Models Of Neuroimaging Data Research Articles

Making the most of errors: Utilizing erroneous classifications generated by machine-learning models of neuroimaging data to capture disorder heterogeneity.

Within-disorder heterogeneity complicates mapping the neurobiological features of psychopathology to Diagnostic and Statistical Manual of Mental Disorders conceptualizations. The present study explored the patterns of diagnostic classification errors among disorders with commonly co-occurring features to examine this heterogeneity. Classification analyses were conducted with the University of California, Los Angeles Phenomics Study database using a support-vector classifier to differentiate disorders via whole brain task-based functional connectivity, predicting that model misclassifications would provide insight about brain connectivity characteristics shared across disorders. Whether symptoms and specific brain networks could account for misclassification rates was also explored. The classification model performed better than chance (44% accuracy, p = .01) and revealed that misclassification of schizophrenia (SCZ) as bipolar disorder (BD; 38%) and BD as SCZ (36%) was symmetrical. Attention-deficit/hyperactivity disorder (ADHD) was misclassified as BD at the highest rate (46%) and higher than the converse (17%). SCZ and ADHD were misclassified least (15% SCZ as ADHD and 22% ADHD as SCZ). Considerable variance in misclassification of SCZ as BD (R2 = .83) and BD as SCZ (R2 = .71) could be accounted for by symptoms of both SCZ and BD. Permutation testing revealed disorder- and network-specific effects, with certain networks improving classification accuracy and others hindering it for specific disorders. An approach focused on classification errors replicated known disorder overlap, producing errors in the expected configuration. Further, it identified clinical and neural features within and across diagnostic categories that contribute to disorder misclassification and within-disorder heterogeneity. This approach may facilitate neurobiologically informed phenotypic differentiation within diagnostic groups. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Supplemental Material for Making the Most of Errors: Utilizing Erroneous Classifications Generated by Machine-Learning Models of Neuroimaging Data to Capture Disorder Heterogeneity

Supplemental Material for Making the Most of Errors: Utilizing Erroneous Classifications Generated by Machine-Learning Models of Neuroimaging Data to Capture Disorder Heterogeneity

NIDM-Terms: community-based terminology management for improved neuroimaging dataset descriptions and query.

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.

Deep and statistical learning in biomedical imaging: State of the art in 3D MRI brain tumor segmentation

Clinical diagnosis and treatment decisions rely upon the integration of patient-specific data with clinical reasoning. Cancer presents a unique context that influences treatment decisions, given its diverse forms of disease evolution. Biomedical imaging allows non-invasive assessment of diseases based on visual evaluations, leading to better clinical outcome prediction and therapeutic planning. Early methods of brain cancer characterization predominantly relied upon the statistical modeling of neuroimaging data. Driven by breakthroughs in computer vision, deep learning has become the de facto standard in medical imaging. Integrated statistical and deep learning methods have recently emerged as a new direction in the automation of medical practice unifying multi-disciplinary knowledge in medicine, statistics, and artificial intelligence. In this study, we critically review major statistical, deep learning, and probabilistic deep learning models and their applications in brain imaging research with a focus on MRI-based brain tumor segmentation. These results highlight that model-driven classical statistics and data-driven deep learning is a potent combination for developing automated systems in clinical oncology.

The Neuroimaging Data Model Linear Regression Tool (nidm_linreg): PyNIDM Project.

The Neuroimaging Data Model (NIDM) is a series of specifications for describing all aspects of the neuroimaging data lifecycle from raw data to analyses and provenance. NIDM uses community-driven terminologies along with unambiguous data dictionaries within a Resource Description Framework (RDF) document to describe data and metadata for integration and query. Data from different studies, using locally defined variable names, can be retrieved by linking them to higher-order concepts from established ontologies and terminologies. Through these capabilities, NIDM documents are expected to improve reproducibility and facilitate data discovery and reuse. PyNIDM is a Python toolbox supporting the creation, manipulation, and querying of NIDM documents. Using the query tools available in PyNIDM, users are able interrogate datasets to find studies that have collected variables measuring similar phenotypic properties. This, in turn, facilitates the transformation and combination of data across multiple studies. The focus of this manuscript is the linear regression tool which is a part of the PyNIDM toolbox and works directly on NIDM documents. It provides a high-level statistical analysis that aids researchers in gaining more insight into the data that they are considering combining across studies. This saves researchers valuable time and effort while showing potential relationships between variables. The linear regression tool operates through a command-line interface integrated with the other tools (pynidm linear-regression) and provides the user with the opportunity to specify variables of interest using the rich query techniques available for NIDM documents and then conduct a linear regression with optional contrast and regularization.

