Quantitative Imaging of Myelin Plasticity

Myelin is increasingly recognised as a key site for the regulation and implementation of brain plasticity. Recent advancements in non-invasive myelin-sensitive neuroimaging have the potential to provide unique insights into the biology of myelin across species. In this talk, I will provide a brief overview of the technical advantages and challenges associated with these techniques, alongside a discussion of the literature validating myelin-sensitive measures (Lazari and Lipp, 2021). I will then highlight individual examples of projects applying myelin-sensitive MRI to investigate the physiology, plasticity and evolution of the brain, using the motor network as a case study. First, I will show that the myelin content of white matter tracts can be linked to cortico-cortical interactions and behaviour (Lazari et al., 2022a). Second, I will demonstrate how myelin-sensitive imaging can be used longitudinally to track changes in myelination induced by non-invasive brain stimulation and to investigate the mechanisms underlying Hebbian myelin plasticity (Lazari et al., 2022b). Third, I will illustrate how myelin-sensitive imaging can provide indirect markers of cortical hierarchy and enable comparisons of network anatomy between species (Lazari et al., 2024). Together, these studies highlight the potential of myelin-sensitive neuroimaging techniques in advancing our understanding of brain structure and function. 

​​The human cerebral cortex undergoes protracted and asynchronous postnatal myelination that extends throughout adolescence and helps to refine ongoing circuit plasticity. Histological and neuroimaging studies have shown that the human cortex does not myelinate synchronously; rather, sensorimotor cortex myelinates early and the prefrontal cortex (PFC) myelinates late. However, when myelin matures across PFC cortical layers—which differ in their connectivity targets, neurobiological features, and functional roles—is not clear, precluding insight into the maturation of layer-stratified cognitive processing hierarchies. This talk will explore findings obtained using 7 Tesla relaxometry data collected longitudinally from adolescents and young adults (ages 10 to 32 years) to chart myelin maturation across deep and superficial layers of the frontal cortex and link myelination to neurocognitive specialization. The talk will first present evidence from intracortical depth profiling of a deep-to-superficial axis of myelin maturational timing in the frontal cortical ribbon. Next, the talk will describe results obtained when integrating cortical myelin imaging with EEG, which link higher myelin in deeper layers of the lateral PFC to a faster timescale of dynamical changes in neural activity. Finally, the talk will highlight data relating myelin in deep and superficial PFC to higher learning rates and faster cognitive, but not sensorimotor, processing speed. Talk attendees will gain an appreciation for how divergent maturational timing in deep and superficial layers may be a mechanism through which late-developing association cortex balances cognitively-relevant increases in circuit stability with extended neuroplasticity. 

This presentation explores the plasticity of cortical myelin and its relationship to intrinsic brain function and behavioral adaptation, with a particular focus on the social domain. We examine myelin plasticity during adolescence and adulthood, highlighting its role in responding to psychosocial stress and social mental training.

Adolescent Myelin Plasticity and Psychosocial Stress: During adolescence, the brain undergoes substantial remodeling of both structure and function, especially in association regions. This developmental stage coincides with a rise in psychiatric disorders, influenced by genetic and environmental factors. Using myelin-sensitive Magnetic Transfer imaging based on the MPM sequence, we investigated how psychosocial stress impacts myelin plasticity and functional connectivity during this critical period. Our findings show that individuals that are more adaptive to psychosocial stress show increased maturation of myelin in the prefrontal cortex which is associated with greater stability in functional networks. These local changes are accompanied by reconfiguration of both microstructure and functional networks, with strongest reconfigurations in more adaptive individuals. These results underscore the relationship between structural plasticity and behavioral adaptation to psychosocial stressors during adolescence.

Social Mental Training in Adults: In a second study with adults, we examined the effects of social mental training on three functional domains—attention-mindfulness, emotion-motivation, and perspective-taking—over three months on brain microstructure, measured using MP2RAGE, and function. We observed domain-specific functional changes in brain networks linked to attention and interoception. Attention-mindfulness training led to distinct functional changes compared to perspective-taking training, with networks showing stronger functional integration following perspective-taking and stronger segregation following attention-mindfulness training. Moreover, between the three training modules, microstructural alterations, largely reflecting myelination changes, varied spatially across cortical regions and showed depth-specific patterns, suggesting that remodeling processes differ between superior and deep cortical layers. Importantly, these structural and functional changes were associated with behavioral outcomes, demonstrating that brain plasticity persists in adulthood and responds to social environmental demands.

Together, these studies reveal that human brain structure dynamically adapts to shifting social and environmental demands across the lifespan. While plasticity during adolescence is linked to resilience under stress, adult plasticity appears to be shaped by targeted interventions like social mental training. Further research is needed to delineate the timing, duration, and functional implications of these changes at finer spatial and temporal scales. 

Imaging myelin has been a long-standing objective of MRI. A recent advancement in quantitative susceptibility mapping (QSM), susceptibility source separation, enables the differentiation of para- and diamagnetic susceptibility sources that co-exist in a voxel, providing information regarding the underlying microstructure. In particular, the method has the potential to reveal the two primary sources of magnetic susceptibility in the brain—iron and myelin—which are known to be related to the pathogenesis of multiple neurodegenerative disorders, such as multiple sclerosis (MS). In this presentation, I will review the method of magnetic susceptibility source separation that has been applied to MS, with a focus on chi-separation. I will then highlight studies that have demonstrated the relationship between diamagnetic susceptibility and myelin content in the brain. Finally, I will conclude by discussing potential artifacts that may obscure the interpretation of diamagnetic susceptibility as it relates to myelin.