Maturation of Dynamic Propagations and Neuromodulatory Substrates in Nonhuman Primates
Poster No:
1741
Submission Type:
Abstract Submission
Authors:
Kyoungseob Byeon1, Thomas Funck2, Alessandro Gozzi3, Nicola Palomero-Gallagher4, Michael Milham5, Ting Xu5
Institutions:
1Child Mind Institue, PALISADES PARK, NJ, 2Child Mind Institue, New York, NY, 3Istituto Italiano di Tecnologia, Rovereto, Trento, 4Research Centre Jülich, Jülich, Jülich, 5Child Mind Institute, New York, NY
First Author:
Co-Author(s):
Introduction:
The brain's dynamic spatiotemporal propagations shape neural circuit function, reflecting mechanisms underlying cognition and behavior (Meyer-Baese, 2022). These processes, evolving during development, are modulated by neurotransmitter systems that drive neurodevelopmental phenomena like neurogenesis and circuit formation (Hansen, 2022). Recent evidence suggests that functional dynamics have evolutionary origins and exhibit primate-specific dynamic states (Pang, 2022). However, the developmental progression of these dynamic propagations in nonhuman primates (NHPs) remains poorly understood, particularly in relation to the role of neuromodulatory systems. In this study, we analyzed resting-state fMRI data from a developmental macaque cohort alongside neurotransmitter receptor maps derived from post-mortem autoradiography. We aim to characterize spatiotemporal propagations in the NHP brain, examine their developmental changes during macaque childhood, and investigate how neuromodulatory systems contribute to the maturation of functional dynamics in NHPs.
Methods:
The fMRI dataset was obtained from the University of Wisconsin-Madison and is publicly available through the PRIMatE Data Exchange (Milham, 2018). It includes two cohorts collected from different scanners. Therefore, the sample was split into discovery (N=103, aged 0.85-4.42 years) and replication (N=346, aged 1.08-2.71 years) cohorts. Neurotransmitter receptor density maps were 3D reconstructed from prior studies (Funck, 2022) and aligned to the macaque brain template (Yerkes19). We applied the Complex Principal Component Analysis (CPCA) framework (Fig. 1A) to extract components that reflect recurring spatiotemporal propagations in brain activity for each animal (Bolt, 2022). The occurrence dominance of each dynamic component was quantified based on the proportion of variance explained. Fluctuation amplitudes and phase delays were further analyzed to map their developmental trajectories. To link functional dynamics to molecular substrates, we compared the spatial patterns of neurotransmitter receptor densities with moment-by-moment propagation maps. Age-related changes in these relationships were examined to reveal developmental trends.
Results:
We extracted complex principal components to reconstruct spatiotemporal propagations across different phases of the cycle (Fig. 1B). These propagations exhibited consistent spatial and temporal characteristics in both the discovery and replication cohorts (Fig. 1C). The first three patterns explained over 50% of fMRI variance, with each accounting for more than 10% individually (Fig. 1D). Pattern 1 showed a significant decline in dominance (ρ=-0.34, p < 0.001) from early juvenile to adolescent stages (Fig. 2A). Age-related changes in propagation amplitudes were observed in the complex coordinate space, with visual and default-mode networks showing the greatest decline, while regions like the principal sulcus and posterior central gyrus exhibited increased amplitudes (Fig. 2B). Figure 2E illustrates the average association between the spatial distribution of dynamic propagations and neurotransmitter receptor gradients for each age group. We observed significant age effects for receptors aligned with Pattern 1. Initially aligned with inhibitory GABAergic receptors (e.g., GABAA), Pattern 1 shifted toward excitatory glutamate receptors (e.g., AMPA, Kainate) with age (Fig. 2F).
Conclusions:
This study characterized the spatiotemporal propagations of neural activity and their significant developmental changes in NHPs. Using CPCA and neurotransmitter receptor mapping, we demonstrated that propagations, particularly Pattern 1, transition from dominance in inhibitory GABAergic systems to excitatory glutamate systems with age, highlighting the dynamic balance of excitatory and inhibitory processes in neural circuit maturation. These findings provide a framework for studying brain maturation and insights into the molecular basis of neural development in NHPs.
Lifespan Development:
Normal Brain Development: Fetus to Adolescence
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Normal Development 1
Transmitter Receptors 2
Keywords:
Development
FUNCTIONAL MRI
Neurotransmitter
1|2Indicates the priority used for review
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Provide references using APA citation style.
Funck, T. (2022). 3D reconstruction of ultra-high resolution neurotransmitter receptor atlases in human and non-human primate brains. bioRxiv, 2022-11.
Hansen, J. Y. (2022). Mapping neurotransmitter systems to the structural and functional organization of the human neocortex. Nature neuroscience, 25(11), 1569-1581.
Meyer-Baese, L. (2022). Spatiotemporal patterns of spontaneous brain activity: a mini-review. Neurophotonics, 9(3), 032209-032209.
Milham, M. P. (2018). An open resource for non-human primate imaging. Neuron, 100(1), 61-74.
Pang, J. C. (2022). Evolutionary shaping of human brain dynamics. Elife, 11, e80627.