Toward Community-Driven Big Open Brain Science: Open Big Data and Tools for Structure, Function, and Genetics.

As acquiring bigger data becomes easier in experimental brain science, computational and statistical brain science must achieve similar advances to fully capitalize on these data. Tackling these problems will benefit from a more explicit and concerted effort to work together. Specifically, brain science can be further democratized by harnessing the power of community-driven tools, which both are built by and benefit from many different people with different backgrounds and expertise. This perspective can be applied across modalities and scales and enables collaborations across previously siloed communities.

Neurodesk: an accessible, flexible and portable data analysis environment for reproducible neuroimaging.

Neuroimaging research requires purpose-built analysis software, which is challenging to install and may produce different results across computing environments. The community-oriented, open-source Neurodesk platform ( https://www.neurodesk.org/ ) harnesses a comprehensive and growing suite of neuroimaging software containers. Neurodesk includes a browser-accessible virtual desktop, command-line interface and computational notebook compatibility, allowing for accessible, flexible, portable and fully reproducible neuroimaging analysis on personal workstations, high-performance computers and the cloud.

A guide to the BRAIN Initiative Cell Census Network data ecosystem.

Characterizing cellular diversity at different levels of biological organization and across data modalities is a prerequisite to understanding the function of cell types in the brain. Classification of neurons is also essential to manipulate cell types in controlled ways and to understand their variation and vulnerability in brain disorders. The BRAIN Initiative Cell Census Network (BICCN) is an integrated network of data-generating centers, data archives, and data standards developers, with the goal of systematic multimodal brain cell type profiling and characterization. Emphasis of the BICCN is on the whole mouse brain with demonstration of prototype feasibility for human and nonhuman primate (NHP) brains. Here, we provide a guide to the cellular and spatial approaches employed by the BICCN, and to accessing and using these data and extensive resources, including the BRAIN Cell Data Center (BCDC), which serves to manage and integrate data across the ecosystem. We illustrate the power of the BICCN data ecosystem through vignettes highlighting several BICCN analysis and visualization tools. Finally, we present emerging standards that have been developed or adopted toward Findable, Accessible, Interoperable, and Reusable (FAIR) neuroscience. The combined BICCN ecosystem provides a comprehensive resource for the exploration and analysis of cell types in the brain.

TemplateFlow: FAIR-sharing of multi-scale, multi-species brain models.

Reference anatomies of the brain ('templates') and corresponding atlases are the foundation for reporting standardized neuroimaging results. Currently, there is no registry of templates and atlases; therefore, the redistribution of these resources occurs either bundled within existing software or in ad hoc ways such as downloads from institutional sites and general-purpose data repositories. We introduce TemplateFlow as a publicly available framework for human and non-human brain models. The framework combines an open database with software for access, management, and vetting, allowing scientists to share their resources under FAIR-findable, accessible, interoperable, and reusable-principles. TemplateFlow enables multifaceted insights into brains across species, and supports multiverse analyses testing whether results generalize across standard references, scales, and in the long term, species.

Detecting suicide risk among U.S. servicemembers and veterans: a deep learning approach using social media data.

BACKGROUND: Military Servicemembers and Veterans are at elevated risk for suicide, but rarely self-identify to their leaders or clinicians regarding their experience of suicidal thoughts. We developed an algorithm to identify posts containing suicide-related content on a military-specific social media platform. METHODS: Publicly-shared social media posts (n = 8449) from a military-specific social media platform were reviewed and labeled by our team for the presence/absence of suicidal thoughts and behaviors and used to train several machine learning models to identify such posts. RESULTS: The best performing model was a deep learning (RoBERTa) model that incorporated post text and metadata and detected the presence of suicidal posts with relatively high sensitivity (0.85), specificity (0.96), precision (0.64), F1 score (0.73), and an area under the precision-recall curve of 0.84. Compared to non-suicidal posts, suicidal posts were more likely to contain explicit mentions of suicide, descriptions of risk factors (e.g. depression, PTSD) and help-seeking, and first-person singular pronouns. CONCLUSIONS: Our results demonstrate the feasibility and potential promise of using social media posts to identify at-risk Servicemembers and Veterans. Future work will use this approach to deliver targeted interventions to social media users at risk for suicide.

