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Pupillometry is a popular method because pupil size is easily measured, sensitive to central neural activity, and associated with behavior, cognition, emotion, and perception. Currently, there is no method for online monitoring phases of pupil size fluctuation. We introduce rtPupilPhase - an open source software that automatically detects trends in pupil size in real time, enabling novel implementations of real time pupillometry towards achieving numerous research and translational goals. We validated the performance of rtPupilPhase on human, rodent, and monkey pupil data and propose future applications of real time pupillometry.

Afterimages are illusory, visual conscious perceptions. A widely accepted theory is that afterimages are caused by retinal signaling that continues after the physical disappearance of a light stimulus. However, afterimages have been reported without preceding visual, sensory stimulation (e.g. conditioned afterimages and afterimages induced by illusory vision). These observations suggest the role of top-down brain mechanisms in afterimage conscious perception. Therefore, some afterimages may share perceptual features with sensory-independent conscious perceptions (e.g. imagery, hallucinations, and dreams) that occur without bottom-up sensory input. In the current investigation, we tested for a link between the vividness of visual imagery and afterimage conscious perception. Participants reported their vividness of visual imagery and perceived sharpness, contrast, and duration of negative afterimages. The afterimage perceptual features were acquired using perception matching paradigms that were validated on image stimuli. Relating these perceptual reports revealed that the vividness of visual imagery positively correlated with afterimage contrast and sharpness. These behavioral results support shared neural mechanisms between visual imagery and afterimages. However, we cannot exclude alternative explanations, including demand characteristics and afterimage perception reporting inaccuracy. This study encourages future research combining neurophysiology recording methods and afterimage paradigms to directly examine the neural mechanisms of afterimage conscious perception., Competing Interests: None declared., (Published by Oxford University Press 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Resting-state fMRI (rs-fMRI) scans-namely those lacking experimentally-controlled stimuli or cognitive demands-are often used to identify aberrant patterns of functional connectivity (FC) in clinical populations. To minimize interpretational uncertainty, researchers control for across-cohort disparities in age, gender, co-morbidities, and head motion. Yet, studies rarely, if ever, consider the possibility that systematic differences in inner experience (i.e., what subjects think and feel during the scan) may directly affect FC measures. Here we demonstrate that is the case using a rs-fMRI dataset comprising 471 scans annotated with experiential data. Wide-spread significant differences in FC are observed between scans that systematically differ in terms of reported in-scanner experience. Additionally, we show that FC can successfully predict specific aspects of in-scanner experience in a manner similar to how it predicts demographics, cognitive abilities, clinical outcomes and labels. Together, these results highlight the key role of in-scanner experience in shaping rs-fMRI estimates of FC.

Recognizing faces regardless of their viewpoint is critical for social interactions. Traditional theories hold that view-selective early visual representations gradually become tolerant to viewpoint changes along the ventral visual hierarchy. Newer theories, based on single-neuron monkey electrophysiological recordings, suggest a three-stage architecture including an intermediate face-selective patch abruptly achieving invariance to mirror-symmetric face views. Human studies combining neuroimaging and multivariate pattern analysis (MVPA) have provided convergent evidence of view selectivity in early visual areas. However, contradictory conclusions have been reached concerning the existence in humans of a mirror-symmetric representation like that observed in macaques. We believe these contradictions arise from low-level stimulus confounds and data analysis choices. To probe for low-level confounds, we analyzed images from two face databases. Analyses of image luminance and contrast revealed biases across face views described by even polynomials-i.e., mirror-symmetric. To explain major trends across neuroimaging studies, we constructed a network model incorporating three constraints: cortical magnification, convergent feedforward projections, and interhemispheric connections. Given the identified low-level biases, we show that a gradual increase of interhemispheric connections across network-layers is sufficient to replicate view-tuning in early processing stages and mirror-symmetry in later stages. Data analysis decisions-pattern dissimilarity measure and data recentering-accounted for the inconsistent observation of mirror-symmetry across prior studies. Pattern analyses of human fMRI data (of either sex) revealed biases compatible with our model. The model provides a unifying explanation of MVPA studies of viewpoint selectivity and suggests observations of mirror-symmetry originate from ineffectively normalized signal imbalances across different face views., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

