A method for comparing group fMRI data using independent component analysis: application to visual, motor and visuomotor tasks

Independent component analysis (ICA) is an approach for decomposing fMRI data into spatially independent maps and time courses. We have recently proposed a method for ICA of multisubject data; in the current paper, an extension is proposed for allowing ICA group comparisons. This method is applied to data from experiments designed to stimulate visual cortex, motor cortex or both visual and motor cortices. Several intergroup and intragroup metrics are proposed for assessing the utility of the components for comparisons of group ICA data. The proposed method may prove to be useful in answering questions requiring multigroup comparisons when a flexible modeling approach is desired.     

Brain oscillatory activity during motor imagery in EEG-fMRI coregistration

The purpose of the present work was to investigate the correlation between topographical changes in brain oscillatory activity and the blood oxygenation level-dependent (BOLD) signal during a motor imagery (MI) task using electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) coregistration.     

Preoperative localization of the sensorimotor area using independent component analysis of resting-state fMRI

Analysis of resting-state functional magnetic resonance imaging (fMRI) data is based on detecting low-frequency signal fluctuations in functionally connected brain areas. These synchronous fluctuations in resting-state networks have been observed in several studies with healthy subjects. In this study, we explored if independent component analysis (ICA) can be used to localize the sensorimotor area from resting-state fMRI data in patients with brain tumors. Finger-tapping activation task and resting-state blood-oxygenation-level-dependent fMRI data were acquired from 8 patients with brain tumors and 10 healthy volunteers. Sensorimotor task independent components (IC_task) were used to verify resting-state independent components (IC_rest) individually. In addition, sensorimotor IC_rests were compared between the groups and no significant differences were detected in volume, spatial correlation or temporal correlation. These results show that it is possible to localize a sensorimotor area from resting-state data using ICA in patients with brain tumors. This offers a complementary method for assessing the sensorimotor area in subjects with brain tumors who have difficulties in performing motor paradigms.     

Separating 4D multi-task fMRI data of multiple subjects by independent component analysis with projection

Independent component analysis (ICA) is a widely accepted method to extract brain networks underlying cognitive processes from functional magnetic resonance imaging (fMRI) data. However, the application of ICA to multi-task fMRI data is limited due to the potential non-independency between task-related components. The ICA with projection (ICAp) method proposed by our group (Hum Brain Mapp 2009;30:417–31) is demonstrated to be able to solve the interactions among task-related components for single subject fMRI data. However, it still must be determined if ICAp is capable of processing multi-task fMRI data over a group of subjects. Moreover, it is unclear whether ICAp can be reliably applied to event-related (ER) fMRI data. In this study, we combined the projection method with the temporal concatenation method reported by Calhoun (Hum Brain Mapp 2008;29:828–38), referred to as group ICAp, to perform the group analysis of multi-task fMRI data. Both a human fMRI rest data-based simulation and real fMRI experiments, of block design and ER design, verified the feasibility and reliability of group ICAp, as well as demonstrated that ICAp had the strength to separate 4D multi-task fMRI data into multiple brain networks engaged in each cognitive task and to adequately find the commonalities and differences among multiple tasks.     

Dissecting cognitive stages with time-resolved fMRI data: a comparison of fuzzy clustering and independent component analysis

In combination with cognitive tasks entailing sequences of sensory and cognitive processes, event-related acquisition schemes allow using functional MRI to examine not only the topography but also the temporal sequence of cortical activation across brain regions (time-resolved fMRI). In this study, we compared two data-driven methods--fuzzy clustering method (FCM) and independent component analysis (ICA)--in the context of time-resolved fMRI data collected during the performance of a newly devised visual imagery task. We analyzed a multisubject fMRI data set using both methods and compared their results in terms of within- and between-subject consistency and spatial and temporal correspondence of obtained maps and time courses. Both FCM and spatial ICA allowed discriminating the contribution of distinct networks of brain regions to the main cognitive stages of the task (auditory perception, mental imagery and behavioural response), with good agreement across methods. Whereas ICA worked optimally on the original time series, averaging with respect to the task onset (and thus introducing some a priori information on the stimulation protocol) was found to be indispensable in the case of FCM. On averaged time series, FCM led to a richer decomposition of the spatio-temporal patterns of activation and allowed a finer separation of the neurocognitive processes subserving the mental imagery task. This study confirms the efficacy of the two examined methods in the data-driven estimation of hemodynamic responses in time-resolved fMRI studies and provides empirical guidelines to their use.     

