.; Miezin, Francis M.; Dosenbach, Nico U.F.; Wenger, Kristin K.; Fox, Michael D.; Snyder, Abraham Z.; Raichle, Marcus E.; Petersen, Steven E.
2007-01-01
Resting state functional connectivity MRI (fcMRI) has become a particularly useful tool for studying regional relationships in typical and atypical populations. Because many investigators have already obtained large datasets of task related fMRI, the ability to use this existing task data for resting state fcMRI is of considerable interest. Two classes of datasets could potentially be modified to emulate resting state data. These datasets include: 1) “interleaved” resting blocks from blocked or mixed blocked/event-related sets, and 2) residual timecourses from event-related sets that lack rest blocks. Using correlation analysis, we compared the functional connectivity of resting epochs taken from a mixed blocked/event-related design fMRI data set and the residuals derived from event-related data with standard continuous resting state data to determine which class of data can best emulate resting state data. We show that despite some differences, the functional connectivity for the interleaved resting periods taken from blocked designs is both qualitatively and quantitatively very similar to that of “continuous” resting state data. In contrast, despite being qualitatively similar to “continuous” resting state data, residuals derived from event-related design data had several distinct quantitative differences. These results suggest that the interleaved resting state data such as those taken from blocked or mixed blocked/event-related fMRI designs are well-suited for resting state functional connectivity analyses. Although using event-related data residuals for resting state functional connectivity may still be useful, results should be interpreted with care. PMID:17239622
Mash, Lisa E; Reiter, Maya A; Linke, Annika C; Townsend, Jeanne; Müller, Ralph-Axel
2018-05-01
Atypical functional connectivity has been implicated in autism spectrum disorders (ASDs). However, the literature to date has been largely inconsistent, with mixed and conflicting reports of hypo- and hyper-connectivity. These discrepancies are partly due to differences between various neuroimaging modalities. Functional magnetic resonance imaging (fMRI), electroencephalography (EEG), and magnetoencephalography (MEG) measure distinct indices of functional connectivity (e.g., blood-oxygenation level-dependent [BOLD] signal vs. electrical activity). Furthermore, each method has unique benefits and disadvantages with respect to spatial and temporal resolution, vulnerability to specific artifacts, and practical implementation. Thus far, functional connectivity research on ASDs has remained almost exclusively unimodal; therefore, interpreting findings across modalities remains a challenge. Multimodal integration of fMRI, EEG, and MEG data is critical in resolving discrepancies in the literature, and working toward a unifying framework for interpreting past and future findings. This review aims to provide a theoretical foundation for future multimodal research on ASDs. First, we will discuss the merits and shortcomings of several popular theories in ASD functional connectivity research, using examples from the literature to date. Next, the neurophysiological relationships between imaging modalities, including their relationship with invasive neural recordings, will be reviewed. Finally, methodological approaches to multimodal data integration will be presented, and their future application to ASDs will be discussed. Analyses relating transient patterns of neural activity ("states") are particularly promising. This strategy provides a comparable measure across modalities, captures complex spatiotemporal patterns, and is a natural extension of recent dynamic fMRI research in ASDs. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 456-473, 2018. © 2017 Wiley Periodicals, Inc.
NASA Astrophysics Data System (ADS)
Liu, Yang; Li, Baojuan; Zhang, Xi; Zhang, Linchuan; Li, Liang; Lu, Hongbing
2016-03-01
To explore the alteration in cerebral blood flow (CBF) and functional connectivity between survivors with recent onset post-traumatic stress disorder (PTSD) and without PTSD, survived from the same coal mine flood disaster. In this study, a processing pipeline using arterial spin labeling (ASL) sequence was proposed. Considering low spatial resolution of ASL sequence, a linear regression method was firstly used to correct the partial volume (PV) effect for better CBF estimation. Then the alterations of CBF between two groups were analyzed using both uncorrected and PV-corrected CBF maps. Based on altered CBF regions detected from the CBF analysis as seed regions, the functional connectivity abnormities in PTSD patients was investigated. The CBF analysis using PV-corrected maps indicates CBF deficits in the bilateral frontal lobe, right superior frontal gyrus and right corpus callosum of PTSD patients, while only right corpus callosum was identified in uncorrected CBF analysis. Furthermore, the regional CBF of the right superior frontal gyrus exhibits significantly negative correlation with the symptom severity in PTSD patients. The resting-state functional connectivity indicates increased connectivity between left frontal lobe and right parietal lobe. These results indicate that PV-corrected CBF exhibits more subtle perfusion changes and may benefit further perfusion and connectivity analysis. The symptom-specific perfusion deficits and aberrant connectivity in above memory-related regions may be putative biomarkers for recent onset PTSD induced by a single prolonged trauma exposure and help predict the severity of PTSD.
Du, Yuhui; Pearlson, Godfrey D; Lin, Dongdong; Sui, Jing; Chen, Jiayu; Salman, Mustafa; Tamminga, Carol A.; Ivleva, Elena I.; Sweeney, John A.; Keshavan, Matcheri S.; Clementz, Brett A.; Bustillo, Juan; Calhoun, Vince D.
2017-01-01
Functional magnetic resonance imaging (fMRI) studies have shown altered brain dynamic functional connectivity (DFC) in mental disorders. Here we aim to explore DFC across a spectrum of symptomatically-related disorders including bipolar disorder with psychosis (BPP), schizoaffective disorder (SAD) and schizophrenia (SZ). We introduce a group information guided independent component analysis (GIG-ICA) procedure to estimate both group-level and subject-specific connectivity states from DFC. Using resting-state fMRI data of 238 healthy controls (HCs), 140 BPP, 132 SAD and 113 SZ patients, we identified measures differentiating groups from the whole-brain DFC and traditional static functional connectivity (SFC), separately. Results show that DFC provided more informative measures than SFC. Diagnosis-related connectivity states were evident using DFC analysis. For the dominant state consistent across groups, we found 22 instances of hypoconnectivity (with decreasing trends from HC to BPP to SAD to SZ) mainly involving post-central, frontal and cerebellar cortices as well as 34 examples of hyperconnectivity (with increasing trends HC through SZ) primarily involving thalamus and temporal cortices. Hypoconnectivities/hyperconnectivities also showed negative/positive correlations, respectively, with clinical symptom scores. Specifically, hypoconnectivities linking postcentral and frontal gyri were significantly negatively correlated with the PANSS positive/negative scores. For frontal connectivities, BPP resembled HC while SAD and SZ were more similar. Three connectivities involving the left cerebellar crus differentiated SZ from other groups and one connection linking frontal and fusiform cortices showed a SAD-unique change. In summary, our method is promising for assessing DFC and may yield imaging biomarkers for quantifying the dimension of psychosis. PMID:28294459
Dopamine Modulates the Functional Organization of the Orbitofrontal Cortex.
Kahnt, Thorsten; Tobler, Philippe N
2017-02-08
Neuromodulators such as dopamine can alter the intrinsic firing properties of neurons and may thereby change the configuration of larger functional circuits. The primate orbitofrontal cortex (OFC) receives dopaminergic input from midbrain nuclei, but the role of dopamine in the OFC is still unclear. Here we tested the idea that dopaminergic activity changes the pattern of connectivity between the OFC and the rest of the brain and thereby reconfigures functional networks in the OFC. To this end, we combined double-blind, placebo-controlled pharmacology [D 2 receptor (D2R) antagonist amisulpride] in humans with resting-state functional magnetic resonance imaging and clustering methods. In the placebo group, we replicated previously observed parcellations of the OFC into two and six subregions based on connectivity patterns with the rest of the brain. Most importantly, while the twofold clustering did not differ significantly between groups, blocking D2Rs significantly changed the composition of the sixfold parcellation, suggesting a dopamine-dependent reconfiguration of functional OFC subregions. Moreover, multivariate decoding analyses revealed that amisulpride changed the whole-brain connectivity patterns of individual OFC subregions. In particular, D2R blockade shifted the balance of OFC connectivity from associative areas in the temporal and parietal lobe toward functional connectivity with the frontal cortex. In summary, our results suggest that dopamine alters the composition of functional OFC circuits, possibly indicating a broader role for neuromodulators in the dynamic reconfiguration of functional brain networks. SIGNIFICANCE STATEMENT A key role of any neuromodulator may be the reconfiguration of functional brain circuits. Here we test this idea with regard to dopamine and the organization of functional networks in the orbitofrontal cortex (OFC). We show that blockade of dopamine D 2 receptors has profound effects on the functional connectivity patterns of the OFC, yielding altered connectivity-based subdivisions of this region. Our results suggest that dopamine changes the connectional configuration of the OFC, possibly leading to transitions between different operating modes that favor either sensory input or recurrent processing in the prefrontal cortex. More generally, our findings support a broader role for neuromodulators in the dynamic reconfiguration of functional brain networks and may have clinical implications for understanding the actions of antipsychotic agents. Copyright © 2017 the authors 0270-6474/17/371493-12$15.00/0.
Disruption of functional networks in dyslexia: a whole-brain, data-driven analysis of connectivity.
Finn, Emily S; Shen, Xilin; Holahan, John M; Scheinost, Dustin; Lacadie, Cheryl; Papademetris, Xenophon; Shaywitz, Sally E; Shaywitz, Bennett A; Constable, R Todd
2014-09-01
Functional connectivity analyses of functional magnetic resonance imaging data are a powerful tool for characterizing brain networks and how they are disrupted in neural disorders. However, many such analyses examine only one or a small number of a priori seed regions. Studies that consider the whole brain frequently rely on anatomic atlases to define network nodes, which might result in mixing distinct activation time-courses within a single node. Here, we improve upon previous methods by using a data-driven brain parcellation to compare connectivity profiles of dyslexic (DYS) versus non-impaired (NI) readers in the first whole-brain functional connectivity analysis of dyslexia. Whole-brain connectivity was assessed in children (n = 75; 43 NI, 32 DYS) and adult (n = 104; 64 NI, 40 DYS) readers. Compared to NI readers, DYS readers showed divergent connectivity within the visual pathway and between visual association areas and prefrontal attention areas; increased right-hemisphere connectivity; reduced connectivity in the visual word-form area (part of the left fusiform gyrus specialized for printed words); and persistent connectivity to anterior language regions around the inferior frontal gyrus. Together, findings suggest that NI readers are better able to integrate visual information and modulate their attention to visual stimuli, allowing them to recognize words on the basis of their visual properties, whereas DYS readers recruit altered reading circuits and rely on laborious phonology-based "sounding out" strategies into adulthood. These results deepen our understanding of the neural basis of dyslexia and highlight the importance of synchrony between diverse brain regions for successful reading. © 2013 Society of Biological Psychiatry Published by Society of Biological Psychiatry All rights reserved.
Ferraro, Stefania; Nigri, Anna; Bruzzone, Maria Grazia; Brivio, Luca; Proietti Cecchini, Alberto; Verri, Mattia; Chiapparini, Luisa; Leone, Massimo
2018-01-01
Objective We tested the hypothesis of a defective functional connectivity between the posterior hypothalamus and diencephalic-mesencephalic regions in chronic cluster headache based on: a) clinical and neuro-endocrinological findings in cluster headache patients; b) neuroimaging findings during cluster headache attacks; c) neuroimaging findings in drug-refractory chronic cluster headache patients improved after successful deep brain stimulation. Methods Resting state functional magnetic resonance imaging, associated with a seed-based approach, was employed to investigate the functional connectivity of the posterior hypothalamus in chronic cluster headache patients (n = 17) compared to age and sex-matched healthy subjects (n = 16). Random-effect analyses were performed to study differences between patients and controls in ipsilateral and contralateral-to-the-pain posterior hypothalamus functional connectivity. Results Cluster headache patients showed an increased functional connectivity between the ipsilateral posterior hypothalamus and a number of diencephalic-mesencephalic structures, comprising ventral tegmental area, dorsal nuclei of raphe, and bilateral substantia nigra, sub-thalamic nucleus, and red nucleus ( p < 0.005 FDR-corrected vs . control group). No difference between patients and controls was found comparing the contralateral hypothalami. Conclusions The observed deranged functional connectivity between the posterior ipsilateral hypothalamus and diencephalic-mesencephalic regions in chronic cluster headache patients mainly involves structures that are part of (i.e. ventral tegmental area, substantia nigra) or modulate (dorsal nuclei of raphe, sub-thalamic nucleus) the midbrain dopaminergic systems. The midbrain dopaminergic systems could play a role in cluster headache pathophysiology and in particular in the chronicization process. Future studies are needed to better clarify if this finding is specific to cluster headache or if it represents an unspecific response to chronic pain.
Time-dependence of graph theory metrics in functional connectivity analysis
Chiang, Sharon; Cassese, Alberto; Guindani, Michele; Vannucci, Marina; Yeh, Hsiang J.; Haneef, Zulfi; Stern, John M.
2016-01-01
Brain graphs provide a useful way to computationally model the network structure of the connectome, and this has led to increasing interest in the use of graph theory to quantitate and investigate the topological characteristics of the healthy brain and brain disorders on the network level. The majority of graph theory investigations of functional connectivity have relied on the assumption of temporal stationarity. However, recent evidence increasingly suggests that functional connectivity fluctuates over the length of the scan. In this study, we investigate the stationarity of brain network topology using a Bayesian hidden Markov model (HMM) approach that estimates the dynamic structure of graph theoretical measures of whole-brain functional connectivity. In addition to extracting the stationary distribution and transition probabilities of commonly employed graph theory measures, we propose two estimators of temporal stationarity: the S-index and N-index. These indexes can be used to quantify different aspects of the temporal stationarity of graph theory measures. We apply the method and proposed estimators to resting-state functional MRI data from healthy controls and patients with temporal lobe epilepsy. Our analysis shows that several graph theory measures, including small-world index, global integration measures, and betweenness centrality, may exhibit greater stationarity over time and therefore be more robust. Additionally, we demonstrate that accounting for subject-level differences in the level of temporal stationarity of network topology may increase discriminatory power in discriminating between disease states. Our results confirm and extend findings from other studies regarding the dynamic nature of functional connectivity, and suggest that using statistical models which explicitly account for the dynamic nature of functional connectivity in graph theory analyses may improve the sensitivity of investigations and consistency across investigations. PMID:26518632
Time-dependence of graph theory metrics in functional connectivity analysis.
Chiang, Sharon; Cassese, Alberto; Guindani, Michele; Vannucci, Marina; Yeh, Hsiang J; Haneef, Zulfi; Stern, John M
2016-01-15
Brain graphs provide a useful way to computationally model the network structure of the connectome, and this has led to increasing interest in the use of graph theory to quantitate and investigate the topological characteristics of the healthy brain and brain disorders on the network level. The majority of graph theory investigations of functional connectivity have relied on the assumption of temporal stationarity. However, recent evidence increasingly suggests that functional connectivity fluctuates over the length of the scan. In this study, we investigate the stationarity of brain network topology using a Bayesian hidden Markov model (HMM) approach that estimates the dynamic structure of graph theoretical measures of whole-brain functional connectivity. In addition to extracting the stationary distribution and transition probabilities of commonly employed graph theory measures, we propose two estimators of temporal stationarity: the S-index and N-index. These indexes can be used to quantify different aspects of the temporal stationarity of graph theory measures. We apply the method and proposed estimators to resting-state functional MRI data from healthy controls and patients with temporal lobe epilepsy. Our analysis shows that several graph theory measures, including small-world index, global integration measures, and betweenness centrality, may exhibit greater stationarity over time and therefore be more robust. Additionally, we demonstrate that accounting for subject-level differences in the level of temporal stationarity of network topology may increase discriminatory power in discriminating between disease states. Our results confirm and extend findings from other studies regarding the dynamic nature of functional connectivity, and suggest that using statistical models which explicitly account for the dynamic nature of functional connectivity in graph theory analyses may improve the sensitivity of investigations and consistency across investigations. Copyright © 2015 Elsevier Inc. All rights reserved.
Mikell, Charles B.; Youngerman, Brett E.; Liston, Conor; Sisti, Michael B.; Bruce, Jeffrey N.; Small, Scott A.; McKhann, Guy M.
2012-01-01
While a tumour in or abutting primary motor cortex leads to motor weakness, how tumours elsewhere in the frontal or parietal lobes affect functional connectivity in a weak patient is less clear. We hypothesized that diminished functional connectivity in a distributed network of motor centres would correlate with motor weakness in subjects with brain masses. Furthermore, we hypothesized that interhemispheric connections would be most vulnerable to subtle disruptions in functional connectivity. We used task-free functional magnetic resonance imaging connectivity to probe motor networks in control subjects and patients with brain tumours (n = 22). Using a control dataset, we developed a method for automated detection of key nodes in the motor network, including the primary motor cortex, supplementary motor area, premotor area and superior parietal lobule, based on the anatomic location of the hand-motor knob in the primary motor cortex. We then calculated functional connectivity between motor network nodes in control subjects, as well as patients with and without brain masses. We used this information to construct weighted, undirected graphs, which were then compared to variables of interest, including performance on a motor task, the grooved pegboard. Strong connectivity was observed within the identified motor networks between all nodes bilaterally, and especially between the primary motor cortex and supplementary motor area. Reduced connectivity was observed in subjects with motor weakness versus subjects with normal strength (P < 0.001). This difference was driven mostly by decreases in interhemispheric connectivity between the primary motor cortices (P < 0.05) and between the left primary motor cortex and the right premotor area (P < 0.05), as well as other premotor area connections. In the subjects without motor weakness, however, performance on the grooved pegboard did not relate to interhemispheric connectivity, but rather was inversely correlated with connectivity between the left premotor area and left supplementary motor area, for both the left and the right hands (P < 0.01). Finally, two subjects who experienced severe weakness following surgery for their brain tumours were followed longitudinally, and the subject who recovered showed reconstitution of her motor network at follow-up. The subject who was persistently weak did not reconstitute his motor network. Motor weakness in subjects with brain tumours that do not involve primary motor structures is associated with decreased connectivity within motor functional networks, particularly interhemispheric connections. Motor networks become weaker as the subjects become weaker, and may become strong again during motor recovery. PMID:22408270
Molloy, Kevin; Shehu, Amarda
2013-01-01
Many proteins tune their biological function by transitioning between different functional states, effectively acting as dynamic molecular machines. Detailed structural characterization of transition trajectories is central to understanding the relationship between protein dynamics and function. Computational approaches that build on the Molecular Dynamics framework are in principle able to model transition trajectories at great detail but also at considerable computational cost. Methods that delay consideration of dynamics and focus instead on elucidating energetically-credible conformational paths connecting two functionally-relevant structures provide a complementary approach. Effective sampling-based path planning methods originating in robotics have been recently proposed to produce conformational paths. These methods largely model short peptides or address large proteins by simplifying conformational space. We propose a robotics-inspired method that connects two given structures of a protein by sampling conformational paths. The method focuses on small- to medium-size proteins, efficiently modeling structural deformations through the use of the molecular fragment replacement technique. In particular, the method grows a tree in conformational space rooted at the start structure, steering the tree to a goal region defined around the goal structure. We investigate various bias schemes over a progress coordinate for balance between coverage of conformational space and progress towards the goal. A geometric projection layer promotes path diversity. A reactive temperature scheme allows sampling of rare paths that cross energy barriers. Experiments are conducted on small- to medium-size proteins of length up to 214 amino acids and with multiple known functionally-relevant states, some of which are more than 13Å apart of each-other. Analysis reveals that the method effectively obtains conformational paths connecting structural states that are significantly different. A detailed analysis on the depth and breadth of the tree suggests that a soft global bias over the progress coordinate enhances sampling and results in higher path diversity. The explicit geometric projection layer that biases the exploration away from over-sampled regions further increases coverage, often improving proximity to the goal by forcing the exploration to find new paths. The reactive temperature scheme is shown effective in increasing path diversity, particularly in difficult structural transitions with known high-energy barriers.
NASA Astrophysics Data System (ADS)
Abd-Elhameed, W. M.
2017-07-01
In this paper, a new formula relating Jacobi polynomials of arbitrary parameters with the squares of certain fractional Jacobi functions is derived. The derived formula is expressed in terms of a certain terminating hypergeometric function of the type _4F3(1) . With the aid of some standard reduction formulae such as Pfaff-Saalschütz's and Watson's identities, the derived formula can be reduced in simple forms which are free of any hypergeometric functions for certain choices of the involved parameters of the Jacobi polynomials and the Jacobi functions. Some other simplified formulae are obtained via employing some computer algebra algorithms such as the algorithms of Zeilberger, Petkovsek and van Hoeij. Some connection formulae between some Jacobi polynomials are deduced. From these connection formulae, some other linearization formulae of Chebyshev polynomials are obtained. As an application to some of the introduced formulae, a numerical algorithm for solving nonlinear Riccati differential equation is presented and implemented by applying a suitable spectral method.
Fiori, Simona; Guzzetta, Andrea; Pannek, Kerstin; Ware, Robert S.; Rossi, Giuseppe; Klingels, Katrijn; Feys, Hilde; Coulthard, Alan; Cioni, Giovanni; Rose, Stephen; Boyd, Roslyn N.
2015-01-01
Aim To provide first evidence of construct validity of a semi-quantitative scale for brain structural MRI (sqMRI scale) in children with unilateral cerebral palsy (UCP) secondary to periventricular white matter (PWM) lesions, by examining the relationship with hand sensorimotor function and whole brain structural connectivity. Methods Cross-sectional study of 50 children with UCP due to PWM lesions using 3 T (MRI), diffusion MRI and assessment of hand sensorimotor function. We explored the relationship of lobar, hemispheric and global scores on the sqMRI scale, with fractional anisotropy (FA), as a measure of brain white matter microstructure, and with hand sensorimotor measures (Assisting Hand Assessment, AHA; Jebsen–Taylor Test for Hand Function, JTTHF; Melbourne Assessment of Unilateral Upper Limb Function, MUUL; stereognosis; 2-point discrimination). Results Lobar and hemispheric scores on the sqMRI scale contralateral to the clinical side of hemiplegia correlated with sensorimotor paretic hand function measures and FA of a number of brain structural connections, including connections of brain areas involved in motor control (postcentral, precentral and paracentral gyri in the parietal lobe). More severe lesions correlated with lower sensorimotor performance, with the posterior limb of internal capsule score being the strongest contributor to impaired hand function. Conclusion The sqMRI scale demonstrates first evidence of construct validity against impaired motor and sensory function measures and brain structural connectivity in a cohort of children with UCP due to PWM lesions. More severe lesions correlated with poorer paretic hand sensorimotor function and impaired structural connectivity in the hemisphere contralateral to the clinical side of hemiplegia. The quantitative structural MRI scoring may be a useful clinical tool for studying brain structure–function relationships but requires further validation in other populations of CP. PMID:26106533
Zeng, Ling-Li; Wang, Huaning; Hu, Panpan; Yang, Bo; Pu, Weidan; Shen, Hui; Chen, Xingui; Liu, Zhening; Yin, Hong; Tan, Qingrong; Wang, Kai; Hu, Dewen
2018-04-01
A lack of a sufficiently large sample at single sites causes poor generalizability in automatic diagnosis classification of heterogeneous psychiatric disorders such as schizophrenia based on brain imaging scans. Advanced deep learning methods may be capable of learning subtle hidden patterns from high dimensional imaging data, overcome potential site-related variation, and achieve reproducible cross-site classification. However, deep learning-based cross-site transfer classification, despite less imaging site-specificity and more generalizability of diagnostic models, has not been investigated in schizophrenia. A large multi-site functional MRI sample (n = 734, including 357 schizophrenic patients from seven imaging resources) was collected, and a deep discriminant autoencoder network, aimed at learning imaging site-shared functional connectivity features, was developed to discriminate schizophrenic individuals from healthy controls. Accuracies of approximately 85·0% and 81·0% were obtained in multi-site pooling classification and leave-site-out transfer classification, respectively. The learned functional connectivity features revealed dysregulation of the cortical-striatal-cerebellar circuit in schizophrenia, and the most discriminating functional connections were primarily located within and across the default, salience, and control networks. The findings imply that dysfunctional integration of the cortical-striatal-cerebellar circuit across the default, salience, and control networks may play an important role in the "disconnectivity" model underlying the pathophysiology of schizophrenia. The proposed discriminant deep learning method may be capable of learning reliable connectome patterns and help in understanding the pathophysiology and achieving accurate prediction of schizophrenia across multiple independent imaging sites. Copyright © 2018 German Center for Neurodegenerative Diseases (DZNE). Published by Elsevier B.V. All rights reserved.
ERIC Educational Resources Information Center
Kostinskiy, Sergey S.; Troitskiy, Anatoly I.
2016-01-01
This article deals with the problem of calculating the additional real-power losses in double-wound supply transformers with voltage class 6 (10)/0,4 kV, caused by unbalanced active inductive load connected in a star connection with an insulated neutral. When solving the problem, authors used the theory of electric circuits, method of balanced…
Abnormal interhemispheric connectivity in male psychopathic offenders
Hoppenbrouwers, Sylco S.; De Jesus, Danilo R.; Sun, Yinming; Stirpe, Tania; Hofman, Dennis; McMaster, Jeff; Hughes, Ginny; Daskalakis, Zafiris J.; Schutter, Dennis J.L.G.
2014-01-01
Background Psychopathic offenders inevitably violate interpersonal norms and frequently resort to aggressive and criminal behaviour. The affective and cognitive deficits underlying these behaviours have been linked to abnormalities in functional interhemispheric connectivity. However, direct neurophysiological evidence for dysfunctional connectivity in psychopathic offenders is lacking. Methods We used transcranial magnetic stimulation combined with electroencephalography to examine interhemispheric connectivity in the dorsolateral and motor cortex in a sample of psychopathic offenders and healthy controls. We also measured intracortical inhibition and facilitation over the left and right motor cortex to investigate the effects of local cortical processes on interhemispheric connectivity. Results We enrolled 17 psychopathic offenders and 14 controls in our study. Global abnormalities in right to left functional connectivity were observed in psychopathic offenders compared with controls. Furthermore, in contrast to controls, psychopathic offenders showed increased intracortical inhibition in the right, but not the left, hemisphere. Limitations The relatively small sample size limited the sensitivity to show that the abnormalities in interhemispheric connectivity were specifically related to the dorsolateral prefrontal cortex in psychopathic offenders. Conclusion To our knowledge, this study provides the first neurophysiological evidence for abnormal interhemispheric connectivity in psychopathic offenders and may further our understanding of the disruptive antisocial behaviour of these offenders. PMID:23937798
Resting state functional MRI reveals abnormal network connectivity in neurofibromatosis 1.
Tomson, Steffie N; Schreiner, Matthew J; Narayan, Manjari; Rosser, Tena; Enrique, Nicole; Silva, Alcino J; Allen, Genevera I; Bookheimer, Susan Y; Bearden, Carrie E
2015-11-01
Neurofibromatosis type I (NF1) is a genetic disorder caused by mutations in the neurofibromin 1 gene at locus 17q11.2. Individuals with NF1 have an increased incidence of learning disabilities, attention deficits, and autism spectrum disorders. As a single-gene disorder, NF1 represents a valuable model for understanding gene-brain-behavior relationships. While mouse models have elucidated molecular and cellular mechanisms underlying learning deficits associated with this mutation, little is known about functional brain architecture in human subjects with NF1. To address this question, we used resting state functional connectivity magnetic resonance imaging (rs-fcMRI) to elucidate the intrinsic network structure of 30 NF1 participants compared with 30 healthy demographically matched controls during an eyes-open rs-fcMRI scan. Novel statistical methods were employed to quantify differences in local connectivity (edge strength) and modularity structure, in combination with traditional global graph theory applications. Our findings suggest that individuals with NF1 have reduced anterior-posterior connectivity, weaker bilateral edges, and altered modularity clustering relative to healthy controls. Further, edge strength and modular clustering indices were correlated with IQ and internalizing symptoms. These findings suggest that Ras signaling disruption may lead to abnormal functional brain connectivity; further investigation into the functional consequences of these alterations in both humans and in animal models is warranted. © 2015 Wiley Periodicals, Inc.
Qiao, Jianping; Weng, Shenhong; Wang, Pengwei; Long, Jun; Wang, Zhishun
2015-05-01
The aim of this study was to investigate the normalization of the intrinsic functional activity and connectivity of TS adolescents before and after the cranial electrotherapy stimulation (CES) with alpha stim device. We performed resting-state functional magnetic resonance imaging on eight adolescents before and after CES with mean age of about nine-years old who had Tourette's syndrome with moderate to severe tics symptom. Independent component analysis (ICA) with hierarchical partner matching method was used to examine the functional connectivity between regions within cortico-striato-thalamo-cortical (CSTC) circuit. Granger causality was used to investigate effective connectivity among these regions detected by ICA. We then performed pattern classification on independent components with significant group differences that served as endophenotype markers to distinguish the adolescents between TS and the normalized ones after CES. Results showed that TS adolescents after CES treatment had stronger functional activity and connectivity in anterior cingulate cortex (ACC), caudate and posterior cingulate cortex while had weaker activity in supplementary motor area within the motor pathway compared with TS before CES. The results suggest that the functional activity and connectivity in motor pathway was suppressed while activities in the control portions within CSTC loop including ACC and caudate were increased in TS adolescents after CES compared with adolescents before CES. The normalization of the balance between motor and control portions of the CSTC circuit may result in the recovery of TS adolescents.
Resting state functional MRI reveals abnormal network connectivity in Neurofibromatosis 1
Tomson, S.N.; Schreiner, M.; Narayan, M.; Rosser, Tena; Enrique, Nicole; Silva, Alcino J.; Allen, G.I.; Bookheimer, S.Y.; Bearden, C.E.
2015-01-01
Neurofibromatosis type I (NF1) is a genetic disorder caused by mutations in the neurofibromin 1 gene at locus 17q11.2. Individuals with NF1 have an increased incidence of learning disabilities, attention deficits and autism spectrum disorders. As a single gene disorder, NF1 represents a valuable model for understanding gene-brain-behavior relationships. While mouse models have elucidated molecular and cellular mechanisms underlying learning deficits associated with this mutation, little is known about functional brain architecture in human subjects with NF1. To address this question, we used resting state functional connectivity MRI (rs-fcMRI) to elucidate the intrinsic network structure of 30 NF1 participants compared with 30 healthy demographically matched controls during an eyes-open rs-fcMRI scan. Novel statistical methods were employed to quantify differences in local connectivity (edge strength) and modularity structure, in combination with traditional global graph theory applications. Our findings suggest that individuals with NF1 have reduced anterior-posterior connectivity, weaker bilateral edges, and altered modularity clustering relative to healthy controls. Further, edge strength and modular clustering indices were correlated with IQ and internalizing symptoms. These findings suggest that Ras signaling disruption may lead to abnormal functional brain connectivity; further investigation into the functional consequences of these alterations in both humans and in animal models is warranted. PMID:26304096
Analysis of turbine-grid interaction of grid-connected wind turbine using HHT
NASA Astrophysics Data System (ADS)
Chen, A.; Wu, W.; Miao, J.; Xie, D.
2018-05-01
This paper processes the output power of the grid-connected wind turbine with the denoising and extracting method based on Hilbert Huang transform (HHT) to discuss the turbine-grid interaction. At first, the detailed Empirical Mode Decomposition (EMD) and the Hilbert Transform (HT) are introduced. Then, on the premise of decomposing the output power of the grid-connected wind turbine into a series of Intrinsic Mode Functions (IMFs), energy ratio and power volatility are calculated to detect the unessential components. Meanwhile, combined with vibration function of turbine-grid interaction, data fitting of instantaneous amplitude and phase of each IMF is implemented to extract characteristic parameters of different interactions. Finally, utilizing measured data of actual parallel-operated wind turbines in China, this work accurately obtains the characteristic parameters of turbine-grid interaction of grid-connected wind turbine.
Bhaya, Amit; Kaszkurewicz, Eugenius
2004-01-01
It is pointed out that the so called momentum method, much used in the neural network literature as an acceleration of the backpropagation method, is a stationary version of the conjugate gradient method. Connections with the continuous optimization method known as heavy ball with friction are also made. In both cases, adaptive (dynamic) choices of the so called learning rate and momentum parameters are obtained using a control Liapunov function analysis of the system.
Shih, Patricia; Keehn, Brandon; Oram, Jessica K.; Leyden, Kelly M.; Keown, Christopher L.; Müller, Ralph-Axel
2012-01-01
Background Socio-communicative impairments are salient features of autism spectrum disorder (ASD). Abnormal development of posterior superior temporal sulcus (pSTS), a key processing area for language, biological motion, and social context, may play a role in these deficits. Methods Functional connectivity MRI (fcMRI) was used to examine the synchronization of low frequency BOLD fluctuations during continuous performance on a visual search task. Twenty-one children and adolescents with ASD and 26 typically developing (TD) individuals, matched on age, sex, and IQ, participated in the study. Three subregions of pSTS were delineated with a data-driven approach, and differentiation of pSTS was examined by comparing the connectivity of each subregion. Results In TD individuals, differentiation of networks was positively associated with age and anatomical maturation (cortical thinning in pSTS, greater white matter volume). In the ASD group, differentiation of pSTS connectivity was significantly reduced and correlations with anatomical measures were weak or absent. Moreover, pSTS differentiation was inversely correlated with autism symptom severity. Conclusions Atypical maturation of pSTS suggests altered trajectories for functional segregation and integration of networks in ASD, potentially related to impaired cognitive and sensorimotor development. Furthermore, our findings provide a novel explanation for atypically increased connectivity in ASD observed in some fcMRI studies. PMID:21601832
NASA Astrophysics Data System (ADS)
Bouslema, Marwa; Frikha, Ahmed; Abdennadhar, Moez; Fakhfakh, Tahar; Nasri, Rachid; Haddar, Mohamed
2017-12-01
The present paper is aimed at the application of a substructure methodology, based on the Frequency Response Function (FRF) simulation technique, to analyze the vibration of a stage reducer connected by a rigid coupling to a planetary gear system. The computation of the vibration response was achieved using the FRF-based substructuring method. First of all, the two subsystems were analyzed separately and their FRF were obtained. Then the coupled model was analyzed indirectly using the substructuring technique. A comparison between the full system response and the coupled model response using the FRF substructuring was investigated to validate the coupling method. Furthermore, a parametric study of the effect of the shaft coupling stiffness on the FRF was discussed and the effects of modal truncation and condensation methods on the FRF of subsystems were analyzed.
Sun, Ya-wen; Chen, Xue; Ding, Wei-na; Wang, Wei; Li, Wei; Du, Ya-song
2015-01-01
Purposes Recent neuroimaging studies have shown that people with Internet gaming disorder (IGD) have structural and functional abnormalities in specific brain areas and connections. However, little is known about the alterations of the interhemispheric resting-state functional connectivity (rsFC) in participants with IGD. In the present study, we used a newly developed voxel-mirrored homotopic connectivity (VMHC) method to investigate the interhemispheric rsFC of the whole brain in participants with IGD. Methods We compared interhemispheric rsFC between 17 participants with IGD and 24 healthy controls, group-matched on age, gender, and education status. All participants were provided written informed consent. Resting-state functional and structural magnetic resonance images were acquired for all participants. The rsFC between bilateral homotopic voxels was calculated. Regions showing abnormal VMHC in IGD participants were adopted as regions of interest for correlation analyses. Results Compared to healthy controls, IGD participants showed decreased VMHC between the left and right superior frontal gyrus (orbital part), inferior frontal gyrus (orbital part), middle frontal gyrus and superior frontal gyrus. Further analyses showed Chen Internet Addiction Scale (CIAS)-related VMHC in superior frontal gyrus (orbital part) and CIAS (r = −0.55, p = 0.02, uncorrected). Conclusions Our findings implicate the important role of altered interhemispheric rsFC in the bilateral prefrontal lobe in the neuropathological mechanism of IGD, and provide further supportive evidence for the reclassification of IGD as a behavioral addiction. PMID:25738502
Feature Extraction with GMDH-Type Neural Networks for EEG-Based Person Identification.
Schetinin, Vitaly; Jakaite, Livija; Nyah, Ndifreke; Novakovic, Dusica; Krzanowski, Wojtek
2018-08-01
The brain activity observed on EEG electrodes is influenced by volume conduction and functional connectivity of a person performing a task. When the task is a biometric test the EEG signals represent the unique "brain print", which is defined by the functional connectivity that is represented by the interactions between electrodes, whilst the conduction components cause trivial correlations. Orthogonalization using autoregressive modeling minimizes the conduction components, and then the residuals are related to features correlated with the functional connectivity. However, the orthogonalization can be unreliable for high-dimensional EEG data. We have found that the dimensionality can be significantly reduced if the baselines required for estimating the residuals can be modeled by using relevant electrodes. In our approach, the required models are learnt by a Group Method of Data Handling (GMDH) algorithm which we have made capable of discovering reliable models from multidimensional EEG data. In our experiments on the EEG-MMI benchmark data which include 109 participants, the proposed method has correctly identified all the subjects and provided a statistically significant ([Formula: see text]) improvement of the identification accuracy. The experiments have shown that the proposed GMDH method can learn new features from multi-electrode EEG data, which are capable to improve the accuracy of biometric identification.
NASA Astrophysics Data System (ADS)
Lopour, Beth A.; Staba, Richard J.; Stern, John M.; Fried, Itzhak; Ringach, Dario L.
2016-04-01
Objective. Quantifying the relationship between microelectrode-recorded multi-unit activity (MUA) and local field potentials (LFPs) in distinct brain regions can provide detailed information on the extent of functional connectivity in spatially widespread networks. These methods are common in studies of cognition using non-human animal models, but are rare in humans. Here we applied a neuronal spike-triggered impulse response to electrophysiological recordings from the human epileptic brain for the first time, and we evaluate functional connectivity in relation to brain areas supporting the generation of seizures. Approach. Broadband interictal electrophysiological data were recorded from microwires adapted to clinical depth electrodes that were implanted bilaterally using stereotactic techniques in six presurgical patients with medically refractory epilepsy. MUA and LFPs were isolated in each microwire, and we calculated the impulse response between the MUA on one microwire and the LFPs on a second microwire for all possible MUA/LFP pairs. Results were compared to clinical seizure localization, including sites of seizure onset and interictal epileptiform discharges. Main results. We detected significant interictal long-range functional connections in each subject, in some cases across hemispheres. Results were consistent between two independent datasets, and the timing and location of significant impulse responses reflected anatomical connectivity. However, within individual subjects, the spatial distribution of impulse responses was unique. In two subjects with clear seizure localization and successful surgery, the epileptogenic zone was associated with significant impulse responses. Significance. The results suggest that the spike-triggered impulse response can provide valuable information about the neuronal networks that contribute to seizures using only interictal data. This technique will enable testing of specific hypotheses regarding functional connectivity in epilepsy and the relationship between functional properties and imaging findings. Beyond epilepsy, we expect that the impulse response could be more broadly applied as a measure of long-range functional connectivity in studies of cognition.
Chong, Joanna Su Xian; Liu, Siwei; Loke, Yng Miin; Hilal, Saima; Ikram, Mohammad Kamran; Xu, Xin; Tan, Boon Yeow; Venketasubramanian, Narayanaswamy; Chen, Christopher Li-Hsian; Zhou, Juan
2017-11-01
Network-sensitive neuroimaging methods have been used to characterize large-scale brain network degeneration in Alzheimer's disease and its prodrome. However, few studies have investigated the combined effect of Alzheimer's disease and cerebrovascular disease on brain network degeneration. Our study sought to examine the intrinsic functional connectivity and structural covariance network changes in 235 prodromal and clinical Alzheimer's disease patients with and without cerebrovascular disease. We focused particularly on two higher-order cognitive networks-the default mode network and the executive control network. We found divergent functional connectivity and structural covariance patterns in Alzheimer's disease patients with and without cerebrovascular disease. Alzheimer's disease patients without cerebrovascular disease, but not Alzheimer's disease patients with cerebrovascular disease, showed reductions in posterior default mode network functional connectivity. By comparison, while both groups exhibited parietal reductions in executive control network functional connectivity, only Alzheimer's disease patients with cerebrovascular disease showed increases in frontal executive control network connectivity. Importantly, these distinct executive control network changes were recapitulated in prodromal Alzheimer's disease patients with and without cerebrovascular disease. Across Alzheimer's disease patients with and without cerebrovascular disease, higher default mode network functional connectivity z-scores correlated with greater hippocampal volumes while higher executive control network functional connectivity z-scores correlated with greater white matter changes. In parallel, only Alzheimer's disease patients without cerebrovascular disease showed increased default mode network structural covariance, while only Alzheimer's disease patients with cerebrovascular disease showed increased executive control network structural covariance compared to controls. Our findings demonstrate the differential neural network structural and functional changes in Alzheimer's disease with and without cerebrovascular disease, suggesting that the underlying pathology of Alzheimer's disease patients with cerebrovascular disease might differ from those without cerebrovascular disease and reflect a combination of more severe cerebrovascular disease and less severe Alzheimer's disease network degeneration phenotype. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.
Influence of cerebrovascular disease on brain networks in prodromal and clinical Alzheimer’s disease
Chong, Joanna Su Xian; Liu, Siwei; Loke, Yng Miin; Hilal, Saima; Ikram, Mohammad Kamran; Xu, Xin; Tan, Boon Yeow; Venketasubramanian, Narayanaswamy; Chen, Christopher Li-Hsian
2017-01-01
Abstract Network-sensitive neuroimaging methods have been used to characterize large-scale brain network degeneration in Alzheimer’s disease and its prodrome. However, few studies have investigated the combined effect of Alzheimer’s disease and cerebrovascular disease on brain network degeneration. Our study sought to examine the intrinsic functional connectivity and structural covariance network changes in 235 prodromal and clinical Alzheimer’s disease patients with and without cerebrovascular disease. We focused particularly on two higher-order cognitive networks—the default mode network and the executive control network. We found divergent functional connectivity and structural covariance patterns in Alzheimer’s disease patients with and without cerebrovascular disease. Alzheimer’s disease patients without cerebrovascular disease, but not Alzheimer’s disease patients with cerebrovascular disease, showed reductions in posterior default mode network functional connectivity. By comparison, while both groups exhibited parietal reductions in executive control network functional connectivity, only Alzheimer’s disease patients with cerebrovascular disease showed increases in frontal executive control network connectivity. Importantly, these distinct executive control network changes were recapitulated in prodromal Alzheimer’s disease patients with and without cerebrovascular disease. Across Alzheimer’s disease patients with and without cerebrovascular disease, higher default mode network functional connectivity z-scores correlated with greater hippocampal volumes while higher executive control network functional connectivity z-scores correlated with greater white matter changes. In parallel, only Alzheimer’s disease patients without cerebrovascular disease showed increased default mode network structural covariance, while only Alzheimer’s disease patients with cerebrovascular disease showed increased executive control network structural covariance compared to controls. Our findings demonstrate the differential neural network structural and functional changes in Alzheimer’s disease with and without cerebrovascular disease, suggesting that the underlying pathology of Alzheimer’s disease patients with cerebrovascular disease might differ from those without cerebrovascular disease and reflect a combination of more severe cerebrovascular disease and less severe Alzheimer’s disease network degeneration phenotype. PMID:29053778
Lopour, Beth A; Staba, Richard J; Stern, John M; Fried, Itzhak; Ringach, Dario L
2017-01-01
Objective Quantifying the relationship between microelectrode-recorded multi-unit activity (MUA) and local field potentials (LFPs) in distinct brain regions can provide detailed information on the extent of functional connectivity in spatially widespread networks. These methods are common in studies of cognition using non-human animal models, but are rare in humans. Here we applied a neuronal spike-triggered impulse response to electrophysiological recordings from the human epileptic brain for the first time, and we evaluate functional connectivity in relation to brain areas supporting the generation of seizures. Approach Broadband interictal electrophysiological data were recorded from microwires adapted to clinical depth electrodes that were implanted bilaterally using stereotactic techniques in six presurgical patients with medically refractory epilepsy. MUA and LFPs were isolated in each microwire, and we calculated the impulse response between the MUA on one microwire and the LFPs on a second microwire for all possible MUA/LFP pairs. Results were compared to clinical seizure localization, including sites of seizure onset and interictal epileptiform discharges. Main results We detected significant interictal long-range functional connections in each subject, in some cases across hemispheres. Results were consistent between two independent datasets, and the timing and location of significant impulse responses reflected anatomical connectivity. However, within individual subjects, the spatial distribution of impulse responses was unique. In two subjects with clear seizure localization and successful surgery, the epileptogenic zone was associated with significant impulse responses. Significance The results suggest that the spike-triggered impulse response can provide valuable information about the neuronal networks that contribute to seizures using only interictal data. This technique will enable testing of specific hypotheses regarding functional connectivity in epilepsy and the relationship between functional properties and imaging findings. Beyond epilepsy, we expect that the impulse response could be more broadly applied as a measure of long-range functional connectivity in studies of cognition. PMID:26975603
Thresholding functional connectomes by means of mixture modeling.