Conventionally, analysis of functional MRI (fMRI) data relies on available information about the experimental paradigm to establish hypothesized models of brain activity. However, this information can be inaccurate, incomplete or unavailable in multiple scenarios such as resting-state, naturalistic paradigms or clinical conditions. In these cases, blind estimates of neuronal-related activity can be obtained with paradigm-free analysis methods such as hemodynamic deconvolution. Yet, current formulations of the hemodynamic deconvolution problem have three important limitations: (1) their efficacy strongly depends on the appropriate selection of regularization parameters, (2) being univariate, they do not take advantage of the information present across the brain, and (3) they do not provide any measure of statistical certainty associated with each detected event. Here we propose a novel approach that addresses all these limitations. Specifically, we introduce multivariate sparse paradigm free mapping (Mv-SPFM), a novel hemodynamic deconvolution algorithm that operates at the whole brain level and adds spatial information via a mixed-norm regularization term over all voxels. Additionally, Mv-SPFM employs a stability selection procedure that removes the need to select regularization parameters and also lets us obtain an estimate of the true probability of having a neuronal-related BOLD event at each voxel and time-point based on the area under the curve (AUC) of the stability paths. Besides, we present a formulation tailored for multi-echo fMRI acquisitions (MvME-SPFM), which allows us to better isolate fluctuations of BOLD origin on the basis of their linear dependence with the echo time (TE) and to assign physiologically interpretable units (i.e., changes in the apparent transverse relaxation ΔR 2 ∗ ) to the resulting deconvolved events. Remarkably, we demonstrate that Mv-SPFM achieves comparable performance even when using a single-echo formulation. We demonstrate that this algorithm outperforms existing state-of-the-art deconvolution approaches, and shows higher spatial and temporal agreement with the activation maps and BOLD signals obtained with a standard model-based linear regression approach, even at the level of individual neuronal events. Furthermore, we show that by employing stability selection, the performance of the algorithm depends less on the selection of temporal and spatial regularization parameters λ and ρ. Consequently, the proposed algorithm provides more reliable estimates of neuronal-related activity, here in terms of ΔR 2 ∗ , for the study of the dynamics of brain activity when no information about the timings of the BOLD events is available. This algorithm will be made publicly available as part of the splora Python package., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Whole-brain functional connectivity ( FC ) measured with functional MRI (fMRI) evolves over time in meaningful ways at temporal scales going from years (e.g., development) to seconds [e.g., within-scan time-varying FC ( tvFC )]. Yet, our ability to explore tvFC is severely constrained by its large dimensionality (several thousands). To overcome this difficulty, researchers often seek to generate low dimensional representations (e.g., 2D and 3D scatter plots) hoping those will retain important aspects of the data (e.g., relationships to behavior and disease progression). Limited prior empirical work suggests that manifold learning techniques ( MLTs )-namely those seeking to infer a low dimensional non-linear surface (i.e., the manifold) where most of the data lies-are good candidates for accomplishing this task. Here we explore this possibility in detail. First, we discuss why one should expect tv FC data to lie on a low dimensional manifold. Second, we estimate what is the intrinsic dimension ( ID ; i.e., minimum number of latent dimensions) of tvFC data manifolds. Third, we describe the inner workings of three state-of-the-art MLTs : Laplacian Eigenmaps ( LEs ), T-distributed Stochastic Neighbor Embedding ( T-SNE ), and Uniform Manifold Approximation and Projection ( UMAP ). For each method, we empirically evaluate its ability to generate neuro-biologically meaningful representations of tvFC data, as well as their robustness against hyper-parameter selection. Our results show that tvFC data has an ID that ranges between 4 and 26, and that ID varies significantly between rest and task states. We also show how all three methods can effectively capture subject identity and task being performed: UMAP and T-SNE can capture these two levels of detail concurrently, but LE could only capture one at a time. We observed substantial variability in embedding quality across MLTs , and within- MLT as a function of hyper-parameter selection. To help alleviate this issue, we provide heuristics that can inform future studies. Finally, we also demonstrate the importance of feature normalization when combining data across subjects and the role that temporal autocorrelation plays in the application of MLTs to tvFC data. Overall, we conclude that while MLTs can be useful to generate summary views of labeled tvFC data, their application to unlabeled data such as resting-state remains challenging., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gonzalez-Castillo, Fernandez, Lam, Handwerker, Pereira and Bandettini.)

