fMRI Networks Research Articles

Randomized EEG functional brain networks in major depressive disorders with greater resilience and lower rich-club coefficient

ObjectiveSome studies have shown that the functional electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) networks in those with major depressive disorders (MDDs) have an abnormal random topology. In this study we aimed to further investigate the characteristics of the randomized functional brain networks in MDDs by examining resting-state scalp-EEG data. MethodsBased on the methods of independent component analysis (ICA) and graph theoretic analysis, the abnormalities in the power spectral density (PSD) functional brain networks were compared between 13 MDDs and 13 matched healthy controls (HCs). Nonparametric permutation tests were performed to explore the between-group differences in multiple network metrics. The Pearson correlation coefficients were calculated to measure the linear relationships between the clinical symptom and network metrics. ResultsCompared with the HCs, the MDDs showed significant randomization of global network metrics, characterized by greater global efficiency, but lower clustering coefficient, characteristic path length, and local efficiency. This randomization was also reflected in the less heterogeneous and less fat-tailed degree distributions in the MDDs. More importantly, the randomized brain networks in MDDs had greater network resilience to both random failure and targeted attack, which might be a protective mechanism to avoid fast deterioration of the integrity of MDDs’ brain networks under pathological attack. In addition, the randomized brain networks in MDDs had a lower level of rich-club coefficient, suggesting that the density of connections among rich-club hubs became sparser. Furthermore, some of the network metrics explored in this study were significantly associated with the severity of depression in all participants. ConclusionsA replicable randomization of the brain network is found in MDDs. The randomization is further characterized by more homogeneous degree distribution, greater resilience and lower rich-club coefficient, reflecting the reconfiguration of the brain network caused by the reduction of hub nodes in MDD. SignificanceOur results may provide new biomarkers of brain network organization in MDD.

Advances in functional magnetic resonance imaging data analysis methods using Empirical Mode Decomposition to investigate temporal changes in early Parkinson's disease

IntroductionPrevious neuroimaging studies of Parkinson's disease (PD) patients have shown changes in whole-brain functional connectivity networks. Whether connectivity changes can be detected in the early stages (first 3 years) of PD by resting-state functional magnetic resonance imaging (fMRI) remains elusive. Research infrastructure including MRI and analytic capabilities is required to investigate this issue. The National Institutes of Health/National Institute of General Medical Sciences Center for Biomedical Research Excellence awards support infrastructure to advance research goals. MethodsStatic and dynamic functional connectivity analyses were conducted on early stage never-medicated PD subjects (N = 18) and matched healthy controls (N = 18) from the Parkinson's Progression Markers Initiative. ResultsAltered static and altered dynamic functional connectivity patterns were found in early PD resting-state fMRI data. Most static networks (with the exception of the default mode network) had a reduction in frequency and energy in specific low-frequency bands. Changes in dynamic networks in PD were associated with a decreased switching rate of brain states. DiscussionThis study demonstrates that in early PD, resting-state fMRI networks show spatial and temporal differences of fMRI signal characteristics. However, the default mode network was not associated with any measurable changes. Furthermore, by incorporating an optimum window size in a dynamic functional connectivity analysis, we found altered whole-brain temporal features in early PD, showing that PD subjects spend significantly more time than healthy controls in a specific brain state. These findings may help in improving diagnosis of early never-medicated PD patients. These key observations emerged in a Center for Biomedical Research Excellence–supported research environment.

