Depth-specific changes in cortical T1w/T2w ratio are associated with impaired executive function in chronic...

Dysmyelination was proposed as a potential mechanism of cognitive dysfunction in schizophrenia. We aimed to characterize intracortical myelin (ICM) changes in chronic schizophrenia and their relationship with cognitive function using T1w/T2w ratio. Right-handed males with chronic schizophrenia 30-55 years old and age-matched healthy controls completed diagnostic and cognitive testing and brain MRI at 3 T. We used T1w/T2w ratio to map ICM across varying cortical depths. A nonlinearity index (NLI) was calculated to characterize the shape of the cortical profile. We found increased T1w/T2w ratio primarily in frontotemporal regions in the patient group. This increase was more pronounced in the deeper layers of the cortex. Higher NLI was significantly associated with increased T1w/T2w ratio and correlated with executive function in 15 regions after controlling for age and group, while T1w/T2w ratio itself did not correlate with cognition. These cortical changes may reflect cortical remyelination, ectopic myelin, iron deposition, or altered glial cells. NLI reflects unique cortical changes not captured by T1w/T2w ratio alone and correlates with executive function. Future studies quantifying intracortical iron as well as the effect of iron on myelin mapping may improve our understanding of cortical changes in schizophrenia.