Interpreting Brain Biomarkers: Challenges and solutions in interpreting machine learning-based predictive neuroimaging.

Predictive modeling of neuroimaging data (predictive neuroimaging) for evaluating individual differences in various behavioral phenotypes and clinical outcomes is of growing interest. However, the field is experiencing challenges regarding the interpretability of the results. Approaches to defining the specific contribution of functional connections, regions, or networks in prediction models are urgently needed, which may help explore the underlying mechanisms. In this article, we systematically review the methods and applications for interpreting brain signatures derived from predictive neuroimaging based on a survey of 326 research articles. Strengths, limitations, and the suitable conditions for major interpretation strategies are also deliberated. In-depth discussion of common issues in existing literature and the corresponding recommendations to address these pitfalls are provided. We highly recommend exhaustive validation on the reliability and interpretability of the biomarkers across multiple datasets and contexts, which thereby could translate technical advances in neuroimaging into concrete improvements in precision medicine.

Pymdp: A Python library for active inference in discrete state spaces

Active inference is an account of cognition and behavior in complex systems which brings together action, perception, and learning under the theoretical mantle of Bayesian inference. Active inference has seen growing applications in academic research, especially in fields that seek to model human or animal behavior. While in recent years, some of the code arising from the active inference literature has been written in open source languages like Python and Julia, to-date, the most popular software for simulating active inference agents is the DEM toolbox of SPM, a MATLAB library originally developed for the statistical analysis and modelling of neuroimaging data. Increasing interest in active inference, manifested both in terms of sheer number as well as diversifying applications across scientific disciplines, has thus created a need for generic, widely-available, and user-friendly code for simulating active inference in open-source scientific computing languages like Python. The Python package we present here, pymdp (see https://github.com/infer-actively/pymdp), represents a significant step in this direction: namely, we provide the first open-source package for simulating active inference with partially-observable Markov Decision Processes or POMDPs. We review the package's structure and explain its advantages like modular design and customizability, while providing in-text code blocks along the way to demonstrate how it can be used to build and run active inference processes with ease. We developed pymdp to increase the accessibility and exposure of the active inference framework to researchers, engineers, and developers with diverse disciplinary backgrounds. In the spirit of open-source software, we also hope that it spurs new innovation, development, and collaboration in the growing active inference community.

Neuroimaging-ITM: A Text Mining Pipeline Combining Deep Adversarial Learning with Interaction Based Topic Modeling for Enabling the FAIR Neuroimaging Study.

Sharing various neuroimaging digital resources have received widespread attention in FAIR (Findable, Accessible, Interoperable and Reusable) neuroscience. In order to support a comprehensive understanding of brain cognition, neuroimaging provenance should be constructed to characterize both research processes and results, and integrates various digital resources for quick replication and open cooperation. This brings new challenges to neuroimaging text mining, including fragmented information, lack of labelled corpora, and vague topics. This paper proposes a text mining pipeline for enabling the FAIR neuroimaging study. In order to avoid fragmented information, the Brain Informatics provenance model is redesigned based on NIDM (Neuroimaging Data Model) and FAIR facets. It can systematically capture the provenance requests from the FAIR neuroimaging study and then transform them into a group of text mining tasks. A neuroimaging text mining pipeline combining deep adversarial learning with interaction based topic modeling, called neuroimaging interaction topic model (Neuroimaging-ITM), is proposed to automatically extract neuroimaging provenance and identify research topics in the few-shot scenario. Finally, a group of experiments is completed by using real data from the journal PloS One. The experimental results show that Neuroimaging-ITM can systematically and accurately extract provenance information and obtain high-quality research topics from the full text of neuroimaging articles. Most of the mean F1 values of provenance extraction exceed 0.9. The topic coherence and KL (Kullback-Leibler) divergence reach 9.95 and 0.96 respectively. The results are obviously better than baseline methods.

