Estimates of locus coeruleus function with functional magnetic resonance imaging are influenced by localization approaches and the use of multi-echo data.

The locus coeruleus (LC) plays a central role in regulating human cognition, arousal, and autonomic states. Efforts to characterize the LC's function in humans using functional magnetic resonance imaging have been hampered by its small size and location near a large source of noise, the fourth ventricle. We tested whether the ability to characterize LC function is improved by employing neuromelanin-T1 weighted images (nmT1) for LC localization and multi-echo functional magnetic resonance imaging (ME-fMRI) for estimating intrinsic functional connectivity (iFC). Analyses indicated that, relative to a probabilistic atlas, utilizing nmT1 images to individually localize the LC increases the specificity of seed time series and clusters in the iFC maps. When combined with independent components analysis (ME-ICA), ME-fMRI data provided significant improvements in the temporal signal to noise ratio and DVARS relative to denoised single echo data (1E-fMRI). The effects of acquiring nmT1 images and ME-fMRI data did not appear to only reflect increases in power: iFC maps for each approach overlapped only moderately. This is consistent with findings that ME-fMRI offers substantial advantages over 1E-fMRI acquisition and denoising. It also suggests that individually identifying LC with nmT1 scans is likely to reduce the influence of other nearby brainstem regions on estimates of LC function.

Age-related differences in regional brain volumes: a comparison of optimized voxel-based morphometry to manual volumetry.

Regional manual volumetry is the gold standard of in vivo neuroanatomy, but is labor-intensive, can be imperfectly reliable, and allows for measuring limited number of regions. Voxel-based morphometry (VBM) has perfect repeatability and assesses local structure across the whole brain. However, its anatomic validity is unclear, and with its increasing popularity, a systematic comparison of VBM to manual volumetry is necessary. The few existing comparison studies are limited by small samples, qualitative comparisons, and limited selection and modest reliability of manual measures. Our goal was to overcome those limitations by quantitatively comparing optimized VBM findings with highly reliable multiple regional measures in a large sample (N=200) across a wide agespan (18-81). We report a complex pattern of similarities and differences. Peak values of VBM volume estimates (modulated density) produced stronger age differences and a different spatial distribution from manual measures. However, when we aggregated VBM-derived information across voxels contained in specific anatomically defined regions (masks), the patterns of age differences became more similar, although important discrepancies emerged. Notably, VBM revealed stronger age differences in the regions bordering CSF and white matter areas prone to leukoaraiosis, and VBM was more likely to report nonlinearities in age-volume relationships. In the white matter regions, manual measures showed stronger negative associations with age than the corresponding VBM-based masks. We conclude that VBM provides realistic estimates of age differences in the regional gray matter only when applied to anatomically defined regions, but overestimates effects when individual peaks are interpreted. It may be beneficial to use VBM as a first-pass strategy, followed by manual measurement of anatomically defined regions.

The implications of cortical recruitment and brain morphology for individual differences in inhibitory function in aging humans.

The authors assessed individual differences in cortical recruitment, brain morphology, and inhibitory task performance. Similar to previous studies, older adults tended toward bilateral activity during task performance more than younger adults. However, better performing older adults showed less bilateral activity than poorer performers, contrary to the idea that additional activity is universally compensatory. A review of the results and of extant literature suggests that compensatory activity in prefrontal cortex may only be effective if the additional cortical processors brought to bear on the task can play a complementary role in task performance. Morphological analyses revealed that frontal white matter tracts differed as a function of performance in older adults, suggesting that hemispheric connectivity might impact both patterns of recruitment and cognitive performance.

Neurocognitive aging and cardiovascular fitness: recent findings and future directions.

In the first century, ce, the Roman satirist Juneval famously observed Orandum est, ut sit mens sana in corpore sano, or "A sound mind in a sound body is something to be prayed for." This implicit link between mental and physical health, also paralleled by Eastern philosophies and practices such as tai chi, has survived the millennia since Juneval and his contemporaries. More recently, controlled examinations of the effects of physical fitness on cognitive performance have shown that improving cardiovascular fitness (CVF) can help to reduce the deleterious effects of age on cognition and brain structure. Thus, as we age, it may well be the case that a sound mind is a natural concomitant of a sound body. Numerous cross-sectional and longitudinal studies have examined the effects of aerobic exercise on cognitive performance in aging humans since earlier studies, which found that physically fit older adults performed better on simple cognitive tasks than their less-fit counterparts. This base of knowledge recently has been furthered through examinations of cortical structure (Colcombe et al., 2003) and neurocognitive function in aging humans via functional and structural magnetic resonance imaging techniques. In this manuscript, we will briefly review some of our recent research on the effects of CVF on brain function, structure, and behavior in older adults. We will then outline some of our current and future directions in this area.