Normative Analysis of Individual Brain Differences Based on a Population MRI-Based Atlas of Cynomolgus Macaques

The developmental trajectory of the primate brain varies substantially with aging across subjects. However, this ubiquitous variability between individuals in brain structure is difficult to quantify and has thus essentially been ignored. Based on a large-scale structural magnetic resonance imaging dataset acquired from 162 cynomolgus macaques, we create a species-specific 3D template atlas of the macaque brain, and deploy normative modeling to characterize individual variations of cortical thickness (CT) and regional gray matter volume (GMV). We observed an overall decrease in total GMV and mean CT, and an increase in white matter volume from juvenile to early adult. Specifically, CT and regional GMV were greater in prefrontal and temporal cortices relative to early unimodal areas. Age-dependent trajectories of thickness and volume for each cortical region revealed an increase in the medial temporal lobe, and decreases in all other regions. A low percentage of highly individualized deviations of CT and GMV were identified (0.0021%, 0.0043%, respectively, P \u3c 0.05, false discovery rate [FDR]-corrected). Our approach provides a natural framework to parse individual neuroanatomical differences for use as a reference standard in macaque brain research, potentially enabling inferences regarding the degree to which behavioral or symptomatic variables map onto brain structure in future disease studies

UNC-Emory Infant Atlases for Macaque Brain Image Analysis: Postnatal Brain Development through 12 Months

Computational anatomical atlases have shown to be of immense value in neuroimaging as they provide age appropriate reference spaces alongside ancillary anatomical information for automated analysis such as subcortical structural definitions, cortical parcellations or white fiber tract regions. Standard workflows in neuroimaging necessitate such atlases to be appropriately selected for the subject population of interest. This is especially of importance in early postnatal brain development, where rapid changes in brain shape and appearance render neuroimaging workflows sensitive to the appropriate atlas choice. We present here a set of novel computation atlases for structural MRI and Diffusion Tensor Imaging as crucial resource for the analysis of MRI data from non-human primate rhesus monkey (Macaca mulatta) data in early postnatal brain development. Forty socially-housed infant macaques were scanned longitudinally at ages 2 weeks, 3, 6, and 12 months in order to create cross-sectional structural and DTI atlases via unbiased atlas building at each of these ages. Probabilistic spatial prior definitions for the major tissue classes were trained on each atlas with expert manual segmentations. In this article we present the development and use of these atlases with publicly available tools, as well as the atlases themselves, which are publicly disseminated to the scientific community

A diffusion tensor imaging study of age-related changes in the white matter structural integrity in a common chimpanzee

Diffusion Tensor Magnetic Resonance Imaging was used to examine the age-related changes in white matter structural integrity in the common chimpanzee. Fractional Anisotropy(FA), a measure derived from the diffusion tensor data is sensitive to developmental and pathological changes in axonal density, myelination, size and coherence of organization of fibers within a voxel and thus reflects the white matter structural integrity. There is substantial evidence that white matter structural integrity decreases with age in humans. The long-term goal of this study is to compare the age-related changes in the white matter structural integrity among humans and chimpanzess to provide potential insights into the unique features of human aging. Different methods, including Region Of Interest (ROI) analysis, Tract Based Spatial Statistics (TBSS) are used to describe age-related changes in FA in a group of 21 chimpanzees. Strengths and limitations of these methods were discussed.M.S.Committee Chair: James K. Rilling; Committee Chair: Xiaoping Hu; Committee Member: Shella Keilholz; Committee Member: Todd M. Preus

A diffusion tensor MRI atlas of the postmortem rhesus macaque brain

The rhesus macaque (Macaca mulatta) is the most widely used nonhuman primate for modeling the structure and function of the brain. Brain atlases, and particularly those based on magnetic resonance imaging (MRI), have become important tools for understanding normal brain structure, and for identifying structural abnormalities resulting from disease states, exposures, and/or aging. Diffusion tensor imaging (DTI) -based MRI brain atlases are widely used in both human and macaque brain imaging studies because of the unique contrasts, quantitative diffusion metrics, and diffusion tractography that they can provide. Previous MRI and DTI atlases of the rhesus brain have been limited by low contrast and/or low spatial resolution imaging. Here we present a microscopic resolution MRI/DTI atlas of the rhesus brain based on 10 postmortem brain specimens. The atlas includes both structural MRI and DTI image data, a detailed three-dimensional segmentation of 241 anatomic structures, diffusion tractography, cortical thickness estimates, and maps of anatomic variability amongst atlas specimens. This atlas incorporates many useful features from previous work, including anatomic label nomenclature and ontology, data orientation, and stereotaxic reference frame, and further extends prior analyses with the inclusion of high-resolution multi-contrast image data

Disentangling the effects of early caregiving experience and heritable factors on brain white matter development in rhesus monkeys

