Macroscopic Brain Structure Research Articles

Deep learning with diffusion MRI as in vivo microscope reveals sex-related differences in human white matter microstructure

Biological sex is a crucial variable in neuroscience studies where sex differences have been documented across cognitive functions and neuropsychiatric disorders. While gross statistical differences have been previously documented in macroscopic brain structure such as cortical thickness or region size, less is understood about sex-related cellular-level microstructural differences which could provide insight into brain health and disease. Studying these microstructural differences between men and women paves the way for understanding brain disorders and diseases that manifest differently in different sexes. Diffusion MRI is an important in vivo, non-invasive methodology that provides a window into brain tissue microstructure. Our study develops multiple end-to-end classification models that accurately estimates the sex of a subject using volumetric diffusion MRI data and uses these models to identify white matter regions that differ the most between men and women. 471 male and 560 female healthy subjects (age range, 22–37 years) from the Human Connectome Project are included. Fractional anisotropy, mean diffusivity and mean kurtosis are used to capture brain tissue microstructure characteristics. Diffusion parametric maps are registered to a standard template to reduce bias that can arise from macroscopic anatomical differences like brain size and contour. This study employ three major model architectures: 2D convolutional neural networks, 3D convolutional neural networks and Vision Transformer (with self-supervised pretraining). Our results show that all 3 models achieve high sex classification performance (test AUC 0.92–0.98) across all diffusion metrics indicating definitive differences in white matter tissue microstructure between males and females. We further use complementary model architectures to inform about the pattern of detected microstructural differences and the influence of short-range versus long-range interactions. Occlusion analysis together with Wilcoxon signed-rank test is used to determine which white matter regions contribute most to sex classification. The results indicate that sex-related differences manifest in both local features as well as global features / longer-distance interactions of tissue microstructure. Our highly consistent findings across models provides new insight supporting differences between male and female brain cellular-level tissue organization particularly in the central white matter.

Genetic map of regional sulcal morphology in the human brain from UK biobank data

Genetic associations with macroscopic brain structure can provide insights into brain function and disease. However, specific associations with measures of local brain folding are largely under-explored. Here, we conducted large-scale genome- and exome-wide associations of regional cortical sulcal measures derived from magnetic resonance imaging scans of 40,169 individuals in UK Biobank. We discovered 388 regional brain folding associations across 77 genetic loci, with genes in associated loci enriched for expression in the cerebral cortex, neuronal development processes, and differential regulation during early brain development. We integrated brain eQTLs to refine genes for various loci, implicated several genes involved in neurodevelopmental disorders, and highlighted global genetic correlations with neuropsychiatric phenotypes. We provide an interactive 3D visualisation of our summary associations, emphasising added resolution of regional analyses. Our results offer new insights into the genetic architecture of brain folding and provide a resource for future studies of sulcal morphology in health and disease.

The macaque brain ONPRC18 template with combined gray and white matter labelmap for multimodal neuroimaging studies of Nonhuman Primates

Macaques are the most common nonhuman primate (NHP) species used in neuroscience research. With the advancement of many neuroimaging techniques, new studies are beginning to apply multiple types of in vivo magnetic resonance imaging (MRI), such as structural imaging (sMRI) with T1 and T2 weighted contrasts alongside diffusion weighed (DW) imaging. In studies involving rhesus macaques, this approach can be used to better understand micro-structural changes that occur during development, in various disease states or with normative aging. However, many of the available rhesus brain atlases have been designed for only one imaging modality, making it difficult to consistently define the same brain regions across multiple imaging modalities in the same subject. To address this, we created a brain atlas from 18 adult rhesus macaques that includes co-registered templates constructed from images frequently used to characterize macroscopic brain structure (T2/SPACE and T1/MP-RAGE), and a diffusion tensor imaging (DTI) template. The DTI template was up-sampled from 1 mm isotropic resolution to resolution match to the T1 and T2-weighted images (0.5 mm isotropic), and the parameter maps were derived for FA, AD, RD and MD.The labelmap volumes delineate 57 gray matter regions of interest (ROIs; 36 cortical regions and 21 subcortical structures), as well as 74 white matter tracts. Importantly, the labelmap overlays both the structural and diffusion templates, enabling the same regions to be consistently identified across imaging modalities. A specialized condensed version of the labelmap ROIs are also included to further extend the usefulness of this tool for imaging data with lower spatial resolution, such as functional MRI (fMRI) or positron emission tomography (PET).

Soccer heading and concussion are not associated with reduced brain volumeor cortical thickness.

