Javier Gonzalez-Castillo

Dynamic functional connectivity: promise, issues, and interpretations.

The brain must dynamically integrate, coordinate, and respond to internal and external stimuli across multiple time scales. Non-invasive measurements of brain activity with fMRI have greatly advanced our understanding of the large-scale functional organization supporting these fundamental features of brain function. Conclusions from previous resting-state fMRI investigations were based upon static descriptions of functional connectivity (FC), and only recently studies have begun to capitalize on the wealth of information contained within the temporal features of spontaneous BOLD FC. Emerging evidence suggests that dynamic FC metrics may index changes in macroscopic neural activity patterns underlying critical aspects of cognition and behavior, though limitations with regard to analysis and interpretation remain. Here, we review recent findings, methodological considerations, neural and behavioral correlates, and future directions in the emerging field of dynamic FC investigations.

Whole-brain, time-locked activation with simple tasks revealed using massive averaging and model-free analysis

The brain is the bodys largest energy consumer, even in the absence of demanding tasks. Electrophysiologists report on-going neuronal firing during stimulation or task in regions beyond those of primary relationship to the perturbation. Although the biological origin of consciousness remains elusive, it is argued that it emerges from complex, continuous whole-brain neuronal collaboration. Despite converging evidence suggesting the whole brain is continuously working and adapting to anticipate and actuate in response to the environment, over the last 20 y, task-based functional MRI (fMRI) have emphasized a localizationist view of brain function, with fMRI showing only a handful of activated regions in response to task/stimulation. Here, we challenge that view with evidence that under optimal noise conditions, fMRI activations extend well beyond areas of primary relationship to the task; and blood-oxygen level-dependent signal changes correlated with task-timing appear in over 95% of the brain for a simple visual stimulation plus attention control task. Moreover, we show that response shape varies substantially across regions, and that whole-brain parcellations based on those differences produce distributed clusters that are anatomically and functionally meaningful, symmetrical across hemispheres, and reproducible across subjects. These findings highlight the exquisite detail lying in fMRI signals beyond what is normally examined, and emphasize both the pervasiveness of false negatives, and how the sparseness of fMRI maps is not a result of localized brain function, but a consequence of high noise and overly strict predictive response models.

Tracking ongoing cognition in individuals using brief, whole-brain functional connectivity patterns

Significance Recently, it was shown that functional connectivity patterns exhibit complex spatiotemporal dynamics at the scale of tens of seconds. Of particular interest is the observation of a limited set of quasi-stable, whole-brain, recurring configurations—commonly referred to as functional connectivity states (FC states)—hypothesized to reflect the continuous flux of cognitive processes. Here, to test this hypothesis, subjects were continuously scanned as they engaged in and transitioned between mental states dictated by tasks. We demonstrate that there is a strong relationship between FC states and ongoing cognition that permits accurate tracking of mental states in individual subjects. We also demonstrate how informative changes in connectivity are not restricted solely to those regions with sustained elevations in activity during task performance. Functional connectivity (FC) patterns in functional MRI exhibit dynamic behavior on the scale of seconds, with rich spatiotemporal structure and limited sets of whole-brain, quasi-stable FC configurations (FC states) recurring across time and subjects. Based on previous evidence linking various aspects of cognition to group-level, minute-to-minute FC changes in localized connections, we hypothesized that whole-brain FC states may reflect the global, orchestrated dynamics of cognitive processing on the scale of seconds. To test this hypothesis, subjects were continuously scanned as they engaged in and transitioned between mental states dictated by tasks. FC states computed within windows as short as 22.5 s permitted robust tracking of cognition in single subjects with near perfect accuracy. Accuracy dropped markedly for subjects with the lowest task performance. Spatially restricting FC information decreased accuracy at short time scales, emphasizing the distributed nature of whole-brain FC dynamics, beyond univariate magnitude changes, as valuable markers of cognition.

The continuing challenge of understanding and modeling hemodynamic variation in fMRI

Interpretation of fMRI data depends on our ability to understand or model the shape of the hemodynamic response (HR) to a neural event. Although the HR has been studied almost since the beginning of fMRI, we are still far from having robust methods to account for the full range of known HR variation in typical fMRI analyses. This paper reviews how the authors and others contributed to our understanding of HR variation. We present an overview of studies that describe HR variation across voxels, healthy volunteers, populations, and dietary or pharmaceutical modulations. We also describe efforts to minimize the effects of HR variation in intrasubject, group, population, and connectivity analyses and the limits of these methods.

