Whole-brain fMRI Signals Research Articles

Characterizing brain stage-dependent pupil dynamics based on lateral hypothalamic activity.

Pupil dynamics presents varied correlation features with brain activity under different vigilant levels. The modulation of brain dynamic stages can arise from the lateral hypothalamus (LH), where diverse neuronal cell types contribute to arousal regulation in opposite directions via the anterior cingulate cortex (ACC). However, the relationship of the LH and pupil dynamics has seldom been investigated. Here, we performed local field potential (LFP) recordings at the LH and ACC, and whole-brain fMRI with simultaneous fiber photometry Ca2+ recording in the ACC, to evaluate their correlation with brain state-dependent pupil dynamics. Both LFP and functional magnetic resonance imaging (fMRI) data showed various correlations to pupil dynamics across trials that span negative, null, and positive correlation values, demonstrating brain state-dependent coupling features. Our results indicate that the correlation of pupil dynamics with ACC LFP and whole-brain fMRI signals depends on LH activity, suggesting a role of the latter in brain dynamic stage regulation.

Gyral-sulcal contrast in intrinsic functional brain networks across task performances

Functional mechanism of the brain and its relationship with the brain structural substrate have been an interest for multiple disciplines for centuries. Recently, gyri and sulci, two basic cortical folding patterns, have been demonstrated to act different functional roles. Specifically, a variety of functional MRI (fMRI) studies have consistently suggested that gyri represent a global functional center while sulci serve as a local functional unit under either resting state or task stimulus, which are further supported by brain structural analysis reporting that gyri have thicker cortex and denser long-distance axonal fibers. However, the consistency of such gyral-sulcal functional difference across different task stimuli, as well as its association with task conditions, remains to be explored. To this end, we used intrinsic networks as the testbed for cross-task comparison, and adopted a computational framework of dictionary learning and sparse representation of whole-brain fMRI signals to systematically examine the potential gyral-sulcal difference in signal representation residual (SRR) which reflected the degree of global functional communication. Using all seven task-based fMRI datasets in Human Connectome Project Q1 release, we found that within the intrinsic functional networks, the fMRI SRR was significantly smaller on gyral regions than on sulcal regions across different task stimuli, indicating that gyral regions were more involved in global functions of the brain and interregional communications. Moreover, the magnitudes of such gyral-sulcal difference varied across task conditions and intrinsic networks. Our work adds novel explanation and insight to the existing knowledge of functional differences between gyri and sulci.

Network analysis of whole-brain fMRI dynamics: A new framework based on dynamic communicability

Neuroimaging techniques such as MRI have been widely used to explore the associations between brain areas. Structural connectivity (SC) captures the anatomical pathways across the brain and functional connectivity (FC) measures the correlation between the activity of brain regions. These connectivity measures have been much studied using network theory in order to uncover the distributed organization of brain structures, in particular FC for task-specific brain communication. However, the application of network theory to study FC matrices is often “static” despite the dynamic nature of time series obtained from fMRI. The present study aims to overcome this limitation by introducing a network-oriented analysis applied to whole-brain effective connectivity (EC) useful to interpret the brain dynamics. Technically, we tune a multivariate Ornstein-Uhlenbeck (MOU) process to reproduce the statistics of the whole-brain resting-state fMRI signals, which provides estimates for MOU-EC as well as input properties (similar to local excitabilities). The network analysis is then based on the Green function (or network impulse response) that describes the interactions between nodes across time for the estimated dynamics. This model-based approach provides time-dependent graph-like descriptor, named communicability, that characterize the roles that either nodes or connections play in the propagation of activity within the network. They can be used at both global and local levels, and also enables the comparison of estimates from real data with surrogates (e.g. random network or ring lattice). In contrast to classical graph approaches to study SC or FC, our framework stresses the importance of taking the temporal aspect of fMRI signals into account. Our results show a merging of functional communities over time, moving from segregated to global integration of the network activity. Our formalism sets a solid ground for the analysis and interpretation of fMRI data, including task-evoked activity.

The Dynamics of Speech Motor Control Revealed with Time-Resolved fMRI.

