Multiple Functional Networks Research Articles

Effects of task complexity and age-differences on task-related functional connectivity of attentional networks

Studies investigating the strength and membership of regions within multiple functional networks primarily focus on either resting state or single cognitive tasks. The goals of the current study were to investigate whether task-related functional connectivity changes with task complexity, and whether this connectivity-complexity relationship is age-sensitive. We assessed seed-to-voxel functional connectivity for the default mode network (DMN) and two attentional networks [cingulo-opercular (CO), fronto-parietal (FP)] in three cognitive control tasks of increasing complexity (Single task, Dual task, and Memory Updating), across younger and older adults (N = 52; NYoung = 23; NOld = 29). The three tasks systematically varied in cognitive control demands due to differing maintenance, switching, and updating requirements. Functional connectivity for all networks, resulting from task > rest contrasts, increased with greater task complexity, irrespective of age and gray matter volume. Moreover, between-network connectivity for DMN, CO, and FP regions was greatest for working memory updating, the most complex task. Regarding age-related differences in accuracy, none were observed for Single or Dual tasks, but older adults had poorer accuracy in Memory Updating. More anterior frontal clusters of functional connectivity were observed for older, compared to younger, adults; these were limited to seeds of the two attentional networks. Importantly, increased connectivity in these additional frontal regions in older adults were non-compensatory, because they were associated with detrimental task performance, especially Memory Updating. For the Memory Updating > Rest, the younger > older contrast resulted in greater DMN seed connectivity to regions in the other two attentional networks, implicating increased reliance on between-network connectivity for the DMN seeds during complex cognitive tasks. Our results also implicate functional connectivity between attentional networks and the cerebellum during cognitive control. Reliability of multiple seeds in the seed-to-voxel connectivity is also discussed.

Shared facial emotion processing functional network findings in medication-na\xefve major depressive disorder and healthy individuals: detection by sICA

BackgroundThe fundamental mechanism underlying emotional processing in major depressive disorder (MDD) remains unclear. To better understand the neural correlates of emotional processing in MDD, we investigated the role of multiple functional networks (FNs) during emotional stimuli processing.MethodsThirty-two medication-naïve subjects with MDD and 36 healthy controls (HCs) underwent an emotional faces fMRI task that included neutral, happy and fearful expressions. Spatial independent component analysis (sICA) and general linear model (GLM) were conducted to examine the main effect of task condition and group, and two-way interactions of group and task conditions.ResultsIn sICA analysis, MDD patients and HCs together showed significant differences in task-related modulations in five FNs across task conditions. One FN mainly involving the ventral medial prefrontal cortex showed lower activation during fearful relative to happy condition. Two FNs mainly involving the bilateral inferior frontal gyrus and temporal cortex, showed opposing modulation relative to the ventral medial prefrontal cortex FN, i.e., greater activation during fearful relative to happy condition. Two remaining FNs involving the fronto-parietal and occipital cortices, showed reduced activation during both fearful and happy conditions relative to the neutral condition. However, MDD and HCs did not show significant differences in expression-related modulations in any FNs in this sample.ConclusionsSICA revealed differing functional activation patterns than typical GLM-based analyses. The sICA findings demonstrated unique FNs involved in processing happy and fearful facial expressions. Potential differences between MDD and HCs in expression-related FN modulation should be investigated further.

Dissociated resting-state functional networks between the dream recall frequency and REM sleep percentage