Network connectivity correlates of variability in fluid intelligence performance

Abstract reasoning requires a pattern of spatial and temporal coordination among regions across the entire brain. Recent evidence suggests a very high similarity between spontaneous and evoked brain activity in humans, implying that a fine characterization of brain dynamics recorded during resting-state might be informative for the understanding of evoked behavior. In a recent work, we listed and detailed the sets of regions showing robust co-activation during the solution of fluid intelligence (gf) tasks, decomposing such meta-analytic maps in stimulus- and reasoning stage-specific sub-maps. However, while anatomical overlap with well-known resting-state fMRI networks (RSNs) has been documented, we here propose a quantitative validation of such findings via functional connectivity analysis in a sample of healthy participants. Results highlight a striking degree of similarity between the connectivity profile of the gf network and that of the dorsal attention network, with additional overlap with the left and right fronto-parietal control networks. Interestingly, a strong negative correlation with structures of the default mode network (DMN) was also identified. Results of regression models built on two independent fMRI datasets confirmed the negative correlation between gf regions and medial prefrontal structures of the DMN as a significant predictor of individual gf scores. These might suggest a framework to interpret previously reported aging-related decline in both gf and the correlation between “task-positive” networks and DMN, possibly pointing to a common neurophysiological substrate.

Resting State fMRI Functional Connectivity-Based Classification Using a Convolutional Neural Network Architecture

Machine learning techniques have become increasingly popular in the field of resting state fMRI (functional magnetic resonance imaging) network based classification. However, the application of convolutional networks has been proposed only very recently and has remained largely unexplored. In this paper we describe a convolutional neural network architecture for functional connectome classification called connectome-convolutional neural network (CCNN). Our results on simulated datasets and a publicly available dataset for amnestic mild cognitive impairment classification demonstrate that our CCNN model can efficiently distinguish between subject groups. We also show that the connectome-convolutional network is capable to combine information from diverse functional connectivity metrics and that models using a combination of different connectivity descriptors are able to outperform classifiers using only one metric. From this flexibility follows that our proposed CCNN model can be easily adapted to a wide range of connectome based classification or regression tasks, by varying which connectivity descriptor combinations are used to train the network.

Functional Subpopulations of Neurons in a Macaque Face Patch Revealed by Single-Unit fMRI Mapping

Neurons within fMRI-defined face patches of the macaque brain exhibit shared categorical responses to flashed images but diverge in their responses under more natural viewing conditions. Here we investigate functional diversity among neurons in the anterior fundus (AF) face patch, combining whole-brain fMRI with longitudinal single-unit recordings in a local population (<1mm3). For each cell, we computed a whole-brain correlation map based on its shared time course with voxels throughout the brain during naturalistic movie viewing. Based on this mapping, neighboring neurons showed markedly different affiliation with distant visually responsive areas and fell coarsely into subpopulations. Of these, only one subpopulation (∼16% of neurons) yielded similar correlation maps to the local fMRI signal. The results employ the readout of large-scale fMRI networks and, by indicating multiple functional domains within a single voxel, present a new view of functional diversity within a local neural population.

Modulation of intrinsic resting-state fMRI networks in women with chronic migraine.

To evaluate the intrinsic resting functional connectivity of the default mode network (DMN), salience network (SN), and central executive network (CEN) network in women with chronic migraine (CM), and whether clinical features are associated with such abnormalities. We analyzed resting-state connectivity in 29 women with CM as compared to age- and sex-matched controls. Relationships between clinical characteristics and changes in targeted networks connectivity were evaluated using a multivariate linear regression model. All 3 major intrinsic brain networks were less coherent in CM (DMN: p = 0.030, SN: p = 0.007, CEN: p = 0.002) as compared to controls. When stratified based on medication overuse headache (MOH) status, CM without MOH (DMN: p = 0.029, SN: p = 0.023, CEN: p = 0.003) and CM with MOH (DMN: p = 0.016, SN: p = 0.016, CEN: p = 0.015) were also less coherent as compared to controls. There was no difference in CM with MOH as compared to CM without MOH (DMN: p = 0.382, SN: p = 0.408, CEN: p = 0.419). The frequency of moderate and severe headache days was associated with decreased connectivity in SN (p = 0.003) and CEN (p = 0.015), while cutaneous allodynia was associated with increased connectivity in SN (p = 0.011). Our results demonstrated decreased overall resting-state functional connectivity of the 3 major intrinsic brain networks in women with CM, and these patterns were associated with frequency of moderate to severe headache and cutaneous allodynia.