Most neuroimaging studies display results that represent only a tiny fraction of the collected data. While it is conventional to present "only the significant results" to the reader, here we suggest that this practice has several negative consequences for both reproducibility and understanding. This practice hides away most of the results of the dataset and leads to problems of selection bias and irreproducibility, both of which have been recognized as major issues in neuroimaging studies recently. Opaque, all-or-nothing thresholding, even if well-intentioned, places undue influence on arbitrary filter values, hinders clear communication of scientific results, wastes data, is antithetical to good scientific practice, and leads to conceptual inconsistencies. It is also inconsistent with the properties of the acquired data and the underlying biology being studied. Instead of presenting only a few statistically significant locations and hiding away the remaining results, studies should "highlight" the former while also showing as much as possible of the rest. This is distinct from but complementary to utilizing data sharing repositories: the initial presentation of results has an enormous impact on the interpretation of a study. We present practical examples and extensions of this approach for voxelwise, regionwise and cross-study analyses using publicly available data that was analyzed previously by 70 teams (NARPS; Botvinik-Nezer, et al., 2020), showing that it is possible to balance the goals of displaying a full set of results with providing the reader reasonably concise and "digestible" findings. In particular, the highlighting approach sheds useful light on the kind of variability present among the NARPS teams' results, which is primarily a varied strength of agreement rather than disagreement. Using a meta-analysis built on the informative "highlighting" approach shows this relative agreement, while one using the standard "hiding" approach does not. We describe how this simple but powerful change in practice-focusing on highlighting results, rather than hiding all but the strongest ones-can help address many large concerns within the field, or at least to provide more complete information about them. We include a list of practical suggestions for results reporting to improve reproducibility, cross-study comparisons and meta-analyses., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Published by Elsevier Inc.)

Although resting-state functional magnetic resonance imaging (fMRI) studies have observed dynamically changing brain-wide networks of correlated activity, fMRI's dependence on hemodynamic signals makes results challenging to interpret. Meanwhile, emerging techniques for real-time recording of large populations of neurons have revealed compelling fluctuations in neuronal activity across the brain that are obscured by traditional trial averaging. To reconcile these observations, we use wide-field optical mapping to simultaneously record pan-cortical neuronal and hemodynamic activity in awake, spontaneously behaving mice. Some components of observed neuronal activity clearly represent sensory and motor function. However, particularly during quiet rest, strongly fluctuating patterns of activity across diverse brain regions contribute greatly to interregional correlations. Dynamic changes in these correlations coincide with changes in arousal state. Simultaneously acquired hemodynamics depict similar brain-state-dependent correlation shifts. These results support a neural basis for dynamic resting-state fMRI, while highlighting the importance of brain-wide neuronal fluctuations in the study of brain state., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Designing and executing a good quality control (QC) process is vital to robust and reproducible science and is often taught through hands on training. As FMRI research trends toward studies with larger sample sizes and highly automated processing pipelines, the people who analyze data are often distinct from those who collect and preprocess the data. While there are good reasons for this trend, it also means that important information about how data were acquired, and their quality, may be missed by those working at later stages of these workflows. Similarly, an abundance of publicly available datasets, where people (not always correctly) assume others already validated data quality, makes it easier for trainees to advance in the field without learning how to identify problematic data. This manuscript is designed as an introduction for researchers who are already familiar with fMRI, but who did not get hands on QC training or who want to think more deeply about QC. This could be someone who has analyzed fMRI data but is planning to personally acquire data for the first time, or someone who regularly uses openly shared data and wants to learn how to better assess data quality. We describe why good QC processes are important, explain key priorities and steps for fMRI QC, and as part of the FMRI Open QC Project, we demonstrate some of these steps by using AFNI software and AFNI's QC reports on an openly shared dataset. A good QC process is context dependent and should address whether data have the potential to answer a scientific question, whether any variation in the data has the potential to skew or hide key results, and whether any problems can potentially be addressed through changes in acquisition or data processing. Automated metrics are essential and can often highlight a possible problem, but human interpretation at every stage of a study is vital for understanding causes and potential solutions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Teves, Gonzalez-Castillo, Holness, Spurney, Bandettini and Handwerker.)

