Semiparametric Confidence Sets for Arbitrary Effect Sizes in Longitudinal Neuroimaging.

The majority of neuroimaging inference focuses on hypothesis testing rather than effect estimation. With concerns about replicability, there is growing interest in reporting standardized effect sizes from neuroimaging group-level analyses. Confidence sets are a recently developed approach to perform inference for effect sizes in neuroimaging but are restricted to univariate effect sizes and cross-sectional data.

Machine learning prediction of tau-PET in Alzheimer's disease using plasma, MRI, and clinical data.

Introduction: Tau positron emission tomography (PET) is a reliable neuroimaging technique for assessing regional load of tau pathology in the brain, but its routine clinical use is limited by cost and accessibility barriers.

Methods: We thoroughly investigated the ability of various machine learning models to predict clinically useful tau-PET composites (load and laterality index) from low-cost and non-invasive features, for example, clinical variables, plasma biomarkers, and structural magnetic resonance imaging (MRI).

Results: Models including plasma biomarkers yielded the most accurate predictions of tau-PET burden (best model: R-squared = 0.

A lifespan-generalizable skull-stripping model for magnetic resonance images that leverages prior knowledge from brain atlases.

In magnetic resonance imaging of the brain, an imaging-preprocessing step removes the skull and other non-brain tissue from the images. But methods for such a skull-stripping process often struggle with large data heterogeneity across medical sites and with dynamic changes in tissue contrast across lifespans. Here we report a skull-stripping model for magnetic resonance images that generalizes across lifespans by leveraging personalized priors from brain atlases.

Structural MRI of brain similarity networks.

Recent advances in structural MRI analytics now allow the network organization of individual brains to be comprehensively mapped through the use of the biologically principled metric of anatomical similarity. In this Review, we offer an overview of the measurement and meaning of structural MRI similarity, especially in relation to two key assumptions that often underlie its interpretation: (i) that MRI similarity can be representative of architectonic similarity between cortical areas and (ii) that similar areas are more likely to be axonally connected, as predicted by the homophily principle. We first introduce the historical roots and technical foundations of MRI similarity analysis and compare it with the distinct MRI techniques of structural covariance and tractography analysis.

Study design features increase replicability in brain-wide association studies.

Brain-wide association studies (BWAS) are a fundamental tool in discovering brain-behaviour associations. Several recent studies have shown that thousands of study participants are required for good replicability of BWAS. Here we performed analyses and meta-analyses of a robust effect size index using 63 longitudinal and cross-sectional MRI studies from the Lifespan Brain Chart Consortium (77,695 total scans) to demonstrate that optimizing study design is critical for increasing standardized effect sizes and replicability in BWAS.

Empowering Data Sharing in Neuroscience: A Deep Learning De-identification Method for Pediatric Brain MRIs.

Background And Purpose: Privacy concerns, such as identifiable facial features within brain scans, have hindered the availability of pediatric neuroimaging datasets for research. Consequently, pediatric neuroscience research lags adult counterparts, particularly in rare disease and under-represented populations. The removal of face regions (image defacing) can mitigate this, however existing defacing tools often fail with pediatric cases and diverse image types, leaving a critical gap in data accessibility.

Molecular signatures of cortical expansion in the human foetal brain.

The third trimester of human gestation is characterised by rapid increases in brain volume and cortical surface area. Recent studies have revealed a remarkable molecular diversity across the prenatal cortex but little is known about how this diversity translates into the differential rates of cortical expansion observed during gestation. We present a digital resource, μBrain, to facilitate knowledge translation between molecular and anatomical descriptions of the prenatal brain.

Integration across biophysical scales identifies molecular and cellular correlates of person-to-person variability in human brain connectivity.

Brain connectivity arises from interactions across biophysical scales, ranging from molecular to cellular to anatomical to network level. To date, there has been little progress toward integrated analysis across these scales. To bridge this gap, from a unique cohort of 98 individuals, we collected antemortem neuroimaging and genetic data, as well as postmortem dendritic spine morphometric, proteomic and gene expression data from the superior frontal and inferior temporal gyri.

Normative trajectories of extra-axial cerebrospinal fluid during childhood and adolescence defined in a clinically-acquired MRI dataset.

Background: Extra-axial cerebrospinal fluid (eaCSF) refers to the CSF in the subarachnoid spaces that surrounds the brain parenchyma. Benign enlargement of the subarachnoid space (BESS), a condition marked by increased eaCSF thickness, has been associated with macrocephaly and may be associated with subdural collections. However, diagnosis of BESS is complicated by the lack of age-specific normative data which hinders rigorous investigation of its clinical associations.

Multimodal evidence for cerebellar influence on cortical development in autism: structural growth amidst functional disruption.