Dissecting the parieto-frontal correlates of fluid intelligence: A comprehensive ALE meta-analysis study

Recent advances in cognitive neuroscience have shown how experience-independent cognitive abilities termed fluid intelligence (Gf) can predict academic achievement, longevity and resilience to neurodegeneration. Therefore, the understanding of the neurobiological underpinnings of Gf becomes a crucial step for the implementation of cognitive rehabilitation as well as enhancement interventions. Here we present the result of a quantitative meta-analysis of available fMRI and PET literature about Gf in humans, including (i) distinct maps for verbal and visuospatial stimuli, (ii) an analysis of brain regions contributing to processing of more complex stimuli as well as (iii) a model-driven distinction of processing stages occurring during Gf-related problem solving. Results highlight the loading of Gf components over functionally defined resting-state fMRI networks, with different degrees of overlap in both hemispheres and subcortical structures. A major role for nodes of the dorsal attention network during both verbal and visuospatial abstract reasoning tasks represents the most consistent correlate of Gf, with additional contributions by regions of the anterior salience and left fronto-parietal control network. Increase in trial difficulty elicits a more pronounced engagement of the language and left fronto-parietal control networks, while inferring the rules subtending a given Gf task relies on a different anatomo-functional substrate than producing novel solutions. Current findings might allow a clearer association between Gf-related activity and brain connectivity, also providing quantitative ALE maps to be used in network-based brain stimulation and cognitive training interventions.

Decoding the encoding of functional brain networks: An fMRI classification comparison of non-negative matrix factorization (NMF), independent component analysis (ICA), and sparse coding algorithms

BackgroundBrain networks in fMRI are typically identified using spatial independent component analysis (ICA), yet other mathematical constraints provide alternate biologically-plausible frameworks for generating brain networks. Non-negative matrix factorization (NMF) would suppress negative BOLD signal by enforcing positivity. Spatial sparse coding algorithms (L1 Regularized Learning and K-SVD) would impose local specialization and a discouragement of multitasking, where the total observed activity in a single voxel originates from a restricted number of possible brain networks. New methodThe assumptions of independence, positivity, and sparsity to encode task-related brain networks are compared; the resulting brain networks within scan for different constraints are used as basis functions to encode observed functional activity. These encodings are then decoded using machine learning, by using the time series weights to predict within scan whether a subject is viewing a video, listening to an audio cue, or at rest, in 304 fMRI scans from 51 subjects. Results and comparison with existing methodThe sparse coding algorithm of L1 Regularized Learning outperformed 4 variations of ICA (p<0.001) for predicting the task being performed within each scan using artifact-cleaned components. The NMF algorithms, which suppressed negative BOLD signal, had the poorest accuracy compared to the ICA and sparse coding algorithms. Holding constant the effect of the extraction algorithm, encodings using sparser spatial networks (containing more zero-valued voxels) had higher classification accuracy (p<0.001). Lower classification accuracy occurred when the extracted spatial maps contained more CSF regions (p<0.001). ConclusionThe success of sparse coding algorithms suggests that algorithms which enforce sparsity, discourage multitasking, and promote local specialization may capture better the underlying source processes than those which allow inexhaustible local processes such as ICA. Negative BOLD signal may capture task-related activations.

Time-varying spectral power of resting-state fMRI networks reveal cross-frequency dependence in dynamic connectivity.

Brain oscillations and synchronicity among brain regions (brain connectivity) have been studied in resting-state (RS) and task-induced settings. RS-connectivity which captures brain functional integration during an unconstrained state is shown to vary with the frequency of oscillations. Indeed, high temporal resolution modalities have demonstrated both between and cross-frequency connectivity spanning across frequency bands such as theta and gamma. Despite high spatial resolution, functional magnetic resonance imaging (fMRI) suffers from low temporal resolution due to modulation with slow-varying hemodynamic response function (HRF) and also relatively low sampling rate. This limits the range of detectable frequency bands in fMRI and consequently there has been no evidence of cross-frequency dependence in fMRI data. In the present work we uncover recurring patterns of spectral power in network timecourses which provides new insight on the actual nature of frequency variation in fMRI network activations. Moreover, we introduce a new measure of dependence between pairs of rs-fMRI networks which reveals significant cross-frequency dependence between functional brain networks specifically default-mode, cerebellar and visual networks. This is the first strong evidence of cross-frequency dependence between functional networks in fMRI and our subject group analysis based on age and gender supports usefulness of this observation for future clinical applications.