Bielczyk, Natalia Z; Walocha, Fabian; Ebel, Patrick W; Haak, Koen V; Llera, Alberto; Buitelaar, Jan K; Glennon, Jeffrey C; Beckmann, Christian F
2018-05-01
Functional connectivity has been shown to be a very promising tool for studying the large-scale functional architecture of the human brain. In network research in fMRI, functional connectivity is considered as a set of pair-wise interactions between the nodes of the network. These interactions are typically operationalized through the full or partial correlation between all pairs of regional time series. Estimating the structure of the latent underlying functional connectome from the set of pair-wise partial correlations remains an open research problem though. Typically, this thresholding problem is approached by proportional thresholding, or by means of parametric or non-parametric permutation testing across a cohort of subjects at each possible connection. As an alternative, we propose a data-driven thresholding approach for network matrices on the basis of mixture modeling. This approach allows for creating subject-specific sparse connectomes by modeling the full set of partial correlations as a mixture of low correlation values associated with weak or unreliable edges in the connectome and a sparse set of reliable connections. Consequently, we propose to use alternative thresholding strategy based on the model fit using pseudo-False Discovery Rates derived on the basis of the empirical null estimated as part of the mixture distribution. We evaluate the method on synthetic benchmark fMRI datasets where the underlying network structure is known, and demonstrate that it gives improved performance with respect to the alternative methods for thresholding connectomes, given the canonical thresholding levels. We also demonstrate that mixture modeling gives highly reproducible results when applied to the functional connectomes of the visual system derived from the n-back Working Memory task in the Human Connectome Project. The sparse connectomes obtained from mixture modeling are further discussed in the light of the previous knowledge of the functional architecture of the visual system in humans. We also demonstrate that with use of our method, we are able to extract similar information on the group level as can be achieved with permutation testing even though these two methods are not equivalent. We demonstrate that with both of these methods, we obtain functional decoupling between the two hemispheres in the higher order areas of the visual cortex during visual stimulation as compared to the resting state, which is in line with previous studies suggesting lateralization in the visual processing. However, as opposed to permutation testing, our approach does not require inference at the cohort level and can be used for creating sparse connectomes at the level of a single subject. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
Cerebro-cerebellar connectivity is increased in primary lateral sclerosis.
Meoded, Avner; Morrissette, Arthur E; Katipally, Rohan; Schanz, Olivia; Gotts, Stephen J; Floeter, Mary Kay
2015-01-01
Increased functional connectivity in resting state networks was found in several studies of patients with motor neuron disorders, although diffusion tensor imaging studies consistently show loss of white matter integrity. To understand the relationship between structural connectivity and functional connectivity, we examined the structural connections between regions with altered functional connectivity in patients with primary lateral sclerosis (PLS), a long-lived motor neuron disease. Connectivity matrices were constructed from resting state fMRI in 16 PLS patients to identify areas of differing connectivity between patients and healthy controls. Probabilistic fiber tracking was used to examine structural connections between regions of differing connectivity. PLS patients had 12 regions with increased functional connectivity compared to controls, with a predominance of cerebro-cerebellar connections. Increased functional connectivity was strongest between the cerebellum and cortical motor areas and between the cerebellum and frontal and temporal cortex. Fiber tracking detected no difference in connections between regions with increased functional connectivity. We conclude that functional connectivity changes are not strongly based in structural connectivity. Increased functional connectivity may be caused by common inputs, or by reduced selectivity of cortical activation, which could result from loss of intracortical inhibition when cortical afferents are intact.
Connection method of separated luminal regions of intestine from CT volumes
NASA Astrophysics Data System (ADS)
Oda, Masahiro; Kitasaka, Takayuki; Furukawa, Kazuhiro; Watanabe, Osamu; Ando, Takafumi; Hirooka, Yoshiki; Goto, Hidemi; Mori, Kensaku
2015-03-01
This paper proposes a connection method of separated luminal regions of the intestine for Crohn's disease diagnosis. Crohn's disease is an inflammatory disease of the digestive tract. Capsule or conventional endoscopic diagnosis is performed for Crohn's disease diagnosis. However, parts of the intestines may not be observed in the endoscopic diagnosis if intestinal stenosis occurs. Endoscopes cannot pass through the stenosed parts. CT image-based diagnosis is developed as an alternative choice of the Crohn's disease. CT image-based diagnosis enables physicians to observe the entire intestines even if stenosed parts exist. CAD systems for Crohn's disease using CT volumes are recently developed. Such CAD systems need to reconstruct separated luminal regions of the intestines to analyze intestines. We propose a connection method of separated luminal regions of the intestines segmented from CT volumes. The luminal regions of the intestines are segmented from a CT volume. The centerlines of the luminal regions are calculated by using a thinning process. We enumerate all the possible sequences of the centerline segments. In this work, we newly introduce a condition using distance between connected ends points of the centerline segments. This condition eliminates unnatural connections of the centerline segments. Also, this condition reduces processing time. After generating a sequence list of the centerline segments, the correct sequence is obtained by using an evaluation function. We connect the luminal regions based on the correct sequence. Our experiments using four CT volumes showed that our method connected 6.5 out of 8.0 centerline segments per case. Processing times of the proposed method were reduced from the previous method.
Disrupted Brain Functional Network Architecture in Chronic Tinnitus Patients
Chen, Yu-Chen; Feng, Yuan; Xu, Jin-Jing; Mao, Cun-Nan; Xia, Wenqing; Ren, Jun; Yin, Xindao
2016-01-01
Purpose: Resting-state functional magnetic resonance imaging (fMRI) studies have demonstrated the disruptions of multiple brain networks in tinnitus patients. Nonetheless, several studies found no differences in network processing between tinnitus patients and healthy controls (HCs). Its neural bases are poorly understood. To identify aberrant brain network architecture involved in chronic tinnitus, we compared the resting-state fMRI (rs-fMRI) patterns of tinnitus patients and HCs. Materials and Methods: Chronic tinnitus patients (n = 24) with normal hearing thresholds and age-, sex-, education- and hearing threshold-matched HCs (n = 22) participated in the current study and underwent the rs-fMRI scanning. We used degree centrality (DC) to investigate functional connectivity (FC) strength of the whole-brain network and Granger causality to analyze effective connectivity in order to explore directional aspects involved in tinnitus. Results: Compared to HCs, we found significantly increased network centrality in bilateral superior frontal gyrus (SFG). Unidirectionally, the left SFG revealed increased effective connectivity to the left middle orbitofrontal cortex (OFC), left posterior lobe of cerebellum (PLC), left postcentral gyrus, and right middle occipital gyrus (MOG) while the right SFG exhibited enhanced effective connectivity to the right supplementary motor area (SMA). In addition, the effective connectivity from the bilateral SFG to the OFC and SMA showed positive correlations with tinnitus distress. Conclusions: Rs-fMRI provides a new and novel method for identifying aberrant brain network architecture. Chronic tinnitus patients have disrupted FC strength and causal connectivity mostly in non-auditory regions, especially the prefrontal cortex (PFC). The current findings will provide a new perspective for understanding the neuropathophysiological mechanisms in chronic tinnitus. PMID:27458377
[Identification of ecological corridors and its importance by integrating circuit theory].
Song, Li Li; Qin, Ming Zhou
2016-10-01
Landscape connectivity is considered as an extraordinarily important factor affecting various ecological processes. The least cost path (LCP) on the basis of minimum cumulative resis-tance model (MCRM) may provide a more efficient approach to identify functional connectivity in heterogeneous landscapes, and is already adopted by the research of landscape functional connecti-vity assessment and ecological corridor simulation. Connectivity model on circuit theory (CMCT) replaced the edges in the graph theory with resistors, cost distance with resistance distance to measure the functional connectivity in heterogeneous landscapes. By means of Linkage Mapper tool and Circuitscape software, the simulated landscape generated from SIMMAP 2.0 software was viewed as the study object in this article, aimed at exploring how to integrate MCRM with CMCT to identify ecological corridors and relative importance of landscape factors. The results showed that two models had their individual advantages and mutual complement. MCRM could effectively identify least cost corridors among habitats. CMCT could effectively identify important landscape factor and pinch point, which had important influence on landscape connectivity. We also found that the position of pinch point was not affected by corridor width, which had obvious advantage in the research of identifying the importance of corridors. The integrated method could provide certain scientific basis for regional ecological protection planning and ecological corridor design.
Patterned Arrays of Functional Lateral Heterostructures via Sequential Template-Directed Printing.
Li, Yifan; Su, Meng; Li, Zheng; Huang, Zhandong; Li, Fengyu; Pan, Qi; Ren, Wanjie; Hu, Xiaotian; Song, Yanlin
2018-04-30
The precise integration of microscale dots and lines with controllable interfacing connections is highly important for the fabrication of functional devices. To date, the solution-processible methods are used to fabricate the heterogeneous micropatterns for different materials. However, for increasingly miniaturized and multifunctional devices, it is extremely challenging to engineer the uncertain kinetics of a solution on the microstructures surfaces, resulting in uncontrollable interface connections and poor device performance. Here, a sequential template-directed printing process is demonstrated for the fabrication of arrayed microdots connected by microwires through the regulation of the Rayleigh-Taylor instability of material solution or suspension. Flexibility in the control of fluidic behaviors can realize precise interface connection between the micropatterns, including the microwires traversing, overlapping or connecting the microdots. Moreover, various morphologies such as circular, rhombic, or star-shaped microdots as well as straight, broken or curved microwires can be achieved. The lateral heterostructure printed with two different quantum dots displays bright dichromatic photoluminescence. The ammonia gas sensor printed by polyaniline and silver nanoparticles exhibits a rapid response time. This strategy can construct heterostructures in a facile manner by eliminating the uncertainty of the multimaterials interface connection, which will be promising for the development of novel lateral functional devices. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Abivardi, Aslan; Bach, Dominik R
2017-08-01
Structural alterations in long-range amygdala connections are proposed to crucially underlie several neuropsychiatric disorders. While progress has been made in elucidating the function of these connections, our understanding of their structure in humans remains sparse and non-systematic. Harnessing diffusion-weighted imaging and probabilistic tractography in humans, we investigate connections between two main amygdala nucleus groups, thalamic nuclei, and cortex. We first parcellated amygdala into deep (basolateral) and superficial (centrocortical) nucleus groups, and thalamus into six subregions, using previously established protocols based on connectivity. Cortex was parcellated based on T1-weighted images. We found substantial amygdala connections to thalamus, with different patterns for the two amygdala nuclei. Crucially, we describe direct subcortical connections between amygdala and paraventricular thalamus. Different from rodents but similar to non-human primates, these are more pronounced for basolateral than centrocortical amygdala. Substantial white-matter connectivity between amygdala and visual pulvinar is also more pronounced for basolateral amygdala. Furthermore, we establish detailed connectivity profiles for basolateral and centrocortical amygdala to cortical regions. These exhibit cascadic connections with sensory cortices as suggested previously based on tracer methods in non-human animals. We propose that the quantitative connectivity profiles provided here may guide future work on normal and pathological function of human amygdala. Hum Brain Mapp 38:3927-3940, 2017. © 2017 Wiley Periodicals, Inc. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.
2017-01-01
Abstract Structural alterations in long‐range amygdala connections are proposed to crucially underlie several neuropsychiatric disorders. While progress has been made in elucidating the function of these connections, our understanding of their structure in humans remains sparse and non‐systematic. Harnessing diffusion‐weighted imaging and probabilistic tractography in humans, we investigate connections between two main amygdala nucleus groups, thalamic nuclei, and cortex. We first parcellated amygdala into deep (basolateral) and superficial (centrocortical) nucleus groups, and thalamus into six subregions, using previously established protocols based on connectivity. Cortex was parcellated based on T1‐weighted images. We found substantial amygdala connections to thalamus, with different patterns for the two amygdala nuclei. Crucially, we describe direct subcortical connections between amygdala and paraventricular thalamus. Different from rodents but similar to non‐human primates, these are more pronounced for basolateral than centrocortical amygdala. Substantial white‐matter connectivity between amygdala and visual pulvinar is also more pronounced for basolateral amygdala. Furthermore, we establish detailed connectivity profiles for basolateral and centrocortical amygdala to cortical regions. These exhibit cascadic connections with sensory cortices as suggested previously based on tracer methods in non‐human animals. We propose that the quantitative connectivity profiles provided here may guide future work on normal and pathological function of human amygdala. Hum Brain Mapp 38:3927–3940, 2017. © 2017 Wiley Periodicals, Inc. PMID:28512761
Estimating Fast Neural Input Using Anatomical and Functional Connectivity
Eriksson, David
2016-01-01
In the last 20 years there has been an increased interest in estimating signals that are sent between neurons and brain areas. During this time many new methods have appeared for measuring those signals. Here we review a wide range of methods for which connected neurons can be identified anatomically, by tracing axons that run between the cells, or functionally, by detecting if the activity of two neurons are correlated with a short lag. The signals that are sent between the neurons are represented by the activity in the neurons that are connected to the target population or by the activity at the corresponding synapses. The different methods not only differ in the accuracy of the signal measurement but they also differ in the type of signal being measured. For example, unselective recording of all neurons in the source population encompasses more indirect pathways to the target population than if one selectively record from the neurons that project to the target population. Infact, this degree of selectivity is similar to that of optogenetic perturbations; one can perturb selectively or unselectively. Thus it becomes possible to match a given signal measurement method with a signal perturbation method, something that allows for an exact input control to any neuronal population. PMID:28066189
Constructing networks from a dynamical system perspective for multivariate nonlinear time series.
Nakamura, Tomomichi; Tanizawa, Toshihiro; Small, Michael
2016-03-01
We describe a method for constructing networks for multivariate nonlinear time series. We approach the interaction between the various scalar time series from a deterministic dynamical system perspective and provide a generic and algorithmic test for whether the interaction between two measured time series is statistically significant. The method can be applied even when the data exhibit no obvious qualitative similarity: a situation in which the naive method utilizing the cross correlation function directly cannot correctly identify connectivity. To establish the connectivity between nodes we apply the previously proposed small-shuffle surrogate (SSS) method, which can investigate whether there are correlation structures in short-term variabilities (irregular fluctuations) between two data sets from the viewpoint of deterministic dynamical systems. The procedure to construct networks based on this idea is composed of three steps: (i) each time series is considered as a basic node of a network, (ii) the SSS method is applied to verify the connectivity between each pair of time series taken from the whole multivariate time series, and (iii) the pair of nodes is connected with an undirected edge when the null hypothesis cannot be rejected. The network constructed by the proposed method indicates the intrinsic (essential) connectivity of the elements included in the system or the underlying (assumed) system. The method is demonstrated for numerical data sets generated by known systems and applied to several experimental time series.
Polanía, Rafael; Paulus, Walter; Antal, Andrea; Nitsche, Michael A
2011-02-01
Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that alters cortical excitability and activity in a polarity-dependent way. Stimulation for a few minutes has been shown to induce plastic alterations of cortical excitability and to improve cognitive performance. These effects might be related to stimulation-induced alterations of functional cortical network connectivity. We aimed to investigate the impact of tDCS on cortical network function by functional connectivity and graph theoretical analysis of the BOLD fMRI spontaneous activity. fMRI resting-state datasets were acquired immediately before and after 10-min bipolar tDCS during rest, with the anode placed over the left primary motor cortex (M1) and the cathode over the contralateral frontopolar cortex. For each dataset, grey matter voxel-based synchronization matrices were calculated and thresholded to construct undirected graphs. Nodal connectivity degree and minimum path length maps were calculated and compared before and after tDCS. Nodal minimum path lengths significantly increased in the left somatomotor (SM1) cortex after anodal tDCS, which means that the number of direct functional connections from the left SM1 to topologically distant grey matter voxels significantly decreased. In contrast, functional coupling between premotor and superior parietal areas with the left SM1 significantly increased. Additionally, the nodal connectivity degree in the left posterior cingulate cortex (PCC) area as well as in the right dorsolateral prefrontal cortex (right DLPFC) significantly increased. In summary, we provide initial support that tDCS-induced neuroplastic alterations might be related to functional connectivity changes in the human brain. Additionally, we propose our approach as a powerful method to track for neuroplastic changes in the human brain. Copyright © 2010 Elsevier Inc. All rights reserved.
Du, Yuhui; Pearlson, Godfrey D; Lin, Dongdong; Sui, Jing; Chen, Jiayu; Salman, Mustafa; Tamminga, Carol A; Ivleva, Elena I; Sweeney, John A; Keshavan, Matcheri S; Clementz, Brett A; Bustillo, Juan; Calhoun, Vince D
2017-05-01
Functional magnetic resonance imaging (fMRI) studies have shown altered brain dynamic functional connectivity (DFC) in mental disorders. Here, we aim to explore DFC across a spectrum of symptomatically-related disorders including bipolar disorder with psychosis (BPP), schizoaffective disorder (SAD), and schizophrenia (SZ). We introduce a group information guided independent component analysis procedure to estimate both group-level and subject-specific connectivity states from DFC. Using resting-state fMRI data of 238 healthy controls (HCs), 140 BPP, 132 SAD, and 113 SZ patients, we identified measures differentiating groups from the whole-brain DFC and traditional static functional connectivity (SFC), separately. Results show that DFC provided more informative measures than SFC. Diagnosis-related connectivity states were evident using DFC analysis. For the dominant state consistent across groups, we found 22 instances of hypoconnectivity (with decreasing trends from HC to BPP to SAD to SZ) mainly involving post-central, frontal, and cerebellar cortices as well as 34 examples of hyperconnectivity (with increasing trends HC through SZ) primarily involving thalamus and temporal cortices. Hypoconnectivities/hyperconnectivities also showed negative/positive correlations, respectively, with clinical symptom scores. Specifically, hypoconnectivities linking postcentral and frontal gyri were significantly negatively correlated with the PANSS positive/negative scores. For frontal connectivities, BPP resembled HC while SAD and SZ were more similar. Three connectivities involving the left cerebellar crus differentiated SZ from other groups and one connection linking frontal and fusiform cortices showed a SAD-unique change. In summary, our method is promising for assessing DFC and may yield imaging biomarkers for quantifying the dimension of psychosis. Hum Brain Mapp 38:2683-2708, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
Harrison, Ben J; Pujol, Jesus; Cardoner, Narcis; Deus, Joan; Alonso, Pino; López-Solà, Marina; Contreras-Rodríguez, Oren; Real, Eva; Segalàs, Cinto; Blanco-Hinojo, Laura; Menchon, José M; Soriano-Mas, Carles
2013-02-15
Functional neuroimaging studies have provided consistent support for the idea that obsessive-compulsive disorder (OCD) is associated with disturbances of brain corticostriatal systems. However, in general, these studies have not sought to account for the disorder's prominent clinical heterogeneity. To address these concerns, we investigated the influence of major OCD symptom dimensions on brain corticostriatal functional systems in a large sample of OCD patients (n = 74) and control participants (n = 74) examined with resting-state functional magnetic resonance imaging. We employed a valid method for mapping ventral and dorsal striatal functional connectivity, which supported both standard group comparisons and linear regression analyses with patients' scores on the Dimensional Yale-Brown Obsessive-Compulsive Scale. Consistent with past findings, patients demonstrated a common connectivity alteration involving the ventral striatum and orbitofrontal cortex that predicted overall illness severity levels. This common alteration was independent of the effect of particular symptom dimensions. Instead, we observed distinct anatomical relationships between the severity of symptom dimensions and striatal functional connectivity. Aggression symptoms modulated connectivity between the ventral striatum, amygdala, and ventromedial frontal cortex, while sexual/religious symptoms had a specific influence on ventral striatal-insular connectivity. Hoarding modulated the strength of ventral and dorsal striatal connectivity with distributed frontal regions. Taken together, these results suggest that pathophysiological changes among orbitofrontal-striatal regions may be common to all forms of OCD. They suggest that a further examination of certain dimensional relationships will also be relevant for advancing current neurobiological models of the disorder. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Apparatus for monitoring high temperature ultrasonic characterization
Lanagan, Michael T.; Kupperman, David S.; Yaconi, George A.
1998-01-01
A method and an apparatus for nondestructive detecting and evaluating chas in the microstructural properties of a material by employing one or more magnetostrictive transducers linked to the material by means of one or more sonic signal conductors. The magnetostrictive transducer or transducers are connected to a pulser/receiver which in turn is connected to an oscilloscope. The oscilloscope is connected to a computer which employs an algorithm to evaluate changes in the velocity of a signal transmitted to the material sample as function of time and temperature.
Eyre, Harris A.; Acevedo, Bianca; Yang, Hongyu; Siddarth, Prabha; Van Dyk, Kathleen; Ercoli, Linda; Leaver, Amber M.; Cyr, Natalie St.; Narr, Katherine; Baune, Bernhard T.; Khalsa, Dharma S.; Lavretsky, Helen
2016-01-01
Background: No study has explored the effect of yoga on cognitive decline and resting-state functional connectivity. Objectives: This study explored the relationship between performance on memory tests and resting-state functional connectivity before and after a yoga intervention versus active control for subjects with mild cognitive impairment (MCI). Methods: Participants ( ≥ 55 y) with MCI were randomized to receive a yoga intervention or active “gold-standard” control (i.e., memory enhancement training (MET)) for 12 weeks. Resting-state functional magnetic resonance imaging was used to map correlations between brain networks and memory performance changes over time. Default mode networks (DMN), language and superior parietal networks were chosen as networks of interest to analyze the association with changes in verbal and visuospatial memory performance. Results: Fourteen yoga and 11 MET participants completed the study. The yoga group demonstrated a statistically significant improvement in depression and visuospatial memory. We observed improved verbal memory performance correlated with increased connectivity between the DMN and frontal medial cortex, pregenual anterior cingulate cortex, right middle frontal cortex, posterior cingulate cortex, and left lateral occipital cortex. Improved verbal memory performance positively correlated with increased connectivity between the language processing network and the left inferior frontal gyrus. Improved visuospatial memory performance correlated inversely with connectivity between the superior parietal network and the medial parietal cortex. Conclusion:Yoga may be as effective as MET in improving functional connectivity in relation to verbal memory performance. These findings should be confirmed in larger prospective studies. PMID:27060939
Lee, Kangjoo; Lina, Jean-Marc; Gotman, Jean; Grova, Christophe
2016-07-01
Functional hubs are defined as the specific brain regions with dense connections to other regions in a functional brain network. Among them, connector hubs are of great interests, as they are assumed to promote global and hierarchical communications between functionally specialized networks. Damage to connector hubs may have a more crucial effect on the system than does damage to other hubs. Hubs in graph theory are often identified from a correlation matrix, and classified as connector hubs when the hubs are more connected to regions in other networks than within the networks to which they belong. However, the identification of hubs from functional data is more complex than that from structural data, notably because of the inherent problem of multicollinearity between temporal dynamics within a functional network. In this context, we developed and validated a method to reliably identify connectors and corresponding overlapping network structure from resting-state fMRI. This new method is actually handling the multicollinearity issue, since it does not rely on counting the number of connections from a thresholded correlation matrix. The novelty of the proposed method is that besides counting the number of networks involved in each voxel, it allows us to identify which networks are actually involved in each voxel, using a data-driven sparse general linear model in order to identify brain regions involved in more than one network. Moreover, we added a bootstrap resampling strategy to assess statistically the reproducibility of our results at the single subject level. The unified framework is called SPARK, i.e. SParsity-based Analysis of Reliable k-hubness, where k-hubness denotes the number of networks overlapping in each voxel. The accuracy and robustness of SPARK were evaluated using two dimensional box simulations and realistic simulations that examined detection of artificial hubs generated on real data. Then, test/retest reliability of the method was assessed using the 1000 Functional Connectome Project database, which includes data obtained from 25 healthy subjects at three different occasions with long and short intervals between sessions. We demonstrated that SPARK provides an accurate and reliable estimation of k-hubness, suggesting a promising tool for understanding hub organization in resting-state fMRI. Copyright © 2016 Elsevier Inc. All rights reserved.
Ard, Tyler; Carver, Frederick W; Holroyd, Tom; Horwitz, Barry; Coppola, Richard
2015-08-01
In typical magnetoencephalography and/or electroencephalography functional connectivity analysis, researchers select one of several methods that measure a relationship between regions to determine connectivity, such as coherence, power correlations, and others. However, it is largely unknown if some are more suited than others for various types of investigations. In this study, the authors investigate seven connectivity metrics to evaluate which, if any, are sensitive to audiovisual integration by contrasting connectivity when tracking an audiovisual object versus connectivity when tracking a visual object uncorrelated with the auditory stimulus. The authors are able to assess the metrics' performances at detecting audiovisual integration by investigating connectivity between auditory and visual areas. Critically, the authors perform their investigation on a whole-cortex all-to-all mapping, avoiding confounds introduced in seed selection. The authors find that amplitude-based connectivity measures in the beta band detect strong connections between visual and auditory areas during audiovisual integration, specifically between V4/V5 and auditory cortices in the right hemisphere. Conversely, phase-based connectivity measures in the beta band as well as phase and power measures in alpha, gamma, and theta do not show connectivity between audiovisual areas. The authors postulate that while beta power correlations detect audiovisual integration in the current experimental context, it may not always be the best measure to detect connectivity. Instead, it is likely that the brain utilizes a variety of mechanisms in neuronal communication that may produce differential types of temporal relationships.
Scientific and Pragmatic Challenges for Bridging Education and Neuroscience
ERIC Educational Resources Information Center
Varma, Sashank; McCandliss, Bruce D.; Schwartz, Daniel L.
2008-01-01
Educational neuroscience is an emerging effort to integrate neuroscience methods, particularly functional neuroimaging, with behavioral methods to address issues of learning and instruction. This article consolidates common concerns about connecting education and neuroscience. One set of concerns is scientific: in-principle differences in methods,…
Das, Anup; Sampson, Aaron L.; Lainscsek, Claudia; Muller, Lyle; Lin, Wutu; Doyle, John C.; Cash, Sydney S.; Halgren, Eric; Sejnowski, Terrence J.
2017-01-01
The correlation method from brain imaging has been used to estimate functional connectivity in the human brain. However, brain regions might show very high correlation even when the two regions are not directly connected due to the strong interaction of the two regions with common input from a third region. One previously proposed solution to this problem is to use a sparse regularized inverse covariance matrix or precision matrix (SRPM) assuming that the connectivity structure is sparse. This method yields partial correlations to measure strong direct interactions between pairs of regions while simultaneously removing the influence of the rest of the regions, thus identifying regions that are conditionally independent. To test our methods, we first demonstrated conditions under which the SRPM method could indeed find the true physical connection between a pair of nodes for a spring-mass example and an RC circuit example. The recovery of the connectivity structure using the SRPM method can be explained by energy models using the Boltzmann distribution. We then demonstrated the application of the SRPM method for estimating brain connectivity during stage 2 sleep spindles from human electrocorticography (ECoG) recordings using an 8 × 8 electrode array. The ECoG recordings that we analyzed were from a 32-year-old male patient with long-standing pharmaco-resistant left temporal lobe complex partial epilepsy. Sleep spindles were automatically detected using delay differential analysis and then analyzed with SRPM and the Louvain method for community detection. We found spatially localized brain networks within and between neighboring cortical areas during spindles, in contrast to the case when sleep spindles were not present. PMID:28095202
Differences in resting corticolimbic functional connectivity in bipolar I euthymia
Torrisi, Salvatore; Moody, Teena D; Vizueta, Nathalie; Thomason, Moriah E; Monti, Martin M; Townsend, Jennifer D; Bookheimer, Susan Y; Altshuler, Lori L
2012-01-01
Objective We examined resting state functional connectivity in the brain between key emotion regulation regions in bipolar I disorder to delineate differences in coupling from healthy subjects. Methods Euthymic subjects with bipolar I disorder (n = 20) and matched healthy subjects (n = 20) participated in a resting state functional magnetic resonance imaging scan. Low frequency fluctuations in blood oxygen level-dependent (BOLD) signal were correlated in the six connections between four anatomically-defined nodes: left and right amygdala and left and right ventrolateral prefrontal cortex (vlPFC). Seed-to-voxel connectivity results were probed for commonly coupled regions. Following this, an identified region was included in a mediation analysis to determine the potential of mediation. Results The bipolar I disorder group exhibited significant hyperconnectivity between right amygdala and right vlPFC relative to healthy subjects. The connectivity between these regions in the bipolar I disorder group was partially mediated by activity in the anterior cingulate cortex (ACC). Conclusions Greater coupling between right amygdala and right vlPFC and their partial mediation by the ACC were found in bipolar I disorder subjects in remission and in the absence of a psychological task. These findings have implications for a trait-related and clinically-important imaging biomarker. PMID:23347587
Disrupted white matter structural connectivity in heroin abusers.
Sun, Yan; Wang, Gui-Bin; Lin, Qi-Xiang; Lu, Lin; Shu, Ni; Meng, Shi-Qiu; Wang, Jun; Han, Hong-Bin; He, Yong; Shi, Jie
2017-01-01
Neurocognitive impairment is one of the factors that put heroin abusers at greater risk for relapse, and deficits in related functional brain connections have been found. However, the alterations in structural brain connections that may underlie these functional and neurocognitive impairments remain largely unknown. In the present study, we investigated topological organization alterations in the structural network of white matter in heroin abusers and examined the relationships between the network changes and clinical measures. We acquired diffusion tensor imaging datasets from 76 heroin abusers and 78 healthy controls. Network-based statistic was applied to identify alterations in interregional white matter connectivity, and graph theory methods were used to analyze the properties of global networks. The participants also completed a battery of neurocognitive measures. One increased subnetwork characterizing widespread abnormalities in structural connectivity was present in heroin users, which mainly composed of default-mode, attentional and visual systems. The connection strength was positively correlated with increases in fractional anisotropy in heroin abusers. Intriguingly, the changes in within-frontal and within-temporal connections in heroin abusers were significantly correlated with daily heroin dosage and impulsivity scores, respectively. These findings suggest that heroin abusers have extensive abnormal white matter connectivity, which may mediate the relationship between heroin dependence and clinical measures. The increase in white matter connectivity may be attributable to the inefficient microstructure integrity of white matter. The present findings extend our understanding of cerebral structural disruptions that underlie neurocognitive and functional deficits in heroin addiction and provide circuit-level markers for this chronic disorder. © 2015 Society for the Study of Addiction.
The method of generating functions in exact scalar field inflationary cosmology
NASA Astrophysics Data System (ADS)
Chervon, Sergey V.; Fomin, Igor V.; Beesham, Aroonkumar
2018-04-01
The construction of exact solutions in scalar field inflationary cosmology is of growing interest. In this work, we review the results which have been obtained with the help of one of the most effective methods, viz., the method of generating functions for the construction of exact solutions in scalar field cosmology. We also include in the debate the superpotential method, which may be considered as the bridge to the slow roll approximation equations. Based on the review, we suggest a classification for the generating functions, and find a connection for all of them with the superpotential.
Shafi, Mouhsin M.; Whitfield-Gabrieli, Susan; Chu, Catherine J.; Pascual-Leone, Alvaro; Chang, Bernard S.
2017-01-01
Resting-state functional connectivity MRI (rs-fcMRI) is a technique that identifies connectivity between different brain regions based on correlations over time in the blood-oxygenation level dependent signal. rs-fcMRI has been applied extensively to identify abnormalities in brain connectivity in different neurologic and psychiatric diseases. However, the relationship among rs-fcMRI connectivity abnormalities, brain electrophysiology and disease state is unknown, in part because the causal significance of alterations in functional connectivity in disease pathophysiology has not been established. Transcranial Magnetic Stimulation (TMS) is a technique that uses electromagnetic induction to noninvasively produce focal changes in cortical activity. When combined with electroencephalography (EEG), TMS can be used to assess the brain's response to external perturbations. Here we provide a protocol for combining rs-fcMRI, TMS and EEG to assess the physiologic significance of alterations in functional connectivity in patients with neuropsychiatric disease. We provide representative results from a previously published study in which rs-fcMRI was used to identify regions with abnormal connectivity in patients with epilepsy due to a malformation of cortical development, periventricular nodular heterotopia (PNH). Stimulation in patients with epilepsy resulted in abnormal TMS-evoked EEG activity relative to stimulation of the same sites in matched healthy control patients, with an abnormal increase in the late component of the TMS-evoked potential, consistent with cortical hyperexcitability. This abnormality was specific to regions with abnormal resting-state functional connectivity. Electrical source analysis in a subject with previously recorded seizures demonstrated that the origin of the abnormal TMS-evoked activity co-localized with the seizure-onset zone, suggesting the presence of an epileptogenic circuit. These results demonstrate how rs-fcMRI, TMS and EEG can be utilized together to identify and understand the physiological significance of abnormal brain connectivity in human diseases. PMID:27911366
Resting-state FMRI confounds and cleanup
Murphy, Kevin; Birn, Rasmus M.; Bandettini, Peter A.
2013-01-01
The goal of resting-state functional magnetic resonance imaging (FMRI) is to investigate the brain’s functional connections by using the temporal similarity between blood oxygenation level dependent (BOLD) signals in different regions of the brain “at rest” as an indicator of synchronous neural activity. Since this measure relies on the temporal correlation of FMRI signal changes between different parts of the brain, any non-neural activity-related process that affects the signals will influence the measure of functional connectivity, yielding spurious results. To understand the sources of these resting-state FMRI confounds, this article describes the origins of the BOLD signal in terms of MR physics and cerebral physiology. Potential confounds arising from motion, cardiac and respiratory cycles, arterial CO2 concentration, blood pressure/cerebral autoregulation, and vasomotion are discussed. Two classes of techniques to remove confounds from resting-state BOLD time series are reviewed: 1) those utilising external recordings of physiology and 2) data-based cleanup methods that only use the resting-state FMRI data itself. Further methods that remove noise from functional connectivity measures at a group level are also discussed. For successful interpretation of resting-state FMRI comparisons and results, noise cleanup is an often over-looked but essential step in the analysis pipeline. PMID:23571418
Fukushima, Makoto; Betzel, Richard F; He, Ye; van den Heuvel, Martijn P; Zuo, Xi-Nian; Sporns, Olaf
2018-04-01
Structural white matter connections are thought to facilitate integration of neural information across functionally segregated systems. Recent studies have demonstrated that changes in the balance between segregation and integration in brain networks can be tracked by time-resolved functional connectivity derived from resting-state functional magnetic resonance imaging (rs-fMRI) data and that fluctuations between segregated and integrated network states are related to human behavior. However, how these network states relate to structural connectivity is largely unknown. To obtain a better understanding of structural substrates for these network states, we investigated how the relationship between structural connectivity, derived from diffusion tractography, and functional connectivity, as measured by rs-fMRI, changes with fluctuations between segregated and integrated states in the human brain. We found that the similarity of edge weights between structural and functional connectivity was greater in the integrated state, especially at edges connecting the default mode and the dorsal attention networks. We also demonstrated that the similarity of network partitions, evaluated between structural and functional connectivity, increased and the density of direct structural connections within modules in functional networks was elevated during the integrated state. These results suggest that, when functional connectivity exhibited an integrated network topology, structural connectivity and functional connectivity were more closely linked to each other and direct structural connections mediated a larger proportion of neural communication within functional modules. Our findings point out the possibility of significant contributions of structural connections to integrative neural processes underlying human behavior.
Link prediction boosted psychiatry disorder classification for functional connectivity network
NASA Astrophysics Data System (ADS)
Li, Weiwei; Mei, Xue; Wang, Hao; Zhou, Yu; Huang, Jiashuang
2017-02-01
Functional connectivity network (FCN) is an effective tool in psychiatry disorders classification, and represents cross-correlation of the regional blood oxygenation level dependent signal. However, FCN is often incomplete for suffering from missing and spurious edges. To accurate classify psychiatry disorders and health control with the incomplete FCN, we first `repair' the FCN with link prediction, and then exact the clustering coefficients as features to build a weak classifier for every FCN. Finally, we apply a boosting algorithm to combine these weak classifiers for improving classification accuracy. Our method tested by three datasets of psychiatry disorder, including Alzheimer's Disease, Schizophrenia and Attention Deficit Hyperactivity Disorder. The experimental results show our method not only significantly improves the classification accuracy, but also efficiently reconstructs the incomplete FCN.
NASA Astrophysics Data System (ADS)
Santosa, Hendrik; Aarabi, Ardalan; Perlman, Susan B.; Huppert, Theodore J.
2017-05-01
Functional near-infrared spectroscopy (fNIRS) is a noninvasive neuroimaging technique that uses low levels of red to near-infrared light to measure changes in cerebral blood oxygenation. Spontaneous (resting state) functional connectivity (sFC) has become a critical tool for cognitive neuroscience for understanding task-independent neural networks, revealing pertinent details differentiating healthy from disordered brain function, and discovering fluctuations in the synchronization of interacting individuals during hyperscanning paradigms. Two of the main challenges to sFC-NIRS analysis are (i) the slow temporal structure of both systemic physiology and the response of blood vessels, which introduces false spurious correlations, and (ii) motion-related artifacts that result from movement of the fNIRS sensors on the participants' head and can introduce non-normal and heavy-tailed noise structures. In this work, we systematically examine the false-discovery rates of several time- and frequency-domain metrics of functional connectivity for characterizing sFC-NIRS. Specifically, we detail the modifications to the statistical models of these methods needed to avoid high levels of false-discovery related to these two sources of noise in fNIRS. We compare these analysis procedures using both simulated and experimental resting-state fNIRS data. Our proposed robust correlation method has better performance in terms of being more reliable to the noise outliers due to the motion artifacts.
Desjardins, Marie-Ève; Carrier, Julie; Lina, Jean-Marc; Fortin, Maxime; Gosselin, Nadia; Montplaisir, Jacques; Zadra, Antonio
2017-04-01
Although sleepwalking (somnambulism) affects up to 4% of adults, its pathophysiology remains poorly understood. Sleepwalking can be preceded by fluctuations in slow-wave sleep EEG signals, but the significance of these pre-episode changes remains unknown and methods based on EEG functional connectivity have yet to be used to better comprehend the disorder. We investigated the sleep EEG of 27 adult sleepwalkers (mean age: 29 ± 7.6 years) who experienced a somnambulistic episode during slow-wave sleep. The 20-second segment of sleep EEG immediately preceding each patient's episode was compared with the 20-second segment occurring 2 minutes prior to episode onset. Results from spectral analyses revealed increased delta and theta spectral power in the 20 seconds preceding the episodes' onset as compared to the 20 seconds occurring 2 minutes before the episodes. The imaginary part of the coherence immediately prior to episode onset revealed (1) decreased delta EEG functional connectivity in parietal and occipital regions, (2) increased alpha connectivity over a fronto-parietal network, and (3) increased beta connectivity involving symmetric inter-hemispheric networks implicating frontotemporal, parietal and occipital areas. Taken together, these modifications in EEG functional connectivity suggest that somnambulistic episodes are preceded by brain processes characterized by the co-existence of arousal and deep sleep. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.
Zhang, Delong; Liu, Bo; Chen, Jun; Peng, Xiaoling; Liu, Xian; Fan, Yuanyuan; Liu, Ming; Huang, Ruiwang
2013-01-01
Recent studies have shown that multivariate pattern analysis (MVPA) can be useful for distinguishing brain disorders into categories. Such analyses can substantially enrich and facilitate clinical diagnoses. Using MPVA methods, whole brain functional networks, especially those derived using different frequency windows, can be applied to detect brain states. We constructed whole brain functional networks for groups of vascular dementia (VaD) patients and controls using resting state BOLD-fMRI (rsfMRI) data from three frequency bands - slow-5 (0.01∼0.027 Hz), slow-4 (0.027∼0.073 Hz), and whole-band (0.01∼0.073 Hz). Then we used the support vector machine (SVM), a type of MVPA classifier, to determine the patterns of functional connectivity. Our results showed that the brain functional networks derived from rsfMRI data (19 VaD patients and 20 controls) in these three frequency bands appear to reflect neurobiological changes in VaD patients. Such differences could be used to differentiate the brain states of VaD patients from those of healthy individuals. We also found that the functional connectivity patterns of the human brain in the three frequency bands differed, as did their ability to differentiate brain states. Specifically, the ability of the functional connectivity pattern to differentiate VaD brains from healthy ones was more efficient in the slow-5 (0.01∼0.027 Hz) band than in the other two frequency bands. Our findings suggest that the MVPA approach could be used to detect abnormalities in the functional connectivity of VaD patients in distinct frequency bands. Identifying such abnormalities may contribute to our understanding of the pathogenesis of VaD. PMID:23359801
Huang, Huiyuan; Wang, Junjing; Seger, Carol; Lu, Min; Deng, Feng; Wu, Xiaoyan; He, Yuan; Niu, Chen; Wang, Jun; Huang, Ruiwang
2018-01-01
Long-term intensive gymnastic training can induce brain structural and functional reorganization. Previous studies have identified structural and functional network differences between world class gymnasts (WCGs) and non-athletes at the whole-brain level. However, it is still unclear how interactions within and between functional networks are affected by long-term intensive gymnastic training. We examined both intra- and inter-network functional connectivity of gymnasts relative to non-athletes using resting-state fMRI (R-fMRI). R-fMRI data were acquired from 13 WCGs and 14 non-athlete controls. Group-independent component analysis (ICA) was adopted to decompose the R-fMRI data into spatial independent components and associated time courses. An automatic component identification method was used to identify components of interest associated with resting-state networks (RSNs). We identified nine RSNs, the basal ganglia network (BG), sensorimotor network (SMN), cerebellum (CB), anterior and posterior default mode networks (aDMN/pDMN), left and right fronto-parietal networks (lFPN/rFPN), primary visual network (PVN), and extrastriate visual network (EVN). Statistical analyses revealed that the intra-network functional connectivity was significantly decreased within the BG, aDMN, lFPN, and rFPN, but increased within the EVN in the WCGs compared to the controls. In addition, the WCGs showed uniformly decreased inter-network functional connectivity between SMN and BG, CB, and PVN, BG and PVN, and pDMN and rFPN compared to the controls. We interpret this generally weaker intra- and inter-network functional connectivity in WCGs during the resting state as a result of greater efficiency in the WCGs' brain associated with long-term motor skill training.
Gopinath, Kaundinya; Krishnamurthy, Venkatagiri; Cabanban, Romeo; Crosson, Bruce A
2015-06-01
A major focus of brain research recently has been to map the resting-state functional connectivity (rsFC) network architecture of the normal brain and pathology through functional magnetic resonance imaging. However, the phenomenon of anticorrelations in resting-state signals between different brain regions has not been adequately examined. The preponderance of studies on resting-state fMRI (rsFMRI) have either ignored anticorrelations in rsFC networks or adopted methods in data analysis, which have rendered anticorrelations in rsFC networks uninterpretable. The few studies that have examined anticorrelations in rsFC networks using conventional methods have found anticorrelations to be weak in strength and not very reproducible across subjects. Anticorrelations in rsFC network architecture could reflect mechanisms that subserve a number of important brain processes. In this preliminary study, we examined the properties of anticorrelated rsFC networks by systematically focusing on negative cross-correlation coefficients (CCs) among rsFMRI voxel time series across the brain with graph theory-based network analysis. A number of methods were implemented to enhance the neuronal specificity of resting-state functional connections that yield negative CCs, although at the cost of decreased sensitivity. Hubs of anticorrelation were seen in a number of cortical and subcortical brain regions. Examination of the anticorrelation maps of these hubs indicated that negative CCs in rsFC network architecture highlight a number of regulatory interactions between brain networks and regions, including reciprocal modulations, suppression, inhibition, and neurofeedback.
Limbic hyperconnectivity in the vegetative state.
Di Perri, Carol; Bastianello, Stefano; Bartsch, Andreas J; Pistarini, Caterina; Maggioni, Giorgio; Magrassi, Lorenzo; Imberti, Roberto; Pichiecchio, Anna; Vitali, Paolo; Laureys, Steven; Di Salle, Francesco
2013-10-15
To investigate functional connectivity between the default mode network (DMN) and other networks in disorders of consciousness. We analyzed MRI data from 11 patients in a vegetative state and 7 patients in a minimally conscious state along with age- and sex-matched healthy control subjects. MRI data analysis included nonlinear spatial normalization to compensate for disease-related anatomical distortions. We studied brain connectivity data from resting-state MRI temporal series, combining noninferential (independent component analysis) and inferential (seed-based general linear model) methods. In DMN hypoconnectivity conditions, a patient's DMN functional connectivity shifts and paradoxically increases in limbic structures, including the orbitofrontal cortex, insula, hypothalamus, and the ventral tegmental area. Concurrently with DMN hypoconnectivity, we report limbic hyperconnectivity in patients in vegetative and minimally conscious states. This hyperconnectivity may reflect the persistent engagement of residual neural activity in self-reinforcing neural loops, which, in turn, could disrupt normal patterns of connectivity.
Aircraft Flight Modeling During the Optimization of Gas Turbine Engine Working Process
NASA Astrophysics Data System (ADS)
Tkachenko, A. Yu; Kuz'michev, V. S.; Krupenich, I. N.
2018-01-01
The article describes a method for simulating the flight of the aircraft along a predetermined path, establishing a functional connection between the parameters of the working process of gas turbine engine and the efficiency criteria of the aircraft. This connection is necessary for solving the optimization tasks of the conceptual design stage of the engine according to the systems approach. Engine thrust level, in turn, influences the operation of aircraft, thus making accurate simulation of the aircraft behavior during flight necessary for obtaining the correct solution. The described mathematical model of aircraft flight provides the functional connection between the airframe characteristics, working process of gas turbine engines (propulsion system), ambient and flight conditions and flight profile features. This model provides accurate results of flight simulation and the resulting aircraft efficiency criteria, required for optimization of working process and control function of a gas turbine engine.
Are Balance Problems Connected to Reading Speed or the Familial Risk of Dyslexia?
