Brain Charts for the Rhesus Macaque Lifespan

Abstract

Recent efforts to chart human brain growth across the lifespan using large-scale MRI data have provided reference standards for human brain development. However, similar models for nonhuman primate (NHP) growth are lacking. The rhesus macaque, a widely used NHP in translational neuroscience due to its similarities in brain anatomy, phylogenetics, cognitive, and social behaviors to humans, serves as an ideal NHP model. This study aimed to create normative growth charts for brain structure across the macaque lifespan, enhancing our understanding of neurodevelopment and aging, and facilitating cross-species translational research. Leveraging data from the PRIMatE Data Exchange (PRIME-DE) and other sources, we aggregated 1,522 MRI scans from 1,024 rhesus macaques. We mapped non-linear developmental trajectories for global and regional brain structural changes in volume, cortical thickness, and surface area over the lifespan. Our findings provided normative charts with centile scores for macaque brain structures and revealed key developmental milestones from prenatal stages to aging, highlighting both species-specific and comparable brain maturation patterns between macaques and humans. The charts offer a valuable resource for future NHP studies, particularly those with small sample sizes. Furthermore, the interactive open resource (https://interspeciesmap.childmind.org) supports cross-species comparisons to advance translational neuroscience research.

Fig 1. |. Macaque brain charts.

a) Comparison of lifespan and age milestones between macaques and human. b) Demographic box plot of rhesus macaque data used in the analysis. Data includes 1,024 macaques with 1,522 MRI scans collected from 23 unique sites. c) Raw total tissue volume (in mL) for cortical gray matter, white matter, subcortical gray matter, and the lateral ventricles. Age (x-axis) is shown on a log scale, with points colored by sex. d) Normative trajectories of the four tissue volumes fit with GAMLSS, incorporating sex stratification and site-specific random effects, represented as median centile (the 50th centile) fitted curves of the population. Dotted lines represent 2.5% and 97.5% centile distributions, with both curves colored by sex. e) Site-specific curves for each tissue type. Trajectories show ranges of each contributing dataset with the site-specific random effect removed. f) Volumetric rate of growth (in mm³ per day) for each of the four global tissue types, colored by sex. Solid vertical lines denote the age at which the growth rate peaked.

Fig 2. |. Global and regional cortical morphometric phenotypes and growth rates.

a) Scatterplots for total cerebrum volume, total cortical surface area, and mean cortical thickness, colored by sex. Volume is measured in mL, surface area in mm² and cortical thickness in mm. All plots are shown on a log-scaled x axis. b) Normative trajectories with associated 2.5% and 97.5% centile distributions for each metric, stratified by sex. c) Growth rates per day of the respective phenotype, stratified by sex. Solid vertical lines again denote peak growth. d) Surface maps of regional growth rate for macaque and human at their respective total gray matter volume peak age (0.74 years for macaque, 5.90 years for human). Sex-stratified models were generated for bilateral averages of each region, and growth rates for male are shown on the left hemisphere for visualization (female maps in Supplementary Information 4.3). Macaque regions are defined by the Markov parcellation and human regions are defined by the Desikan-Killiany parcellation. Human growth rate data was obtained from the human brain charts project.

Fig. 3 |

Cross-species comparison of neurodevelopmental milestones. Normative trajectories of each global MRI phenotype for both human (top) and macaque (middle) as a function of age (log-scaled). Regional gray matter volume are shown at highlighted developmental milestones^,–. Both trajectories and regional gray matter volume are shown as a proportion of their maximum. Circles on the trajectories indicate the peak value of each phenotype (i.e. the maxima of the median trajectories), and triangles represent the peak growth velocity. Developmental milestones are approximately matched for each species for visualization purposes. Bottom panel depicts commonly used developmental milestones in macaque stratified by sex. Ranges depict time of expected onset (bars: walking onset, teeth eruption, age of first birth, first reproduction, weaning) or completion of specific behavioral or physiological maturity (lines: sexual maturation, brain resting metabolic rate (RMR), synaptic density, gestation)^,–.

Fig 4. |. Regional peak age of morphological phenotypes, proportion of gray matter volume for each networks and cognition decoding of gray matter growth.

a) Regional peak age of gray matter volume, surface area, and cortical thickness for human and macaque. Top: Macaque peak age maps. Middle: Human peak age maps from the human charts project. Bottom: Relative differences in peak age rank between humans and macaques calculated by subtracting macaque peak age rank from the human peak age rank. Macaque peak age maps were ranked and transformed into human space for direct comparison. Red color indicates regions where humans mature later than macaques, compared to other cortical regional development; blue color indicates that macaque matures later in cortical development. b) Averaged proportional growth within networks at each developmental stage for both human and macaque. The developmental stages were approximately matched between human and macaque by averaging the respective proportions of total lifespan at each stage as noted in Fig 3). c) Decoded cognition development trajectories from birth to adolescence for human (0-18 years) and macaque (0-6 years). Regional growth maps of gray matter volume with a progressively increased interval (human: per 3 months; macaque: per month) were decoded using Neurosynth meta-analysis. Shaded lines represent individual terms associated with a topic, and solid lines represent the average.

Fig 5. |. Demonstration of interactive cross-species brain charts.

Top panel depicts normative models of the morphological measurements derived from MRI for macaque and human. Bottom panel depicts homologous regions between human and macaque on cortical surface maps with associated growth trajectories. Growth trajectories for each region are shown on a log scale, including centile trajectories, stratification by sex, and annotations for its maximum (circles) and peak growth velocity (triangles).