Rapid eye movement (REM) sleep has been frequently associated with dreaming. However, mounting evidence obtained from behavioral, pharmacological, and brain imaging studies suggests that REM sleep is not indicative of the dream report and may originate from diverse neural substrates in brain functionality. The aim of the current study was to investigate the functional systems associated with inter-individual differences in dream recall and REM sleep through assessments of the resting-state functional connectivity. We collected resting-state functional magnetic resonance imaging (fMRI) data for functional connectivity evaluations from 43 healthy adult volunteers (23 men) before and after sleep. For assessment of the dream recall frequency, a 2-week sleep diary was maintained by all volunteers. In addition, whole-night polysomnography was performed for measuring the REM sleep percentage. Voxel-wise correlation analyses of 12 functional connectivity networks of interest with the dream recall frequency and REM sleep percentage were conducted using general linear model analysis. Both the dream recall frequency and REM sleep percentage showed negative associations with multiple brain functional networks. However, the dream recall frequency was mainly related to functional connectivity within the lateral visual network and thalamus, whereas the REM sleep percentage was mainly associated with connectivity within the frontoparietal networks and cerebellum. In addition, the dream recall frequency showed stronger coupling with the lateral visual network connectivity at night, whereas the coupling between the REM sleep percentage and cerebellum was higher in the morning. This indicated a significant time of day effect. Our results provide neuroimaging evidence that the functional system associated with the dream recall frequency is different from that associated with the REM sleep percentage.

Electroencephalographic Resting-State Networks: Source Localization of Microstates.

Using electroencephalography (EEG) to elucidate the spontaneous activation of brain resting-state networks (RSNs) is nontrivial as the signal of interest is of low amplitude and it is difficult to distinguish the underlying neural sources. Using the principles of electric field topographical analysis, it is possible to estimate the meta-stable states of the brain (i.e., the resting-state topographies, so-called microstates). We estimated seven resting-state topographies explaining the EEG data set with k-means clustering (N = 164, 256 electrodes). Using a method specifically designed to localize the sources of broadband EEG scalp topographies by matching sensor and source space temporal patterns, we demonstrated that we can estimate the EEG RSNs reliably by measuring the reproducibility of our findings. After subtracting their mean from the seven EEG RSNs, we identified seven state-specific networks. The mean map includes regions known to be densely anatomically and functionally connected (superior frontal, superior parietal, insula, and anterior cingulate cortices). While the mean map can be interpreted as a "router," crosslinking multiple functional networks, the seven state-specific RSNs partly resemble and extend previous functional magnetic resonance imaging-based networks estimated as the hemodynamic correlates of four canonical EEG microstates.

Multiple functional networks modeling for autism spectrum disorder diagnosis.

Despite countless studies on autism spectrum disorder (ASD), diagnosis relies on specific behavioral criteria and neuroimaging biomarkers for the disorder are still relatively scarce and irrelevant for diagnostic workup. Many researchers have focused on functional networks of brain activities using resting-state functional magnetic resonance imaging (rsfMRI) to diagnose brain diseases, including ASD. Although some existing methods are able to reveal the abnormalities in functional networks, they are either highly dependent on prior assumptions for modeling these networks or do not focus on latent functional connectivities (FCs) by considering discriminative relations among FCs in a nonlinear way. In this article, we propose a novel framework to model multiple networks of rsfMRI with data-driven approaches. Specifically, we construct large-scale functional networks with hierarchical clustering and find discriminative connectivity patterns between ASD and normal controls (NC). We then learn features and classifiers for each cluster through discriminative restricted Boltzmann machines (DRBMs). In the testing phase, each DRBM determines whether a test sample is ASD or NC, based on which we make a final decision with a majority voting strategy. We assess the diagnostic performance of the proposed method using public datasets and describe the effectiveness of our method by comparing it to competing methods. We also rigorously analyze FCs learned by DRBMs on each cluster and discover dominant FCs that play a major role in discriminating between ASD and NC. Hum Brain Mapp 38:5804-5821, 2017. © 2017 Wiley Periodicals, Inc.

Making group inferences using sparse representation of resting-state functional mRI data with application to sleep deprivation.

Past studies on drawing group inferences for functional magnetic resonance imaging (fMRI) data usually assume that a brain region is involved in only one functional brain network. However, recent evidence has demonstrated that some brain regions might simultaneously participate in multiple functional networks. Here, we presented a novel approach for making group inferences using sparse representation of resting-state fMRI data and its application to the identification of changes in functional networks in the brains of 37 healthy young adult participants after 36 h of sleep deprivation (SD) in contrast to the rested wakefulness (RW) stage. Our analysis based on group-level sparse representation revealed that multiple functional networks involved in memory, emotion, attention, and vigilance processing were impaired by SD. Of particular interest, the thalamus was observed to contribute to multiple functional networks in which differentiated response patterns were exhibited. These results not only further elucidate the impact of SD on brain function but also demonstrate the ability of the proposed approach to provide new insights into the functional organization of the resting-state brain by permitting spatial overlap between networks and facilitating the description of the varied relationships of the overlapping regions with other regions of the brain in the context of different functional systems. Hum Brain Mapp 38:4671-4689, 2017. © 2017 Wiley Periodicals, Inc.

