Biology subjects

Nikolaidis, A.

Publications and source records attributed to Nikolaidis, A..

6 recordsLinked to original sources

bioRxiv2025

Disentangling Brain-Psychopathology Associations: A Systematic Evaluation of Transdiagnostic Bifactor Models

Identifying robust brain-psychopathology associations with neuroimaging remains difficult, in part due to substantial heterogeneity within and comorbidity between diagnostic categories. Transdiagnostic latent factor models aim to address this structure by separating shared and unique symptom variance. However, it remains unclear whether latent factor modeling translates into stronger and more interpretable brain-psychopathology associations within contemporary whole-brain prediction frameworks. Using two large developmental cohorts, we systematically compared transdiagnostic bifactor models, correlated factor models, and typical summary scores derived from the Child Behaviour Checklist (CBCL) in their reliability and multivariate associations with whole-brain structure (MRI) and function (resting-state fMRI). General psychopathology, internalising, externalising, and attention dimensions could be significantly predicted from resting-state connectivity but not cortical thickness. We found no consistent evidence that latent factors (bifactor or correlated factor models) strengthened reliability or brain-psychopathology associations, relative to summary scores. Neural signatures were also highly consistent across all scoring methods, with triple network (DMN, FPN, CO) involvement in general, internalizing, and externalising psychopathology. Bifactor scores did, however, display more distinct neural signatures between general, internalising, and externalising dimensions than did summary or correlated factor scores. Collectively, results suggest that additional phenotypic modelling of psychopathology alone does not systematically strengthen the predictive utility of neuroimaging, possibly reflecting fundamental limits on the amount of explainable symptom variance by brain features. While latent factor models may aid in distinguishing neural correlates between constructs, improving phenotypic assessment may be necessary for improvements to brain-psychopathology association strength.

neuroscience↗

bioRxiv2022

Suboptimal phenotypic reliability impedes reproducible human neuroscience

Summary ParagraphBiomarkers of behavior and psychiatric illness for cognitive and clinical neuroscience remain out of reach1-4. Suboptimal reliability of biological measurements, such as functional magnetic resonance imaging (fMRI), is increasingly cited as a primary culprit for discouragingly large sample size requirements and poor reproducibility of brain-based biomarker discovery1,5-7. In response, steps are being taken towards optimizing MRI reliability and increasing sample sizes8-11, though this will not be enough. Optimizing biological measurement reliability and increasing sample sizes are necessary but insufficient steps for biomarker discovery; this focus has overlooked the other side of the equation - the reliability of clinical and cognitive assessments - which are often suboptimal or unassessed. Through a combination of simulation analysis and empirical studies using neuroimaging data, we demonstrate that the joint reliability of both biological and clinical/cognitive phenotypic measurements must be optimized in order to ensure biomarkers are reproducible and accurate. Even with best-case scenario high reliability neuroimaging measurements and large sample sizes, we show that suboptimal reliability of phenotypic data (i.e., clinical diagnosis, behavioral and cognitive measurements) will continue to impede meaningful biomarker discovery for the field. Improving reliability through development of novel assessments of phenotypic variation is needed, but it is not the sole solution. We emphasize the potential to improve the reliability of established phenotypic methods through aggregation across multiple raters and/or measurements12-15, which is becoming increasingly feasible with recent innovations in data acquisition (e.g., web- and smart-phone-based administration, ecological momentary assessment, burst sampling, wearable devices, multimodal recordings)16-20. We demonstrate that such aggregation can achieve better biomarker discovery for a fraction of the cost engendered by large-scale samples. Although the current study has been motivated by ongoing developments in neuroimaging, the prioritization of reliable phenotyping will revolutionize neurobiological and clinical endeavors that are focused on brain and behavior.

