Alterations in the myelination of the cerebral cortex may underlie abnormal cortical function in a variety of brain diseases. Here, we describe a technique for investigating changes in intracortical myelin in clinical populations on the basis of cortical thickness measurements with magnetic resonance imaging (MRI) at 3 Tesla. For this, we separately compute the thickness of the shallower, lightly myelinated portion of the cortex and its deeper, heavily myelinated portion (referred to herein as unmyelinated and myelinated cortex, respectively). Our expectation is that the thickness of the myelinated cortex will be a specific biomarker for disruptions in myeloarchitecture. We show representative atlases of total cortical thickness, T, unmyelinated cortical thickness, G, and myelinated cortical thickness, M, for a healthy group of 20 female subjects. We further demonstrate myelinated cortical thickness measurements in a preliminary clinical study of 10 bipolar disorder type-I subjects and 10 healthy controls, and report significant decreases in the middle frontal gyrus in T, G, and M in the disorder, with the largest percentage change occurring in M. This study highlights the potential of myelinated cortical thickness measurements for investigating intracortical myelin involvement in brain disease at clinically relevant field strengths and resolutions.

Our study shows a dose-dependent association between the severity of depressive symptoms and degree of biological rhythms disturbance. Biological rhythms disturbance was also an independent predictor of functional impairment. Although the directionality of this relationship remains unknown, our results suggest that stability of biological rhythms should be an important target of acute and long-term management of bipolar disorder and may aid in the improvement of functioning.

Magnetic resonance imaging (MRI) studies in humans have reported that the T -weighted signal in the cerebral cortex follows an inverted "U" trajectory over the lifespan. Here, we investigated the T -weighted signal trajectory from late adolescence to middle adulthood in humans to characterize the age range when mental illnesses tend to present, and efficacy of treatments are evaluated. We compared linear to quadratic predictors of age on signal in 67 healthy individuals, 17-45 years old. We investigated ¼, ½, and ¾ depths in the cortex representing intracortical myelin (ICM), in the superficial white matter (SWM), and in a reference deep white matter tract. We found that the quadratic fit was superior in all regions of the cortex, while signal in the SWM and deep white matter showed no global dependence on age over this range. The signal trajectory in any region followed a similar shape regardless of cortical depth. The quadratic fit was analyzed in 70 cortical regions to obtain the age of maximum signal intensity. We found that visual, cingulate, and left ventromedial prefrontal cortices peak first around 34 years old, whereas motor and premotor areas peak latest at ∼38 years. Our analysis suggests that ICM trajectories over this range can be modeled well in small cohorts of subjects using quadratic functions, which are amenable to statistical analysis, thus suitable for investigating regional changes in ICM with disease. This study highlights a novel approach to map ICM trajectories using an age range that coincides with the onset of many mental illnesses. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Imaging and postmortem studies into the severe mental illnesses of major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ) have revealed deficiencies in the myelination of deep white matter tracts of the brain. Recent studies have further suggested that deficits could extend to myelinated fibers running through the cortex in those illnesses. Disruptions in this intracortical myelin may underlie functional symptomology in MDD, BD, and SZ; thus, in this study, we hypothesized that individuals with these illnesses may have reduced myelin staining relative to controls in the cerebral cortex. We stained 60 sections of dorsolateral prefrontal cortex for myelin with Luxol fast blue in four groups: 15 BD, 15 MDD, 15 SZ, and 15 controls with no psychiatric illness. We digitally measured optical tissue attenuation reflecting the amount of myelin staining across six cortical depths in the middle frontal gyrus (MFG), in superficial white matter in the crown of the MFG, and in deep white matter. We found that a diagnosis of MDD or SZ meant that optical tissue attenuation was significantly reduced in the shallowest depths of the cortex. Furthermore, there was a trend toward reduced optical tissue attenuation in all illnesses across all myelinated regions we studied. These results encourage future studies into potential reductions in intracortical myelin in severe mental illness.

Background: Previous studies have implicated white-matter-related changes in the pathophysiology of bipolar disorder. However, most of what is known is derived from in vivo subcortical white-matter imaging or postmortem studies. In this study, we investigated wholebrain intracortical myelin (ICM) content in people with bipolar disorder type I and controls. Methods: Between Sept. 1, 2014, and Jan. 31, 2017, we used a 3 T General Electric scanner to collect T 1 -weighted images in 45 people with bipolar disorder type I and 60 controls aged 17 to 45 years using an optimized sequence that was sensitive to ICM content. We analyzed images using a surfacebased approach. We used general linear models with quadratic age terms to examine the signal trajectory of ICM across the age range. Results: In healthy controls, the T 1 -weighted signal followed an inverted-U trajectory over age; in people with bipolar disorder type I, the association between ICM and age followed a flat trajectory (p < 0.05, Bonferroni corrected). Exploratory analyses showed that ICM signal intensity was associated with duration of illness, age of onset, and anticonvulsant and antipsychotic use in people with bipolar disorder type I (p < 0.05, uncorrected). Limitations: Because of the cross-sectional nature of the study, we were unable to comment on whether the effects were due to dysmyelination or demyelination in bipolar disorder. Conclusion: This foundational study is, to our knowledge, the first to show global age-related deficits in ICM maturation throughout the cortex in bipolar disorder. Considering the impact of myelination on the maintenance of neural synchrony and the integrity of neural connections, this work may help us better understand the cognitive and behavioural deficits seen in bipolar disorder.