Holding a conversation means that speech must be started, maintained, and stopped continuously. The brain networks that underlie these aspects of speech motor control remain poorly understood. Here we collected functional magnetic resonance imaging (fMRI) data while participants produced normal and fast rate speech in response to sequences of visually presented objects. We took a non-conventional approach to fMRI data analysis that allowed us to study speech motor behavior as it unfolded over time. To this end, whole-brain fMRI signals were extracted in stimulus-locked epochs using slice-based fMRI. These data were then subjected to group independent component analysis to discover spatially independent networks that were associated with different temporal activation profiles. The results revealed two basic brain networks with different temporal dynamics: a cortical network that was activated continuously during speech production, and a second cortico-subcortical network that increased in activity during the initiation and suppression of speech production. Additional analyses explored whether key areas involved in motor suppression such as the right inferior frontal gyrus, sub-thalamic nucleus and pre-supplementary motor area provide first-order signals to stop speech. The results reveal for the first time the brain networks associated with the initiation, maintenance, and suppression of speech motor behavior.

Contribution of systemic vascular effects to fMRI activity in white matter

To investigate a potential contribution of systemic physiology to recently reported BOLD fMRI signals in white matter, we compared photo-plethysmography (PPG) and whole-brain fMRI signals recorded simultaneously during long resting-state scans from an overnight sleep study. We found that intermittent drops in the amplitude of the PPG signal exhibited strong and widespread correlations with the fMRI signal, both in white matter (WM) and in gray matter (GM). The WM signal pattern resembled that seen in previous resting-state fMRI studies and closely tracked the location of medullary veins. Its temporal cross-correlation with the PPG amplitude was bipolar, with an early negative value. In GM, the correlation was consistently positive. Consistent with previous studies comparing physiological signals with fMRI, these findings point to a systemic vascular contribution to WM fMRI signals. The PPG drops are interpreted as systemic vasoconstrictive events, possibly related to intermittent increases in sympathetic tone related to fluctuations in arousal state. The counter-intuitive polarity of the WM signal is explained by long blood transit times in the medullary vasculature of WM, which cause blood oxygenation loss and a substantial timing mismatch between blood volume and blood oxygenation effects. A similar mechanism may explain previous findings of negative WM signals around large draining veins during both task- and resting-state fMRI.

Sparse coding reveals greater functional connectivity in female brains during naturalistic emotional experience.

Functional neuroimaging is widely used to examine changes in brain function associated with age, gender or neuropsychiatric conditions. FMRI (functional magnetic resonance imaging) studies employ either laboratory-designed tasks that engage the brain with abstracted and repeated stimuli, or resting state paradigms with little behavioral constraint. Recently, novel neuroimaging paradigms using naturalistic stimuli are gaining increasing attraction, as they offer an ecologically-valid condition to approximate brain function in real life. Wider application of naturalistic paradigms in exploring individual differences in brain function, however, awaits further advances in statistical methods for modeling dynamic and complex dataset. Here, we developed a novel data-driven strategy that employs group sparse representation to assess gender differences in brain responses during naturalistic emotional experience. Comparing to independent component analysis (ICA), sparse coding algorithm considers the intrinsic sparsity of neural coding and thus could be more suitable in modeling dynamic whole-brain fMRI signals. An online dictionary learning and sparse coding algorithm was applied to the aggregated fMRI signals from both groups, which was subsequently factorized into a common time series signal dictionary matrix and the associated weight coefficient matrix. Our results demonstrate that group sparse representation can effectively identify gender differences in functional brain network during natural viewing, with improved sensitivity and reliability over ICA-based method. Group sparse representation hence offers a superior data-driven strategy for examining brain function during naturalistic conditions, with great potential for clinical application in neuropsychiatric disorders.

Automatic Recognition of fMRI-Derived Functional Networks Using 3-D Convolutional Neural Networks.

Current functional magnetic resonance imaging (fMRI) data modeling techniques, such as independent component analysis and sparse coding methods, can effectively reconstruct dozens or hundreds of concurrent interacting functional brain networks simultaneously from the whole brain fMRI signals. However, such reconstructed networks have no correspondences across different subjects. Thus, automatic, effective, and accurate classification and recognition of these large numbers of fMRI-derived functional brain networks are very important for subsequent steps of functional brain analysis in cognitive and clinical neuroscience applications. However, this task is still a challenging and open problem due to the tremendous variability of various types of functional brain networks and the presence of various sources of noises. In recognition of the fact that convolutional neural networks (CNN) has superior capability of representing spatial patterns with huge variability and dealing with large noises, in this paper, we design, apply, and evaluate a deep 3-D CNN framework for automatic, effective, and accurate classification and recognition of large number of functional brain networks reconstructed by sparse representation of whole-brain fMRI signals. Our extensive experimental results based on the Human Connectome Project fMRI data showed that the proposed deep 3-D CNN can effectively and robustly perform functional networks classification and recognition tasks, while maintaining a high tolerance for mistakenly labeled training instances. This study provides a new deep learning approach for modeling functional connectomes based on fMRI data.