Soccer is the most popular sport in the world and, since it is a contact sport, players are at risk for head injury, including concussion. Here, we proposed to investigate the association of heading and concussion with macroscopic brain structure among adult amateur soccer players. For this study, 375 amateur soccer players (median age 23 years) completed HeadCount-12m to estimate heading over the 12 months prior to MRI and lifetime concussion. T1-weighted 3D magnetization prepared rapid acquisition gradient echo (MP-RAGE) MRI was performed at 3 Tesla. Parcellation was performed using Freesurfer to extract regional gray and white matter volumes as well as regional cortical thickness and total intracranial volume. Regional cortical brain volumes were normalized by total intracranial volume. We categorized heading into quartiles and concussion as 0, 1 or 2 or more. Generalized linear regressions were used to test the association of heading or concussion with each brain morphometry metric, including age and sex, as covariates. Neither heading nor concussion were associated with reduced brain volume or cortical thickness. We observed that greater heading was associated with greater gray matter volume in the left inferior parietal area, which may reflect effects related to training.

Genes, Cells and Brain Areas of Intelligence.

What is the neurobiological basis of human intelligence? The brains of some people seem to be more efficient than those of others. Understanding the biological foundations of these differences is of great interest to basic and applied neuroscience. Somehow, the secret must lie in the cells in our brain with which we think. However, at present, research into the neurobiology of intelligence is divided between two main strategies: brain imaging studies investigate macroscopic brain structure and function to identify brain areas involved in intelligence, while genetic associations studies aim to pinpoint genes and genetic loci associated with intelligence. Nothing is known about how properties of brain cells relate to intelligence. The emergence of transcriptomics and cellular neuroscience of intelligence might, however, provide a third strategy and bridge the gap between identified genes for intelligence and brain function and structure. Here, we discuss the latest developments in the search for the biological basis of intelligence. In particular, the recent availability of very large cohorts with hundreds of thousands of individuals have propelled exciting developments in the genetics of intelligence. Furthermore, we discuss the first studies that show that specific populations of brain cells associate with intelligence. Finally, we highlight how specific genes that have been identified generate cellular properties associated with intelligence and may ultimately explain structure and function of the brain areas involved. Thereby, the road is paved for a cellular understanding of intelligence, which will provide a conceptual scaffold for understanding how the constellation of identified genes benefit cellular functions that support intelligence.

Structural alterations in functional neurological disorder and related conditions: a software and hardware problem?

Functional neurological (conversion) disorder (FND) is a condition at the interface of neurology and psychiatry. A “software” vs. “hardware” analogy describes abnormal neurobiological mechanisms occurring in the context of intact macroscopic brain structure. While useful for explanatory and treatment models, this framework may require more nuanced considerations in the context of quantitative structural neuroimaging findings in FND. Moreover, high co-occurrence of FND and somatic symptom disorders (SSD) as defined in DSM-IV (somatization disorder, somatoform pain disorder, and undifferentiated somatoform disorder; referred to as SSD for brevity in this article) raises the possibility of a partially overlapping pathophysiology. In this systematic review, we use a transdiagnostic approach to review and appraise the structural neuroimaging literature in FND and SSD. While larger sample size studies are needed for definitive characterization, this article highlights that individuals with FND and SSD may exhibit sensorimotor, prefrontal, striatal-thalamic, paralimbic, and limbic structural alterations. The structural neuroimaging literature is contextualized within the neurobiology of stress-related neuroplasticity, gender differences, psychiatric comorbidities, and the greater spectrum of functional somatic disorders. Future directions that could accelerate the characterization of the pathophysiology of FND and DSM-5 SSD are outlined, including “disease staging” discussions to contextualize subgroups with or without structural changes. Emerging neuroimaging evidence suggests that some individuals with FND and SSD may have a “software” and “hardware” problem, although if structural alterations are present the neural mechanisms of functional disorders remain distinct from lesional neurological conditions. Furthermore, it remains unclear whether structural alterations relate to predisposing vulnerabilities or consequences of the disorder.

Childhood Music Training Induces Change in Micro and Macroscopic Brain Structure: Results from a Longitudinal Study.

Several studies comparing adult musicians and nonmusicians have shown that music training is associated with structural brain differences. It is not been established, however, whether such differences result from pre-existing biological traits, lengthy musical training, or an interaction of the two factors, or if comparable changes can be found in children undergoing music training. As part of an ongoing longitudinal study, we investigated the effects of music training on the developmental trajectory of children's brain structure, over two years, beginning at age 6. We compared these children with children of the same socio-economic background but either involved in sports training or not involved in any systematic after school training. We established at the onset that there were no pre-existing structural differences among the groups. Two years later we observed that children in the music group showed (1) a different rate of cortical thickness maturation between the right and left posterior superior temporal gyrus, and (2) higher fractional anisotropy in the corpus callosum, specifically in the crossing pathways connecting superior frontal, sensory, and motor segments. We conclude that music training induces macro and microstructural brain changes in school-age children, and that those changes are not attributable to pre-existing biological traits.