OME-Zarr: a cloud-optimized bioimaging file format with international community support.

A growing community is constructing a next-generation file format (NGFF) for bioimaging to overcome problems of scalability and heterogeneity. Organized by the Open Microscopy Environment (OME), individuals and institutes across diverse modalities facing these problems have designed a format specification process (OME-NGFF) to address these needs. This paper brings together a wide range of those community members to describe the cloud-optimized format itself-OME-Zarr-along with tools and data resources available today to increase FAIR access and remove barriers in the scientific process. The current momentum offers an opportunity to unify a key component of the bioimaging domain-the file format that underlies so many personal, institutional, and global data management and analysis tasks.

fMRIPrep: a robust preprocessing pipeline for functional MRI.

Preprocessing of functional magnetic resonance imaging (fMRI) involves numerous steps to clean and standardize the data before statistical analysis. Generally, researchers create ad hoc preprocessing workflows for each dataset, building upon a large inventory of available tools. The complexity of these workflows has snowballed with rapid advances in acquisition and processing. We introduce fMRIPrep, an analysis-agnostic tool that addresses the challenge of robust and reproducible preprocessing for fMRI data. fMRIPrep automatically adapts a best-in-breed workflow to the idiosyncrasies of virtually any dataset, ensuring high-quality preprocessing without manual intervention. By introducing visual assessment checkpoints into an iterative integration framework for software testing, we show that fMRIPrep robustly produces high-quality results on a diverse fMRI data collection. Additionally, fMRIPrep introduces less uncontrolled spatial smoothness than observed with commonly used preprocessing tools. fMRIPrep equips neuroscientists with an easy-to-use and transparent preprocessing workflow, which can help ensure the validity of inference and the interpretability of results.

Functional Alterations in Cerebellar Functional Connectivity in Anxiety Disorders.

Adolescents with anxiety disorders exhibit excessive emotional and somatic arousal. Neuroimaging studies have shown abnormal cerebral cortical activation and connectivity in this patient population. The specific role of cerebellar output circuitry, specifically the dentate nuclei (DN), in adolescent anxiety disorders remains largely unexplored. Resting-state functional connectivity analyses have parcellated the DN, the major output nuclei of the cerebellum, into three functional territories (FTs) that include default-mode, salience-motor, and visual networks. The objective of this study was to understand whether FTs of the DN are implicated in adolescent anxiety disorders. Forty-one adolescents (mean age 15.19 ± 0.82, 26 females) with one or more anxiety disorders and 55 age- and gender-matched healthy controls completed resting-state fMRI scans and a self-report survey on anxiety symptoms. Seed-to-voxel functional connectivity analyses were performed using the FTs from DN parcellation. Brain connectivity metrics were then correlated with State-Trait Anxiety Inventory (STAI) measures within each group. Adolescents with an anxiety disorder showed significant hyperconnectivity between salience-motor DN FT and cerebral cortical salience-motor regions compared to controls. Salience-motor FT connectivity with cerebral cortical sensorimotor regions was significantly correlated with STAI-trait scores in HC (R2 = 0.41). Here, we report DN functional connectivity differences in adolescents diagnosed with anxiety, as well as in HC with variable degrees of anxiety traits. These observations highlight the relevance of DN as a potential clinical and sub-clinical marker of anxiety.

Remote Digital Psychiatry for Mobile Mental Health Assessment and Therapy: MindLogger Platform Development Study.