Wakefulness levels modulate estimates of functional connectivity (FC), and, if unaccounted for, can become a substantial confound in resting-state fMRI. Unfortunately, wakefulness is rarely monitored due to the need for additional concurrent recordings (e.g., eye tracking, EEG). Recent work has shown that strong fluctuations around 0.05Hz, hypothesized to be CSF inflow, appear in the fourth ventricle (FV) when subjects fall asleep, and that they correlate significantly with the global signal. The analysis of these fluctuations could provide an easy way to evaluate wakefulness in fMRI-only data and improve our understanding of FC during sleep. Here we evaluate this possibility using the 7T resting-state sample from the Human Connectome Project (HCP). Our results replicate the observation that fourth ventricle ultra-slow fluctuations (∼0.05Hz) with inflow-like characteristics (decreasing in intensity for successive slices) are present in scans during which subjects did not comply with instructions to keep their eyes open (i.e., drowsy scans). This is true despite the HCP data not being optimized for the detection of inflow-like effects. In addition, time-locked BOLD fluctuations of the same frequency could be detected in large portions of grey matter with a wide range of temporal delays and contribute in significant ways to our understanding of how FC changes during sleep. First, these ultra-slow fluctuations explain half of the increase in global signal that occurs during descent into sleep. Similarly, global shifts in FC between awake and sleep states are driven by changes in this slow frequency band. Second, they can influence estimates of inter-regional FC. For example, disconnection between frontal and posterior components of the Defulat Mode Network (DMN) typically reported during sleep were only detectable after regression of these ultra-slow fluctuations. Finally, we report that the temporal evolution of the power spectrum of these ultra-slow FV fluctuations can help us reproduce sample-level sleep patterns (e.g., a substantial number of subjects descending into sleep 3 minutes following scanning onset), partially rank scans according to overall drowsiness levels, and predict individual segments of elevated drowsiness (at 60 seconds resolution) with 71% accuracy., Competing Interests: Declaration of Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

The recent paper by Marek et al. 1 has shown that, to capture brain-wide associations using fMRI and MRI measures, thousands of individuals are required. These results can be potentially misunderstood to imply that MRI or fMRI lack sensitivity or specificity. This commentary discusses the demonstrated sensitivity of fMRI and focuses on methodology that may allow improvements in BWA studies. While individual variation may be an ultimate constraint, refinements in acquisition, population selection, and processing may bring about higher correlations., Competing Interests: Declaration of interests The authors declare no competing interests., (Published by Elsevier Inc.)

Resting-state fMRI (rsfMRI) reveals brain dynamics in a task-unconstrained environment as subjects let their minds wander freely. Consequently, resting subjects navigate a rich space of cognitive and perceptual states (i.e., ongoing experience). How this ongoing experience shapes rsfMRI summary metrics (e.g., functional connectivity) is unknown, yet likely to contribute uniquely to within- and between-subject differences. Here we argue that understanding the role of ongoing experience in rsfMRI requires access to standardized, temporally resolved, scientifically validated first-person descriptions of those experiences. We suggest best practices for obtaining those descriptions via introspective methods appropriately adapted for use in fMRI research. We conclude with a set of guidelines for fusing these two data types to answer pressing questions about the etiology of rsfMRI., (Copyright © 2021 the authors.)