Joint representation of consistent structural and functional profiles for identification of common cortical landmarks.

In the brain mapping field, there have been significant interests in representation of structural/functional profiles to establish structural/functional landmark correspondences across individuals and populations. For example, from the structural perspective, our previous studies have identified hundreds of consistent DICCCOL (dense individualized and common connectivity-based cortical landmarks) landmarks across individuals and populations, each of which possess consistent DTI-derived fiber connection patterns. From the functional perspective, a large collection of well-characterized HAFNI (holistic atlases of functional networks and interactions) networks based on sparse representation of whole-brain fMRI signals have been identified in our prior studies. However, due to the remarkable variability of structural and functional architectures in the human brain, it is challenging for earlier studies to jointly represent the connectome-scale structural and functional profiles for establishing a common cortical architecture which can comprehensively encode both structural and functional characteristics across individuals. To address this challenge, we propose an effective computational framework to jointly represent the structural and functional profiles for identification of consistent and common cortical landmarks with both structural and functional correspondences across different brains based on DTI and fMRI data. Experimental results demonstrate that 55 structurally and functionally common cortical landmarks can be successfully identified.

Mixed Signals: On Separating Brain Signal from Noise

Accurate description of human brain function requires the separation of true neural signal from noise. Recent work examining spatial and temporal properties of whole-brain fMRI signals demonstrates how artifacts from a variety of sources can persist after rigorous processing, and highlights the lack of consensus on how to address this challenge.

Sources and implications of whole-brain fMRI signals in humans

Whole-brain fMRI signals are a subject of intense interest: variance in the global fMRI signal (the spatial mean of all signals in the brain) indexes subject arousal, and psychiatric conditions such as schizophrenia and autism have been characterized by differences in the global fMRI signal. Further, vigorous debates exist on whether global signals ought to be removed from fMRI data. However, surprisingly little research has focused on the empirical properties of whole-brain fMRI signals. Here we map the spatial and temporal properties of the global signal, individually, in 1000+ fMRI scans. Variance in the global fMRI signal is strongly linked to head motion, to hardware artifacts, and to respiratory patterns and their attendant physiologic changes. Many techniques used to prepare fMRI data for analysis fail to remove these uninteresting kinds of global signal fluctuations. Thus, many studies include, at the time of analysis, prominent global effects of yawns, breathing changes, and head motion, among other signals. Such artifacts will mimic dynamic neural activity and will spuriously alter signal covariance throughout the brain. Methods capable of isolating and removing global artifactual variance while preserving putative “neural” variance are needed; this paper adopts no position on the topic of global signal regression.

HAFNI-enabled largescale platform for neuroimaging informatics (HELPNI).

Tremendous efforts have thus been devoted on the establishment of functional MRI informatics systems that recruit a comprehensive collection of statistical/computational approaches for fMRI data analysis. However, the state-of-the-art fMRI informatics systems are especially designed for specific fMRI sessions or studies of which the data size is not really big, and thus has difficulty in handling fMRI ‘big data.’ Given the size of fMRI data are growing explosively recently due to the advancement of neuroimaging technologies, an effective and efficient fMRI informatics system which can process and analyze fMRI big data is much needed. To address this challenge, in this work, we introduce our newly developed informatics platform, namely, ‘HAFNI-enabled largescale platform for neuroimaging informatics (HELPNI).’ HELPNI implements our recently developed computational framework of sparse representation of whole-brain fMRI signals which is called holistic atlases of functional networks and interactions (HAFNI) for fMRI data analysis. HELPNI provides integrated solutions to archive and process large-scale fMRI data automatically and structurally, to extract and visualize meaningful results information from raw fMRI data, and to share open-access processed and raw data with other collaborators through web. We tested the proposed HELPNI platform using publicly available 1000 Functional Connectomes dataset including over 1200 subjects. We identified consistent and meaningful functional brain networks across individuals and populations based on resting state fMRI (rsfMRI) big data. Using efficient sampling module, the experimental results demonstrate that our HELPNI system has superior performance than other systems for large-scale fMRI data in terms of processing and storing the data and associated results much faster.