ERIC Educational Resources Information Center
Viholainen, Helena; Aro, Mikko; Ahonen, Timo; Crawford, Susan; Cantell, Marja; Kooistra, Libbe
2011-01-01
Aim: The aim of this study was to examine the connection between balance problems and reading speed in children with and without a familial risk of dyslexia by controlling for the effects of attention, hyperactivity, and cognitive and motor functioning. Method: The prevalence of balance problems was studied in 94 children (48 females, 46 males)…
Mills, Kathryn L.; Bathula, Deepti; Dias, Taciana G. Costa; Iyer, Swathi P.; Fenesy, Michelle C.; Musser, Erica D.; Stevens, Corinne A.; Thurlow, Bria L.; Carpenter, Samuel D.; Nagel, Bonnie J.; Nigg, Joel T.; Fair, Damien A.
2012-01-01
Introduction: Attention deficit hyperactivity disorder (ADHD) captures a heterogeneous group of children, who are characterized by a range of cognitive and behavioral symptoms. Previous resting-state functional connectivity MRI (rs-fcMRI) studies have sought to understand the neural correlates of ADHD by comparing connectivity measurements between those with and without the disorder, focusing primarily on cortical–striatal circuits mediated by the thalamus. To integrate the multiple phenotypic features associated with ADHD and help resolve its heterogeneity, it is helpful to determine how specific circuits relate to unique cognitive domains of the ADHD syndrome. Spatial working memory has been proposed as a key mechanism in the pathophysiology of ADHD. Methods: We correlated the rs-fcMRI of five thalamic regions of interest (ROIs) with spatial span working memory scores in a sample of 67 children aged 7–11 years [ADHD and typically developing children (TDC)]. In an independent dataset, we then examined group differences in thalamo-striatal functional connectivity between 70 ADHD and 89 TDC (7–11 years) from the ADHD-200 dataset. Thalamic ROIs were created based on previous methods that utilize known thalamo-cortical loops and rs-fcMRI to identify functional boundaries in the thalamus. Results/Conclusion: Using these thalamic regions, we found atypical rs-fcMRI between specific thalamic groupings with the basal ganglia. To identify the thalamic connections that relate to spatial working memory in ADHD, only connections identified in both the correlational and comparative analyses were considered. Multiple connections between the thalamus and basal ganglia, particularly between medial and anterior dorsal thalamus and the putamen, were related to spatial working memory and also altered in ADHD. These thalamo-striatal disruptions may be one of multiple atypical neural and cognitive mechanisms that relate to the ADHD clinical phenotype. PMID:22291667
2013-01-01
Background Many proteins tune their biological function by transitioning between different functional states, effectively acting as dynamic molecular machines. Detailed structural characterization of transition trajectories is central to understanding the relationship between protein dynamics and function. Computational approaches that build on the Molecular Dynamics framework are in principle able to model transition trajectories at great detail but also at considerable computational cost. Methods that delay consideration of dynamics and focus instead on elucidating energetically-credible conformational paths connecting two functionally-relevant structures provide a complementary approach. Effective sampling-based path planning methods originating in robotics have been recently proposed to produce conformational paths. These methods largely model short peptides or address large proteins by simplifying conformational space. Methods We propose a robotics-inspired method that connects two given structures of a protein by sampling conformational paths. The method focuses on small- to medium-size proteins, efficiently modeling structural deformations through the use of the molecular fragment replacement technique. In particular, the method grows a tree in conformational space rooted at the start structure, steering the tree to a goal region defined around the goal structure. We investigate various bias schemes over a progress coordinate for balance between coverage of conformational space and progress towards the goal. A geometric projection layer promotes path diversity. A reactive temperature scheme allows sampling of rare paths that cross energy barriers. Results and conclusions Experiments are conducted on small- to medium-size proteins of length up to 214 amino acids and with multiple known functionally-relevant states, some of which are more than 13Å apart of each-other. Analysis reveals that the method effectively obtains conformational paths connecting structural states that are significantly different. A detailed analysis on the depth and breadth of the tree suggests that a soft global bias over the progress coordinate enhances sampling and results in higher path diversity. The explicit geometric projection layer that biases the exploration away from over-sampled regions further increases coverage, often improving proximity to the goal by forcing the exploration to find new paths. The reactive temperature scheme is shown effective in increasing path diversity, particularly in difficult structural transitions with known high-energy barriers. PMID:24565158
NASA Astrophysics Data System (ADS)
Yi, Guo-Sheng; Wang, Jiang; Han, Chun-Xiao; Deng, Bin; Wei, Xi-Le; Li, Nuo
2013-02-01
Manual acupuncture is widely used for pain relief and stress control. Previous studies on acupuncture have shown its modulatory effects on the functional connectivity associated with one or a few preselected brain regions. To investigate how manual acupuncture modulates the organization of functional networks at a whole-brain level, we acupuncture at ST36 of a right leg to obtain electroencephalograph (EEG) signals. By coherence estimation, we determine the synchronizations between all pairwise combinations of EEG channels in three acupuncture states. The resulting synchronization matrices are converted into functional networks by applying a threshold, and the clustering coefficients and path lengths are computed as a function of threshold. The results show that acupuncture can increase functional connections and synchronizations between different brain areas. For a wide range of thresholds, the clustering coefficient during acupuncture and post-acupuncture period is higher than that during the pre-acupuncture control period, whereas the characteristic path length is shorter. We provide further support for the presence of “small-world" network characteristics in functional networks by using acupuncture. These preliminary results highlight the beneficial modulations of functional connectivity by manual acupuncture, which could contribute to the understanding of the effects of acupuncture on the entire brain, as well as the neurophysiological mechanisms underlying acupuncture. Moreover, the proposed method may be a useful approach to the further investigation of the complexity of patterns of interrelations between EEG channels.
Connections between Vision, Hearing, and Cognitive Function in Old Age.
ERIC Educational Resources Information Center
Wahl, Hans-Werner; Heyl, Vera
2003-01-01
Discusses findings of studies that examined the relationship between vision, hearing, and cognitive function in normally aging adults. Indicates that most found at least modest significant relationships between sensory and cognitive measures based on diverse assessment and design methods. (Contains 42 references.) (JOW)
Stefano Filho, Carlos A; Attux, Romis; Castellano, Gabriela
2017-01-01
Hands motor imagery (MI) has been reported to alter synchronization patterns amongst neurons, yielding variations in the mu and beta bands' power spectral density (PSD) of the electroencephalography (EEG) signal. These alterations have been used in the field of brain-computer interfaces (BCI), in an attempt to assign distinct MI tasks to commands of such a system. Recent studies have highlighted that information may be missing if knowledge about brain functional connectivity is not considered. In this work, we modeled the brain as a graph in which each EEG electrode represents a node. Our goal was to understand if there exists any linear correlation between variations in the synchronization patterns-that is, variations in the PSD of mu and beta bands-induced by MI and alterations in the corresponding functional networks. Moreover, we (1) explored the feasibility of using functional connectivity parameters as features for a classifier in the context of an MI-BCI; (2) investigated three different types of feature selection (FS) techniques; and (3) compared our approach to a more traditional method using the signal PSD as classifier inputs. Ten healthy subjects participated in this study. We observed significant correlations ( p < 0.05) with values ranging from 0.4 to 0.9 between PSD variations and functional network alterations for some electrodes, prominently in the beta band. The PSD method performed better for data classification, with mean accuracies of (90 ± 8)% and (87 ± 7)% for the mu and beta band, respectively, versus (83 ± 8)% and (83 ± 7)% for the same bands for the graph method. Moreover, the number of features for the graph method was considerably larger. However, results for both methods were relatively close, and even overlapped when the uncertainties of the accuracy rates were considered. Further investigation regarding a careful exploration of other graph metrics may provide better alternatives.
Analysis of evoked deep brain connectivity.
Klimeš, Petr; Janeček, Jiři; Jurák, Pavel; Halámek, Josef; Chládek, Han; Brázdil, Milan
2013-01-01
Establishing dependencies and connectivity among different structures in the human brain is an extremely complex issue. Methods that are often used for connectivity analysis are based on correlation mechanisms. Correlation methods can analyze changes in signal shape or instantaneous power level. Although recent studies imply that observation of results from both groups of methods together can disclose some of the basic functions and behavior of the human brain during mental activity and decision-making, there is no technique covering changes in the shape of signals along with changes in their power levels. We present a method using a time evaluation of the correlation along with a comparison of power levels in every available contact pair from intracranial electrodes placed in deep brain structures. Observing shape changes in signals after stimulation together with their power levels provides us with new information about signal character between different structures in the brain during task-related events - visual stimulation with motor response. The results for a subject with 95 intracerebral contacts used in this paper demonstrate a clear methodology capable of spatially analyzing connectivity among deep brain structures.
A literature-driven method to calculate similarities among diseases.
Kim, Hyunjin; Yoon, Youngmi; Ahn, Jaegyoon; Park, Sanghyun
2015-11-01
"Our lives are connected by a thousand invisible threads and along these sympathetic fibers, our actions run as causes and return to us as results". It is Herman Melville's famous quote describing connections among human lives. To paraphrase the Melville's quote, diseases are connected by many functional threads and along these sympathetic fibers, diseases run as causes and return as results. The Melville's quote explains the reason for researching disease-disease similarity and disease network. Measuring similarities between diseases and constructing disease network can play an important role in disease function research and in disease treatment. To estimate disease-disease similarities, we proposed a novel literature-based method. The proposed method extracted disease-gene relations and disease-drug relations from literature and used the frequencies of occurrence of the relations as features to calculate similarities among diseases. We also constructed disease network with top-ranking disease pairs from our method. The proposed method discovered a larger number of answer disease pairs than other comparable methods and showed the lowest p-value. We presume that our method showed good results because of using literature data, using all possible gene symbols and drug names for features of a disease, and determining feature values of diseases with the frequencies of co-occurrence of two entities. The disease-disease similarities from the proposed method can be used in computational biology researches which use similarities among diseases. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Deen, Ben; Saxe, Rebecca; Bedny, Marina
2015-08-01
In congenital blindness, the occipital cortex responds to a range of nonvisual inputs, including tactile, auditory, and linguistic stimuli. Are these changes in functional responses to stimuli accompanied by altered interactions with nonvisual functional networks? To answer this question, we introduce a data-driven method that searches across cortex for functional connectivity differences across groups. Replicating prior work, we find increased fronto-occipital functional connectivity in congenitally blind relative to blindfolded sighted participants. We demonstrate that this heightened connectivity extends over most of occipital cortex but is specific to a subset of regions in the inferior, dorsal, and medial frontal lobe. To assess the functional profile of these frontal areas, we used an n-back working memory task and a sentence comprehension task. We find that, among prefrontal areas with overconnectivity to occipital cortex, one left inferior frontal region responds to language over music. By contrast, the majority of these regions responded to working memory load but not language. These results suggest that in blindness occipital cortex interacts more with working memory systems and raise new questions about the function and mechanism of occipital plasticity.
NASA Astrophysics Data System (ADS)
Zhang, Yu-Jin; Lu, Chun-Ming; Biswal, Bharat B.; Zang, Yu-Feng; Peng, Dan-Lin; Zhu, Chao-Zhe
2010-07-01
Functional connectivity has become one of the important approaches to understanding the functional organization of the human brain. Recently, functional near-infrared spectroscopy (fNIRS) was demonstrated as a feasible method to study resting-state functional connectivity (RSFC) in the sensory and motor systems. However, whether such fNIRS-based RSFC can be revealed in high-level and complex functional systems remains unknown. In the present study, the feasibility of such an approach is tested on the language system, of which the neural substrates have been well documented in the literature. After determination of a seed channel by a language localizer task, the correlation strength between the low frequency fluctuations of the fNIRS signal at the seed channel and those at all other channels is used to evaluate the language system RSFC. Our results show a significant RSFC between the left inferior frontal cortex and superior temporal cortex, components both associated with dominant language regions. Moreover, the RSFC map demonstrates left lateralization of the language system. In conclusion, the present study successfully utilized fNIRS-based RSFC to study a complex and high-level neural system, and provides further evidence for the validity of the fNIRS-based RSFC approach.
Disrupted resting-state functional connectivity in minimally treated chronic schizophrenia.
Wang, Xijin; Xia, Mingrui; Lai, Yunyao; Dai, Zhengjia; Cao, Qingjiu; Cheng, Zhang; Han, Xue; Yang, Lei; Yuan, Yanbo; Zhang, Yong; Li, Keqing; Ma, Hong; Shi, Chuan; Hong, Nan; Szeszko, Philip; Yu, Xin; He, Yong
2014-07-01
The pathophysiology of chronic schizophrenia may reflect long term brain changes related to the disorder. The effect of chronicity on intrinsic functional connectivity patterns in schizophrenia without the potentially confounding effect of antipsychotic medications, however, remains largely unknown. We collected resting-state fMRI data in 21 minimally treated chronic schizophrenia patients and 20 healthy controls. We computed regional functional connectivity strength for each voxel in the brain, and further divided regional functional connectivity strength into short-range regional functional connectivity strength and long-range regional functional connectivity strength. General linear models were used to detect between-group differences in these regional functional connectivity strength metrics and to further systematically investigate the relationship between these differences and clinical/behavioral variables in the patients. Compared to healthy controls, the minimally treated chronic schizophrenia patients showed an overall reduced regional functional connectivity strength especially in bilateral sensorimotor cortex, right lateral prefrontal cortex, left insula and right lingual gyrus, and these regional functional connectivity strength decreases mainly resulted from disruption of short-range regional functional connectivity strength. The minimally treated chronic schizophrenia patients also showed reduced long-range regional functional connectivity strength in the bilateral posterior cingulate cortex/precuneus, and increased long-range regional functional connectivity strength in the right lateral prefrontal cortex and lingual gyrus. Notably, disrupted short-range regional functional connectivity strength mainly correlated with duration of illness and negative symptoms, whereas disrupted long-range regional functional connectivity strength correlated with neurocognitive performance. All of the results were corrected using Monte-Carlo simulation. This exploratory study demonstrates a disruption of intrinsic functional connectivity without long-term exposure to antipsychotic medications in chronic schizophrenia. Furthermore, this disruption was connection-distance dependent, thus raising the possibility for differential neural pathways in neurocognitive impairment and psychiatric symptoms in schizophrenia. Copyright © 2014 Elsevier B.V. All rights reserved.
Neural correlates of childhood trauma with executive function in young healthy adults.
Lu, Shaojia; Pan, Fen; Gao, Weijia; Wei, Zhaoguo; Wang, Dandan; Hu, Shaohua; Huang, Manli; Xu, Yi; Li, Lingjiang
2017-10-03
The aim of this study was to investigate the relationship among childhood trauma, executive impairments, and altered resting-state brain function in young healthy adults. Twenty four subjects with childhood trauma and 24 age- and gender-matched subjects without childhood trauma were recruited. Executive function was assessed by a series of validated test procedures. Localized brain activity was evaluated by fractional amplitude of low frequency fluctuation (fALFF) method and compared between two groups. Areas with altered fALFF were further selected as seeds in subsequent functional connectivity analysis. Correlations of fALFF and connectivity values with severity of childhood trauma and executive dysfunction were analyzed as well. Subjects with childhood trauma exhibited impaired executive function as assessed by Wisconsin Card Sorting Test and Stroop Color Word Test. Traumatic individuals also showed increased fALFF in the right precuneus and decreased fALFF in the right superior temporal gyrus. Significant correlations of specific childhood trauma severity with executive dysfunction and fALFF value in the right precuneus were found in the whole sample. In addition, individuals with childhood trauma also exhibited diminished precuneus-based connectivity in default mode network with left ventromedial prefrontal cortex, left orbitofrontal cortex, and right cerebellum. Decreased default mode network connectivity was also associated with childhood trauma severity and executive dysfunction. The present findings suggest that childhood trauma is associated with executive deficits and aberrant default mode network functions even in healthy adults. Moreover, this study demonstrates that executive dysfunction is related to disrupted default mode network connectivity.
Altered Intrinsic Functional Brain Architecture in Children at Familial Risk of Major Depression
Chai, Xiaoqian J.; Hirshfeld-Becker, Dina; Biederman, Joseph; Uchida, Mai; Doehrmann, Oliver; Leonard, Julia; Salvatore, John; Kenworthy, Tara; Brown, Ariel; Kagan, Elana; de los Angeles, Carlo; Gabrieli, John D.E.; Whitfield-Gabrieli, Susan
2015-01-01
Background Neuroimaging studies of patients with major depression have revealed abnormal intrinsic functional connectivity measured during the resting state in multiple, distributed networks. However, it is unclear whether these findings reflect the state of major depression or reflect trait neurobiological underpinnings of risk for major depression. Methods We compared resting-state functional connectivity, measured with functional magnetic resonance imaging (fMRI), between unaffected children of parents who had documented histories of major depression (at-risk, n = 27; 8–14 years of age) and age-matched children of parents with no lifetime history of depression (controls, n = 16). Results At-risk children exhibited hyperconnectivity between the default mode network (DMN) and subgenual anterior cingulate cortex (sgACC) / orbital frontal cortex (OFC), and the magnitude of connectivity positively correlated with individual symptom scores. At-risk children also exhibited (1) hypoconnectivity within the cognitive control network, which also lacked the typical anticorrelation with the DMN; (2) hypoconnectivity between left dorsolateral prefrontal cortex (DLPFC) and sgACC; and (3) hyperconnectivity between the right amygdala and right inferior frontal gyrus, a key region for top-down modulation of emotion. Classification between at-risk children and controls based on resting-state connectivity yielded high accuracy with high sensitivity and specificity that was superior to clinical rating scales. Conclusions Children at familial risk for depression exhibited atypical functional connectivity in the default-mode, cognitive-control, and affective networks. Such task-independent functional brain measures of risk for depression in children could be used to promote early intervention to reduce the likelihood of developing depression. PMID:26826874
Network modelling methods for FMRI.
Smith, Stephen M; Miller, Karla L; Salimi-Khorshidi, Gholamreza; Webster, Matthew; Beckmann, Christian F; Nichols, Thomas E; Ramsey, Joseph D; Woolrich, Mark W
2011-01-15
There is great interest in estimating brain "networks" from FMRI data. This is often attempted by identifying a set of functional "nodes" (e.g., spatial ROIs or ICA maps) and then conducting a connectivity analysis between the nodes, based on the FMRI timeseries associated with the nodes. Analysis methods range from very simple measures that consider just two nodes at a time (e.g., correlation between two nodes' timeseries) to sophisticated approaches that consider all nodes simultaneously and estimate one global network model (e.g., Bayes net models). Many different methods are being used in the literature, but almost none has been carefully validated or compared for use on FMRI timeseries data. In this work we generate rich, realistic simulated FMRI data for a wide range of underlying networks, experimental protocols and problematic confounds in the data, in order to compare different connectivity estimation approaches. Our results show that in general correlation-based approaches can be quite successful, methods based on higher-order statistics are less sensitive, and lag-based approaches perform very poorly. More specifically: there are several methods that can give high sensitivity to network connection detection on good quality FMRI data, in particular, partial correlation, regularised inverse covariance estimation and several Bayes net methods; however, accurate estimation of connection directionality is more difficult to achieve, though Patel's τ can be reasonably successful. With respect to the various confounds added to the data, the most striking result was that the use of functionally inaccurate ROIs (when defining the network nodes and extracting their associated timeseries) is extremely damaging to network estimation; hence, results derived from inappropriate ROI definition (such as via structural atlases) should be regarded with great caution. Copyright © 2010 Elsevier Inc. All rights reserved.
The Neural Substrates of Cognitive Control Deficits in Autism Spectrum Disorders
Solomon, Marjorie; Ozonoff, Sally; Ursu, Stefan; Ravizza, Susan; Cummings, Neil; Ly, Stanford; Carter, Cameron
2009-01-01
Executive functions deficits are among the most frequently reported symptoms of autism spectrum disorders (ASDs), however, there have been few functional magnetic resonance imaging (fMRI) studies that investigate the neural substrates of executive functions deficits in ASDs, and only one in adolescents. The current study examined cognitive control –the ability to maintain task context online to support adaptive functioning in the face of response competition—in 22 adolescents aged 12–18 with autism spectrum disorders and 23 age, gender, and IQ matched typically developing subjects. During the cue phase of the task, where subjects must maintain information online to overcome a prepotent response tendency, typically developing subjects recruited significantly more anterior frontal (BA 10), parietal (BA 7, 40), and occipital regions (BA 18) for high control trials (25% of trials) versus low control trials (75% of trials). Both groups showed similar activation for low control cues, however the ASD group exhibited significantly less activation for high control cues. Functional connectivity analysis using time series correlation, factor analysis, and beta series correlation methods provided convergent evidence that the ASD group exhibited lower levels of functional connectivity and less network integration between frontal, parietal, and occipital regions. In the typically developing group, fronto-parietal connectivity was related to lower error rates on high control trials. In the autism group, reduced fronto-parietal connectivity was related to attention deficit hyperactivity disorder symptoms. PMID:19410583
Early Math Achievement and Functional Connectivity in the Fronto-Parietal Network
Emerson, Robert W.; Cantlon, Jessica F.
2011-01-01
In this study we test the hypothesis that the functional connectivity of the frontal and parietal regions that children recruit during a basic numerical task (matching Arabic numerals to arrays of dots) is predictive of their math test scores (TEMA-3; Ginsburg 2003). Specifically, we tested 4- to 11-year-old children on a matching task during fMRI to localize a fronto-parietal network that responds more strongly during numerical matching than matching faces, words, or shapes. We then tested the functional connectivity between those regions during an independent task: natural viewing of an educational video that included math topics. Using this novel natural viewing method, we found that the connectivity between frontal and parietal regions during task-independent free-viewing of educational material is correlated with children's basic number matching ability, as well as their scores on the standardized test of mathematical ability (the TEMA). The correlation between children's mathematics scores and fronto-parietal connectivity is math-specific in the sense that it is independent of children's verbal IQ scores. Moreover, a control network, selective for faces, showed no correlation with mathematics performance. Finally, brain regions that correlate with subjects’ overall response times in the matching task do not account for our number- and math-related effects. We suggest that the functional intersection of number-related frontal and parietal regions is math-specific. PMID:22682903
Shaw, Emily E; Schultz, Aaron P; Sperling, Reisa A; Hedden, Trey
2015-10-01
Intrinsic functional connectivity MRI has become a widely used tool for measuring integrity in large-scale cortical networks. This study examined multiple cortical networks using Template-Based Rotation (TBR), a method that applies a priori network and nuisance component templates defined from an independent dataset to test datasets of interest. A priori templates were applied to a test dataset of 276 older adults (ages 65-90) from the Harvard Aging Brain Study to examine the relationship between multiple large-scale cortical networks and cognition. Factor scores derived from neuropsychological tests represented processing speed, executive function, and episodic memory. Resting-state BOLD data were acquired in two 6-min acquisitions on a 3-Tesla scanner and processed with TBR to extract individual-level metrics of network connectivity in multiple cortical networks. All results controlled for data quality metrics, including motion. Connectivity in multiple large-scale cortical networks was positively related to all cognitive domains, with a composite measure of general connectivity positively associated with general cognitive performance. Controlling for the correlations between networks, the frontoparietal control network (FPCN) and executive function demonstrated the only significant association, suggesting specificity in this relationship. Further analyses found that the FPCN mediated the relationships of the other networks with cognition, suggesting that this network may play a central role in understanding individual variation in cognition during aging.
Bhaumik, Runa; Jenkins, Lisanne M; Gowins, Jennifer R; Jacobs, Rachel H; Barba, Alyssa; Bhaumik, Dulal K; Langenecker, Scott A
2017-01-01
Understanding abnormal resting-state functional connectivity of distributed brain networks may aid in probing and targeting mechanisms involved in major depressive disorder (MDD). To date, few studies have used resting state functional magnetic resonance imaging (rs-fMRI) to attempt to discriminate individuals with MDD from individuals without MDD, and to our knowledge no investigations have examined a remitted (r) population. In this study, we examined the efficiency of support vector machine (SVM) classifier to successfully discriminate rMDD individuals from healthy controls (HCs) in a narrow early-adult age range. We empirically evaluated four feature selection methods including multivariate Least Absolute Shrinkage and Selection Operator (LASSO) and Elastic Net feature selection algorithms. Our results showed that SVM classification with Elastic Net feature selection achieved the highest classification accuracy of 76.1% (sensitivity of 81.5% and specificity of 68.9%) by leave-one-out cross-validation across subjects from a dataset consisting of 38 rMDD individuals and 29 healthy controls. The highest discriminating functional connections were between the left amygdala, left posterior cingulate cortex, bilateral dorso-lateral prefrontal cortex, and right ventral striatum. These appear to be key nodes in the etiopathophysiology of MDD, within and between default mode, salience and cognitive control networks. This technique demonstrates early promise for using rs-fMRI connectivity as a putative neurobiological marker capable of distinguishing between individuals with and without rMDD. These methods may be extended to periods of risk prior to illness onset, thereby allowing for earlier diagnosis, prevention, and intervention.
Petersson, K M; Nichols, T E; Poline, J B; Holmes, A P
1999-01-01
Functional neuroimaging (FNI) provides experimental access to the intact living brain making it possible to study higher cognitive functions in humans. In this review and in a companion paper in this issue, we discuss some common methods used to analyse FNI data. The emphasis in both papers is on assumptions and limitations of the methods reviewed. There are several methods available to analyse FNI data indicating that none is optimal for all purposes. In order to make optimal use of the methods available it is important to know the limits of applicability. For the interpretation of FNI results it is also important to take into account the assumptions, approximations and inherent limitations of the methods used. This paper gives a brief overview over some non-inferential descriptive methods and common statistical models used in FNI. Issues relating to the complex problem of model selection are discussed. In general, proper model selection is a necessary prerequisite for the validity of the subsequent statistical inference. The non-inferential section describes methods that, combined with inspection of parameter estimates and other simple measures, can aid in the process of model selection and verification of assumptions. The section on statistical models covers approaches to global normalization and some aspects of univariate, multivariate, and Bayesian models. Finally, approaches to functional connectivity and effective connectivity are discussed. In the companion paper we review issues related to signal detection and statistical inference. PMID:10466149
Human grasp assist device and method of use
NASA Technical Reports Server (NTRS)
Linn, Douglas Martin (Inventor); Ihrke, Chris A. (Inventor); Diftler, Myron A. (Inventor)
2012-01-01
A grasp assist device includes a glove portion having phalange rings, contact sensors for measuring a grasping force applied by an operator wearing the glove portion, and a tendon drive system (TDS). The device has flexible tendons connected to the phalange rings for moving the rings in response to feedback signals from the sensors. The TDS is connected to each of the tendons, and applies an augmenting tensile force thereto via a microcontroller adapted for determining the augmenting tensile force as a function of the grasping force. A method of augmenting a grasping force of an operator includes measuring the grasping force using the sensors, encoding the grasping force as the feedback signals, and calculating the augmenting tensile force as a function of the feedback signals using the microcontroller. The method includes energizing at least one actuator of a tendon drive system (TDS) to thereby apply the augmenting tensile force.
Hierarchical multivariate covariance analysis of metabolic connectivity.
Carbonell, Felix; Charil, Arnaud; Zijdenbos, Alex P; Evans, Alan C; Bedell, Barry J
2014-12-01
Conventional brain connectivity analysis is typically based on the assessment of interregional correlations. Given that correlation coefficients are derived from both covariance and variance, group differences in covariance may be obscured by differences in the variance terms. To facilitate a comprehensive assessment of connectivity, we propose a unified statistical framework that interrogates the individual terms of the correlation coefficient. We have evaluated the utility of this method for metabolic connectivity analysis using [18F]2-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. As an illustrative example of the utility of this approach, we examined metabolic connectivity in angular gyrus and precuneus seed regions of mild cognitive impairment (MCI) subjects with low and high β-amyloid burdens. This new multivariate method allowed us to identify alterations in the metabolic connectome, which would not have been detected using classic seed-based correlation analysis. Ultimately, this novel approach should be extensible to brain network analysis and broadly applicable to other imaging modalities, such as functional magnetic resonance imaging (MRI).
Electron transport property of tetrathiafulvalene molecule
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mondal, Rajkumar; Bhattacharya, Barnali; Deb, Jyotirmoy
2016-05-23
We have investigated electron transport behavior of tetrathiafulvalene molecule connected with zigzag graphene nanoribbon (zGNR) using density functional theory combined with non-equilibrium Green’s function method. We have reported the transmission coefficient of the scattering region at different bias voltage to explain the nature of the current.
Normative development of ventral striatal resting state connectivity in humans.
Fareri, Dominic S; Gabard-Durnam, Laurel; Goff, Bonnie; Flannery, Jessica; Gee, Dylan G; Lumian, Daniel S; Caldera, Christina; Tottenham, Nim
2015-09-01
Incentives play a crucial role in guiding behavior throughout our lives, but perhaps no more so than during the early years of life. The ventral striatum is a critical piece of an incentive-based learning circuit, sharing robust anatomical connections with subcortical (e.g., amygdala, hippocampus) and cortical structures (e.g., medial prefrontal cortex (mPFC), insula) that collectively support incentive valuation and learning. Resting-state functional connectivity (rsFC) is a powerful method that provides insight into the development of the functional architecture of these connections involved in incentive-based learning. We employed a seed-based correlation approach to investigate ventral striatal rsFC in a cross-sectional sample of typically developing individuals between the ages of 4.5 and 23-years old (n=66). Ventral striatal rsFC with the mPFC showed regionally specific linear age-related changes in connectivity that were associated with age-related increases in circulating testosterone levels. Further, ventral striatal connectivity with the posterior hippocampus and posterior insula demonstrated quadratic age-related changes characterized by negative connectivity in adolescence. Finally, across this age range, the ventral striatum demonstrated positive coupling with the amygdala beginning during childhood and remaining consistently positive across age. In sum, our findings suggest that normative ventral striatal rsFC development is dynamic and characterized by early establishment of connectivity with medial prefrontal and limbic structures supporting incentive-based learning, as well as substantial functional reorganization with later developing regions during transitions into and out of adolescence. Copyright © 2015. Published by Elsevier Inc.
Baker, Christopher A; Elyada, Yishai M; Parra, Andres; Bolton, M McLean
2016-01-01
We describe refinements in optogenetic methods for circuit mapping that enable measurements of functional synaptic connectivity with single-neuron resolution. By expanding a two-photon beam in the imaging plane using the temporal focusing method and restricting channelrhodopsin to the soma and proximal dendrites, we are able to reliably evoke action potentials in individual neurons, verify spike generation with GCaMP6s, and determine the presence or absence of synaptic connections with patch-clamp electrophysiological recording. DOI: http://dx.doi.org/10.7554/eLife.14193.001 PMID:27525487
Weiler, Marina; de Campos, Brunno Machado; de Ligo Teixeira, Camila Vieira; Casseb, Raphael Fernandes; Mac Knight Carletti-Cassani, Ana Flávia; Vicentini, Jéssica Elias; Magalhães, Thamires Naela Cardoso; Talib, Leda Leme; Forlenza, Orestes Vicente; Balthazar, Marcio Luiz Figueredo
2017-01-01
Background In the last decade, many studies have reported abnormal connectivity within the default mode network (DMN) in patients with Alzheimer disease. Few studies, however, have investigated other networks and their association with pathophysiological proteins obtained from cerebrospinal fluid (CSF). Methods We performed 3 T imaging in patients with mild Alzheimer disease, patients with amnestic mild cognitive impairment (aMCI) and healthy controls, and we collected CSF samples from the patients with aMCI and mild Alzheimer disease. We analyzed 57 regions from 8 networks. Additionally, we performed correlation tests to investigate possible associations between the networks’ functional connectivity and the protein levels obtained from the CSF of patients with aMCI and Alzheimer disease. Results Our sample included 41 patients with Alzheimer disease, 35 with aMCI and 48 controls. We found that the main connectivity abnormalities in those with Alzheimer disease occurred between the DMN and task-positive networks: these patients presented not only a decreased anticorrelation between some regions, but also an inversion of the correlation signal (positive correlation instead of anti-correlation). Those with aMCI did not present statistically different connectivity from patients with Alzheimer disease or controls. Abnormal levels of CSF proteins were associated with functional disconnectivity between several regions in both the aMCI and mild Alzheimer disease groups, extending well beyond the DMN or temporal areas. Limitations The presented data are cross-sectional in nature, and our findings are dependent on the choice of seed regions used. Conclusion We found that the main functional connectivity abnormalities occur between the DMN and task-positive networks and that the pathological levels of CSF biomarkers correlate with functional connectivity disruption in patients with Alzheimer disease. PMID:28375076
Name recognition in autism: EEG evidence of altered patterns of brain activity and connectivity.
Nowicka, Anna; Cygan, Hanna B; Tacikowski, Paweł; Ostaszewski, Paweł; Kuś, Rafał
2016-01-01
Impaired orienting to social stimuli is one of the core early symptoms of autism spectrum disorder (ASD). However, in contrast to faces, name processing has rarely been studied in individuals with ASD. Here, we investigated brain activity and functional connectivity associated with recognition of names in the high-functioning ASD group and in the control group. EEG was recorded in 15 young males with ASD and 15 matched one-to-one control individuals. EEG data were analyzed with the event-related potential (ERP), event-related desynchronization and event-related synchronization (ERD/S), as well as coherence and direct transfer function (DTF) methods. Four categories of names were presented visually: one's own, close-other's, famous, and unknown. Differences between the ASD and control groups were found for ERP, coherence, and DTF. In individuals with ASD, P300 (a positive ERP component) to own-name and to a close-other's name were similar whereas in control participants, P300 to own-name was enhanced when compared to all other names. Analysis of coherence and DTF revealed disruption of fronto-posterior task-related connectivity in individuals with ASD within the beta range frequencies. Moreover, DTF indicated the directionality of those impaired connections-they were going from parieto-occipital to frontal regions. DTF also showed inter-group differences in short-range connectivity: weaker connections within the frontal region and stronger connections within the occipital region in the ASD group in comparison to the control group. Our findings suggest a lack of the self-preference effect and impaired functioning of the attentional network during recognition of visually presented names in individuals with ASD.
Localization in abelian Chern-Simons theory
NASA Astrophysics Data System (ADS)
McLellan, B. D. K.
2013-02-01
Chern-Simons theory on a closed contact three-manifold is studied when the Lie group for gauge transformations is compact, connected, and abelian. The abelian Chern-Simons partition function is derived using the Faddeev-Popov gauge fixing method. The partition function is then formally computed using the technique of non-abelian localization. This study leads to a natural identification of the abelian Reidemeister-Ray-Singer torsion as a specific multiple of the natural unit symplectic volume form on the moduli space of flat abelian connections for the class of Sasakian three-manifolds. The torsion part of the abelian Chern-Simons partition function is computed explicitly in terms of Seifert data for a given Sasakian three-manifold.
Guo, Wenbin; Liu, Feng; Chen, Jindong; Wu, Renrong; Zhang, Zhikun; Yu, Miaoyu; Xue, Zhimin; Zhao, Jingping
2016-08-01
Abnormal functional connectivity has been observed in major depressive disorder. Anatomical distance may affect functional connectivity in patients with major depressive disorder. However, whether and how anatomical distance affects functional connectivity at rest remains unclear in drug-naive patients with major depressive disorder. Forty-four patients with major depressive disorder, as well as 44 age-, sex- and education-matched healthy controls, underwent resting-state functional magnetic resonance imaging scanning. Regional functional connectivity strength was calculated for each voxel in the whole brain, which was further divided into short- and long-range functional connectivity strength. The patients showed decreased long-range positive functional connectivity strength in the right inferior parietal lobule, as well as decreased short-range positive functional connectivity strength in the right insula and right superior temporal gyrus relative to those of the controls. No significant correlations existed between abnormal functional connectivity strength and the clinical variables of the patients. The findings revealed that anatomical distance decreases long- and short-range functional connectivity strength in patients with major depressive disorder, which may underlie the neurobiology of major depressive disorder. © The Royal Australian and New Zealand College of Psychiatrists 2015.
ERIC Educational Resources Information Center
Ladouceur, Cecile D.; Farchione, Tiffany; Diwadkar, Vaibhav; Pruitt, Patrick; Radwan, Jacqueline; Axelson, David A.; Birmaher, Boris; Phillips, Mary L.
2011-01-01
Objective: The functioning of neural systems supporting emotion processing and regulation in youth with bipolar disorder not otherwise specified (BP-NOS) remains poorly understood. We sought to examine patterns of activity and connectivity in youth with BP-NOS relative to youth with bipolar disorder type I (BP-I) and healthy controls (HC). Method:…
Apparatus for monitoring high temperature ultrasonic characterization
Lanagan, M.T.; Kupperman, D.S.; Yaconi, G.A.
1998-03-24
A method and an apparatus for nondestructive detecting and evaluating changes in the microstructural properties of a material by employing one or more magnetostrictive transducers linked to the material by means of one or more sonic signal conductors. The magnetostrictive transducer or transducers are connected to a pulser/receiver which in turn is connected to an oscilloscope. The oscilloscope is connected to a computer which employs an algorithm to evaluate changes in the velocity of a signal transmitted to the material sample as function of time and temperature. 6 figs.
Ochoa, John Fredy; Alonso, Joan Francesc; Duque, Jon Edinson; Tobón, Carlos Andrés; Mañanas, Miguel Angel; Lopera, Francisco; Hernández, Alher Mauricio
2016-01-01
Background: Recent studies report increases in neural activity in brain regions critical to episodic memory at preclinical stages of Alzheimer’s disease (AD). Although electroencephalography (EEG) is widely used in AD studies, given its non-invasiveness and low cost, there is a need to translate the findings in other neuroimaging methods to EEG. Objective: To examine how the previous findings using functional magnetic resonance imaging (fMRI) at preclinical stage in presenilin-1 E280A mutation carriers could be assessed and extended, using EEG and a connectivity approach. Methods: EEG signals were acquired during resting and encoding in 30 normal cognitive young subjects, from an autosomal dominant early-onset AD kindred from Antioquia, Colombia. Regions of the brain previously reported as hyperactive were used for connectivity analysis. Results: Mutation carriers exhibited increasing connectivity at analyzed regions. Among them, the right precuneus exhibited the highest changes in connectivity. Conclusion: Increased connectivity in hyperactive cerebral regions is seen in individuals, genetically-determined to develop AD, at preclinical stage. The use of a connectivity approach and a widely available neuroimaging technique opens the possibility to increase the use of EEG in early detection of preclinical AD. PMID:27792014
How Different EEG References Influence Sensor Level Functional Connectivity Graphs
Huang, Yunzhi; Zhang, Junpeng; Cui, Yuan; Yang, Gang; He, Ling; Liu, Qi; Yin, Guangfu
2017-01-01
Highlights: Hamming Distance is applied to distinguish the difference of functional connectivity networkThe orientations of sources are testified to influence the scalp Functional Connectivity Graph (FCG) from different references significantlyREST, the reference electrode standardization technique, is proved to have an overall stable and excellent performance in variable situations. The choice of an electroencephalograph (EEG) reference is a practical issue for the study of brain functional connectivity. To study how EEG reference influence functional connectivity estimation (FCE), this study compares the differences of FCE resulting from the different references such as REST (the reference electrode standardization technique), average reference (AR), linked mastoids (LM), and left mastoid references (LR). Simulations involve two parts. One is based on 300 dipolar pairs, which are located on the superficial cortex with a radial source direction. The other part is based on 20 dipolar pairs. In each pair, the dipoles have various orientation combinations. The relative error (RE) and Hamming distance (HD) between functional connectivity matrices of ideal recordings and that of recordings obtained with different references, are metrics to compare the differences of the scalp functional connectivity graph (FCG) derived from those two kinds of recordings. Lower RE and HD values imply more similarity between the two FCGs. Using the ideal recording (IR) as a standard, the results show that AR, LM and LR perform well only in specific conditions, i.e., AR performs stable when there is no upward component in sources' orientation. LR achieves desirable results when the sources' locations are away from left ear. LM achieves an indistinct difference with IR, i.e., when the distribution of source locations is symmetric along the line linking the two ears. However, REST not only achieves excellent performance for superficial and radial dipolar sources, but also achieves a stable and robust performance with variable source locations and orientations. Benefitting from the stable and robust performance of REST vs. other reference methods, REST might best recover the real FCG of EEG. Thus, REST based FCG may be a good candidate to compare the FCG of EEG based on different references from different labs. PMID:28725175
Functional Brain Connectivity as a New Feature for P300 Speller.
Kabbara, Aya; Khalil, Mohamad; El-Falou, Wassim; Eid, Hassan; Hassan, Mahmoud
2016-01-01
The brain is a large-scale complex network often referred to as the "connectome". Cognitive functions and information processing are mainly based on the interactions between distant brain regions. However, most of the 'feature extraction' methods used in the context of Brain Computer Interface (BCI) ignored the possible functional relationships between different signals recorded from distinct brain areas. In this paper, the functional connectivity quantified by the phase locking value (PLV) was introduced to characterize the evoked responses (ERPs) obtained in the case of target and non-targets visual stimuli. We also tested the possibility of using the functional connectivity in the context of 'P300 speller'. The proposed approach was compared to the well-known methods proposed in the state of the art of "P300 Speller", mainly the peak picking, the area, time/frequency based features, the xDAWN spatial filtering and the stepwise linear discriminant analysis (SWLDA). The electroencephalographic (EEG) signals recorded from ten subjects were analyzed offline. The results indicated that phase synchrony offers relevant information for the classification in a P300 speller. High synchronization between the brain regions was clearly observed during target trials, although no significant synchronization was detected for a non-target trial. The results showed also that phase synchrony provides higher performance than some existing methods for letter classification in a P300 speller principally when large number of trials is available. Finally, we tested the possible combination of both approaches (classical features and phase synchrony). Our findings showed an overall improvement of the performance of the P300-speller when using Peak picking, the area and frequency based features. Similar performances were obtained compared to xDAWN and SWLDA when using large number of trials.
Semework, Mulugeta; DiStasio, Marcello
2014-01-01
Recording the activity of large populations of neurons requires new methods to analyze and use the large volumes of time series data thus created. Fast and clear methods for finding functional connectivity are an important step toward the goal of understanding neural processing. This problem presents itself readily in somatosensory neuroprosthesis (SSNP) research, which uses microstimulation (MiSt) to activate neural tissue to mimic natural stimuli, and has the capacity to potentiate, depotentiate, or even destroy functional connections. As the aim of SSNP engineering is artificially creating neural responses that resemble those observed during natural inputs, a central goal is describing the influence of MiSt on activity structure among groups of neurons, and how this structure may be altered to affect perception or behavior. In this paper, we demonstrate the concept of Granger causality, combined with maximum likelihood methods, applied to neural signals recorded before, during, and after natural and electrical stimulation. We show how these analyses can be used to evaluate the changing interactions in the thalamocortical somatosensory system in response to repeated perturbation. Using LFPs recorded from the ventral posterolateral thalamus (VPL) and somatosensory cortex (S1) in anesthetized rats, we estimated pair-wise functional interactions between functional microdomains. The preliminary results demonstrate input-dependent modulations in the direction and strength of information flow during and after application of MiSt. Cortico-cortical interactions during cortical MiSt and baseline conditions showed the largest causal influence differences, while there was no statistically significant difference between pre- and post-stimulation baseline causal activities. These functional connectivity changes agree with physiologically accepted communication patterns through the network, and their particular parameters have implications for both rehabilitation and brain—machine interface SSNP applications. PMID:25249973
Improving Response Inhibition in Parkinson’s Disease with Atomoxetine
Ye, Zheng; Altena, Ellemarije; Nombela, Cristina; Housden, Charlotte R.; Maxwell, Helen; Rittman, Timothy; Huddleston, Chelan; Rae, Charlotte L.; Regenthal, Ralf; Sahakian, Barbara J.; Barker, Roger A.; Robbins, Trevor W.; Rowe, James B.
