A deep-to-superficial axis of prefrontal cortex myelin maturation balances plasticity and stability
Poster No:
1011
Submission Type:
Abstract Submission
Authors:
Valerie Sydnor1, Daniel Petrie1, Shane McKeon1, Alyssa Famalette1, Will Foran1, Finnegan Calabro1, Bea Luna1
Institutions:
1University of Pittsburgh, Pittsburgh, PA
First Author:
Co-Author(s):
Introduction:
The human prefrontal cortex (PFC) is an evolutionarily-expanded core of association cortex that exhibits protracted developmental plasticity (Larsen, 2018; Sydnor, 2023). Understanding when regulators of plasticity mature in the PFC can reveal when higher-order cognitive circuits are malleable, as well as when they transition to a state of stability. Animal studies have established that the growth of intracortical myelin is key restrictor of neuronal plasticity (McGee, 2005, Xin, 2024). Complementary human studies show that myelin matures last in the PFC (Baum, 2022). However, how trajectories of myelin growth vary across PFC layers−which differ in their connectivity targets, biological properties, and functional roles−is not known. Here, we harness ultra-high field quantitative imaging of intracortical myelin collected from youth longitudinally to characterize timescales of plasticity across deep and superficial layers of frontal cortex and link PFC myelination to neurocognitive specialization.
Methods:
We leveraged 7T R1 data collected from an accelerated longitudinal sample (10-32 years; 140 individuals with 215 scans; 70 female) to map myelin in the frontal cortical mantle. R1 is a histologically-validated and quantitative myelin imaging metric (Lazari, 2021; Lutti, 2014). R1 maps were derived from B1+ corrected T1 maps, projected to individual-specific cortical surfaces, and applied to index myelin at 7 cortical depths in frontal regions (excluding depths near pia and white matter). Generalized additive mixed models (GAMMs) were used to model relationships between depth-specific R1 and age; the first derivative of age splines was calculated to index myelination rates and maturation ages. GAMMs were also used to quantify relationships between R1 and both EEG-derived cortical activity and task-based indices of learning and processing speed.
Results:
R1 significantly increased (pFDR < 0.05) in > 85% of frontal regions at all 7 cortical depths. A gradient of R1 maturational rate and timing was evident across depths: R1 increased at a slower rate and matured at older ages moving from deeper to superficial depths (Fig. 1A-B). Within each intracortical depth, regional variation in the rate of R1 increase correlated with hierarchical axes of cortical organization and cytoarchitectural variation; correlations were significant and strongest in superficial depths (Fig. 1C-H). Clustering of frontal regions based on depth-wise myelination trajectories uncovered a motor cluster (Neurosynth decoding: "movement") with early plateauing R1 trajectories at all depths, a lateral PFC cluster ("cognitive control") with adolescent plateauing trajectories in deep cortex but linear trajectories in superficial cortex, and a medial PFC cluster ("emotion regulation") with near-linear trajectories at all depths (Fig. 2). Relating R1 to EEG activity revealed that higher R1 was associated with a flatter aperiodic slope−a functional index of higher E/I balance and faster timescales of activity (Halgren, 2021, McKeon 2024). This association was significantly stronger for R1 in deep than superficial cortex for all EEG electrodes in lateral PFC (depth interaction ps < 0.05). Finally, higher R1 in both deep and superficial depths of the dorsolateral PFC was significantly (pFDR < 0.05) related to enhanced learning rates and faster cognitive (but not sensorimotor) processing speed.
·Figure 1. Deep-to-superficial and hierarchical axes of frontal cortex R1 maturation
·Figure 2. Depth-wise R1 maturational profiles diverge between functionally distinct cortical areas
Conclusions:
Myelin maturation is heterochronous in deep and superficial PFC and has dissociable functional consequences. Deep PFC layers, which comprise cortical-subcortical and feed-back "output" projections, show earlier myelin maturation and consolidation of circuitry. Superficial PFC layers, the main source of cortico-cortical "computational" connections, exhibit temporally-extended myelination that may endow them with protracted malleability. Asynchronous laminar maturation of myelin may allow the PFC to co-express stability and plasticity at different stages in layer-stratified processing hierarchies.
Higher Cognitive Functions:
Executive Function, Cognitive Control and Decision Making
Lifespan Development:
Normal Brain Development: Fetus to Adolescence 1
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Cortical Cyto- and Myeloarchitecture 2
Novel Imaging Acquisition Methods:
Anatomical MRI
EEG
Keywords:
Cognition
Cortical Layers
Development
Electroencephaolography (EEG)
HIGH FIELD MR
Myelin
Plasticity
Other - quantitative MRI; association cortex; excitation/inhibition balance
1|2Indicates the priority used for review
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Provide references using APA citation style.
Halgren, M., et al. (2021). The timescale and magnitude of 1/f aperiodic activity decrease with cortical depth in humans, macaques, and mice. bioRxiv. doi.org/10.1101/2021.07.28.454235
Larsen, B., & Luna, B. (2018). Adolescence as a neurobiological critical period for the development of higher-order cognition. Neuroscience & Biobehavioral Reviews, 94, 179-195.
Lazari, A., & Lipp, I. (2021). Can MRI measure myelin? Systematic review, qualitative assessment, and meta-analysis of studies validating microstructural imaging with myelin histology. Neuroimage, 230, 117744.
Lutti, A., et al. (2014). Using high-resolution quantitative mapping of R1 as an index of cortical myelination. NeuroImage, 93, 176–188.
McGee, A. W., et al. (2005). Experience-Driven Plasticity of Visual Cortex Limited by Myelin and Nogo Receptor. Science, 309(5744), 2222–2226.
McKeon, S. D., et al. (2024). Aperiodic EEG and 7T MRSI evidence for maturation of E/I balance supporting the development of working memory through adolescence. Developmental Cognitive Neuroscience, 66, 101373.
Sydnor, V. J., et al. (2023). Intrinsic activity development unfolds along a sensorimotor–association cortical axis in youth. Nature Neuroscience, 26(4), Article 4.
Xin, W., et al. (2024). Oligodendrocytes and myelin limit neuronal plasticity in visual cortex. Nature, 633(8031), 856–863.