The Neuroimaging Data Model Linear Regression Tool (nidm_linreg): PyNIDM Project

The Neuroimaging Data Model (NIDM) is a series of specifications for describing all aspects of the neuroimaging data lifecycle from raw data to analyses and provenance. NIDM uses community-driven terminologies along with unambiguous data dictionaries within a Resource Description Framework (RDF) document to describe data and metadata for integration and query. Data from different studies, using locally defined variable names, can be retrieved by linking them to higher-order concepts from established ontologies and terminologies. Through these capabilities, NIDM documents are expected to improve reproducibility and facilitate data discovery and reuse. PyNIDM is a Python toolbox supporting the creation, manipulation, and querying of NIDM documents. Using the query tools available in PyNIDM, users are able interrogate datasets to find studies that have collected variables measuring similar phenotypic properties. This, in turn, facilitates the transformation and combination of data across multiple studies. The focus of this manuscript is the linear regression tool which is a part of the PyNIDM toolbox and works directly on NIDM documents. It provides a high-level statistical analysis that aids researchers in gaining more insight into the data that they are considering combining across studies. This saves researchers valuable time and effort while showing potential relationships between variables. The linear regression tool operates through a command-line interface integrated with the other tools (pynidm linear-regression) and provides the user with the opportunity to specify variables of interest using the rich query techniques available for NIDM documents and then conduct a linear regression with optional contrast and regularization.

BIDS and the NeuroImaging Data Model (NIDM)

The following statement is designed to clarify the complementary nature of the Brain Imaging Data Structure (BIDS) and the NeuroImaging Data Model (NIDM). It is not designed to be a comprehensive review of either of these initiatives, but rather to highlight the synergy of the co-application of each of these emerging technologies. The context for this statement is the preservation and communication of neuroimaging data and the additional experimental data and analytics that are associated with the neuroimaging data.

Improving mass-univariate analysis of neuroimaging data by modelling important unknown covariates: Application to Epigenome-Wide Association Studies

Statistical inference on neuroimaging data is often conducted using a mass-univariate model, equivalent to fitting a linear model at every voxel with a known set of covariates. Due to the large number of linear models, it is challenging to check if the selection of covariates is appropriate and to modify this selection adequately. The use of standard diagnostics, such as residual plotting, is clearly not practical for neuroimaging data. However, the selection of covariates is crucial for linear regression to ensure valid statistical inference. In particular, the mean model of regression needs to be reasonably well specified. Unfortunately, this issue is often overlooked in the field of neuroimaging. This study aims to adopt the existing Confounder Adjusted Testing and Estimation (CATE) approach and to extend it for use with neuroimaging data. We propose a modification of CATE that can yield valid statistical inferences using Principal Component Analysis (PCA) estimators instead of Maximum Likelihood (ML) estimators. We then propose a non-parametric hypothesis testing procedure that can improve upon parametric testing. Monte Carlo simulations show that the modification of CATE allows for more accurate modelling of neuroimaging data and can in turn yield a better control of False Positive Rate (FPR) and Family-Wise Error Rate (FWER). We demonstrate its application to an Epigenome-Wide Association Study (EWAS) on neonatal brain imaging and umbilical cord DNA methylation data obtained as part of a longitudinal cohort study. Software for this CATE study is freely available at http://www.bioeng.nus.edu.sg/cfa/Imaging_Genetics2.html.

A Semantic Cross-Species Derived Data Management Application

Managing dynamic information in large multi-site, multi-species, and multi-discipline consortia is a challenging task for data management applications. Often in academic research studies the goals for informatics teams are to build applications that provide extract-transform-load (ETL) functionality to archive and catalog source data that has been collected by the research teams. In consortia that cross species and methodological or scientific domains, building interfaces which supply data in a usable fashion and make intuitive sense to scientists from dramatically different backgrounds increases the complexity for developers. Further, reusing source data from outside one’s scientific domain is fraught with ambiguities in understanding the data types, analysis methodologies, and how to combine the data with those from other research teams. We report on the design, implementation, and performance of a semantic data management application to support the NIMH funded Conte Center at the University of California, Irvine. The Center is testing a theory of the consequences of “fragmented” (unpredictable, high entropy) early-life experiences on adolescent cognitive and emotional outcomes in both humans and rodents. It employs cross-species neuroimaging, epigenomic, molecular, and neuroanatomical approaches in humans and rodents to assess the potential consequences of fragmented unpredictable experience on brain structure and circuitry. To address this multi-technology, multi-species approach, the system uses semantic web techniques based on the Neuroimaging Data Model (NIDM) to facilitate data ETL functionality. We find this approach enables a low-cost, easy to maintain, and semantically meaningful information management system, enabling the diverse research teams to access and use the data.

