Batch effects, undesirable sources of variability across multiple experiments, present significant challenges for scientific and clinical discoveries. Batch effects can (i) produce spurious signals and/or (ii) obscure genuine signals, contributing to the ongoing reproducibility crisis. Because batch effects are typically modeled as classical statistical effects, they often cannot differentiate between sources of variability due to confounding biases, which may lead them to erroneously conclude batch effects are present (or not). We formalize batch effects as causal effects, and introduce algorithms leveraging causal machinery, to address these concerns. Simulations illustrate that when non-causal methods provide the wrong answer, our methods either produce more accurate answers or “no answer,” meaning they assert the data are inadequate to confidently conclude on the presence of a batch effect. Applying our causal methods to 27 neuroimaging datasets yields qualitatively similar results: in situations where it is unclear whether batch effects are present, non-causal methods confidently identify (or fail to identify) batch effects, whereas our causal methods assert that it is unclear whether there are batch effects or not. In instances where batch effects should be discernable, our techniques produce different results from prior art, each of which produce results more qualitatively similar to not applying any batch effect correction to the data at all. This work, therefore, provides a causal framework for understanding the potential capabilities and limitations of analysis of multi-site data.

With a growing interest in personalized medicine, functional neuroimaging research has recently shifted focus from the evaluation of group-level summaries to associating individual differences in brain function with behaviors. However, this new focus brings forth challenges related to accurately measuring the sources of individual variation in functional signals. In this perspective, we highlight the impact of within-individual variations and discuss the concept of measurement reliability as a critical tool for accounting for within- and between-individual variations when measuring individual differences in brain function.

In recent years, brain research has indisputably entered a new epoch, driven by substantial methodological advances and digitally enabled data integration and modelling at multiple scales—from molecules to the whole brain. Major advances are emerging at the intersection of neuroscience with technology and computing. This new science of the brain combines high-quality research, data integration across multiple scales, a new culture of multidisciplinary large-scale collaboration, and translation into applications. As pioneered in Europe’s Human Brain Project (HBP), a systematic approach will be essential for meeting the coming decade’s pressing medical and technological challenges. The aims of this paper are to: develop a concept for the coming decade of digital brain research, discuss this new concept with the research community at large, identify points of convergence, and derive therefrom scientific common goals; provide a scientific framework for the current and future development of EBRAINS, a research infrastructure resulting from the HBP’s work; inform and engage stakeholders, funding organisations and research institutions regarding future digital brain research; identify and address the transformational potential of comprehensive brain models for artificial intelligence, including machine learning and deep learning; outline a collaborative approach that integrates reflection, dialogues, and societal engagement on ethical and societal opportunities and challenges as part of future neuroscience research.

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.

Neuroimaging research faces a crisis of reproducibility. With massive sample sizes and greater data complexity, this problem becomes more acute. Software that operates on imaging data defined using the Brain Imaging Data Structure (BIDS)—the BIDS App—has provided a substantial advance. However, even using BIDS Apps, a full audit trail of data processing is a necessary prerequisite for fully reproducible research. Obtaining a faithful record of the audit trail is challenging—especially for large datasets. Recently, the FAIRly big framework was introduced as a way to facilitate reproducible processing of large-scale data by leveraging DataLad—a version control system for data management. However, the current implementation of this framework was more of a proof of concept, and could not be immediately reused by other investigators for different use cases. Here, we introduce the B IDS A pp B oot s trap (BABS), a user-friendly and generalizable Python package for reproducible image processing at scale. BABS facilitates the reproducible application of BIDS Apps to large-scale datasets. Leveraging DataLad and the FAIRly big framework, BABS tracks the full audit trail of data processing in a scalable way by automatically preparing all scripts necessary for data processing and version tracking on high performance computing (HPC) systems. Currently, BABS supports jobs submissions and audits on Sun Grid Engine (SGE) and Slurm HPCs with a parsimonious set of programs. To demonstrate its scalability, we applied BABS to data from the Healthy Brain Network (HBN; n = 2,565). Taken together, BABS allows reproducible and scalable image processing and is broadly extensible via an open-source development model.