Sparsity-Constrained fMRI Decoding of Visual Saliency in Naturalistic Video Streams

Naturalistic stimuli such as video watching have been increasingly used in functional magnetic resonance imaging (fMRI)-based brain encoding and decoding studies since they can provide real and dynamic information that the human brain has to process in everyday life. In this paper, we propose a sparsity- constrained decoding model to explore whether bottom-up visual saliency in continuous video streams can be effectively decoded by brain activity recorded by fMRI, and to examine whether sparsity constraints can improve visual saliency decoding. Specifically, we use a biologically-plausible computational model to quantify the visual saliency in video streams, and adopt a sparse representation algorithm to learn the atomic fMRI signal dictionaries that are representative of the patterns of whole-brain fMRI signals. Sparse representation also links the learned atomic dictionary with the quantified video saliency. Experimental results show that the temporal visual saliency in video stream can be well decoded and the sparse constraints can improve the performance of fMRI decoding models.

Holistic atlases of functional networks and interactions reveal reciprocal organizational architecture of cortical function.

For decades, it has been largely unknown to what extent multiple functional networks spatially overlap/interact with each other and jointly realize the total cortical function. Here, by developing novel sparse representation of whole-brain fMRI signals and by using the recently publicly released large-scale Human Connectome Project high-quality fMRI data, we show that a number of reproducible and robust functional networks, including both task-evoked and resting state networks, are simultaneously distributed in distant neuroanatomic areas and substantially spatially overlapping with each other, thus forming an initial collection of holistic atlases of functional networks and interactions (HAFNIs). More interestingly, the HAFNIs revealed two distinct patterns of highly overlapped regions and highly specialized regions and exhibited that these two patterns of areas are reciprocally localized, revealing a novel organizational principle of cortical function.

Sparse representation of whole-brain fMRI signals for identification of functional networks.

There have been several recent studies that used sparse representation for fMRI signal analysis and activation detection based on the assumption that each voxel's fMRI signal is linearly composed of sparse components. Previous studies have employed sparse coding to model functional networks in various modalities and scales. These prior contributions inspired the exploration of whether/how sparse representation can be used to identify functional networks in a voxel-wise way and on the whole brain scale. This paper presents a novel, alternative methodology of identifying multiple functional networks via sparse representation of whole-brain task-based fMRI signals. Our basic idea is that all fMRI signals within the whole brain of one subject are aggregated into a big data matrix, which is then factorized into an over-complete dictionary basis matrix and a reference weight matrix via an effective online dictionary learning algorithm. Our extensive experimental results have shown that this novel methodology can uncover multiple functional networks that can be well characterized and interpreted in spatial, temporal and frequency domains based on current brain science knowledge. Importantly, these well-characterized functional network components are quite reproducible in different brains. In general, our methods offer a novel, effective and unified solution to multiple fMRI data analysis tasks including activation detection, de-activation detection, and functional network identification.

Correlated slow fluctuations in respiration, EEG, and BOLD fMRI

Low-frequency temporal fluctuations of physiological signals (<0.1 Hz), such as the respiration and cardiac pulse rate, occur naturally during rest and have been shown to be correlated with blood-oxygenation-level-dependent (BOLD) signal fluctuation. Such physiological signal modulations have been considered as sources of noise and their effects on BOLD signal are commonly removed in functional magnetic resonance imaging (fMRI) studies. However, possible neural correlates of the physiological fluctuations have not been considered nor examined in detail. In the present study we investigated this possibility by simultaneously acquiring electroencephalogram (EEG) with BOLD fMRI data, respiratory and cardiac waveforms in healthy human subjects at eyes-closed and eyes-open resting. We quantified the concurrent changes of the EEG power in the alpha frequency band, the respiration volume, and the cardiac pulse rate, then assessed the temporal correlations between alpha EEG power and physiological signal fluctuations. In addition, time-shifted time courses of alpha EEG power or physiological data were included as regressors to examine their correlations with the whole-brain BOLD fMRI signals. We observed a significant correlation between alpha EEG global field power and respiration, particularly at eyes-closed resting condition. Similar spatial patterns were observed between the correlation maps of BOLD with alpha EEG power and respiration, with negative correlations coinciding in the visual cortex, superior/middle temporal gyrus, inferior frontal gyrus, and inferior parietal lobule and positive correlations in the thalamus and caudate. Regressing out the physiological variations in the BOLD signal resulted in reduced correlation between BOLD and alpha EEG power. These results suggest a mutual link of neuronal origin between alpha EEG power, respiration, and BOLD signals.