Discussion on the choice of separated components in fMRI data analysis by spatial independent component analysis

By measuring the changes of magnetic resonance signals during a stimulation, the functional magnetic resonance imaging (fMRI) is able to localize the neural activation in the brain. In this report, we discuss the fMRI application of the spatial independent component analysis (spatial ICA), which maximizes statistical independence over spatial images. Included simulations show the possibility of the spatial ICA on discriminating asynchronous activations or different response patterns in an fMRI data set. An in vivo visual stimulation fMRI test was conducted, and the result shows a proper sum of the separated components as the final image is better than a single component, using fMRI data analysis by spatial ICA. Our result means that spatial ICA is a useful tool for the detection of different response activations and suggests that a proper sum of the separated independent components should be used for the imaging result of fMRI data processing.     

Performance of blind source separation algorithms for fMRI analysis using a group ICA method

Independent component analysis (ICA) is a popular blind source separation technique that has proven to be promising for the analysis of functional magnetic resonance imaging (fMRI) data. A number of ICA approaches have been used for fMRI data analysis, and even more ICA algorithms exist; however, the impact of using different algorithms on the results is largely unexplored. In this paper, we study the performance of four major classes of algorithms for spatial ICA, namely, information maximization, maximization of non-Gaussianity, joint diagonalization of cross-cumulant matrices and second-order correlation-based methods, when they are applied to fMRI data from subjects performing a visuo-motor task. We use a group ICA method to study variability among different ICA algorithms, and we propose several analysis techniques to evaluate their performance. We compare how different ICA algorithms estimate activations in expected neuronal areas. The results demonstrate that the ICA algorithms using higher-order statistical information prove to be quite consistent for fMRI data analysis. Infomax, FastICA and joint approximate diagonalization of eigenmatrices (JADE) all yield reliable results, with each having its strengths in specific areas. Eigenvalue decomposition (EVD), an algorithm using second-order statistics, does not perform reliably for fMRI data. Additionally, for iterative ICA algorithms, it is important to investigate the variability of estimates from different runs. We test the consistency of the iterative algorithms Infomax and FastICA by running the algorithm a number of times with different initializations, and we note that they yield consistent results over these multiple runs. Our results greatly improve our confidence in the consistency of ICA for fMRI data analysis.     

A SVM-based quantitative fMRI method for resting-state functional network detection

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.     

Cortex-based independent component analysis of fMRI time series

The cerebral cortex is the main target of analysis in many functional magnetic resonance imaging (fMRI) studies. Since only about 20% of the voxels of a typical fMRI data set lie within the cortex, statistical analysis can be restricted to the subset of the voxels obtained after cortex segmentation. While such restriction does not influence conventional univariate statistical tests, it may have a substantial effect on the performance of multivariate methods.

Here, we describe a novel approach for data-driven analysis of single-subject fMRI time series that combines techniques for the segmentation and reconstruction of the cortical surface of the brain and the spatial independent component analysis (sICA) of the functional time courses (TCs). We use the mesh of the white matter/gray matter boundary, automatically reconstructed from high-spatial-resolution anatomical MR images, to limit the sICA decomposition of a coregistered functional time series to those voxels which are within a specified region with respect to the cortical sheet (cortex-based ICA, or cbICA). We illustrate our analysis method in the context of fMRI blocked and event-related experimental designs and in an fMRI experiment with perceptually ambiguous stimulation, in which an a priori specification of the stimulation protocol is not possible.

A comparison between cbICA and conventional hypothesis-driven statistical methods shows that cortical surface maps and component TCs blindly obtained with cbICA reliably reflect task-related spatiotemporal activation patterns. Furthermore, the advantages of using cbICA when the specification of a temporal model of the expected hemodynamic response is not straightforward are illustrated and discussed. A comparison between cbICA and anatomically unconstrained ICA reveals that — beside reducing computational demand — the cortex-based approach improves the fitting of the ICA model in the gray matter voxels, the separation of cortical components and the estimation of their TCs, particularly in the case of fMRI data sets with a complex spatiotemporal statistical structure.     