Enhancing Efficiency of Protein Functional Prediction Through Association Network Using Greedy Weighting Method

Background: In spite of the significant data surrounding complex gene networks including gene function, the occurrence of huge redundancy affects the efficiency. Objective: This work proposes a mining method to reduce the number of redundant nodes in a composite weighted network. Method: The idea is to eliminate the redundancies of nodes via a hybrid approach, i.e. the integration of multiple functional association networks using a Greedy Algorithm. This is achieved by mining the gene function from weighted gene co-expression networks based on neighbor similarity, as per the available datasets. Subsequently, Linear Regression and Greedy Algorithm are applied simultaneously for exclusion of the redundant nodes. Then, assigning the indexing rates for the remaining nodes in the dataset further assists the process. Results and Conclusion: In comparison with other well-known algorithms, this method is 93% more efficient, as per three selected benchmarks.

The Human Thalamus Is an Integrative Hub for Functional Brain Networks.

The thalamus is globally connected with distributed cortical regions, yet the functional significance of this extensive thalamocortical connectivity remains largely unknown. By performing graph-theoretic analyses on thalamocortical functional connectivity data collected from human participants, we found that most thalamic subdivisions display network properties that are capable of integrating multimodal information across diverse cortical functional networks. From a meta-analysis of a large dataset of functional brain-imaging experiments, we further found that the thalamus is involved in multiple cognitive functions. Finally, we found that focal thalamic lesions in humans have widespread distal effects, disrupting the modular organization of cortical functional networks. This converging evidence suggests that the human thalamus is a critical hub region that could integrate diverse information being processed throughout the cerebral cortex as well as maintain the modular structure of cortical functional networks.SIGNIFICANCE STATEMENT The thalamus is traditionally viewed as a passive relay station of information from sensory organs or subcortical structures to the cortex. However, the thalamus has extensive connections with the entire cerebral cortex, which can also serve to integrate information processing between cortical regions. In this study, we demonstrate that multiple thalamic subdivisions display network properties that are capable of integrating information across multiple functional brain networks. Moreover, the thalamus is engaged by tasks requiring multiple cognitive functions. These findings support the idea that the thalamus is involved in integrating information across cortical networks.

Neuropsychology of humor: an introduction. Part II. Humor and the brain.

Impairment of the perception or comprehension of humor is observed in patients with focal brain lesions in both hemispheres, but mainly in the right frontal lobe. Studies by functional magnetic resonance imaging in healthy subjects show that humor is associated with activation of two main neural systems in both hemispheres. The detection and resolution of incongruity, cognitive groundings of humor, are associated with activation of the medial prefrontal and temporoparietal cortex, and the humor appreciation with activation of the orbito-frontal and insular cortex, amygdala and the brain reward system. However, activation of these areas is not humor-specific and can be observed in various cognitive or emotional processes. Event-related potential studies confirm the involvement of both hemispheres in humor processing, and suggest that left prefrontal area is associated with joke comprehension and right prefrontal area with the resolution stage. Humor thus appears to be a complex and dynamic functional process involving, on one hand, two specialized but not specific neural systems linked to humor apprehension and appreciation, and, on the other hand, multiple interconnected functional brain networks including neural patterns underlying the moral framework and belief system, acquired by conditioning or imitation during the cognitive development and social interactions of the individual, and more distributed systems associated with the analysis of the current context of humor occurrence. Disturbances of the sense of humor could then result from focal brain alterations localized in one or two of the specialized areas underlying the comprehension or appreciation of humor, or from perturbations of the network interconnectivity in non-focal brain disorders such as Alzheimer's disease or schizophrenia.