The spatial structure of resting state connectivity stability on the scale of minutes

Resting state functional MRI (rsfMRI) connectivity patterns are not temporally stable, but fluctuate in time at scales shorter than most common rest scan durations (5–10 min). Consequently, connectivity patterns for two different portions of the same scan can differ drastically. To better characterize this temporal variability and understand how it is spatially distributed across the brain, we scanned subjects continuously for 60 min, at a temporal resolution of 1 s, while they rested inside the scanner. We then computed connectivity matrices between functionally-defined regions of interest for non-overlapping 1 min windows, and classified connections according to their strength, polarity, and variability. We found that the most stable connections correspond primarily to inter-hemispheric connections between left/right homologous ROIs. However, only 32% of all within-network connections were classified as most stable. This shows that resting state networks have some long-term stability, but confirms the flexible configuration of these networks, particularly those related to higher order cognitive functions. The most variable connections correspond primarily to inter-hemispheric, across-network connections between non-homologous regions in occipital and frontal cortex. Finally we found a series of connections with negative average correlation, but further analyses revealed that such average negative correlations may be related to the removal of CSF signals during pre-processing. Using the same dataset, we also evaluated how similarity of within-subject whole-brain connectivity matrices changes as a function of window duration (used here as a proxy for scan duration). Our results suggest scanning for a minimum of 10 min to optimize within-subject reproducibility of connectivity patterns across the entire brain, rather than a few predefined networks.

Physiological noise effects on the flip angle selection in BOLD fMRI

This work addresses the choice of imaging flip angle in blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI). When noise of physiological origin becomes the dominant noise source in fMRI timeseries, it causes a nonlinear dependence of the temporal signal-to-noise ratio (TSNR) versus signal-to-noise ratio (SNR) that can be exploited to perform BOLD fMRI at angles well below the Ernst angle without any detrimental effect on our ability to detect sites of neuronal activation. We show, both experimentally and theoretically, that for situations where available SNR is high and physiological noise dominates over system/thermal noise, although TSNR still reaches it maximum for the Ernst angle, reduction of imaging flip angle well below this angle results in negligible loss in TSNR. Moreover, we provide a way to compute a suggested imaging flip angle, which constitutes a conservative estimate of the minimum flip angle that can be used under given experimental SNR and physiological noise levels. For our experimental conditions, this suggested angle equals 7.63° for the grey matter compartment, while the Ernst angle=77°. Finally, using data from eight subjects with a combined visual-motor task we show that imaging at angles as low as 9° introduces no significant differences in observed hemodynamic response time-course, contrast-to-noise ratio, voxel-wise effect size or statistical maps of activation as compared to imaging at 75° (an angle close to the Ernst angle). These results suggest that using low flip angles in BOLD fMRI experimentation to obtain benefits such as (1) reduction of RF power, (2) limitation of apparent T(1)-related inflow effects, (3) reduction of through-plane motion artifacts, (4) lower levels of physiological noise, and (5) improved tissue contrast is feasible when physiological noise dominates and SNR is high.

2015 Brainhack Proceedings

Table of contentsI1 Introduction to the 2015 Brainhack ProceedingsR. Cameron Craddock, Pierre Bellec, Daniel S. Margules, B. Nolan Nichols, Jörg P. PfannmöllerA1 Distributed collaboration: the case for the enhancement of Brainspell’s interfaceAmanPreet Badhwar, David Kennedy, Jean-Baptiste Poline, Roberto ToroA2 Advancing open science through NiDataBen Cipollini, Ariel RokemA3 Integrating the Brain Imaging Data Structure (BIDS) standard into C-PACDaniel Clark, Krzysztof J. Gorgolewski, R. Cameron CraddockA4 Optimized implementations of voxel-wise degree centrality and local functional connectivity density mapping in AFNIR. Cameron Craddock, Daniel J. ClarkA5 LORIS: DICOM anonymizerSamir Das, Cécile Madjar, Ayan Sengupta, Zia MohadesA6 Automatic extraction of academic collaborations in neuroimagingSebastien DeryA7 NiftyView: a zero-footprint web application for viewing DICOM and NIfTI filesWeiran DengA8 Human Connectome Project Minimal Preprocessing Pipelines to NipypeEric Earl, Damion V. Demeter, Kate Mills, Glad Mihai, Luka Ruzic, Nick Ketz, Andrew Reineberg, Marianne C. Reddan, Anne-Lise Goddings, Javier Gonzalez-Castillo, Krzysztof J. GorgolewskiA9 Generating music with resting-state fMRI dataCaroline Froehlich, Gil Dekel, Daniel S. Margulies, R. Cameron CraddockA10 Highly comparable time-series analysis in NitimeBen D. FulcherA11 Nipype interfaces in CBRAINTristan Glatard, Samir Das, Reza Adalat, Natacha Beck, Rémi Bernard, Najmeh Khalili-Mahani, Pierre Rioux, Marc-Étienne Rousseau, Alan C. EvansA12 DueCredit: automated collection of citations for software, methods, and dataYaroslav O. Halchenko, Matteo Visconti di Oleggio CastelloA13 Open source low-cost device to register dog’s heart rate and tail movementRaúl Hernández-Pérez, Edgar A. Morales, Laura V. CuayaA14 Calculating the Laterality Index Using FSL for Stroke Neuroimaging DataKaori L. Ito, Sook-Lei LiewA15 Wrapping FreeSurfer 6 for use in high-performance computing environmentsHans J. JohnsonA16 Facilitating big data meta-analyses for clinical neuroimaging through ENIGMA wrapper scriptsErik Kan, Julia Anglin, Michael Borich, Neda Jahanshad, Paul Thompson, Sook-Lei LiewA17 A cortical surface-based geodesic distance package for PythonDaniel S Margulies, Marcel Falkiewicz, Julia M HuntenburgA18 Sharing data in the cloudDavid O’Connor, Daniel J. Clark, Michael P. Milham, R. Cameron CraddockA19 Detecting task-based fMRI compliance using plan abandonment techniquesRamon Fraga Pereira, Anibal Sólon Heinsfeld, Alexandre Rosa Franco, Augusto Buchweitz, Felipe MeneguzziA20 Self-organization and brain functionJörg P. Pfannmöller, Rickson Mesquita, Luis C.T. Herrera, Daniela DenticoA21 The Neuroimaging Data Model (NIDM) APIVanessa Sochat, B Nolan NicholsA22 NeuroView: a customizable browser-base utilityAnibal Sólon Heinsfeld, Alexandre Rosa Franco, Augusto Buchweitz, Felipe MeneguzziA23 DIPY: Brain tissue classificationJulio E. Villalon-Reina, Eleftherios Garyfallidis