No association between schizophrenia susceptibility variants and macroscopic structural brain volume variation in healthy subjects.

Previous studies have suggested that genetic variants for schizophrenia susceptibility might contribute to structural brain volume variations in schizophrenia patients, including total brain volume, hippocampal volume, and amygdalar volume. However, whether these schizophrenia susceptibility variants are associated with macroscopic structural brain volume (i.e., intracranial volume, total brain volume, and hippocampal volume) in healthy subjects is still unclear. In this study, we investigated the associations between 47 schizophrenia susceptibility variants (from 25 well-characterized schizophrenia susceptibility genes) and cranial volume variation in a healthy Chinese sample (N = 1,013). We also extracted the association between these 47 schizophrenia risk variants and the macroscopic structural brain volume (intracranial volume, total brain volume and hippocampal volume) in a large healthy sample of European ancestry (ENIGMA sample, N = 5,775). We identified several single-nucleotide polymorphisms (SNPs) nominally associated with intracranial volume, total brain volume, and hippocampal volume at P < 0.05 (uncorrected). However, after Bonferroni corrections for multiple testing, no SNP showed significant association. Hence, our results do not support previous observations that schizophrenia susceptibility variants are associated with brain structure (e.g., hippocampal volume) in healthy individuals, and indicate that single schizophrenia risk variant may not contribute significantly to macroscopic brain structure (e.g., intracranial volume or hippocampal volume) variation in healthy subjects.

No effect of schizophrenia risk genes MIR137, TCF4, and ZNF804A on macroscopic brain structure

Single nucleotide polymorphisms (SNPs) within the MIR137, TCF4, and ZNF804A genes show genome-wide association to schizophrenia. However, the biological basis for the associations is unknown. Here, we tested the effects of these genes on brain structure in 1300 healthy adults. Using volumetry and voxel-based morphometry, neither gene-wide effects—including the combined effect of the genes—nor single SNP effects—including specific psychosis risk SNPs—were found on total brain volume, grey matter, white matter, or hippocampal volume. These results suggest that the associations between these risk genes and schizophrenia are unlikely to be mediated via effects on macroscopic brain structure.

Structural brain correlates of human sleep oscillations

Sleep is strongly conserved within species, yet marked and perplexing inter-individual differences in sleep physiology are observed. Combining EEG sleep recordings and high-resolution structural brain imaging, here we demonstrate that the morphology of the human brain offers one explanatory factor of such inter-individual variability. Gray matter volume in interoceptive and exteroceptive cortices correlated with the expression of slower NREM sleep spindle frequencies, supporting their proposed role in sleep protection against conscious perception. Conversely, and consistent with an involvement in declarative memory processing, gray matter volume in bilateral hippocampus was associated with faster NREM sleep spindle frequencies. In contrast to spindles, gray matter volume in the homeostatic sleep-regulating center of the basal forebrain/hypothalamus, together with the medial prefrontal cortex, accounted for individual differences in NREM slow wave oscillations. Together, such findings indicate that the qualitative and quantitative expression of human sleep physiology is significantly related to anatomically specific differences in macroscopic brain structure.

Schizophrenia risk gene ZNF804A does not influence macroscopic brain structure: an MRI study in 892 volunteers

Schizophrenia risk gene ZNF804A does not influence macroscopic brain structure: an MRI study in 892 volunteers

Dynamic Properties of Human Brain Structure: Learning-Related Changes in Cortical Areas and Associated Fiber Connections

Recent findings in neuroscience suggest that adult brain structure changes in response to environmental alterations and skill learning. Whereas much is known about structural changes after intensive practice for several months, little is known about the effects of single practice sessions on macroscopic brain structure and about progressive (dynamic) morphological alterations relative to improved task proficiency during learning for several weeks. Using T1-weighted and diffusion tensor imaging in humans, we demonstrate significant gray matter volume increases in frontal and parietal brain areas following only two sessions of practice in a complex whole-body balancing task. Gray matter volume increase in the prefrontal cortex correlated positively with subject's performance improvements during a 6 week learning period. Furthermore, we found that microstructural changes of fractional anisotropy in corresponding white matter regions followed the same temporal dynamic in relation to task performance. The results make clear how marginal alterations in our ever changing environment affect adult brain structure and elucidate the interrelated reorganization in cortical areas and associated fiber connections in correlation with improvements in task performance.