Frequency-specific electrophysiologic correlates of resting state fMRI networks

Resting state functional MRI (R-fMRI) studies have shown that slow (<0.1Hz), intrinsic fluctuations of the blood oxygen level dependent (BOLD) signal are temporally correlated within hierarchically organized functional systems known as resting state networks (RSNs) (Doucet et al., 2011). Most broadly, this hierarchy exhibits a dichotomy between two opposed systems (Fox et al., 2005). One system engages with the environment and includes the visual, auditory, and sensorimotor (SMN) networks as well as the dorsal attention network (DAN), which controls spatial attention. The other system includes the default mode network (DMN) and the fronto-parietal control system (FPC), RSNs that instantiate episodic memory and executive control, respectively. Here, we test the hypothesis, based on the spectral specificity of electrophysiologic responses to perceptual vs. memory tasks (Klimesch, 1999; Pfurtscheller and Lopes da Silva, 1999), that these two large-scale neural systems also manifest frequency specificity in the resting state. We measured the spatial correspondence between electrocorticographic (ECoG) band-limited power (BLP) and R-fMRI correlation patterns in awake, resting, human subjects. Our results show that, while gamma BLP correspondence was common throughout the brain, theta (4–8Hz) BLP correspondence was stronger in the DMN and FPC, whereas alpha (8–12Hz) correspondence was stronger in the SMN and DAN. Thus, the human brain, at rest, exhibits frequency specific electrophysiology, respecting both the spectral structure of task responses and the hierarchical organization of RSNs.

How restful is it with all that noise? Comparison of Interleaved silent steady state (ISSS) and conventional imaging in resting-state fMRI

Resting-state fMRI studies have become very important in cognitive neuroscience because they are able to identify BOLD fluctuations in brain circuits involved in motor, cognitive, or perceptual processes without the use of an explicit task. Such approaches have been fruitful when applied to various disordered populations, or to children or the elderly. However, insufficient attention has been paid to the consequences of the loud acoustic scanner noise associated with conventional fMRI acquisition, which could be an important confounding factor affecting auditory and/or cognitive networks in resting-state fMRI. Several approaches have been developed to mitigate the effects of acoustic noise on fMRI signals, including sparse sampling protocols and interleaved silent steady state (ISSS) acquisition methods, the latter being used only for task-based fMRI. Here, we developed an ISSS protocol for resting-state fMRI (rs-ISSS) consisting of rapid acquisition of a set of echo planar imaging volumes following each silent period, during which the steady state longitudinal magnetization was maintained with a train of relatively silent slice-selective excitation pulses. We evaluated the test-retest reliability of intensity and spatial extent of connectivity networks of fMRI BOLD signal across three different days for rs-ISSS and compared it with a standard resting-state fMRI (rs-STD). We also compared the strength and distribution of connectivity networks between rs-ISSS and rs-STD. We found that both rs-ISSS and rs-STD showed high reproducibility of fMRI signal across days. In addition, rs-ISSS showed a more robust pattern of functional connectivity within the somatosensory and motor networks, as well as an auditory network compared with rs-STD. An increased connectivity between the default mode network and the language network and with the anterior cingulate cortex (ACC) network was also found for rs-ISSS compared with rs-STD. Finally, region of interest analysis showed higher interhemispheric connectivity in Heschl's gyri in rs-ISSS compared with rs-STD, with lower variability across days. The present findings suggest that rs-ISSS may be advantageous for detecting network connectivity in a less noisy environment, and that resting-state studies carried out with standard scanning protocols should consider the potential effects of loud noise on the measured networks.