High-Resolution CBV-fMRI Allows Mapping of Laminar Activity and Connectivity of Cortical Input and Output in Human M1

Layer-dependent fMRI allows measurements of information flow in cortical circuits, as afferent and efferent connections terminate in different cortical layers. However, it is unknown to what level human fMRI is specific and sensitive enough to reveal directional functional activity across layers. To answer this question, we developed acquisition and analysis methods for blood-oxygen-level-dependent (BOLD) and cerebral-blood-volume (CBV)-based laminar fMRI and used these to discriminate four different tasks in the human motor cortex (M1). In agreement with anatomical data from animal studies, we found evidence for somatosensory and premotor input in superficial layers of M1 and for cortico-spinal motor output in deep layers. Laminar resting-state fMRI showed directional functional connectivity of M1 with somatosensory and premotor areas. Our findings demonstrate that CBV-fMRI can be used to investigate cortical activity in humans with unprecedented detail, allowing investigations of information flow between brain regions and outperforming conventional BOLD results that are often buried under vascular biases.

Auditory neuroimaging with fMRI and PET.

For much of the past 30 years, investigations of auditory perception and language have been enhanced or even driven by the use of functional neuroimaging techniques that specialize in localization of central responses. Beginning with investigations using positron emission tomography (PET) and gradually shifting primarily to usage of functional magnetic resonance imaging (fMRI), auditory neuroimaging has greatly advanced our understanding of the organization and response properties of brain regions critical to the perception of and communication with the acoustic world in which we live. As the complexity of the questions being addressed has increased, the techniques, experiments and analyses applied have also become more nuanced and specialized. A brief review of the history of these investigations sets the stage for an overview and analysis of how these neuroimaging modalities are becoming ever more effective tools for understanding the auditory brain. We conclude with a brief discussion of open methodological issues as well as potential clinical applications for auditory neuroimaging. This article is part of a Special Issue entitled Human Auditory Neuroimaging.

Task-based dynamic functional connectivity: Recent findings and open questions

The temporal evolution of functional connectivity (FC) within the confines of individual scans is nowadays often explored with functional neuroimaging. This is particularly true for resting-state; yet, FC-dynamics have also been investigated as subjects engage on numerous tasks. It is these research efforts that constitute the core of this survey. First, empirical observations on how FC differs between task and rest-independent of temporal scale-are reviewed, as they underscore how, despite overall preservation of network topography, the brains FC does reconfigure in systematic ways to accommodate task demands. Next, reports on the relationships between instantaneous FC and perception/performance in subsequent trials are discussed. Similarly, research where different aspects of task-concurrent FC-dynamics are explored or utilized to predict ongoing mental states are also examined. The manuscript finishes with an incomplete list of challenges that hopefully fuels future work in this vibrant area of neuroscientific research. Overall, this review concludes that task-concurrent FC-dynamics, when properly characterized, are relevant to behavior, and that their translational value holds considerable promise.