Humans process faces by using a network of face-selective regions distributed across the brain. Neuropsychological patient studies demonstrate that focal damage to nodes in this network can impair face recognition, but such patients are rare. We approximated the effects of damage to the face network in neurologically normal human participants by using theta burst transcranial magnetic stimulation (TBS). Multi-echo functional magnetic resonance imaging (fMRI) resting-state data were collected pre- and post-TBS delivery over the face-selective right superior temporal sulcus (rpSTS), or a control site in the right motor cortex. Results showed that TBS delivered over the rpSTS reduced resting-state connectivity across the extended face processing network. This connectivity reduction was observed not only between the rpSTS and other face-selective areas, but also between nonstimulated face-selective areas across the ventral, medial, and lateral brain surfaces (e.g., between the right amygdala and bilateral fusiform face areas and occipital face areas). TBS delivered over the motor cortex did not produce significant changes in resting-state connectivity across the face processing network. These results demonstrate that, even without task-induced fMRI signal changes, disrupting a single node in a brain network can decrease the functional connectivity between nodes in that network that have not been directly stimulated., Competing Interests: Competing Interests: The authors have declared that no competing interests exist., (No rights reserved. This work was authored as part of the Contributor’s official duties as an Employee of the United States Government and is therefore the work of the United States Government. In accordance with 17 U.S.C. 105, no copyright protection is available for such works under U.S. law.)

We compared resting state (RS) functional connectivity and task-based fMRI to lateralize language dominance in 30 epilepsy patients (mean age = 33; SD = 11; 12 female), a measure used for presurgical planning. Language laterality index (LI) was calculated from task fMRI in frontal, temporal, and frontal + temporal regional masks using LI bootstrap method from SPM12. RS language LI was assessed using two novel methods of calculating RS language LI from bilateral Broca's area seed based connectivity maps across regional masks and multiple thresholds (p < .05, p < .01, p < .001, top 10% connections). We compared LI from task and RS fMRI continuous values and dominance classifications. We found significant positive correlations between task LI and RS LI when functional connectivity thresholds were set to the top 10% of connections. Concordance of dominance classifications ranged from 20% to 30% for the intrahemispheric resting state LI method and 50% to 63% for the resting state LI intra- minus interhemispheric difference method. Approximately 40% of patients left dominant on task showed RS bilateral dominance. There was no difference in LI concordance between patients with right-sided and left-sided resections. Early seizure onset (<6 years old) was not associated with atypical language dominance during task-based or RS fMRI. While a relationship between task LI and RS LI exists in patients with epilepsy, language dominance is less lateralized on RS than task fMRI. Concordance of language dominance classifications between task and resting state fMRI depends on brain regions surveyed and RS LI calculation method., (Published [2020]. This article is a U.S. Government work and is in the public domain in the USA.)

Brain functional connectivity (FC) changes have been measured across seconds using fMRI. This is true for both rest and task scenarios. Moreover, it is well accepted that task engagement alters FC, and that dynamic estimates of FC during and before task events can help predict their nature and performance. Yet, when it comes to dynamic FC (dFC) during rest, there is no consensus about its origin or significance. Some argue that rest dFC reflects fluctuations in on-going cognition, or is a manifestation of intrinsic brain maintenance mechanisms, which could have predictive clinical value. Conversely, others have concluded that rest dFC is mostly the result of sampling variability, head motion or fluctuating sleep states. Here, we present novel analyses suggesting that rest dFC is influenced by short periods of spontaneous cognitive-task-like processes, and that the cognitive nature of such mental processes can be inferred blindly from the data. As such, several different behaviorally relevant whole-brain FC configurations may occur during a single rest scan even when subjects were continuously awake and displayed minimal motion. In addition, using low dimensional embeddings as visualization aids, we show how FC states-commonly used to summarize and interpret resting dFC-can accurately and robustly reveal periods of externally imposed tasks; however, they may be less effective in capturing periods of distinct cognition during rest., (Published by Elsevier Inc.)