Magnetoencephalographic and functional MRI connectomics in schizophrenia via intra- and inter-network connectivity

Examination of intrinsic functional connectivity using functional MRI (fMRI) has provided important findings regarding dysconnectivity in schizophrenia. Extending these results using a complementary neuroimaging modality, magnetoencephalography (MEG), we present the first direct comparison of functional connectivity between schizophrenia patients and controls, using these two modalities combined. We developed a novel MEG approach for estimation of networks using MEG that incorporates spatial independent component analysis (ICA) and pairwise correlations between independent component timecourses, to estimate intra- and intern-network connectivity. This analysis enables group-level inference and testing of between-group differences. Resting state MEG and fMRI data were acquired from a large sample of healthy controls (n=45) and schizophrenia patients (n=46). Group spatial ICA was performed on fMRI and MEG data to extract intrinsic fMRI and MEG networks and to compensate for signal leakage in MEG. Similar, but not identical spatial independent components were detected for MEG and fMRI. Analysis of functional network connectivity (FNC; i.e., pairwise correlations in network (ICA component) timecourses) revealed a differential between-modalities pattern, with greater connectivity among occipital networks in fMRI and among frontal networks in MEG. Most importantly, significant differences between controls and patients were observed in both modalities. MEG FNC results in particular indicated dysfunctional hyperconnectivity within frontal and temporal networks in patients, while in fMRI FNC was always greater for controls than for patients. This is the first study to apply group spatial ICA as an approach to leakage correction, and as such our results may be biased by spatial leakage effects. Results suggest that combining these two neuroimaging modalities reveals additional disease-relevant patterns of connectivity that were not detectable with fMRI or MEG alone.

Archetypal Analysis for Modeling Multisubject fMRI Data

Functional magnetic resonance imaging (fMRI) is widely used to measure brain function during various cognitive states. However, it remains a challenge to obtain low-rank models of functional networks in fMRI that have interpretable latent features and generalize across groups of subjects, due to significant intersubject variability in the signal structure and noise. Group-level modeling is typically performed using component decompositions such as independent component analysis (ICA), which represent data as a linear combination of latent brain patterns, or using clustering models, where data are assumed to be generated by a set of “prototype” time series. Archetypal analysis (AA) provides a promising alternative, combining the advantages of component-model flexibility with highly interpretable latent “archetypes” (similar to cluster-model prototypes). To date, AA has not been applied to group-level fMRI; a major limitation is that it does not generalize to multi-subject datasets, which may have significant variations in blood oxygenation-level-dependent signal and heteroscedastic noise. We develop multi-subject AA (MS-AA), which accounts for group-level data by assuming that archetypal temporal profiles have a common latent generator across subjects, ensuring that the temporal components are derived from a consistent set of brain regions. In addition, the model accounts for noise heteroscedasticity by modeling subject- and voxel-specific noise variance. This provides a novel approach to group-level modeling and an alternative to preexisting methods that account for inter-subject variability by extracting individual maps as a postprocessing step (e.g., dual-regression ICA), or assuming spatial dependency of maps across subjects (e.g., independent vector analysis). MS-AA shows robust performance when modelling archetypes for a motor task experiment. The procedure extracts a “seed map” across subjects, used to provide brain parcellations with subject-specific temporal profiles. Our approach thus decomposes multisubject fMRI data into distinct interpretable component archetypes that may help to model both consistent group-level measures of fMRI data and individual variability.

A Method for Intertemporal Functional-Domain Connectivity Analysis: Application to Schizophrenia Reveals Distorted Directional Information Flow.

We introduce a method for analyzing dynamically changing functional magnetic resonance imaging (fMRI) network connectivity estimates as they vary within and between broad functional domains. The method captures evidence of intertemporal directionality incross joint functional-domaininfluence and extends standard whole-brain dynamic network connectivity approaches into additional functionally meaningful dimensions by evaluating transition probabilities between clustered intradomain and interdomain connectivity patterns. Results: In applying this method to a large (N = 314) multisite resting-state fMRI dataset balanced between schizophrenia patients and healthy controls, we find evidence of joint functional domains that areglobal catalyzers, broadly shaping downstream functional relationships throughout the brain. Multiple interesting differences between patients and controls in both time-varying joint functional-domain connectivity patterns and in cross joint functional-domain intertemporal information flow were identified.Conclusion and Significance:Our proposed approach, thus, unifies the concepts of brain connectivity and interdomain connectivity and provides a powerful new way to evaluate functional connectivity data in the context of both the healthy and diseased brain.

