A proposal for a coordinated effort for the determination of brainwide neuroanatomical connectivity in model organisms at a mesoscopic scale

In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is however critical both for basic and clinical research into brain function. Here we advocate for a concerted effort to fill this gap, through systematic, experimental mapping of neural circuits at a mesoscopic scale of resolution suitable for comprehensive, brain-wide coverage, using injections of tracers or viral vectors. We detail the scientific and medical rationale and briefly review existing knowledge and experimental techniques. We define a set of desiderata, including brain-wide coverage; validated and extensible experimental techniques suitable for standardization and automation; centralized, open access data repository; compatibility with existing resources, and tractability with current informatics technology. We discuss a hypothetical but tractable plan for mouse, additional efforts for the macaque, and technique development for human. We estimate that the mouse connectivity project could be completed within five years with a comparatively modest budget.Comment: 41 page

The Japan Monkey Centre Primates Brain Imaging Repository for comparative neuroscience: an archive of digital records including records for endangered species

Advances in magnetic resonance imaging (MRI) and computational analysis technology have enabled comparisons among various primate brains in a three-dimensional electronic format. Results from comparative studies provide information about common features across primates and species-specific features of neuroanatomy. Investigation of various species of non-human primates is important for understanding such features, but the majority of comparative MRI studies have been based on experimental primates, such as common marmoset, macaques, and chimpanzee. A major obstacle has been the lack of a database that includes non-experimental primates’ brain MRIs. To facilitate scientific discoveries in the field of comparative neuroanatomy and brain evolution, we launched a collaborative project to develop an open-resource repository of non-human primate brain images obtained using ex vivo MRI. As an initial open resource, here we release a collection of structural MRI and diffusion tensor images obtained from 12 species: pygmy marmoset, owl monkey, white-fronted capuchin, crab-eating macaque, Japanese macaque, bonnet macaque, toque macaque, Sykes’ monkey, red-tailed monkey, Schmidt’s guenon, de Brazza’s guenon, and lar gibbon. Sixteen postmortem brain samples from the 12 species, stored in the Japan Monkey Centre (JMC), were scanned using a 9.4-T MRI scanner and made available through the JMC collaborative research program (http://www.j-monkey.jp/BIR/index_e.html). The expected significant contributions of the JMC Primates Brain Imaging Repository include (1) resources for comparative neuroscience research, (2) preservation of various primate brains, including those of endangered species, in a permanent digital form, (3) resources with higher resolution for identifying neuroanatomical features, compared to previous MRI atlases, (4) resources for optimizing methods of scanning large fixed brains, and (5) references for veterinary neuroradiology. User-initiated research projects beyond these contributions are also anticipated

The Japan Monkey Centre Primates Brain Imaging Repository of high-resolution postmortem magnetic resonance imaging: the second phase of the archive of digital records

超高磁場MRIで見る霊長類「全脳」神経回路の多様性 --分野横断型の霊長類脳標本画像リポジトリ：ヒト脳と精神・神経疾患の理解を加速する国際研究基盤--. 京都大学プレスリリース. 2023-05-22.A comparison of neuroanatomical features of the brain between humans and our evolutionary relatives, nonhuman primates, is key to understanding the human brain system and the neural basis of mental and neurological disorders. Although most comparative MRI studies of human and nonhuman primate brains have been based on brains of primates that had been used as subjects in experiments, it is essential to investigate various species of nonhuman primates in order to elucidate and interpret the diversity of neuroanatomy features among humans and nonhuman primates. To develop a research platform for this purpose, it is necessary to harmonize the scientific contributions of studies with the standards of animal ethics, animal welfare, and the conservation of brain information for long-term continuation of the field. In previous research, we first developed a gated data-repository of anatomical images obtained using 9.4-T ex vivo MRI of postmortem brain samples from 12 nonhuman primate species, and which are stored at the Japan Monkey Centre. In the present study, as a second phase, we released a collection of T2-weighted images and diffusion tensor images obtained in nine species: white-throated capuchin, Bolivian squirrel monkey, stump-tailed macaque, Tibet monkey, Sykes’ monkey, Assamese macaque, pig-tailed macaque, crested macaque, and chimpanzee. Our image repository should facilitate scientific discoveries in the field of comparative neuroscience. This repository can also promote animal ethics and animal welfare in experiments with nonhuman primate models by optimizing methods for in vivo and ex vivo MRI scanning of brains and supporting veterinary neuroradiological education. In addition, the repository is expected to contribute to conservation, preserving information about the brains of various primates, including endangered species, in a permanent digital form