Temporal Dynamics Assessment of Spatial Overlap Pattern of Functional Brain Networks Reveals Novel Functional Architecture of Cerebral Cortex.

Various studies in the brain mapping field have demonstrated that there exist multiple concurrent functional networks that are spatially overlapped and interacting with each other during specific task performance to jointly realize the total brain function. Assessing such spatial overlap patterns of functional networks (SOPFNs) based on functional magnetic resonance imaging (fMRI) has thus received increasing interest for brain function studies. However, there are still two crucial issues to be addressed. First, the SOPFNs are assessed over the entire fMRI scan assuming the temporal stationarity, while possibly time-dependent dynamics of the SOPFNs is not sufficiently explored. Second, the SOPFNs are assessed within individual subjects, while group-wise consistency of the SOPFNs is largely unknown. To address the two issues, we propose a novel computational framework of group-wise sparse representation of whole-brain fMRI temporal segments to assess the temporal dynamic spatial patterns of SOPFNs that are consistent across different subjects. Experimental results based on the recently publicly released Human Connectome Project grayordinate task fMRI data demonstrate that meaningful SOPFNs exhibiting dynamic spatial patterns across different time periods are effectively and robustly identified based on the reconstructed concurrent functional networks via the proposed framework. Specifically, those SOPFNs locate significantly more on gyral regions than on sulcal regions across different time periods. These results reveal novel functional architecture of cortical gyri and sulci. Moreover, these results help better understand functional dynamics mechanisms of cerebral cortex in the future.

Contrasting Evolutionary Patterns of Functional Connectivity in Sensorimotor and Cognitive Regions after Stroke.

The human brain is a highly connected and integrated system. Local stroke lesions can evoke reorganization in multiple functional networks. However, the temporally-evolving patterns in different functional networks after stroke remain unclear. Here, we aimed to investigate the dynamic evolutionary patterns of functional connectivity density (FCD) and strength (FCS) of the brain after subcortical stroke involving in the motor pathways. Eight male patients with left subcortical infarctions were longitudinally examined at five time points within a year. Voxel-wise FCD analysis was used to identify brain regions with significant dynamic changes. The temporally-evolving patterns in FCD and FCS in these regions were analyzed by a mixed-effects model. Associations between these measures and clinical variables were also explored in stroke patients. Voxel-wise analysis revealed dynamic FCD changes only in the sensorimotor and cognitive regions after stroke. FCD and FCS in the sensorimotor regions decreased initially, as compared to controls, remaining at lower levels for months, and finally returned to normal levels. In contrast, FCD and FCS in the cognitive regions increased initially, remaining at higher levels for months, and finally returned to normal levels. Most of these measures were correlated with patients’ motor scores. These findings suggest a network-specific dynamic functional reorganization after stroke. Besides the sensorimotor regions, the spared cognitive regions may also play an important role in stroke recovery.

Connectome-scale group-wise consistent resting-state network analysis in autism spectrum disorder.

Understanding the organizational architecture of human brain function and its alteration patterns in diseased brains such as Autism Spectrum Disorder (ASD) patients are of great interests. In-vivo functional magnetic resonance imaging (fMRI) offers a unique window to investigate the mechanism of brain function and to identify functional network components of the human brain. Previously, we have shown that multiple concurrent functional networks can be derived from fMRI signals using whole-brain sparse representation. Yet it is still an open question to derive group-wise consistent networks featured in ASD patients and controls. Here we proposed an effective volumetric network descriptor, named connectivity map, to compactly describe spatial patterns of brain network maps and implemented a fast framework in Apache Spark environment that can effectively identify group-wise consistent networks in big fMRI dataset. Our experiment results identified 144 group-wisely common intrinsic connectivity networks (ICNs) shared between ASD patients and healthy control subjects, where some ICNs are substantially different between the two groups. Moreover, further analysis on the functional connectivity and spatial overlap between these 144 common ICNs reveals connectomics signatures characterizing ASD patients and controls. In particular, the computing time of our Spark-enabled functional connectomics framework is significantly reduced from 240 hours (C ++ code, single core) to 20 hours, exhibiting a great potential to handle fMRI big data in the future.•A new effective volumetric network descriptor, named connectivity map.•A novel Spark-enabled functional connectomics framework•Identified 144 group-wisely common intrinsic connectivity networks (ICNs).•Revealed connectomics signatures characterizing and differentiating ASD patients and controls.