Task-irrelevant fear enhances amygdala-FFG inhibition and decreases subsequent face processing

Facial threat is associated with changes in limbic activity as well as modifications in the cortical face-related N170. It remains unclear if task-irrelevant threat modulates the response to a subsequent facial stimulus, and whether the amygdala's role in early threat perception is independent and direct, or modulatory. In 19 participants, crowds of emotional faces were followed by target faces and a rating task while simultaneous EEG-fMRI were recorded. In addition to conventional analyses, fMRI-informed EEG analyses and fMRI dynamic causal modeling (DCM) were performed. Fearful crowds reduced EEG N170 target face amplitudes and increased responses in a fMRI network comprising insula, amygdala and inferior frontal cortex. Multimodal analyses showed that amygdala response was present ∼60 ms before the right fusiform gyrus-derived N170. DCM indicated inhibitory connections from amygdala to fusiform gyrus, strengthened when fearful crowds preceded a target face. Results demonstrated the suppressing influence of task-irrelevant fearful crowds on subsequent face processing. The amygdala may be sensitive to task-irrelevant fearful crowds and subsequently strengthen its inhibitory influence on face-responsive fusiform N170 generators. This provides spatiotemporal evidence for a feedback mechanism of the amygdala by narrowing attention in order to focus on potential threats.

Signal Fluctuation Sensitivity: An Improved Metric for Optimizing Detection of Resting-State fMRI Networks

Task-free connectivity analyses have emerged as a powerful tool in functional neuroimaging. Because the cross-correlations that underlie connectivity measures are sensitive to distortion of time-series, here we used a novel dynamic phantom to provide a ground truth for dynamic fidelity between blood oxygen level dependent (BOLD)-like inputs and fMRI outputs. We found that the de facto quality-metric for task-free fMRI, temporal signal to noise ratio (tSNR), correlated inversely with dynamic fidelity; thus, studies optimized for tSNR actually produced time-series that showed the greatest distortion of signal dynamics. Instead, the phantom showed that dynamic fidelity is reasonably approximated by a measure that, unlike tSNR, dissociates signal dynamics from scanner artifact. We then tested this measure, signal fluctuation sensitivity (SFS), against human resting-state data. As predicted by the phantom, SFS—and not tSNR—is associated with enhanced sensitivity to both local and long-range connectivity within the brain's default mode network.

Large-Scale Granger Causality Analysis on Resting-State Functional MRI.

We demonstrate an approach to measure the information flow between each pair of time series in resting-state functional MRI (fMRI) data of the human brain and subsequently recover its underlying network structure. By integrating dimensionality reduction into predictive time series modeling, large-scale Granger Causality (lsGC) analysis method can reveal directed information flow suggestive of causal influence at an individual voxel level, unlike other multivariate approaches. This method quantifies the influence each voxel time series has on every other voxel time series in a multivariate sense and hence contains information about the underlying dynamics of the whole system, which can be used to reveal functionally connected networks within the brain. To identify such networks, we perform non-metric network clustering, such as accomplished by the Louvain method. We demonstrate the effectiveness of our approach to recover the motor and visual cortex from resting state human brain fMRI data and compare it with the network recovered from a visuomotor stimulation experiment, where the similarity is measured by the Dice Coefficient (DC). The best DC obtained was 0.59 implying a strong agreement between the two networks. In addition, we thoroughly study the effect of dimensionality reduction in lsGC analysis on network recovery. We conclude that our approach is capable of detecting causal influence between time series in a multivariate sense, which can be used to segment functionally connected networks in the resting-state fMRI.

