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Key Points There is growing concern about the reproducibility of scientific research, and neuroimaging research suffers from many features that are thought to lead to high levels of false results. Statistical power of neuroimaging studies has increased over time but remains relatively low, especially for group comparison studies. An analysis of effect sizes in the Human Connectome Project demonstrates that most functional MRI studies are not sufficiently powered to find reasonable effect sizes. Neuroimaging analysis has a high degree of flexibility in analysis methods, which can lead to inflated false-positive rates unless controlled for. Pre-registration of analysis plans and clear delineation of hypothesis-driven and exploratory research are potential solutions to this problem. The use of appropriate corrections for multiple tests has increased, but some common methods can have highly inflated false-positive rates. The use of non-parametric methods is encouraged to provide accurate correction for multiple tests. Software errors have the potential to lead to incorrect or irreproducible results. The adoption of improved software engineering methods and software testing strategies can help to reduce such problems. Reproducibility will be improved through greater transparency in methods reporting and through increased sharing of data and code. Neuroimaging techniques are increasingly applied by the wider neuroscience community. However, problems such as low statistical power, flexibility in data analysis and software issues pose challenges to interpreting neuroimaging data in a meaningful and reliable way. Here, Poldrack et al . discuss these and other problems, and suggest solutions. Functional neuroimaging techniques have transformed our ability to probe the neurobiological basis of behaviour and are increasingly being applied by the wider neuroscience community. However, concerns have recently been raised that the conclusions that are drawn from some human neuroimaging studies are either spurious or not generalizable. Problems such as low statistical power, flexibility in data analysis, software errors and a lack of direct replication apply to many fields, but perhaps particularly to functional MRI. Here, we discuss these problems, outline current and suggested best practices, and describe how we think the field should evolve to produce the most meaningful and reliable answers to neuroscientific questions.

Electroencephalography (EEG) recordings have been rarely included in large-scale studies. This is arguably not due to a lack of information that lies in EEG recordings but mainly on account of methodological issues. In many cases, particularly in clinical, pediatric and aging populations, the EEG has a high degree of artifact contamination and the quality of EEG recordings often substantially differs between subjects. Although there exists a variety of standardized preprocessing methods to clean EEG from artifacts, currently there is no method to objectively quantify the quality of preprocessed EEG. This makes the commonly accepted procedure of excluding subjects from analyses due to exceeding contamination of artifacts highly subjective. As a consequence, P-hacking is fostered, the replicability of results is decreased, and it is difficult to pool data from different study sites. In addition, in large-scale studies, data are collected over years or even decades, requiring software that controls and manages the preprocessing of ongoing and dynamically growing studies. To address these challenges, we developed Automagic, an open-source MATLAB toolbox that acts as a wrapper to run currently available preprocessing methods and offers objective standardized quality assessment for growing studies. The software is compatible with the Brain Imaging Data Structure (BIDS) standard and hence facilitates data sharing. In the present paper we outline the functionality of Automagic and examine the effect of applying combinations of methods on a sample of resting and task-based EEG data. This examination suggests that applying a pipeline of algorithms to detect artifactual channels in combination with Multiple Artifact Rejection Algorithm (MARA), an independent component analysis (ICA)-based artifact correction method, is sufficient to reduce a large extent of artifacts. •Automagic is a new EEG preprocessing toolbox for large and growing studies.•Automagic is open source and wraps a selection of available preprocessing tools.•Automagic is BIDS compatible and offers standardized quality metrics.•Bad channel detection and MARA sufficiently reduces artifacts from resting EEG.

The dependence between pairs of time series is commonly quantified by Pearson's correlation. However, if the time series are themselves dependent (i.e. exhibit temporal autocorrelation), the effective degrees of freedom (EDF) are reduced, the standard error of the sample correlation coefficient is biased, and Fisher's transformation fails to stabilise the variance. Since fMRI time series are notoriously autocorrelated, the issue of biased standard errors – before or after Fisher's transformation – becomes vital in individual-level analysis of resting-state functional connectivity (rsFC) and must be addressed anytime a standardised Z-score is computed. We find that the severity of autocorrelation is highly dependent on spatial characteristics of brain regions, such as the size of regions of interest and the spatial location of those regions. We further show that the available EDF estimators make restrictive assumptions that are not supported by the data, resulting in biased rsFC inferences that lead to distorted topological descriptions of the connectome on the individual level. We propose a practical “xDF” method that accounts not only for distinct autocorrelation in each time series, but instantaneous and lagged cross-correlation. We find the xDF correction varies substantially over node pairs, indicating the limitations of global EDF corrections used previously. In addition to extensive synthetic and real data validations, we investigate the impact of this correction on rsFC measures in data from the Young Adult Human Connectome Project, showing that accounting for autocorrelation dramatically changes fundamental graph theoretical measures relative to no correction. •Autocorrelation is a problem for sample correlation, breaking the variance-stabilising property of Fisher's transformation.•We show that fMRI autocorrelation varies systematically with region of interest size, and is heterogeneous over subjects.•Existing adjustment methods are themselves biased when true correlation is non-zero due to a confounding effect.•Our “xDF” method provides accurate Z-scores based on either of Pearson's or Fisher's transformed correlations.•Resting state fMRI autocorrelation considerably alters the graph theoretical description of human connectome.