Despite perinatal damage to the cerebellum being one of the highest risk factors for later being diagnosed with autism spectrum disorder (ASD), it is not yet clear how the cerebellum might influence the development of cerebral cortex and whether this co-developmental process is distinct between neurotypical and ASD children. Leveraging a large structural brain MRI dataset of neurotypical children and those diagnosed with ASD, we examined whether structural variation in cerebellar tissue across individuals was correlated with neocortical variation during development, including the thalamus as a coupling factor. We found that the thalamus plays a distinct role in moderating cerebro-cerebellar structural coordination in ASD.

The genetics of spatiotemporal variation in cortical thickness in youth.

Prior studies have shown strong genetic effects on cortical thickness (CT), structural covariance, and neurodevelopmental trajectories in childhood and adolescence. However, the importance of genetic factors on the induction of spatiotemporal variation during neurodevelopment remains poorly understood. Here, we explore the genetics of maturational coupling by examining 308 MRI-derived regional CT measures in a longitudinal sample of 677 twins and family members.

Molecular and micro-architectural mapping of gray matter alterations in psychosis.

The psychosis spectrum encompasses a heterogeneous range of clinical conditions associated with abnormal brain development. Detecting patterns of atypical neuroanatomical maturation across psychiatric disorders requires an interpretable metric standardized by age-, sex- and site-effect. The molecular and micro-architectural attributes that account for these deviations in brain structure from typical neurodevelopment are still unknown.

Fetal Gene Regulatory Gene Deletions are Associated with Poor Cognition and Altered Cortical Morphology in Schizophrenia and Community-Based Samples.

Schizophrenia spectrum disorders (SSDs) are characterized by substantial clinical and genetic heterogeneity. Multiple recurrent copy number variants (CNVs) increase risk for SSDs; however, how known risk CNVs and broader genome-wide CNVs influence clinical variability is unclear. The current study examined associations between borderline intellectual functioning or childhood-onset psychosis, known risk CNVs, and burden of deletions affecting genes in 18 previously validated neurodevelopmental gene-sets in 618 SSD individuals.

A bimodal taxonomy of adult human brain sulcal morphology related to timing of fetal sulcation and trans-sulcal gene expression gradients.

We developed a computational pipeline (now provided as a resource) for measuring morphological similarity between cortical surface sulci to construct a sulcal phenotype network (SPN) from each magnetic resonance imaging (MRI) scan in an adult cohort (n = 34,725; 45-82 years). Networks estimated from pairwise similarities of 40 sulci on 5 morphological metrics comprised two clusters of sulci, represented also by the bimodal distribution of sulci on a linear-to-complex dimension. Linear sulci were more heritable and typically located in unimodal cortex, and complex sulci were less heritable and typically located in heteromodal cortex.

ComBatLS: A location- and scale-preserving method for multi-site image harmonization.

Recent work has leveraged massive datasets and advanced harmonization methods to construct normative models of neuroanatomical features and benchmark individuals' morphology. However, current harmonization tools do not preserve the effects of biological covariates including sex and age on features' variances; this failure may induce error in normative scores, particularly when such factors are distributed unequally across sites. Here, we introduce a new extension of the popular ComBat harmonization method, ComBatLS, that preserves biological variance in features' locations and scales.

Assessing CT-based Volumetric Analysis via Transfer Learning with MRI and Manual Labels for Idiopathic Normal Pressure Hydrocephalus.

Background: Brain computed tomography (CT) is an accessible and commonly utilized technique for assessing brain structure. In cases of idiopathic normal pressure hydrocephalus (iNPH), the presence of ventriculomegaly is often neuroradiologically evaluated by visual rating and manually measuring each image. Previously, we have developed and tested a deep-learning-model that utilizes transfer learning from magnetic resonance imaging (MRI) for CT-based intracranial tissue segmentation.

A sensorimotor-association axis of thalamocortical connection development.

Human cortical development follows a sensorimotor-to-association sequence during childhood and adolescence. The brain's capacity to enact this sequence over decades indicates that it relies on intrinsic mechanisms to regulate inter-regional differences in the timing of cortical maturation, yet regulators of human developmental chronology are not well understood. Given evidence from animal models that thalamic axons modulate windows of cortical plasticity, here we evaluate the overarching hypothesis that structural connections between the thalamus and cortex help to coordinate cortical maturational heterochronicity during youth.

Deciphering the functional specialization of whole-brain spatiomolecular gradients in the adult brain.

Cortical arealization arises during neurodevelopment from the confluence of molecular gradients representing patterned expression of morphogens and transcription factors. However, whether similar gradients are maintained in the adult brain remains unknown. Here, we uncover three axes of topographic variation in gene expression in the adult human brain that specifically capture previously identified rostral-caudal, dorsal-ventral, and medial-lateral axes of early developmental patterning.

A machine learning-based prediction of tau load and distribution in Alzheimer's disease using plasma, MRI and clinical variables.

Tau positron emission tomography (PET) is a reliable neuroimaging technique for assessing regional load of tau pathology in the brain, commonly used in Alzheimer's disease (AD) research and clinical trials. However, its routine clinical use is limited by cost and accessibility barriers. Here we explore using machine learning (ML) models to predict clinically useful tau-PET composites from low-cost and non-invasive features, e.