Functional Connectivity Network Fusion with Dynamic Thresholding for MCI Diagnosis.

The resting-state functional MRI (rs-fMRI) has been demonstrated as a valuable neuroimaging tool to identify mild cognitive impairment (MCI) patients. Previous studies showed network breakdown in MCI patients with thresholded rs-fMRI connectivity networks. Recently, machine learning techniques have assisted MCI diagnosis by integrating information from multiple networks constructed with a range of thresholds. However, due to the difficulty of searching optimal thresholds, they are often predetermined and uniformly applied to the entire network. Here, we propose an element-wise thresholding strategy to dynamically construct multiple functional networks, i.e., using possibly different thresholds for different elements in the connectivity matrix. These dynamically generated networks are then integrated with a network fusion scheme to capture their common and complementary information. Finally, the features extracted from the fused network are fed into support vector machine (SVM) for MCI diagnosis. Compared to the previous methods, our proposed framework can greatly improve MCI classification performance.

Self-organization of computation in neural systems by interaction between homeostatic and synaptic plasticity

The ability to perform complex motor control tasks is essentially enabled by the nervous system via the self-organization of large groups of neurons into coherent dynamic activity patterns. During learning, this is brought about by synaptic plasticity, resulting in the formation of multiple functional networks - commonly termed 'cell-assemblies'. A multitude of such cell assemblies provide the requisite machinery for non-linear computations needed for the mastery of a large number of motor skills. However, given the fact that there exists considerable overlap between the usage of the same neurons within such assemblies, for a wide range of motor tasks, creation and sustenance of such computationally powerful networks poses a challenging problem. How such interwoven assembly networks self-organize and how powerful assemblies can coexist therein, without catastrophically interfering with each other remains largely unknown. One the one side, it is already known that networks can be trained to perform complex nonlinear calculations [1], such that, if the network possesses a reservoir of rich, transient dynamics, desired outputs can be extracted from these reservoirs in order to enable motor control. On the other side, cell assemblies are created by Hebbian learning rules that strengthen a synapse if pre- and post-synaptic neurons are co-active within a small enough time window [2]. Therefore it appears relatively straightforward to combine these mechanisms in order to construct powerful assembly networks. However, given that the self-organization of neurons into cell assemblies by the processes of synaptic plasticity induces ordered or synchronized neuronal dynamics, which can destroy the required complexity of a reservoir network, such a combination remains a very challenging problem [3]. Furthermore, simultaneous creation of multiple cell assemblies can also lead to catastrophic interference if one cannot prevent them from growing into each other. In this study, we exploit for the first time the interaction between neuronal and synaptic processes acting on different time scales to enable, on a long time scale, the self-organized formation of assembly networks (Fig. ​(Fig.1),1), while on a shorter timescale, to conjointly perform several non-linear calculations needed for motor fine-control. Specifically, by the combination of synaptic plasticity and synaptic scaling [4], as a homeostatic mechanism, we demonstrate that such self-organization allows executing a difficult, six degrees of freedom, manipulation task with a robot where assemblies need to learn computing complex nonlinear transforms and - for execution - must cooperate with each other without interference. This mechanism, thus, permits for the first time, the guided self-organization of computationally powerful sub-structures in dynamic networks for behavior control. Furthermore, comparing our assembly network to networks with unchanging synapses (static networks) shows that it is indeed the embedding of a strongly connected assembly that creates the necessary computational power. Figure 1 Cell assembly size and computational performance are correlated. (A) Input-driven formation of cell assemblies brought about by the interaction long-term potentiation (LTP) and synaptic scaling (Syn. Sca.). (B) With more learning trials the assembly grows ...

