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The use of submillimeter resolution functional magnetic resonance imaging (fMRI) is increasing in popularity due to the prospect of studying human brain activation non-invasively at the scale of cortical layers and columns. This method, known as laminar fMRI, is inherently signal-to-noise ratio (SNR)-limited, especially at lower field strengths, with the dominant noise source being of thermal origin. Furthermore, laminar fMRI is challenged with signal displacements due to draining vein effects in conventional gradient-echo blood oxygen level-dependent (BOLD) imaging contrasts. fMRI contrasts such as cerebral blood volume (CBV)-sensitive vascular space occupancy (VASO) sequences have the potential to mitigate draining vein effects. However, VASO comes along with another reduction in detection sensitivity. NOise Reduction with DIstribution Corrected (NORDIC) PCA (principal component analysis) is a denoising technique specifically aimed at suppressing thermal noise, which has proven useful for increasing the SNR of high-resolution functional data. While NORDIC has been examined for BOLD acquisitions, its application to VASO data has been limited, which was the focus of the present study. We present a preliminary analysis to evaluate NORDIC’s capability to suppress thermal noise while preserving the VASO signal across a wide parameter space at 3T. For the data presented here, with a proper set of parameters, NORDIC reduced thermal noise with minimal bias on the underlying signal and preserved spatial resolution. Denoising performance was found to vary with different implementation strategies and parameter choices, for which we provide recommendations. We conclude that when applied properly, NORDIC has the potential to overcome the sensitivity limitations of laminar-specific VASO fMRI. Since very few groups currently have 3T VASO data, by sharing our analysis and code, we can compile and compare the effects of NORDIC across a broader range of acquisition parameters and study designs. Such a communal effort will help develop robust recommendations that will increase the utility of laminar fMRI at lower field strengths.

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.

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.

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.

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.

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.