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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., Competing Interests: Gaia Rizzo is an employee of Invicro. No other authors have competing interests to declare., (© 2024 Massachusetts Institute of Technology. Published under a Creative Commons Attribution 4.0 International (CC BY 4.0) license.)

Background: Whole genome sequencing is increasingly being used for the diagnosis of patients with rare diseases. However, the diagnostic yields of many studies, particularly those conducted in a healthcare setting, are often disappointingly low, at 25-30%. This is in part because although entire genomes are sequenced, analysis is often confined to in silico gene panels or coding regions of the genome., Methods: We undertook WGS on a cohort of 122 unrelated rare disease patients and their relatives (300 genomes) who had been pre-screened by gene panels or arrays. Patients were recruited from a broad spectrum of clinical specialties. We applied a bioinformatics pipeline that would allow comprehensive analysis of all variant types. We combined established bioinformatics tools for phenotypic and genomic analysis with our novel algorithms (SVRare, ALTSPLICE and GREEN-DB) to detect and annotate structural, splice site and non-coding variants., Results: Our diagnostic yield was 43/122 cases (35%), although 47/122 cases (39%) were considered solved when considering novel candidate genes with supporting functional data into account. Structural, splice site and deep intronic variants contributed to 20/47 (43%) of our solved cases. Five genes that are novel, or were novel at the time of discovery, were identified, whilst a further three genes are putative novel disease genes with evidence of causality. We identified variants of uncertain significance in a further fourteen candidate genes. The phenotypic spectrum associated with RMND1 was expanded to include polymicrogyria. Two patients with secondary findings in FBN1 and KCNQ1 were confirmed to have previously unidentified Marfan and long QT syndromes, respectively, and were referred for further clinical interventions. Clinical diagnoses were changed in six patients and treatment adjustments made for eight individuals, which for five patients was considered life-saving., Conclusions: Genome sequencing is increasingly being considered as a first-line genetic test in routine clinical settings and can make a substantial contribution to rapidly identifying a causal aetiology for many patients, shortening their diagnostic odyssey. We have demonstrated that structural, splice site and intronic variants make a significant contribution to diagnostic yield and that comprehensive analysis of the entire genome is essential to maximise the value of clinical genome sequencing., (© 2023. Crown.)

Humans are generally risk averse, preferring smaller certain over larger uncertain outcomes. Economic theories usually explain this by assuming concave utility functions. Here, we provide evidence that risk aversion can also arise from relative underestimation of larger monetary payoffs, a perceptual bias rooted in the noisy logarithmic coding of numerical magnitudes. We confirmed this with psychophysics and functional magnetic resonance imaging, by measuring behavioural and neural acuity of magnitude representations during a magnitude perception task and relating these measures to risk attitudes during separate risky financial decisions. Computational modelling indicated that participants use similar mental magnitude representations in both tasks, with correlated precision across perceptual and risky choices. Participants with more precise magnitude representations in parietal cortex showed less variable behaviour and less risk aversion. Our results highlight that at least some individual characteristics of economic behaviour can reflect capacity limitations in perceptual processing rather than processes that assign subjective values to monetary outcomes., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

The subthalamic nucleus (STN) is a small, subcortical brain structure. It is a target for deep brain stimulation, an invasive treatment that reduces motor symptoms of Parkinson's disease. Side effects of DBS are commonly explained using the tripartite model of STN organization, which proposes three functionally distinct subregions in the STN specialized in cognitive, limbic, and motor processing. However, evidence for the tripartite model exclusively comes from anatomical studies and functional studies using clinical patients. Here, we provide the first experimental tests of the tripartite model in healthy volunteers using ultra-high field 7 Tesla (T) functional magnetic resonance imaging (fMRI). Thirty-four participants performed a random-dot motion decision-making task with a difficulty manipulation and a choice payoff manipulation aimed to differentially affect cognitive and limbic networks. Moreover, participants responded with their left and right index finger, differentially affecting motor networks. We analysed BOLD signal in three subregions of the STN along the dorsolateral-ventromedial axis, identified using manually delineated high resolution anatomical images and based on a previously published atlas. Using these paradigms, all segments responded equally to the experimental manipulations, and the tasks did not provide evidence for the tripartite model., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The Brain Imaging Data Structure (BIDS) established community consensus on the organization of data and metadata for several neuroimaging modalities. Traditionally, BIDS had a strong focus on functional magnetic resonance imaging (MRI) datasets and lacked guidance on how to store multimodal structural MRI datasets. Here, we present and describe the BIDS Extension Proposal 001 (BEP001), which adds a range of quantitative MRI (qMRI) applications to the BIDS. In general, the aim of qMRI is to characterize brain microstructure by quantifying the physical MR parameters of the tissue via computational, biophysical models. By proposing this new standard, we envision standardization of qMRI through multicenter dissemination of interoperable datasets. This way, BIDS can act as a catalyst of convergence between qMRI methods development and application-driven neuroimaging studies that can help develop quantitative biomarkers for neural tissue characterization. In conclusion, this BIDS extension offers a common ground for developers to exchange novel imaging data and tools, reducing the entrance barrier for qMRI in the field of neuroimaging., (© 2022. The Author(s).)

