Frontiers in Neuroinformatics最新文献

Quantification of microglial activation through morphometric analysis has long been a staple of the neuroimmunologist's toolkit. Microglial morphological phenomics can be conducted through either manual classification or constructing a digital skeleton and extracting morphometric data from it. Multiple open-access and paid software packages are available to generate these skeletons via semi-automated and/or fully automated methods with varying degrees of accuracy. Despite advancements in methods to generate morphometrics (quantitative measures of cellular morphology), there has been limited development of tools to analyze the datasets they generate, in particular those containing parameters from tens of thousands of cells analyzed by fully automated pipelines. In this review, we compare and critique the approaches using cluster analysis and machine learning driven predictive algorithms that have been developed to tackle these large datasets, and propose improvements for these methods. In particular, we highlight the need for a commitment to open science from groups developing these classifiers. Furthermore, we call attention to a need for communication between those with a strong software engineering/computer science background and neuroimmunologists to produce effective analytical tools with simplified operability if we are to see their wide-spread adoption by the glia biology community.

Background: Despite the efforts of the neuroscience community, there are many published neuroimaging studies with data that are still not findable or accessible. Users face significant challenges in reusing neuroimaging data due to the lack of provenance metadata, such as experimental protocols, study instruments, and details about the study participants, which is also required for interoperability. To implement the FAIR guidelines for neuroimaging data, we have developed an iterative ontology engineering process and used it to create the NeuroBridge ontology. The NeuroBridge ontology is a computable model of provenance terms to implement FAIR principles and together with an international effort to annotate full text articles with ontology terms, the ontology enables users to locate relevant neuroimaging datasets.

Methods: Building on our previous work in metadata modeling, and in concert with an initial annotation of a representative corpus, we modeled diagnosis terms (e.g., schizophrenia, alcohol usage disorder), magnetic resonance imaging (MRI) scan types (T1-weighted, task-based, etc.), clinical symptom assessments (PANSS, AUDIT), and a variety of other assessments. We used the feedback of the annotation team to identify missing metadata terms, which were added to the NeuroBridge ontology, and we restructured the ontology to support both the final annotation of the corpus of neuroimaging articles by a second, independent set of annotators, as well as the functionalities of the NeuroBridge search portal for neuroimaging datasets.

Results: The NeuroBridge ontology consists of 660 classes with 49 properties with 3,200 axioms. The ontology includes mappings to existing ontologies, enabling the NeuroBridge ontology to be interoperable with other domain specific terminological systems. Using the ontology, we annotated 186 neuroimaging full-text articles describing the participant types, scanning, clinical and cognitive assessments.

Conclusion: The NeuroBridge ontology is the first computable metadata model that represents the types of data available in recent neuroimaging studies in schizophrenia and substance use disorders research; it can be extended to include more granular terms as needed. This metadata ontology is expected to form the computational foundation to help both investigators to make their data FAIR compliant and support users to conduct reproducible neuroimaging research.

The biomedical research community is motivated to share and reuse data from studies and projects by funding agencies and publishers. Effectively combining and reusing neuroimaging data from publicly available datasets, requires the capability to query across datasets in order to identify cohorts that match both neuroimaging and clinical/behavioral data criteria. Critical barriers to operationalizing such queries include, in part, the broad use of undefined study variables with limited or no annotations that make it difficult to understand the data available without significant interaction with the original authors. Using the Brain Imaging Data Structure (BIDS) to organize neuroimaging data has made querying across studies for specific image types possible at scale. However, in BIDS, beyond file naming and tightly controlled imaging directory structures, there are very few constraints on ancillary variable naming/meaning or experiment-specific metadata. In this work, we present NIDM-Terms, a set of user-friendly terminology management tools and associated software to better manage individual lab terminologies and help with annotating BIDS datasets. Using these tools to annotate BIDS data with a Neuroimaging Data Model (NIDM) semantic web representation, enables queries across datasets to identify cohorts with specific neuroimaging and clinical/behavioral measurements. This manuscript describes the overall informatics structures and demonstrates the use of tools to annotate BIDS datasets to perform integrated cross-cohort queries.