Validating the performance of one-time decomposition for fMRI analysis using ICA with automatic target generation process

Independent component analysis (ICA) has been proven to be effective for functional magnetic resonance imaging (fMRI) data analysis. However, ICA decomposition requires to optimize the unmixing matrix iteratively whose initial values are generated randomly. Thus the randomness of the initialization leads to different ICA decomposition results. Therefore, just one-time decomposition for fMRI data analysis is not usually reliable. Under this circumstance, several methods about repeated decompositions with ICA (RDICA) were proposed to reveal the stability of ICA decomposition. Although utilizing RDICA has achieved satisfying results in validating the performance of ICA decomposition, RDICA cost much computing time. To mitigate the problem, in this paper, we propose a method, named ATGP-ICA, to do the fMRI data analysis. This method generates fixed initial values with automatic target generation process (ATGP) instead of being produced randomly. We performed experimental tests on both hybrid data and fMRI data to indicate the effectiveness of the new method and made a performance comparison of the traditional one-time decomposition with ICA (ODICA), RDICA and ATGP-ICA. The proposed method demonstrated that it not only could eliminate the randomness of ICA decomposition, but also could save much computing time compared to RDICA. Furthermore, the ROC (Receiver Operating Characteristic) power analysis also denoted the better signal reconstruction performance of ATGP-ICA than that of RDICA.     

Functional MRI changes in the central motor system in myotonic dystrophy type 1

Myotonic dystrophy type 1 (DM1) is a multisystemic disease involving multiple organ systems including central nervous system (CNS) and muscles. Few studies have focused on the central motor system in DM1, pointing to a subclinical abnormality in the CNS. The aim of our study was to investigate patterns of cerebral activation in DM1 during a motor task using functional MRI (fMRI). Fifteen DM1 patients, aged 20 to 59 years, and 15 controls of comparable age were scanned during a self-paced sequential finger-to-thumb opposition task of their dominant right hand. Functional MRI images were analyzed using SPM99. Patients underwent clinical and genetic assessment; all subjects underwent a conventional MR study. Myotonic dystrophy type 1 patients showed greater activation than controls in bilateral sensorimotor areas and inferior parietal lobules, basal ganglia and thalami, in the ipsilateral premotor area, insula and supplementary motor area (corrected P<.05). Analysis of the interaction between disease and age showed that correlation with age was significantly greater in patients than in controls in bilateral sensorimotor areas and in contralateral parietal areas. Other clinical and MR characteristics did not correlate with fMRI. Functional changes in DM1 may represent compensatory mechanisms such as reorganization and redistribution of functional networks to compensate for ultrastructural and neurochemical changes occurring as part of the accelerated aging process.     

Functional MRI of the motor cortex using a conventional gradient system: comparison of FLASH and EPI techniques

Gradient echo (GE) and echo planar imaging (EPI) techniques are two different approaches to functional MRI (fMRI). In contrast to GE sequences, the ultra short EPI technique facilitates fMRI experiments with high spatial and temporal resolution or mapping of the whole brain. Although it has become the method of choice for fMRI, EPI is generally restricted to modern scanners with a strong gradient system. The aim of our study was to evaluate the applicability of EPI for fMRI of the motor cortex using a 1.5 T scanner with a conventional gradient system of 10 mT/m (rise time: 1 ms). Therefore, EPI was compared with a well-established high resolution fast low angle shot (FLASH) technique (matrix size 128²). The FLASH technique was applied additionally with a 64² matrix size to exclude influences caused by different spatial resolution, because the EPI sequence was restricted to a 64² matrix size. A total of 35 healthy volunteers were included in this study. The task consisted of clenching and spreading of the right hand. FLASH and EPI techniques were compared regarding geometric distortions as well as qualitative and quantitative fMRI criteria: Mean signal increase between activation and rest and the area of activation were measured within the contralateral, ipsilateral, and supplementary motor cortex. The quality of subtraction images between activation and rest, as well as the quality of z-maps and time course within activated regions of interest, was evaluated visually. EPI revealed significant distortions of the anterior and postior brain margins; lateral distortions (relevant for the motor cortex) could be neglected in most cases. The mean signal increase was significantly higher using FLASH 128² compared to FLASH 64² and EPI 64², whereas the activated areas proved to be smaller in FLASH 128² functional images. Both results can be explained by well-documented partial volume effects, caused by different voxel size. Similar quality of the subtraction images and of the time courses in different regions of interest were found for all techniques under investigation, but slightly reduced quality of z-map in FLASH 128². Within the limits of reproducibility and measurement accuracy, the location of contralateral activation was similar using FLASH and EPI sequences. In conclusion, EPI proved to be a reliable technique for fMRI of the motor cortex, even on an MR scanner with a conventional gradient system.     