neuroscience↗

bioRxiv2020

TOWARD A CONNECTIVITY GRADIENT-BASED FRAMEWORK FOR REPRODUCIBLE BIOMARKER DISCOVERY

AO_SCPLOWBSTRACTC_SCPLOWDespite myriad demonstrations of feasibility, the high dimensionality of fMRI data remains a critical barrier to its utility for reproducible biomarker discovery. Recent studies applying dimensionality reduction techniques to resting-state fMRI (R-fMRI) have unveiled neurocognitively meaningful connectivity gradients that are present in both human and primate brains, and appear to differ meaningfully among individuals and clinical populations. Here, we provide a critical assessment of the suitability of connectivity gradients for biomarker discovery. Using the Human Connectome Project (discovery subsample=209; two replication subsamples= 209x2) and the Midnight scan club (n=9), we tested the following key biomarker traits - reliability, reproducibility and predictive validity - of functional gradients. In doing so, we systematically assessed the effects of three analytical settings, including i) dimensionality reduction algorithms (i.e., linear vs. non-linear methods), ii) input data types (i.e., raw time series, [un-]thresholded functional connectivity), and iii) amount of the data (R-fMRI time-series lengths). We found that the reproducibility of functional gradients across algorithms and subsamples is generally higher for those explaining more variances of whole-brain connectivity data, as well as those having higher reliability. Notably, among different analytical settings, a linear dimensionality reduction (principal component analysis in our study), more conservatively thresholded functional connectivity (e.g., 95-97%) and longer time-series data (at least [≥]20mins) was found to be preferential conditions to obtain higher reliability. Those gradients with higher reliability were able to predict unseen phenotypic scores with a higher accuracy, highlighting reliability as a critical prerequisite for validity. Importantly, prediction accuracy with connectivity gradients exceeded that observed with more traditional edge-based connectivity measures, suggesting the added value of a low-dimensional gradient approach. Finally, the present work highlights the importance and benefits of systematically exploring the parameter space for new imaging methods before widespread deployment. HO_SCPLOWIGHLIGHTSC_SCPLOW- There is a growing need to identify benchmark parameters in advancing functional connectivity gradients into a reliable biomarker. - Here, we explored multidimensional parameter space in calculating functional gradients to improve their reproducibility, reliability and predictive validity. - We demonstrated that more reproducible and reliable gradient markers tend to have higher predictive power for unseen phenotypic scores across various cognitive domains. - We showed that the low-dimensional connectivity gradient approach could outperform raw edge-based analyses in terms of predicting phenotypic scores. - We highlight the necessity of optimizing parameters for new imaging methods before their widespread deployment.

neuroscience↗

bioRxiv2019

Standardizing Human Brain Parcellations

Using brain atlases to localize regions of interest is a requirement for making neuroscientifically valid statistical inferences. These atlases, represented in volumetric or surface coordinate spaces, can describe brain topology from a variety of perspectives. Although many human brain atlases have circulated the field over the past fifty years, limited effort has been devoted to their standardization. Standardization can facilitate consistency and transparency with respect to orientation, resolution, labeling scheme, file storage format, and coordinate space designation. Our group has worked to consolidate an extensive selection of popular human brain atlases into a single, curated, open-source library, where they are stored following a standardized protocol with accompanying metadata, which can serve as the basis for future atlases. The repository containing the atlases, the specification, as well as relevant transformation functions is available at https://github.com/neurodata/neuroparc.

neuroscience↗

bioRxiv2018

Improving Corticostriatal Parcellation Through Multilevel Bagging with PyBASC

Increasing the reproducibility of neuroimaging measurement addresses a central impediment to the advancement of human neuroscience and its clinical applications. Recent efforts demonstrating variance in functional brain organization within and between individuals shows a need for improving reproducibility of functional parcellations without long scan times. We apply bootstrap aggregation, or bagging, to the problem of improving reproducibility in functional parcellation. We use two large datasets to demonstrate that compared to a standard clustering framework, bagging improves the reproducibility and test-retest reliability of both cortical and subcortical functional parcellations across a range of sites, scanners, samples, scan lengths, clustering algorithms, and clustering parameters (e.g., number of clusters, spatial constraints). With as little as six minutes of scan time, bagging creates more reproducible group and individual level parcellations than standard approaches with twice as much data. This suggests that regardless of the specific parcellation strategy employed, bagging may be a key method for improving functional parcellation and bringing functional neuroimaging-based measurement closer to clinical impact.

neuroscience↗

bioRxiv2016

Network Dynamics Theory of Human Intelligence

Scientific discovery and insight into the biological foundations of human intelligence have advanced considerably with progress in neuroimaging. Neuroimaging methods allow for not only an exploration of what biological characteristics underlie intelligence and creativity, but also a detailed assessment of how these biological characteristics emerge through child and adolescent development. In the past 10 years, functional connectivity, a metric of coherence in activation across brain regions, has been used extensively to probe cognitive function; however more recently neuroscientists have begun to investigate the dynamics of these functional connectivity patterns, revealing important insight into these networks as a result. In the present article, we expand current theories on the neural basis of human intelligence by developing a framework that integrates both how short-term dynamic fluctuations in brain networks and long-term development of brain networks over time contribute to intelligence and creativity. Applying this framework, we propose testable hypotheses regarding the neural and developmental correlates of intelligence. We review important topics in both network neuroscience and developmental neuroscience, and we consolidate these insights into a Network Dynamics Theory of human intelligence.

neuroscience↗