Training spiking recurrent neural networks on neuronal recordings or behavioral tasks has become a popular way to study computations performed by the nervous system. As the size and complexity of neural recordings increase, there is a need for efficient algorithms that can train models in a short period of time using minimal resources. We present optimized CPU and GPU implementations of the recursive least-squares algorithm in spiking neural networks. The GPU implementation can train networks of one million neurons, with 100 million plastic synapses and a billion static synapses, about 1,000 times faster than an unoptimized reference CPU implementation. We demonstrate the code's utility by training a network, in less than an hour, to reproduce the activity of > 66, 000 recorded neurons of a mouse performing a decision-making task. The fast implementation enables a more interactive in-silico study of the dynamics and connectivity underlying multi-area computations. It also admits the possibility to train models as in-vivo experiments are being conducted, thus closing the loop between modeling and experiments.

Deep brain stimulation (DBS) is a widely used clinical therapy that modulates neuronal firing in subcortical structures, eliciting downstream network effects. Its effectiveness is determined by electrode geometry and location as well as adjustable stimulation parameters including pulse width, interstimulus interval, frequency, and amplitude. These parameters are often determined empirically during clinical or intraoperative programming and can be altered to an almost unlimited number of combinations. Conventional high-frequency stimulation uses a continuous high-frequency square-wave pulse (typically 130-160 Hz), but other stimulation patterns may prove efficacious, such as continuous or bursting theta-frequencies, variable frequencies, and coordinated reset stimulation. Here we summarize the current landscape and potential clinical applications for novel stimulation patterns.

The analysis of whole brain networks started in the 1980s when only a handful of connectomes were available. In these early days, information about the human connectome was absent and one could only dream about having information about connectivity in a single human subject. Thanks to non-invasive methods such as diffusion imaging, we now know about connectivity in many species and, for some species, in many individuals. To illustrate the rapid change in availability of connectome data, the UK Biobank is on track to record structural and functional connectivity in 100,000 human subjects. Moreover, connectome data from a range of species is now available: from Caenorhabditis elegans and the fruit fly to pigeons, rodents, cats, non-human primates, and humans. This review will give a brief overview of what structural connectivity data is now available, how connectomes are organized, and how their organization shows common features across species. Finally, I will outline some of the current challenges and potential future work in making use of connectome information.

Introduction: The exorbitant cost of accurately annotating the large-scale serial scanning electron microscope (SEM) images as the ground truth for training has always been a great challenge for brain map reconstruction by deep learning methods in neural connectome studies. The representation ability of the model is strongly correlated with the number of such high-quality labels. Recently, the masked autoencoder (MAE) has been shown to effectively pre-train Vision Transformers (ViT) to improve their representational capabilities.

Methods: In this paper, we investigated a self-pre-training paradigm for serial SEM images with MAE to implement downstream segmentation tasks. We randomly masked voxels in three-dimensional brain image patches and trained an autoencoder to reconstruct the neuronal structures.

Results and discussion: We tested different pre-training and fine-tuning configurations on three different serial SEM datasets of mouse brains, including two public ones, SNEMI3D and MitoEM-R, and one acquired in our lab. A series of masking ratios were examined and the optimal ratio for pre-training efficiency was spotted for 3D segmentation. The MAE pre-training strategy significantly outperformed the supervised learning from scratch. Our work shows that the general framework of can be a unified approach for effective learning of the representation of heterogeneous neural structural features in serial SEM images to greatly facilitate brain connectome reconstruction.