Combining independent component analysis and correlation analysis to probe interregional connectivity in fMRI task activation datasets

A new approach in studying interregional functional connectivity using functional magnetic resonance imaging (fMRI) is presented. Functional connectivity may be detected by means of cross correlating time course data from functionally related brain regions. These data exhibit high temporal coherence of low frequency fluctuations due to synchronized blood flow changes. In the past, this fMRI technique for studying functional connectivity has been applied to subjects that performed no prescribed task ("resting" state). This paper presents the results of applying the same method to task-related activation datasets. Functional connectivity analysis is first performed in areas not involved with the task. Then a method is devised to remove the effects of activation from the data using independent component analysis (ICA) and functional connectivity analysis is repeated. Functional connectivity, which is demonstrated in the "resting brain," is not affected by tasks which activate unrelated brain regions. In addition, ICA effectively removes activation from the data and may allow us to study functional connectivity even in the activated regions.     

Derivative temporal clustering analysis: detecting prolonged neuronal activity

Temporal clustering analysis (TCA) and independent component analysis (ICA) are promising data-driven techniques in functional magnetic resonance imaging (fMRI) experiments to obtain brain activation maps in conditions with unknown temporal information regarding the neuronal activity. Although comparable to ICA in detecting transient neuronal activities, TCA fails to detect prolonged plateau brain activations. To eliminate this pitfall, a novel derivative TCA (DTCA) method was introduced and its algorithms with different subtraction intervals were tested on simulated data with a pattern of prolonged plateau brain activation. It was found that the best performance of DTCA method in generating functional maps could be obtained if the subtraction interval is equal to or larger than the length of the rising time of the fMRI response. The DTCA method and its theoretical predication were further investigated and validated using in vivo fMRI data sets. By removing the limitations in the previous TCA, DTCA has shown its powerful capability in detecting prolonged plateau neuronal activities.     

Fixed-point algorithms for constrained ICA and their applications in fMRI data analysis

Constrained independent component analysis (CICA) eliminates the order ambiguity of standard ICA by incorporating prior information into the learning process to sort the components intrinsically. However, the original CICA (OCICA) and its variants depend on a learning rate, which is not easy to be tuned for various applications. To solve this problem, two learning-rate-free CICA algorithms were derived in this paper using the fixed-point learning concept. A complete stability analysis was provided for the proposed methods, which also made a correction to the stability analysis given to OCICA. Variations for adding constraints either to the components or to the associated time courses were derived too. Using synthetic data, the proposed methods yielded a better stability and a better source separation quality in terms of higher signal-to-noise-ratio and smaller performance index than OCICA. For the artificially generated brain activations, the new CICAs demonstrated a better sensitivity/specificity performance than standard univariate general linear model (GLM) and standard ICA. Original CICA showed a similar sensitivity/specificity gain but failed to converge for several times. Using functional magnetic resonance imaging (fMRI) data acquired with a well-characterized sensorimotor task, the proposed CICAs yielded better sensitivity than OCICA, standard ICA and GLM in all the target functional regions in terms of either higher t values or larger suprathreshold cluster extensions using the same significance threshold. In addition, they were more stable than OCICA and standard ICA for analyzing the sensorimotor fMRI data.     

A new quantitative analysis of significant timing differences between externally cued and self-initiated motor tasks in an fMRI study

It is generally accepted that the temporal resolution of blood oxygenation level dependent functional MRI is limited due to the inherent latency and longevity of the haemodynamic response. However, in this study we introduce a technique for measurement of timing differences from within the same brain region in two (or more) separate tasks that allows accurate determination of cortical timing differences 200 ms. Our technique, based on a novel use of linear regression analysis, is shown to yield accurate results both in simulated and experimental data. We show that cortical timing differences measured using fMRI are consistent with published electrophysiological results. Measurement of timing differences using this technique could prove a useful strategy for identifying neural network components in a wide range of cognitive paradigms.     

Independent component analysis in the presence of noise in fMRI

A noisy version of independent component analysis (noisy ICA) is applied to simulated and real functional magnetic resonance imaging (fMRI) data. The noise covariance is explicitly modeled by an autoregressive (AR) model of order 1. The unmixing matrix of the data is determined using a variant of the FastICA algorithm based on Gaussian moments. The sources are estimated using the principle of maximum likelihood by modeling the source densities as asymmetric exponential functions. Effect of dimensionality reduction on the effective noise covariance used, accuracy of the obtained mixing matrix and degree of improvement in estimating fMRI sources are investigated. The primary conclusions after using this method of evaluation are as follows: (a) weighting matrix estimates are similar for noisy and conventional ICA in the realm of typical fMRI data, and (b) source estimates are improved by 5% (as measured by the correlation coefficient) in realistic simulated data by explicitly modeling the source densities and the noise, even when just a simple white noise model is used.     

