Proton functional magnetic resonance spectroscopy (H fMRS) is a noninvasive neuroimaging technique capable of detecting dynamic changes in glutamate related to task-related demands at a temporal resolution under 1 min. Several recent H fMRS studies demonstrated elevated steady-state levels of glutamate of 2% or greater during different 'task-active' conditions, relative to a 'non-task-active' control condition. However, the 'control' condition from these studies does vary with respect to the degree of constraining behavior, which may lead to different glutamate levels or variability between 'control' conditions. The purpose of thisH fMRS study was to compare the steady-state levels and variability of glutamate in the left dorsolateral prefrontal cortex (dlPFC) of 16 healthy adults across four different putative 'non-task-active' conditions: relaxed with eyes closed, passive visual fixation crosshair, visual flashing checkerboard, and finger tapping. Results showed significantly lower glutamate levels during the passive visual fixation crosshair than the visual flashing checkerboard and the finger tapping conditions. Moreover, glutamate was significantly less variable during the passive visual fixation crosshair and the visual flashing checkerboard than the relaxed eyes closed condition. Of the four conditions, the passive visual fixation crosshair condition demonstrated the lowest and least variable glutamate levels potentially reflecting the least dlPFC engagement, but greatest behavioral constraint. These results emphasize the importance of selecting a proper 'control' condition to reflect accurately a 'non-task-active' steady-state level of glutamate with minimal variability during H MRS investigations.

The myeloarchitecture of the corpus callosum (CC) is characterized as a mosaic of distinct differences in fiber density of small- and large-diameter axons along the anterior–posterior axis; however, regional and age differences across the lifespan are not fully understood. Using multiecho T2 magnetic resonance imaging combined with multi-T2 fitting, the myelin water fraction (MWF) and geometric-mean of the intra-/extracellular water T2 (geomT2IEW) in 395 individuals (7–85 years; 41% males) were examined. The approach was validated where regional patterns along the CC closely resembled the histology; MWF matched mean axon diameter and geomT2IEW mirrored the density of large-caliber axons. Across the lifespan, MWF exhibited a quadratic association with age in all 10 CC regions with evidence of a positive linear MWF-age relationship among younger participants and minimal age differences in the remainder of the lifespan. Regarding geomT2IEW, a significant linear age × region interaction reflected positive linear age dependence mostly prominent in the regions with the highest density of small-caliber fibers—genu and splenium. In all, these two indicators characterize distinct attributes that are consistent with histology, which is a first. In addition, these results conform to rapid developmental progression of CC myelination leveling in middle age as well as age-related degradation of axon sheaths in older adults.

White-matter microstructural properties of the corpus callosum: Test-retest and repositioning effects in two parcellation schemes. Brain Structure and Function, 224(9),[3373][3374][3375][3376][3377][3378][3379][3380][3381][3382][3383][3384][3385]

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Background and Purpose: Myelin water fraction (MWF) deficits as measured by myelin water imaging (MWI) have been related to worse motor function in persons with multiple sclerosis (PwMS). However, it is unknown if measures from MWI metrics in motor areas relate to fall risk measures in PwMS. The objective of this study was to examine the relationship between MWI measures in motor areas to performance on clinical measures of fall risk and disability in PwMS. Methods: Sixteen individuals with relapsing-remitting MS participated (1 male, 15 female; age 47.1 years [12.3]; Expanded Disability Status Scale 4.0 [range 0-6.5]) and completed measures of walking and fall risk (Timed 25 Foot Walk [T25FW] and Timed Up and Go). MWF and the geometric mean of the intra-/extracellular water T 2 (geomT 2IEW ) values reflecting myelin content and contribution of large-diameter axons/density, respectively, were assessed in three motor-related regions. Results:The geomT 2IEW of the corticospinal tract (r = -.599; p = .018) and superior cerebellar peduncles (r = -.613; p = .015) demonstrated significant inverse relationships with T25FW, suggesting that decreased geomT 2IEW was related to slower walking. Though not significant, MWF in the corticospinal tract and superior cerebellar peduncles also demonstrated fair relationships with the T25FW, suggesting that worse performance on the T25FW was associated with lower MWF values.Conclusions: MWI of key motor regions was associated with walking performance in PwMS. Further MWI studies are needed to identify relationships between pathology and clinical function in PwMS to guide targeted rehabilitation therapies aimed at preventing falls.