2015-01-01
Background Dopaminergic drugs remain the mainstay of Parkinson’s disease therapy but often fail to improve cognitive problems such as impulsivity. This may be due to the loss of other neurotransmitters, including noradrenaline, which is linked to impulsivity and response inhibition. We therefore examined the effect of the selective noradrenaline reuptake inhibitor atomoxetine on response inhibition in a stop-signal paradigm. Methods This pharmacological functional magnetic resonance imaging study used a double-blinded randomized crossover design with low-frequency inhibition trials distributed among frequent Go trials. Twenty-one patients received 40 mg atomoxetine or placebo. Control subjects were tested on no-drug. The effects of disease and drug on behavioral performance, regional brain activity, and functional connectivity were analyzed using general linear models. Anatomical connectivity was examined using diffusion-weighted imaging. Results Patients with Parkinson’s disease had longer stop-signal reaction times, less stop-related activation in the right inferior frontal gyrus (RIFG), and weaker functional connectivity between the RIFG and striatum compared with control subjects. Atomoxetine enhanced stop-related RIFG activation in proportion to disease severity. Although there was no overall behavioral benefit from atomoxetine, analyses of individual differences revealed that enhanced response inhibition by atomoxetine was associated with increased RIFG activation and functional frontostriatal connectivity. Improved performance was more likely in patients with higher structural frontostriatal connectivity. Conclusions This study suggests that enhanced prefrontal cortical activation and frontostriatal connectivity by atomoxetine may improve response inhibition in Parkinson’s disease. These results point the way to new stratified clinical trials of atomoxetine to treat impulsivity in selected patients with Parkinson’s disease. PMID:24655598
Connectome analysis for pre-operative brain mapping in neurosurgery
Hart, Michael G.; Price, Stephen J.; Suckling, John
2016-01-01
Abstract Object: Brain mapping has entered a new era focusing on complex network connectivity. Central to this is the search for the connectome or the brains ‘wiring diagram’. Graph theory analysis of the connectome allows understanding of the importance of regions to network function, and the consequences of their impairment or excision. Our goal was to apply connectome analysis in patients with brain tumours to characterise overall network topology and individual patterns of connectivity alterations. Methods: Resting-state functional MRI data were acquired using multi-echo, echo planar imaging pre-operatively from five participants each with a right temporal–parietal–occipital glioblastoma. Complex networks analysis was initiated by parcellating the brain into anatomically regions amongst which connections were identified by retaining the most significant correlations between the respective wavelet decomposed time-series. Results: Key characteristics of complex networks described in healthy controls were preserved in these patients, including ubiquitous small world organization. An exponentially truncated power law fit to the degree distribution predicted findings of general network robustness to injury but with a core of hubs exhibiting disproportionate vulnerability. Tumours produced a consistent reduction in local and long-range connectivity with distinct patterns of connection loss depending on lesion location. Conclusions: Connectome analysis is a feasible and novel approach to brain mapping in individual patients with brain tumours. Applications to pre-surgical planning include identifying regions critical to network function that should be preserved and visualising connections at risk from tumour resection. In the future one could use such data to model functional plasticity and recovery of cognitive deficits. PMID:27447756
Manning, Joshua; Reynolds, Gretchen; Saygin, Zeynep M; Hofmann, Stefan G; Pollack, Mark; Gabrieli, John D E; Whitfield-Gabrieli, Susan
2015-01-01
We investigated differences in the intrinsic functional brain organization (functional connectivity) of the human reward system between healthy control participants and patients with social anxiety disorder. Functional connectivity was measured in the resting-state via functional magnetic resonance imaging (fMRI). 53 patients with social anxiety disorder and 33 healthy control participants underwent a 6-minute resting-state fMRI scan. Functional connectivity of the reward system was analyzed by calculating whole-brain temporal correlations with a bilateral nucleus accumbens seed and a ventromedial prefrontal cortex seed. Patients with social anxiety disorder, relative to the control group, had (1) decreased functional connectivity between the nucleus accumbens seed and other regions associated with reward, including ventromedial prefrontal cortex; (2) decreased functional connectivity between the ventromedial prefrontal cortex seed and lateral prefrontal regions, including the anterior and dorsolateral prefrontal cortices; and (3) increased functional connectivity between both the nucleus accumbens seed and the ventromedial prefrontal cortex seed with more posterior brain regions, including anterior cingulate cortex. Social anxiety disorder appears to be associated with widespread differences in the functional connectivity of the reward system, including markedly decreased functional connectivity between reward regions and between reward regions and lateral prefrontal cortices, and markedly increased functional connectivity between reward regions and posterior brain regions.
Gene function prediction with gene interaction networks: a context graph kernel approach.
Li, Xin; Chen, Hsinchun; Li, Jiexun; Zhang, Zhu
2010-01-01
Predicting gene functions is a challenge for biologists in the postgenomic era. Interactions among genes and their products compose networks that can be used to infer gene functions. Most previous studies adopt a linkage assumption, i.e., they assume that gene interactions indicate functional similarities between connected genes. In this study, we propose to use a gene's context graph, i.e., the gene interaction network associated with the focal gene, to infer its functions. In a kernel-based machine-learning framework, we design a context graph kernel to capture the information in context graphs. Our experimental study on a testbed of p53-related genes demonstrates the advantage of using indirect gene interactions and shows the empirical superiority of the proposed approach over linkage-assumption-based methods, such as the algorithm to minimize inconsistent connected genes and diffusion kernels.
The visual white matter: The application of diffusion MRI and fiber tractography to vision science
Rokem, Ariel; Takemura, Hiromasa; Bock, Andrew S.; Scherf, K. Suzanne; Behrmann, Marlene; Wandell, Brian A.; Fine, Ione; Bridge, Holly; Pestilli, Franco
2017-01-01
Visual neuroscience has traditionally focused much of its attention on understanding the response properties of single neurons or neuronal ensembles. The visual white matter and the long-range neuronal connections it supports are fundamental in establishing such neuronal response properties and visual function. This review article provides an introduction to measurements and methods to study the human visual white matter using diffusion MRI. These methods allow us to measure the microstructural and macrostructural properties of the white matter in living human individuals; they allow us to trace long-range connections between neurons in different parts of the visual system and to measure the biophysical properties of these connections. We also review a range of findings from recent studies on connections between different visual field maps, the effects of visual impairment on the white matter, and the properties underlying networks that process visual information supporting visual face recognition. Finally, we discuss a few promising directions for future studies. These include new methods for analysis of MRI data, open datasets that are becoming available to study brain connectivity and white matter properties, and open source software for the analysis of these data. PMID:28196374
A probabilistic framework to infer brain functional connectivity from anatomical connections.
Deligianni, Fani; Varoquaux, Gael; Thirion, Bertrand; Robinson, Emma; Sharp, David J; Edwards, A David; Rueckert, Daniel
2011-01-01
We present a novel probabilistic framework to learn across several subjects a mapping from brain anatomical connectivity to functional connectivity, i.e. the covariance structure of brain activity. This prediction problem must be formulated as a structured-output learning task, as the predicted parameters are strongly correlated. We introduce a model selection framework based on cross-validation with a parametrization-independent loss function suitable to the manifold of covariance matrices. Our model is based on constraining the conditional independence structure of functional activity by the anatomical connectivity. Subsequently, we learn a linear predictor of a stationary multivariate autoregressive model. This natural parameterization of functional connectivity also enforces the positive-definiteness of the predicted covariance and thus matches the structure of the output space. Our results show that functional connectivity can be explained by anatomical connectivity on a rigorous statistical basis, and that a proper model of functional connectivity is essential to assess this link.
Rosskopf, Johannes; Gorges, Martin; Müller, Hans-Peter; Lulé, Dorothée; Uttner, Ingo; Ludolph, Albert C; Pinkhardt, Elmar; Juengling, Freimut D; Kassubek, Jan
2017-07-01
The topography of functional network changes in progressive supranuclear palsy can be mapped by intrinsic functional connectivity MRI. The objective of this study was to study functional connectivity and its clinical and behavioral correlates in dedicated networks comprising the cognition-related default mode and the motor and midbrain functional networks in patients with PSP. Whole-brain-based "resting-state" functional MRI and high-resolution T1-weighted magnetic resonance imaging data together with neuropsychological and video-oculographic data from 34 PSP patients (22 with Richardson subtype and 12 with parkinsonian subtype) and 35 matched healthy controls were subjected to network-based functional connectivity and voxel-based morphometry analysis. After correction for global patterns of brain atrophy, the group comparison between PSP patients and controls revealed significantly decreased functional connectivity (P < 0.05, corrected) in the prefrontal cortex, which was significantly correlated with cognitive performance (P = 0.006). Of note, midbrain network connectivity in PSP patients showed increased connectivity with the thalamus, on the one hand, whereas, on the other hand, lower functional connectivity within the midbrain was significantly correlated with vertical gaze impairment, as quantified by video-oculography (P = 0.004). PSP Richardson subtype showed significantly increased functional motor network connectivity with the medial prefrontal gyrus. PSP-associated neurodegeneration was attributed to both decreased and increased functional connectivity. Decreasing functional connectivity was associated with worse behavioral performance (ie, dementia severity and gaze palsy), whereas the pattern of increased functional connectivity may be a potential adaptive mechanism. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.
Multi-thread parallel algorithm for reconstructing 3D large-scale porous structures
NASA Astrophysics Data System (ADS)
Ju, Yang; Huang, Yaohui; Zheng, Jiangtao; Qian, Xu; Xie, Heping; Zhao, Xi
2017-04-01
Geomaterials inherently contain many discontinuous, multi-scale, geometrically irregular pores, forming a complex porous structure that governs their mechanical and transport properties. The development of an efficient reconstruction method for representing porous structures can significantly contribute toward providing a better understanding of the governing effects of porous structures on the properties of porous materials. In order to improve the efficiency of reconstructing large-scale porous structures, a multi-thread parallel scheme was incorporated into the simulated annealing reconstruction method. In the method, four correlation functions, which include the two-point probability function, the linear-path functions for the pore phase and the solid phase, and the fractal system function for the solid phase, were employed for better reproduction of the complex well-connected porous structures. In addition, a random sphere packing method and a self-developed pre-conditioning method were incorporated to cast the initial reconstructed model and select independent interchanging pairs for parallel multi-thread calculation, respectively. The accuracy of the proposed algorithm was evaluated by examining the similarity between the reconstructed structure and a prototype in terms of their geometrical, topological, and mechanical properties. Comparisons of the reconstruction efficiency of porous models with various scales indicated that the parallel multi-thread scheme significantly shortened the execution time for reconstruction of a large-scale well-connected porous model compared to a sequential single-thread procedure.
NASA Astrophysics Data System (ADS)
Hu, Bin; Dong, Qunxi; Hao, Yanrong; Zhao, Qinglin; Shen, Jian; Zheng, Fang
2017-08-01
Objective. Neuro-electrophysiological tools have been widely used in heroin addiction studies. Previous studies indicated that chronic heroin abuse would result in abnormal functional organization of the brain, while few heroin addiction studies have applied the effective connectivity tool to analyze the brain functional system (BFS) alterations induced by heroin abuse. The present study aims to identify the abnormality of resting-state heroin abstinent BFS using source decomposition and effective connectivity tools. Approach. The resting-state electroencephalograph (EEG) signals were acquired from 15 male heroin abstinent (HA) subjects and 14 male non-addicted (NA) controls. Multivariate autoregressive models combined independent component analysis (MVARICA) was applied for blind source decomposition. Generalized partial directed coherence (GPDC) was applied for effective brain connectivity analysis. Effective brain networks of both HA and NA groups were constructed. The two groups of effective cortical networks were compared by the bootstrap method. Abnormal causal interactions between decomposed source regions were estimated in the 1-45 Hz frequency domain. Main results. This work suggested: (a) there were clear effective network alterations in heroin abstinent subject groups; (b) the parietal region was a dominant hub of the abnormally weaker causal pathways, and the left occipital region was a dominant hub of the abnormally stronger causal pathways. Significance. These findings provide direct evidence that chronic heroin abuse induces brain functional abnormalities. The potential value of combining effective connectivity analysis and brain source decomposition methods in exploring brain alterations of heroin addicts is also implied.
Hu, Bin; Dong, Qunxi; Hao, Yanrong; Zhao, Qinglin; Shen, Jian; Zheng, Fang
2017-08-01
Neuro-electrophysiological tools have been widely used in heroin addiction studies. Previous studies indicated that chronic heroin abuse would result in abnormal functional organization of the brain, while few heroin addiction studies have applied the effective connectivity tool to analyze the brain functional system (BFS) alterations induced by heroin abuse. The present study aims to identify the abnormality of resting-state heroin abstinent BFS using source decomposition and effective connectivity tools. The resting-state electroencephalograph (EEG) signals were acquired from 15 male heroin abstinent (HA) subjects and 14 male non-addicted (NA) controls. Multivariate autoregressive models combined independent component analysis (MVARICA) was applied for blind source decomposition. Generalized partial directed coherence (GPDC) was applied for effective brain connectivity analysis. Effective brain networks of both HA and NA groups were constructed. The two groups of effective cortical networks were compared by the bootstrap method. Abnormal causal interactions between decomposed source regions were estimated in the 1-45 Hz frequency domain. This work suggested: (a) there were clear effective network alterations in heroin abstinent subject groups; (b) the parietal region was a dominant hub of the abnormally weaker causal pathways, and the left occipital region was a dominant hub of the abnormally stronger causal pathways. These findings provide direct evidence that chronic heroin abuse induces brain functional abnormalities. The potential value of combining effective connectivity analysis and brain source decomposition methods in exploring brain alterations of heroin addicts is also implied.
Mazzucchi, Edoardo; Vollono, Catello; Losurdo, Anna; Testani, Elisa; Gnoni, Valentina; Di Blasi, Chiara; Giannantoni, Nadia M; Lapenta, Leonardo; Brunetti, Valerio; Della Marca, Giacomo
2017-01-01
Hyperventilation (HV) is a commonly used electroencephalogram activation method. We analyzed EEG recordings in 22 normal subjects and 22 patients with focal epilepsy of unknown cause. We selected segments before (PRE), during (HYPER), and 5 minutes after (POST) HV. To analyze the neural generators of EEG signal, we used standard low-resolution electromagnetic tomography (sLORETA software). We then computed EEG lagged coherence, an index of functional connectivity, between 19 regions of interest. A weighted graph was built for each band in every subject, and characteristic path length (L) and clustering coefficient (C) have been computed. Statistical comparisons were performed by means of analysis of variance (Group X Condition X Band) for mean lagged coherence, L and C. Hyperventilation significantly increases EEG neural generators (P < 0.001); the effect is particularly evident in cingulate cortex. Functional connectivity was increased by HV in delta, theta, alpha, and beta bands in the Epileptic group (P < 0.01) and only in theta band in Control group. Intergroup analysis of mean lagged coherence, C and L, showed significant differences for Group (P < 0.001), Condition (P < 0.001), and Band (P < 0.001). Analysis of variance for L also showed significant interactions: Group X Condition (P = 0.003) and Group X Band (P < 0.001). In our relatively small group of epileptic patients, HV is associated with activation of cingulate cortex; moreover, it modifies brain connectivity. The significant differences in mean lagged coherence, path length, and clustering coefficient permit to hypothesize that this activation method leads to different brain connectivity patterns in patients with epilepsy when compared with normal subjects. If confirmed by other studies involving larger populations, this analysis could become a diagnostic tool in epilepsy.
Spisák, Tamás; Jakab, András; Kis, Sándor A; Opposits, Gábor; Aranyi, Csaba; Berényi, Ervin; Emri, Miklós
2014-01-01
Functional Magnetic Resonance Imaging (fMRI) based brain connectivity analysis maps the functional networks of the brain by estimating the degree of synchronous neuronal activity between brain regions. Recent studies have demonstrated that "resting-state" fMRI-based brain connectivity conclusions may be erroneous when motion artifacts have a differential effect on fMRI BOLD signals for between group comparisons. A potential explanation could be that in-scanner displacement, due to rotational components, is not spatially constant in the whole brain. However, this localized nature of motion artifacts is poorly understood and is rarely considered in brain connectivity studies. In this study, we initially demonstrate the local correspondence between head displacement and the changes in the resting-state fMRI BOLD signal. Than, we investigate how connectivity strength is affected by the population-level variation in the spatial pattern of regional displacement. We introduce Regional Displacement Interaction (RDI), a new covariate parameter set for second-level connectivity analysis and demonstrate its effectiveness in reducing motion related confounds in comparisons of groups with different voxel-vise displacement pattern and preprocessed using various nuisance regression methods. The effect of using RDI as second-level covariate is than demonstrated in autism-related group comparisons. The relationship between the proposed method and some of the prevailing subject-level nuisance regression techniques is evaluated. Our results show that, depending on experimental design, treating in-scanner head motion as a global confound may not be appropriate. The degree of displacement is highly variable among various brain regions, both within and between subjects. These regional differences bias correlation-based measures of brain connectivity. The inclusion of the proposed second-level covariate into the analysis successfully reduces artifactual motion-related group differences and preserves real neuronal differences, as demonstrated by the autism-related comparisons.
Lie, Octavian V; van Mierlo, Pieter
2017-01-01
The visual interpretation of intracranial EEG (iEEG) is the standard method used in complex epilepsy surgery cases to map the regions of seizure onset targeted for resection. Still, visual iEEG analysis is labor-intensive and biased due to interpreter dependency. Multivariate parametric functional connectivity measures using adaptive autoregressive (AR) modeling of the iEEG signals based on the Kalman filter algorithm have been used successfully to localize the electrographic seizure onsets. Due to their high computational cost, these methods have been applied to a limited number of iEEG time-series (<60). The aim of this study was to test two Kalman filter implementations, a well-known multivariate adaptive AR model (Arnold et al. 1998) and a simplified, computationally efficient derivation of it, for their potential application to connectivity analysis of high-dimensional (up to 192 channels) iEEG data. When used on simulated seizures together with a multivariate connectivity estimator, the partial directed coherence, the two AR models were compared for their ability to reconstitute the designed seizure signal connections from noisy data. Next, focal seizures from iEEG recordings (73-113 channels) in three patients rendered seizure-free after surgery were mapped with the outdegree, a graph-theory index of outward directed connectivity. Simulation results indicated high levels of mapping accuracy for the two models in the presence of low-to-moderate noise cross-correlation. Accordingly, both AR models correctly mapped the real seizure onset to the resection volume. This study supports the possibility of conducting fully data-driven multivariate connectivity estimations on high-dimensional iEEG datasets using the Kalman filter approach.
Sex-related differences in amygdala functional connectivity during resting conditions.
Kilpatrick, L A; Zald, D H; Pardo, J V; Cahill, L F
2006-04-01
Recent neuroimaging studies have established a sex-related hemispheric lateralization of amygdala involvement in memory for emotionally arousing material. Here, we examine the possibility that sex-related differences in amygdala involvement in memory for emotional material develop from differential patterns of amygdala functional connectivity evident in the resting brain. Seed voxel partial least square analyses of regional cerebral blood flow data revealed significant sex-related differences in amygdala functional connectivity during resting conditions. The right amygdala was associated with greater functional connectivity in men than in women. In contrast, the left amygdala was associated with greater functional connectivity in women than in men. Furthermore, the regions displaying stronger functional connectivity with the right amygdala in males (sensorimotor cortex, striatum, pulvinar) differed from those displaying stronger functional connectivity with the left amygdala in females (subgenual cortex, hypothalamus). These differences in functional connectivity at rest may link to sex-related differences in medical and psychiatric disorders.
White matter structural connectivity is associated with sensorimotor function in stroke survivors☆
Kalinosky, Benjamin T.; Schindler-Ivens, Sheila; Schmit, Brian D.
2013-01-01
Purpose Diffusion tensor imaging (DTI) provides functionally relevant information about white matter structure. Local anatomical connectivity information combined with fractional anisotropy (FA) and mean diffusivity (MD) may predict functional outcomes in stroke survivors. Imaging methods for predicting functional outcomes in stroke survivors are not well established. This work uses DTI to objectively assess the effects of a stroke lesion on white matter structure and sensorimotor function. Methods A voxel-based approach is introduced to assess a stroke lesion's global impact on motor function. Anatomical T1-weighted and diffusion tensor images of the brain were acquired for nineteen subjects (10 post-stroke and 9 age-matched controls). A manually selected volume of interest was used to alleviate the effects of stroke lesions on image registration. Images from all subjects were registered to the images of the control subject that was anatomically closest to Talairach space. Each subject's transformed image was uniformly seeded for DTI tractography. Each seed was inversely transformed into the individual subject space, where DTI tractography was conducted and then the results were transformed back to the reference space. A voxel-wise connectivity matrix was constructed from the fibers, which was then used to calculate the number of directly and indirectly connected neighbors of each voxel. A novel voxel-wise indirect structural connectivity (VISC) index was computed as the average number of direct connections to a voxel's indirect neighbors. Voxel-based analyses (VBA) were performed to compare VISC, FA, and MD for the detection of lesion-induced changes in sensorimotor function. For each voxel, a t-value was computed from the differences between each stroke brain and the 9 controls. A series of linear regressions was performed between Fugl-Meyer (FM) assessment scores of sensorimotor impairment and each DTI metric's log number of voxels that differed from the control group. Results Correlation between the logarithm of the number of significant voxels in the ipsilesional hemisphere and total Fugl-Meyer score was moderate for MD (R2 = 0.512), and greater for VISC (R2 = 0.796) and FA (R2 = 0.674). The slopes of FA (p = 0.0036), VISC (p = 0.0005), and MD (p = 0.0199) versus the total FM score were significant. However, these correlations were driven by the upper extremity motor component of the FM score (VISC: R2 = 0.879) with little influence of the lower extremity motor component (FA: R2 = 0.177). Conclusion The results suggest that a voxel-wise metric based on DTI tractography can predict upper extremity sensorimotor function of stroke survivors, and that supraspinal intraconnectivity may have a less dominant role in lower extremity function. PMID:24179827
Tsvetanov, Kamen A; Henson, Richard N A; Tyler, Lorraine K; Razi, Adeel; Geerligs, Linda; Ham, Timothy E; Rowe, James B
2016-03-16
The maintenance of wellbeing across the lifespan depends on the preservation of cognitive function. We propose that successful cognitive aging is determined by interactions both within and between large-scale functional brain networks. Such connectivity can be estimated from task-free functional magnetic resonance imaging (fMRI), also known as resting-state fMRI (rs-fMRI). However, common correlational methods are confounded by age-related changes in the neurovascular signaling. To estimate network interactions at the neuronal rather than vascular level, we used generative models that specified both the neural interactions and a flexible neurovascular forward model. The networks' parameters were optimized to explain the spectral dynamics of rs-fMRI data in 602 healthy human adults from population-based cohorts who were approximately uniformly distributed between 18 and 88 years (www.cam-can.com). We assessed directed connectivity within and between three key large-scale networks: the salience network, dorsal attention network, and default mode network. We found that age influences connectivity both within and between these networks, over and above the effects on neurovascular coupling. Canonical correlation analysis revealed that the relationship between network connectivity and cognitive function was age-dependent: cognitive performance relied on neural dynamics more strongly in older adults. These effects were driven partly by reduced stability of neural activity within all networks, as expressed by an accelerated decay of neural information. Our findings suggest that the balance of excitatory connectivity between networks, and the stability of intrinsic neural representations within networks, changes with age. The cognitive function of older adults becomes increasingly dependent on these factors. Maintaining cognitive function is critical to successful aging. To study the neural basis of cognitive function across the lifespan, we studied a large population-based cohort (n = 602, 18-88 years), separating neural connectivity from vascular components of fMRI signals. Cognitive ability was influenced by the strength of connection within and between functional brain networks, and this positive relationship increased with age. In older adults, there was more rapid decay of intrinsic neuronal activity in multiple regions of the brain networks, which related to cognitive performance. Our data demonstrate increased reliance on network flexibility to maintain cognitive function, in the presence of more rapid decay of neural activity. These insights will facilitate the development of new strategies to maintain cognitive ability. Copyright © 2016 Tsvetanov et al.
Henson, Richard N.A.; Tyler, Lorraine K.; Razi, Adeel; Geerligs, Linda; Ham, Timothy E.; Rowe, James B.
2016-01-01
The maintenance of wellbeing across the lifespan depends on the preservation of cognitive function. We propose that successful cognitive aging is determined by interactions both within and between large-scale functional brain networks. Such connectivity can be estimated from task-free functional magnetic resonance imaging (fMRI), also known as resting-state fMRI (rs-fMRI). However, common correlational methods are confounded by age-related changes in the neurovascular signaling. To estimate network interactions at the neuronal rather than vascular level, we used generative models that specified both the neural interactions and a flexible neurovascular forward model. The networks' parameters were optimized to explain the spectral dynamics of rs-fMRI data in 602 healthy human adults from population-based cohorts who were approximately uniformly distributed between 18 and 88 years (www.cam-can.com). We assessed directed connectivity within and between three key large-scale networks: the salience network, dorsal attention network, and default mode network. We found that age influences connectivity both within and between these networks, over and above the effects on neurovascular coupling. Canonical correlation analysis revealed that the relationship between network connectivity and cognitive function was age-dependent: cognitive performance relied on neural dynamics more strongly in older adults. These effects were driven partly by reduced stability of neural activity within all networks, as expressed by an accelerated decay of neural information. Our findings suggest that the balance of excitatory connectivity between networks, and the stability of intrinsic neural representations within networks, changes with age. The cognitive function of older adults becomes increasingly dependent on these factors. SIGNIFICANCE STATEMENT Maintaining cognitive function is critical to successful aging. To study the neural basis of cognitive function across the lifespan, we studied a large population-based cohort (n = 602, 18–88 years), separating neural connectivity from vascular components of fMRI signals. Cognitive ability was influenced by the strength of connection within and between functional brain networks, and this positive relationship increased with age. In older adults, there was more rapid decay of intrinsic neuronal activity in multiple regions of the brain networks, which related to cognitive performance. Our data demonstrate increased reliance on network flexibility to maintain cognitive function, in the presence of more rapid decay of neural activity. These insights will facilitate the development of new strategies to maintain cognitive ability. PMID:26985024
Early Functional Connectome Integrity and 1-Year Recovery in Comatose Survivors of Cardiac Arrest.
Sair, Haris I; Hannawi, Yousef; Li, Shanshan; Kornbluth, Joshua; Demertzi, Athena; Di Perri, Carol; Chabanne, Russell; Jean, Betty; Benali, Habib; Perlbarg, Vincent; Pekar, James; Luyt, Charles-Edouard; Galanaud, Damien; Velly, Lionel; Puybasset, Louis; Laureys, Steven; Caffo, Brian; Stevens, Robert D
2018-04-01
Purpose To assess whether early brain functional connectivity is associated with functional recovery 1 year after cardiac arrest (CA). Materials and Methods Enrolled in this prospective multicenter cohort were 46 patients who were comatose after CA. Principal outcome was cerebral performance category at 12 months, with favorable outcome (FO) defined as cerebral performance category 1 or 2. All participants underwent multiparametric structural and functional magnetic resonance (MR) imaging less than 4 weeks after CA. Within- and between-network connectivity was measured in dorsal attention network (DAN), default-mode network (DMN), salience network (SN), and executive control network (ECN) by using seed-based analysis of resting-state functional MR imaging data. Structural changes identified with fluid-attenuated inversion recovery and diffusion-weighted imaging sequences were analyzed by using validated morphologic scales. The association between connectivity measures, structural changes, and the principal outcome was explored with multivariable modeling. Results Patients underwent MR imaging a mean 12.6 days ± 5.6 (standard deviation) after CA. At 12 months, 11 patients had an FO. Patients with FO had higher within-DMN connectivity and greater anticorrelation between SN and DMN and between SN and ECN compared with patients with unfavorable outcome, an effect that was maintained after multivariable adjustment. Anticorrelation of SN-DMN predicted outcomes with higher accuracy than fluid-attenuated inversion recovery or diffusion-weighted imaging scores (area under the receiver operating characteristic curves, respectively, 0.88, 0.74, and 0.71). Conclusion MR imaging-based measures of cerebral functional network connectivity obtained in the acute phase of CA were independently associated with FO at 1 year, warranting validation as early markers of long-term recovery potential in patients with anoxic-ischemic encephalopathy. © RSNA, 2017.
Segmentation of the Thalamus Based on BOLD Frequencies Affected in Temporal Lobe Epilepsy
Morgan, Victoria L.; Rogers, Baxter P.; Abou-Khalil, Bassel
2015-01-01
Objective Temporal lobe epilepsy is associated with functional changes throughout the brain, particularly including a putative seizure propagation network involving the hippocampus, insula and thalamus. We identified a specified frequency range where functional connectivity in this network was related to duration of disease. Then, to identify specific thalamic nuclei involved in seizure propagation, we determined the subregions of the thalamus that have increased resting functional oscillations in this frequency range. Methods Resting-state functional MRI (fMRI) was acquired from twenty unilateral TLE (14 right, 6 left) patients and twenty healthy controls who were each age and gender matched to a specific patient. Wavelet based functional MRI connectivity mapping across the network was computed at each frequency to determine those frequencies where connectivity significantly decreases with duration of disease consistent with impairment due to repeated seizures. The voxel-wise power of the spontaneous blood oxygenation fluctuations of this frequency band was computed in the thalamus of each subject. Results Functional connectivity was impaired in the proposed seizure propagation network over a specific range (0.0067–0.013 Hz and 0.024–0.032 Hz) of blood oxygenation oscillations. Increased power in this frequency band (<0.032 Hz) was detected bilaterally in the pulvinar and anterior nucleus of the thalamus of healthy controls, and was increased over the ipsilateral thalamus compared to the contralateral thalamus in TLE. Significance This study identified frequencies of impaired connectivity in a TLE seizure propagation network and used them to localize the anterior nucleus and pulvinar of the thalamus as subregions most susceptible to TLE seizures. Further examinations of these frequencies in healthy and TLE subjects may provide unique information relating to the mechanism of seizure propagation and potential treatment using electrical stimulation. PMID:26360535
Mamashli, Fahimeh; Khan, Sheraz; Bharadwaj, Hari; Losh, Ainsley; Pawlyszyn, Stephanie M; Hämäläinen, Matti S; Kenet, Tal
2018-06-26
Autism spectrum disorder (ASD) is characterized neurophysiologically by, among other things, functional connectivity abnormalities in the brain. Recent evidence suggests that the nature of these functional connectivity abnormalities might not be uniform throughout maturation. Comparing between adolescents and young adults (ages 14-21) with ASD and age- and IQ-matched typically developing (TD) individuals, we previously documented, using magnetoencephalography (MEG) data, that local functional connectivity in the fusiform face areas (FFA) and long-range functional connectivity between FFA and three higher order cortical areas were all reduced in ASD. Given the findings on abnormal maturation trajectories in ASD, we tested whether these results extend to preadolescent children (ages 7-13). We found that both local and long-range functional connectivity were in fact normal in this younger age group in ASD. Combining the two age groups, we found that local and long-range functional connectivity measures were positively correlated with age in TD, but negatively correlated with age in ASD. Last, we showed that local functional connectivity was the primary feature in predicting age in ASD group, but not in the TD group. Furthermore, local functional connectivity was only correlated with ASD severity in the older group. These results suggest that the direction of maturation of functional connectivity for processing of faces from childhood to young adulthood is itself abnormal in ASD, and that during the processing of faces, these trajectory abnormalities are more pronounced for local functional connectivity measures than they are for long-range functional connectivity measures. © 2018 Wiley Periodicals, Inc.
NASA Astrophysics Data System (ADS)
O'Neill, George C.; Barratt, Eleanor L.; Hunt, Benjamin A. E.; Tewarie, Prejaas K.; Brookes, Matthew J.
2015-11-01
The human brain can be divided into multiple areas, each responsible for different aspects of behaviour. Healthy brain function relies upon efficient connectivity between these areas and, in recent years, neuroimaging has been revolutionised by an ability to estimate this connectivity. In this paper we discuss measurement of network connectivity using magnetoencephalography (MEG), a technique capable of imaging electrophysiological brain activity with good (~5 mm) spatial resolution and excellent (~1 ms) temporal resolution. The rich information content of MEG facilitates many disparate measures of connectivity between spatially separate regions and in this paper we discuss a single metric known as power envelope correlation. We review in detail the methodology required to measure power envelope correlation including (i) projection of MEG data into source space, (ii) removing confounds introduced by the MEG inverse problem and (iii) estimation of connectivity itself. In this way, we aim to provide researchers with a description of the key steps required to assess envelope based functional networks, which are thought to represent an intrinsic mode of coupling in the human brain. We highlight the principal findings of the techniques discussed, and furthermore, we show evidence that this method can probe how the brain forms and dissolves multiple transient networks on a rapid timescale in order to support current processing demand. Overall, power envelope correlation offers a unique and verifiable means to gain novel insights into network coordination and is proving to be of significant value in elucidating the neural dynamics of the human connectome in health and disease.
Iyer, Parameswaran Mahadeva; Egan, Catriona; Pinto-Grau, Marta; Burke, Tom; Elamin, Marwa; Nasseroleslami, Bahman; Pender, Niall; Lalor, Edmund C.; Hardiman, Orla
2015-01-01
Background Amyotrophic Lateral Sclerosis (ALS) is heterogeneous and overlaps with frontotemporal dementia. Spectral EEG can predict damage in structural and functional networks in frontotemporal dementia but has never been applied to ALS. Methods 18 incident ALS patients with normal cognition and 17 age matched controls underwent 128 channel EEG and neuropsychology assessment. The EEG data was analyzed using FieldTrip software in MATLAB to calculate simple connectivity measures and scalp network measures. sLORETA was used in nodal analysis for source localization and same methods were applied as above to calculate nodal network measures. Graph theory measures were used to assess network integrity. Results Cross spectral density in alpha band was higher in patients. In ALS patients, increased degree values of the network nodes was noted in the central and frontal regions in the theta band across seven of the different connectivity maps (p<0.0005). Among patients, clustering coefficient in alpha and gamma bands was increased in all regions of the scalp and connectivity were significantly increased (p=0.02). Nodal network showed increased assortativity in alpha band in the patients group. The Clustering Coefficient in Partial Directed Connectivity (PDC) showed significantly higher values for patients in alpha, beta, gamma, theta and delta frequencies (p=0.05). Discussion There is increased connectivity in the fronto-central regions of the scalp and areas corresponding to Salience and Default Mode network in ALS, suggesting a pathologic disruption of neuronal networking in early disease states. Spectral EEG has potential utility as a biomarker in ALS. PMID:26091258
A minimization method on the basis of embedding the feasible set and the epigraph
NASA Astrophysics Data System (ADS)
Zabotin, I. Ya; Shulgina, O. N.; Yarullin, R. S.
2016-11-01
We propose a conditional minimization method of the convex nonsmooth function which belongs to the class of cutting-plane methods. During constructing iteration points a feasible set and an epigraph of the objective function are approximated by the polyhedral sets. In this connection, auxiliary problems of constructing iteration points are linear programming problems. In optimization process there is some opportunity of updating sets which approximate the epigraph. These updates are performed by periodically dropping of cutting planes which form embedding sets. Convergence of the proposed method is proved, some realizations of the method are discussed.
Akiki, Teddy J; Averill, Christopher L; Wrocklage, Kristen M; Scott, J Cobb; Averill, Lynnette A; Schweinsburg, Brian; Alexander-Bloch, Aaron; Martini, Brenda; Southwick, Steven M; Krystal, John H; Abdallah, Chadi G
2018-08-01
Disruption in the default mode network (DMN) has been implicated in numerous neuropsychiatric disorders, including posttraumatic stress disorder (PTSD). However, studies have largely been limited to seed-based methods and involved inconsistent definitions of the DMN. Recent advances in neuroimaging and graph theory now permit the systematic exploration of intrinsic brain networks. In this study, we used resting-state functional magnetic resonance imaging (fMRI), diffusion MRI, and graph theoretical analyses to systematically examine the DMN connectivity and its relationship with PTSD symptom severity in a cohort of 65 combat-exposed US Veterans. We employed metrics that index overall connectivity strength, network integration (global efficiency), and network segregation (clustering coefficient). Then, we conducted a modularity and network-based statistical analysis to identify DMN regions of particular importance in PTSD. Finally, structural connectivity analyses were used to probe whether white matter abnormalities are associated with the identified functional DMN changes. We found decreased DMN functional connectivity strength to be associated with increased PTSD symptom severity. Further topological characterization suggests decreased functional integration and increased segregation in subjects with severe PTSD. Modularity analyses suggest a spared connectivity in the posterior DMN community (posterior cingulate, precuneus, angular gyrus) despite overall DMN weakened connections with increasing PTSD severity. Edge-wise network-based statistical analyses revealed a prefrontal dysconnectivity. Analysis of the diffusion networks revealed no alterations in overall strength or prefrontal structural connectivity. DMN abnormalities in patients with severe PTSD symptoms are characterized by decreased overall interconnections. On a finer scale, we found a pattern of prefrontal dysconnectivity, but increased cohesiveness in the posterior DMN community and relative sparing of connectivity in this region. The DMN measures established in this study may serve as a biomarker of disease severity and could have potential utility in developing circuit-based therapeutics. Published by Elsevier Inc.
Ding, Wei-na; Sun, Jin-hua; Sun, Ya-wen; Zhou, Yan; Li, Lei; Xu, Jian-rong; Du, Ya-song
2013-01-01
Excessive use of the Internet has been linked to a variety of negative psychosocial consequences. This study used resting-state functional magnetic resonance imaging (fMRI) to investigate whether functional connectivity is altered in adolescents with Internet gaming addiction (IGA). Seventeen adolescents with IGA and 24 normal control adolescents underwent a 7.3 minute resting-state fMRI scan. Posterior cingulate cortex (PCC) connectivity was determined in all subjects by investigating synchronized low-frequency fMRI signal fluctuations using a temporal correlation method. To assess the relationship between IGA symptom severity and PCC connectivity, contrast images representing areas correlated with PCC connectivity were correlated with the scores of the 17 subjects with IGA on the Chen Internet Addiction Scale (CIAS) and Barratt Impulsiveness Scale-11 (BIS-11) and their hours of Internet use per week. There were no significant differences in the distributions of the age, gender, and years of education between the two groups. The subjects with IGA showed longer Internet use per week (hours) (p<0.0001) and higher CIAS (p<0.0001) and BIS-11 (p = 0.01) scores than the controls. Compared with the control group, subjects with IGA exhibited increased functional connectivity in the bilateral cerebellum posterior lobe and middle temporal gyrus. The bilateral inferior parietal lobule and right inferior temporal gyrus exhibited decreased connectivity. Connectivity with the PCC was positively correlated with CIAS scores in the right precuneus, posterior cingulate gyrus, thalamus, caudate, nucleus accumbens, supplementary motor area, and lingual gyrus. It was negatively correlated with the right cerebellum anterior lobe and left superior parietal lobule. Our results suggest that adolescents with IGA exhibit different resting-state patterns of brain activity. As these alterations are partially consistent with those in patients with substance addiction, they support the hypothesis that IGA as a behavioral addiction that may share similar neurobiological abnormalities with other addictive disorders.
Sourty, Marion; Thoraval, Laurent; Roquet, Daniel; Armspach, Jean-Paul; Foucher, Jack; Blanc, Frédéric
2016-01-01
Exploring time-varying connectivity networks in neurodegenerative disorders is a recent field of research in functional MRI. Dementia with Lewy bodies (DLB) represents 20% of the neurodegenerative forms of dementia. Fluctuations of cognition and vigilance are the key symptoms of DLB. To date, no dynamic functional connectivity (DFC) investigations of this disorder have been performed. In this paper, we refer to the concept of connectivity state as a piecewise stationary configuration of functional connectivity between brain networks. From this concept, we propose a new method for group-level as well as for subject-level studies to compare and characterize connectivity state changes between a set of resting-state networks (RSNs). Dynamic Bayesian networks, statistical and graph theory-based models, enable one to learn dependencies between interacting state-based processes. Product hidden Markov models (PHMM), an instance of dynamic Bayesian networks, are introduced here to capture both statistical and temporal aspects of DFC of a set of RSNs. This analysis was based on sliding-window cross-correlations between seven RSNs extracted from a group independent component analysis performed on 20 healthy elderly subjects and 16 patients with DLB. Statistical models of DFC differed in patients compared to healthy subjects for the occipito-parieto-frontal network, the medial occipital network and the right fronto-parietal network. In addition, pairwise comparisons of DFC of RSNs revealed a decrease of dependency between these two visual networks (occipito-parieto-frontal and medial occipital networks) and the right fronto-parietal control network. The analysis of DFC state changes thus pointed out networks related to the cognitive functions that are known to be impaired in DLB: visual processing as well as attentional and executive functions. Besides this context, product HMM applied to RSNs cross-correlations offers a promising new approach to investigate structural and temporal aspects of brain DFC.
Mills, Brian D; Grayson, David S; Shunmugavel, Anandakumar; Miranda-Dominguez, Oscar; Feczko, Eric; Earl, Eric; Neve, Kim; Fair, Damien A
2018-05-22
Cognition and behavior depend on synchronized intrinsic brain activity that is organized into functional networks across the brain. Research has investigated how anatomical connectivity both shapes and is shaped by these networks, but not how anatomical connectivity interacts with intra-areal molecular properties to drive functional connectivity. Here, we present a novel linear model to explain functional connectivity by integrating systematically obtained measurements of axonal connectivity, gene expression, and resting state functional connectivity MRI in the mouse brain. The model suggests that functional connectivity arises from both anatomical links and inter-areal similarities in gene expression. By estimating these effects, we identify anatomical modules in which correlated gene expression and anatomical connectivity support functional connectivity. Along with providing evidence that not all genes equally contribute to functional connectivity, this research establishes new insights regarding the biological underpinnings of coordinated brain activity measured by BOLD fMRI. SIGNIFICANCE STATEMENT Efforts at characterizing the functional connectome with fMRI have risen exponentially over the last decade. Yet despite this rise, the biological underpinnings of these functional measurements are still largely unknown. The current report begins to fill this void by investigating the molecular underpinnings of the functional connectome through an integration of systematically obtained structural information and gene expression data throughout the rodent brain. We find that both white matter connectivity and similarity in regional gene expression relate to resting state functional connectivity. The current report furthers our understanding of the biological underpinnings of the functional connectome and provides a linear model that can be utilized to streamline preclinical animal studies of disease. Copyright © 2018 the authors.
Glerean, Enrico; Salmi, Juha; Lahnakoski, Juha M; Jääskeläinen, Iiro P; Sams, Mikko
2012-01-01
Functional brain activity and connectivity have been studied by calculating intersubject and seed-based correlations of hemodynamic data acquired with functional magnetic resonance imaging (fMRI). To inspect temporal dynamics, these correlation measures have been calculated over sliding time windows with necessary restrictions on the length of the temporal window that compromises the temporal resolution. Here, we show that it is possible to increase temporal resolution by using instantaneous phase synchronization (PS) as a measure of dynamic (time-varying) functional connectivity. We applied PS on an fMRI dataset obtained while 12 healthy volunteers watched a feature film. Narrow frequency band (0.04-0.07 Hz) was used in the PS analysis to avoid artifactual results. We defined three metrics for computing time-varying functional connectivity and time-varying intersubject reliability based on estimation of instantaneous PS across the subjects: (1) seed-based PS, (2) intersubject PS, and (3) intersubject seed-based PS. Our findings show that these PS-based metrics yield results consistent with both seed-based correlation and intersubject correlation methods when inspected over the whole time series, but provide an important advantage of maximal single-TR temporal resolution. These metrics can be applied both in studies with complex naturalistic stimuli (e.g., watching a movie or listening to music in the MRI scanner) and more controlled (e.g., event-related or blocked design) paradigms. A MATLAB toolbox FUNPSY ( http://becs.aalto.fi/bml/software.html ) is openly available for using these metrics in fMRI data analysis.
2016-02-01
Modified Cheeger and Ratio Cut Methods Using the Ginzburg-Landau Functional for Classification of High-Dimensional Data Ekaterina Merkurjev*, Andrea...bertozzi@math.ucla.edu, xiaoran@isi.edu, lerman@isi.edu. Abstract Recent advances in clustering have included continuous relaxations of the Cheeger cut ...fully nonlinear Cheeger cut problem, as well as the ratio cut optimization task. Both problems are connected to total variation minimization, and the
Semi-supervised clustering for parcellating brain regions based on resting state fMRI data
NASA Astrophysics Data System (ADS)
Cheng, Hewei; Fan, Yong
2014-03-01
Many unsupervised clustering techniques have been adopted for parcellating brain regions of interest into functionally homogeneous subregions based on resting state fMRI data. However, the unsupervised clustering techniques are not able to take advantage of exiting knowledge of the functional neuroanatomy readily available from studies of cytoarchitectonic parcellation or meta-analysis of the literature. In this study, we propose a semi-supervised clustering method for parcellating amygdala into functionally homogeneous subregions based on resting state fMRI data. Particularly, the semi-supervised clustering is implemented under the framework of graph partitioning, and adopts prior information and spatial consistent constraints to obtain a spatially contiguous parcellation result. The graph partitioning problem is solved using an efficient algorithm similar to the well-known weighted kernel k-means algorithm. Our method has been validated for parcellating amygdala into 3 subregions based on resting state fMRI data of 28 subjects. The experiment results have demonstrated that the proposed method is more robust than unsupervised clustering and able to parcellate amygdala into centromedial, laterobasal, and superficial parts with improved functionally homogeneity compared with the cytoarchitectonic parcellation result. The validity of the parcellation results is also supported by distinctive functional and structural connectivity patterns of the subregions and high consistency between coactivation patterns derived from a meta-analysis and functional connectivity patterns of corresponding subregions.
NASA Astrophysics Data System (ADS)
Fernandez Rojas, Raul; Huang, Xu; Ou, Keng-Liang
2016-12-01
Near-infrared spectroscopy (NIRS) has been used in medical imaging to obtain oxygenation and hemodynamic response in the cerebral cortex. This technique has been applied in cortical activation detection and functional connectivity in brain research. Despite some advances in functional connectivity, most of the studies have focused on the prefrontal cortex and little has been done to study the somatosensory region (S1). For that reason, the aim of our present study is to assess bilateral connectivity in the somatosensory region by using NIRS and noxious stimulation. Eleven healthy subjects were investigated using near-infrared spectroscopy during an acupuncture stimulation procedure to safely induce pain in subjects. A multiscale analysis based on wavelet transform coherence (WTC) was designed to assess the functional connectivity of corresponding channel pairs within the left and right s1 region. The cortical activation in the somatosensory region was higher after the acupuncture stimulation, which was consistent with similar studies. The coherence in time-frequency domain between homologous signals generated by contralateral channel pairs revealed two main periods (3.2 s and 12.8 s) with high coherence. Based on the WTC analysis, it was also found that the coherence increase in these periods was task-related. This study contributes to the research field to investigate cerebral hemodynamic response of pain perception using NIRS and demonstrates the use of wavelet transform as a method to investigate functional lateralization in the cerebral cortex.
