Investigation of myelin development in human visual cortex with qMRI and immunohistochemistry.
Poster No:
1737
Submission Type:
Abstract Submission
Authors:
Clara Bacmeister1, Vaidehi Natu2, Sarah Tung2, Christina Tyagi2, Xiaoqian Yan3, Alex Rezai4, Congyu Liao1, Nan Wang1, Xiaozhi Cao1, Kawin Setsompop1, Mercedes Paredes5, Kalanit Grill-Spector6
Institutions:
1Stanford University, Stanford, CA, 2Stanford Universtiy, Stanford, CA, 3Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, Fudan, 4Emory University, Atlanta, GA, 5University of California San Francisco, San Francisco, CA, 6Department of Psychology, Stanford University, Stanford, CA
First Author:
Co-Author(s):
Xiaoqian Yan
Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University
Shanghai, Fudan
Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University
Shanghai, Fudan
Introduction:
Myelination is a lifelong process that can be modified by experience and exert profound effects on circuit function, learning, and memory. Yet, how myelin contributes to the development of human visual circuits is unknown.
Methods:
We examined the development of myelin using a combination of ex vivo histology (immunohistochemistry, IHC) (Fig. 1a) and in vivo quantitative MRI (qMRI) of tissue relaxation rate R1 in three functionally-distinct regions of human visual cortex: primary visual cortex (V1) in calcarine sulcus, and high-level face- and place-selective cortex in fusiform gyrus (FG) and collateral sulcus (CoS), respectively. We chose these regions as they include early and high-level visual areas that can be identified using anatomical landmarks alone in ex-vivo samples (Holmes 1918, Weiner 2014; Weiner 2018). IHC of myelin basic protein (MBP) was done in 5 infant samples (0 to 6 months old), a 2 year old, a 9 year old, and a 25 year old. Myelin coverage was analyzed using semi-automated thresholding of MBP+ immunolabeling to calculate total cortical area covered by MBP+ signal. Cross-sectional and longitudinal qMRI was done in 34 infants (newborn-12 month olds) and cross-sectional qMRI was done in 52 5-25 year olds. In adults, R1 in cortex depends on myelin (Gomez 2017; Natu 2018) and the physiochemical tissue properties (Mezer 2013; Edwards 2018).
Results:
Using IHC, we find that myelin increases in infancy in all areas, but more rapidly in the calcarine sulcus (V1) than in the collateral sulcus (CoS; place-selective) and fusiform gyrus (FG; face-selective) (Fig. 1a,b). Surprisingly, there is little myelin development from 6 to 24 months of age, while childhood (2 to 9 years old) shows a second wave of myelination. Within visual areas, cortical layers show distinct myelin development: deep layers of cortex (L4-L6) myelinate earlier and more rapidly than superficial layers (L1-L3). However, deep layers of V1 show earlier and more rapid myelination relative to Cos and FG. Furthermore, while myelin coverage in superficial V1 and CoS is similar in childhood and adulthood (9 vs. 25 years old), in the FG, myelin coverage is lower in the 9 year old than in the adult, suggesting continued myelination of superficial FG during adolescence. Cortical R1 is higher in V1 than face- and place-selective cortex at birth, but both higher-level regions show larger increases in R1 in the first year of life (Fig. 1c). Additionally, cortical R1 plateaus earliest in V1. In contrast, cortical R1 reaches adult levels in place-selective cortex in childhood (5-9 years old), and cortical R1 is still lower in 10-12 year-old children than in adults in face-selective cortex, suggesting prolonged development of face-selective cortex into adulthood. Across ages and areas, there is a positive linear relationship between cortical R1 and myelin level estimated from IHC (Fig. 1d), suggesting that myelin contributes to cortical R1, such that linear increases in myelin will linearly increase R1. Additionally, both primary and high-level visual cortex are largely devoid of myelin at birth, suggesting that cortical R1 value at birth (0.49 s-1, similar value as ventricular R1) is not driven by myelin.
·Myelination across three human visual areas (V1; CoS, place-; and FG, face-selective) from 0 to 25 years of life, measured by immunohistochemistry (a,b), qMRI (c), and compared across modalities (d).
Conclusions:
We observe waves of myelin development in cortex: myelination proceeds rapidly during the first 6 months of life, stagnates from 6 to 24 months, and then develops slowly in childhood. Deep cortical layers myelinate earlier than superficial layers, and deep V1 myelinates more rapidly than high-level areas in infancy. Superficial layers of FG show prolonged myelination, the majority of which occurs from 2 years old into adulthood. We confirm that developmental changes in R1 are correlated to changes in myelin and identify a baseline cortical R1 value independent of myelin. These findings identify differences in spatiotemporal development of myelin within the human visual system, suggesting the window of plasticity may be extended in higher-level than primary visual cortex.
Lifespan Development:
Normal Brain Development: Fetus to Adolescence 2
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Cortical Cyto- and Myeloarchitecture 1
Keywords:
Cellular
Cortex
Development
Myelin
NORMAL HUMAN
STRUCTURAL MRI
Vision
1|2Indicates the priority used for review
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Provide references using APA citation style.
Gomez J, Barnett MA, Natu V, Mezer A, Palomero-Gallagher N, Weiner KS, Amunts K, Zilles K, Grill-Spector K. (2017) Microstructural proliferation in human cortex is coupled with the development of face processing. Science 355,68-71(2017).
Holmes, G. (1918) Disturbances of visual orientation. Br J Ophthalmol. 2(9):449–468.
Mezer A, Yeatman JD, Stikov N, Kay KN, Cho NJ, Dougherty RF, Perry ML, Parvizi J, Hua le H, Butts-Pauly K, Wandell BA. (2013) Quantifying the local tissue volume and composition in individual brains with magnetic resonance imaging. Nat Med. 19(12):1667-72.
Natu VS, Gomez J, Barnett M, Jeska B, Kirilina E, Jaeger C, Zhen Z, Cox S, Weiner KS, Weiskopf N, and Grill- Spector K. (2019) Apparent thinning of human visual cortex during childhood is associated with myelination. Proc Natl Acad Sci USA 116:20750–20759.
Weiner KS, Golarai G, Caspers J, Chuapoco MR, Mohlberg H, Zilles K, Amunts K, Grill-Spector K. (2014). The mid-fusiform sulcus: A landmark identifying both cytoarchitectonic and functional divisions of human ventral temporal cortex. NeuroImage. 84,453-465.
Weiner KS, Barnett MA, Lorenz S, Caspers J, Stigliani A, Amunts K, Zilles K, Fischl B, Grill-Spector K. (2017) The Cytoarchitecture of Domain-specific Regions in Human High-level Visual Cortex. Cerebral Cortex. 27(1)146–161.