Neuroanatomical changes observed over the course of a human pregnancy.

Pregnancy is a period of profound hormonal and physiological change experienced by millions of women annually, yet the neural changes unfolding in the maternal brain throughout gestation have not been studied in humans. Leveraging precision imaging, we mapped neuroanatomical changes in an individual from preconception through two years postpartum. Pronounced decreases in gray matter volume and cortical thickness were evident across the brain, which stand in contrast to increases in white matter microstructural integrity, ventricle volume, and cerebrospinal fluid, with few regions untouched by the transition to motherhood. This dataset serves as the first comprehensive map of the human brain across gestation, providing an open-access resource for the brain imaging community to stimulate further exploration and discovery.

Visual imagery vividness correlates with afterimage conscious perception.

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. This study encourages future research combining neurophysiology recording methods and afterimage paradigms to directly examine the neural mechanisms of afterimage conscious perception.

The Past, Present, and Future of the Brain Imaging Data Structure (BIDS).

The Brain Imaging Data Structure (BIDS) is a community-driven standard for the organization of data and metadata from a growing range of neuroscience modalities. This paper is meant as a history of how the standard has developed and grown over time. We outline the principles behind the project, the mechanisms by which it has been extended, and some of the challenges being addressed as it evolves. We also discuss the lessons learned through the project, with the aim of enabling researchers in other domains to learn from the success of BIDS.

Manifold learning for fMRI time-varying functional connectivity.

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 tvFC 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.

Cortex-wide neural dynamics predict behavioral states and provide a neural basis for resting-state dynamic functional connectivity.

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.

The art and science of using quality control to understand and improve fMRI data.

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.

Highlight results, don't hide them: Enhance interpretation, reduce biases and improve reproducibility.

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.

Manifold Learning for fMRI time-varying FC.

Whole-brain functional connectivity ( FC ) measured with functional MRI (fMRI) evolve 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 seek to generate low dimensional representations (e.g., 2D and 3D scatter plots) expected to retain its most informative aspects (e.g., relationships to behavior, 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 (i.e., minimum number of latent dimensions; ID ) of tvFC data manifolds. Third, we describe the inner workings of three state-of-the-art MLTs : Laplacian Eigenmaps ( LE ), 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 L E 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.

Ultra-slow fMRI fluctuations in the fourth ventricle as a marker of drowsiness.

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.

Layer-specific activation in human primary somatosensory cortex during tactile temporal prediction error processing.

The human brain continuously generates predictions of incoming sensory input and calculates corresponding prediction errors from the perceived inputs to update internal predictions. In human primary somatosensory cortex (area 3b), different cortical layers are involved in receiving the sensory input and generation of error signals. It remains unknown, however, how the layers in the human area 3b contribute to the temporal prediction error processing. To investigate prediction error representation in the area 3b across layers, we acquired layer-specific functional magnetic resonance imaging (fMRI) data at 7T from human area 3b during a task of index finger poking with no-delay, short-delay and long-delay touching sequences. We demonstrate that all three tasks increased activity in both superficial and deep layers of area 3b compared to the random sensory input. The fMRI signal was differentially modulated solely in the deep layers rather than the superficial layers of area 3b by the delay time. Compared with the no-delay stimuli, activity was greater in the deep layers of area 3b during the short-delay stimuli but lower during the long-delay stimuli. This difference activity features in the superficial and deep layers suggest distinct functional contributions of area 3b layers to tactile temporal prediction error processing. The functional segregation in area 3b across layers may reflect that the excitatory and inhibitory interplay in the sensory cortex contributions to flexible communication between cortical layers or between cortical areas.

Topographical and laminar distribution of audiovisual processing within human planum temporale.

The brain is capable of integrating signals from multiple sensory modalities. Such multisensory integration can occur in areas that are commonly considered unisensory, such as planum temporale (PT) representing the auditory association cortex. However, the roles of different afferents (feedforward vs. feedback) to PT in multisensory processing are not well understood. Our study aims to understand that by examining laminar activity patterns in different topographical subfields of human PT under unimodal and multisensory stimuli. To this end, we adopted an advanced mesoscopic (sub-millimeter) fMRI methodology at 7 T by acquiring BOLD (blood-oxygen-level-dependent contrast, which has higher sensitivity) and VAPER (integrated blood volume and perfusion contrast, which has superior laminar specificity) signal concurrently, and performed all analyses in native fMRI space benefiting from an identical acquisition between functional and anatomical images. We found a division of function between visual and auditory processing in PT and distinct feedback mechanisms in different subareas. Specifically, anterior PT was activated more by auditory inputs and received feedback modulation in superficial layers. This feedback depended on task performance and likely arose from top-down influences from higher-order multimodal areas. In contrast, posterior PT was preferentially activated by visual inputs and received visual feedback in both superficial and deep layers, which is likely projected directly from the early visual cortex. Together, these findings provide novel insights into the mechanism of multisensory interaction in human PT at the mesoscopic spatial scale.

Different activation signatures in the primary sensorimotor and higher-level regions for haptic three-dimensional curved surface exploration.