Reconstructing Large-Scale Brain Resting-State Networks from High-Resolution EEG: Spatial and Temporal Comparisons with fMRI.

Functional magnetic resonance imaging (fMRI) studies utilizing measures of hemodynamic signal, such as the blood oxygenation level-dependent (BOLD) signal, have discovered that resting-state brain activities are organized into multiple large-scale functional networks, coined as resting-state networks (RSNs). However, an important limitation of the available fMRI studies is that hemodynamic signals only provide an indirect measure of the neuronal activity. In contrast, electroencephalography (EEG) directly measures electrophysiological activity of the brain. However, little is known about the brain-wide organization of such spontaneous neuronal population signals at the resting state. It is not entirely clear if or how the network structure built upon slowly fluctuating hemodynamic signals is represented in terms of fast, dynamic, and spontaneous neuronal activity. In this study, we investigated the electrophysiological representation of RSNs from simultaneously acquired EEG and fMRI data in the resting human brain. We developed a data-driven analysis approach that reconstructed multiple large-scale electrophysiological networks from high-resolution EEG data alone. The networks derived from EEG were then compared with RSNs independently derived from simultaneously acquired fMRI in their spatial structures as well as temporal dynamics. Results reveal spatially and temporally specific electrophysiological correlates for the fMRI-RSNs. Findings suggest that the spontaneous activity of various large-scale cortical networks is reflected in macroscopic EEG potentials.

Functional constraints in the evolution of brain circuits.

Regardless of major anatomical and neurodevelopmental differences, the vertebrate isocortex shows a remarkably well-conserved organization. In the isocortex, reciprocal connections between excitatory and inhibitory neurons are distributed across multiple layers, encompassing modular, dynamical and recurrent functional networks during information processing. These dynamical brain networks are often organized in neuronal assemblies interacting through rhythmic phase relationships. Accordingly, these oscillatory interactions are observed across multiple brain scale levels, and they are associated with several sensory, motor, and cognitive processes. Most notably, oscillatory interactions are also found in the complete spectrum of vertebrates. Yet, it is unknown why this functional organization is so well conserved in evolution. In this perspective, we propose some ideas about how functional requirements of the isocortex can account for the evolutionary stability observed in microcircuits across vertebrates. We argue that isocortex architectures represent canonical microcircuits resulting from: (i) the early selection of neuronal architectures based on the oscillatory excitatory-inhibitory balance, which lead to the implementation of compartmentalized oscillations and (ii) the subsequent emergence of inferential coding strategies (predictive coding), which are able to expand computational capacities. We also argue that these functional constraints may be the result of several advantages that oscillatory activity contributes to brain network processes, such as information transmission and code reliability. In this manner, similarities in mesoscale brain circuitry and input-output organization between different vertebrate groups may reflect evolutionary constraints imposed by these functional requirements, which may or may not be traceable to a common ancestor.

Predicting Protein Function via Semantic Integration of Multiple Networks

Determining the biological functions of proteins is one of the key challenges in the post-genomic era. The rapidly accumulated large volumes of proteomic and genomic data drives to develop computational models for automatically predicting protein function in large scale. Recent approaches focus on integrating multiple heterogeneous data sources and they often get better results than methods that use single data source alone. In this paper, we investigate how to integrate multiple biological data sources with the biological knowledge, i.e., Gene Ontology (GO), for protein function prediction. We propose a method, called SimNet, to Semantically integrate multiple functional association Networks derived from heterogenous data sources. SimNet firstly utilizes GO annotations of proteins to capture the semantic similarity between proteins and introduces a semantic kernel based on the similarity. Next, SimNet constructs a composite network, obtained as a weighted summation of individual networks, and aligns the network with the kernel to get the weights assigned to individual networks. Then, it applies a network-based classifier on the composite network to predict protein function. Experiment results on heterogenous proteomic data sources of Yeast, Human, Mouse, and Fly show that, SimNet not only achieves better (or comparable) results than other related competitive approaches, but also takes much less time. The Matlab codes of SimNet are available at https://sites.google.com/site/guoxian85/simnet.