Inhibitor of nuclear factor kappa B kinase alpha (IKKα) is critical for p100/NF-κB2 phosphorylation and processing into p52 and activation of the noncanonical NF-κB pathway. A patient with recurrent infections, skeletal abnormalities, absent secondary lymphoid structures, reduced B cell numbers, hypogammaglobulinemia, and lymphocytic infiltration of intestine and liver was found to have a homozygous p.Y580C mutation in the helix-loop-helix domain of IKKα. The mutation preserves IKKα kinase activity but abolishes the interaction of IKKα with its activator NF-κB–inducing kinase and impairs lymphotoxin-β–driven p100/NF-κB2 processing and VCAM1 expression. Homozygous IKKα Y580C/Y580C mutant mice phenocopy the patient findings; lack marginal zone B cells, germinal centers, and antigen-specific T cell response to cutaneous immunization; have impaired Il17a expression; and are susceptible to cutaneous Staphylococcus aureus infection. In addition, these mice demonstrate a severe reduction in medullary thymic epithelial cells, impaired thymocyte negative selection, a restricted TCRVβ repertoire, a selective expansion of potentially autoreactive T cell clones, a decreased frequency of regulatory T cells, and infiltration of liver, pancreas, and lung by activated T cells coinciding with organ damage. Hence, this study identifies IKKα deficiency as a previously undescribed cause of primary immunodeficiency with associated autoimmunity.

The pupil provides a rich, non-invasive measure of the neural bases of perception and cognition and has been of particular value in uncovering the role of arousal-linked neuromodulation, which alters both cortical processing and pupil size. But pupil size is subject to a multitude of influences, which complicates unique interpretation. We measured pupils of observers experiencing perceptual multistability-an ever-changing subjective percept in the face of unchanging but inconclusive sensory input. In separate conditions, the endogenously generated perceptual changes were either task-relevant or not, allowing a separation between perception-related and task-related pupil signals. Perceptual changes were marked by a complex pupil response that could be decomposed into two components: a dilation tied to task execution and plausibly indicative of an arousal-linked noradrenaline surge, and an overlapping constriction tied to the perceptual transient and plausibly a marker of altered visual cortical representation. Constriction, but not dilation, amplitude systematically depended on the time interval between perceptual changes, possibly providing an overt index of neural adaptation. These results show that the pupil provides a simultaneous reading on interacting but dissociable neural processes during perceptual multistability, and suggest that arousal-linked neuromodulator release shapes action but not perception in these circumstances., Competing Interests: JB, Gd, MW, AD, TK No competing interests declared, (© 2021, Brascamp et al.)

Ultra-high field MRI can functionally image the cerebral cortex of human subjects at the submillimeter scale of cortical columns and laminae. Here, we investigate both in concert, by imaging ocular dominance columns (ODCs) in primary visual cortex (V1) across different cortical depths. We ensured that putative ODC patterns in V1 (a) are stable across runs, sessions, and scanners located in different continents, (b) have a width (~1.3 mm) expected from post-mortem and animal work and (c) are absent at the retinotopic location of the blind spot. We then dissociated the effects of bottom-up thalamo-cortical input and attentional feedback processes on activity in V1 across cortical depth. Importantly, the separation of bottom-up information flows into ODCs allowed us to validly compare attentional conditions while keeping the stimulus identical throughout the experiment. We find that, when correcting for draining vein effects and using both model-based and model-free approaches, the effect of monocular stimulation is largest at deep and middle cortical depths. Conversely, spatial attention influences BOLD activity exclusively near the pial surface. Our findings show that simultaneous interrogation of columnar and laminar dimensions of the cortical fold can dissociate thalamocortical inputs from top-down processing, and allow the investigation of their interactions without any stimulus manipulation., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Blood vessels provide supportive microenvironments for maintaining tissue functions. Age-associated vascular changes and their relation to tissue aging and pathology are poorly understood. Here, we perform 3D imaging of young and aging vascular beds. Multiple organs in mice and humans demonstrate an age-dependent decline in vessel density and pericyte numbers, while highly remodeling tissues such as skin preserve the vasculature. Vascular attrition precedes the appearance of cellular hallmarks of aging such as senescence. Endothelial VEGFR2 loss-of-function mice demonstrate that vascular perturbations are sufficient to stimulate cellular changes coupled with aging. Age-associated tissue-specific molecular changes in the endothelium drive vascular loss and dictate pericyte to fibroblast differentiation. Lineage tracing of perivascular cells with inducible PDGFRβ and NG2 Cre mouse lines demonstrated that increased pericyte to fibroblast differentiation distinguishes injury-induced organ fibrosis and zymosan-induced arthritis. To spur further discoveries, we provide a freely available resource with 3D vascular and tissue maps., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).)

