On the stability of canonical correlation analysis and partial least squares with application to brain-behavior associations.

Associations between datasets can be discovered through multivariate methods like Canonical Correlation Analysis (CCA) or Partial Least Squares (PLS). A requisite property for interpretability and generalizability of CCA/PLS associations is stability of their feature patterns. However, stability of CCA/PLS in high-dimensional datasets is questionable, as found in empirical characterizations. To study these issues systematically, we developed a generative modeling framework to simulate synthetic datasets. We found that when sample size is relatively small, but comparable to typical studies, CCA/PLS associations are highly unstable and inaccurate; both in their magnitude and importantly in the feature pattern underlying the association. We confirmed these trends across two neuroimaging modalities and in independent datasets with n ≈ 1000 and n = 20,000, and found that only the latter comprised sufficient observations for stable mappings between imaging-derived and behavioral features. We further developed a power calculator to provide sample sizes required for stability and reliability of multivariate analyses. Collectively, we characterize how to limit detrimental effects of overfitting on CCA/PLS stability, and provide recommendations for future studies.

Generalising XTRACT tractography protocols across common macaque brain templates.

Non-human primates are extensively used in neuroscience research as models of the human brain, with the rhesus macaque being a prominent example. We have previously introduced a set of tractography protocols (XTRACT) for reconstructing 42 corresponding white matter (WM) bundles in the human and the macaque brain and have shown cross-species comparisons using such bundles as WM landmarks. Our original XTRACT protocols were developed using the F99 macaque brain template. However, additional macaque template brains are becoming increasingly common. Here, we generalise the XTRACT tractography protocol definitions across five macaque brain templates, including the F99, D99, INIA, Yerkes and NMT. We demonstrate equivalence of such protocols in two ways: (a) Firstly by comparing the bodies of the tracts derived using protocols defined across the different templates considered, (b) Secondly by comparing the projection patterns of the reconstructed tracts across the different templates in two cross-species (human-macaque) comparison tasks. The results confirm similarity of all predictions regardless of the macaque brain template used, providing direct evidence for the generalisability of these tractography protocols across the five considered templates.

The spatial extent of anatomical connections within the thalamus varies across the cortical hierarchy in humans and macaques.

Each cortical area has a distinct pattern of anatomical connections within the thalamus, a central subcortical structure composed of functionally and structurally distinct nuclei. Previous studies have suggested that certain cortical areas may have more extensive anatomical connections that target multiple thalamic nuclei, which potentially allows them to modulate distributed information flow. However, there is a lack of quantitative investigations into anatomical connectivity patterns within the thalamus. Consequently, it remains unknown if cortical areas exhibit systematic differences in the extent of their anatomical connections within the thalamus. To address this knowledge gap, we used diffusion magnetic resonance imaging (dMRI) to perform brain-wide probabilistic tractography for 828 healthy adults from the Human Connectome Project. We then developed a framework to quantify the spatial extent of each cortical area's anatomical connections within the thalamus. Additionally, we leveraged resting-state functional MRI, cortical myelin, and human neural gene expression data to test if the extent of anatomical connections within the thalamus varied along the cortical hierarchy. Our results revealed two distinct corticothalamic tractography motifs: 1) a sensorimotor cortical motif characterized by focal thalamic connections targeting posterolateral thalamus, associated with fast, feed-forward information flow; and 2) an associative cortical motif characterized by diffuse thalamic connections targeting anteromedial thalamus, associated with slow, feed-back information flow. These findings were consistent across human subjects and were also observed in macaques, indicating cross-species generalizability. Overall, our study demonstrates that sensorimotor and association cortical areas exhibit differences in the spatial extent of their anatomical connections within the thalamus, which may support functionally-distinct cortico-thalamic information flow.

QuNex-An integrative platform for reproducible neuroimaging analytics.

Introduction: Neuroimaging technology has experienced explosive growth and transformed the study of neural mechanisms across health and disease. However, given the diversity of sophisticated tools for handling neuroimaging data, the field faces challenges in method integration, particularly across multiple modalities and species. Specifically, researchers often have to rely on siloed approaches which limit reproducibility, with idiosyncratic data organization and limited software interoperability. Methods: To address these challenges, we have developed Quantitative Neuroimaging Environment & Toolbox (QuNex), a platform for consistent end-to-end processing and analytics. QuNex provides several novel functionalities for neuroimaging analyses, including a "turnkey" command for the reproducible deployment of custom workflows, from onboarding raw data to generating analytic features. Results: The platform enables interoperable integration of multi-modal, community-developed neuroimaging software through an extension framework with a software development kit (SDK) for seamless integration of community tools. Critically, it supports high-throughput, parallel processing in high-performance compute environments, either locally or in the cloud. Notably, QuNex has successfully processed over 10,000 scans across neuroimaging consortia, including multiple clinical datasets. Moreover, QuNex enables integration of human and non-human workflows via a cohesive translational platform. Discussion: Collectively, this effort stands to significantly impact neuroimaging method integration across acquisition approaches, pipelines, datasets, computational environments, and species. Building on this platform will enable more rapid, scalable, and reproducible impact of neuroimaging technology across health and disease.