Ensemble tractography

Fiber tractography uses diffusion MRI to estimate the trajectory and cortical projection zones of white matter fascicles in the living human brain. There are many different tractography algorithms and each requires the user to set several parameters, such as curvature threshold. Choosing a single algorithm with a specific parameters sets poses two challenges. First, different algorithms and parameter values produce different results. Second, the optimal choice of algorithm and parameter value may differ between different white matter regions or different fascicles, subjects, and acquisition parameters. We propose using ensemble methods to reduce algorithm and parameter dependencies. To do so we separate the processes of fascicle generation and evaluation. Specifically, we analyze the value of creating optimized connectomes by systematically combining candidate fascicles from an ensemble of algorithms (deterministic and probabilistic) and sweeping through key parameters (curvature and stopping criterion). The ensemble approach leads to optimized connectomes that provide better cross-validatedprediction error of the diffusion MRI data than optimized connectomes generated using the singlealgorithms or parameter set. Furthermore, the ensemble approach produces connectomes that contain both short- and long-range fascicles, whereas single-parameter connectomes are biased towards one or the other. In summary, a systematic ensemble tractography approach can produce connectomes that are superior to standard single parameter estimates both for predicting the diffusion measurements and estimating white matter fascicles.Fil: Takemura, Hiromasa. University of Stanford; Estados Unidos. Osaka University; JapónFil: Caiafa, César Federico. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Wandell, Brian A.. University of Stanford; Estados UnidosFil: Pestilli, Franco. Indiana University; Estados Unido

Comparison of In Vivo and Ex Vivo Diffusion Tensor Imaging in Rhesus Macaques at Short and Long Diffusion Times

Diffusion tensor imaging (DTI) is widely used to non-invasively study neural tissue micro-structure. While DTI tractography of large nerve fibers is well accepted, visualization of smaller fibers and resolution of branching fibers is challenging. Sensitivity of DTI to diffusion anisotropy can be further enhanced using long diffusion time that can provide a more accurate representation of the tissue micro-structure. We previously reported that ex vivo fixed brain DTI at long tdiff (192 ms) showed improved sensitivity to fiber tracking compared to short tdiff (48 ms) in 4% formalin-fixed non-human primate (NHP) brains. This study further tested the hypothesis that DTI at longer diffusion time improves DTI fiber tracking in the in vivo NHP brains on a clinical 3 Tesla MRI scanner. Compared to fixed brains, the in vivo ADC was larger by a factor of 5. Also, the white-matter FA was 28% higher in the in vivo study as compared to our ex vivo experiments. Compared to short tdiff, long tdiff increased white-matter FA by 6.0±0.5%, diffusion was more anisotropic, tensor orientations along major fiber tracts were more coherent, and tracked fibers were about 10.1±2.9% longer in the corpus callosum and 7.3±2.8% longer along the cortico-spinal tract. The overall improvements in tractography were, however, less pronounced in the in vivo brain than in fixed brains. Nonetheless, these in vivo findings reinforce that DTI tractography at long diffusion time improves tracking of smaller fibers in regions of low fractional anisotropy

Relationships between human auditory cortical structure and function

The human auditory cortex comprises multiple areas, largely distributed across the supratemporal plane, but the precise number and configuration of auditory areas and their functional significance have not yet been clearly established. In this paper, we discuss recent research concerning architectonic and functional organisation within the human auditory cortex, as well as architectonic and neurophysiological studies in non-human species, which can provide a broad conceptual framework for interpreting functional specialisation in humans. We review the pattern in human auditory cortex of the functional responses to various acoustic cues, such as frequency, pitch, sound level, temporal variation, motion and spatial location, and we discuss their correspondence to what is known about the organisation of the auditory cortex in other primates. There is some neuroimaging evidence of multiple tonotopically organised fields in humans and of functional specialisations of the fields in the processing of different sound features. It is thought that the primary area, on Heschl's gyrus, may have a larger involvement in processing basic sound features, such as frequency and level, and that posterior non-primary areas on the planum temporale may play a larger role in processing more spectrotemporally complex sounds. Ways in which current knowledge of auditory cortical organisation and different data analysis approaches may benefit future functional neuroimaging studies which seek to link auditory cortical structure and function are discussed

Detailed mapping of the complex fiber structure and white matter pathways of the chimpanzee brain

Long-standing questions about human brain evolution may only be resolved through comparisons with close living evolutionary relatives, such as chimpanzees. This applies in particular to structural white matter (WM) connectivity, which continuously expanded throughout evolution. However, due to legal restrictions on chimpanzee research, neuroscience research currently relies largely on data with limited detail or on comparisons with evolutionarily distant monkeys. Here, we present a detailed magnetic resonance imaging resource to study structural WM connectivity in the chimpanzee. This open-access resource contains (1) WM reconstructions of a postmortem chimpanzee brain, using the highest-quality diffusion magnetic resonance imaging data yet acquired from great apes; (2) an optimized and validated method for high-quality fiber orientation reconstructions; and (3) major fiber tract segmentations for cross-species morphological comparisons. This dataset enabled us to identify phylogenetically relevant details of the chimpanzee connectome, and we anticipate that it will substantially contribute to understanding human brain evolution