BACKGROUND: Universal access to assessment and treatment of mental health and learning disorders remains a significant and unmet need. There are many people without access to care because of economic, geographic, and cultural barriers, as well as the limited availability of clinical experts who could help advance our understanding and treatment of mental health. OBJECTIVE: This study aims to create an open, configurable software platform to build clinical measures, mobile assessments, tasks, and interventions without programming expertise. Specifically, our primary requirements include an administrator interface for creating and scheduling recurring and customized questionnaires where end users receive and respond to scheduled notifications via an iOS or Android app on a mobile device. Such a platform would help relieve overwhelmed health systems and empower remote and disadvantaged subgroups in need of accurate and effective information, assessment, and care. This platform has the potential to advance scientific research by supporting the collection of data with instruments tailored to specific scientific questions from large, distributed, and diverse populations. METHODS: We searched for products that satisfy these requirements. We designed and developed a new software platform called MindLogger, which exceeds the requirements. To demonstrate the platform's configurability, we built multiple applets (collections of activities) within the MindLogger mobile app and deployed several of them, including a comprehensive set of assessments underway in a large-scale, longitudinal mental health study. RESULTS: Of the hundreds of products we researched, we found 10 that met our primary requirements with 4 that support end-to-end encryption, 2 that enable restricted access to individual users' data, 1 that provides open-source software, and none that satisfy all three. We compared features related to information presentation and data capture capabilities; privacy and security; and access to the product, code, and data. We successfully built MindLogger mobile and web applications, as well as web browser-based tools for building and editing new applets and for administering them to end users. MindLogger has end-to-end encryption, enables restricted access, is open source, and supports a variety of data collection features. One applet is currently collecting data from children and adolescents in our mental health study, and other applets are in different stages of testing and deployment for use in clinical and research settings. CONCLUSIONS: We demonstrated the flexibility and applicability of the MindLogger platform through its deployment in a large-scale, longitudinal, mobile mental health study and by building a variety of other mental health-related applets. With this release, we encourage a broad range of users to apply the MindLogger platform to create and test applets to advance health care and scientific research. We hope that increasing the availability of applets designed to assess and administer interventions will facilitate access to health care in the general population.

Neurodevelopmental and Psychiatric Symptoms in Patients with a Cyst Compressing the Cerebellum: an Ongoing Enigma.

A patient diagnosed with developmental delay, intellectual disability, and autistic and obsessive-compulsive symptoms was found to have a posterior fossa arachnoid cyst (PFAC) compressing the cerebellum. The patient was referred to our Ataxia Unit for consideration of surgical drainage of the cyst to improve his clinical constellation. This scenario led to an in-depth analysis including a literature review, functional resting-state MRI analysis of our patient compared to a group of controls, and genetic testing. While it is reasonable to consider that there may be a causal relationship between PFAC and neurodevelopmental or psychiatric symptoms in some patients, there is also a nontrivial prevalence of PFAC in the asymptomatic population and a significant possibility that many PFAC are incidental findings in the context of primary cognitive or psychiatric symptoms. Our functional MRI analysis is the first to examine brain function, and to report cerebellar dysfunction, in a patient presenting with cognitive/psychiatric symptoms found to have a structural abnormality compressing the cerebellum. These neuroimaging findings are inherently limited due to their correlational nature but provide unprecedented evidence suggesting that cerebellar compression may be associated with cerebellar dysfunction. Exome gene sequencing revealed additional etiological possibilities, highlighting the complexity of this field of cerebellar clinical and scientific practice. Our findings and discussion may guide future investigations addressing an important knowledge gap-namely, is there a link between cerebellar compression (including arachnoid cysts and possibly other forms of cerebellar compression such as Chiari malformation), cerebellar dysfunction (including fMRI abnormalities reported here), and neuropsychiatric symptoms?

Natural Language Processing Reveals Vulnerable Mental Health Support Groups and Heightened Health Anxiety on Reddit During COVID-19: Observational Study.