Concurrent mapping of brain ontogeny and phylogeny within a common space: Standardized tractography and applications.

Developmental and evolutionary effects on brain organization are complex, yet linked, as evidenced by the correspondence in cortical area expansion across these vastly different time scales. However, it is still not possible to study concurrently the ontogeny and phylogeny of cortical areal connections, which is arguably more relevant to brain function than allometric measurements. Here, we propose a novel framework that allows the integration of structural connectivity maps from humans (adults and neonates) and nonhuman primates (macaques) onto a common space. We use white matter bundles to anchor the common space and use the uniqueness of cortical connection patterns to these bundles to probe area specialization. This enabled us to quantitatively study divergences and similarities in connectivity over evolutionary and developmental scales, to reveal brain maturation trajectories, including the effect of premature birth, and to translate cortical atlases between diverse brains. Our findings open new avenues for an integrative approach to imaging neuroanatomy.

Predicting time-resolved electrophysiological brain networks from structural eigenmodes.

How temporal modulations in functional interactions are shaped by the underlying anatomical connections remains an open question. Here, we analyse the role of structural eigenmodes, in the formation and dissolution of temporally evolving functional brain networks using resting-state magnetoencephalography and diffusion magnetic resonance imaging data at the individual subject level. Our results show that even at short timescales, phase and amplitude connectivity can partly be expressed by structural eigenmodes, but hardly by direct structural connections. Albeit a stronger relationship was found between structural eigenmodes and time-resolved amplitude connectivity. Time-resolved connectivity for both phase and amplitude was mostly characterised by a stationary process, superimposed with very brief periods that showed deviations from this stationary process. For these brief periods, dynamic network states were extracted that showed different expressions of eigenmodes. Furthermore, the eigenmode expression was related to overall cognitive performance and co-occurred with fluctuations in community structure of functional networks. These results implicate that ongoing time-resolved resting-state networks, even at short timescales, can to some extent be understood in terms of activation and deactivation of structural eigenmodes and that these eigenmodes play a role in the dynamic integration and segregation of information across the cortex, subserving cognitive functions.

XTRACT - Standardised protocols for automated tractography in the human and macaque brain.

We present a new software package with a library of standardised tractography protocols devised for the robust automated extraction of white matter tracts both in the human and the macaque brain. Using in vivo data from the Human Connectome Project (HCP) and the UK Biobank and ex vivo data for the macaque brain datasets, we obtain white matter atlases, as well as atlases for tract endpoints on the white-grey matter boundary, for both species. We illustrate that our protocols are robust against data quality, generalisable across two species and reflect the known anatomy. We further demonstrate that they capture inter-subject variability by preserving tract lateralisation in humans and tract similarities stemming from twinship in the HCP cohort. Our results demonstrate that the presented toolbox will be useful for generating imaging-derived features in large cohorts, and in facilitating comparative neuroanatomy studies. The software, tractography protocols, and atlases are publicly released through FSL, allowing users to define their own tractography protocols in a standardised manner, further contributing to open science.

A Method of Correcting for the Effect of Temperature on Low-Contrast Penetration Measurement in Urethane Phantoms.

Urethane-based test objects are routinely used for ultrasound quality assurance because of their durability and robustness. The acoustic properties of these phantoms including speed of sound and attenuation, however, have a strong dependence on temperature. Reliable measurement of low-contrast penetration, which is widely used for ultrasound system quality assurance testing, with these phantoms is therefore problematic. To alleviate this, a correction method was proposed using speed of sound estimated by measuring filament target separation. The method was developed using a range of 17 transducer geometry and frequency combinations across 5 ultrasound systems and validated using a further 5 systems. This was found to reduce the uncertainty of low-contrast penetration measurement from an average 17.6 mm to 4.9 mm over the temperature range 8°C to 32°C. This represents a greater than threefold improvement in precision of low-contrast penetration measurement.