Sharing brain mapping statistical results with the neuroimaging data model.

Only a tiny fraction of the data and metadata produced by an fMRI study is finally conveyed to the community. This lack of transparency not only hinders the reproducibility of neuroimaging results but also impairs future meta-analyses. In this work we introduce NIDM-Results, a format specification providing a machine-readable description of neuroimaging statistical results along with key image data summarising the experiment. NIDM-Results provides a unified representation of mass univariate analyses including a level of detail consistent with available best practices. This standardized representation allows authors to relay methods and results in a platform-independent regularized format that is not tied to a particular neuroimaging software package. Tools are available to export NIDM-Result graphs and associated files from the widely used SPM and FSL software packages, and the NeuroVault repository can import NIDM-Results archives. The specification is publically available at: http://nidm.nidash.org/specs/nidm-results.html.

A hierarchical model for integrating unsupervised generative embedding and empirical Bayes

BackgroundGenerative models of neuroimaging data, such as dynamic causal models (DCMs), are commonly used for inferring effective connectivity from individual subject data. Recently introduced “generative embedding” approaches have used DCM-based connectivity parameters for supervised classification of individual patients or to find unknown subgroups in heterogeneous groups using unsupervised clustering methods. New methodWe present a novel framework which combines DCMs with finite mixture models into a single hierarchical model. This approach unifies the inference of connectivity parameters in individual subjects with inference on population structure, i.e. the existence of subgroups defined by model parameters, and allows for empirical Bayesian estimates of a subject’s connectivity based on subgroup-specific prior distributions. We introduce a Markov chain Monte Carlo sampling method for inversion of this hierarchical generative model. ResultsThis paper formally introduces the idea behind our novel concept and demonstrates the face validity of the model in application to both simulated data as well as an empirical fMRI dataset from healthy controls and patients with schizophrenia. Comparison with existing method(s)The analysis of our empirical fMRI data demonstrates that our approach results in superior model evidence than the conventional non-hierarchical inversion of DCMs. ConclusionsIn this paper, we have presented a novel unified framework to jointly infer the effective connectivity parameters in DCMs for multiple subjects and, at the same time, discover connectivity-defined cluster structure of the whole population, using a mixture model approach.

Describing Assessments and Experiment Metadata with the Neuroimaging Data Model (NIDM)

Describing Assessments and Experiment Metadata with the Neuroimaging Data Model (NIDM)

Inversion of hierarchical Bayesian models using Gaussian processes

Over the past decade, computational approaches to neuroimaging have increasingly made use of hierarchical Bayesian models (HBMs), either for inferring on physiological mechanisms underlying fMRI data (e.g., dynamic causal modelling, DCM) or for deriving computational trajectories (from behavioural data) which serve as regressors in general linear models. However, an unresolved problem is that standard methods for inverting the hierarchical Bayesian model are either very slow, e.g. Markov Chain Monte Carlo Methods (MCMC), or are vulnerable to local minima in non-convex optimisation problems, such as variational Bayes (VB).This article considers Gaussian process optimisation (GPO) as an alternative approach for global optimisation of sufficiently smooth and efficiently evaluable objective functions. GPO avoids being trapped in local extrema and can be computationally much more efficient than MCMC. Here, we examine the benefits of GPO for inverting HBMs commonly used in neuroimaging, including DCM for fMRI and the Hierarchical Gaussian Filter (HGF). Importantly, to achieve computational efficiency despite high-dimensional optimisation problems, we introduce a novel combination of GPO and local gradient-based search methods. The utility of this GPO implementation for DCM and HGF is evaluated against MCMC and VB, using both synthetic data from simulations and empirical data. Our results demonstrate that GPO provides parameter estimates with equivalent or better accuracy than the other techniques, but at a fraction of the computational cost required for MCMC. We anticipate that GPO will prove useful for robust and efficient inversion of high-dimensional and nonlinear models of neuroimaging data.

