Mapping orbitofrontal-limbic maturation in non-human primates: A longitudinal magnetic resonance imaging study
Introduction
Brain development is accompanied by a range of spatiotemporally complex neural events (Bakken et al., 2016, Giedd et al., 1999, Lebel et al., 2008, Wierenga et al., 2014). Such complexity may result in vulnerability to abnormal structural and functional maturation of the brain, and associated neuropathological changes. Indeed, abnormalities in the fronto-limbic regions of the brain have been reported in a number of neuropsychiatric disorders and diseases (Kujawa et al., 2016, Saitoh et al., 2001, Schumann et al., 2004, Vai et al., 2015). These brain regions include the orbitofrontal cortex, cingulate cortex, amygdala, and hippocampus, which are important for construction and maintenance of smooth social relationships between individuals by inducing and regulating emotion, self-monitoring, and control, associating memories, expecting outcomes from actions, and enhancing memories for emotionally-arousing events (Clarke et al., 2015, Law et al., 2009a, Law et al., 2009b, Jackson et al., 2016, Kujawa et al., 2016, Rolls, 2015, Shenhav et al., 2013, Yu et al., 2014).
A detailed understanding of the normal developmental patterns and connectivity of these front-limbic regions may help to clarify the anatomical mechanisms underlying their functions. Proper structural maturation in the front-limbic regions is likely important for optimal development of these functions. However, the deep locations of the orbitofrontal-limbic regions in the brain and their marked individual variability limits in vivo physiological studies, such as those using electrodes and tracer injection, when compared with neocortical areas. Further, previous studies on orbitofrontal-limbic regions have produced inconsistent results in terms of gender and hemispheric effects (Dennison et al., 2013, Giedd et al., 1996, Goddings et al., 2014, Marwha et al., 2017, Pedraza et al., 2004, Wierenga et al., 2014). Thus, the detailed patterns of development of the orbitofrontal-limbic regions structures remain elusive.
Magnetic resonance imaging (MRI) is an ideal, noninvasive method for studying longitudinal development of deep brain regions in vivo, and can minimize confounding factors such as individual differences in growth. MRI can also provide multiple types of image contrast by using different scanning acquisition sequences. In particular, diffusion-weighted MRI data provides information through a set of mathematical operations, including diffusion tensor imaging (DTI) data sets such as fractional anisotropy (FA), apparent mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD). These variables are calculated from the eigenvectors and eigenvalues of apparent water diffusivity, which is influenced by the structure and characteristics of tissues (Hüppi and Dubois, 2006, Mori and Zhang, 2006). Hence, DTI data can be used to assess developmental changes at the microstructural level, including local axonal myelination (Deoni et al., 2012; deIpolyi et al., 2005; Hüppi and Dubois, 2006, Oishi et al., 2013, Tournier et al., 2004). Diffusion tractography can also be used to delineate development of structural neural networks (Aggarwal et al., 2015, Hüppi and Dubois, 2006, Oishi et al., 2013).
However, it is difficult to assess longitudinal brain development in humans using MRI or other techniques, as it is time-consuming, costly, and limited to a few time points. Further, it is difficult to control for genetic and environmental factors that are likely to cause individual variability. Thus, in the present study, we examined front-limbic region development in a non-human primate, the common marmoset (Callithrix jachus), which provides an excellent model for studying human-like traits (Abbott et al., 2003, Miller et al., 2016, Okano et al., 2016, t'Hart et al., 2012). Despite having smooth surface, the marmoset brain shares many anatomical features and neural growth patterns found in other primates including humans, especially in the temporal lobes and internal structures (Newman et al., 2009, Ichinohe, 2015, Oga et al., 2013, Sasaki et al., 2015). A particular strength of marmosets over other non-human primates used in research (e.g., rhesus macaque) is their colony structure. Marmoset colonies are organized into a family unit (Rothe and Darms, 1993). The presence of both maternal and paternal care, and even elder siblings' care, allows the assessment of parenting and familial effects on brain development. Human imaging studies of psychiatric disorders/disease have reported a relationship among anatomical structures in the fronto-limbic regions and familial factors (Vai et al., 2015, Whittle et al., 2008). These regions are also affected by parenting in marmosets (Law et al., 2009a, Law et al., 2009b, Schultz-Darken et al., 2016). Importantly, marmosets mature faster than other primates, reaching puberty at approximately 9 months, and sexually maturity at 2 years (de Castro Leão et al., 2009, Schultz-Darken et al., 2016, Yamamoto, 1993). This makes the common marmoset an ideal primate species to collect longitudinal data over a relatively short time period. Nevertheless, the degree to which the developmental patterns in the marmoset are similar to those in humans remain unclear.
