Previous research has reported on the development trajectory of the corpus callosum morphology. However, there have been only a few studies that have included data on infants. The goal of the present study was to examine the morphology of the corpus callosum in healthy participants of both sexes, from infancy to early adulthood. We sought to characterize normal development of the corpus callosum and possible sex differences in development. We performed a morphometric magnetic resonance imaging (MRI) study of 114 healthy individuals, aged 1 month to 25 years old, measuring the size of the corpus callosum. The corpus callosum was segmented into seven subareas of the rostrum, genu, rostral body, anterior midbody, posterior midbody, isthmus and splenium. Locally weighted regression analysis (LOESS) indicated significant non-linear age-related changes regardless of sex, particularly during the first few years of life. After this increase, curve slopes gradually became flat during adolescence and adulthood in both sexes. Age of local maximum for each subarea of the corpus callosum differed across the sexes. Ratios of total corpus callosum and genu, posterior midbody, as well as splenium to the whole brain were significantly higher in females compared with males. The present results demonstrate that the developmental trajectory of the corpus callosum during early life in healthy individuals is non-linear and dynamic. This pattern resembles that found for the cerebral cortex, further suggesting that this period plays a very important role in neural and functional development. In addition, developmental trajectories and changes in growth do show some sex differences.

Ex vivo brains have different MRI properties than in vivo brains because of chemical changes caused by fixative solutions, which change the signal intensity and/or tissue contrast on MR images. In this study, we investigated and compared the MRI properties of in vivo and ex vivo brains.

Functional near infrared spectroscopy (fNIRS), which is compact, portable, and tolerant of body movement, is suitable for monitoring infant brain functions. Nevertheless, fNIRS also poses a technical problem in that it cannot provide structural information. Supplementation with structural magnetic resonance images (MRI) is not always feasible for infants who undergo fNIRS measurement. Probabilistic registration methods using an MRI database instead of subjects' own MRIs are optimized for adult studies and offer only limited resources for infant studies. To overcome this, we used high-quality infant MRI data for a 12-month-old infant and manually delineated segmented gyri from among the highly visible macroanatomies on the lateral cortical surface. These macroanatomical regions are primarily linked to the spherical coordinate system based on external cranial landmarks, and further to traditional 10-20-based head-surface positioning systems. While macroanatomical structures were generally comparable between adult and infant atlases, differences were found in the parietal lobe, which was positioned posteriorly at the vertex in the infant brain. The present study provides a referential framework for macroanatomical analyses in infant fNIRS studies. With this resource, multichannel fNIRS functional data could be analyzed in reference to macroanatomical structures through virtual and probabilistic registrations without acquiring subject-specific MRIs.

Morphometry studies of human brain development have revealed characteristics of some growth patterns, such as gray matter (GM) and white matter (WM), but the features that make human neurodevelopment distinct from that in other species remain unclear. Studies of the common marmoset (Callithrix jacchus), a small New World primate, can provide insights into unique features such as cooperative behaviors complementary to those from comparative analyses using mouse and rhesus monkey. In the present study, we analyzed developmental patterns of GM, WM, and cortical regions with volume measurements using longitudinal sample (23 marmosets; 11 male, 12 female) between the ages of one and 30months. Regional analysis using a total of 164 magnetic resonance imaging datasets revealed that GM volume increased before puberty (5.4months), but subsequently declined until adulthood, whereas WM volume increased rapidly before stabilizing around puberty (9.9months). Cortical regions showed similar patterns of increase and decrease, patterns with global GM but differed in the timing of volume peak and degree of decline across regions. The progressive-regressive pattern detected in both global and cortical GM was well correlated to phases of synaptogenesis and synaptic pruning reported in previous marmoset studies. A rapid increase in WM in early development may represent a distinctive aspect of human neurodevelopment. These findings suggest that studies of marmoset brain development can provide valuable comparative information that will facilitate a deeper understanding of human brain growth and neurodevelopmental disorders.

Brain development involves spatiotemporally complex microstructural changes. A number of neuropsychiatric disorders are linked to the neural processes of development and aging. Thus, it is important to understanding the typical developmental patterns of various brain structures, which will help to define critical periods of vulnerability for neural maturation, as well as anatomical mechanisms of brain structure-related neuropathology. In this study, we used magnetic resonance imaging to assess development of the orbitofrontal cortex, cingulate cortex, amygdala, and hippocampus in a non-human primate species, the common marmoset (Callithrix jacchus). We collected a total of 114 T2-weighted and 91 diffusion-weighted scans from 23 animals from infancy to early adulthood. Quantitative and qualitative evaluation of age-related brain growth patterns showed non-linear structural developmental changes in all measured brain regions, consistent with reported human data. Overall, robust volumetric growth was observed from 1 to 3 months of age (from infancy to the early juvenile period). This rapid brain growth was associated with the largest decrease in mean, axial, and radial diffusivities of diffusion tensor imaging in all brain regions, suggesting an increase in the number and size of cells, dendrites, and spines during this period. After this developmental period, the volume of various brain regions steadily increased until adolescence (7-13 months of age, depending on the region). Further, structural connectivity derived from tractography data in various brain regions continuously changed from infancy to adolescence, suggesting that the increase in brain volume was related to continued axonal myelination during adolescence. Thereafter, the volume of the cortical regions decreased considerably, while there was no change in subcortical regions. Familial factors, rather than sex, contributed the development of the front-limbic brain regions. Overall, this study provides further data on the factors and timing important for normal brain development, and suggest that the common marmoset is a useful animal model for human neural development.

