Typical Brain Maturation Reveals Clues to Clinical Manifestation of Psychiatric Disorders in Adolescence

Cortical shrinkage in adolescence is associated with intracortical magnetization transfer (MT), a validated MRI marker for myelination, with the greatest myelination rates in association cortical areas, found a recent study.

“This observation supports myelination models of shrinkage and, more generally, confirms association cortical myelinogenesis as a key neurodevelopmental process in adolescence,” the researchers wrote.

Kirstie J. Whitaker, PhD, of the University of Cambridge and her colleagues used MRI to measure cortical thickness and intracortical myelination at 308 cortical regions in 297 healthy young adults ages 14 to 24. The population was divided into two cohorts of 100 and 197 adults, and approximately 60 adults fell within each of five pairs of ages between 14 and 24. The researchers used the first group of 100 individuals as a discovery cohort and then replicated their results with greater statistical power using the second cohort of 197 people.

The researchers aimed to determine whether cortical shrinkage and intracortical myelination were linked in adolescents’ brains.

“We focused on the degree and closeness of each node—as measures of nodal “hubness”—and the community structure of the network—defined as a set of sparsely interconnected modules,” the researchers explained.

Cortical thickness at age 14 ranged from 1.93 mm to 3.8 mm in different areas, with significant cortical shrinkage occurring at an estimated loss rate of 0.011 mm/year from age 14 to 24. Only 79 of 308 nodes, however, showed statistically significant shrinkage, occurring with the highest rates in association cortex.

Then they found that the change in baseline MT from age 14 to age 24 “increased monotonically as a function of increasing depth from the pial surface, reflecting greater density of myelinated fibers in deeper cortical layers.” But in individual regions, the change in MT varied. At age 14, greater MT existed in areas of primary sensory cortex than in association cortical areas.

Additionally, the highest rates of myelination occurred in association cortices, leading to expected strong negative correlations between baseline cortical thickness and myelination (MT) and between cortical shrinkage rates and intracortical myelination.

“Adolescent cortical shrinkage was significantly but not entirely mediated by age-dependent changes in MT, indicating that myelination is necessary but not sufficient to account for cortical shrinkage,” they reported.

The authors then examined measurements of cortical thickness and MT over time with regards to genomic patterning. Clear associations emerged between gene expressions “enriched for normal synaptic and myelin-related processes and risk of schizophrenia” and overall cortical consolidation.

“We predict that age-related cortical consolidation of human cortical network hubs will prove to be relevant to the normal acquisition of cognitive and behavioral skills during the adolescent transition from childhood to adulthood and may also prove to be implicated in the clinical emergence of neurodevelopmental and psychiatric disorders, such as schizophrenia, in young people,” the authors concluded.

Reference

Whitaker KJ, Vertes PE, Romero-Garcia, et al. Adolescence is associated with genomically patterned consolidation of the hubs of the human brain connectome. PNAS. 2016; 113:9105-9110.