Functional topography of the thalamocortical system in human.

Various studies have indicated that the thalamus is involved in controlling both cortico-cortical information flow and cortical communication with the rest of the brain. Detailed anatomy and functional connectivity patterns of the thalamocortical system are essential to understanding the cortical organization and pathophysiology of a wide range of thalamus-related neurological and neuropsychiatric diseases. The current study used resting-state fMRI to investigate the topography of the human thalamocortical system from a functional perspective. The thalamus-related cortical networks were identified by performing independent component analysis on voxel-based thalamic functional connectivity maps across a large group of subjects. The resulting functional brain networks were very similar to well-established resting-state network maps. Using these brain network components in a spatial regression model with each thalamic voxel's functional connectivity map, we localized the thalamic subdivisions related to each brain network. For instance, the medial dorsal nucleus was shown to be associated with the default mode, the bilateral executive, the medial visual networks; and the pulvinar nucleus was involved in both the dorsal attention and the visual networks. These results revealed that a single nucleus may have functional connections with multiple cortical regions or even multiple functional networks, and may be potentially related to the function of mediation or modulation of multiple cortical networks. This observed organization of thalamocortical system provided a reference for studying the functions of thalamic sub-regions. The importance of intrinsic connectivity-based mapping of the thalamocortical relationship is discussed, as well as the applicability of the approach for future studies.

Enhanced disease characterization through multi network functional normalization in fMRI.

Conventionally, structural topology is used for spatial normalization during the pre-processing of fMRI. The co-existence of multiple intrinsic networks which can be detected in the resting brain are well-studied. Also, these networks exhibit temporal and spatial modulation during cognitive task vs. rest which shows the existence of common spatial excitation patterns between these identified networks. Previous work (Khullar et al., 2011) has shown that structural and functional data may not have direct one-to-one correspondence and functional activation patterns in a well-defined structural region can vary across subjects even for a well-defined functional task. The results of this study and the existence of the neural activity patterns in multiple networks motivates us to investigate multiple resting-state networks as a single fusion template for functional normalization for multi groups of subjects. We extend the previous approach (Khullar et al., 2011) by co-registering multi group of subjects (healthy control and schizophrenia patients) and by utilizing multiple resting-state networks (instead of just one) as a single fusion template for functional normalization. In this paper we describe the initial steps toward using multiple resting-state networks as a single fusion template for functional normalization. A simple wavelet-based image fusion approach is presented in order to evaluate the feasibility of combining multiple functional networks. Our results showed improvements in both the significance of group statistics (healthy control and schizophrenia patients) and the spatial extent of activation when a multiple resting-state network applied as a single fusion template for functional normalization after the conventional structural normalization. Also, our results provided evidence that the improvement in significance of group statistics lead to better accuracy results for classification of healthy controls and schizophrenia patients.

Integrating multiple networks for protein function prediction.

BackgroundHigh throughput techniques produce multiple functional association networks. Integrating these networks can enhance the accuracy of protein function prediction. Many algorithms have been introduced to generate a composite network, which is obtained as a weighted sum of individual networks. The weight assigned to an individual network reflects its benefit towards the protein functional annotation inference. A classifier is then trained on the composite network for predicting protein functions. However, since these techniques model the optimization of the composite network and the prediction tasks as separate objectives, the resulting composite network is not necessarily optimal for the follow-up protein function prediction.ResultsWe address this issue by modeling the optimization of the composite network and the prediction problems within a unified objective function. In particular, we use a kernel target alignment technique and the loss function of a network based classifier to jointly adjust the weights assigned to the individual networks. We show that the proposed method, called MNet, can achieve a performance that is superior (with respect to different evaluation criteria) to related techniques using the multiple networks of four example species (yeast, human, mouse, and fly) annotated with thousands (or hundreds) of GO terms.ConclusionMNet can effectively integrate multiple networks for protein function prediction and is robust to the input parameters. Supplementary data is available at https://sites.google.com/site/guoxian85/home/mnet. The Matlab code of MNet is available upon request.