Lesions causing freezing of gait localize to a cerebellar functional network
Fasano, Alfonso; Laganiere, Simon E.; Lam, Susy; Fox, Michael D.
2016-01-01
Objective Freezing of gait is a disabling symptom in Parkinson’s disease and related disorders, but the brain regions involved in symptom generation remain unclear. Here we analyze brain lesions causing acute onset freezing of gait to identify regions causally involved in symptom generation. Methods Fourteen cases of lesion-induced freezing of gait were identified from the literature and lesions were mapped to a common brain atlas. Because lesion-induced symptoms can come from sites connected to the lesion location, not just the lesion location itself, we also identified brain regions functionally connected to each lesion location. This technique, termed lesion network mapping, has been recently shown to identify regions involved in symptom generation across a variety of lesion-induced disorders. Results Lesion location was heterogeneous and no single region could be considered necessary for symptom generation. However, over 90% (13/14) of lesions were functionally connected to a focal area in the dorsal medial cerebellum. This cerebellar area overlapped previously recognized regions that are activated by locomotor tasks, termed the cerebellar locomotor region. Connectivity to this region was specific to lesions causing freezing of gait compared to lesions causing other movement disorders (hemichorea or asterixis). Interpretation Lesions causing freezing of gait are located within a common functional network characterized by connectivity to the cerebellar locomotor region. These results based on causal brain lesions complement prior neuroimaging studies in Parkinson’s disease patients, advancing our understanding of the brain regions involved in freezing of gait. PMID:28009063
Reduced hippocampal functional connectivity in Alzheimer disease.
Allen, Greg; Barnard, Holly; McColl, Roderick; Hester, Andrea L; Fields, Julie A; Weiner, Myron F; Ringe, Wendy K; Lipton, Anne M; Brooker, Matthew; McDonald, Elizabeth; Rubin, Craig D; Cullum, C Munro
2007-10-01
To determine if functional connectivity of the hippocampus is reduced in patients with Alzheimer disease. Functional connectivity magnetic resonance imaging was used to investigate coherence in the magnetic resonance signal between the hippocampus and all other regions of the brain. Eight patients with probable Alzheimer disease and 8 healthy volunteers. Control subjects showed hippocampal functional connectivity with diffuse cortical, subcortical, and cerebellar sites, while patients demonstrated markedly reduced functional connectivity, including an absence of connectivity with the frontal lobes. These findings suggest a functional disconnection between the hippocampus and other brain regions in patients with Alzheimer disease.
Rashid, Barnaly; Damaraju, Eswar; Pearlson, Godfrey D; Calhoun, Vince D
2014-01-01
Schizophrenia (SZ) and bipolar disorder (BP) share significant overlap in clinical symptoms, brain characteristics, and risk genes, and both are associated with dysconnectivity among large-scale brain networks. Resting state functional magnetic resonance imaging (rsfMRI) data facilitates studying macroscopic connectivity among distant brain regions. Standard approaches to identifying such connectivity include seed-based correlation and data-driven clustering methods such as independent component analysis (ICA) but typically focus on average connectivity. In this study, we utilize ICA on rsfMRI data to obtain intrinsic connectivity networks (ICNs) in cohorts of healthy controls (HCs) and age matched SZ and BP patients. Subsequently, we investigated difference in functional network connectivity, defined as pairwise correlations among the timecourses of ICNs, between HCs and patients. We quantified differences in both static (average) and dynamic (windowed) connectivity during the entire scan duration. Disease-specific differences were identified in connectivity within different dynamic states. Notably, results suggest that patients make fewer transitions to some states (states 1, 2, and 4) compared to HCs, with most such differences confined to a single state. SZ patients showed more differences from healthy subjects than did bipolars, including both hyper and hypo connectivity in one common connectivity state (dynamic state 3). Also group differences between SZ and bipolar patients were identified in patterns (states) of connectivity involving the frontal (dynamic state 1) and frontal-parietal regions (dynamic state 3). Our results provide new information about these illnesses and strongly suggest that state-based analyses are critical to avoid averaging together important factors that can help distinguish these clinical groups.
DELTACON: A Principled Massive-Graph Similarity Function with Attribution
DOE Office of Scientific and Technical Information (OSTI.GOV)
Koutra, Danai; Shah, Neil; Vogelstein, Joshua T.
How much did a network change since yesterday? How different is the wiring between Bob's brain (a left-handed male) and Alice's brain (a right-handed female)? Graph similarity with known node correspondence, i.e. the detection of changes in the connectivity of graphs, arises in numerous settings. In this work, we formally state the axioms and desired properties of the graph similarity functions, and evaluate when state-of-the-art methods fail to detect crucial connectivity changes in graphs. We propose DeltaCon, a principled, intuitive, and scalable algorithm that assesses the similarity between two graphs on the same nodes (e.g. employees of a company, customersmore » of a mobile carrier). In our experiments on various synthetic and real graphs we showcase the advantages of our method over existing similarity measures. We also employ DeltaCon to real applications: (a) we classify people to groups of high and low creativity based on their brain connectivity graphs, and (b) do temporal anomaly detection in the who-emails-whom Enron graph.« less
DELTACON: A Principled Massive-Graph Similarity Function with Attribution
Koutra, Danai; Shah, Neil; Vogelstein, Joshua T.; ...
2014-05-22
How much did a network change since yesterday? How different is the wiring between Bob's brain (a left-handed male) and Alice's brain (a right-handed female)? Graph similarity with known node correspondence, i.e. the detection of changes in the connectivity of graphs, arises in numerous settings. In this work, we formally state the axioms and desired properties of the graph similarity functions, and evaluate when state-of-the-art methods fail to detect crucial connectivity changes in graphs. We propose DeltaCon, a principled, intuitive, and scalable algorithm that assesses the similarity between two graphs on the same nodes (e.g. employees of a company, customersmore » of a mobile carrier). In our experiments on various synthetic and real graphs we showcase the advantages of our method over existing similarity measures. We also employ DeltaCon to real applications: (a) we classify people to groups of high and low creativity based on their brain connectivity graphs, and (b) do temporal anomaly detection in the who-emails-whom Enron graph.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Taylor, Ronald C.; Sanfilippo, Antonio P.; McDermott, Jason E.
2011-02-18
Transcriptional regulatory networks are being determined using “reverse engineering” methods that infer connections based on correlations in gene state. Corroboration of such networks through independent means such as evidence from the biomedical literature is desirable. Here, we explore a novel approach, a bootstrapping version of our previous Cross-Ontological Analytic method (XOA) that can be used for semi-automated annotation and verification of inferred regulatory connections, as well as for discovery of additional functional relationships between the genes. First, we use our annotation and network expansion method on a biological network learned entirely from the literature. We show how new relevant linksmore » between genes can be iteratively derived using a gene similarity measure based on the Gene Ontology that is optimized on the input network at each iteration. Second, we apply our method to annotation, verification, and expansion of a set of regulatory connections found by the Context Likelihood of Relatedness algorithm.« less
Capecci, Elisa; Kasabov, Nikola; Wang, Grace Y
2015-08-01
The paper presents a methodology for the analysis of functional changes in brain activity across different conditions and different groups of subjects. This analysis is based on the recently proposed NeuCube spiking neural network (SNN) framework and more specifically on the analysis of the connectivity of a NeuCube model trained with electroencephalography (EEG) data. The case study data used to illustrate this method is EEG data collected from three groups-subjects with opiate addiction, patients undertaking methadone maintenance treatment, and non-drug users/healthy control group. The proposed method classifies more accurately the EEG data than traditional statistical and artificial intelligence (AI) methods and can be used to predict response to treatment and dose-related drug effect. But more importantly, the method can be used to compare functional brain activities of different subjects and the changes of these activities as a result of treatment, which is a step towards a better understanding of both the EEG data and the brain processes that generated it. The method can also be used for a wide range of applications, such as a better understanding of disease progression or aging. Copyright © 2015 Elsevier Ltd. All rights reserved.
Time-frequency dynamics of resting-state brain connectivity measured with fMRI.
Chang, Catie; Glover, Gary H
2010-03-01
Most studies of resting-state functional connectivity using fMRI employ methods that assume temporal stationarity, such as correlation and data-driven decompositions computed across the duration of the scan. However, evidence from both task-based fMRI studies and animal electrophysiology suggests that functional connectivity may exhibit dynamic changes within time scales of seconds to minutes. In the present study, we investigated the dynamic behavior of resting-state connectivity across the course of a single scan, performing a time-frequency coherence analysis based on the wavelet transform. We focused on the connectivity of the posterior cingulate cortex (PCC), a primary node of the default-mode network, examining its relationship with both the "anticorrelated" ("task-positive") network as well as other nodes of the default-mode network. It was observed that coherence and phase between the PCC and the anticorrelated network was variable in time and frequency, and statistical testing based on Monte Carlo simulations revealed the presence of significant scale-dependent temporal variability. In addition, a sliding-window correlation procedure identified other regions across the brain that exhibited variable connectivity with the PCC across the scan, which included areas previously implicated in attention and salience processing. Although it is unclear whether the observed coherence and phase variability can be attributed to residual noise or modulation of cognitive state, the present results illustrate that resting-state functional connectivity is not static, and it may therefore prove valuable to consider measures of variability, in addition to average quantities, when characterizing resting-state networks. Copyright (c) 2009 Elsevier Inc. All rights reserved.
Default Mode Functional Connectivity is Associated with Social Functioning in Schizophrenia
Fox, Jaclyn M.; Abram, Samantha V.; Reilly, James L.; Eack, Shaun; Goldman, Morris B.; Csernansky, John G.; Wang, Lei; Smith, Matthew J.
2017-01-01
Individuals with schizophrenia display notable deficits in social functioning. Research indicates that neural connectivity within the default mode network (DMN) is related to social cognition and social functioning in healthy and clinical populations. However, the association between DMN connectivity, social cognition, and social functioning has not been studied in schizophrenia. For the present study, we used resting-state neuroimaging data to evaluate connectivity between the main DMN hubs (i.e., the medial prefrontal cortex (mPFC) and the posterior cingulate cortex-anterior precuneus (PPC)) in individuals with schizophrenia (n=28) and controls (n=32). We also examined whether DMN connectivity was associated with social functioning via social attainment (measured by the Specific Levels of Functioning Scale) and social competence (measured by the Social Skills Performance Assessment), and if social cognition mediates the association between DMN connectivity and these measures of social functioning. Results revealed that DMN connectivity did not differ between individuals with schizophrenia and controls. However, connectivity between the mPFC and PCC hubs was significantly associated with social competence and social attainment in individuals with schizophrenia but not in controls as reflected by a significant group-by-connectivity interaction. Social cognition did not mediate the association between social functioning and DMN connectivity in individuals with schizophrenia. Our findings suggest that fronto-parietal DMN connectivity in particular may be differentially associated with social functioning in schizophrenia and controls. As a result, DMN connectivity may be used as a neuroimaging marker to monitor treatment response or as a potential target for interventions that aim to enhance social functioning in schizophrenia. PMID:28358526
NASA Astrophysics Data System (ADS)
Zhang, Aiying; Jia, Bochao; Wang, Yu-Ping
2018-03-01
Adolescence is a transitional period between childhood and adulthood with physical changes, as well as increasing emotional activity. Studies have shown that the emotional sensitivity is related to a second dramatical brain growth. However, there is little focus on the trend of brain development during this period. In this paper, we aim to track the functional brain connectivity development in adolescence using resting state fMRI (rs-fMRI), which amounts to a time-series analysis problem. Most existing methods either require the time point to be fairly long or are only applicable to small graphs. To this end, we adapted a fast Bayesian integrative analysis (FBIA) to address the short time-series difficulty, and combined with adaptive sum of powered score (aSPU) test for group difference. The data we used are the resting state fMRI (rs-fMRI) obtained from the publicly available Philadelphia Neurodevelopmental Cohort (PNC). They include 861 individuals aged 8-22 years who were divided into five different adolescent stages. We summarized the networks with global measurements: segregation and integration, and provided full brain functional connectivity pattern in various stages of adolescence. Moreover, our research revealed several brain functional modules development trends. Our results are shown to be both statistically and biologically significant.
Stress assessment based on EEG univariate features and functional connectivity measures.
Alonso, J F; Romero, S; Ballester, M R; Antonijoan, R M; Mañanas, M A
2015-07-01
The biological response to stress originates in the brain but involves different biochemical and physiological effects. Many common clinical methods to assess stress are based on the presence of specific hormones and on features extracted from different signals, including electrocardiogram, blood pressure, skin temperature, or galvanic skin response. The aim of this paper was to assess stress using EEG-based variables obtained from univariate analysis and functional connectivity evaluation. Two different stressors, the Stroop test and sleep deprivation, were applied to 30 volunteers to find common EEG patterns related to stress effects. Results showed a decrease of the high alpha power (11 to 12 Hz), an increase in the high beta band (23 to 36 Hz, considered a busy brain indicator), and a decrease in the approximate entropy. Moreover, connectivity showed that the high beta coherence and the interhemispheric nonlinear couplings, measured by the cross mutual information function, increased significantly for both stressors, suggesting that useful stress indexes may be obtained from EEG-based features.
Changes in resting-state connectivity in musicians with embouchure dystonia.
Haslinger, Bernhard; Noé, Jonas; Altenmüller, Eckart; Riedl, Valentin; Zimmer, Claus; Mantel, Tobias; Dresel, Christian
2017-03-01
Embouchure dystonia is a highly disabling task-specific dystonia in professional brass musicians leading to spasms of perioral muscles while playing the instrument. As they are asymptomatic at rest, resting-state functional magnetic resonance imaging in these patients can reveal changes in functional connectivity within and between brain networks independent from dystonic symptoms. We therefore compared embouchure dystonia patients to healthy musicians with resting-state functional magnetic resonance imaging in combination with independent component analyses. Patients showed increased functional connectivity of the bilateral sensorimotor mouth area and right secondary somatosensory cortex, but reduced functional connectivity of the bilateral sensorimotor hand representation, left inferior parietal cortex, and mesial premotor cortex within the lateral motor function network. Within the auditory function network, the functional connectivity of bilateral secondary auditory cortices, right posterior parietal cortex and left sensorimotor hand area was increased, the functional connectivity of right primary auditory cortex, right secondary somatosensory cortex, right sensorimotor mouth representation, bilateral thalamus, and anterior cingulate cortex was reduced. Negative functional connectivity between the cerebellar and lateral motor function network and positive functional connectivity between the cerebellar and primary visual network were reduced. Abnormal resting-state functional connectivity of sensorimotor representations of affected and unaffected body parts suggests a pathophysiological predisposition for abnormal sensorimotor and audiomotor integration in embouchure dystonia. Altered connectivity to the cerebellar network highlights the important role of the cerebellum in this disease. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.
Copper and the Prion Protein: Methods, Structures, Function, and Disease
NASA Astrophysics Data System (ADS)
Millhauser, Glenn L.
2007-05-01
The transmissible spongiform encephalopathies (TSEs) arise from conversion of the membrane-bound prion protein from PrPC to PrPSc. Examples of the TSEs include mad cow disease, chronic wasting disease in deer and elk, scrapie in goats and sheep, and kuru and Creutzfeldt-Jakob disease in humans. Although the precise function of PrPC in healthy tissues is not known, recent research demonstrates that it binds Cu(II) in an unusual and highly conserved region of the protein termed the octarepeat domain. This review describes recent connections between copper and PrPC, with an emphasis on the electron paramagnetic resonance elucidation of the specific copper-binding sites, insights into PrPC function, and emerging connections between copper and prion disease.
Son, Seong-Jin; Kim, Jonghoon; Park, Hyunjin
2017-01-01
Regional volume atrophy and functional degeneration are key imaging hallmarks of Alzheimer's disease (AD) in structural and functional magnetic resonance imaging (MRI), respectively. We jointly explored regional volume atrophy and functional connectivity to better characterize neuroimaging data of AD and mild cognitive impairment (MCI). All data were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We compared regional volume atrophy and functional connectivity in 10 subcortical regions using structural MRI and resting-state functional MRI (rs-fMRI). Neuroimaging data of normal controls (NC) (n = 35), MCI (n = 40), and AD (n = 30) were compared. Significant differences of regional volumes and functional connectivity measures between groups were assessed using permutation tests in 10 regions. The regional volume atrophy and functional connectivity of identified regions were used as features for the random forest classifier to distinguish among three groups. The features of the identified regions were also regarded as connectional fingerprints that could distinctively separate a given group from the others. We identified a few regions with distinctive regional atrophy and functional connectivity patterns for NC, MCI, and AD groups. A three label classifier using the information of regional volume atrophy and functional connectivity of identified regions achieved classification accuracy of 53.33% to distinguish among NC, MCI, and AD. We identified distinctive regional atrophy and functional connectivity patterns that could be regarded as a connectional fingerprint.
Son, Seong-Jin; Kim, Jonghoon
2017-01-01
Regional volume atrophy and functional degeneration are key imaging hallmarks of Alzheimer’s disease (AD) in structural and functional magnetic resonance imaging (MRI), respectively. We jointly explored regional volume atrophy and functional connectivity to better characterize neuroimaging data of AD and mild cognitive impairment (MCI). All data were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We compared regional volume atrophy and functional connectivity in 10 subcortical regions using structural MRI and resting-state functional MRI (rs-fMRI). Neuroimaging data of normal controls (NC) (n = 35), MCI (n = 40), and AD (n = 30) were compared. Significant differences of regional volumes and functional connectivity measures between groups were assessed using permutation tests in 10 regions. The regional volume atrophy and functional connectivity of identified regions were used as features for the random forest classifier to distinguish among three groups. The features of the identified regions were also regarded as connectional fingerprints that could distinctively separate a given group from the others. We identified a few regions with distinctive regional atrophy and functional connectivity patterns for NC, MCI, and AD groups. A three label classifier using the information of regional volume atrophy and functional connectivity of identified regions achieved classification accuracy of 53.33% to distinguish among NC, MCI, and AD. We identified distinctive regional atrophy and functional connectivity patterns that could be regarded as a connectional fingerprint. PMID:28333946
Toward a standardized structural-functional group connectome in MNI space.
Horn, Andreas; Blankenburg, Felix
2016-01-01
The analysis of the structural architecture of the human brain in terms of connectivity between its subregions has provided profound insights into its underlying functional organization and has coined the concept of the "connectome", a structural description of the elements forming the human brain and the connections among them. Here, as a proof of concept, we introduce a novel group connectome in standard space based on a large sample of 169 subjects from the Enhanced Nathan Kline Institute-Rockland Sample (eNKI-RS). Whole brain structural connectomes of each subject were estimated with a global tracking approach, and the resulting fiber tracts were warped into standard stereotactic (MNI) space using DARTEL. Employing this group connectome, the results of published tracking studies (i.e., the JHU white matter and Oxford thalamic connectivity atlas) could be largely reproduced directly within MNI space. In a second analysis, a study that examined structural connectivity between regions of a functional network, namely the default mode network, was reproduced. Voxel-wise structural centrality was then calculated and compared to others' findings. Furthermore, including additional resting-state fMRI data from the same subjects, structural and functional connectivity matrices between approximately forty thousand nodes of the brain were calculated. This was done to estimate structure-function agreement indices of voxel-wise whole brain connectivity. Taken together, the combination of a novel whole brain fiber tracking approach and an advanced normalization method led to a group connectome that allowed (at least heuristically) performing fiber tracking directly within MNI space. Such an approach may be used for various purposes like the analysis of structural connectivity and modeling experiments that aim at studying the structure-function relationship of the human connectome. Moreover, it may even represent a first step toward a standard DTI template of the human brain in stereotactic space. The standardized group connectome might thus be a promising new resource to better understand and further analyze the anatomical architecture of the human brain on a population level. Copyright © 2015 Elsevier Inc. All rights reserved.
Anti-correlated cortical networks of intrinsic connectivity in the rat brain.
Schwarz, Adam J; Gass, Natalia; Sartorius, Alexander; Risterucci, Celine; Spedding, Michael; Schenker, Esther; Meyer-Lindenberg, Andreas; Weber-Fahr, Wolfgang
2013-01-01
In humans, resting-state blood oxygen level-dependent (BOLD) signals in the default mode network (DMN) are temporally anti-correlated with those from a lateral cortical network involving the frontal eye fields, secondary somatosensory and posterior insular cortices. Here, we demonstrate the existence of an analogous lateral cortical network in the rat brain, extending laterally from anterior secondary sensorimotor regions to the insular cortex and exhibiting low-frequency BOLD fluctuations that are temporally anti-correlated with a midline "DMN-like" network comprising posterior/anterior cingulate and prefrontal cortices. The primary nexus for this anti-correlation relationship was the anterior secondary motor cortex, close to regions that have been identified with frontal eye fields in the rat brain. The anti-correlation relationship was corroborated after global signal removal, underscoring this finding as a robust property of the functional connectivity signature in the rat brain. These anti-correlated networks demonstrate strong anatomical homology to networks identified in human and monkey connectivity studies, extend the known preserved functional connectivity relationships between rodent and primates, and support the use of resting-state functional magnetic resonance imaging as a translational imaging method between rat models and humans.
Anti-Correlated Cortical Networks of Intrinsic Connectivity in the Rat Brain
Gass, Natalia; Sartorius, Alexander; Risterucci, Celine; Spedding, Michael; Schenker, Esther; Meyer-Lindenberg, Andreas; Weber-Fahr, Wolfgang
2013-01-01
Abstract In humans, resting-state blood oxygen level-dependent (BOLD) signals in the default mode network (DMN) are temporally anti-correlated with those from a lateral cortical network involving the frontal eye fields, secondary somatosensory and posterior insular cortices. Here, we demonstrate the existence of an analogous lateral cortical network in the rat brain, extending laterally from anterior secondary sensorimotor regions to the insular cortex and exhibiting low-frequency BOLD fluctuations that are temporally anti-correlated with a midline “DMN-like” network comprising posterior/anterior cingulate and prefrontal cortices. The primary nexus for this anti-correlation relationship was the anterior secondary motor cortex, close to regions that have been identified with frontal eye fields in the rat brain. The anti-correlation relationship was corroborated after global signal removal, underscoring this finding as a robust property of the functional connectivity signature in the rat brain. These anti-correlated networks demonstrate strong anatomical homology to networks identified in human and monkey connectivity studies, extend the known preserved functional connectivity relationships between rodent and primates, and support the use of resting-state functional magnetic resonance imaging as a translational imaging method between rat models and humans. PMID:23919836
Rational assembly of nanoparticle superlattices with designed lattice symmetries
Gang, Oleg; Lu, Fang; Tagawa, Miho
2017-09-05
A method for lattice design via multivalent linkers (LDML) is disclosed that introduces a rationally designed symmetry of connections between particles in order to achieve control over the morphology of their assembly. The method affords the inclusion of different programmable interactions within one linker that allow an assembly of different types of particles. The designed symmetry of connections is preferably provided utilizing DNA encoding. The linkers may include fabricated "patchy" particles, DNA scaffold constructs and Y-shaped DNA linkers, anisotropic particles, which are preferably functionalized with DNA, multimeric protein-DNA complexes, and particles with finite numbers of DNA linkers.
A Cyber Security Self-Assessment Method for Nuclear Power Plants
DOE Office of Scientific and Technical Information (OSTI.GOV)
Glantz, Clifford S.; Coles, Garill A.; Bass, Robert B.
2004-11-01
A cyber security self-assessment method (the Method) has been developed by Pacific Northwest National Laboratory. The development of the Method was sponsored and directed by the U.S. Nuclear Regulatory Commission. Members of the Nuclear Energy Institute Cyber Security Task Force also played a substantial role in developing the Method. The Method's structured approach guides nuclear power plants in scrutinizing their digital systems, assessing the potential consequences to the plant of a cyber exploitation, identifying vulnerabilities, estimating cyber security risks, and adopting cost-effective protective measures. The focus of the Method is on critical digital assets. A critical digital asset is amore » digital device or system that plays a role in the operation, maintenance, or proper functioning of a critical system (i.e., a plant system that can impact safety, security, or emergency preparedness). A critical digital asset may have a direct or indirect connection to a critical system. Direct connections include both wired and wireless communication pathways. Indirect connections include sneaker-net pathways by which software or data are manually transferred from one digital device to another. An indirect connection also may involve the use of instructions or data stored on a critical digital asset to make adjustments to a critical system. The cyber security self-assessment begins with the formation of an assessment team, and is followed by a six-stage process.« less
Favaro, Angela; Clementi, Maurizio; Manara, Renzo; Bosello, Romina; Forzan, Monica; Bruson, Alice; Tenconi, Elena; Degortes, Daniela; Titton, Francesca; Di Salle, Francesco; Santonastaso, Paolo
2013-01-01
Background Anorexia nervosa is characterized by high levels of perseveration and inflexibility, which interfere with successful treatments. Dopamine (DA) signalling seems to play a key role in modulating the prefrontal cortex, since both DA deficiency and excess negatively influence the efficiency of cognitive functions. The present study explores the effect of a functional polymorphism (Val158Met) in the catechol-O-methyltransferase (COMT) gene on the set-shifting abilities and prefrontal functional connectivity of patients with anorexia nervosa. Methods All participants performed the Wisconsin Card Sorting Task, and a subsample underwent resting-state functional magnetic resonance imaging. Results We included 166 patients with DSM-IV lifetime anorexia nervosa and 140 healthy women in our study. Both underweight and weight-recovered patients with anorexia nervosa showed high levels of perseveration, but only in the underweight group did the Val158Met polymorphism affect cognitive performance, showing the U-shaped curve characteristic of increased DA signalling in the prefrontal cortex. Underweight patients with anorexia nervosa who are Met homozygotes had significantly higher levels of perseveration and increased prefrontal functional connectivity than underweight patients in the other genotype groups, indicating abnormal regional cortical processing. Limitations Although our data show that grey matter reduction in starving patients with anorexia nervosa did not explain our findings, the cross-sectional design of the present study did not allow us to distinguish between the effects of starvation and those of low estrogen levels. Conclusion Starvation affects DA release in the prefrontal cortex of patients with anorexia nervosa with different effects on executive functioning and prefrontal functional connectivity according to the COMT genotype. This observation has several therapeutic implications that need to be addressed by future studies. PMID:23046831
Lin, Hsiang-Yuan
2016-01-01
Background: Although atomoxetine demonstrates efficacy in individuals with attention-deficit hyperactivity disorder, its treatment effects on brain resting-state functional connectivity remain unknown. Therefore, we aimed to investigate major brain functional networks in medication-naïve adults with attention-deficit hyperactivity disorder and the efficacy of atomoxetine treatment on resting-state functional connectivity. Methods: After collecting baseline resting-state functional MRI scans from 24 adults with attention-deficit hyperactivity disorder (aged 18–52 years) and 24 healthy controls (matched in demographic characteristics), the participants with attention-deficit hyperactivity disorder were randomly assigned to atomoxetine (n=12) and placebo (n=12) arms in an 8-week, double-blind, placebo-controlled trial. The primary outcome was functional connectivity assessed by a resting-state functional MRI. Seed-based functional connectivity was calculated and compared for the affective, attention, default, and cognitive control networks. Results: At baseline, we found atypical cross talk between the default, cognitive control, and dorsal attention networks and hypoconnectivity within the dorsal attention and default networks in adults with attention-deficit hyperactivity disorder. Our first-ever placebo-controlled clinical trial incorporating resting-state functional MRI showed that treatment with atomoxetine strengthened an anticorrelated relationship between the default and task-positive networks and modulated all major brain networks. The strengthened anticorrelations were associated with improving clinical symptoms in the atomoxetine-treated adults. Conclusions: Our results support the idea that atypical default mode network task-positive network interaction plays an important role in the pathophysiology of adult attention-deficit hyperactivity disorder. Strengthening this atypical relationship following atomoxetine treatment suggests an important pathway to treat attention-deficit hyperactivity disorder. PMID:26377368
Abnormal small-world architecture of top–down control networks in obsessive–compulsive disorder
Zhang, Tijiang; Wang, Jinhui; Yang, Yanchun; Wu, Qizhu; Li, Bin; Chen, Long; Yue, Qiang; Tang, Hehan; Yan, Chaogan; Lui, Su; Huang, Xiaoqi; Chan, Raymond C.K.; Zang, Yufeng; He, Yong; Gong, Qiyong
2011-01-01
Background Obsessive–compulsive disorder (OCD) is a common neuropsychiatric disorder that is characterized by recurrent intrusive thoughts, ideas or images and repetitive ritualistic behaviours. Although focal structural and functional abnormalities in specific brain regions have been widely studied in populations with OCD, changes in the functional relations among them remain poorly understood. This study examined OCD–related alterations in functional connectivity patterns in the brain’s top–down control network. Methods We applied resting-state functional magnetic resonance imaging to investigate the correlation patterns of intrinsic or spontaneous blood oxygen level–dependent signal fluctuations in 18 patients with OCD and 16 healthy controls. The brain control networks were first constructed by thresholding temporal correlation matrices of 39 brain regions associated with top–down control and then analyzed using graph theory-based approaches. Results Compared with healthy controls, the patients with OCD showed decreased functional connectivity in the posterior temporal regions and increased connectivity in various control regions such as the cingulate, precuneus, thalamus and cerebellum. Furthermore, the brain’s control networks in the healthy controls showed small-world architecture (high clustering coefficients and short path lengths), suggesting an optimal balance between modularized and distributed information processing. In contrast, the patients with OCD showed significantly higher local clustering, implying abnormal functional organization in the control network. Further analysis revealed that the changes in network properties occurred in regions of increased functional connectivity strength in patients with OCD. Limitations The patient group in the present study was heterogeneous in terms of symptom clusters, and most of the patients with OCD were medicated. Conclusion Our preliminary results suggest that the organizational patterns of intrinsic brain activity in the control networks are altered in patients with OCD and thus provide empirical evidence for aberrant functional connectivity in the large-scale brain systems in people with this disorder. PMID:20964957
Translational MR Neuroimaging of Stroke and Recovery
Mandeville, Emiri T.; Ayata, Cenk; Zheng, Yi; Mandeville, Joseph B.
2016-01-01
Multiparametric magnetic resonance imaging (MRI) has become a critical clinical tool for diagnosing focal ischemic stroke severity, staging treatment, and predicting outcome. Imaging during the acute phase focuses on tissue viability in the stroke vicinity, while imaging during recovery requires the evaluation of distributed structural and functional connectivity. Preclinical MRI of experimental stroke models provides validation of non-invasive biomarkers in terms of cellular and molecular mechanisms, while also providing a translational platform for evaluation of prospective therapies. This brief review of translational stroke imaging discusses the acute to chronic imaging transition, the principles underlying common MRI methods employed in stroke research, and experimental results obtained by clinical and preclinical imaging to determine tissue viability, vascular remodeling, structural connectivity of major white matter tracts, and functional connectivity using task-based and resting-state fMRI during the stroke recovery process. PMID:27578048
He, Hao; Sui, Jing; Du, Yuhui; Yu, Qingbao; Lin, Dongdong; Drevets, Wayne C; Savitz, Jonathan B; Yang, Jian; Victor, Teresa A; Calhoun, Vince D
2017-12-01
Bipolar disorder (BD) and major depressive disorder (MDD) share similar clinical characteristics that often obscure the diagnostic distinctions between their depressive conditions. Both functional and structural brain abnormalities have been reported in these two disorders. However, the direct link between altered functioning and structure in these two diseases is unknown. To elucidate this relationship, we conducted a multimodal fusion analysis on the functional network connectivity (FNC) and gray matter density from MRI data from 13 BD, 40 MDD, and 33 matched healthy controls (HC). A data-driven fusion method called mCCA+jICA was used to identify the co-altered FNC and gray matter components. Comparing to HC, BD exhibited reduced gray matter density in the parietal and occipital cortices, which correlated with attenuated functional connectivity within sensory and motor networks, as well as hyper-connectivity in regions that are putatively engaged in cognitive control. In addition, lower gray matter density was found in MDD in the amygdala and cerebellum. High accuracy in discriminating across groups was also achieved by trained classification models, implying that features extracted from the fusion analysis hold the potential to ultimately serve as diagnostic biomarkers for mood disorders.
Miller, Robyn L; Yaesoubi, Maziar; Turner, Jessica A; Mathalon, Daniel; Preda, Adrian; Pearlson, Godfrey; Adali, Tulay; Calhoun, Vince D
2016-01-01
Resting-state functional brain imaging studies of network connectivity have long assumed that functional connections are stationary on the timescale of a typical scan. Interest in moving beyond this simplifying assumption has emerged only recently. The great hope is that training the right lens on time-varying properties of whole-brain network connectivity will shed additional light on previously concealed brain activation patterns characteristic of serious neurological or psychiatric disorders. We present evidence that multiple explicitly dynamical properties of time-varying whole-brain network connectivity are strongly associated with schizophrenia, a complex mental illness whose symptomatic presentation can vary enormously across subjects. As with so much brain-imaging research, a central challenge for dynamic network connectivity lies in determining transformations of the data that both reduce its dimensionality and expose features that are strongly predictive of important population characteristics. Our paper introduces an elegant, simple method of reducing and organizing data around which a large constellation of mutually informative and intuitive dynamical analyses can be performed. This framework combines a discrete multidimensional data-driven representation of connectivity space with four core dynamism measures computed from large-scale properties of each subject's trajectory, ie., properties not identifiable with any specific moment in time and therefore reasonable to employ in settings lacking inter-subject time-alignment, such as resting-state functional imaging studies. Our analysis exposes pronounced differences between schizophrenia patients (Nsz = 151) and healthy controls (Nhc = 163). Time-varying whole-brain network connectivity patterns are found to be markedly less dynamically active in schizophrenia patients, an effect that is even more pronounced in patients with high levels of hallucinatory behavior. To the best of our knowledge this is the first demonstration that high-level dynamic properties of whole-brain connectivity, generic enough to be commensurable under many decompositions of time-varying connectivity data, exhibit robust and systematic differences between schizophrenia patients and healthy controls.
Miller, Robyn L.; Yaesoubi, Maziar; Turner, Jessica A.; Mathalon, Daniel; Preda, Adrian; Pearlson, Godfrey; Adali, Tulay; Calhoun, Vince D.
2016-01-01
Resting-state functional brain imaging studies of network connectivity have long assumed that functional connections are stationary on the timescale of a typical scan. Interest in moving beyond this simplifying assumption has emerged only recently. The great hope is that training the right lens on time-varying properties of whole-brain network connectivity will shed additional light on previously concealed brain activation patterns characteristic of serious neurological or psychiatric disorders. We present evidence that multiple explicitly dynamical properties of time-varying whole-brain network connectivity are strongly associated with schizophrenia, a complex mental illness whose symptomatic presentation can vary enormously across subjects. As with so much brain-imaging research, a central challenge for dynamic network connectivity lies in determining transformations of the data that both reduce its dimensionality and expose features that are strongly predictive of important population characteristics. Our paper introduces an elegant, simple method of reducing and organizing data around which a large constellation of mutually informative and intuitive dynamical analyses can be performed. This framework combines a discrete multidimensional data-driven representation of connectivity space with four core dynamism measures computed from large-scale properties of each subject’s trajectory, ie., properties not identifiable with any specific moment in time and therefore reasonable to employ in settings lacking inter-subject time-alignment, such as resting-state functional imaging studies. Our analysis exposes pronounced differences between schizophrenia patients (Nsz = 151) and healthy controls (Nhc = 163). Time-varying whole-brain network connectivity patterns are found to be markedly less dynamically active in schizophrenia patients, an effect that is even more pronounced in patients with high levels of hallucinatory behavior. To the best of our knowledge this is the first demonstration that high-level dynamic properties of whole-brain connectivity, generic enough to be commensurable under many decompositions of time-varying connectivity data, exhibit robust and systematic differences between schizophrenia patients and healthy controls. PMID:26981625
Functional connectivity in autosomal dominant and late-onset Alzheimer disease.
Thomas, Jewell B; Brier, Matthew R; Bateman, Randall J; Snyder, Abraham Z; Benzinger, Tammie L; Xiong, Chengjie; Raichle, Marcus; Holtzman, David M; Sperling, Reisa A; Mayeux, Richard; Ghetti, Bernardino; Ringman, John M; Salloway, Stephen; McDade, Eric; Rossor, Martin N; Ourselin, Sebastien; Schofield, Peter R; Masters, Colin L; Martins, Ralph N; Weiner, Michael W; Thompson, Paul M; Fox, Nick C; Koeppe, Robert A; Jack, Clifford R; Mathis, Chester A; Oliver, Angela; Blazey, Tyler M; Moulder, Krista; Buckles, Virginia; Hornbeck, Russ; Chhatwal, Jasmeer; Schultz, Aaron P; Goate, Alison M; Fagan, Anne M; Cairns, Nigel J; Marcus, Daniel S; Morris, John C; Ances, Beau M
2014-09-01
Autosomal dominant Alzheimer disease (ADAD) is caused by rare genetic mutations in 3 specific genes in contrast to late-onset Alzheimer disease (LOAD), which has a more polygenetic risk profile. To assess the similarities and differences in functional connectivity changes owing to ADAD and LOAD. We analyzed functional connectivity in multiple brain resting state networks (RSNs) in a cross-sectional cohort of participants with ADAD (n = 79) and LOAD (n = 444), using resting-state functional connectivity magnetic resonance imaging at multiple international academic sites. For both types of AD, we quantified and compared functional connectivity changes in RSNs as a function of dementia severity measured by the Clinical Dementia Rating Scale. In ADAD, we qualitatively investigated functional connectivity changes with respect to estimated years from onset of symptoms within 5 RSNs. A decrease in functional connectivity with increasing Clinical Dementia Rating scores were similar for both LOAD and ADAD in multiple RSNs. Ordinal logistic regression models constructed in one type of Alzheimer disease accurately predicted clinical dementia rating scores in the other, further demonstrating the similarity of functional connectivity loss in each disease type. Among participants with ADAD, functional connectivity in multiple RSNs appeared qualitatively lower in asymptomatic mutation carriers near their anticipated age of symptom onset compared with asymptomatic mutation noncarriers. Resting-state functional connectivity magnetic resonance imaging changes with progressing AD severity are similar between ADAD and LOAD. Resting-state functional connectivity magnetic resonance imaging may be a useful end point for LOAD and ADAD therapy trials. Moreover, the disease process of ADAD may be an effective model for the LOAD disease process.
Anwar, A R; Muthalib, M; Perrey, S; Galka, A; Granert, O; Wolff, S; Deuschl, G; Raethjen, J; Heute, U; Muthuraman, M
2012-01-01
Directionality analysis of signals originating from different parts of brain during motor tasks has gained a lot of interest. Since brain activity can be recorded over time, methods of time series analysis can be applied to medical time series as well. Granger Causality is a method to find a causal relationship between time series. Such causality can be referred to as a directional connection and is not necessarily bidirectional. The aim of this study is to differentiate between different motor tasks on the basis of activation maps and also to understand the nature of connections present between different parts of the brain. In this paper, three different motor tasks (finger tapping, simple finger sequencing, and complex finger sequencing) are analyzed. Time series for each task were extracted from functional magnetic resonance imaging (fMRI) data, which have a very good spatial resolution and can look into the sub-cortical regions of the brain. Activation maps based on fMRI images show that, in case of complex finger sequencing, most parts of the brain are active, unlike finger tapping during which only limited regions show activity. Directionality analysis on time series extracted from contralateral motor cortex (CMC), supplementary motor area (SMA), and cerebellum (CER) show bidirectional connections between these parts of the brain. In case of simple finger sequencing and complex finger sequencing, the strongest connections originate from SMA and CMC, while connections originating from CER in either direction are the weakest ones in magnitude during all paradigms.
Tutte polynomial in functional magnetic resonance imaging
NASA Astrophysics Data System (ADS)
García-Castillón, Marlly V.
2015-09-01
Methods of graph theory are applied to the processing of functional magnetic resonance images. Specifically the Tutte polynomial is used to analyze such kind of images. Functional Magnetic Resonance Imaging provide us connectivity networks in the brain which are represented by graphs and the Tutte polynomial will be applied. The problem of computing the Tutte polynomial for a given graph is #P-hard even for planar graphs. For a practical application the maple packages "GraphTheory" and "SpecialGraphs" will be used. We will consider certain diagram which is depicting functional connectivity, specifically between frontal and posterior areas, in autism during an inferential text comprehension task. The Tutte polynomial for the resulting neural networks will be computed and some numerical invariants for such network will be obtained. Our results show that the Tutte polynomial is a powerful tool to analyze and characterize the networks obtained from functional magnetic resonance imaging.
Exploring the Function Space of Deep-Learning Machines
NASA Astrophysics Data System (ADS)
Li, Bo; Saad, David
2018-06-01
The function space of deep-learning machines is investigated by studying growth in the entropy of functions of a given error with respect to a reference function, realized by a deep-learning machine. Using physics-inspired methods we study both sparsely and densely connected architectures to discover a layerwise convergence of candidate functions, marked by a corresponding reduction in entropy when approaching the reference function, gain insight into the importance of having a large number of layers, and observe phase transitions as the error increases.
One cutting plane algorithm using auxiliary functions
NASA Astrophysics Data System (ADS)
Zabotin, I. Ya; Kazaeva, K. E.
2016-11-01
We propose an algorithm for solving a convex programming problem from the class of cutting methods. The algorithm is characterized by the construction of approximations using some auxiliary functions, instead of the objective function. Each auxiliary function bases on the exterior penalty function. In proposed algorithm the admissible set and the epigraph of each auxiliary function are embedded into polyhedral sets. In connection with the above, the iteration points are found by solving linear programming problems. We discuss the implementation of the algorithm and prove its convergence.
Functionalized magnetic nanoparticle analyte sensor
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yantasee, Wassana; Warner, Maryin G; Warner, Cynthia L
2014-03-25
A method and system for simply and efficiently determining quantities of a preselected material in a particular solution by the placement of at least one superparamagnetic nanoparticle having a specified functionalized organic material connected thereto into a particular sample solution, wherein preselected analytes attach to the functionalized organic groups, these superparamagnetic nanoparticles are then collected at a collection site and analyzed for the presence of a particular analyte.
Gómez-Velázquez, Fabiola R; Vélez-Pérez, Hugo; Espinoza-Valdez, Aurora; Romo-Vazquez, Rebeca; Salido-Ruiz, Ricardo A; Ruiz-Stovel, Vanessa; Gallardo-Moreno, Geisa B; González-Garrido, Andrés A; Berumen, Gustavo
2017-02-08
Children with mathematical difficulties usually have an impaired ability to process symbolic representations. Functional MRI methods have suggested that early frontoparietal connectivity can predict mathematic achievements; however, the study of brain connectivity during numerical processing remains unexplored. With the aim of evaluating this in children with different math proficiencies, we selected a sample of 40 children divided into two groups [high achievement (HA) and low achievement (LA)] according to their arithmetic scores in the Wide Range Achievement Test, 4th ed.. Participants performed a symbolic magnitude comparison task (i.e. determining which of two numbers is numerically larger), with simultaneous electrophysiological recording. Partial directed coherence and graph theory methods were used to estimate and depict frontoparietal connectivity in both groups. The behavioral measures showed that children with LA performed significantly slower and less accurately than their peers in the HA group. Significantly higher frontocentral connectivity was found in LA compared with HA; however, when the connectivity analysis was restricted to parietal locations, no relevant group differences were observed. These findings seem to support the notion that LA children require greater memory and attentional efforts to meet task demands, probably affecting early stages of symbolic comparison.
Advanced lesion symptom mapping analyses and implementation as BCBtoolkit.
Foulon, Chris; Cerliani, Leonardo; Kinkingnéhun, Serge; Levy, Richard; Rosso, Charlotte; Urbanski, Marika; Volle, Emmanuelle; Thiebaut de Schotten, Michel
2018-03-01
Patients with brain lesions provide a unique opportunity to understand the functioning of the human mind. However, even when focal, brain lesions have local and remote effects that impact functionally and structurally connected circuits. Similarly, function emerges from the interaction between brain areas rather than their sole activity. For instance, category fluency requires the associations between executive, semantic, and language production functions. Here, we provide, for the first time, a set of complementary solutions for measuring the impact of a given lesion on the neuronal circuits. Our methods, which were applied to 37 patients with a focal frontal brain lesions, revealed a large set of directly and indirectly disconnected brain regions that had significantly impacted category fluency performance. The directly disconnected regions corresponded to areas that are classically considered as functionally engaged in verbal fluency and categorization tasks. These regions were also organized into larger directly and indirectly disconnected functional networks, including the left ventral fronto-parietal network, whose cortical thickness correlated with performance on category fluency. The combination of structural and functional connectivity together with cortical thickness estimates reveal the remote effects of brain lesions, provide for the identification of the affected networks, and strengthen our understanding of their relationship with cognitive and behavioral measures. The methods presented are available and freely accessible in the BCBtoolkit as supplementary software [1].
