Multimodal Magnetic Resonance Imaging Assessment of White Matter Aging Trajectories Over the Lifespan of Healthy Individuals
Department of Psychiatry, The David Geffen School of Medicine at UCLA, Los Angeles, California Biological psychiatry
(Impact Factor: 10.26).
09/2012; 72(12). DOI: 10.1016/j.biopsych.2012.07.010
Postmortem and volumetric imaging data suggest that brain myelination is a dynamic lifelong process that, in vulnerable late-myelinating regions, peaks in middle age. We examined whether known regional differences in axon size and age at myelination influence the timing and rates of development and degeneration/repair trajectories of white matter (WM) microstructure biomarkers.
Healthy subjects (n = 171) 14-93 years of age were examined with transverse relaxation rate (R(2)) and four diffusion tensor imaging measures (fractional anisotropy [FA] and radial, axial, and mean diffusivity [RD, AxD, MD, respectively]) of frontal lobe, genu, and splenium of the corpus callosum WM (FWM, GWM, and SWM, respectively).
Only R(2) reflected known levels of myelin content with high values in late-myelinating FWM and GWM regions and low ones in early-myelinating SWM. In FWM and GWM, all metrics except FA had significant quadratic components that peaked at different ages (R(2) < RD < MD < AxD), with FWM peaking later than GWM. Factor analysis revealed that, although they defined different factors, R(2) and RD were the metrics most closely associated with each other and differed from AxD, which entered into a third factor.
The R(2) and RD trajectories were most dynamic in late-myelinating regions and reflect age-related differences in myelination, whereas AxD reflects axonal size and extra-axonal space. The FA and MD had limited specificity. The data suggest that the healthy adult brain undergoes continual change driven by development and repair processes devoted to creating and maintaining synchronous function among neural networks on which optimal cognition and behavior depend.
Available from: Marina Guizzetti
- "al . , 2013 ) . Developmentally , myelination occurs as one of the final stages of brain development . In humans , most myelination takes place during the first 20 years of postnatal life ( Lebel et al . , 2008 ) . While the bulk of myelination occurs in relatively early postnatal life , it is now clear that myelination continues throughout life ( Bartzokis et al . , 2012 ; Young et al . , 2013 ) . Coinciding with their later development , oligodendrocytes are the final cells of the CNS to mature . Nevertheless , oligodendrocyte precursor cells ( OPCs ) are present at embryonic day 12 . 5 in mice . Production of OPCs is localized to distinct areas , thus , migration of this cell type throughout the brain"
[Show abstract] [Hide abstract]
ABSTRACT: Alcohol consumption during pregnancy can produce a variety of central nervous system (CNS) abnormalities in the offspring resulting in a broad spectrum of cognitive and behavioral impairments that constitute the most severe and long-lasting effects observed in fetal alcohol spectrum disorders (FASD). Alcohol-induced abnormalities in glial cells have been suspected of contributing to the adverse effects of alcohol on the developing brain for several years, although much research still needs to be done to causally link the effects of alcohol on specific brain structures and behavior to alterations in glial cell development and function. Damage to radial glia due to prenatal alcohol exposure may underlie observations of abnormal neuronal and glial migration in humans with Fetal Alcohol Syndrome (FAS), as well as primate and rodent models of FAS. A reduction in cell number and altered development has been reported for several glial cell types in animal models of FAS. In utero alcohol exposure can cause microencephaly when alcohol exposure occurs during the brain growth spurt a period characterized by rapid astrocyte proliferation and maturation; since astrocytes are the most abundant cells in the brain, microenchephaly may be caused by reduced astrocyte proliferation or survival, as observed in in vitro and in vivo studies. Delayed oligodendrocyte development and increased oligodendrocyte precursor apoptosis has also been reported in experimental models of FASD, which may be linked to altered myelination/white matter integrity found in FASD children. Children with FAS exhibit hypoplasia of the corpus callosum and anterior commissure, two areas requiring guidance from glial cells and proper maturation of oligodendrocytes. Finally, developmental alcohol exposure disrupts microglial function and induces microglial apoptosis; given the role of microglia in synaptic pruning during brain development, the effects of alcohol on microglia may be involved in the abnormal brain plasticity reported in FASD. The consequences of prenatal alcohol exposure on glial cells, including radial glia and other transient glial structures present in the developing brain, astrocytes, oligodendrocytes and their precursors, and microglia contributes to abnormal neuronal development, reduced neuron survival and disrupted brain architecture and connectivity. This review highlights the CNS structural abnormalities caused by in utero alcohol exposure and outlines which abnormalities are likely mediated by alcohol effects on glial cell development and function.