Quantification of the power changes in BOLD signals using Welch spectrum method during different single-hand motor imageries

Motor imagery is an experimental paradigm implemented in cognitive neuroscience and cognitive psychology. To investigate the asymmetry of the strength of cortical functional activity due to different single-hand motor imageries, functional magnetic resonance imaging (fMRI) data from right handed normal subjects were recorded and analyzed during both left-hand and right-hand motor imagery processes. Then the average power of blood oxygenation level-dependent (BOLD) signals in temporal domain was calculated using the developed tool that combines Welch power spectrum and the integral of power spectrum approach of BOLD signal changes during motor imagery. Power change analysis results indicated that cortical activity exhibited a stronger power in the precentral gyrus and medial frontal gyrus with left-hand motor imagery tasks compared with that from right-hand motor imagery tasks. These observations suggest that right handed normal subjects mobilize more cortical nerve cells for left-hand motor imagery. Our findings also suggest that the approach based on power differences of BOLD signals is a suitable quantitative analysis tool for quantification of asymmetry of brain activity intensity during motor imagery tasks.     

A conditional Granger causality model approach for group analysis in functional magnetic resonance imaging

Granger causality model (GCM) derived from multivariate vector autoregressive models of data has been employed to identify effective connectivity in the human brain with functional magnetic resonance imaging (fMRI) and to reveal complex temporal and spatial dynamics underlying a variety of cognitive processes. In the most recent fMRI effective connectivity measures, pair-wise GCM has commonly been applied based on single-voxel values or average values from special brain areas at the group level. Although a few novel conditional GCM methods have been proposed to quantify the connections between brain areas, our study is the first to propose a viable standardized approach for group analysis of fMRI data with GCM. To compare the effectiveness of our approach with traditional pair-wise GCM models, we applied a well-established conditional GCM to preselected time series of brain regions resulting from general linear model (GLM) and group spatial kernel independent component analysis of an fMRI data set in the temporal domain. Data sets consisting of one task-related and one resting-state fMRI were used to investigate connections among brain areas with the conditional GCM method. With the GLM-detected brain activation regions in the emotion-related cortex during the block design paradigm, the conditional GCM method was proposed to study the causality of the habituation between the left amygdala and pregenual cingulate cortex during emotion processing. For the resting-state data set, it is possible to calculate not only the effective connectivity between networks but also the heterogeneity within a single network. Our results have further shown a particular interacting pattern of default mode network that can be characterized as both afferent and efferent influences on the medial prefrontal cortex and posterior cingulate cortex. These results suggest that the conditional GCM approach based on a linear multivariate vector autoregressive model can achieve greater accuracy in detecting network connectivity than the widely used pair-wise GCM, and this group analysis methodology can be quite useful to extend the information obtainable in fMRI.     

Independent component model of the default-mode brain function: combining individual-level and population-level analyses in resting-state fMRI

Resting-state functional magnetic resonance imaging (RS-fMRI) is a technique used to investigate the spontaneous correlations of blood-oxygen-level-dependent signals across different regions of the brain. Using functional connectivity tools, it is possible to investigate a specific RS-fMRI network, referred to as "default-mode" (DM) network, that involves cortical regions deactivated in fMRI experiments with cognitive tasks. Previous works have reported a significant effect of aging on DM regions activity. Independent component analysis (ICA) is often used for generating spatially distributed DM functional connectivity patterns from RS-fMRI data without the need for a reference region. This aspect and the relatively easy setup of an RS-fMRI experiment even in clinical trials have boosted the combined use of RS-fMRI and ICA-based DM analysis for noninvasive research of brain disorders. In this work, we considered different strategies for combining ICA results from individual-level and population-level analyses and used them to evaluate and predict the effect of aging on the DM component. Using RS-fMRI data from 20 normal subjects and a previously developed group-level ICA methodology, we generated group DM maps and showed that the overall ICA-DM connectivity is negatively correlated with age. A negative correlation of the ICA voxel weights with age existed in all DM regions at a variable degree. As an alternative approach, we generated a distributed DM spatial template and evaluated the correlation of each individual DM component fit to this template with age. Using a "leave-one-out" procedure, we discuss the importance of removing the bias from the DM template-generation process.