Head motion systematically distorts clinical and research MRI data. Motion artifacts have biased findings from many structural and functional brain MRI studies. An effective way to remove motion artifacts is to exclude MRI data frames affected by head motion. However, such post-hoc frame censoring can lead to data loss rates of 50% or more in our pediatric patient cohorts. Hence, many scanner operators collect additional ‘buffer data’, an expensive practice that, by itself, does not guarantee sufficient high-quality MRI data for a given participant. Therefore, we developed an easy-to-setup, easy-to-use Framewise Integrated Real-time MRI Monitoring (FIRMM) software suite that provides scanner operators with head motion analytics in real-time, allowing them to scan each subject until the desired amount of low-movement data has been collected. Our analyses show that using FIRMM to identify the ideal scan time for each person can reduce total brain MRI scan times and associated costs by 50% or more. [Display omitted]

Head motion represents one of the greatest technical obstacles in magnetic resonance imaging (MRI) of the human brain. Accurate detection of artifacts induced by head motion requires precise estimation of movement. However, head motion estimates may be corrupted by artifacts due to magnetic main field fluctuations generated by body motion. In the current report, we examine head motion estimation in multiband resting state functional connectivity MRI (rs-fcMRI) data from the Adolescent Brain and Cognitive Development (ABCD) Study and comparison ‘single-shot’ datasets. We show that respirations contaminate movement estimates in functional MRI and that respiration generates apparent head motion not associated with functional MRI quality reductions. We have developed a novel approach using a band-stop filter that accurately removes these respiratory effects from motion estimates. Subsequently, we demonstrate that utilizing a band-stop filter improves post-processing fMRI data quality. Lastly, we demonstrate the real-time implementation of motion estimate filtering in our FIRMM (Framewise Integrated Real-Time MRI Monitoring) software package. •Respiratory perturbations of the main field inflate fMRI head motion estimates.•Breathing-related head motion artifacts compromise functional connectivity quality.•Notch filtering motion estimates (respiratory frequency band) improves data quality.•Motion estimate filtering can be achieved in real-time with FIRMM software.

For the robust estimation of evoked brain activity from functional Near-Infrared Spectroscopy (fNIRS) signals, it is crucial to reduce nuisance signals from systemic physiology and motion. The current best practice incorporates short-separation (SS) fNIRS measurements as regressors in a General Linear Model (GLM). However, several challenging signal characteristics such as non-instantaneous and non-constant coupling are not yet addressed by this approach and additional auxiliary signals are not optimally exploited. We have recently introduced a new methodological framework for the unsupervised multivariate analysis of fNIRS signals using Blind Source Separation (BSS) methods. Building onto the framework, in this manuscript we show how to incorporate the advantages of regularized temporally embedded Canonical Correlation Analysis (tCCA) into the supervised GLM. This approach allows flexible integration of any number of auxiliary modalities and signals. We provide guidance for the selection of optimal parameters and auxiliary signals for the proposed GLM extension. Its performance in the recovery of evoked HRFs is then evaluated using both simulated ground truth data and real experimental data and compared with the GLM with short-separation regression. Our results show that the GLM with tCCA significantly improves upon the current best practice, yielding significantly better results across all applied metrics: Correlation (HbO max. +45%), Root Mean Squared Error (HbO max. −55%), F-Score (HbO up to 3.25-fold) and p-value as well as power spectral density of the noise floor. The proposed method can be incorporated into the GLM in an easily applicable way that flexibly combines any available auxiliary signals into optimal nuisance regressors. This work has potential significance both for conventional neuroscientific fNIRS experiments as well as for emerging applications of fNIRS in everyday environments, medicine and BCI, where high Contrast to Noise Ratio is of importance for single trial analysis. •Reducing nuisance signals in fNIRS leads to more robust estimation of evoked brain activity.•GLM with tCCA flexibly combines any available auxiliary signals into optimal nuisance regressors.•The proposed method significantly improves upon conventional GLM with short separation regression.•Improved HRF recovery particularly for low Contrast to Noise Ratios and low number of stimuli/trials.