Haptic object perception begins with continuous exploratory contact, and the human brain needs to accumulate sensory information continuously over time. However, it is still unclear how the primary sensorimotor cortex (PSC) interacts with these higher-level regions during haptic exploration over time. This functional magnetic resonance imaging (fMRI) study investigates time-dependent haptic object processing by examining brain activity during haptic 3D curve and roughness estimations. For this experiment, we designed sixteen haptic stimuli (4 kinds of curves × 4 varieties of roughness) for the haptic curve and roughness estimation tasks. Twenty participants were asked to move their right index and middle fingers along the surface twice and to estimate one of the two features-roughness or curvature-depending on the task instruction. We found that the brain activity in several higher-level regions (e.g., the bilateral posterior parietal cortex) linearly increased as the number of curves increased during the haptic exploration phase. Surprisingly, we found that the contralateral PSC was parametrically modulated by the number of curves only during the late exploration phase but not during the early exploration phase. In contrast, we found no similar parametric modulation activity patterns during the haptic roughness estimation task in either the contralateral PSC or in higher-level regions. Thus, our findings suggest that haptic 3D object perception is processed across the cortical hierarchy, whereas the contralateral PSC interacts with other higher-level regions across time in a manner that is dependent upon the features of the object.

Theta-burst TMS to the posterior superior temporal sulcus decreases resting-state fMRI connectivity across the face processing network.

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.

Fast detection and reduction of local transient artifacts in resting-state fMRI.

Image quality control (QC) is a critical and computationally intensive component of functional magnetic resonance imaging (fMRI). Artifacts caused by physiologic signals or hardware malfunctions are usually identified and removed during data processing offline, well after scanning sessions are complete. A system with the computational efficiency to identify and remove artifacts during image acquisition would permit rapid adjustment of protocols as issues arise during experiments. To improve the speed and accuracy of QC and functional image correction, we developed Fast Anatomy-Based Image Correction (Fast ANATICOR) with newly implemented nuisance models and an improved pipeline. We validated its performance on a dataset consisting of normal scans and scans containing known hardware-driven artifacts. Fast ANATICOR's increased processing speed may make real-time QC and image correction feasible as compared with the existing offline method.

Idiosynchrony: From shared responses to individual differences during naturalistic neuroimaging.

Two ongoing movements in human cognitive neuroscience have researchers shifting focus from group-level inferences to characterizing single subjects, and complementing tightly controlled tasks with rich, dynamic paradigms such as movies and stories. Yet relatively little work combines these two, perhaps because traditional analysis approaches for naturalistic imaging data are geared toward detecting shared responses rather than between-subject variability. Here, we review recent work using naturalistic stimuli to study individual differences, and advance a framework for detecting structure in idiosyncratic patterns of brain activity, or "idiosynchrony". Specifically, we outline the emerging technique of inter-subject representational similarity analysis (IS-RSA), including its theoretical motivation and an empirical demonstration of how it recovers brain-behavior relationships during movie watching using data from the Human Connectome Project. We also consider how stimulus choice may affect the individual signal and discuss areas for future research. We argue that naturalistic neuroimaging paradigms have the potential to reveal meaningful individual differences above and beyond those observed during traditional tasks or at rest.

Sub-millimeter fMRI reveals multiple topographical digit representations that form action maps in human motor cortex.

The human brain coordinates a wide variety of motor activities. On a large scale, the cortical motor system is topographically organized such that neighboring body parts are represented by neighboring brain areas. This homunculus-like somatotopic organization along the central sulcus has been observed using neuroimaging for large body parts such as the face, hands and feet. However, on a finer scale, invasive electrical stimulation studies show deviations from this somatotopic organization that suggest an organizing principle based on motor actions rather than body part moved. It has not been clear how the action-map organization principle of the motor cortex in the mesoscopic (sub-millimeter) regime integrates into a body map organization principle on a macroscopic scale (cm). Here we developed and applied advanced mesoscopic (sub-millimeter) fMRI and analysis methodology to non-invasively investigate the functional organization topography across columnar and laminar structures in humans. Compared to previous methods, in this study, we could capture locally specific blood volume changes across entire brain regions along the cortical curvature. We find that individual fingers have multiple mirrored representations in the primary motor cortex depending on the movements they are involved in. We find that individual digits have cortical representations up to 3 â€‹mm apart from each other arranged in a column-like fashion. These representations are differentially engaged depending on whether the digits' muscles are used for different motor actions such as flexion movements, like grasping a ball or retraction movements like releasing a ball. This research provides a starting point for non-invasive investigation of mesoscale topography across layers and columns of the human cortex and bridges the gap between invasive electrophysiological investigations and large coverage non-invasive neuroimaging.

Imaging the spontaneous flow of thought: Distinct periods of cognition contribute to dynamic functional connectivity during rest.

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.

Layer-specific activation of sensory input and predictive feedback in the human primary somatosensory cortex.

When humans perceive a sensation, their brains integrate inputs from sensory receptors and process them based on their expectations. The mechanisms of this predictive coding in the human somatosensory system are not fully understood. We fill a basic gap in our understanding of the predictive processing of somatosensation by examining the layer-specific activity in sensory input and predictive feedback in the human primary somatosensory cortex (S1). We acquired submillimeter functional magnetic resonance imaging data at 7T (n = 10) during a task of perceived, predictable, and unpredictable touching sequences. We demonstrate that the sensory input from thalamic projects preferentially activates the middle layer, while the superficial and deep layers in S1 are more engaged for cortico-cortical predictive feedback input. These findings are pivotal to understanding the mechanisms of tactile prediction processing in the human somatosensory cortex.

Visual temporal frequency preference shows a distinct cortical architecture using fMRI.

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.

Time-varying whole-brain functional network connectivity coupled to task engagement.

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.