Multivariate dynamical systems-based estimation of causal brain interactions in fMRI: Group-level validation using benchmark data, neurophysiological models and human connectome project data

BackgroundCausal estimation methods are increasingly being used to investigate functional brain networks in fMRI, but there are continuing concerns about the validity of these methods. New methodMultivariate dynamical systems (MDS) is a state-space method for estimating dynamic causal interactions in fMRI data. Here we validate MDS using benchmark simulations as well as simulations from a more realistic stochastic neurophysiological model. Finally, we applied MDS to investigate dynamic casual interactions in a fronto-cingulate-parietal control network using human connectome project (HCP) data acquired during performance of a working memory task. Crucially, since the ground truth in experimental data is unknown, we conducted novel stability analysis to determine robust causal interactions within this network. ResultsMDS accurately recovered dynamic causal interactions with an area under receiver operating characteristic (AUC) above 0.7 for benchmark datasets and AUC above 0.9 for datasets generated using the neurophysiological model. In experimental fMRI data, bootstrap procedures revealed a stable pattern of causal influences from the anterior insula to other nodes of the fronto-cingulate-parietal network. Comparison with existing methodsMDS is effective in estimating dynamic causal interactions in both the benchmark and neurophysiological model based datasets in terms of AUC, sensitivity and false positive rates. ConclusionsOur findings demonstrate that MDS can accurately estimate causal interactions in fMRI data. Neurophysiological models and stability analysis provide a general framework for validating computational methods designed to estimate causal interactions in fMRI. The right anterior insula functions as a causal hub during working memory.

Approaches to Capture Variance Differences in Rest fMRI Networks in the Spatial Geometric Features: Application to Schizophrenia.

Identification of functionally connected regions while at rest has been at the forefront of research focusing on understanding interactions between different brain regions. Studies have utilized a variety of approaches including seed based as well as data-driven approaches to identifying such networks. Most such techniques involve differentiating groups based on group mean measures. There has been little work focused on differences in spatial characteristics of resting fMRI data. We present a method to identify between group differences in the variability in the cluster characteristics of network regions within components estimated via independent vector analysis (IVA). IVA is a blind source separation approach shown to perform well in capturing individual subject variability within a group model. We evaluate performance of the approach using simulations and then apply to a relatively large schizophrenia data set (82 schizophrenia patients and 89 healthy controls). We postulate, that group differences in the intra-network distributional characteristics of resting state network voxel intensities might indirectly capture important distinctions between the brain function of healthy and clinical populations. Results demonstrate that specific areas of the brain, superior, and middle temporal gyrus that are involved in language and recognition of emotions, show greater component level variance in amplitude weights for schizophrenia patients than healthy controls. Statistically significant correlation between component level spatial variance and component volume was observed in 19 of the 27 non-artifactual components implying an evident relationship between the two parameters. Additionally, the greater spread in the distance of the cluster peak of a component from the centroid in schizophrenia patients compared to healthy controls was observed for seven components. These results indicate that there is hidden potential in exploring variance and possibly higher-order measures in resting state networks to better understand diseases such as schizophrenia. It furthers comprehension of how spatial characteristics can highlight previously unexplored differences between populations such as schizophrenia patients and healthy controls.

The Lateralization of Intrinsic Networks in the Aging Brain Implicates the Effects of Cognitive Training.

Lateralization of function is an important organization of the human brain. The distribution of intrinsic networks in the resting brain is strongly related to cognitive function, gender and age. In this study, a longitudinal design with 1 year’s duration was used to evaluate the cognitive training effects on the lateralization of intrinsic networks among healthy older adults. The subjects were divided into two groups randomly: one with multi-domain cognitive training over 3 months and the other as a wait-list control group. Resting state fMRI data were acquired before training and 1 year after training. We analyzed the functional lateralization in 10 common resting state fMRI networks. We observed statically significant training effects on the lateralization of two important RSNs related to high-level cognition: right- and left- frontoparietal networks (FPNs). The lateralization of the left-FPN was retained especially well in the training group but decreased in the control group. The increased lateralization with aging was observed in the cerebellum network (CereN), in which the lateralization was significantly increased in the control group, although the same change tendency was observed in the training group. These findings indicate that the lateralization of the high-level cognitive intrinsic networks is sensitive to multi-domain cognitive training. This study provides neuroimaging evidence to support the hypothesis that cognitive training should have an advantage in preventing cognitive decline in healthy older adults.