Multimodal neuroimaging is an emerging field that leverages multiple sources of information to diagnose specific brain disorders, especially when deep learning‐based AI algorithms are applied. The successful combination of different brain imaging modalities using deep learning remains a challenging yet crucial research topic. The integration of structural and functional modalities is particularly important for the diagnosis of various brain disorders, where structural information plays a crucial role in diseases such as Alzheimer's, while functional imaging is more critical for disorders such as schizophrenia. However, the combination of functional and structural imaging modalities can provide a more comprehensive diagnosis. In this work, we present MultiViT, a novel diagnostic deep learning model that utilizes vision transformers and cross‐attention mechanisms to effectively fuse information from 3D gray matter maps derived from structural MRI with functional network connectivity matrices obtained from functional MRI using the ICA algorithm. MultiViT achieves an AUC of 0.833, outperforming both our unimodal and multimodal baselines, enabling more accurate classification and diagnosis of schizophrenia. In addition, using vision transformer's unique attentional maps in combination with cross‐attentional mechanisms and brain function information, we identify critical brain regions in 3D gray matter space associated with the characteristics of schizophrenia. Our research not only significantly improves the accuracy of AI‐based automated imaging diagnostics for schizophrenia, but also pioneers a rational and advanced data fusion approach by replacing complex, high‐dimensional fMRI information with functional network connectivity, integrating it with representative structural data from 3D gray matter images, and further providing interpretative biomarker localization in a 3D structural space. The MultiViT model combines structural and functional neuroimaging data for the prediction of schizophrenia and integrates vision transformers with cross‐attention layers in order to preserve mutual information. The pipeline generates highly interpretable cross‐attention‐based brain saliency maps and emphasizes functional network connectivity patterns related to the disorder.

Increasing numbers of 7 T (7 T) magnetic resonance imaging (MRI) scanners are in research and clinical use. 7 T MRI can increase the scanning speed, spatial resolution and contrast-to-noise-ratio of many neuroimaging protocols, but technical challenges in implementation have been addressed in a variety of ways across sites. In order to facilitate multi-centre studies and ensure consistency of findings across sites, it is desirable that 7 T MRI sites implement common high-quality neuroimaging protocols that can accommodate different scanner models and software versions. With the installation of several new 7 T MRI scanners in the United Kingdom, the UK7T Network was established with an aim to create a set of harmonized structural and functional neuroimaging sequences and protocols. The Network currently includes five sites, which use three different scanner platforms, provided by two different vendors. Here we describe the harmonization of functional and anatomical imaging protocols across the three different scanner models, detailing the necessary changes to pulse sequences and reconstruction methods. The harmonized sequences are fully described, along with implementation details. Example datasets acquired from the same subject on all Network scanners are made available. Based on these data, an evaluation of the harmonization is provided. In addition, the implementation and validation of a common system calibration process is described. •Harmonised neuroimaging is established on 7 tesla MRI scanners at five sites.•Efficacy of harmonisation is demonstrated with scans on one subject at all sites.•Common calibration protocols achieve better standardisation than vendor’s own.•Protocols and data are available online for all current 7 tesla scanner models.

Most neuroscientific studies have focused on task-evoked activations (activity amplitudes at specific brain locations), providing limited insight into the functional relationships between separate brain locations. Task-state functional connectivity (FC) – statistical association between brain activity time series during task performance – moves beyond task-evoked activations by quantifying functional interactions during tasks. However, many task-state FC studies do not remove the first-order effect of task-evoked activations prior to estimating task-state FC. It has been argued that this results in the ambiguous inference \"likely active or interacting during the task\", rather than the intended inference \"likely interacting during the task\". Utilizing a neural mass computational model, we verified that task-evoked activations substantially and inappropriately inflate task-state FC estimates, especially in functional MRI (fMRI) data. Various methods attempting to address this problem have been developed, yet the efficacies of these approaches have not been systematically assessed. We found that most standard approaches for fitting and removing mean task-evoked activations were unable to correct these inflated correlations. In contrast, methods that flexibly fit mean task-evoked response shapes effectively corrected the inflated correlations without reducing effects of interest. Results with empirical fMRI data confirmed the model's predictions, revealing activation-induced task-state FC inflation for both Pearson correlation and psychophysiological interaction (PPI) approaches. These results demonstrate that removal of mean task-evoked activations using an approach that flexibly models task-evoked response shape is an important preprocessing step for valid estimation of task-state FC. •Computational model shows task inflation of functional connectivity estimates.•Hemodynamic responses cause task activations to further inflate estimates.•Standard approaches to remove task activations leave many false positives.•Methods that flexibly fit hemodynamic response shape effectively correct inflation.•Correction of functional connectivity inflation verified with empirical fMRI data.

The ability to discriminate signal from noise plays a key role in the analysis and interpretation of functional magnetic resonance imaging (fMRI) measures of brain activity. Over the past two decades, a number of major sources of noise have been identified, including system-related instabilities, subject motion, and physiological fluctuations. This article reviews the characteristics of the various noise sources as well as the mechanisms through which they affect the fMRI signal. Approaches for distinguishing signal from noise and the associated challenges are also reviewed. These challenges reflect the fact that some noise sources, such as respiratory activity, are generated by the same underlying brain networks that give rise to functional signals that are of interest.