This work introduces a novel algorithm for deconvolution of the BOLD signal in multi-echo fMRI data: Multi-echo Sparse Paradigm Free Mapping (ME-SPFM). Assuming a linear dependence of the BOLD percent signal change on the echo time (TE) and using sparsity-promoting regularized least squares estimation, ME-SPFM yields voxelwise time-varying estimates of the changes in the apparent transverse relaxation (ΔR 2 ⁎ ) without prior knowledge of the timings of individual BOLD events. Our results in multi-echo fMRI data collected during a multi-task event-related paradigm at 3 Tesla demonstrate that the maps of R 2 ⁎ changes obtained with ME-SPFM at the times of the stimulus trials show high spatial and temporal concordance with the activation maps and BOLD signals obtained with standard model-based analysis. This method yields estimates of ΔR 2 ⁎ having physiologically plausible values. Owing to its ability to blindly detect events, ME-SPFM also enables us to map ΔR 2 ⁎ associated with spontaneous, transient BOLD responses occurring between trials. This framework is a step towards deciphering the dynamic nature of brain activity in naturalistic paradigms, resting-state or experimental paradigms with unknown timing of the BOLD events., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Studies of visual temporal frequency preference typically examine frequencies under 20 Hz and measure local activity to evaluate the sensitivity of different cortical areas to variations in temporal frequencies. Most of these studies have not attempted to map preferred temporal frequency within and across visual areas, nor have they explored in detail, stimuli at gamma frequency, which recent research suggests may have potential clinical utility. In this study, we address this gap by using functional magnetic resonance imaging (fMRI) to measure response to flickering visual stimuli varying in frequency from 1 to 40 Hz. We apply stimulation in both a block design to examine task response and a steady-state design to examine functional connectivity. We observed distinct activation patterns between 1 Hz and 40 Hz stimuli. We also found that the correlation between medial thalamus and visual cortex was modulated by the temporal frequency. The modulation functions and tuned frequencies are different for the visual activity and thalamo-visual correlations. Using both fMRI activity and connectivity measurements, we show evidence for a temporal frequency specific organization across the human visual system., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Interest in real-time fMRI neurofeedback has grown exponentially over the past few years, both for use as a basic science research tool, and as part of the search for novel clinical interventions for neurological and psychiatric illnesses. In order to expand the range of questions which can be addressed with this tool however, new neurofeedback methods must be developed, going beyond feedback of activations in a single region. These new methods, several of which have already been proposed, are by their nature complex, involving many possible parameters. Here we suggest a framework for evaluating and optimizing algorithms for use in a real-time setting, before beginning the neurofeedback experiment, by offline simulations of algorithm output using a previously collected dataset. We demonstrate the application of this framework on the instantaneous proxy for correlations which we developed for training connectivity between different network nodes, identify the optimal parameters for use with this algorithm, and compare it to more traditional correlation methods. We also examine the effects of advanced imaging techniques, such as multi-echo acquisition, and the integration of these into the real-time processing stream., (Published by Elsevier Inc.)

Given the dynamic nature of the human brain, there has been an increasing interest in investigating short-term temporal changes in functional connectivity, also known as dynamic functional connectivity (dFC), i.e., the time-varying inter-regional statistical dependence of blood oxygenation level-dependent (BOLD) signal within the constraints of a single scan. Numerous methodologies have been proposed to characterize dFC during rest and task, but few studies have compared them in terms of their efficacy to capture behavioral and clinically relevant dynamics. This is mostly due to lack of a well-defined ground truth, especially for rest scans. In this study, with a multitask dataset (rest, memory, video, and math) serving as ground truth, we investigated the efficacy of several dFC estimation techniques at capturing cognitively relevant dFC modulation induced by external tasks. We evaluated two framewise methods (dFC estimates for a single time point): dynamic conditional correlation (DCC) and jackknife correlation (JC); and five window-based methods: sliding window correlation (SWC), sliding window correlation with L1-regularization (SWC&#95;L1), a combination of DCC and SWC called moving average DCC (DCC&#95;MA), multiplication of temporal derivatives (MTD), and a variant of jackknife correlation called delete-d jackknife correlation (dJC). The efficacy is defined as each dFC metric's ability to successfully subdivide multitask scans into cognitively homogenous segments (even if those segments are not temporally continuous). We found that all window-based dFC methods performed well for commonly used window lengths (WL ≥ 30sec), with sliding window methods (SWC, SWC&#95;L1) as well as the hybrid DCC&#95;MA approach performing slightly better. For shorter window lengths (WL ≤ 15sec), DCC&#95;MA and dJC produced the best results. Neither framewise method (i.e., DCC and JC) led to dFC estimates with high accuracy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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 brain's 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., (Published by Elsevier Inc.)