Standardizing Metadata in Brain Imaging

Standardizing Metadata in Brain Imaging

Resting state functional MRI in Parkinson’s disease: the impact of deep brain stimulation on ‘effective’ connectivity

Depleted of dopamine, the dynamics of the parkinsonian brain impact on both 'action' and 'resting' motor behaviour. Deep brain stimulation has become an established means of managing these symptoms, although its mechanisms of action remain unclear. Non-invasive characterizations of induced brain responses, and the effective connectivity underlying them, generally appeals to dynamic causal modelling of neuroimaging data. When the brain is at rest, however, this sort of characterization has been limited to correlations (functional connectivity). In this work, we model the 'effective' connectivity underlying low frequency blood oxygen level-dependent fluctuations in the resting Parkinsonian motor network-disclosing the distributed effects of deep brain stimulation on cortico-subcortical connections. Specifically, we show that subthalamic nucleus deep brain stimulation modulates all the major components of the motor cortico-striato-thalamo-cortical loop, including the cortico-striatal, thalamo-cortical, direct and indirect basal ganglia pathways, and the hyperdirect subthalamic nucleus projections. The strength of effective subthalamic nucleus afferents and efferents were reduced by stimulation, whereas cortico-striatal, thalamo-cortical and direct pathways were strengthened. Remarkably, regression analysis revealed that the hyperdirect, direct, and basal ganglia afferents to the subthalamic nucleus predicted clinical status and therapeutic response to deep brain stimulation; however, suppression of the sensitivity of the subthalamic nucleus to its hyperdirect afferents by deep brain stimulation may subvert the clinical efficacy of deep brain stimulation. Our findings highlight the distributed effects of stimulation on the resting motor network and provide a framework for analysing effective connectivity in resting state functional MRI with strong a priori hypotheses.

Dynamic and stochastic models of neuroimaging data: A comment on Lohmann et al.

DCM is a platform for inferring the architecture of dynamical systems, combining a user-dependent model specification step with a Bayesian model selection scheme. In their critique of the model selection procedure, Lohmann et al confine themselves to models generated from the classic bilinear deterministic DCM. Although brief reference is made to recent modeling advances, such as stochastic DCM and nonlinear DCM, these are negatively cast as guilty of further exploding the combinatorial problem that is proposed to plague model selection. Yet this is only a problem if a naïve approach is adopted towards the model generation process. Where the user draws on prior knowledge of the system being modeled and the statistical properties of the particular data set, these advances can be employed precisely to address the type of concerns Lohmann et al raise in their exemplar analysis (Fig. 6). This note provides a putative generative model for their data by adding stochastic effects, using independent evidence to increase its biological plausibility and challenging the notion that model fit should be assessed using simple linear correlations. Rather than encouraging reliance on future developments in imaging hardware and data-driven multivariate algorithms, informed engagement with causal models of neuronal dynamics allows imaging researchers develop detailed theories of brain function across a broad range of data sets and cognitive phenomena.

Gestures Orchestrate Brain Networks for Language Understanding

Although the linguistic structure of speech provides valuable communicative information, nonverbal behaviors can offer additional, often disambiguating cues. In particular, being able to see the face and hand movements of a speaker facilitates language comprehension [1]. But how does the brain derive meaningful information from these movements? Mouth movements provide information about phonological aspects of speech [2-3]. In contrast, cospeech gestures display semantic information relevant to the intended message [4-6]. We show that when language comprehension is accompanied by observable face movements, there is strong functional connectivity between areas of cortex involved in motor planning and production and posterior areas thought to mediate phonological aspects of speech perception. In contrast, language comprehension accompanied by cospeech gestures is associated with tuning of and strong functional connectivity between motor planning and production areas and anterior areas thought to mediate semantic aspects of language comprehension. These areas are not tuned to hand and arm movements that are not meaningful. Results suggest that when gestures accompany speech, the motor system works with language comprehension areas to determine the meaning of those gestures. Results also suggest that the cortical networks underlying language comprehension, rather than being fixed, are dynamically organized by the type of contextual information available to listeners during face-to-face communication.