Synchrony dynamics underlying effective connectivity reconstruction of neuronal circuits
NASA Astrophysics Data System (ADS)
Yu, Haitao; Guo, Xinmeng; Qin, Qing; Deng, Yun; Wang, Jiang; Liu, Jing; Cao, Yibin
2017-04-01
Reconstruction of effective connectivity between neurons is essential for neural systems with function-related significance, characterizing directionally causal influences among neurons. In this work, causal interactions between neurons in spinal dorsal root ganglion, activated by manual acupuncture at Zusanli acupoint of experimental rats, are estimated using Granger causality (GC) method. Different patterns of effective connectivity are obtained for different frequencies and types of acupuncture. Combined with synchrony analysis between neurons, we show a dependence of effective connection on the synchronization dynamics. Based on the experimental findings, a neuronal circuit model with synaptic connections is constructed. The variation of neuronal effective connectivity with respect to its structural connectivity and synchronization dynamics is further explored. Simulation results show that reciprocally causal interactions with statistically significant are formed between well-synchronized neurons. The effective connectivity may be not necessarily equivalent to synaptic connections, but rather depend on the synchrony relationship. Furthermore, transitions of effective interaction between neurons are observed following the synchronization transitions induced by conduction delay and synaptic conductance. These findings are helpful to further investigate the dynamical mechanisms underlying the reconstruction of effective connectivity of neuronal population.
Homotopic connectivity in drug-naïve, first-episode, early-onset schizophrenia
Li, Hui-Jie; Xu, Yong; Zhang, Ke-Rang; Hoptman, Matthew J.; Zuo, Xi-Nian
2014-01-01
Background The disconnection hypothesis of schizophrenia has been extensively tested in adults. Recent studies have reported the presence of brain disconnection in younger patients, adding evidence to support the neurodevelopmental hypothesis of schizophrenia. Because of drug confounds in chronic and medicated patients, it has been extremely challenging for researchers to directly investigate abnormalities in the development of connectivity and their role in the pathophysiology of schizophrenia. The present study aimed to examine functional homotopy – a measure of interhemispheric connection – and its relevance to clinical symptoms in first-episode drug-naïve early-onset schizophrenia (EOS) patients. Methods Resting-state functional magnetic resonance imaging was performed in 26 first-episode drug-naïve EOS patients (age: 14.5 ± 1.94, 13 males) and 25 matched typically developing controls (TDCs) (age: 14.4 ± 2.97, 13 males). We were mainly concerned with the functional connectivity between any pair of symmetric inter-hemispheric voxels (i.e., functional homotopy) measured by voxel-mirrored homotopic connectivity (VMHC). Results EOS patients exhibited both global and regional VMHC reductions in comparison with TDCs. Reduced VMHC values were observed within the superior temporal cortex and postcentral gyrus. These interhemispheric synchronization deficits were negatively correlated with negative symptom of the Positive and Negative Syndrome Scale. Moreover, regions of interest analyses based on left and right clusters of temporal cortex and postcentral gyrus revealed abnormal heterotopic connectivity in EOS patients. Conclusions Our findings provide novel neurodevelopmental evidence for the disconnection hypothesis of schizophrenia and suggest that these alterations occur early in the course of the disease and are independent of medication status. PMID:25130214
Parent, Maxime; Li, Ying; Santhakumar, Vijayalakshmi; Hyder, Fahmeed; Sanganahalli, Basavaraju G; Kannurpatti, Sridhar
2018-06-01
TBI is a leading cause of morbidity in children. To investigate outcome of early developmental TBI during adolescence, a rat model of fluid percussion injury was developed, where previous work reported deficits in sensorimotor behavior and cortical blood flow at adolescence. 1 Based on the non-localized outcome, we hypothesized that multiple neurophysiological components of brain function, namely neuronal connectivity, synapse/axonal microstructural integrity and neurovascular function are altered and magnetic resonance imaging (MRI) methods could be used to determine regional alterations. Adolescent outcomes of developmental TBI were studied 2-months after injury, using functional MRI (fMRI) and Diffusion Tensor Imaging (DTI). fMRI based resting state functional connectivity (RSFC), representing neural connectivity, was significantly altered between sham and TBI. RSFC strength decreased in the cortex, hippocampus and thalamus accompanied by decrease in the spatial extent of their corresponding RSFC networks and inter-hemispheric asymmetry. Cerebrovascular reactivity to arterial CO2 changes diminished after TBI across both hemispheres, with a more pronounced decrease in the ipsilateral hippocampus, thalamus and motor cortex. DTI measures of fractional anisotropy (FA) and apparent diffusion coefficient (ADC), reporting on axonal and microstructural integrity of the brain, indicated similar inter-hemispheric asymmetry, with highest change in the ipsilateral hippocampus and regions adjoining the ipsilateral thalamus, hypothalamus and amygdala. TBI-induced corpus callosal microstructural alterations indicated measurable changes in inter-hemispheric structural connectivity. Hippocampus, thalamus and select cortical regions were most consistently affected in multiple imaging markers. The multi-modal MRI results demonstrate cortical and subcortical alterations in neural connectivity, cerebrovascular resistance and parenchymal microstructure in the adolescent brain, indicating the highly diffuse and persistent nature of the lateral fluid percussion TBI early in development.
Estimation of Dynamic Sparse Connectivity Patterns From Resting State fMRI.
Cai, Biao; Zille, Pascal; Stephen, Julia M; Wilson, Tony W; Calhoun, Vince D; Wang, Yu Ping
2018-05-01
Functional connectivity (FC) estimated from functional magnetic resonance imaging (fMRI) time series, especially during resting state periods, provides a powerful tool to assess human brain functional architecture in health, disease, and developmental states. Recently, the focus of connectivity analysis has shifted toward the subnetworks of the brain, which reveals co-activating patterns over time. Most prior works produced a dense set of high-dimensional vectors, which are hard to interpret. In addition, their estimations to a large extent were based on an implicit assumption of spatial and temporal stationarity throughout the fMRI scanning session. In this paper, we propose an approach called dynamic sparse connectivity patterns (dSCPs), which takes advantage of both matrix factorization and time-varying fMRI time series to improve the estimation power of FC. The feasibility of analyzing dynamic FC with our model is first validated through simulated experiments. Then, we use our framework to measure the difference between young adults and children with real fMRI data set from the Philadelphia Neurodevelopmental Cohort (PNC). The results from the PNC data set showed significant FC differences between young adults and children in four different states. For instance, young adults had reduced connectivity between the default mode network and other subnetworks, as well as hyperconnectivity within the visual system in states 1 and 3, and hypoconnectivity in state 2. Meanwhile, they exhibited temporal correlation patterns that changed over time within functional subnetworks. In addition, the dSCPs model indicated that older people tend to spend more time within a relatively connected FC pattern. Overall, the proposed method provides a valid means to assess dynamic FC, which could facilitate the study of brain networks.
Radulescu, Eugenia; Minati, Ludovico; Ganeshan, Balaji; Harrison, Neil A.; Gray, Marcus A.; Beacher, Felix D.C.C.; Chatwin, Chris; Young, Rupert C.D.; Critchley, Hugo D.
2013-01-01
Asperger syndrome (AS) is an Autism Spectrum Disorder (ASD) characterised by qualitative impairment in the development of emotional and social skills with relative preservation of general intellectual abilities, including verbal language. People with AS may nevertheless show atypical language, including rate and frequency of speech production. We previously observed that abnormalities in grey matter homogeneity (measured with texture analysis of structural MR images) in AS individuals when compared with controls are also correlated with the volume of caudate nucleus. Here, we tested a prediction that these distributed abnormalities in grey matter compromise the functional integrity of brain networks supporting verbal communication skills. We therefore measured the functional connectivity between caudate nucleus and cortex during a functional neuroimaging study of language generation (verbal fluency), applying psycho-physiological interaction (PPI) methods to test specifically for differences attributable to grey matter heterogeneity in AS participants. Furthermore, we used dynamic causal modelling (DCM) to characterise the causal directionality of these differences in interregional connectivity during word production. Our results revealed a diagnosis-dependent influence of grey matter heterogeneity on the functional connectivity of the caudate nuclei with right insula/inferior frontal gyrus and anterior cingulate, respectively with the left superior frontal gyrus and right precuneus. Moreover, causal modelling of interactions between inferior frontal gyri, caudate and precuneus, revealed a reliance on bottom-up (stimulus-driven) connections in AS participants that contrasted with a dominance of top-down (cognitive control) connections from prefrontal cortex observed in control participants. These results provide detailed support for previously hypothesised central disconnectivity in ASD and specify discrete brain network targets for diagnosis and therapy in ASD. PMID:24179823
Smagula, Stephen F; Karim, Helmet T; Rangarajan, Anusha; Santos, Fernando Pasquini; Wood, Sossena C; Santini, Tales; Jakicic, John M; Reynolds, Charles F; Cameron, Judy L; Vallejo, Abbe N; Butters, Meryl A; Rosano, Caterina; Ibrahim, Tamer S; Erickson, Kirk I; Aizenstein, Howard J
2018-06-01
Hippocampal hyperactivation marks preclinical dementia pathophysiology, potentially due to differences in the connectivity of specific medial temporal lobe structures. Our aims were to characterize the resting-state functional connectivity of medial temporal lobe sub-structures in older adults, and evaluate whether specific substructural (rather than global) functional connectivity relates to memory function. In 15 adults (mean age: 69 years), we evaluated the resting state functional connectivity of medial temporal lobe substructures: dentate/Cornu Ammonis (CA) 4, CA1, CA2/3, subiculum, the molecular layer, entorhinal cortex, and parahippocampus. We used 7-Tesla susceptibility weighted imaging and magnetization-prepared rapid gradient echo sequences to segment substructures of the hippocampus, which were used as structural seeds for examining functional connectivity in a resting BOLD sequence. We then assessed correlations between functional connectivity with memory performance (short and long delay free recall on the California Verbal Learning Test [CVLT]). All the seed regions had significant connectivity within the temporal lobe (including the fusiform, temporal, and lingual gyri). The left CA1 was the only seed with significant functional connectivity to the amygdala. The left entorhinal cortex was the only seed to have significant functional connectivity with frontal cortex (anterior cingulate and superior frontal gyrus). Only higher left dentate-left lingual connectivity was associated with poorer CVLT performance (Spearman r = -0.81, p = 0.0003, Benjamini-Hochberg false discovery rate: 0.01) after multiple comparison correction. Rather than global hyper-connectivity of the medial temporal lobe, left dentate-lingual connectivity may provide a specific assay of medial temporal lobe hyper-connectivity relevant to memory in aging. Copyright © 2018 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.
McGrath, Jane; Johnson, Katherine; O'Hanlon, Erik; Garavan, Hugh; Leemans, Alexander; Gallagher, Louise
2013-01-01
Disruption of structural and functional neural connectivity has been widely reported in Autism Spectrum Disorder (ASD) but there is a striking lack of research attempting to integrate analysis of functional and structural connectivity in the same study population, an approach that may provide key insights into the specific neurobiological underpinnings of altered functional connectivity in autism. The aims of this study were (1) to determine whether functional connectivity abnormalities were associated with structural abnormalities of white matter (WM) in ASD and (2) to examine the relationships between aberrant neural connectivity and behavior in ASD. Twenty-two individuals with ASD and 22 age, IQ-matched controls completed a high-angular-resolution diffusion MRI scan. Structural connectivity was analysed using constrained spherical deconvolution (CSD) based tractography. Regions for tractography were generated from the results of a previous study, in which 10 pairs of brain regions showed abnormal functional connectivity during visuospatial processing in ASD. WM tracts directly connected 5 of the 10 region pairs that showed abnormal functional connectivity; linking a region in the left occipital lobe (left BA19) and five paired regions: left caudate head, left caudate body, left uncus, left thalamus, and left cuneus. Measures of WM microstructural organization were extracted from these tracts. Fractional anisotropy (FA) reductions in the ASD group relative to controls were significant for WM connecting left BA19 to left caudate head and left BA19 to left thalamus. Using a multimodal imaging approach, this study has revealed aberrant WM microstructure in tracts that directly connect brain regions that are abnormally functionally connected in ASD. These results provide novel evidence to suggest that structural brain pathology may contribute (1) to abnormal functional connectivity and (2) to atypical visuospatial processing in ASD. PMID:24133425
Ji, Junzhong; Liu, Jinduo; Liang, Peipeng; Zhang, Aidong
2016-01-01
Many approaches have been designed to extract brain effective connectivity from functional magnetic resonance imaging (fMRI) data. However, few of them can effectively identify the connectivity network structure due to different defects. In this paper, a new algorithm is developed to infer the effective connectivity between different brain regions by combining artificial immune algorithm (AIA) with the Bayes net method, named as AIAEC. In the proposed algorithm, a brain effective connectivity network is mapped onto an antibody, and four immune operators are employed to perform the optimization process of antibodies, including clonal selection operator, crossover operator, mutation operator and suppression operator, and finally gets an antibody with the highest K2 score as the solution. AIAEC is then tested on Smith’s simulated datasets, and the effect of the different factors on AIAEC is evaluated, including the node number, session length, as well as the other potential confounding factors of the blood oxygen level dependent (BOLD) signal. It was revealed that, as contrast to other existing methods, AIAEC got the best performance on the majority of the datasets. It was also found that AIAEC could attain a relative better solution under the influence of many factors, although AIAEC was differently affected by the aforementioned factors. AIAEC is thus demonstrated to be an effective method for detecting the brain effective connectivity. PMID:27045295
Hierarchical multivariate covariance analysis of metabolic connectivity
Carbonell, Felix; Charil, Arnaud; Zijdenbos, Alex P; Evans, Alan C; Bedell, Barry J
2014-01-01
Conventional brain connectivity analysis is typically based on the assessment of interregional correlations. Given that correlation coefficients are derived from both covariance and variance, group differences in covariance may be obscured by differences in the variance terms. To facilitate a comprehensive assessment of connectivity, we propose a unified statistical framework that interrogates the individual terms of the correlation coefficient. We have evaluated the utility of this method for metabolic connectivity analysis using [18F]2-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. As an illustrative example of the utility of this approach, we examined metabolic connectivity in angular gyrus and precuneus seed regions of mild cognitive impairment (MCI) subjects with low and high β-amyloid burdens. This new multivariate method allowed us to identify alterations in the metabolic connectome, which would not have been detected using classic seed-based correlation analysis. Ultimately, this novel approach should be extensible to brain network analysis and broadly applicable to other imaging modalities, such as functional magnetic resonance imaging (MRI). PMID:25294129
Development of large-scale functional brain networks in children.
Supekar, Kaustubh; Musen, Mark; Menon, Vinod
2009-07-01
The ontogeny of large-scale functional organization of the human brain is not well understood. Here we use network analysis of intrinsic functional connectivity to characterize the organization of brain networks in 23 children (ages 7-9 y) and 22 young-adults (ages 19-22 y). Comparison of network properties, including path-length, clustering-coefficient, hierarchy, and regional connectivity, revealed that although children and young-adults' brains have similar "small-world" organization at the global level, they differ significantly in hierarchical organization and interregional connectivity. We found that subcortical areas were more strongly connected with primary sensory, association, and paralimbic areas in children, whereas young-adults showed stronger cortico-cortical connectivity between paralimbic, limbic, and association areas. Further, combined analysis of functional connectivity with wiring distance measures derived from white-matter fiber tracking revealed that the development of large-scale brain networks is characterized by weakening of short-range functional connectivity and strengthening of long-range functional connectivity. Importantly, our findings show that the dynamic process of over-connectivity followed by pruning, which rewires connectivity at the neuronal level, also operates at the systems level, helping to reconfigure and rebalance subcortical and paralimbic connectivity in the developing brain. Our study demonstrates the usefulness of network analysis of brain connectivity to elucidate key principles underlying functional brain maturation, paving the way for novel studies of disrupted brain connectivity in neurodevelopmental disorders such as autism.
Development of Large-Scale Functional Brain Networks in Children
Supekar, Kaustubh; Musen, Mark; Menon, Vinod
2009-01-01
The ontogeny of large-scale functional organization of the human brain is not well understood. Here we use network analysis of intrinsic functional connectivity to characterize the organization of brain networks in 23 children (ages 7–9 y) and 22 young-adults (ages 19–22 y). Comparison of network properties, including path-length, clustering-coefficient, hierarchy, and regional connectivity, revealed that although children and young-adults' brains have similar “small-world” organization at the global level, they differ significantly in hierarchical organization and interregional connectivity. We found that subcortical areas were more strongly connected with primary sensory, association, and paralimbic areas in children, whereas young-adults showed stronger cortico-cortical connectivity between paralimbic, limbic, and association areas. Further, combined analysis of functional connectivity with wiring distance measures derived from white-matter fiber tracking revealed that the development of large-scale brain networks is characterized by weakening of short-range functional connectivity and strengthening of long-range functional connectivity. Importantly, our findings show that the dynamic process of over-connectivity followed by pruning, which rewires connectivity at the neuronal level, also operates at the systems level, helping to reconfigure and rebalance subcortical and paralimbic connectivity in the developing brain. Our study demonstrates the usefulness of network analysis of brain connectivity to elucidate key principles underlying functional brain maturation, paving the way for novel studies of disrupted brain connectivity in neurodevelopmental disorders such as autism. PMID:19621066
Peeters, Sanne C T; van de Ven, Vincent; Gronenschild, Ed H B M; Patel, Ameera X; Habets, Petra; Goebel, Rainer; van Os, Jim; Marcelis, Machteld
2015-01-01
Research suggests that altered interregional connectivity in specific networks, such as the default mode network (DMN), is associated with cognitive and psychotic symptoms in schizophrenia. In addition, frontal and limbic connectivity alterations have been associated with trauma, drug use and urban upbringing, though these environmental exposures have never been examined in relation to DMN functional connectivity in psychotic disorder. Resting-state functional MRI scans were obtained from 73 patients with psychotic disorder, 83 non-psychotic siblings of patients with psychotic disorder and 72 healthy controls. Posterior cingulate cortex (PCC) seed-based correlation analysis was used to estimate functional connectivity within the DMN. DMN functional connectivity was examined in relation to group (familial risk), group × environmental exposure (to cannabis, developmental trauma and urbanicity) and symptomatology. There was a significant association between group and PCC connectivity with the inferior parietal lobule (IPL), the precuneus (PCu) and the medial prefrontal cortex (MPFC). Compared to controls, patients and siblings had increased PCC connectivity with the IPL, PCu and MPFC. In the IPL and PCu, the functional connectivity of siblings was intermediate to that of controls and patients. No significant associations were found between DMN connectivity and (subclinical) psychotic/cognitive symptoms. In addition, there were no significant interactions between group and environmental exposures in the model of PCC functional connectivity. Increased functional connectivity in individuals with (increased risk for) psychotic disorder may reflect trait-related network alterations. The within-network "connectivity at rest" intermediate phenotype was not associated with (subclinical) psychotic or cognitive symptoms. The association between familial risk and DMN connectivity was not conditional on environmental exposure.
NASA Astrophysics Data System (ADS)
Erhard, Jannis; Bleiziffer, Patrick; Görling, Andreas
2016-09-01
A power series approximation for the correlation kernel of time-dependent density-functional theory is presented. Using this approximation in the adiabatic-connection fluctuation-dissipation (ACFD) theorem leads to a new family of Kohn-Sham methods. The new methods yield reaction energies and barriers of unprecedented accuracy and enable a treatment of static (strong) correlation with an accuracy of high-level multireference configuration interaction methods but are single-reference methods allowing for a black-box-like handling of static correlation. The new methods exhibit a better scaling of the computational effort with the system size than rivaling wave-function-based electronic structure methods. Moreover, the new methods do not suffer from the problem of singularities in response functions plaguing previous ACFD methods and therefore are applicable to any type of electronic system.
White matter lesions relate to tract-specific reductions in functional connectivity.
Langen, Carolyn D; Zonneveld, Hazel I; White, Tonya; Huizinga, Wyke; Cremers, Lotte G M; de Groot, Marius; Ikram, Mohammad Arfan; Niessen, Wiro J; Vernooij, Meike W
2017-03-01
White matter lesions play a role in cognitive decline and dementia. One presumed pathway is through disconnection of functional networks. Little is known about location-specific effects of lesions on functional connectivity. This study examined location-specific effects within anatomically-defined white matter tracts in 1584 participants of the Rotterdam Study, aged 50-95. Tracts were delineated from diffusion magnetic resonance images using probabilistic tractography. Lesions were segmented on fluid-attenuated inversion recovery images. Functional connectivity was defined across each tract on resting-state functional magnetic resonance images by using gray matter parcellations corresponding to the tract ends and calculating the correlation of the mean functional activity between the gray matter regions. A significant relationship between both local and brain-wide lesion load and tract-specific functional connectivity was found in several tracts using linear regressions, also after Bonferroni correction. Indirect connectivity analyses revealed that tract-specific functional connectivity is affected by lesions in several tracts simultaneously. These results suggest that local white matter lesions can decrease tract-specific functional connectivity, both in direct and indirect connections. Copyright © 2016 Elsevier Inc. All rights reserved.
Zhang, Daoqiang; Tu, Liyang; Zhang, Long-Jiang; Jie, Biao; Lu, Guang-Ming
2018-06-01
Hepatic encephalopathy (HE), as a complication of cirrhosis, is a serious brain disease, which may lead to death. Accurate diagnosis of HE and its intermediate stage, i.e., minimal HE (MHE), is very important for possibly early diagnosis and treatment. Brain connectivity network, as a simple representation of brain interaction, has been widely used for the brain disease (e.g., HE and MHE) analysis. However, those studies mainly focus on finding disease-related abnormal connectivity between brain regions, although a large number of studies have indicated that some brain diseases are usually related to local structure of brain connectivity network (i.e., subnetwork), rather than solely on some single brain regions or connectivities. Also, mining such disease-related subnetwork is a challenging task because of the complexity of brain network. To address this problem, we proposed a novel frequent-subnetwork-based method to mine disease-related subnetworks for MHE classification. Specifically, we first mine frequent subnetworks from both groups, i.e., MHE patients and non-HE (NHE) patients, respectively. Then we used the graph-kernel based method to select the most discriminative subnetworks for subsequent classification. We evaluate our proposed method on a MHE dataset with 77 cirrhosis patients, including 38 MHE patients and 39 NHE patients. The results demonstrate that our proposed method can not only obtain the improved classification performance in comparison with state-of-the-art network-based methods, but also identify disease-related subnetworks which can help us better understand the pathology of the brain diseases.
Graph Lasso-Based Test for Evaluating Functional Brain Connectivity in Sickle Cell Disease.
Coloigner, Julie; Phlypo, Ronald; Coates, Thomas D; Lepore, Natasha; Wood, John C
2017-09-01
Sickle cell disease (SCD) is a vascular disorder that is often associated with recurrent ischemia-reperfusion injury, anemia, vasculopathy, and strokes. These cerebral injuries are associated with neurological dysfunction, limiting the full developing potential of the patient. However, recent large studies of SCD have demonstrated that cognitive impairment occurs even in the absence of brain abnormalities on conventional magnetic resonance imaging (MRI). These observations support an emerging consensus that brain injury in SCD is diffuse and that conventional neuroimaging often underestimates the extent of injury. In this article, we postulated that alterations in the cerebral connectivity may constitute a sensitive biomarker of SCD severity. Using functional MRI, a connectivity study analyzing the SCD patients individually was performed. First, a robust learning scheme based on graphical lasso model and Fréchet mean was used for estimating a consistent descriptor of healthy brain connectivity. Then, we tested a statistical method that provides an individual index of similarity between this healthy connectivity model and each SCD patient's connectivity matrix. Our results demonstrated that the reference connectivity model was not appropriate to model connectivity for only 4 out of 27 patients. After controlling for the gender, two separate predictors of this individual similarity index were the anemia (p = 0.02) and white matter hyperintensities (WMH) (silent stroke) (p = 0.03), so that patients with low hemoglobin level or with WMH have the least similarity to the reference connectivity model. Further studies are required to determine whether the resting-state connectivity changes reflect pathological changes or compensatory responses to chronic anemia.
Statistical testing and power analysis for brain-wide association study.
Gong, Weikang; Wan, Lin; Lu, Wenlian; Ma, Liang; Cheng, Fan; Cheng, Wei; Grünewald, Stefan; Feng, Jianfeng
2018-04-05
The identification of connexel-wise associations, which involves examining functional connectivities between pairwise voxels across the whole brain, is both statistically and computationally challenging. Although such a connexel-wise methodology has recently been adopted by brain-wide association studies (BWAS) to identify connectivity changes in several mental disorders, such as schizophrenia, autism and depression, the multiple correction and power analysis methods designed specifically for connexel-wise analysis are still lacking. Therefore, we herein report the development of a rigorous statistical framework for connexel-wise significance testing based on the Gaussian random field theory. It includes controlling the family-wise error rate (FWER) of multiple hypothesis testings using topological inference methods, and calculating power and sample size for a connexel-wise study. Our theoretical framework can control the false-positive rate accurately, as validated empirically using two resting-state fMRI datasets. Compared with Bonferroni correction and false discovery rate (FDR), it can reduce false-positive rate and increase statistical power by appropriately utilizing the spatial information of fMRI data. Importantly, our method bypasses the need of non-parametric permutation to correct for multiple comparison, thus, it can efficiently tackle large datasets with high resolution fMRI images. The utility of our method is shown in a case-control study. Our approach can identify altered functional connectivities in a major depression disorder dataset, whereas existing methods fail. A software package is available at https://github.com/weikanggong/BWAS. Copyright © 2018 Elsevier B.V. All rights reserved.
Xia, Wenqing; Wang, Shaohua; Spaeth, Andrea M.; Rao, Hengyi; Wang, Pin; Yang, Yue; Huang, Rong; Cai, Rongrong; Sun, Haixia
2015-01-01
We aim to investigate whether decreased interhemispheric functional connectivity exists in patients with type 2 diabetes mellitus (T2DM) by using resting-state functional magnetic resonance imaging (rs-fMRI). In addition, we sought to determine whether interhemispheric functional connectivity deficits associated with cognition and insulin resistance (IR) among T2DM patients. We compared the interhemispheric resting state functional connectivity of 32 T2DM patients and 30 healthy controls using rs-fMRI. Partial correlation coefficients were used to detect the relationship between rs-fMRI information and cognitive or clinical data. Compared with healthy controls, T2DM patients showed bidirectional alteration of functional connectivity in several brain regions. Functional connectivity values in the middle temporal gyrus (MTG) and in the superior frontal gyrus were inversely correlated with Trail Making Test-B score of patients. Notably, insulin resistance (log homeostasis model assessment-IR) negatively correlated with functional connectivity in the MTG of patients. In conclusion, T2DM patients exhibit abnormal interhemispheric functional connectivity in several default mode network regions, particularly in the MTG, and such alteration is associated with IR. Alterations in interhemispheric functional connectivity might contribute to cognitive dysfunction in T2DM patients. PMID:26064945
Information processing architecture of functionally defined clusters in the macaque cortex.
Shen, Kelly; Bezgin, Gleb; Hutchison, R Matthew; Gati, Joseph S; Menon, Ravi S; Everling, Stefan; McIntosh, Anthony R
2012-11-28
Computational and empirical neuroimaging studies have suggested that the anatomical connections between brain regions primarily constrain their functional interactions. Given that the large-scale organization of functional networks is determined by the temporal relationships between brain regions, the structural limitations may extend to the global characteristics of functional networks. Here, we explored the extent to which the functional network community structure is determined by the underlying anatomical architecture. We directly compared macaque (Macaca fascicularis) functional connectivity (FC) assessed using spontaneous blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) to directed anatomical connectivity derived from macaque axonal tract tracing studies. Consistent with previous reports, FC increased with increasing strength of anatomical connection, and FC was also present between regions that had no direct anatomical connection. We observed moderate similarity between the FC of each region and its anatomical connectivity. Notably, anatomical connectivity patterns, as described by structural motifs, were different within and across functional modules: partitioning of the functional network was supported by dense bidirectional anatomical connections within clusters and unidirectional connections between clusters. Together, our data directly demonstrate that the FC patterns observed in resting-state BOLD-fMRI are dictated by the underlying neuroanatomical architecture. Importantly, we show how this architecture contributes to the global organizational principles of both functional specialization and integration.
Immediate and Longitudinal Alterations of Functional Networks after Thalamotomy in Essential Tremor
Jang, Changwon; Park, Hae-Jeong; Chang, Won Seok; Pae, Chongwon; Chang, Jin Woo
2016-01-01
Thalamotomy at the ventralis intermedius nucleus has been an effective treatment method for essential tremor, but how the brain network changes immediately responding to this deliberate lesion and then reorganizes afterwards are not clear. Taking advantage of a non-cranium-opening MRI-guided focused ultrasound ablation technique, we investigated functional network changes due to a focal lesion. To classify the diverse time courses of those network changes with respect to symptom-related long-lasting treatment effects and symptom-unrelated transient effects, we applied graph-theoretic analyses to longitudinal resting-state functional magnetic resonance imaging data before and 1 day, 7 days, and 3 months after thalamotomy with essential tremor. We found reduced average connections among the motor-related areas, reduced connectivity between substantia nigra and external globus pallidum and reduced total connection in the thalamus after thalamotomy, which are all associated with clinical rating scales. The average connectivity among whole brain regions and inter-hemispheric network asymmetry show symptom-unrelated transient increases, indicating temporary reconfiguration of the whole brain network. In summary, thalamotomy regulates interactions over the motor network via symptom-related connectivity changes but accompanies transient, symptom-unrelated diaschisis in the global brain network. This study suggests the significance of longitudinal network analysis, combined with minimal-invasive treatment techniques, in understanding time-dependent diaschisis in the brain network due to a focal lesion. PMID:27822200
Zhang, Qiushi; Zhang, Gaoyan; Yao, Li; Zhao, Xiaojie
2015-01-01
Working memory (WM) refers to the temporary holding and manipulation of information during the performance of a range of cognitive tasks, and WM training is a promising method for improving an individual's cognitive functions. Our previous work demonstrated that WM performance can be improved through self-regulation of dorsal lateral prefrontal cortex (PFC) activation using real-time functional magnetic resonance imaging (rtfMRI), which enables individuals to control local brain activities volitionally according to the neurofeedback. Furthermore, research concerning large-scale brain networks has demonstrated that WM training requires the engagement of several networks, including the central executive network (CEN), the default mode network (DMN) and the salience network (SN), and functional connectivity within the CEN and DMN can be changed by WM training. Although a switching role of the SN between the CEN and DMN has been demonstrated, it remains unclear whether WM training can affect the interactions between the three networks and whether a similar mechanism also exists during the training process. In this study, we investigated the dynamic functional connectivity between the three networks during the rtfMRI feedback training using independent component analysis (ICA) and correlation analysis. The results indicated that functional connectivity within and between the three networks were significantly enhanced by feedback training, and most of the changes were associated with the insula and correlated with behavioral improvements. These findings suggest that the insula plays a critical role in the reorganization of functional connectivity among the three networks induced by rtfMRI training and in WM performance, thus providing new insights into the mechanisms of high-level functions and the clinical treatment of related functional impairments.
MDD diagnosis based on partial-brain functional connection network
NASA Astrophysics Data System (ADS)
Yan, Gaoliang; Hu, Hailong; Zhao, Xiang; Zhang, Lin; Qu, Zehui; Li, Yantao
2018-04-01
Artificial intelligence (AI) is a hotspot in computer science research nowadays. To apply AI technology in all industries has been the developing direction for researchers. Major depressive disorder (MDD) is a common disease of serious mental disorders. The World Health Organization (WHO) reports that MDD is projected to become the second most common cause of death and disability by 2020. At present, the way of MDD diagnosis is single. Applying AI technology to MDD diagnosis and pathophysiological research will speed up the MDD research and improve the efficiency of MDD diagnosis. In this study, we select the higher degree of brain network functional connectivity by statistical methods. And our experiments show that the average accuracy of Logistic Regression (LR) classifier using feature filtering reaches 88.48%. Compared with other classification methods, both the efficiency and accuracy of this method are improved, which will greatly improve the process of MDD diagnose. In these experiments, we also define the brain regions associated with MDD, which plays a vital role in MDD pathophysiological research.
Dominant partition method. [based on a wave function formalism
NASA Technical Reports Server (NTRS)
Dixon, R. M.; Redish, E. F.
1979-01-01
By use of the L'Huillier, Redish, and Tandy (LRT) wave function formalism, a partially connected method, the dominant partition method (DPM) is developed for obtaining few body reductions of the many body problem in the LRT and Bencze, Redish, and Sloan (BRS) formalisms. The DPM maps the many body problem to a fewer body one by using the criterion that the truncated formalism must be such that consistency with the full Schroedinger equation is preserved. The DPM is based on a class of new forms for the irreducible cluster potential, which is introduced in the LRT formalism. Connectivity is maintained with respect to all partitions containing a given partition, which is referred to as the dominant partition. Degrees of freedom corresponding to the breakup of one or more of the clusters of the dominant partition are treated in a disconnected manner. This approach for simplifying the complicated BRS equations is appropriate for physical problems where a few body reaction mechanism prevails.
Li, Rui; Yin, Shufei; Zhu, Xinyi; Ren, Weicong; Yu, Jing; Wang, Pengyun; Zheng, Zhiwei; Niu, Ya-Nan; Huang, Xin; Li, Juan
2017-01-01
Increasing evidence suggests that functional brain connectivity is an important determinant of cognitive aging. However, the fundamental concept of inter-individual variations in functional connectivity in older individuals is not yet completely understood. It is essential to evaluate the extent to which inter-individual variability in connectivity impacts cognitive performance at an older age. In the current study, we aimed to characterize individual variability of functional connectivity in the elderly and to examine its significance to individual cognition. We mapped inter-individual variability of functional connectivity by analyzing whole-brain functional connectivity magnetic resonance imaging data obtained from a large sample of cognitively normal older adults. Our results demonstrated a gradual increase in variability in primary regions of the visual, sensorimotor, and auditory networks to specific subcortical structures, particularly the hippocampal formation, and the prefrontal and parietal cortices, which largely constitute the default mode and fronto-parietal networks, to the cerebellum. Further, the inter-individual variability of the functional connectivity correlated significantly with the degree of cognitive relevance. Regions with greater connectivity variability demonstrated more connections that correlated with cognitive performance. These results also underscored the crucial function of the long-range and inter-network connections in individual cognition. Thus, individual connectivity–cognition variability mapping findings may provide important information for future research on cognitive aging and neurocognitive diseases. PMID:29209203
Geng, Xiangfei; Xu, Junhai; Liu, Baolin; Shi, Yonggang
2018-01-01
Major depressive disorder (MDD) is a mental disorder characterized by at least 2 weeks of low mood, which is present across most situations. Diagnosis of MDD using rest-state functional magnetic resonance imaging (fMRI) data faces many challenges due to the high dimensionality, small samples, noisy and individual variability. To our best knowledge, no studies aim at classification with effective connectivity and functional connectivity measures between MDD patients and healthy controls. In this study, we performed a data-driving classification analysis using the whole brain connectivity measures which included the functional connectivity from two brain templates and effective connectivity measures created by the default mode network (DMN), dorsal attention network (DAN), frontal-parietal network (FPN), and silence network (SN). Effective connectivity measures were extracted using spectral Dynamic Causal Modeling (spDCM) and transformed into a vectorial feature space. Linear Support Vector Machine (linear SVM), non-linear SVM, k-Nearest Neighbor (KNN), and Logistic Regression (LR) were used as the classifiers to identify the differences between MDD patients and healthy controls. Our results showed that the highest accuracy achieved 91.67% (p < 0.0001) when using 19 effective connections and 89.36% when using 6,650 functional connections. The functional connections with high discriminative power were mainly located within or across the whole brain resting-state networks while the discriminative effective connections located in several specific regions, such as posterior cingulate cortex (PCC), ventromedial prefrontal cortex (vmPFC), dorsal cingulate cortex (dACC), and inferior parietal lobes (IPL). To further compare the discriminative power of functional connections and effective connections, a classification analysis only using the functional connections from those four networks was conducted and the highest accuracy achieved 78.33% (p < 0.0001). Our study demonstrated that the effective connectivity measures might play a more important role than functional connectivity in exploring the alterations between patients and health controls and afford a better mechanistic interpretability. Moreover, our results showed a diagnostic potential of the effective connectivity for the diagnosis of MDD patients with high accuracies allowing for earlier prevention or intervention. PMID:29515348
Carpenter, Kimberly L. H.; Angold, Adrian; Chen, Nan-Kuei; Copeland, William E.; Gaur, Pooja; Pelphrey, Kevin; Song, Allen W.; Egger, Helen L.
2015-01-01
Objective In this prospective, longitudinal study of young children, we examined whether a history of preschool generalized anxiety, separation anxiety, and/or social phobia is associated with amygdala-prefrontal dysregulation at school-age. As an exploratory analysis, we investigated whether distinct anxiety disorders differ in the patterns of this amygdala-prefrontal dysregulation. Methods Participants were children taking part in a 5-year study of early childhood brain development and anxiety disorders. Preschool symptoms of generalized anxiety, separation anxiety, and social phobia were assessed with the Preschool Age Psychiatric Assessment (PAPA) in the first wave of the study when the children were between 2 and 5 years old. The PAPA was repeated at age 6. We conducted functional MRIs when the children were 5.5 to 9.5 year old to assess neural responses to viewing of angry and fearful faces. Results A history of preschool social phobia predicted less school-age functional connectivity between the amygdala and the ventral prefrontal cortices to angry faces. Preschool generalized anxiety predicted less functional connectivity between the amygdala and dorsal prefrontal cortices in response to fearful faces. Finally, a history of preschool separation anxiety predicted less school-age functional connectivity between the amygdala and the ventral prefrontal cortices to angry faces and greater school-age functional connectivity between the amygdala and dorsal prefrontal cortices to angry faces. Conclusions Our results suggest that there are enduring neurobiological effects associated with a history of preschool anxiety, which occur over-and-above the effect of subsequent emotional symptoms. Our results also provide preliminary evidence for the neurobiological differentiation of specific preschool anxiety disorders. PMID:25625285
Lang, Stefan; Gaxiola-Valdez, Ismael; Opoku-Darko, Michael; Partlo, Lisa A; Goodyear, Bradley G; Kelly, John J P; Federico, Paolo
2017-09-01
Patients with diffuse glioma are known to have impaired cognitive functions preoperatively. However, the mechanism of these cognitive deficits remains unclear. Resting-state functional connectivity in the frontoparietal network (FPN) is associated with cognitive performance in healthy subjects. For this reason, it was hypothesized that functional connectivity of the FPN would be related to cognitive functioning in patients with glioma. To assess this relationship, preoperative cognitive status was correlated to patient-specific connectivity within the FPN. Further, we assessed whether connectivity could predict neuropsychologic outcome following surgery. Sixteen patients with diffuse glioma underwent neuropsychologic assessment and preoperative functional magnetic resonance imaging using task (n-back) and resting-state scans. Thirteen patients had postoperative cognitive assessment. An index of patient-specific functional connectivity in the FPN was derived by averaging connectivity values between 2 prefrontal and 2 parietal cortex regions defined by activation during the n-back task. The relationship of these indices with cognitive performance was assessed. Higher average connectivity within the FPN is associated with lower composite cognitive scores. Higher connectivity of the parietal region of the tumor-affected hemisphere is associated specifically with lower fluid cognition. Lower connectivity of the parietal region of the nontumor hemisphere is associated with worse neuropsychologic outcome 1 month after surgery. Resting-state functional connectivity between key regions of the FPN is associated with cognitive performance in patients with glioma and is related to cognitive outcome following surgery. Copyright © 2017 Elsevier Inc. All rights reserved.
Ma, Qiongmin; Wu, Donglin; Zeng, Ling-Li; Shen, Hui; Hu, Dewen; Qiu, Shijun
2016-07-01
The study aims to investigate the radiation-induced brain functional alterations in nasopharyngeal carcinoma (NPC) patients who received radiotherapy (RT) using functional magnetic resonance imaging (fMRI) and statistic scale.The fMRI data of 35 NPC patients with RT and 24 demographically matched untreated NPC patients were acquired. Montreal Cognitive Assessment (MoCA) was also measured to evaluate their global cognition performance. Multivariate pattern analysis was performed to find the significantly altered functional connections between these 2 groups, while the linear correlation level was detected between the altered functional connections and the MoCA scores.Forty-five notably altered functional connections were found, which were mainly located between 3 brain networks, the cerebellum, sensorimotor, and cingulo-opercular. With strictly false discovery rate correction, 5 altered functional connections were shown to have significant linear correlations with the MoCA scores, that is, the connections between the vermis and hippocampus, cerebellum lobule VI and dorsolateral prefrontal cortex, precuneus and dorsal frontal cortex, cuneus and middle occipital lobe, and insula and cuneus. Besides, the connectivity between the vermis and hippocampus was also significantly correlated with the attention score, 1 of the 7 subscores of the MoCA.The present study provides new insights into the radiation-induced functional connectivity impairments in NPC patients. The results showed that the RT may induce the cognitive impairments, especially the attention alterations. The 45 altered functional connections, especially the 5 altered functional connections that were significantly correlated to the MoCA scores, may serve as the potential biomarkers of the RT-induced brain functional impairments and provide valuable targets for further functional recovery treatment.
Smith, Jason F.; Pillai, Ajay; Chen, Kewei; Horwitz, Barry
2012-01-01
Analysis of directionally specific or causal interactions between regions in functional magnetic resonance imaging (fMRI) data has proliferated. Here we identify six issues with existing effective connectivity methods that need to be addressed. The issues are discussed within the framework of linear dynamic systems for fMRI (LDSf). The first concerns the use of deterministic models to identify inter-regional effective connectivity. We show that deterministic dynamics are incapable of identifying the trial-to-trial variability typically investigated as the marker of connectivity while stochastic models can capture this variability. The second concerns the simplistic (constant) connectivity modeled by most methods. Connectivity parameters of the LDSf model can vary at the same timescale as the input data. Further, extending LDSf to mixtures of multiple models provides more robust connectivity variation. The third concerns the correct identification of the network itself including the number and anatomical origin of the network nodes. Augmentation of the LDSf state space can identify additional nodes of a network. The fourth concerns the locus of the signal used as a “node” in a network. A novel extension LDSf incorporating sparse canonical correlations can select most relevant voxels from an anatomically defined region based on connectivity. The fifth concerns connection interpretation. Individual parameter differences have received most attention. We present alternative network descriptors of connectivity changes which consider the whole network. The sixth concerns the temporal resolution of fMRI data relative to the timescale of the inter-regional interactions in the brain. LDSf includes an “instantaneous” connection term to capture connectivity occurring at timescales faster than the data resolution. The LDS framework can also be extended to statistically combine fMRI and EEG data. The LDSf framework is a promising foundation for effective connectivity analysis. PMID:22279430
Gabard-Durnam, Laurel Joy; Gee, Dylan Grace; Goff, Bonnie; Flannery, Jessica; Telzer, Eva; Humphreys, Kathryn Leigh; Lumian, Daniel Stephen; Fareri, Dominic Stephen; Caldera, Christina; Tottenham, Nim
2016-04-27
Although the functional architecture of the brain is indexed by resting-state connectivity networks, little is currently known about the mechanisms through which these networks assemble into stable mature patterns. The current study posits and tests the long-term phasic molding hypothesis that resting-state networks are gradually shaped by recurring stimulus-elicited connectivity across development by examining how both stimulus-elicited and resting-state functional connections of the human brain emerge over development at the systems level. Using a sequential design following 4- to 18-year-olds over a 2 year period, we examined the predictive associations between stimulus-elicited and resting-state connectivity in amygdala-cortical circuitry as an exemplar case (given this network's protracted development across these ages). Age-related changes in amygdala functional connectivity converged on the same regions of medial prefrontal cortex (mPFC) and inferior frontal gyrus when elicited by emotional stimuli and when measured at rest. Consistent with the long-term phasic molding hypothesis, prospective analyses for both connections showed that the magnitude of an individual's stimulus-elicited connectivity unidirectionally predicted resting-state functional connectivity 2 years later. For the amygdala-mPFC connection, only stimulus-elicited connectivity during childhood and the transition to adolescence shaped future resting-state connectivity, consistent with a sensitive period ending with adolescence for the amygdala-mPFC circuit. Together, these findings suggest that resting-state functional architecture may arise from phasic patterns of functional connectivity elicited by environmental stimuli over the course of development on the order of years. A fundamental issue in understanding the ontogeny of brain function is how resting-state (intrinsic) functional networks emerge and relate to stimulus-elicited functional connectivity. Here, we posit and test the long-term phasic molding hypothesis that resting-state network development is influenced by recurring stimulus-elicited connectivity through prospective examination of the developing human amygdala-cortical functional connections. Our results provide critical insight into how early environmental events sculpt functional network architecture across development and highlight childhood as a potential developmental period of heightened malleability for the amygdala-medial prefrontal cortex circuit. These findings have implications for how both positive and adverse experiences influence the developing brain and motivate future investigations of whether this molding mechanism reflects a general phenomenon of brain development. Copyright © 2016 the authors 0270-6474/16/364772-14$15.00/0.