BACKGROUND: The COVID-19 pandemic is impacting mental health, but it is not clear how people with different types of mental health problems were differentially impacted as the initial wave of cases hit. OBJECTIVE: The aim of this study is to leverage natural language processing (NLP) with the goal of characterizing changes in 15 of the world's largest mental health support groups (eg, r/schizophrenia, r/SuicideWatch, r/Depression) found on the website Reddit, along with 11 non-mental health groups (eg, r/PersonalFinance, r/conspiracy) during the initial stage of the pandemic. METHODS: We created and released the Reddit Mental Health Dataset including posts from 826,961 unique users from 2018 to 2020. Using regression, we analyzed trends from 90 text-derived features such as sentiment analysis, personal pronouns, and semantic categories. Using supervised machine learning, we classified posts into their respective support groups and interpreted important features to understand how different problems manifest in language. We applied unsupervised methods such as topic modeling and unsupervised clustering to uncover concerns throughout Reddit before and during the pandemic. RESULTS: We found that the r/HealthAnxiety forum showed spikes in posts about COVID-19 early on in January, approximately 2 months before other support groups started posting about the pandemic. There were many features that significantly increased during COVID-19 for specific groups including the categories "economic stress," "isolation," and "home," while others such as "motion" significantly decreased. We found that support groups related to attention-deficit/hyperactivity disorder, eating disorders, and anxiety showed the most negative semantic change during the pandemic out of all mental health groups. Health anxiety emerged as a general theme across Reddit through independent supervised and unsupervised machine learning analyses. For instance, we provide evidence that the concerns of a diverse set of individuals are converging in this unique moment of history; we discovered that the more users posted about COVID-19, the more linguistically similar (less distant) the mental health support groups became to r/HealthAnxiety (ρ=-0.96, P<.001). Using unsupervised clustering, we found the suicidality and loneliness clusters more than doubled in the number of posts during the pandemic. Specifically, the support groups for borderline personality disorder and posttraumatic stress disorder became significantly associated with the suicidality cluster. Furthermore, clusters surrounding self-harm and entertainment emerged. CONCLUSIONS: By using a broad set of NLP techniques and analyzing a baseline of prepandemic posts, we uncovered patterns of how specific mental health problems manifest in language, identified at-risk users, and revealed the distribution of concerns across Reddit, which could help provide better resources to its millions of users. We then demonstrated that textual analysis is sensitive to uncover mental health complaints as they appear in real time, identifying vulnerable groups and alarming themes during COVID-19, and thus may have utility during the ongoing pandemic and other world-changing events such as elections and protests.

Situating the default-mode network along a principal gradient of macroscale cortical organization.

Understanding how the structure of cognition arises from the topographical organization of the cortex is a primary goal in neuroscience. Previous work has described local functional gradients extending from perceptual and motor regions to cortical areas representing more abstract functions, but an overarching framework for the association between structure and function is still lacking. Here, we show that the principal gradient revealed by the decomposition of connectivity data in humans and the macaque monkey is anchored by, at one end, regions serving primary sensory/motor functions and at the other end, transmodal regions that, in humans, are known as the default-mode network (DMN). These DMN regions exhibit the greatest geodesic distance along the cortical surface-and are precisely equidistant-from primary sensory/motor morphological landmarks. The principal gradient also provides an organizing spatial framework for multiple large-scale networks and characterizes a spectrum from unimodal to heteromodal activity in a functional metaanalysis. Together, these observations provide a characterization of the topographical organization of cortex and indicate that the role of the DMN in cognition might arise from its position at one extreme of a hierarchy, allowing it to process transmodal information that is unrelated to immediate sensory input.

Mindboggling morphometry of human brains.

Mindboggle (http://mindboggle.info) is an open source brain morphometry platform that takes in preprocessed T1-weighted MRI data and outputs volume, surface, and tabular data containing label, feature, and shape information for further analysis. In this article, we document the software and demonstrate its use in studies of shape variation in healthy and diseased humans. The number of different shape measures and the size of the populations make this the largest and most detailed shape analysis of human brains ever conducted. Brain image morphometry shows great potential for providing much-needed biological markers for diagnosing, tracking, and predicting progression of mental health disorders. Very few software algorithms provide more than measures of volume and cortical thickness, while more subtle shape measures may provide more sensitive and specific biomarkers. Mindboggle computes a variety of (primarily surface-based) shapes: area, volume, thickness, curvature, depth, Laplace-Beltrami spectra, Zernike moments, etc. We evaluate Mindboggle's algorithms using the largest set of manually labeled, publicly available brain images in the world and compare them against state-of-the-art algorithms where they exist. All data, code, and results of these evaluations are publicly available.

BIDS apps: Improving ease of use, accessibility, and reproducibility of neuroimaging data analysis methods.

The rate of progress in human neurosciences is limited by the inability to easily apply a wide range of analysis methods to the plethora of different datasets acquired in labs around the world. In this work, we introduce a framework for creating, testing, versioning and archiving portable applications for analyzing neuroimaging data organized and described in compliance with the Brain Imaging Data Structure (BIDS). The portability of these applications (BIDS Apps) is achieved by using container technologies that encapsulate all binary and other dependencies in one convenient package. BIDS Apps run on all three major operating systems with no need for complex setup and configuration and thanks to the comprehensiveness of the BIDS standard they require little manual user input. Previous containerized data processing solutions were limited to single user environments and not compatible with most multi-tenant High Performance Computing systems. BIDS Apps overcome this limitation by taking advantage of the Singularity container technology. As a proof of concept, this work is accompanied by 22 ready to use BIDS Apps, packaging a diverse set of commonly used neuroimaging algorithms.