In the present study, we acquired longitudinal MRI data in common marmosets from infancy to early adulthood to assess the anatomical development of orbitofrontal-limbic regions, including the orbitofrontal cortex, cingulate cortex, amygdala, and hippocampus. Specifically, we tested the hypothesis that the orbitofrontal-limbic regions in common marmosets grow non-linearly with age, and with sex and hemispheric influences, as observed in humans (Giedd et al., 1996, Goddings et al., 2014, Sussman et al., 2016). As these regions are functionally related in common marmosets (Clarke et al., 2015), we also hypothesized that their developmental patterns would be synchronized.
Section snippets
Animals
This study was approved by the local Animal Experiment Committee and was conducted in accordance with the Guidelines for Conducting Animal Experiments of Central Institute for Experimental Animals (Approval number 14040A, 16017A). Ongoing longitudinal brain MRI data were obtained from 23 normal developing common marmosets from five families (11 males, 12 females). All except one animal grew in the same size cages with their parents, littermates, and elder and/or younger siblings until at least
Results
The spaghetti plots and regression lines for the orbitofrontal cortex, cingulate cortex, amygdala, and hippocampus are shown in Fig. 3, Fig. 4, Fig. 5, Fig. 6. The regression coefficients are shown in Table 1, Table 2. The averaged T2WI, FA, MD, RD, AD, and FOD maps of the samples across the ages (1, 3, 6, 9, 12, 15, and 18 months of age) can be accessed at https://doi.org/10.24475/bminds.mri.kau.3236.
Structural development
In the present study, we found non-linear morphometric changes in growth and microstructure of the orbitofrontal-limbic regions in common marmosets from infancy to early adulthood. The volumetric trajectories of all measured regions followed biexponential curves. Such non-linear growth patterns are also seen in humans (Giedd et al., 1996, Goddings et al., 2014, Sussman et al., 2016) and other non-human primates (Hunsaker et al., 2014, Scott et al., 2016).
A period of marked brain growth was
Funding
This study was supported by a Grant-in-Aid from the Japan Society for the Promotion of Science (JSPS) Research Fellowship [grant number 16J07159]; and the program for Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) from the Japan Agency for Medical Research and development (AMED) [grant number 15653395].
Declaration of interest
Conflicts of interest: None.
Acknowledgements
We thank Alexander Woodward for help in recreating the Hashikawa label for the MRI brain template, Ryosuke Ishihara, Ryutaro Yano, Marin Nishio, and Yawara Haga for technical support, Misaki Naganuma and other staff at CIEA for animal care, and Makoto Fukushima for writing assistance.
References (93)
- et al.
An integrated approach to correction for off-resonance effects and subject movement in diffusion MR imaging
Neuroimage
(2016) - et al.
MR diffusion tensor spectroscopy and imaging
Biophys. J.
(1994) - et al.
Track-density imaging (TDI): super-resolution white matter imaging using whole-brain track-density mapping
Neuroimage
(2010) - et al.
New developmental stages for common marmosets (Callithrix jacchus) using mass and age variables obtained by K-means algorithm and self-organizing maps (SOM)
Comput. Biol. Med.
(2009) - et al.
Comparing microstructural and macrostructural development of the cerebral cortex in premature newborns: diffusion tensor imaging versus cortical gyration.
NeuroImage
(2005) - et al.
Investigating white matter development in infancy and early childhood using myelin water faction and relaxation time mapping
NeuroImage
(2012) - et al.
The influence of puberty on subcortical brain development
NeuroImage
(2014) - et al.
Current models of the marmoset brain
Neurosci. Res.
(2015) - et al.
Hand preference depends on posture in common marmosets
Behav. Brain Res.
(2013) - et al.
Population-averaged standard template brain atlas for the common marmoset (Callithrix jacchus)
NeuroImage
(2011)
Diffusion tensor imaging of brain development
Semin. Fetal Neonatal Med.
On-going elucidation of mechanisms of primate specific synaptic spine development using the common marmoset (Callithrix jacchus)
Neurosci. Res.
Altered development of amygdala-anterior cingulate cortex connectivity in anxious youth and young adults
Biol. Psychiatry Cognit. Neurosci. Neuroimaging
Meta-analysis reveals a lack of sexual dimorphism in human amygdala volume
NeuroImage
Marmosets: a neuroscientific model of human social behavior
Neuron
Principles of diffusion tensor imaging and its applications to basic neuroscience research
Neuron
A combined histological and MRI brain atlas of the common marmoset monkey, Callithrix jacchus
Brain Res. Rev.