Functional connectivity (FC) has been widely used to study the functional organization of temporally correlated and spatially distributed brain regions. Recent studies of FC dynamics, quantified by windowed correlations, provide new insights to analyze dynamic, context-dependent reconfiguration of brain networks. A set of reoccurring whole-brain connectivity patterns at rest, referred to as FC states, have been identified, hypothetically reflecting underlying cognitive processes or mental states. We posit that the mean FC information for a given subject represents a significant contribution to the group-level FC dynamics. We show that the subject-specific FC profile, termed as FC individuality, can be removed to increase sensitivity to cognitively relevant FC states. To assess the impact of the FC individuality and task-specific FC modulation on the group-level FC dynamics analysis, we generate and analyze group studies of four subjects engaging in four cognitive conditions (rest, simple math, two-back memory, and visual attention task). We also propose a model to quantitatively evaluate the effect of two factors, namely, subject-specific and task-specific modulation on FC dynamics. We show that FC individuality is a predominant factor in group-level FC variability, and the embedded cognitively relevant FC states are clearly visible after removing the individual's connectivity profile. Our results challenge the current understanding of FC states and emphasize the importance of individual heterogeneity in connectivity dynamics analysis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Brain functional connectivity (FC), as measured by blood oxygenation level-dependent (BOLD) signal, fluctuates at the scale of 10s of seconds. It has recently been found that whole-brain dynamic FC (dFC) patterns contain sufficient information to permit identification of ongoing tasks. Here, we hypothesize that dFC patterns carry fine-grained information that allows for tracking short-term task engagement levels (i.e., 10s of seconds long). To test this hypothesis, 25 subjects were scanned continuously for 25 min while they performed and transitioned between four different tasks: working memory, visual attention, math, and rest. First, we estimated dFC patterns by using a sliding window approach. Next, we extracted two engagement-specific FC patterns representing active engagement and passive engagement by using k -means clustering. Then, we derived three metrics from whole-brain dFC patterns to track engagement level, that is, dissimilarity between dFC patterns and engagement-specific FC patterns, and the level of brainwide integration level. Finally, those engagement markers were evaluated against windowed task performance by using a linear mixed effects model. Significant relationships were observed between abovementioned metrics and windowed task performance for the working memory task only. These findings partially confirm our hypothesis and underscore the potential of whole-brain dFC to track short-term task engagement levels., Competing Interests: Competing Interests: The authors have declared that no competing interests exist.

Little is known about how our brains dynamically adapt for efficient functioning. Most previous work has focused on analyzing changes in co-fluctuations between a set of brain regions over several temporal segments of the data. We argue that by collapsing data in space or time, we stand to lose useful information about the brain's dynamical organization. Here we use Topological Data Analysis to reveal the overall organization of whole-brain activity maps at a single-participant level-as an interactive representation-without arbitrarily collapsing data in space or time. Using existing multitask fMRI datasets, with the known ground truth about the timing of transitions from one task-block to next, our approach tracks both within- and between-task transitions at a much faster time scale (~4-9 s) than before. The individual differences in the revealed dynamical organization predict task performance. In summary, our approach distills complex brain dynamics into interactive and behaviorally relevant representations.

Sustaining attention to the task at hand is a crucial part of everyday life, from following a lecture at school to maintaining focus while driving. Lapses in sustained attention are frequent and often problematic, with conditions such as attention deficit hyperactivity disorder affecting millions of people worldwide. Recent work has had some success in finding signatures of sustained attention in whole-brain functional connectivity (FC) measures during basic tasks, but since FC can be dynamic and task-dependent, it remains unclear how fully these signatures would generalize to a more complex and naturalistic scenario. To this end, we used a previously defined whole-brain FC network - a marker of attention that was derived from a sustained attention task - to predict the ability of participants to recall material during a free-viewing reading task. Though the predictive network was trained on a different task and set of participants, the strength of FC in the sustained attention network predicted reading recall significantly better than permutation tests where behavior was scrambled to simulate chance performance. To test the generalization of the method used to derive the sustained attention network, we applied the same method to our reading task data to find a new FC network whose strength specifically predicts reading recall. Even though the sustained attention network provided significant prediction of recall, the reading network was more predictive of recall accuracy. The new reading network's spatial distribution indicates that reading recall is highest when temporal pole regions have higher FC with left occipital regions and lower FC with bilateral supramarginal gyrus. Right cerebellar to right frontal connectivity is also indicative of poor reading recall. We examine these and other differences between the two predictive FC networks, providing new insight into the task-dependent nature of FC-based performance metrics., (Published by Elsevier Inc.)