Gee, Dylan Grace; Goff, Bonnie; Flannery, Jessica; Telzer, Eva; Humphreys, Kathryn Leigh; Lumian, Daniel Stephen; Fareri, Dominic Stephen; Caldera, Christina; Tottenham, Nim
2016-01-01
Although the functional architecture of the brain is indexed by resting-state connectivity networks, little is currently known about the mechanisms through which these networks assemble into stable mature patterns. The current study posits and tests the long-term phasic molding hypothesis that resting-state networks are gradually shaped by recurring stimulus-elicited connectivity across development by examining how both stimulus-elicited and resting-state functional connections of the human brain emerge over development at the systems level. Using a sequential design following 4- to 18-year-olds over a 2 year period, we examined the predictive associations between stimulus-elicited and resting-state connectivity in amygdala-cortical circuitry as an exemplar case (given this network's protracted development across these ages). Age-related changes in amygdala functional connectivity converged on the same regions of medial prefrontal cortex (mPFC) and inferior frontal gyrus when elicited by emotional stimuli and when measured at rest. Consistent with the long-term phasic molding hypothesis, prospective analyses for both connections showed that the magnitude of an individual's stimulus-elicited connectivity unidirectionally predicted resting-state functional connectivity 2 years later. For the amygdala-mPFC connection, only stimulus-elicited connectivity during childhood and the transition to adolescence shaped future resting-state connectivity, consistent with a sensitive period ending with adolescence for the amygdala-mPFC circuit. Together, these findings suggest that resting-state functional architecture may arise from phasic patterns of functional connectivity elicited by environmental stimuli over the course of development on the order of years. SIGNIFICANCE STATEMENT A fundamental issue in understanding the ontogeny of brain function is how resting-state (intrinsic) functional networks emerge and relate to stimulus-elicited functional connectivity. Here, we posit and test the long-term phasic molding hypothesis that resting-state network development is influenced by recurring stimulus-elicited connectivity through prospective examination of the developing human amygdala-cortical functional connections. Our results provide critical insight into how early environmental events sculpt functional network architecture across development and highlight childhood as a potential developmental period of heightened malleability for the amygdala-medial prefrontal cortex circuit. These findings have implications for how both positive and adverse experiences influence the developing brain and motivate future investigations of whether this molding mechanism reflects a general phenomenon of brain development. PMID:27122035
Tanaka, Nobuaki K.; Dye, Louis; Stopfer, Mark
2010-01-01
Light and electron microscopy (LM and EM) both offer important advantages for characterizing neuronal circuitry in intact brains: LM can reveal the general patterns neurons trace between brain areas, and EM can confirm synaptic connections between identified neurons within a small area. In a few species, genetic labeling with fluorescent proteins has been used with LM to visualize many kinds of neurons and to analyze their morphologies and projection patterns. However, combining these large-scale patterns with the fine detail available in EM analysis has been a technical challenge. To analyze the synaptic connectivity of neurons expressing fluorescent markers with EM, we developed a dual-labeling method for use with pre-embedded brains. In Drosophila expressing genetic labels and also injected with markers we visualized synaptic connections among two populations of neurons in the AL, one of which has been shown to mediate a specific function, odor evoked neural oscillation. PMID:21074556
van der Wal, Jaap
2009-01-01
The architecture of the connective tissue, including structures such as fasciae, sheaths, and membranes, is more important for understanding functional meaning than is more traditional anatomy, whose anatomical dissection method neglects and denies the continuity of the connective tissue as integrating matrix of the body. The connective tissue anatomy and architecture exhibits two functional tendencies that are present in all areas of the body in different ways and relationships. In body cavities, the “disconnecting” quality of shaping space enables mobility; between organs and body parts, the “connecting” dimension enables functional mechanical interactions. In the musculoskeletal system, those two features of the connective tissue are also present. They cannot be found by the usual analytic dissection procedures. An architectural description is necessary. This article uses such a methodologic approach and gives such a description for the lateral elbow region. The result is an alternative architectural view of the anatomic substrate involved in the transmission and conveyance of forces over synovial joints. An architectural description of the muscular and connective tissue organized in series with each other to enable the transmission of forces over these dynamic entities is more appropriate than is the classical concept of “passive” force-guiding structures such as ligaments organized in parallel to actively force-transmitting structures such as muscles with tendons. The discrimination between so-called joint receptors and muscle receptors is an artificial distinction when function is considered. Mechanoreceptors, also the so-called muscle receptors, are arranged in the context of force circumstances—that is, of the architecture of muscle and connective tissue rather than of the classical anatomic structures such as muscle, capsules, and ligaments. In the lateral cubital region of the rat, a spectrum of mechanosensitive substrate occurs at the transitional areas between regular dense connective tissue layers and the muscle fascicles organized in series with them. This substrate exhibits features of type and location of the mechanosensitive nerve terminals that usually are considered characteristic for “joint receptors” as well as for “muscle receptors.” The receptors for proprioception are concentrated in those areas where tensile stresses are conveyed over the elbow joint. Structures cannot be divided into either joint receptors or muscle receptors when muscular and collagenous connective tissue structures function in series to maintain joint integrity and stability. In vivo, those connective tissue structures are strained during movements of the skeletal parts, those movements in turn being induced and led by tension in muscular tissue. In principle, because of the architecture, receptors can also be stimulated by changes in muscle tension without skeletal movement, or by skeletal movement without change in muscle tension. A mutual relationship exists between structure (and function) of the mechanoreceptors and the architecture of the muscular and regular dense connective tissue. Both are instrumental in the coding of proprioceptive information to the central nervous system. PMID:21589740
Wu, Zhao-Min; Bralten, Janita; An, Li; Cao, Qing-Jiu; Cao, Xiao-Hua; Sun, Li; Liu, Lu; Yang, Li; Mennes, Maarten; Zang, Yu-Feng; Franke, Barbara; Hoogman, Martine; Wang, Yu-Feng
2017-08-01
Few studies have investigated verbal working memory-related functional connectivity patterns in participants with attention-deficit/hyperactivity disorder (ADHD). Thus, we aimed to compare working memory-related functional connectivity patterns in healthy children and those with ADHD, and study effects of methylphenidate (MPH). Twenty-two boys with ADHD were scanned twice, under either MPH (single dose, 10 mg) or placebo, in a randomised, cross-over, counterbalanced placebo-controlled design. Thirty healthy boys were scanned once. We used fMRI during a numerical n-back task to examine functional connectivity patterns in case-control and MPH-placebo comparisons, using independent component analysis. There was no significant difference in behavioural performance between children with ADHD, treated with MPH or placebo, and healthy controls. Compared with controls, participants with ADHD under placebo showed increased functional connectivity within fronto-parietal and auditory networks, and decreased functional connectivity within the executive control network. MPH normalized the altered functional connectivity pattern and significantly enhanced functional connectivity within the executive control network, though in non-overlapping areas. Our study contributes to the identification of the neural substrates of working memory. Single dose of MPH normalized the altered brain functional connectivity network, but had no enhancing effect on (non-impaired) behavioural performance.
A strategy to load balancing for non-connectivity MapReduce job
NASA Astrophysics Data System (ADS)
Zhou, Huaping; Liu, Guangzong; Gui, Haixia
2017-09-01
MapReduce has been widely used in large scale and complex datasets as a kind of distributed programming model. Original Hash partitioning function in MapReduce often results the problem of data skew when data distribution is uneven. To solve the imbalance of data partitioning, we proposes a strategy to change the remaining partitioning index when data is skewed. In Map phase, we count the amount of data which will be distributed to each reducer, then Job Tracker monitor the global partitioning information and dynamically modify the original partitioning function according to the data skew model, so the Partitioner can change the index of these partitioning which will cause data skew to the other reducer that has less load in the next partitioning process, and can eventually balance the load of each node. Finally, we experimentally compare our method with existing methods on both synthetic and real datasets, the experimental results show our strategy can solve the problem of data skew with better stability and efficiency than Hash method and Sampling method for non-connectivity MapReduce task.
Multimodal connectivity of motor learning-related dorsal premotor cortex.
Hardwick, Robert M; Lesage, Elise; Eickhoff, Claudia R; Clos, Mareike; Fox, Peter; Eickhoff, Simon B
2015-12-01
The dorsal premotor cortex (dPMC) is a key region for motor learning and sensorimotor integration, yet we have limited understanding of its functional interactions with other regions. Previous work has started to examine functional connectivity in several brain areas using resting state functional connectivity (RSFC) and meta-analytical connectivity modelling (MACM). More recently, structural covariance (SC) has been proposed as a technique that may also allow delineation of functional connectivity. Here, we applied these three approaches to provide a comprehensive characterization of functional connectivity with a seed in the left dPMC that a previous meta-analysis of functional neuroimaging studies has identified as playing a key role in motor learning. Using data from two sources (the Rockland sample, containing resting state data and anatomical scans from 132 participants, and the BrainMap database, which contains peak activation foci from over 10,000 experiments), we conducted independent whole-brain functional connectivity mapping analyses of a dPMC seed. RSFC and MACM revealed similar connectivity maps spanning prefrontal, premotor, and parietal regions, while the SC map identified more widespread frontal regions. Analyses indicated a relatively consistent pattern of functional connectivity between RSFC and MACM that was distinct from that identified by SC. Notably, results indicate that the seed is functionally connected to areas involved in visuomotor control and executive functions, suggesting that the dPMC acts as an interface between motor control and cognition. Copyright © 2015 Elsevier Inc. All rights reserved.
Kandala, Sridhar; Nolan, Dan; Laumann, Timothy O.; Power, Jonathan D.; Adeyemo, Babatunde; Harms, Michael P.; Petersen, Steven E.; Barch, Deanna M.
2016-01-01
Abstract Like all resting-state functional connectivity data, the data from the Human Connectome Project (HCP) are adversely affected by structured noise artifacts arising from head motion and physiological processes. Functional connectivity estimates (Pearson's correlation coefficients) were inflated for high-motion time points and for high-motion participants. This inflation occurred across the brain, suggesting the presence of globally distributed artifacts. The degree of inflation was further increased for connections between nearby regions compared with distant regions, suggesting the presence of distance-dependent spatially specific artifacts. We evaluated several denoising methods: censoring high-motion time points, motion regression, the FMRIB independent component analysis-based X-noiseifier (FIX), and mean grayordinate time series regression (MGTR; as a proxy for global signal regression). The results suggest that FIX denoising reduced both types of artifacts, but left substantial global artifacts behind. MGTR significantly reduced global artifacts, but left substantial spatially specific artifacts behind. Censoring high-motion time points resulted in a small reduction of distance-dependent and global artifacts, eliminating neither type. All denoising strategies left differences between high- and low-motion participants, but only MGTR substantially reduced those differences. Ultimately, functional connectivity estimates from HCP data showed spatially specific and globally distributed artifacts, and the most effective approach to address both types of motion-correlated artifacts was a combination of FIX and MGTR. PMID:27571276
Zero, Victoria H.; Barocas, Adi; Jochimsen, Denim M.; Pelletier, Agnès; Giroux-Bougard, Xavier; Trumbo, Daryl R.; Castillo, Jessica A.; Evans Mack, Diane; Linnell, Mark A.; Pigg, Rachel M.; Hoisington-Lopez, Jessica; Spear, Stephen F.; Murphy, Melanie A.; Waits, Lisette P.
2017-01-01
The persistence of small populations is influenced by genetic structure and functional connectivity. We used two network-based approaches to understand the persistence of the northern Idaho ground squirrel (Urocitellus brunneus) and the southern Idaho ground squirrel (U. endemicus), two congeners of conservation concern. These graph theoretic approaches are conventionally applied to social or transportation networks, but here are used to study population persistence and connectivity. Population graph analyses revealed that local extinction rapidly reduced connectivity for the southern species, while connectivity for the northern species could be maintained following local extinction. Results from gravity models complemented those of population graph analyses, and indicated that potential vegetation productivity and topography drove connectivity in the northern species. For the southern species, development (roads) and small-scale topography reduced connectivity, while greater potential vegetation productivity increased connectivity. Taken together, the results of the two network-based methods (population graph analyses and gravity models) suggest the need for increased conservation action for the southern species, and that management efforts have been effective at maintaining habitat quality throughout the current range of the northern species. To prevent further declines, we encourage the continuation of management efforts for the northern species, whereas conservation of the southern species requires active management and additional measures to curtail habitat fragmentation. Our combination of population graph analyses and gravity models can inform conservation strategies of other species exhibiting patchy distributions. PMID:28659969
Zero, Victoria H; Barocas, Adi; Jochimsen, Denim M; Pelletier, Agnès; Giroux-Bougard, Xavier; Trumbo, Daryl R; Castillo, Jessica A; Evans Mack, Diane; Linnell, Mark A; Pigg, Rachel M; Hoisington-Lopez, Jessica; Spear, Stephen F; Murphy, Melanie A; Waits, Lisette P
2017-01-01
The persistence of small populations is influenced by genetic structure and functional connectivity. We used two network-based approaches to understand the persistence of the northern Idaho ground squirrel ( Urocitellus brunneus) and the southern Idaho ground squirrel ( U. endemicus ), two congeners of conservation concern. These graph theoretic approaches are conventionally applied to social or transportation networks, but here are used to study population persistence and connectivity. Population graph analyses revealed that local extinction rapidly reduced connectivity for the southern species, while connectivity for the northern species could be maintained following local extinction. Results from gravity models complemented those of population graph analyses, and indicated that potential vegetation productivity and topography drove connectivity in the northern species. For the southern species, development (roads) and small-scale topography reduced connectivity, while greater potential vegetation productivity increased connectivity. Taken together, the results of the two network-based methods (population graph analyses and gravity models) suggest the need for increased conservation action for the southern species, and that management efforts have been effective at maintaining habitat quality throughout the current range of the northern species. To prevent further declines, we encourage the continuation of management efforts for the northern species, whereas conservation of the southern species requires active management and additional measures to curtail habitat fragmentation. Our combination of population graph analyses and gravity models can inform conservation strategies of other species exhibiting patchy distributions.
Raz, Gal; Touroutoglou, Alexandra; Wilson-Mendenhall, Christine; Gilam, Gadi; Lin, Tamar; Gonen, Tal; Jacob, Yael; Atzil, Shir; Admon, Roee; Bleich-Cohen, Maya; Maron-Katz, Adi; Hendler, Talma; Barrett, Lisa Feldman
2016-08-01
Recent theoretical and empirical work has highlighted the role of domain-general, large-scale brain networks in generating emotional experiences. These networks are hypothesized to process aspects of emotional experiences that are not unique to a specific emotional category (e.g., "sadness," "happiness"), but rather that generalize across categories. In this article, we examined the dynamic interactions (i.e., changing cohesiveness) between specific domain-general networks across time while participants experienced various instances of sadness, fear, and anger. We used a novel method for probing the network connectivity dynamics between two salience networks and three amygdala-based networks. We hypothesized, and found, that the functional connectivity between these networks covaried with the intensity of different emotional experiences. Stronger connectivity between the dorsal salience network and the medial amygdala network was associated with more intense ratings of emotional experience across six different instances of the three emotion categories examined. Also, stronger connectivity between the dorsal salience network and the ventrolateral amygdala network was associated with more intense ratings of emotional experience across five out of the six different instances. Our findings demonstrate that a variety of emotional experiences are associated with dynamic interactions of domain-general neural systems.
Deshpande, Gopikrishna; Wang, Peng; Rangaprakash, D; Wilamowski, Bogdan
2015-12-01
Automated recognition and classification of brain diseases are of tremendous value to society. Attention deficit hyperactivity disorder (ADHD) is a diverse spectrum disorder whose diagnosis is based on behavior and hence will benefit from classification utilizing objective neuroimaging measures. Toward this end, an international competition was conducted for classifying ADHD using functional magnetic resonance imaging data acquired from multiple sites worldwide. Here, we consider the data from this competition as an example to illustrate the utility of fully connected cascade (FCC) artificial neural network (ANN) architecture for performing classification. We employed various directional and nondirectional brain connectivity-based methods to extract discriminative features which gave better classification accuracy compared to raw data. Our accuracy for distinguishing ADHD from healthy subjects was close to 90% and between the ADHD subtypes was close to 95%. Further, we show that, if properly used, FCC ANN performs very well compared to other classifiers such as support vector machines in terms of accuracy, irrespective of the feature used. Finally, the most discriminative connectivity features provided insights about the pathophysiology of ADHD and showed reduced and altered connectivity involving the left orbitofrontal cortex and various cerebellar regions in ADHD.
Solomon, Marjorie; Yoon, Jong; Ragland, J. Daniel; Niendam, Tara; Lesh, Tyler A.; Fairbrother, Wonja; Carter, Cameron S.
2013-01-01
Background Autism spectrum disorders (ASD) involve impairments in cognitive control. In typical development (TYP), neural systems underlying cognitive control undergo substantial maturation during adolescence. Development is delayed in adolescents with ASD. Little is known about the neural substrates of this delay. Method We used event-related functional magnetic resonance imaging (fMRI) and a cognitive control task involving overcoming a prepotent response tendency to examine the development of cognitive control in young (ages 12–15; n = 13 with ASD and n = 13 with TYP) and older (ages 16–18; n= 14 with ASD and n = 14 with TYP) adolescents with whole-brain voxel-wise univariate and task-related functional connectivity analyses. Results Older ASD and TYP showed reduced activation in sensory and premotor areas relative to younger ones. The older ASD group showed reduced left parietal activation relative to TYP. Functional connectivity analyses showed a significant age by group interaction with the older ASD group exhibiting increased functional connectivity strength between the ventrolateral prefrontal cortex (VLPFC) and the anterior cingulate cortex (ACC), bilaterally. This functional connectivity strength was related to task performance in ASD, whereas that between DLPFC and parietal cortex (BA 9 and BA 40) was related to task performance in TYP. Conclusions Adolescents with ASD rely more on “reactive” cognitive control, involving last minute conflict detection and control implementation by the ACC and VLPFC, versus “proactive” cognitive control requiring processing by DLPFC and parietal cortex. Findings await replication in larger longitudinal studies that examine their functional consequences and amenability to intervention. PMID:24209777
Cheng, Wei; Rolls, Edmund T; Qiu, Jiang; Liu, Wei; Tang, Yanqing; Huang, Chu-Chung; Wang, XinFa; Zhang, Jie; Lin, Wei; Zheng, Lirong; Pu, JunCai; Tsai, Shih-Jen; Yang, Albert C; Lin, Ching-Po; Wang, Fei; Xie, Peng; Feng, Jianfeng
2016-12-01
The first brain-wide voxel-level resting state functional connectivity neuroimaging analysis of depression is reported, with 421 patients with major depressive disorder and 488 control subjects. Resting state functional connectivity between different voxels reflects correlations of activity between those voxels and is a fundamental tool in helping to understand the brain regions with altered connectivity and function in depression. One major circuit with altered functional connectivity involved the medial orbitofrontal cortex Brodmann area 13, which is implicated in reward, and which had reduced functional connectivity in depression with memory systems in the parahippocampal gyrus and medial temporal lobe, especially involving the perirhinal cortex Brodmann area 36 and entorhinal cortex Brodmann area 28. The Hamilton Depression Rating Scale scores were correlated with weakened functional connectivity of the medial orbitofrontal cortex Brodmann area 13. Thus in depression there is decreased reward-related and memory system functional connectivity, and this is related to the depressed symptoms. The lateral orbitofrontal cortex Brodmann area 47/12, involved in non-reward and punishing events, did not have this reduced functional connectivity with memory systems. Second, the lateral orbitofrontal cortex Brodmann area 47/12 had increased functional connectivity with the precuneus, the angular gyrus, and the temporal visual cortex Brodmann area 21. This enhanced functional connectivity of the non-reward/punishment system (Brodmann area 47/12) with the precuneus (involved in the sense of self and agency), and the angular gyrus (involved in language) is thus related to the explicit affectively negative sense of the self, and of self-esteem, in depression. A comparison of the functional connectivity in 185 depressed patients not receiving medication and 182 patients receiving medication showed that the functional connectivity of the lateral orbitofrontal cortex Brodmann area 47/12 with these three brain areas was lower in the medicated than the unmedicated patients. This is consistent with the hypothesis that the increased functional connectivity of the lateral orbitofrontal cortex Brodmann area 47/12 is related to depression. Relating the changes in cortical connectivity to our understanding of the functions of different parts of the orbitofrontal cortex in emotion helps to provide new insight into the brain changes related to depression. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Functional Connectivity of the Amygdala in Early Childhood Onset Depression
Luking, Katherine R.; Repovs, Grega; Belden, Andy C.; Gaffrey, Michael S.; Botteron, Kelly N.; Luby, Joan L.; Barch, Deanna M.
2011-01-01
Objective Adult major depressive disorder (MDD) is associated with reduced cortico-limbic functional connectivity thought to indicate decreased top-down control of emotion. However, it is unclear whether such connectivity alterations are also present in early childhood onset MDD. Method Fifty-one children ages 7–11 years, prospectively studied since preschool age, completed resting state fMRI and were assigned to four groups: 1) C-MDD (N=13) personal history of early childhood onset MDD; 2) M-MDD (N=11) a maternal history of affective disorders; 3) CM-MDD (N=13) both maternal and early childhood onset MDD or 4) CON (N=14) without either a personal or maternal history. We used seed-based resting state functional connectivity (rsfcMRI) analysis in an independent sample of adults to identify networks showing both positive (e.g., limbic regions) and negative (e.g., dorsal frontal/parietal regions) connectivity with the amygdala. These regions were then used in ROI based analyses of our child sample. Results We found a significant interaction between maternal affective disorder history and the child's MDD history for both positive and negative rsfcMRI networks. Specifically, when copared to CON, we found reduced connectivity between the amygdala and the “Negative Network” in children with C-MDD, M-MDD and CM-MDD. Children with either C-MDD or a maternal history of MDD (but not CM-MDD) displayed reduced connectivity between the amygdala and the “Positive Network”. Conclusions Our finding of an attenuated relationship between the amygdala, a region affected in MDD and involved in emotion processing, and cognitive control regions is consistent with a hypothesis of altered regulation of emotional processing in C-MDD suggesting developmental continuity of this alteration into early childhood. PMID:21961777
A symmetric multivariate leakage correction for MEG connectomes
Colclough, G.L.; Brookes, M.J.; Smith, S.M.; Woolrich, M.W.
2015-01-01
Ambiguities in the source reconstruction of magnetoencephalographic (MEG) measurements can cause spurious correlations between estimated source time-courses. In this paper, we propose a symmetric orthogonalisation method to correct for these artificial correlations between a set of multiple regions of interest (ROIs). This process enables the straightforward application of network modelling methods, including partial correlation or multivariate autoregressive modelling, to infer connectomes, or functional networks, from the corrected ROIs. Here, we apply the correction to simulated MEG recordings of simple networks and to a resting-state dataset collected from eight subjects, before computing the partial correlations between power envelopes of the corrected ROItime-courses. We show accurate reconstruction of our simulated networks, and in the analysis of real MEGresting-state connectivity, we find dense bilateral connections within the motor and visual networks, together with longer-range direct fronto-parietal connections. PMID:25862259
NASA Astrophysics Data System (ADS)
Abidin, Anas Zainul; D'Souza, Adora M.; Nagarajan, Mahesh B.; Wismüller, Axel
2016-03-01
About 50% of subjects infected with HIV present deficits in cognitive domains, which are known collectively as HIV associated neurocognitive disorder (HAND). The underlying synaptodendritic damage can be captured using resting state functional MRI, as has been demonstrated by a few earlier studies. Such damage may induce topological changes of brain connectivity networks. We test this hypothesis by capturing the functional interdependence of 90 brain network nodes using a Mutual Connectivity Analysis (MCA) framework with non-linear time series modeling based on Generalized Radial Basis function (GRBF) neural networks. The network nodes are selected based on the regions defined in the Automated Anatomic Labeling (AAL) atlas. Each node is represented by the average time series of the voxels of that region. The resulting networks are then characterized using graph-theoretic measures that quantify various network topology properties at a global as well as at a local level. We tested for differences in these properties in network graphs obtained for 10 subjects (6 male and 4 female, 5 HIV+ and 5 HIV-). Global network properties captured some differences between these subject cohorts, though significant differences were seen only with the clustering coefficient measure. Local network properties, such as local efficiency and the degree of connections, captured significant differences in regions of the frontal lobe, precentral and cingulate cortex amongst a few others. These results suggest that our method can be used to effectively capture differences occurring in brain network connectivity properties revealed by resting-state functional MRI in neurological disease states, such as HAND.
Haut, Kristen; Saxena, Abhishek; Yin, Hong; Carol, Emily; Dodell-Feder, David; Lincoln, Sarah Hope; Tully, Laura; Keshavan, Matcheri; Seidman, Larry J.; Nahum, Mor; Hooker, Christine
2017-01-01
Abstract Background: Deficits in social cognition are prominent features of schizophrenia that play a large role in functional impairments and disability. Performance deficits in these domains are associated with altered activity in functional networks, including those that support social cognitive abilities such as emotion recognition. These social cognitive deficits and alterations in neural networks are present prior to the onset of frank psychotic symptoms and thus present a potential target for intervention in early phases of the illness, including in individuals at clinical high risk (CHR) for psychosis. This study assessed changes in social cognitive functional networks following targeted cognitive training (TCT) in CHR individuals. Methods: 14 CHR subjects (7 male, mean age = 21.9) showing attenuated psychotic symptoms as assessed by the SIPS were included in the study. Subjects underwent a clinical evaluation and a functional MRI session prior to and subsequent to completing 40 hours (8 weeks) of targeted cognitive and social cognitive training using Lumosity and SocialVille. 14 matched healthy control (HC) subjects also underwent a single fMRI session as a comparison group for functional activity. Resting state fMRI was acquired as well as fMRI during performance of an emotion recognition task. Group level differences in BOLD activity between HC and CHR group before TCT, and CHR group before and after TCT were computed. Changes in social cognitive network functional connectivity at rest and during task performance was evaluated using seed-based connectivity analyses and psychophysiological interaction (PPI). Results: Prior to training, CHR individuals demonstrated hyperactivity in the amygdala, posterior cingulate, and superior temporal sulcus (STS) during emotion recognition, suggesting inefficient processing. This hyperactivity normalized somewhat after training, with CHR individuals showing less hyperactivity in the amygdala in response to emotional faces. In addition, training was associated with increased connectivity in emotion processing networks, including greater STS-medial prefrontal connectivity and normalization of amygdala connectivity patterns. Conclusion: These results suggest that targeted cognitive training produced improvements in emotion recognition and may be effective in altering functional network connectivity in networks associated with psychosis risk. TCT may be a useful tool for early intervention in individuals at risk for psychotic disorders to address behaviors that impact functional outcome.
Cell-type Specific Optogenetic Mice for Dissecting Neural Circuitry Function
Zhao, Shengli; Ting, Jonathan T.; Atallah, Hisham E.; Qiu, Li; Tan, Jie; Gloss, Bernd; Augustine, George J.; Deisseroth, Karl; Luo, Minmin; Graybiel, Ann M.; Feng, Guoping
2011-01-01
Optogenetic methods have emerged as powerful tools for dissecting neural circuit connectivity, function, and dysfunction. We used a Bacterial Artificial Chromosome (BAC) transgenic strategy to express Channelrhodopsin2 (ChR2) under the control of cell-type specific promoter elements. We provide a detailed functional characterization of the newly established VGAT-ChR2-EYFP, ChAT-ChR2-EYFP, TPH2-ChR2-EYFP and Pvalb-ChR2-EYFP BAC transgenic mouse lines and demonstrate the utility of these lines for precisely controlling action potential firing of GABAergic, cholinergic, serotonergic, and parvalbumin+ neuron subsets using blue light. This resource of cell type-specific ChR2 mouse lines will facilitate the precise mapping of neuronal connectivity and the dissection of the neural basis of behavior. PMID:21985008
Altered Brain Functional Connectivity in Betel Quid-Dependent Chewers.
Huang, Xiaojun; Pu, Weidan; Liu, Haihong; Li, Xinmin; Greenshaw, Andrew J; Dursun, Serdar M; Xue, Zhimin; Liu, Zhening
2017-01-01
Betel quid (BQ) is a common psychoactive substance worldwide with particularly high usage in many Asian countries. This study aimed to explore the effect of BQ use on functional connectivity by comparing global functional brain networks and their subset between BQ chewers and healthy controls (HCs). Resting-state functional magnetic resonance imaging (fMRI) was obtained from 24 betel quid-dependent (BQD) male chewers and 27 healthy male individuals on a 3.0T scanner. We used independent component analysis (ICA) to determine components that represent the brain's functional networks and their spatial aspects of functional connectivity. Two sample t -tests were used to identify the functional connectivity differences in each network between these two groups. Seventeen networks were identified by ICA. Nine of them showed connectivity differences between BQD and HCs (two sample t -tests, p < 0.001 uncorrected). We found increased functional connectivity in the orbitofrontal, bilateral frontoparietal, frontotemporal, occipital/parietal, frontotemporal/cerebellum, and temporal/limbic networks, and decreased connectivity in the parietal and medial frontal/anterior cingulate networks in the BQD compared to the HCs. The betel quid dependence scale scores were positively related to the increased functional connectivity in the orbitofrontal ( r = 0.39, p = 0.03) while negatively related to the decreased functional connectivity in medial frontal/anterior cingulate networks ( r = -0.35, p = 0.02). Our findings provide further evidence that BQ chewing may lead to brain functional connectivity changes, which may play a key role in the psychological and physiological effects of BQ.
Stepwise Connectivity of the Modal Cortex Reveals the Multimodal Organization of the Human Brain
Sepulcre, Jorge; Sabuncu, Mert R.; Yeo, Thomas B.; Liu, Hesheng; Johnson, Keith A.
2012-01-01
How human beings integrate information from external sources and internal cognition to produce a coherent experience is still not well understood. During the past decades, anatomical, neurophysiological and neuroimaging research in multimodal integration have stood out in the effort to understand the perceptual binding properties of the brain. Areas in the human lateral occipito-temporal, prefrontal and posterior parietal cortices have been associated with sensory multimodal processing. Even though this, rather patchy, organization of brain regions gives us a glimpse of the perceptual convergence, the articulation of the flow of information from modality-related to the more parallel cognitive processing systems remains elusive. Using a method called Stepwise Functional Connectivity analysis, the present study analyzes the functional connectome and transitions from primary sensory cortices to higher-order brain systems. We identify the large-scale multimodal integration network and essential connectivity axes for perceptual integration in the human brain. PMID:22855814
Jung, Kwanghee; Takane, Yoshio; Hwang, Heungsun; Woodward, Todd S
2016-06-01
We extend dynamic generalized structured component analysis (GSCA) to enhance its data-analytic capability in structural equation modeling of multi-subject time series data. Time series data of multiple subjects are typically hierarchically structured, where time points are nested within subjects who are in turn nested within a group. The proposed approach, named multilevel dynamic GSCA, accommodates the nested structure in time series data. Explicitly taking the nested structure into account, the proposed method allows investigating subject-wise variability of the loadings and path coefficients by looking at the variance estimates of the corresponding random effects, as well as fixed loadings between observed and latent variables and fixed path coefficients between latent variables. We demonstrate the effectiveness of the proposed approach by applying the method to the multi-subject functional neuroimaging data for brain connectivity analysis, where time series data-level measurements are nested within subjects.
Li, Yanwei; Yu, Dongchuan
2016-10-01
Functional near infrared spectroscopy (fNIRS) is particularly suited for the young population and ecological measurement. However, thus far, not enough effort has been given to the clinical diagnosis of young children with Autism Spectrum Disorder (ASD) by using fNIRS. The current study provided some insights into the quantitative analysis of functional networks in young children (ages 4.8-8.0years old) with and without ASD and, in particular, investigated the network efficiency and lobe-level connectivity of their functional networks while watching a cartoon. The main results included that: (i) Weak network efficiency was observed in young children with ASD, even for a wide range of threshold for the binarization of functional networks; (ii) A maximum classification accuracy rate of 83.3% was obtained for all participants by using the k-means clustering method with network efficiencies as the feature parameters; and (iii) Weak lobe-level inter-region connections were uncovered in the right prefrontal cortex, including its linkages with the left prefrontal cortex and the bilateral temporal cortex. Such results indicate that the right prefrontal cortex might make a major contribution to the psychopathology of young children with ASD at the functional network architecture level, and at the functional lobe-connectivity level, respectively. Copyright © 2016 Elsevier Inc. All rights reserved.
Reproducibility of graph metrics of human brain structural networks.
Duda, Jeffrey T; Cook, Philip A; Gee, James C
2014-01-01
Recent interest in human brain connectivity has led to the application of graph theoretical analysis to human brain structural networks, in particular white matter connectivity inferred from diffusion imaging and fiber tractography. While these methods have been used to study a variety of patient populations, there has been less examination of the reproducibility of these methods. A number of tractography algorithms exist and many of these are known to be sensitive to user-selected parameters. The methods used to derive a connectivity matrix from fiber tractography output may also influence the resulting graph metrics. Here we examine how these algorithm and parameter choices influence the reproducibility of proposed graph metrics on a publicly available test-retest dataset consisting of 21 healthy adults. The dice coefficient is used to examine topological similarity of constant density subgraphs both within and between subjects. Seven graph metrics are examined here: mean clustering coefficient, characteristic path length, largest connected component size, assortativity, global efficiency, local efficiency, and rich club coefficient. The reproducibility of these network summary measures is examined using the intraclass correlation coefficient (ICC). Graph curves are created by treating the graph metrics as functions of a parameter such as graph density. Functional data analysis techniques are used to examine differences in graph measures that result from the choice of fiber tracking algorithm. The graph metrics consistently showed good levels of reproducibility as measured with ICC, with the exception of some instability at low graph density levels. The global and local efficiency measures were the most robust to the choice of fiber tracking algorithm.
Widjaja, E; Zamyadi, M; Raybaud, C; Snead, O C; Smith, M L
2013-12-01
Epilepsy is considered a disorder of neural networks. The aims of this study were to assess functional connectivity within resting-state networks and functional network connectivity across resting-state networks by use of resting-state fMRI in children with frontal lobe epilepsy and to relate changes in resting-state networks with neuropsychological function. Fifteen patients with frontal lobe epilepsy and normal MR imaging and 14 healthy control subjects were recruited. Spatial independent component analysis was used to identify the resting-state networks, including frontal, attention, default mode network, sensorimotor, visual, and auditory networks. The Z-maps of resting-state networks were compared between patients and control subjects. The relation between abnormal connectivity and neuropsychological function was assessed. Correlations from all pair-wise combinations of independent components were performed for each group and compared between groups. The frontal network was the only network that showed reduced connectivity in patients relative to control subjects. The remaining 5 networks demonstrated both reduced and increased functional connectivity within resting-state networks in patients. There was a weak association between connectivity in frontal network and executive function (P = .029) and a significant association between sensorimotor network and fine motor function (P = .004). Control subjects had 79 pair-wise independent components that showed significant temporal coherence across all resting-state networks except for default mode network-auditory network. Patients had 66 pairs of independent components that showed significant temporal coherence across all resting-state networks. Group comparison showed reduced functional network connectivity between default mode network-attention, frontal-sensorimotor, and frontal-visual networks and increased functional network connectivity between frontal-attention, default mode network-sensorimotor, and frontal-visual networks in patients relative to control subjects. We found abnormal functional connectivity within and across resting-state networks in children with frontal lobe epilepsy. Impairment in functional connectivity was associated with impaired neuropsychological function.
Calhoun, V. D.; Pearlson, G. D.
2011-01-01
Naturalistic paradigms such as movie watching or simulated driving that mimic closely real-world complex activities are becoming more widely used in functional magnetic resonance imaging (fMRI) studies both because of their ability to robustly stimulate brain connectivity and the availability of analysis methods which are able to capitalize on connectivity within and among intrinsic brain networks identified both during a task and in resting fMRI data. In this paper we review over a decade of work from our group and others on the use of simulated driving paradigms to study both the healthy brain as well as the effects of acute alcohol administration on functional connectivity during such paradigms. We briefly review our initial work focused on the configuration of the driving simulator and the analysis strategies. We then describe in more detail several recent studies from our group including a hybrid study examining distracted driving and compare resulting data with those from a separate visual oddball task. The analysis of these data were performed primarily using a combination of group independent component analysis (ICA) and the general linear model (GLM) and in the various studies we highlight novel findings which result from an analysis of either 1) within-network connectivity, 2) inter-network connectivity, also called functional network connectivity, or 3) the degree to which the modulation of the various intrinsic networks were associated with the alcohol administration and the task context. Despite the fact that the behavioral effects of alcohol intoxication are relatively well known, there is still much to discover on how acute alcohol exposure modulates brain function in a selective manner, associated with behavioral alterations. Through the above studies, we have learned more regarding the impact of acute alcohol intoxication on organization of the brain’s intrinsic connectivity networks during performance of a complex, real-world cognitive operation. Lessons learned from the above studies have broader applicability to designing ecologically valid, complex, functional MRI cognitive paradigms and incorporating pharmacologic challenges into such studies. Overall, the use of hybrid driving studies is a particularly promising area of neuroscience investigation. PMID:21718791
Ma, Qiongmin; Wu, Donglin; Zeng, Ling-Li; Shen, Hui; Hu, Dewen; Qiu, Shijun
2016-01-01
Abstract The study aims to investigate the radiation-induced brain functional alterations in nasopharyngeal carcinoma (NPC) patients who received radiotherapy (RT) using functional magnetic resonance imaging (fMRI) and statistic scale. The fMRI data of 35 NPC patients with RT and 24 demographically matched untreated NPC patients were acquired. Montreal Cognitive Assessment (MoCA) was also measured to evaluate their global cognition performance. Multivariate pattern analysis was performed to find the significantly altered functional connections between these 2 groups, while the linear correlation level was detected between the altered functional connections and the MoCA scores. Forty-five notably altered functional connections were found, which were mainly located between 3 brain networks, the cerebellum, sensorimotor, and cingulo-opercular. With strictly false discovery rate correction, 5 altered functional connections were shown to have significant linear correlations with the MoCA scores, that is, the connections between the vermis and hippocampus, cerebellum lobule VI and dorsolateral prefrontal cortex, precuneus and dorsal frontal cortex, cuneus and middle occipital lobe, and insula and cuneus. Besides, the connectivity between the vermis and hippocampus was also significantly correlated with the attention score, 1 of the 7 subscores of the MoCA. The present study provides new insights into the radiation-induced functional connectivity impairments in NPC patients. The results showed that the RT may induce the cognitive impairments, especially the attention alterations. The 45 altered functional connections, especially the 5 altered functional connections that were significantly correlated to the MoCA scores, may serve as the potential biomarkers of the RT-induced brain functional impairments and provide valuable targets for further functional recovery treatment. PMID:27442663
Solomon, Marjorie; Ragland, J. Daniel; Niendam, Tara A.; Lesh, Tyler A.; Beck, Jonathan S.; Matter, John C.; Frank, Michael J.; Carter, Cameron S.
2015-01-01
Objective To investigate the neural mechanisms underlying impairments in generalizing learning shown by adolescents with autism spectrum disorder (ASD). Method Twenty-one high-functioning individuals with ASD aged 12–18 years, and 23 gender, IQ, and age-matched adolescents with typical development (TYP) completed a transitive inference (TI) task implemented using rapid event-related functional magnetic resonance imaging (fMRI). They were trained on overlapping pairs in a stimulus hierarchy of colored ovals where A>B>C>D>E>F and then tested on generalizing this training to new stimulus pairings (AF, BD, BE) in a “Big Game.” Whole-brain univariate, region of interest, and functional connectivity analyses were used. Results During training, TYP exhibited increased recruitment of the prefrontal cortex (PFC), while the group with ASD showed greater functional connectivity between the PFC and the anterior cingulate cortex (ACC). Both groups recruited the hippocampus and caudate comparably; however, functional connectivity between these regions was positively associated with TI performance for only the group with ASD. During the Big Game, TYP showed greater recruitment of the PFC, parietal cortex, and the ACC. Recruitment of these regions increased with age in the group with ASD. Conclusion During TI, TYP recruited cognitive control-related brain regions implicated in mature problem solving/reasoning including the PFC, parietal cortex, and ACC, while the group with ASD showed functional connectivity of the hippocampus and the caudate that was associated with task performance. Failure to reliably engage cognitive control-related brain regions may produce less integrated flexible learning in those with ASD unless they are provided with task support that in essence provides them with cognitive control, but this pattern may normalize with age. PMID:26506585
Venkataraman, Archana; Duncan, James S.; Yang, Daniel Y.-J.; Pelphrey, Kevin A.
2015-01-01
Resting-state functional magnetic resonance imaging (rsfMRI) studies reveal a complex pattern of hyper- and hypo-connectivity in children with autism spectrum disorder (ASD). Whereas rsfMRI findings tend to implicate the default mode network and subcortical areas in ASD, task fMRI and behavioral experiments point to social dysfunction as a unifying impairment of the disorder. Here, we leverage a novel Bayesian framework for whole-brain functional connectomics that aggregates population differences in connectivity to localize a subset of foci that are most affected by ASD. Our approach is entirely data-driven and does not impose spatial constraints on the region foci or dictate the trajectory of altered functional pathways. We apply our method to data from the openly shared Autism Brain Imaging Data Exchange (ABIDE) and pinpoint two intrinsic functional networks that distinguish ASD patients from typically developing controls. One network involves foci in the right temporal pole, left posterior cingulate cortex, left supramarginal gyrus, and left middle temporal gyrus. Automated decoding of this network by the Neurosynth meta-analytic database suggests high-level concepts of “language” and “comprehension” as the likely functional correlates. The second network consists of the left banks of the superior temporal sulcus, right posterior superior temporal sulcus extending into temporo-parietal junction, and right middle temporal gyrus. Associated functionality of these regions includes “social” and “person”. The abnormal pathways emanating from the above foci indicate that ASD patients simultaneously exhibit reduced long-range or inter-hemispheric connectivity and increased short-range or intra-hemispheric connectivity. Our findings reveal new insights into ASD and highlight possible neural mechanisms of the disorder. PMID:26106561
Xu, Nan; Spreng, R Nathan; Doerschuk, Peter C
2017-01-01
Resting-state functional MRI (rs-fMRI) is widely used to noninvasively study human brain networks. Network functional connectivity is often estimated by calculating the timeseries correlation between blood-oxygen-level dependent (BOLD) signal from different regions of interest (ROIs). However, standard correlation cannot characterize the direction of information flow between regions. In this paper, we introduce and test a new concept, prediction correlation, to estimate effective connectivity in functional brain networks from rs-fMRI. In this approach, the correlation between two BOLD signals is replaced by a correlation between one BOLD signal and a prediction of this signal via a causal system driven by another BOLD signal. Three validations are described: (1) Prediction correlation performed well on simulated data where the ground truth was known, and outperformed four other methods. (2) On simulated data designed to display the "common driver" problem, prediction correlation did not introduce false connections between non-interacting driven ROIs. (3) On experimental data, prediction correlation recovered the previously identified network organization of human brain. Prediction correlation scales well to work with hundreds of ROIs, enabling it to assess whole brain interregional connectivity at the single subject level. These results provide an initial validation that prediction correlation can capture the direction of information flow and estimate the duration of extended temporal delays in information flow between regions of interest ROIs based on BOLD signal. This approach not only maintains the high sensitivity to network connectivity provided by the correlation analysis, but also performs well in the estimation of causal information flow in the brain.
Disruption of posteromedial large-scale neural communication predicts recovery from coma
de Pasquale, Francesco; Vuillaume, Corine; Riu, Beatrice; Loubinoux, Isabelle; Geeraerts, Thomas; Seguin, Thierry; Bounes, Vincent; Fourcade, Olivier; Demonet, Jean-Francois; Péran, Patrice
2015-01-01
Objective: We hypothesize that the major consciousness deficit observed in coma is due to the breakdown of long-range neuronal communication supported by precuneus and posterior cingulate cortex (PCC), and that prognosis depends on a specific connectivity pattern in these networks. Methods: We compared 27 prospectively recruited comatose patients who had severe brain injury (Glasgow Coma Scale score <8; 14 traumatic and 13 anoxic cases) with 14 age-matched healthy participants. Standardized clinical assessment and fMRI were performed on average 4 ± 2 days after withdrawal of sedation. Analysis of resting-state fMRI connectivity involved a hypothesis-driven, region of interest–based strategy. We assessed patient outcome after 3 months using the Coma Recovery Scale–Revised (CRS-R). Results: Patients who were comatose showed a significant disruption of functional connectivity of brain areas spontaneously synchronized with PCC, globally notwithstanding etiology. The functional connectivity strength between PCC and medial prefrontal cortex (mPFC) was significantly different between comatose patients who went on to recover and those who eventually scored an unfavorable outcome 3 months after brain injury (Kruskal-Wallis test, p < 0.001; linear regression between CRS-R and PCC-mPFC activity coupling at rest, Spearman ρ = 0.93, p < 0.003). Conclusion: In both etiology groups (traumatic and anoxic), changes in the connectivity of PCC-centered, spontaneously synchronized, large-scale networks account for the loss of external and internal self-centered awareness observed during coma. Sparing of functional connectivity between PCC and mPFC may predict patient outcome, and further studies are needed to substantiate this potential prognosis biomarker. PMID:26561296
Sitek, Kevin R; Cai, Shanqing; Beal, Deryk S; Perkell, Joseph S; Guenther, Frank H; Ghosh, Satrajit S
2016-01-01
Persistent developmental stuttering is characterized by speech production disfluency and affects 1% of adults. The degree of impairment varies widely across individuals and the neural mechanisms underlying the disorder and this variability remain poorly understood. Here we elucidate compensatory mechanisms related to this variability in impairment using whole-brain functional and white matter connectivity analyses in persistent developmental stuttering. We found that people who stutter had stronger functional connectivity between cerebellum and thalamus than people with fluent speech, while stutterers with the least severe symptoms had greater functional connectivity between left cerebellum and left orbitofrontal cortex (OFC). Additionally, people who stutter had decreased functional and white matter connectivity among the perisylvian auditory, motor, and speech planning regions compared to typical speakers, but greater functional connectivity between the right basal ganglia and bilateral temporal auditory regions. Structurally, disfluency ratings were negatively correlated with white matter connections to left perisylvian regions and to the brain stem. Overall, we found increased connectivity among subcortical and reward network structures in people who stutter compared to controls. These connections were negatively correlated with stuttering severity, suggesting the involvement of cerebellum and OFC may underlie successful compensatory mechanisms by more fluent stutterers.