Quantitative evaluation of brain development using anatomical MRI and diffusion tensor imaging
Int. J. Dev. Neurosci.
Brain/MINDS: a Japanese national brain project for marmoset neuroscience
Neuron
The common marmoset as a novel animal model system for biomedical and neuroscience research applications
Semin. Fetal Neonatal Med.
Limbic systems for emotion and for memory, but no single limbic system
Cortex
BrainSuite: an automated cortical surface identification tool
Med. Image Anal.
The expected value of control: an integrative theory of anterior cingulate cortex function
Neuron
Advances in functional and structural MR image analysis and implementation as FSL
Neuroimage
The human hippocampus is not sexually-dimorphic: meta-analysis of structural MRI volumes
Neuroimage
The marmoset monkey: a multi-purpose preclinical and translational model of human biology and disease
Drug Discov. Today
Robust determination of the fibre orientation distribution in diffusion MRI: non-negativity constrained super-resolved spherical deconvolution
NeuroImage
Direct estimation of the fiber orientation density function from diffusion-weighted MRI data using spherical deconvolution
NeuroImage
Abnormal cortico-limbic connectivity during emotional processing correlates with symptom severity in schizophrenia
Eur. Psychiatr.
Denoising of diffusion MRI using random matrix theory
NeuroImage
Weighted linear least squares estimation of diffusion MRI parameters: strengths, limitations, and pitfalls
NeuroImage
Functional differences in emotion processing during adolescence and early adulthood
NeuroImage
Typical development of basal ganglia, hippocampus, amygdala and cerebellum from age 7 to 24
NeuroImage
Physical, hormonal and behavioural aspects of sexual development in the marmoset monkey, Callithrix jacchus
J. Reprod. Fertil.
Aspects of common marmoset basic biology and life history important for biomedical research
Comp. Med.
Diffusion MR microscopy of cortical development in the mouse embryo
Cereb. Cortex
Factor analysis and AIC
Psychometrika
Advanced normalization tools (ANTS)
Insight J.
A comprehensive transcriptional map of primate brain development
Nature
Myelination of a key relay zone in the hippocampal formation occurs in the human brain during childhood, adolescence, and adulthood
Arch. General Psychiatr.
Hand preference of the common marmoset (Callithrix jacchus): problem solving and responses in a novel setting
J. Comp. Psychol.
Inflection: Finds the Inflection Point of a Curve
Regional inactivations of primate ventral prefrontal cortex reveal two distinct mechanisms underlying negative bias in decision making
Proc. Natl. Acad. Sci. U. S. A.
Mapping subcortical brain maturation during adolescence: evidence of hemisphere- and sex-specific longitudinal changes
Dev. Sci.
Informative drop-out in longitudinal data analysis
Appl. Stat.
Brain development during childhood and adolescence: a longitudinal MRI study
Nat. Neurosci.
Cited by (16)
Autism spectrum disorder
2022, Neurobiology of Brain Disorders: Biological Basis of Neurological and Psychiatric Disorders, Second EditionRats exposed to intermittent ethanol during late adolescence exhibit enhanced habitual behavior following reward devaluation
2021, AlcoholCitation Excerpt :Brain maturation during early adolescence is associated with reductions of volume within the striatum (Goddings et al., 2014; Lenroot et al., 2007), and increases in dopaminergic innervation (Hoops et al., 2018; Willing, Cortes, Brodsky, Kim, & Juraska, 2017) and synaptic pruning in the PFC (Drzewiecki, Willing, & Juraska, 2016; Mallya, Wang, Lee, & Deutch, 2019). In contrast, maturational changes during late adolescence and emerging adulthood are characterized by further refinement and strengthening of circuitry involving the PFC (Baker et al., 2015; Uematsu et al., 2017; van Duijvenvoorde, Westhoff, de Vos, Wierenga, & Crone, 2019). Thus, ethanol exposure during adolescence may influence different aspects of brain maturation due to the timing of that exposure.
Commonality and variance of resting-state networks in common marmoset brains
2024, Scientific ReportsLongitudinal mapping of the development of cortical thickness and surface area in rhesus macaques during the first three years
2023, Proceedings of the National Academy of Sciences of the United States of AmericaAn analysis of neurovascular disease markers in the hippocampus of Tupaia chinensis at different growth stages
2023, Frontiers in Neurology