Diffeomorphic functional brain surface alignment: Functional demons.

Aligning brain structures across individuals is a central prerequisite for comparative neuroimaging studies. Typically, registration approaches assume a strong association between the features used for alignment, such as macro-anatomy, and the variable observed, such as functional activation or connectivity. Here, we propose to use the structure of intrinsic resting state fMRI signal correlation patterns as a basis for alignment of the cortex in functional studies. Rather than assuming the spatial correspondence of functional structures between subjects, we have identified locations with similar connectivity profiles across subjects. We mapped functional connectivity relationships within the brain into an embedding space, and aligned the resulting maps of multiple subjects. We then performed a diffeomorphic alignment of the cortical surfaces, driven by the corresponding features in the joint embedding space. Results show that functional alignment based on resting state fMRI identifies functionally homologous regions across individuals with higher accuracy than alignment based on the spatial correspondence of anatomy. Further, functional alignment enables measurement of the strength of the anatomo-functional link across the cortex, and reveals the uneven distribution of this link. Stronger anatomo-functional dissociation was found in higher association areas compared to primary sensory- and motor areas. Functional alignment based on resting state features improves group analysis of task based functional MRI data, increasing statistical power and improving the delineation of task-specific core regions. Finally, a comparison of the anatomo-functional dissociation between cohorts is demonstrated with a group of left and right handed subjects.

NeuroVault.org: A repository for sharing unthresholded statistical maps, parcellations, and atlases of the human brain.

NeuroVault.org is dedicated to storing outputs of analyses in the form of statistical maps, parcellations and atlases, a unique strategy that contrasts with most neuroimaging repositories that store raw acquisition data or stereotaxic coordinates. Such maps are indispensable for performing meta-analyses, validating novel methodology, and deciding on precise outlines for regions of interest (ROIs). NeuroVault is open to maps derived from both healthy and clinical populations, as well as from various imaging modalities (sMRI, fMRI, EEG, MEG, PET, etc.). The repository uses modern web technologies such as interactive web-based visualization, cognitive decoding, and comparison with other maps to provide researchers with efficient, intuitive tools to improve the understanding of their results. Each dataset and map is assigned a permanent Universal Resource Locator (URL), and all of the data is accessible through a REST Application Programming Interface (API). Additionally, the repository supports the NIDM-Results standard and has the ability to parse outputs from popular FSL and SPM software packages to automatically extract relevant metadata. This ease of use, modern web-integration, and pioneering functionality holds promise to improve the workflow for making inferences about and sharing whole-brain statistical maps.

Crowdsourced estimation of cognitive decline and resilience in Alzheimer's disease.

Identifying accurate biomarkers of cognitive decline is essential for advancing early diagnosis and prevention therapies in Alzheimer's disease. The Alzheimer's disease DREAM Challenge was designed as a computational crowdsourced project to benchmark the current state-of-the-art in predicting cognitive outcomes in Alzheimer's disease based on high dimensional, publicly available genetic and structural imaging data. This meta-analysis failed to identify a meaningful predictor developed from either data modality, suggesting that alternate approaches should be considered for prediction of cognitive performance.

Identifying bias in models that detect vocal fold paralysis from audio recordings using explainable machine learning and clinician ratings.