The bed nucleus of the stria terminalis (BNST) and central amygdala (CeA) of the extended amygdala are small, anatomically interconnected brain regions. They are thought to mediate responses to sustained, unpredictable threat stimuli and phasic, predictable threat stimuli, respectively. They perform these operations largely through their interconnected networks. In two previous studies, we mapped and contrasted the resting functional connectivity networks of the BNST and CeA at 7 Tesla with high resolution. This follow-up study investigates the changes in functional connectivity of these structures during sustained anticipation of electric shock. Results show that the BNST and CeA become less strongly coupled with the ventromedial prefrontal cortex (vmPFC), cingulate, and nucleus accumbens in shock threat relative to a safety condition. In addition, the CeA becomes more strongly coupled with the thalamus under threat. An exploratory, whole-brain connectivity analysis reveals that, although the BNST/CeA exhibits generally decreased connectivity, many other cortical regions demonstrate greater coupling under threat than safety. Understanding the differential network structures of these two regions and how they contribute to processing under threat will help elucidate the building blocks of the anxious state.

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., (Published by Elsevier Inc.)

The existence of abnormal connectivity patterns between resting state networks in neuropsychiatric disorders, including Autism Spectrum Disorder (ASD), has been well established. Traditional treatment methods in ASD are limited, and do not address the aberrant network structure. Using real-time fMRI neurofeedback, we directly trained three brain nodes in participants with ASD, in which the aberrant connectivity has been shown to correlate with symptom severity. Desired network connectivity patterns were reinforced in real-time, without participants' awareness of the training taking place. This training regimen produced large, significant long-term changes in correlations at the network level, and whole brain analysis revealed that the greatest changes were focused on the areas being trained. These changes were not found in the control group. Moreover, changes in ASD resting state connectivity following the training were correlated to changes in behavior, suggesting that neurofeedback can be used to directly alter complex, clinically relevant network connectivity patterns.

Here we report an exploratory within-subject variance decomposition analysis conducted on a task-based fMRI dataset with an unusually large number of repeated measures (i.e., 500 trials in each of three different subjects) distributed across 100 functional scans and 9 to 10 different sessions. Within-subject variance was segregated into four primary components: variance across-sessions, variance across-runs within a session, variance across-blocks within a run, and residual measurement/modeling error. Our results reveal inhomogeneous and distinct spatial distributions of these variance components across significantly active voxels in grey matter. Measurement error is dominant across the whole brain. Detailed evaluation of the remaining three components shows that across-session variance is the second largest contributor to total variance in occipital cortex, while across-runs variance is the second dominant source for the rest of the brain. Network-specific analysis revealed that across-block variance contributes more to total variance in higher-order cognitive networks than in somatosensory cortex. Moreover, in some higher-order cognitive networks across-block variance can exceed across-session variance. These results help us better understand the temporal (i.e., across blocks, runs and sessions) and spatial distributions (i.e., across different networks) of within-subject natural variability in estimates of task responses in fMRI. They also suggest that different brain regions will show different natural levels of test-retest reliability even in the absence of residual artifacts and sufficiently high contrast-to-noise measurements. Further confirmation with a larger sample of subjects and other tasks is necessary to ensure generality of these results., (Published by Elsevier Inc.)

In fMRI research, one often aims to examine activation in specific functional regions of interest (fROIs). Current statistical methods tend to localize fROIs inconsistently, focusing on avoiding detection of false activation. Not missing true activation is however equally important in this context. In this study, we explored the potential of an alternative-based thresholding (ABT) procedure, where evidence against the null hypothesis of no effect and evidence against a prespecified alternative hypothesis is measured to control both false positives and false negatives directly. The procedure was validated in the context of localizer tasks on simulated brain images and using a real data set of 100 runs per subject. Voxels categorized as active with ABT can be confidently included in the definition of the fROI, while inactive voxels can be confidently excluded. Additionally, the ABT method complements classic null hypothesis significance testing with valuable information by making a distinction between voxels that show evidence against both the null and alternative and voxels for which the alternative hypothesis cannot be rejected despite lack of evidence against the null.