Early social experiences, particularly maternal care, shape behavioral and physiological development in primates. Thus, it is not surprising that adverse caregiving, such as child maltreatment leads to a vast array of poor developmental outcomes, including increased risk for psychopathology across the lifespan. Studies of the underlying neurobiology of this risk have identified structural and functional alterations in cortico-limbic brain circuits that seem particularly sensitive to these early adverse experiences and are associated with anxiety and affective disorders. However, it is not understood how these neurobiological alterations unfold during development as it is very difficult to study these early phases in humans, where the effects of maltreatment experience cannot be disentangled from heritable traits. The current study examined the specific effects of experience (“nurture”)versus heritable factors (“nature”)on the development of brain white matter (WM)tracts with putative roles in socioemotional behavior in primates from birth through the juvenile period. For this we used a randomized crossfostering experimental design in a naturalistic rhesus monkey model of infant maltreatment, where infant monkeys were randomly assigned at birth to either a mother with a history of maltreating her infants, or a competent mother. Using a longitudinal diffusion tensor imaging (DTI)atlas-based tract-profile approach we identified widespread, but also specific, maturational changes on major brain tracts, as well as alterations in a measure of WM integrity (fractional anisotropy, FA)in the middle longitudinal fasciculus (MdLF)and the inferior longitudinal fasciculus (ILF), of maltreated animals, suggesting decreased structural integrity in these tracts due to early adverse experience. Exploratory voxelwise analyses confirmed the tract-based approach, finding additional effects of early adversity, biological mother, social dominance rank, and sex in other WM tracts. These results suggest tract-specific effects of postnatal maternal care experience versus heritable or biological factors on primate WM microstructural development. Further studies are needed to determine the specific behavioral outcomes and biological mechanisms associated with these alterations in WM integrity

Structural alterations in cortical and thalamocortical white matter tracts after recovery from prefrontal cortex lesions in macaques

Unilateral damage to the frontoparietal network typically impairs saccade target selection within the contralesional visual hemifield. Severity of deficits and the degree of recovery have been associated with widespread network dysfunction, yet it is not clear how these behavioural and functional brain changes relate with the underlying structural white matter tracts. Here, we investigated whether recovery after unilateral prefrontal cortex (PFC) lesions was associated with changes in white matter microstructure across large-scale frontoparietal cortical and thalamocortical networks. Diffusion-weighted imaging was acquired in four male rhesus macaques at pre-lesion, week 1, and week 8-16 post-lesion when target selection deficits largely recovered. Probabilistic tractography was used to reconstruct cortical frontoparietal fiber tracts, including the superior longitudinal fasciculus (SLF) and transcallosal fibers connecting the PFC or posterior parietal cortex (PPC), as well as thalamocortical fiber tracts connecting the PFC and PPC to thalamic nuclei. We found that the two animals with small PFC lesions showed increased fractional anisotropy in both cortical and thalamocortical fiber tracts when behaviour had recovered. However, we found that fractional anisotropy decreased in cortical frontoparietal tracts after larger PFC lesions yet increased in some thalamocortical tracts at the time of behavioural recovery. These findings indicate that behavioural recovery after small PFC lesions may be supported by both cortical and subcortical areas, whereas larger PFC lesions may have induced widespread structural damage and hindered compensatory remodeling in the cortical frontoparietal network

Three-dimensional digital template atlas of the Macaque brain

We present a new 3D template atlas of the anatomical subdivisions of the macaque brain, which is based on and aligned to the magnetic resonance imaging (MRI) data set and histological sections of the Saleem and Logothetis atlas. We describe the creation and validation of the atlas that, when registered with macaque structural or functional MRI scans, provides a straightforward means to estimate the boundaries between architectonic areas, either in a 3D volume with different planesof sections, or on an inflated brain surface (cortical flat map). As such, this new template atlas is intended for use as a reference standard for macaque brain research. Atlases and templates are available as both volumes and surfaces in standard NIFTI and GIFTI formats

An Open Resource for Non-human Primate Imaging

Non-human primate neuroimaging is a rapidly growing area of research that promises to transform and scale translational and cross-species comparative neuroscience. Unfortunately, the technological and methodological advances of the past two decades have outpaced the accrual of data, which is particularly challenging given the relatively few centers that have the necessary facilities and capabilities. The PRIMatE Data Exchange (PRIME-DE) addresses this challenge by aggregating independently acquired non-human primate magnetic resonance imaging (MRI) datasets and openly sharing them via the International Neuroimaging Data-sharing Initiative (INDI). Here, we present the rationale, design, and procedures for the PRIME-DE consortium, as well as the initial release, consisting of 25 independent data collections aggregated across 22 sites (total = 217 non-human primates). We also outline the unique pitfalls and challenges that should be considered in the analysis of non-human primate MRI datasets, including providing automated quality assessment of the contributed datasets