Introduction: Detecting voice disorders from voice recordings could allow for frequent, remote, and low-cost screening before costly clinical visits and a more invasive laryngoscopy examination. Our goals were to detect unilateral vocal fold paralysis (UVFP) from voice recordings using machine learning, to identify which acoustic variables were important for prediction to increase trust, and to determine model performance relative to clinician performance. Methods: Patients with confirmed UVFP through endoscopic examination (N=77) and controls with normal voices matched for age and sex (N=77) were included. Voice samples were elicited by reading the Rainbow Passage and sustaining phonation of the vowel "a". Four machine learning models of differing complexity were used. SHapley Additive explanations (SHAP) was used to identify important features. Results: The highest median bootstrapped ROC AUC score was 0.87 and beat clinician's performance (range: 0.74 - 0.81) based on the recordings. Recording durations were different between UVFP recordings and controls due to how that data was originally processed when storing, which we can show can classify both groups. And counterintuitively, many UVFP recordings had higher intensity than controls, when UVFP patients tend to have weaker voices, revealing a dataset-specific bias which we mitigate in an additional analysis. Conclusion: We demonstrate that recording biases in audio duration and intensity created dataset-specific differences between patients and controls, which models used to improve classification. Furthermore, clinician's ratings provide further evidence that patients were over-projecting their voices and being recorded at a higher amplitude signal than controls. Interestingly, after matching audio duration and removing variables associated with intensity in order to mitigate the biases, the models were able to achieve a similar high performance. We provide a set of recommendations to avoid bias when building and evaluating machine learning models for screening in laryngology.

Identifying bias in models that detect vocal fold paralysis from audio recordings using explainable machine learning and clinician ratings.

Detecting voice disorders from voice recordings could allow for frequent, remote, and low-cost screening before costly clinical visits and a more invasive laryngoscopy examination. Our goals were to detect unilateral vocal fold paralysis (UVFP) from voice recordings using machine learning, to identify which acoustic variables were important for prediction to increase trust, and to determine model performance relative to clinician performance. Patients with confirmed UVFP through endoscopic examination (N = 77) and controls with normal voices matched for age and sex (N = 77) were included. Voice samples were elicited by reading the Rainbow Passage and sustaining phonation of the vowel "a". Four machine learning models of differing complexity were used. SHapley Additive exPlanations (SHAP) was used to identify important features. The highest median bootstrapped ROC AUC score was 0.87 and beat clinician's performance (range: 0.74-0.81) based on the recordings. Recording durations were different between UVFP recordings and controls due to how that data was originally processed when storing, which we can show can classify both groups. And counterintuitively, many UVFP recordings had higher intensity than controls, when UVFP patients tend to have weaker voices, revealing a dataset-specific bias which we mitigate in an additional analysis. We demonstrate that recording biases in audio duration and intensity created dataset-specific differences between patients and controls, which models used to improve classification. Furthermore, clinician's ratings provide further evidence that patients were over-projecting their voices and being recorded at a higher amplitude signal than controls. Interestingly, after matching audio duration and removing variables associated with intensity in order to mitigate the biases, the models were able to achieve a similar high performance. We provide a set of recommendations to avoid bias when building and evaluating machine learning models for screening in laryngology.

Resting-State Functional Connectivity of the Amygdala in Autism: A Preregistered Large-Scale Study.

OBJECTIVE: Three leading neurobiological hypotheses about autism spectrum disorder (ASD) propose underconnectivity between brain regions, atypical function of the amygdala, and generally higher variability between individuals with ASD than between neurotypical individuals. Past work has often failed to generalize, because of small sample sizes, unquantified data quality, and analytic flexibility. This study addressed these limitations while testing the above three hypotheses, applied to amygdala functional connectivity. METHODS: In a comprehensive preregistered study, the three hypotheses were tested in a subset (N=488 after exclusions; N=212 with ASD) of the Autism Brain Imaging Data Exchange data sets. The authors analyzed resting-state functional connectivity (FC) from functional MRI data from two anatomically defined amygdala subdivisions, in three hypotheses with respect to magnitude, pattern similarity, and variability, across different anatomical scales ranging from whole brain to specific regions and networks. RESULTS: A Bayesian approach to hypothesis evaluation produced inconsistent evidence in ASD for atypical amygdala FC magnitude, strong evidence that the multivariate pattern of FC was typical, and no consistent evidence of increased interindividual variability in FC. The results strongly depended on analytic choices, including preprocessing pipeline for the neuroimaging data, anatomical specificity, and subject exclusions. CONCLUSIONS: A preregistered set of analyses found no reliable evidence for atypical functional connectivity of the amygdala in autism, contrary to leading hypotheses. Future studies should test an expanded set of hypotheses across multiple processing pipelines, collect deeper data per individual, and include a greater diversity of participants to ensure robust generalizability of findings on amygdala FC in ASD.