There is common consensus that data sharing accelerates science. Data sharing enhances the utility of data and promotes the creation and competition of scientific ideas. Within the Alzheimer's disease and related dementias (ADRD) community, data types and modalities are spread across many organizations, geographies, and governance structures. The ADRD community is not alone in facing these challenges, however, the problem is even more difficult because of the need to share complex biomarker data from centers around the world. Heavy-handed data sharing mandates have, to date, been met with limited success and often outright resistance. Interest in making data Findable, Accessible, Interoperable, and Reusable (FAIR) has often resulted in centralized platforms. However, when data governance and sovereignty structures do not allow the movement of data, other methods, such as federation, must be pursued. Implementation of fully federated data approaches are not without their challenges. The user experience may become more complicated, and federated analysis of unstructured data types remains challenging. Advancement in federated data sharing should be accompanied by improvement in federated learning methodologies so that federated data sharing becomes functionally equivalent to direct access to record level data. In this article, we discuss federated data sharing approaches implemented by three data platforms in the ADRD field: Dementia's Platform UK (DPUK) in 2014, the Global Alzheimer's Association Interactive Network (GAAIN) in 2012, and the Alzheimer's Disease Data Initiative (ADDI) in 2020. We conclude by addressing open questions that the research community needs to solve together.

Functional connectivity (FC) of the brain changes in various brain disorders. Its complexity, however, makes it difficult to obtain a systematic understanding of these alterations, especially when they are found individually and through hypothesis-based methods. It would be easier if the variety of brain connectivity alterations is extracted through data-driven approaches and expressed as variation modules (subnetworks). In the present study, we modified a blind approach to determine inter-group brain variations at the network level and applied it specifically to schizophrenia (SZ) disorder. The analysis is based on the application of independent component analysis (ICA) over the subject's dimension of the FC matrices, obtained from resting-state functional magnetic resonance imaging (rs-fMRI). The dataset included 27 SZ people and 27 completely matched healthy controls (HC). This hypothesis-free approach led to the finding of three brain subnetworks significantly discriminating SZ from HC. The area associated with these subnetworks mostly covers regions in visual, ventral attention, and somatomotor areas, which are in line with previous studies. Moreover, from the graph perspective, significant differences were observed between SZ and HC for these subnetworks, while there was no significant difference when the same parameters (path length, network strength, global/local efficiency, and clustering coefficient) across the same limited data were calculated for the whole brain network. The increased sensitivity of those subnetworks to SZ-induced alterations of connectivity suggested whether an individual scoring method based on their connectivity values can be applied to classify subjects. A simple scoring classifier was then suggested based on two of these subnetworks and resulted in acceptable sensitivity and specificity with an area under the ROC curve of 77.5%. The third subnetwork was found to be a less specific building block (module) for describing SZ alterations. It projected a wider range of inter-individual variations and, therefore, had a lower chance to be considered as a SZ biomarker. These findings confirmed that investigating brain variations from a modular viewpoint can help to find subnetworks that are more sensitive to SZ-induced alterations. Altogether, our study results illustrated the developed method's ability to systematically find brain alterations caused by SZ disorder from a network perspective.

The effective sharing of health research data within the healthcare ecosystem can have tremendous impact on the advancement of disease understanding, prevention, treatment, and monitoring. By combining and reusing health research data, increasingly rich insights can be made about patients and populations that feed back into the health system resulting in more effective best practices and better patient outcomes. To achieve the promise of a learning health system, data needs to meet the FAIR principles of findability, accessibility, interoperability, and reusability. Since the inception of the Brain-CODE platform and services in 2012, the Ontario Brain Institute (OBI) has pioneered data sharing activities aligned with FAIR principles in neuroscience. Here, we describe how Brain-CODE has operationalized data sharing according to the FAIR principles. Findable-Brain-CODE offers an interactive and itemized approach for requesters to generate data cuts of interest that align with their research questions. Accessible-Brain-CODE offers multiple data access mechanisms. These mechanisms-that distinguish between metadata access, data access within a secure computing environment on Brain-CODE and data access via export will be discussed. Interoperable-Standardization happens at the data capture level and the data release stage to allow integration with similar data elements. Reusable - Brain-CODE implements several quality assurances measures and controls to maximize data value for reusability. We will highlight the successes and challenges of a FAIR-focused neuroinformatics platform that facilitates the widespread collection and sharing of neuroscience research data for learning health systems.