NASA Astrophysics Data System (ADS)
Jin, N.; Yang, F.; Shang, S. Y.; Tao, T.; Liu, J. S.
2016-08-01
According to the limitations of the LVRT technology of traditional photovoltaic inverter existed, this paper proposes a low voltage ride through (LVRT) control method based on model current predictive control (MCPC). This method can effectively improve the photovoltaic inverter output characteristics and response speed. The MCPC method of photovoltaic grid-connected inverter designed, the sum of the absolute value of the predictive current and the given current error is adopted as the cost function with the model predictive control method. According to the MCPC, the optimal space voltage vector is selected. Photovoltaic inverter has achieved automatically switches of priority active or reactive power control of two control modes according to the different operating states, which effectively improve the inverter capability of LVRT. The simulation and experimental results proves that the proposed method is correct and effective.
Classifying Different Emotional States by Means of EEG-Based Functional Connectivity Patterns
Lee, You-Yun; Hsieh, Shulan
2014-01-01
This study aimed to classify different emotional states by means of EEG-based functional connectivity patterns. Forty young participants viewed film clips that evoked the following emotional states: neutral, positive, or negative. Three connectivity indices, including correlation, coherence, and phase synchronization, were used to estimate brain functional connectivity in EEG signals. Following each film clip, participants were asked to report on their subjective affect. The results indicated that the EEG-based functional connectivity change was significantly different among emotional states. Furthermore, the connectivity pattern was detected by pattern classification analysis using Quadratic Discriminant Analysis. The results indicated that the classification rate was better than chance. We conclude that estimating EEG-based functional connectivity provides a useful tool for studying the relationship between brain activity and emotional states. PMID:24743695
Identifying pathogenic processes by integrating microarray data with prior knowledge
2014-01-01
Background It is of great importance to identify molecular processes and pathways that are involved in disease etiology. Although there has been an extensive use of various high-throughput methods for this task, pathogenic pathways are still not completely understood. Often the set of genes or proteins identified as altered in genome-wide screens show a poor overlap with canonical disease pathways. These findings are difficult to interpret, yet crucial in order to improve the understanding of the molecular processes underlying the disease progression. We present a novel method for identifying groups of connected molecules from a set of differentially expressed genes. These groups represent functional modules sharing common cellular function and involve signaling and regulatory events. Specifically, our method makes use of Bayesian statistics to identify groups of co-regulated genes based on the microarray data, where external information about molecular interactions and connections are used as priors in the group assignments. Markov chain Monte Carlo sampling is used to search for the most reliable grouping. Results Simulation results showed that the method improved the ability of identifying correct groups compared to traditional clustering, especially for small sample sizes. Applied to a microarray heart failure dataset the method found one large cluster with several genes important for the structure of the extracellular matrix and a smaller group with many genes involved in carbohydrate metabolism. The method was also applied to a microarray dataset on melanoma cancer patients with or without metastasis, where the main cluster was dominated by genes related to keratinocyte differentiation. Conclusion Our method found clusters overlapping with known pathogenic processes, but also pointed to new connections extending beyond the classical pathways. PMID:24758699
Berente, Imre; Czinki, Eszter; Náray-Szabó, Gábor
2007-09-01
We report an approach for the determination of atomic monopoles of macromolecular systems using connectivity and geometry parameters alone. The method is appropriate also for the calculation of charge distributions based on the quantum mechanically determined wave function and does not suffer from the mathematical instability of other electrostatic potential fit methods. Copyright 2007 Wiley Periodicals, Inc.
Herrera-Díaz, Adianes; Mendoza-Quiñones, Raúl; Melie-Garcia, Lester; Martínez-Montes, Eduardo; Sanabria-Diaz, Gretel; Romero-Quintana, Yuniel; Salazar-Guerra, Iraklys; Carballoso-Acosta, Mario; Caballero-Moreno, Antonio
2016-05-01
This study was aimed at exploring the electroencephalographic features associated with alcohol use disorders (AUD) during a resting-state condition, by using quantitative EEG and Functional Connectivity analyses. In addition, we explored whether EEG functional connectivity is associated with trait impulsivity. Absolute and relative powers and Synchronization Likelihood (SL) as a measure of functional connectivity were analyzed in 15 AUD women and fifteen controls matched in age, gender and education. Correlation analysis between self-report impulsivity as measured by the Barratt impulsiveness Scale (BIS-11) and SL values of AUD patients were performed. Our results showed increased absolute and relative beta power in AUD patients compared to matched controls, and reduced functional connectivity in AUD patients predominantly in the beta and alpha bands. Impaired connectivity was distributed at fronto-central and occipito-parietal regions in the alpha band, and over the entire scalp in the beta band. We also found that impaired functional connectivity particularly in alpha band at fronto-central areas was negative correlated with non-planning dimension of impulsivity. These findings suggest that functional brain abnormalities are present in AUD patients and a disruption of resting-state EEG functional connectivity is associated with psychopathological traits of addictive behavior.
Laterality patterns of brain functional connectivity: gender effects.
Tomasi, Dardo; Volkow, Nora D
2012-06-01
Lateralization of brain connectivity may be essential for normal brain function and may be sexually dimorphic. Here, we study the laterality patterns of short-range (implicated in functional specialization) and long-range (implicated in functional integration) connectivity and the gender effects on these laterality patterns. Parallel computing was used to quantify short- and long-range functional connectivity densities in 913 healthy subjects. Short-range connectivity was rightward lateralized and most asymmetrical in areas around the lateral sulcus, whereas long-range connectivity was rightward lateralized in lateral sulcus and leftward lateralizated in inferior prefrontal cortex and angular gyrus. The posterior inferior occipital cortex was leftward lateralized (short- and long-range connectivity). Males had greater rightward lateralization of brain connectivity in superior temporal (short- and long-range), inferior frontal, and inferior occipital cortices (short-range), whereas females had greater leftward lateralization of long-range connectivity in the inferior frontal cortex. The greater lateralization of the male's brain (rightward and predominantly short-range) may underlie their greater vulnerability to disorders with disrupted brain asymmetries (schizophrenia, autism).
Laterality Patterns of Brain Functional Connectivity: Gender Effects
Tomasi, Dardo; Volkow, Nora D.
2012-01-01
Lateralization of brain connectivity may be essential for normal brain function and may be sexually dimorphic. Here, we study the laterality patterns of short-range (implicated in functional specialization) and long-range (implicated in functional integration) connectivity and the gender effects on these laterality patterns. Parallel computing was used to quantify short- and long-range functional connectivity densities in 913 healthy subjects. Short-range connectivity was rightward lateralized and most asymmetrical in areas around the lateral sulcus, whereas long-range connectivity was rightward lateralized in lateral sulcus and leftward lateralizated in inferior prefrontal cortex and angular gyrus. The posterior inferior occipital cortex was leftward lateralized (short- and long-range connectivity). Males had greater rightward lateralization of brain connectivity in superior temporal (short- and long-range), inferior frontal, and inferior occipital cortices (short-range), whereas females had greater leftward lateralization of long-range connectivity in the inferior frontal cortex. The greater lateralization of the male's brain (rightward and predominantly short-range) may underlie their greater vulnerability to disorders with disrupted brain asymmetries (schizophrenia, autism). PMID:21878483
A computational study of whole-brain connectivity in resting state and task fMRI
Goparaju, Balaji; Rana, Kunjan D.; Calabro, Finnegan J.; Vaina, Lucia Maria
2014-01-01
Background We compared the functional brain connectivity produced during resting-state in which subjects were not actively engaged in a task with that produced while they actively performed a visual motion task (task-state). Material/Methods In this paper we employed graph-theoretical measures and network statistics in novel ways to compare, in the same group of human subjects, functional brain connectivity during resting-state fMRI with brain connectivity during performance of a high level visual task. We performed a whole-brain connectivity analysis to compare network statistics in resting and task states among anatomically defined Brodmann areas to investigate how brain networks spanning the cortex changed when subjects were engaged in task performance. Results In the resting state, we found strong connectivity among the posterior cingulate cortex (PCC), precuneus, medial prefrontal cortex (MPFC), lateral parietal cortex, and hippocampal formation, consistent with previous reports of the default mode network (DMN). The connections among these areas were strengthened while subjects actively performed an event-related visual motion task, indicating a continued and strong engagement of the DMN during task processing. Regional measures such as degree (number of connections) and betweenness centrality (number of shortest paths), showed that task performance induces stronger inter-regional connections, leading to a denser processing network, but that this does not imply a more efficient system as shown by the integration measures such as path length and global efficiency, and from global measures such as small-worldness. Conclusions In spite of the maintenance of connectivity and the “hub-like” behavior of areas, our results suggest that the network paths may be rerouted when performing the task condition. PMID:24947491
Jin, Seung-Hyun; Chung, Chun Kee
2017-01-01
The main aim of the present study was to evaluate whether resting-state functional connectivity of magnetoencephalography (MEG) signals can differentiate patients with mesial temporal lobe epilepsy (MTLE) from healthy controls (HC) and can differentiate between right and left MTLE as a diagnostic biomarker. To this end, a support vector machine (SVM) method among various machine learning algorithms was employed. We compared resting-state functional networks between 46 MTLE (right MTLE=23; left MTLE=23) patients with histologically proven HS who were free of seizure after surgery, and 46 HC. The optimal SVM group classifier distinguished MTLE patients with a mean accuracy of 95.1% (sensitivity=95.8%; specificity=94.3%). Increased connectivity including the right posterior cingulate gyrus and decreased connectivity including at least one sensory-related resting-state network were key features reflecting the differences between MTLE patients and HC. The optimal SVM model distinguished between right and left MTLE patients with a mean accuracy of 76.2% (sensitivity=76.0%; specificity=76.5%). We showed the potential of electrophysiological resting-state functional connectivity, which reflects brain network reorganization in MTLE patients, as a possible diagnostic biomarker to differentiate MTLE patients from HC and differentiate between right and left MTLE patients. Copyright © 2016 Elsevier B.V. All rights reserved.
Broca’s area network in language function: a pooling-data connectivity study
Bernal, Byron; Ardila, Alfredo; Rosselli, Monica
2015-01-01
Background and Objective: Modern neuroimaging developments have demonstrated that cognitive functions correlate with brain networks rather than specific areas. The purpose of this paper was to analyze the connectivity of Broca’s area based on language tasks. Methods: A connectivity modeling study was performed by pooling data of Broca’s activation in language tasks. Fifty-seven papers that included 883 subjects in 84 experiments were analyzed. Analysis of Likelihood Estimates of pooled data was utilized to generate the map; thresholds at p < 0.01 were corrected for multiple comparisons and false discovery rate. Resulting images were co-registered into MNI standard space. Results: A network consisting of 16 clusters of activation was obtained. Main clusters were located in the frontal operculum, left posterior temporal region, supplementary motor area, and the parietal lobe. Less common clusters were seen in the sub-cortical structures including the left thalamus, left putamen, secondary visual areas, and the right cerebellum. Conclusion: Broca’s area-44-related networks involved in language processing were demonstrated utilizing a pooling-data connectivity study. Significance, interpretation, and limitations of the results are discussed. PMID:26074842
Quantitative evaluation of simulated functional brain networks in graph theoretical analysis.
Lee, Won Hee; Bullmore, Ed; Frangou, Sophia
2017-02-01
There is increasing interest in the potential of whole-brain computational models to provide mechanistic insights into resting-state brain networks. It is therefore important to determine the degree to which computational models reproduce the topological features of empirical functional brain networks. We used empirical connectivity data derived from diffusion spectrum and resting-state functional magnetic resonance imaging data from healthy individuals. Empirical and simulated functional networks, constrained by structural connectivity, were defined based on 66 brain anatomical regions (nodes). Simulated functional data were generated using the Kuramoto model in which each anatomical region acts as a phase oscillator. Network topology was studied using graph theory in the empirical and simulated data. The difference (relative error) between graph theory measures derived from empirical and simulated data was then estimated. We found that simulated data can be used with confidence to model graph measures of global network organization at different dynamic states and highlight the sensitive dependence of the solutions obtained in simulated data on the specified connection densities. This study provides a method for the quantitative evaluation and external validation of graph theory metrics derived from simulated data that can be used to inform future study designs. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
Electro-acupuncture at different acupoints modulating the relative specific brain functional network
NASA Astrophysics Data System (ADS)
Fang, Jiliang; Wang, Xiaoling; Wang, Yin; Liu, Hesheng; Hong, Yang; Liu, Jun; Zhou, Kehua; Wang, Lei; Xue, Chao; Song, Ming; Liu, Baoyan; Zhu, Bing
2010-11-01
Objective: The specific brain effects of acupoint are important scientific concern in acupuncture. However, previous acupuncture fMRI studies focused on acupoints in muscle layer on the limb. Therefore, researches on acupoints within connective tissue at trunk are warranted. Material and Methods: Brain effects of acupuncture on abdomen at acupoints Guanyuan (CV4) and Zhongwan (CV12) were tested using fMRI on 21 healthy volunteers. The data acquisition was performed at resting state, during needle retention, electroacupuncture (EA) and post-EA resting state. Needling sensations were rated after every electroacupuncture (EA) procedure. The needling sensations and the brain functional activity and connectivity were compared between CV4 and CV12 using SPSS, SPM2 and the local and remote connectivity maps. Results and conclusion: EA at CV4 and CV12 induced apparent deactivation effects in the limbic-paralimbic-neocortical network. The default mode of the brain was modified by needle retention and EA, respectively. The functional brain network was significantly changed post EA. However, the minor differences existed between these two acupoints. The results demonstrated similarity between functional brain network mode of acupuncture modulation and functional circuits of emotional and cognitive regulation. Acupuncture may produce analgesia, anti-anxiety and anti-depression via the limbic-paralimbic-neocortical network (LPNN).
Functional Connectivity in Brain Networks Underlying Cognitive Control in Chronic Cannabis Users
Harding, Ian H; Solowij, Nadia; Harrison, Ben J; Takagi, Michael; Lorenzetti, Valentina; Lubman, Dan I; Seal, Marc L; Pantelis, Christos; Yücel, Murat
2012-01-01
The long-term effect of regular cannabis use on brain function underlying cognitive control remains equivocal. Cognitive control abilities are thought to have a major role in everyday functioning, and their dysfunction has been implicated in the maintenance of maladaptive drug-taking patterns. In this study, the Multi-Source Interference Task was employed alongside functional magnetic resonance imaging and psychophysiological interaction methods to investigate functional interactions between brain regions underlying cognitive control. Current cannabis users with a history of greater than 10 years of daily or near-daily cannabis smoking (n=21) were compared with age, gender, and IQ-matched non-using controls (n=21). No differences in behavioral performance or magnitude of task-related brain activations were evident between the groups. However, greater connectivity between the prefrontal cortex and the occipitoparietal cortex was evident in cannabis users, as compared with controls, as cognitive control demands increased. The magnitude of this connectivity was positively associated with age of onset and lifetime exposure to cannabis. These findings suggest that brain regions responsible for coordinating behavioral control have an increased influence on the direction and switching of attention in cannabis users, and that these changes may have a compensatory role in mitigating cannabis-related impairments in cognitive control or perceptual processes. PMID:22534625
Chen, Hui Juan; Wang, Yun Fei; Qi, Rongfeng; Schoepf, U Joseph; Varga-Szemes, Akos; Ball, B Devon; Zhang, Zhe; Kong, Xiang; Wen, Jiqiu; Li, Xue; Lu, Guang Ming; Zhang, Long Jiang
2017-04-01
The purpose of this study was to investigate patterns in the amygdala-based emotional processing circuit of hemodialysis patients using resting-state functional MR imaging (rs-fMRI). Fifty hemodialysis patients (25 with depressed mood and 25 without depressed mood) and 26 healthy controls were included. All subjects underwent neuropsychological tests and rs-fMRI, and patients also underwent laboratory tests. Functional connectivity of the bilateral amygdala was compared among the three groups. The relationship between functional connectivity and clinical markers was investigated. Depressed patients showed increased positive functional connectivity of the left amygdala with the left superior temporal gyrus and right parahippocampal gyrus (PHG) but decreased amygdala functional connectivity with the left precuneus, angular gyrus, posterior cingulate cortex (PCC), and left inferior parietal lobule compared with non-depressed patients (P < 0.05, AlphaSim corrected). Depressed patients had increased positive functional connectivity of the right amygdala with bilateral supplementary motor areas and PHG but decreased amygdala functional connectivity with the right superior frontal gyrus, superior parietal lobule, bilateral precuneus, and PCC (P < 0.05, AlphaSim corrected). After including anxiety as a covariate, we discovered additional decreased functional connectivity with anterior cingulate cortex (ACC) for bilateral amygdala (P < 0.05, AlphaSim corrected). For the depressed, neuropsychological test scores were correlated with functional connectivity of multiple regions (P < 0.05, AlphaSim corrected). In conclusion, functional connectivity in the amygdala-prefrontal-PCC-limbic circuits was impaired in depressive hemodialysis patients, with a gradual decrease in ACC between controls, non-depressed, and depressed patients for the right amygdala. This indicates that ACC plays a role in amygdala-based emotional regulatory circuits in these patients.
Atalayer, Deniz; Pantazatos, Spiro P; Gibson, Charlisa D; McOuatt, Haley; Puma, Lauren; Astbury, Nerys M; Geliebter, Allan
2014-10-15
Sexually-dimorphic behavioral and biological aspects of human eating have been described. Using psychophysiological interaction (PPI) analysis, we investigated sex-based differences in functional connectivity with a key emotion-processing region (amygdala, AMG) and a key reward-processing area (ventral striatum, VS) in response to high vs. low energy-dense (ED) food images using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in obese persons in fasted and fed states. When fed, in response to high vs. low-ED food cues, obese men (vs. women) had greater functional connectivity with AMG in right subgenual anterior cingulate, whereas obese women had greater functional connectivity with AMG in left angular gyrus and right primary motor areas. In addition, when fed, AMG functional connectivity with pre/post-central gyrus was more associated with BMI in women (vs. men). When fasted, obese men (vs. women) had greater functional connectivity with AMG in bilateral supplementary frontal and primary motor areas, left precuneus, and right cuneus, whereas obese women had greater functional connectivity with AMG in left inferior frontal gyrus, right thalamus, and dorsomedial prefrontal cortex. When fed, greater functional connectivity with VS was observed in men in bilateral supplementary and primary motor areas, left postcentral gyrus, and left precuneus. These sex-based differences in functional connectivity in response to visual food cues may help partly explain differential eating behavior, pathology prevalence, and outcomes in men and women. Published by Elsevier Inc.
Degnan, Andrew J.; Wisnowski, Jessica L.; Choi, SoYoung; Ceschin, Rafael; Bhushan, Chitresh; Leahy, Richard M.; Corby, Patricia; Schmithorst, Vincent J.; Panigrahy, Ashok
2015-01-01
Objective Late preterm birth confers increased risk of developmental delay, academic difficulties and social deficits. The late third trimester may represent a critical period of development of neural networks including the default mode network (DMN), which is essential to normal cognition. Our objective is to identify functional and structural connectivity differences in the posteromedial cortex related to late preterm birth. Methods Thirty-eight preadolescents (ages 9–13; 19 born in the late preterm period (≥32 weeks gestational age) and 19 at term) without access to advanced neonatal care were recruited from a low socioeconomic status community in Brazil. Participants underwent neurocognitive testing, 3-dimensional T1-weighted imaging, diffusion-weighted imaging and resting state functional MRI (RS-fMRI). Seed-based probabilistic diffusion tractography and RS-fMRI analyses were performed using unilateral seeds within the posterior DMN (posterior cingulate cortex, precuneus) and lateral parietal DMN (superior marginal and angular gyri). Results Late preterm children demonstrated increased functional connectivity within the posterior default mode networks and increased anti-correlation with the central-executive network when seeded from the posteromedial cortex (PMC). Key differences were demonstrated between PMC components with increased anti-correlation with the salience network seen only with posterior cingulate cortex seeding but not with precuneus seeding. Probabilistic tractography showed increased streamlines within the right inferior longitudinal fasciculus and inferior fronto-occipital fasciculus within late preterm children while decreased intrahemispheric streamlines were also observed. No significant differences in neurocognitive testing were demonstrated between groups. Conclusion Late preterm preadolescence is associated with altered functional connectivity from the PMC and lateral parietal cortex to known distributed functional cortical networks despite no significant executive neurocognitive differences. Selective increased structural connectivity was observed in the setting of decreased posterior interhemispheric connections. Future work is needed to determine if these findings represent a compensatory adaptation employing alternate neural circuitry or could reflect subtle pathology resulting in emotional processing deficits not seen with neurocognitive testing. PMID:26098888
Kullmann, Stephanie; Heni, Martin; Veit, Ralf; Scheffler, Klaus; Machann, Jürgen; Häring, Hans-Ulrich; Fritsche, Andreas; Preissl, Hubert
2017-05-09
Brain insulin sensitivity is an important link between metabolism and cognitive dysfunction. Intranasal insulin is a promising tool to investigate central insulin action in humans. We evaluated the acute effects of 160 U intranasal insulin on resting-state brain functional connectivity in healthy young adults. Twenty-five lean and twenty-two overweight and obese participants underwent functional magnetic resonance imaging, on two separate days, before and after intranasal insulin or placebo application. Insulin compared to placebo administration resulted in increased functional connectivity between the prefrontal regions of the default-mode network and the hippocampus as well as the hypothalamus. The change in hippocampal functional connectivity significantly correlated with visceral adipose tissue and the change in subjective feeling of hunger after intranasal insulin. Mediation analysis revealed that the intranasal insulin induced hippocampal functional connectivity increase served as a mediator, suppressing the relationship between visceral adipose tissue and hunger. The insulin-induced hypothalamic functional connectivity change showed a significant interaction with peripheral insulin sensitivity. Only participants with high peripheral insulin sensitivity showed a boost in hypothalamic functional connectivity. Hence, brain insulin action may regulate eating behavior and facilitate weight loss by modifying brain functional connectivity within and between cognitive and homeostatic brain regions.
Tewarie, Prejaas; Steenwijk, Martijn D; Brookes, Matthew J; Uitdehaag, Bernard M J; Geurts, Jeroen J G; Stam, Cornelis J; Schoonheim, Menno M
2018-06-01
To understand the heterogeneity of functional connectivity results reported in the literature, we analyzed the separate effects of grey and white matter damage on functional connectivity and networks in multiple sclerosis. For this, we employed a biophysical thalamo-cortical model consisting of interconnected cortical and thalamic neuronal populations, informed and amended by empirical diffusion MRI tractography data, to simulate functional data that mimic neurophysiological signals. Grey matter degeneration was simulated by decreasing within population connections and white matter degeneration by lowering between population connections, based on lesion predilection sites in multiple sclerosis. For all simulations, functional connectivity and functional network organization are quantified by phase synchronization and network integration, respectively. Modeling results showed that both cortical and thalamic grey matter damage induced a global increase in functional connectivity, whereas white matter damage induced an initially increased connectivity followed by a global decrease. Both white and especially grey matter damage, however, induced a decrease in network integration. These empirically informed simulations show that specific topology and timing of structural damage are nontrivial aspects in explaining functional abnormalities in MS. Insufficient attention to these aspects likely explains contradictory findings in multiple sclerosis functional imaging studies so far. © 2018 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.
Damaraju, E; Allen, E A; Belger, A; Ford, J M; McEwen, S; Mathalon, D H; Mueller, B A; Pearlson, G D; Potkin, S G; Preda, A; Turner, J A; Vaidya, J G; van Erp, T G; Calhoun, V D
2014-01-01
Schizophrenia is a psychotic disorder characterized by functional dysconnectivity or abnormal integration between distant brain regions. Recent functional imaging studies have implicated large-scale thalamo-cortical connectivity as being disrupted in patients. However, observed connectivity differences in schizophrenia have been inconsistent between studies, with reports of hyperconnectivity and hypoconnectivity between the same brain regions. Using resting state eyes-closed functional imaging and independent component analysis on a multi-site data that included 151 schizophrenia patients and 163 age- and gender matched healthy controls, we decomposed the functional brain data into 100 components and identified 47 as functionally relevant intrinsic connectivity networks. We subsequently evaluated group differences in functional network connectivity, both in a static sense, computed as the pairwise Pearson correlations between the full network time courses (5.4 minutes in length), and a dynamic sense, computed using sliding windows (44 s in length) and k-means clustering to characterize five discrete functional connectivity states. Static connectivity analysis revealed that compared to healthy controls, patients show significantly stronger connectivity, i.e., hyperconnectivity, between the thalamus and sensory networks (auditory, motor and visual), as well as reduced connectivity (hypoconnectivity) between sensory networks from all modalities. Dynamic analysis suggests that (1), on average, schizophrenia patients spend much less time than healthy controls in states typified by strong, large-scale connectivity, and (2), that abnormal connectivity patterns are more pronounced during these connectivity states. In particular, states exhibiting cortical-subcortical antagonism (anti-correlations) and strong positive connectivity between sensory networks are those that show the group differences of thalamic hyperconnectivity and sensory hypoconnectivity. Group differences are weak or absent during other connectivity states. Dynamic analysis also revealed hypoconnectivity between the putamen and sensory networks during the same states of thalamic hyperconnectivity; notably, this finding cannot be observed in the static connectivity analysis. Finally, in post-hoc analyses we observed that the relationships between sub-cortical low frequency power and connectivity with sensory networks is altered in patients, suggesting different functional interactions between sub-cortical nuclei and sensorimotor cortex during specific connectivity states. While important differences between patients with schizophrenia and healthy controls have been identified, one should interpret the results with caution given the history of medication in patients. Taken together, our results support and expand current knowledge regarding dysconnectivity in schizophrenia, and strongly advocate the use of dynamic analyses to better account for and understand functional connectivity differences.
Damaraju, E.; Allen, E.A.; Belger, A.; Ford, J.M.; McEwen, S.; Mathalon, D.H.; Mueller, B.A.; Pearlson, G.D.; Potkin, S.G.; Preda, A.; Turner, J.A.; Vaidya, J.G.; van Erp, T.G.; Calhoun, V.D.
2014-01-01
Schizophrenia is a psychotic disorder characterized by functional dysconnectivity or abnormal integration between distant brain regions. Recent functional imaging studies have implicated large-scale thalamo-cortical connectivity as being disrupted in patients. However, observed connectivity differences in schizophrenia have been inconsistent between studies, with reports of hyperconnectivity and hypoconnectivity between the same brain regions. Using resting state eyes-closed functional imaging and independent component analysis on a multi-site data that included 151 schizophrenia patients and 163 age- and gender matched healthy controls, we decomposed the functional brain data into 100 components and identified 47 as functionally relevant intrinsic connectivity networks. We subsequently evaluated group differences in functional network connectivity, both in a static sense, computed as the pairwise Pearson correlations between the full network time courses (5.4 minutes in length), and a dynamic sense, computed using sliding windows (44 s in length) and k-means clustering to characterize five discrete functional connectivity states. Static connectivity analysis revealed that compared to healthy controls, patients show significantly stronger connectivity, i.e., hyperconnectivity, between the thalamus and sensory networks (auditory, motor and visual), as well as reduced connectivity (hypoconnectivity) between sensory networks from all modalities. Dynamic analysis suggests that (1), on average, schizophrenia patients spend much less time than healthy controls in states typified by strong, large-scale connectivity, and (2), that abnormal connectivity patterns are more pronounced during these connectivity states. In particular, states exhibiting cortical–subcortical antagonism (anti-correlations) and strong positive connectivity between sensory networks are those that show the group differences of thalamic hyperconnectivity and sensory hypoconnectivity. Group differences are weak or absent during other connectivity states. Dynamic analysis also revealed hypoconnectivity between the putamen and sensory networks during the same states of thalamic hyperconnectivity; notably, this finding cannot be observed in the static connectivity analysis. Finally, in post-hoc analyses we observed that the relationships between sub-cortical low frequency power and connectivity with sensory networks is altered in patients, suggesting different functional interactions between sub-cortical nuclei and sensorimotor cortex during specific connectivity states. While important differences between patients with schizophrenia and healthy controls have been identified, one should interpret the results with caution given the history of medication in patients. Taken together, our results support and expand current knowledge regarding dysconnectivity in schizophrenia, and strongly advocate the use of dynamic analyses to better account for and understand functional connectivity differences. PMID:25161896
Roth, Jennifer K.; Johnson, Marcia K.; Tokoglu, Fuyuze; Murphy, Isabella; Constable, R. Todd
2014-01-01
Supplementary motor area (SMA), the inferior frontal junction (IFJ), superior frontal junction (SFJ) and parietal cortex are active in many cognitive tasks. In a previous study, we found that subregions of each of these major areas were differentially active in component processes of executive function during working memory tasks. In the present study, each of these subregions was used as a seed in a whole brain functional connectivity analysis of working memory and resting state data. These regions show functional connectivity to different networks, thus supporting the parcellation of these major regions into functional subregions. Many regions showing significant connectivity during the working memory residual data (with task events regressed from the data) were also significantly connected during rest suggesting that these network connections to subregions within major regions of cortex are intrinsic. For some of these connections, task demands modulate activity in these intrinsic networks. Approximately half of the connections significant during task were significant during rest, indicating that some of the connections are intrinsic while others are recruited only in the service of the task. Furthermore, the network connections to traditional ‘task positive’ and ‘task negative’ (a.k.a ‘default mode’) regions shift from positive connectivity to negative connectivity depending on task demands. These findings demonstrate that such task-identified subregions are part of distinct networks, and that these networks have different patterns of connectivity for task as they do during rest, engaging connections both to task positive and task negative regions. These results have implications for understanding the parcellation of commonly active regions into more specific functional networks. PMID:24637793
Power, Jonathan D; Barnes, Kelly A; Snyder, Abraham Z; Schlaggar, Bradley L; Petersen, Steven E
2011-01-01
Here, we demonstrate that subject motion produces substantial changes in the timecourses of resting state functional connectivity MRI (rs-fcMRI) data despite compensatory spatial registration and regression of motion estimates from the data. These changes cause systematic but spurious correlation structures throughout the brain. Specifically, many long-distance correlations are decreased by subject motion, whereas many short-distance correlations are increased. These changes in rs-fcMRI correlations do not arise from, nor are they adequately countered by, some common functional connectivity processing steps. Two indices of data quality are proposed, and a simple method to reduce motion-related effects in rs-fcMRI analyses is demonstrated that should be flexibly implementable across a variety of software platforms. We demonstrate how application of this technique impacts our own data, modifying previous conclusions about brain development. These results suggest the need for greater care in dealing with subject motion, and the need to critically revisit previous rs-fcMRI work that may not have adequately controlled for effects of transient subject movements. PMID:22019881
Cerebral cartography and connectomics
Sporns, Olaf
2015-01-01
Cerebral cartography and connectomics pursue similar goals in attempting to create maps that can inform our understanding of the structural and functional organization of the cortex. Connectome maps explicitly aim at representing the brain as a complex network, a collection of nodes and their interconnecting edges. This article reflects on some of the challenges that currently arise in the intersection of cerebral cartography and connectomics. Principal challenges concern the temporal dynamics of functional brain connectivity, the definition of areal parcellations and their hierarchical organization into large-scale networks, the extension of whole-brain connectivity to cellular-scale networks, and the mapping of structure/function relations in empirical recordings and computational models. Successfully addressing these challenges will require extensions of methods and tools from network science to the mapping and analysis of human brain connectivity data. The emerging view that the brain is more than a collection of areas, but is fundamentally operating as a complex networked system, will continue to drive the creation of ever more detailed and multi-modal network maps as tools for on-going exploration and discovery in human connectomics. PMID:25823870
Disrupted functional brain connectivity in partial epilepsy: a resting-state fMRI study.
Luo, Cheng; Qiu, Chuan; Guo, Zhiwei; Fang, Jiajia; Li, Qifu; Lei, Xu; Xia, Yang; Lai, Yongxiu; Gong, Qiyong; Zhou, Dong; Yao, Dezhong
2011-01-01
Examining the spontaneous activity to understand the neural mechanism of brain disorder is a focus in recent resting-state fMRI. In the current study, to investigate the alteration of brain functional connectivity in partial epilepsy in a systematical way, two levels of analyses (functional connectivity analysis within resting state networks (RSNs) and functional network connectivity (FNC) analysis) were carried out on resting-state fMRI data acquired from the 30 participants including 14 healthy controls(HC) and 16 partial epilepsy patients. According to the etiology, all patients are subdivided into temporal lobe epilepsy group (TLE, included 7 patients) and mixed partial epilepsy group (MPE, 9 patients). Using group independent component analysis, eight RSNs were identified, and selected to evaluate functional connectivity and FNC between groups. Compared with the controls, decreased functional connectivity within all RSNs was found in both TLE and MPE. However, dissociating patterns were observed within the 8 RSNs between two patient groups, i.e, compared with TLE, we found decreased functional connectivity in 5 RSNs increased functional connectivity in 1 RSN, and no difference in the other 2 RSNs in MPE. Furthermore, the hierarchical disconnections of FNC was found in two patient groups, in which the intra-system connections were preserved for all three subsystems while the lost connections were confined to intersystem connections in patients with partial epilepsy. These findings may suggest that decreased resting state functional connectivity and disconnection of FNC are two remarkable characteristics of partial epilepsy. The selective impairment of FNC implicated that it is unsuitable to understand the partial epilepsy only from global or local perspective. We presumed that studying epilepsy in the multi-perspective based on RSNs may be a valuable means to assess the functional changes corresponding to specific RSN and may contribute to the understanding of the neuro-pathophysiological mechanism of epilepsy.
Advanced lesion symptom mapping analyses and implementation as BCBtoolkit
Foulon, Chris; Cerliani, Leonardo; Kinkingnéhun, Serge; Levy, Richard; Rosso, Charlotte; Urbanski, Marika
2018-01-01
Abstract Background Patients with brain lesions provide a unique opportunity to understand the functioning of the human mind. However, even when focal, brain lesions have local and remote effects that impact functionally and structurally connected circuits. Similarly, function emerges from the interaction between brain areas rather than their sole activity. For instance, category fluency requires the associations between executive, semantic, and language production functions. Findings Here, we provide, for the first time, a set of complementary solutions for measuring the impact of a given lesion on the neuronal circuits. Our methods, which were applied to 37 patients with a focal frontal brain lesions, revealed a large set of directly and indirectly disconnected brain regions that had significantly impacted category fluency performance. The directly disconnected regions corresponded to areas that are classically considered as functionally engaged in verbal fluency and categorization tasks. These regions were also organized into larger directly and indirectly disconnected functional networks, including the left ventral fronto-parietal network, whose cortical thickness correlated with performance on category fluency. Conclusions The combination of structural and functional connectivity together with cortical thickness estimates reveal the remote effects of brain lesions, provide for the identification of the affected networks, and strengthen our understanding of their relationship with cognitive and behavioral measures. The methods presented are available and freely accessible in the BCBtoolkit as supplementary software [1]. PMID:29432527
Code of Federal Regulations, 2013 CFR
2013-04-01
... intangible property to add substantial value to the tangible goods. (2) Determination of arm's length price... terms or economic conditions could materially affect the amount charged in an uncontrolled transaction... transactions. The resale price method measures the value of functions performed, and is ordinarily used in...
Tzourio-Mazoyer, Nathalie; Perrone-Bertolotti, Marcela; Jobard, Gael; Mazoyer, Bernard; Baciu, Monica
2017-01-01
This review synthesizes anatomo-functional variability of language hemispheric representation and specialization (hemispheric specialization for language, HSL) as well as its modulation by several variables (demographic, anatomical, developmental, genetic, clinical, and psycholinguistic) in physiological and pathological conditions. The left hemisphere (LH) dominance for language, observed in approximately 90% of healthy individuals and in 70% of patients, is grounded by intra-hemispheric connections mediated by associative bundles such as the arcuate fasciculus and inter-hemispheric transcallosal connections mediated by the corpus callosum that connects homotopic regions of the left and right hemispheres (RH). In typical brains, inter-hemispheric inhibition, exerted from the LH to the RH, permits the LH to maintain language dominance. In pathological conditions, inter- and intra-hemispheric inhibition is decreased, inducing modifications on the degree of HSL and of language networks. HSL evaluation is classically performed in clinical practice with the Wada test and electro-cortical stimulation, gold standard methods. The advent of functional neuroimaging has allowed a more detailed assessment of the language networks and their lateralization, consistent with the results provided by the gold standard methods. In the first part, we describe anatomo-functional support for HSL in healthy conditions, its developmental course, its relationship with cognitive skills, and the various modulatory factors acting on HSL. The second section is devoted to the assessment of HSL in patients with focal and drug-resistant epilepsy (FDRE). FDRE is considered a neurological model associated with patterns of language plasticity, both before and after surgery: FDRE patients show significant modification of language networks induced by changes mediated by transcallosal connections (explaining inter-hemispheric patterns of language reorganization) or collateral connections (explaining intra-hemispheric patterns of language reorganization). Finally, we propose several predictive and explicative models of language organization and reorganization. Copyright © 2016 Elsevier Ltd. All rights reserved.
Netscape Communicator 4.5. Volume I: The Basic Functions of the Navigator Component.
ERIC Educational Resources Information Center
Gallo, Gail; Wichowski, Chester P.
This first of two guides on Netscape Communicator 4.5 contains six lessons on the basic functions of the Navigator component. Lesson 1 covers terminology and methods to connect to the World Wide Web, hardware needed, and a Netscape Communicator overview. Lesson 2 introduces the Navigator window, toolbars, and menus, and how to change the default…
2017-07-01
Reports an error in "Default mode functional connectivity is associated with social functioning in schizophrenia" by Jaclyn M. Fox, Samantha V. Abram, James L. Reilly, Shaun Eack, Morris B. Goldman, John G. Csernansky, Lei Wang and Matthew J. Smith ( Journal of Abnormal Psychology , 2017[May], Vol 126[4], 392-405). In the article, the email address of corresponding author Matthew J. Smith was set as matthewsmith@northwestern.edu. It should have been mattjsmi@umich.edu. The online version of this article has been corrected. (The following abstract of the original article appeared in record 2017-14073-001.) Individuals with schizophrenia display notable deficits in social functioning. Research indicates that neural connectivity within the default mode network (DMN) is related to social cognition and social functioning in healthy and clinical populations. However, the association between DMN connectivity, social cognition, and social functioning has not been studied in schizophrenia. For the present study, the authors used resting-state neuroimaging data to evaluate connectivity between the main DMN hubs (i.e., the medial prefrontal cortex [mPFC] and the posterior cingulate cortex-anterior precuneus [PPC]) in individuals with schizophrenia (n = 28) and controls (n = 32). The authors also examined whether DMN connectivity was associated with social functioning via social attainment (measured by the Specific Levels of Functioning Scale) and social competence (measured by the Social Skills Performance Assessment), and if social cognition mediates the association between DMN connectivity and these measures of social functioning. Results revealed that DMN connectivity did not differ between individuals with schizophrenia and controls. However, connectivity between the mPFC and PCC hubs was significantly associated with social competence and social attainment in individuals with schizophrenia but not in controls as reflected by a significant group-by-connectivity interaction. Social cognition did not mediate the association between DMN connectivity and social functioning in individuals with schizophrenia. The findings suggest that fronto-parietal DMN connectivity in particular may be differentially associated with social functioning in schizophrenia and controls. As a result, DMN connectivity may be used as a neuroimaging marker to monitor treatment response or as a potential target for interventions that aim to enhance social functioning in schizophrenia. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
DOE Office of Scientific and Technical Information (OSTI.GOV)
Shumilov, V. N., E-mail: vnshumilov@rambler.ru; Syryamkin, V. I., E-mail: maximus70sir@gmail.com; Syryamkin, M. V., E-mail: maximus70sir@gmail.com
The paper puts forward principles of action of devices operating similarly to the nervous system and the brain of biological systems. We propose an alternative method of studying diseases of the nervous system, which may significantly influence prevention, medical treatment, or at least retardation of development of these diseases. This alternative is to use computational and electronic models of the nervous system. Within this approach, we represent the brain in the form of a huge electrical circuit composed of active units, namely, neuron-like units and connections between them. As a result, we created computational and electronic models of elementary nervousmore » systems, which are based on the principles of functioning of biological nervous systems that we have put forward. Our models demonstrate reactions to external stimuli and their change similarly to the behavior of simplest biological organisms. The models possess the ability of self-training and retraining in real time without human intervention and switching operation/training modes. In our models, training and memorization take place constantly under the influence of stimuli on the organism. Training is without any interruption and switching operation modes. Training and formation of new reflexes occur by means of formation of new connections between excited neurons, between which formation of connections is physically possible. Connections are formed without external influence. They are formed under the influence of local causes. Connections are formed between outputs and inputs of two neurons, when the difference between output and input potentials of excited neurons exceeds a value sufficient to form a new connection. On these grounds, we suggest that the proposed principles truly reflect mechanisms of functioning of biological nervous systems and the brain. In order to confirm the correspondence of the proposed principles to biological nature, we carry out experiments for the study of processes of formation of connections between neurons in simplest biological objects. Based on the correspondence of function of the created models to function of biological nervous systems we suggest the use of computational and electronic models of the brain for the study of its function under normal and pathological conditions, because operating principles of the models are built on principles imitating the function of biological nervous systems and the brain.« less
NASA Astrophysics Data System (ADS)
Shumilov, V. N.; Syryamkin, V. I.; Syryamkin, M. V.
2015-11-01
The paper puts forward principles of action of devices operating similarly to the nervous system and the brain of biological systems. We propose an alternative method of studying diseases of the nervous system, which may significantly influence prevention, medical treatment, or at least retardation of development of these diseases. This alternative is to use computational and electronic models of the nervous system. Within this approach, we represent the brain in the form of a huge electrical circuit composed of active units, namely, neuron-like units and connections between them. As a result, we created computational and electronic models of elementary nervous systems, which are based on the principles of functioning of biological nervous systems that we have put forward. Our models demonstrate reactions to external stimuli and their change similarly to the behavior of simplest biological organisms. The models possess the ability of self-training and retraining in real time without human intervention and switching operation/training modes. In our models, training and memorization take place constantly under the influence of stimuli on the organism. Training is without any interruption and switching operation modes. Training and formation of new reflexes occur by means of formation of new connections between excited neurons, between which formation of connections is physically possible. Connections are formed without external influence. They are formed under the influence of local causes. Connections are formed between outputs and inputs of two neurons, when the difference between output and input potentials of excited neurons exceeds a value sufficient to form a new connection. On these grounds, we suggest that the proposed principles truly reflect mechanisms of functioning of biological nervous systems and the brain. In order to confirm the correspondence of the proposed principles to biological nature, we carry out experiments for the study of processes of formation of connections between neurons in simplest biological objects. Based on the correspondence of function of the created models to function of biological nervous systems we suggest the use of computational and electronic models of the brain for the study of its function under normal and pathological conditions, because operating principles of the models are built on principles imitating the function of biological nervous systems and the brain.
Simple functionalization method for single conical pores with a polydopamine layer
NASA Astrophysics Data System (ADS)
Horiguchi, Yukichi; Goda, Tatsuro; Miyahara, Yuji
2018-04-01
Resistive pulse sensing (RPS) is an interesting analytical system in which micro- to nanosized pores are used to evaluate particles or small analytes. Recently, molecular immobilization techniques to improve the performance of RPS have been reported. The problem in functionalization for RPS is that molecular immobilization by chemical reaction is restricted by the pore material type. Herein, a simple functionalization is performed using mussel-inspired polydopamine as an intermediate layer to connect the pore material with functional molecules.
Brain Network Regional Synchrony Analysis in Deafness
Xu, Lei; Liang, Mao-Jin
2018-01-01
Deafness, the most common auditory disease, has greatly affected people for a long time. The major treatment for deafness is cochlear implantation (CI). However, till today, there is still a lack of objective and precise indicator serving as evaluation of the effectiveness of the cochlear implantation. The goal of this EEG-based study is to effectively distinguish CI children from those prelingual deafened children without cochlear implantation. The proposed method is based on the functional connectivity analysis, which focuses on the brain network regional synchrony. Specifically, we compute the functional connectivity between each channel pair first. Then, we quantify the brain network synchrony among regions of interests (ROIs), where both intraregional synchrony and interregional synchrony are computed. And finally the synchrony values are concatenated to form the feature vector for the SVM classifier. What is more, we develop a new ROI partition method of 128-channel EEG recording system. That is, both the existing ROI partition method and the proposed ROI partition method are used in the experiments. Compared with the existing EEG signal classification methods, our proposed method has achieved significant improvements as large as 87.20% and 86.30% when the existing ROI partition method and the proposed ROI partition method are used, respectively. It further demonstrates that the new ROI partition method is comparable to the existing ROI partition method. PMID:29854776