Psychiatric and neurological disorders are afflictions of the brain that can affect individuals throughout their lifespan. Many brain magnetic resonance imaging (MRI) studies have been conducted; however, imaging-based biomarkers are not yet well established for diagnostic and therapeutic use. This article describes an outline of the planned study, the Brain/MINDS Beyond human brain MRI project (BMB-HBM, FY2018 ~ FY2023), which aims to establish clinically-relevant imaging biomarkers with multi-site harmonization by collecting data from healthy traveling subjects (TS) at 13 research sites. Collection of data in psychiatric and neurological disorders across the lifespan is also scheduled at 13 sites, whereas designing measurement procedures, developing and analyzing neuroimaging protocols, and databasing are done at three research sites. A high-quality scanning protocol, Harmonization Protocol (HARP), was established for five high-quality 3 T scanners to obtain multimodal brain images including T1 and T2-weighted, resting-state and task functional and diffusion-weighted MRI. Data are preprocessed and analyzed using approaches developed by the Human Connectome Project. Preliminary results in 30 TS demonstrated cortical thickness, myelin, functional connectivity measures are comparable across 5 scanners, suggesting sensitivity to subject-specific connectome. A total of 75 TS and more than two thousand patients with various psychiatric and neurological disorders are scheduled to participate in the project, allowing a mixed model statistical harmonization. The HARP protocols are publicly available online, and all the imaging, demographic and clinical information, harmonizing database will also be made available by 2024. To the best of our knowledge, this is the first project to implement a prospective, multi-level harmonization protocol with multi-site TS data. It explores intractable brain disorders across the lifespan and may help to identify the disease-specific pathophysiology and imaging biomarkers for clinical practice.

Localising accurate brain regions needs careful evaluation in each experimental species due to their individual variability. However, the function and connectivity of brain areas is commonly studied using a single-subject cranial landmark-based stereotactic atlas in animal neuroscience. Here, we address this issue in a small primate, the common marmoset, which is increasingly widely used in systems neuroscience. We developed a non-invasive multi-modal neuroimaging-based targeting pipeline, which accounts for intersubject anatomical variability in cranial and cortical landmarks in marmosets. This methodology allowed creation of multi-modal templates (MarmosetRIKEN20) including head CT and brain MR images, embedded in coordinate systems of anterior and posterior commissures (AC-PC) and CIFTI grayordinates. We found that the horizontal plane of the stereotactic coordinate was significantly rotated in pitch relative to the AC-PC coordinate system (10 degrees, frontal downwards), and had a significant bias and uncertainty due to positioning procedures. We also found that many common cranial and brain landmarks (e.g., bregma, intraparietal sulcus) vary in location across subjects and are substantial relative to average marmoset cortical area dimensions. Combining the neuroimaging-based targeting pipeline with robot-guided surgery enabled proof-of-concept targeting of deep brain structures with an accuracy of 0.2 mm. Altogether, our findings demonstrate substantial intersubject variability in marmoset brain and cranial landmarks, implying that subject-specific neuroimaging-based localization is needed for precision targeting in marmosets. The population-based templates and atlases in grayordinates, created for the first time in marmoset monkeys, should help bridging between macroscale and microscale analyses.

Schizophrenia is a common severe psychiatric disorder that affects approximately 1% of general population through the life course. Historically, in Kraepelin's time, schizophrenia was a disease unit conceptualized as dementia praecox; however, since then, the disease concept has changed. Recent MRI studies had shown that the neuropathology of the brain in this disorder was characterized by mild progression before and after the onset of the disease, and that the brain alterations were relatively smaller than assumed. Although genetic factors contribute to the brain alterations in schizophrenia, which are thought to be trait differences, other changes include factors that are common in psychiatric diseases. Furthermore, it has been shown that the brain differences specific to schizophrenia were relatively small compared to other changes, such as those caused by brain development, aging, and gender. In addition, compared to the disease and participant factors, machine and imaging protocol differences could affect MRI signals, which should be addressed in multi-site studies. Recent advances in MRI modalities, such as multi-shell diffusion-weighted imaging, magnetic resonance spectroscopy, and multimodal brain imaging analysis, may be candidates to sharpen the characterization of schizophrenia-specific factors and provide new insights. The Brain/MINDS Beyond Human Brain MRI (BMB-HBM) project has been launched considering the differences and noises irrespective of the disease pathologies and includes the future perspectives of MRI studies for various psychiatric and neurological disorders. The sites use restricted MRI machines and harmonized multi-modal protocols, standardized image preprocessing, and traveling subject harmonization. Data sharing to the public will be planned in FY 2024. In the future, we believe that combining a high-quality human MRI dataset with genetic data, randomized controlled trials, and MRI for non-human primates and animal models will enable us to understand schizophrenia, elucidate its neural bases and therapeutic targets, and provide tools for clinical application at bedside.