Background: Inflammation is the hallmark of coronary artery disease (CAD) and CTD. There are reports of increased prevalence of CAD among patients with CTD such as Rheumatoid Arthritis. However, there is a paucity of data regarding the outcomes of PCI among patients with CTD., Methods: Using the National Inpatient Database, patients that underwent PCI between 2007 and 2015 were identified using ICD-9-CM codes. Propensity match analysis with 1: 3 matching of patients with and without CTD was performed. Outcomes were acute kidney injury (AKI), access site complication (ASC), ventricular fibrillation (VF), cardiogenic shock (CS), Stroke, In-hospital mortality and hospital length of stay (LOS) compared between both groups., Result: We identified 17,422 patients with CTD and matched with 52, 266 patients without CTD. Patients were predominantly female (63.1%) and white (77.2%), with a mean age of 63 ± 12.1 years. AKI (8.3% vs. 6.6%, p < 0.001), ASC (3.2% vs. 2.7%, p = 0.01) and hospital stay (4.2 ± 4.8 vs. 3.8 ± 5.2, p < 0.001) were higher among patients with CTD. There was no statistically significant difference in rates of VF, CS, stroke, and In-hospital mortality among the two groups. However, in subgroup analysis, rates of VF were lower among patients with Systemic Lupus Erythematosus (SLE) (1.5% vs. 2.2%, p = 0.006)., Conclusions: Patients with CTD undergoing PCI have a higher rate of AKI, Access site complications, and prolonged hospital stay., Competing Interests: Declaration of competing interest The authors report no relationships that could be construed as a conflict of interest., (Published by Elsevier B.V.)

The subthalamic nucleus (STN) is successfully used as a surgical target for deep brain stimulation in the treatment of movement disorders. Interestingly, the internal structure of the STN is still incompletely understood. The objective of the present study was to investigate three-dimensional (3D) immunoreactivity patterns for 12 individual protein markers for GABA-ergic, serotonergic, dopaminergic as well as glutamatergic signaling. We analyzed the immunoreactivity using optical densities and created a 3D reconstruction of seven postmortem human STNs. Quantitative modeling of the reconstructed 3D immunoreactivity patterns revealed that the applied protein markers show a gradient distribution in the STN. These gradients were predominantly organized along the ventromedial to dorsolateral axis of the STN. The results are of particular interest in view of the theoretical underpinning for surgical targeting, which is based on a tripartite distribution of cognitive, limbic and motor function in the STN.

The Target Article by Lee et al. (2019) highlights the ways in which ongoing concerns about research reproducibility extend to model-based approaches in cognitive science. Whereas Lee et al. focus primarily on the importance of research practices to improve model robustness, we propose that the transparent sharing of model specifications, including their inputs and outputs, is also essential to improving the reproducibility of model-based analyses. We outline an ongoing effort (within the context of the Brain Imaging Data Structure community) to develop standards for the sharing of the structure of computational models and their outputs.

Quantitative magnetic resonance imaging generates images of meaningful physical or chemical variables measured in physical units that allow quantitative comparisons between tissue regions and among subjects scanned at the same or different sites. Here, we show that we can acquire quantitative T 1 , T 2 * , and quantitative susceptibility mapping (QSM) information in a single acquisition, using a multi-echo (ME) extension of the second gradient-echo image of the MP2RAGE sequence. This combination is called MP2RAGE ME, or MP2RAGEME. The simultaneous acquisition results in large time savings, perfectly coregistered data, and minimal image quality differences compared to separately acquired data. Following a correction for residual transmit B 1 + -sensitivity, quantitative T 1 , T 2 * , and QSM values were in excellent agreement with those obtained from separately acquired, also B 1 + -corrected, MP2RAGE data and ME gradient echo data. The quantitative values from reference regions of interests were also in very good correspondence with literature values. From the MP2RAGEME data, we further derived a multiparametric cortical parcellation, as well as a combined arterial and venous map. In sum, our MP2RAGEME sequence has the benefit in large time savings, perfectly coregistered data and minor image quality differences., (© 2018 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