Available from: Marina Guizzetti
- "In humans, most myelination takes place during the first 20 years of postnatal life (Lebel et al., 2008). While the bulk of myelination occurs in relatively early postnatal life, it is now clear that myelination continues throughout life (Bartzokis et al., 2012;Young et al., 2013). Coinciding with their later development, oligodendrocytes are the final cells of the CNS to mature. "
[Show abstract] [Hide abstract]
ABSTRACT: Alcohol abuse during pregnancy may lead to fetal alcohol spectrum disorders (FASD), characterized by structural brain abnormalities and compromised cognitive and behavioral functions. Ethanol interferes with every step of central nervous system development; the cognitive and behavioral abnormalities associated with prenatal alcohol exposure are therefore due to a combination of effects exerted by ethanol throughout gestation. This chapter describes the physical and neurobehavioral consequences of in utero alcohol exposure and the brain structures affected in humans. Animal models used in FASD research are also described. Finally, this chapter provides an overview of the main mechanisms implicated in the developmental effects of ethanol as well as of experimental treatments under investigation for the amelioration of the consequences of FASD.
Available from: Karen Blackmon
- "During adolescence, reduction in CT might be associated with neuronal pruning (Kanai and Rees 2011; Huttenlocher and Dabholkar 1997), which results in more efficient cortical networks (Kharitonova et al. 2013). The frontal lobes are the last region to complete the myelination process; with frontal lobe myelination peaking in the 4th decade of life (Bartzokis et al. 2012). Therefore, thicker cortex in our healthy adult population may confer a functional disadvantage because it reflects either insufficient pruning or myelination. "
[Show abstract] [Hide abstract]
ABSTRACT: Surface-based cortical thickness (CT) analyses are increasingly being used to investigate variations in brain morphology across the spectrum of brain health, from neurotypical to neuropathological. An outstanding question is whether individual differences in cortical morphology, such as regionally increased or decreased CT, are associated with domain-specific performance deficits in healthy adults. Since CT studies are correlational, they cannot establish causality between brain morphology and cognitive performance. A direct comparison with classic lesion methods is needed to determine whether the regional specificity of CT-cognition correlations is similar to that observed in patients with brain lesions. We address this question by comparing the neuroanatomical overlap of effects when 1) whole brain vertex-wise CT is tested as a correlate of performance variability on a commonly used neuropsychological test of executive function, Trailmaking Test Part B (TMT-B), in healthy adults and 2) voxel-based lesion-symptom mapping (VBLSM) is used to map lesion location to performance decrements on the same task in patients with frontal lobe lesions. We found that reduced performance on the TMT-B was associated with increased CT in bilateral prefrontal regions in healthy adults and that results spatially overlapped in the left dorsomedial prefrontal cortex with findings from the VBLSM analysis in patients with frontal brain lesions. Findings indicate that variations in the structural integrity of the left dorsomedial prefrontal lobe, ranging from individual CT differences in healthy adults to structural lesions in patients with neurological disorders, are associated with poor performance on the TMT-B. These converging results suggest that the left dorsomedial prefrontal region houses a critical region for the complex processing demands of TMT-B, which include visuomotor tracking, sequencing, and cognitive flexibility.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.