Knowledge of amygdalar and hippocampal development as they pertain to sex differences and laterality would help to understand not only brain development but also the relationship between brain volume and brain functions. However, few studies investigated development of these two regions, especially during infancy. The purpose of this study was to examine typical volumetric trajectories of amygdala and hippocampus from infancy to early adulthood by predicting sexual dimorphism and laterality. We performed a cross-sectional morphometric MRI study of amygdalar and hippocampal growth from 1 month to 25 years old, using 109 healthy individuals. The findings indicated significant non-linear age-related volume changes, especially during the first few years of life, in both the amygdala and hippocampus regardless of sex. The peak ages of amygdalar and hippocampal volumes came at the timing of preadolescence (9-11 years old). The female amygdala reached its peak age about one year and a half earlier than the male amygdala did. In addition, its rate of growth change decreased earlier in the females. Furthermore, both females and males displayed rightward laterality in the hippocampus, but only the males in the amygdala. The robust growth of the amygdala and hippocampus during infancy highlight the importance of this period for neural and functional development. The sex differences and laterality during development of these two regions suggest that sex-related factors such as sex hormones and functional laterality might affect brain development.

Resting-state functional connectivity (rs-FC) is widely used to examine the functional architecture of the brain, and the blood-oxygenation-level-dependent (BOLD) signal is often utilized for determining rs-FC. However, the BOLD signal is susceptible to various factors that have less influence on the cerebral blood flow (CBF). Therefore, CBF could comprise an alternative for determining rs-FC. Since acquisition duration is one of the essential parameters for obtaining reliable rs-FC, we investigated the effect of acquisition duration on CBF-based rs-FC to examine the reliability of CBF-based rs-FC. Nineteen participants underwent CBF scanning for a total duration of 50 min. Variance of CBF-based rs-FC within the whole brain and 13 large-scale brain networks at various acquisition durations was compared to that with a 50-min duration using the Levene's test. Variance of CBF-based rs-FC at any durations did not differ from that at a 50-min duration (p > .05). Regarding variance of rs-FC within each large-scale brain network, the acquisition duration required to obtain reliable estimates of CBF-based rs-FC was shorter than 10 min and varied across large-scale brain networks. Altogether, an acquisition duration of at least 10 min is required to obtain reliable CBF-based rs-FC. These results indicate that CBF-based resting-state functional magnetic resonance imaging (rs-fMRI) with more than 10 min of total acquisition duration could be an alternative method to BOLD-based rs-fMRI to obtain reliable rs-FC.

Multisite magnetic resonance imaging (MRI) is increasingly used in clinical research and development. Measurement biases-caused by site differences in scanner/image-acquisition protocols-negatively influence the reliability and reproducibility of image-analysis methods. Harmonization can reduce bias and improve the reproducibility of multisite datasets. Herein, a traveling-subject (TS) dataset including 56 T1-weighted MRI scans of 20 healthy participants in three different MRI procedures-20, 19, and 17 subjects in Procedures 1, 2, and 3, respectively-was considered to compare the reproducibility of TS-GLM, ComBat, and TS-ComBat harmonization methods. The minimum participant count required for harmonization was determined, and the Cohen's d between different MRI procedures was evaluated as a measurement-bias indicator. The measurement-bias reduction realized with different methods was evaluated by comparing test-retest scans for 20 healthy participants. Moreover, the minimum subject count for harmonization was determined by comparing test-retest datasets. The results revealed that TS-GLM and TS-ComBat reduced measurement bias by up to 85 and 81.3%, respectively. Meanwhile, ComBat showed a reduction of only 59.0%. At least 6 TSs were required to harmonize data obtained from different MRI scanners, complying with the imaging protocol predetermined for multisite investigations and operated with similar scan parameters. The results indicate that TS-based harmonization outperforms ComBat for measurement-bias reduction and is optimal for MRI data in well-prepared multisite investigations. One drawback is the small sample size used, potentially limiting the applicability of ComBat. Investigation on the number of subjects needed for a large-scale study is an interesting future problem.

Magnetic resonance imaging (MRI) is a non-invasive neuroimaging technique that is useful for identifying normal developmental and aging processes and for data sharing. Marmosets have a relatively shorter life expectancy than other primates, including humans, because they grow and age faster. Therefore, the common marmoset model is effective in aging research. The current study investigated the aging process of the marmoset brain and provided an open MRI database of marmosets across a wide age range. The Brain/MINDS Marmoset Brain MRI Dataset contains brain MRI information from 216 marmosets ranging in age from 1 and 10 years. At the time of its release, it is the largest public dataset in the world. It also includes multi-contrast MRI images. In addition, 91 of 216 animals have corresponding high-resolution ex vivo MRI datasets. Our MRI database, available at the Brain/MINDS Data Portal, might help to understand the effects of various factors, such as age, sex, body size, and fixation, on the brain. It can also contribute to and accelerate brain science studies worldwide.