Studies that aim to understand the neural correlates of response conflicts commonly probe frontal brain areas associated with controlled inhibition and decision processes. However, untimely fast conflict errors happen even before these top-down processes are engaged. The dual-route model proposes that during conflict tasks, as soon as the stimulus is presented, two early processes are immediately at play. The task-relevant and task-irrelevant processes generate either compatible responses, when all stimulus features align, or incompatible responses, when stimulus features are in conflict. We aimed to find a neural substrate of these two processes by means of relating the quality of the representation of stimulus features in visual and somatosensory brain areas to responses in conflict tasks. Participants were scanned using fMRI while performing somatosensory and visual Simon tasks. The fMRI data were then analysed using a MVPA in early visual and somatosensory cortices. In agreement with our hypotheses, results suggest that the sensory representation of the task-relevant and task-irrelevant features drive erroneous trials. These results demonstrate that traces of response conflicts can arise already in sensory brain areas and that the quality of the representations in these regions can account for an early response capture by irrelevant stimulus features., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: We aim to evaluate the efficacy of dual versus single anti-platelet therapy (SAPT) after TAVR through a systematic review and meta-analysis of published research., Background: Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel is a commonly practiced strategy after transcatheter aortic valve replacement (TAVR). However, there is lack of sufficient evidence supporting this approach., Method: We searched PubMed, EMBASE, the Cochrane Central Register of Controlled trials, and the clinical trial registry maintained at clinicaltrials.gov for randomized control trials (RCT) and observational studies comparing DAPT with SAPT post TAVR. Event rates were compared using a forest plot of relative risk with 95% confidence intervals using a random-effects model assuming inter-study heterogeneity., Results: A total of six studies (3 RCTs and 3 observational studies, n = 840) were included in the final analysis. Compared to SAPT, DAPT was associated with increased risk of significant bleeding (life threatening and major) [RR = 2.52 (95% CI 1.62-3.92, P < 0.0001)] with the number needed to harm for major or life-threatening bleeding calculated to be 10.4. There was no significant difference in the incidence of stroke [RR = 1.06 (95% CI, 0.43-2.60, P = 0.90)], spontaneous myocardial infarction [RR = 2.08 (95% CI, 0.56-7.70, P = 0.27)] and all-cause mortality [RR = 1.18 (95% CI, 0.68-2.05, P = 0.56] in the DAPT and SAPT groups., Conclusion: In this small meta-analysis of DAPT versus SAPT after TAVR, DAPT did not prevent stroke, myocardial infarction or death while the risk of bleeding was higher. Results from ongoing trials are awaited to determine the best anti-thrombotic approach after TAVR., (© 2018 Wiley Periodicals, Inc.)

Ankylosing spondylitis (AS) is a rheumatological disorder of the spine, and like many other rheumatological diseases, it can manifest as a systemic inflammation. We present a rare case of cardiac manifestations of AS in a 25-year-old man with recurrent chest pain and pericardial effusions. He initially presented with pleuritic chest pain, was diagnosed with cardiac tamponade and required emergent pericardiocentesis. The patient returned again with chest pain and was found to have reaccumulation of pericardial effusion. The cardiac symptoms were finally resolved when he was diagnosed and treated for AS., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Acute alcohol intoxication has been associated with cardiac arrhythmias but the electrocardiogram (ECG) changes associated with acute alcohol intoxication are not well defined in the literature., Objective: Highlight the best evidence regarding the ECG changes associated with acute alcohol intoxication in otherwise healthy patients and the pathophysiology of the changes., Methods: A literature search was carried out; 4 studies relating to ECG changes with acute alcohol intoxication were included in this review., Results: Of the total 141 patients included in the review, 90 (63.8%) patients had P-wave prolongation, 80 (56%) patients had QTc prolongation, 19 (13.5%) patients developed T-wave abnormalities, 10 (7%) patients had QRS complex prolongation, 3 (2.12%) patients developed ST-segment depressions., Conclusion: The most common ECG changes associated with acute alcohol intoxication are (in decreasing order of frequency) P-wave and QTc prolongation, followed by T-wave abnormalities and QRS complex prolongation. Mostly, these changes are completely reversible.