Frontal connections and cognitive changes in normal aging rhesus monkeys: A DTI study

Makris, Nikos; Papadimitriou, George; Kouwe, André van der; Kennedy, David N.; Hodge, Steven; Dale, Anders M.; Benner, Thomas; Wald, Lawrence L.; Wu, Ona; Tuch, David S.; Caviness, Verne S.; Moore, Tara; Killiany, Ronald J.; Moss, Mark B.; Rosene, Douglas L.

doi:10.1016/j.neurobiolaging.2006.07.005

Cited by 103 publications

(116 citation statements)

References 76 publications

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“…The functional ramifications of the DTI metrics have been regularly verified with observations of correlations between regionally-specific low FA or high diffusivity and poor cognitive Charlton et al, 2007;Grieve et al, 2007;Madden et al, 2007;O'Sullivan et al, 2001;Shenkin et al, 2003;Stebbins et al, 2001;Sullivan et al, 2006) or motor ) test performance in humans and also a monkey model of aging (Makris et al, 2007). A recent study reported that decreased frontostriatal transverse diffusivity, suggestive of increasing myelination, correlated with speeded reaction time in a cognitive control (GO/ NOGO) task engaged in by 21 individuals, age 7-31 years (Liston et al, 2006) and lending functional relevance to fiber tracking methods.…”

Section: Introductionmentioning

confidence: 77%

Quantitative fiber tracking of lateral and interhemispheric white matter systems in normal aging: Relations to timed performance

Sullivan

Rohlfing

Pfefferbaum

2010

Neurobiology of Aging

302

305

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The integrity of white matter, as measured in vivo with diffusion tensor imaging (DTI), is disrupted in normal aging. A current consensus is that in adults advancing age affects anterior brain regions disproportionately more than posterior regions; however, the mainstay of studies supporting this anterior-posterior gradient is based primarily on measures of the corpus callosum. Using our quantitative fiber tracking approach, we assessed fiber tract integrity of samples of major white matter cortical, subcortical, interhemispheric, and cerebellar systems (11 bilateral and 2 callosal) on DTI data collected at 1.5 T magnet strength. Participants were 55 men (age 20-78 years) and 65 women (age 28-81 years), deemed healthy and cognitively intact following interview and behavioral testing. Fiber integrity was measured as orientational diffusion coherence (fractional anisotropy, FA) and magnitude of diffusion, which was quantified separately for longitudinal diffusivity (λL), an index of axonal length or number, and transverse diffusivity (λT), an index of myelin integrity. Aging effects were more evident in diffusivity than FA measures. Men and women, examined separately, showed similar age-related increases in longitudinal and transverse diffusivity in fibers of the internal and external capsules bilaterally and the fornix. FA was lower and diffusivity higher in anterior than posterior fibers of regional paired comparisons (genu versus splenium and frontal versus occipital forceps). Diffusivity with older age was generally greater or FA lower in the superior than inferior fiber systems (longitudinal fasciculi, cingulate bundles), with little to no evidence for age-related degradation in pontine or cerebellar systems. The most striking sex difference emerged for the corpus callosum, for which men showed significant decline in FA and increase in longitudinal and transverse diffusivity in the genu but not splenium. By contrast, in women the age effect was present in both callosal regions, albeit modestly more so in the genu than splenium. Functional meaningfulness of these age-related differences was supported by significant correlations between DTI signs of white matter degradation and poorer performance on cognitive or motor tests. This survey of multiple fiber systems throughout the brain revealed a differential pattern of age's effect on regional FA and diffusivity and suggests mechanisms of functional degradation, attributed at least in part to compromised fiber microstructure affecting myelin and axonal morphology.

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Section: Introductionmentioning

confidence: 77%

Quantitative fiber tracking of lateral and interhemispheric white matter systems in normal aging: Relations to timed performance

Sullivan

Rohlfing

Pfefferbaum

2010

Neurobiology of Aging

302

305

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“…Alzheimer's disease patients show a decreased level of functional connectivity within the default mode network (Greicius et al, 2004;Rombouts et al, 2005) as well as reduced FA values in the cingulum tract (Xie et al, 2005;Zhang et al, 2007). In addition, normal aging has been associated with decreased resting-state activation within the default mode network (Andrews-Hanna et al, 2007;Damoiseaux et al, 2008) and with lower FA values of the cingulum (Makris et al, 2007;Schneiderman et al, 2007;Yoon et al, 2008). Furthermore, decreased default mode functional connectivity (Friston, 1999;Liang et al, 2006;Micheloyannis et al, 2006;Bluhm et al, 2007;Salvador et al, 2007;Williamson, 2007;Liu et al, 2008) and reduced microstructural organization of the cingulum tract (Sun et al, 2003;Nestor et al, 2007) have been suggested to play an important role in schizophrenia.…”

Section: Discussionmentioning

confidence: 99%

Microstructural Organization of the Cingulum Tract and the Level of Default Mode Functional Connectivity

et al. 2008

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The default mode network is a functionally connected network of brain regions that show highly synchronized intrinsic neuronal activation during rest. However, less is known about the structural connections of this network, which could play an important role in the observed functional connectivity patterns. In this study, we examined the microstructural organization of the cingulum tract in relation to the level of resting-state default mode functional synchronization. Resting-state functional magnetic resonance imaging and diffusion tensor imaging data of 45 healthy subjects were acquired on a 3 tesla scanner. Both structural and functional connectivity of the default mode network were examined. In all subjects, the cingulum tract was identified from the total collection of reconstructed tracts to interconnect the precuneus/posterior cingulate cortex and medial frontal cortex, key regions of the default mode network. A significant positive correlation was found between the average fractional anisotropy value of the cingulum tract and the level of functional connectivity between the precuneus/posterior cingulate cortex and medial frontal cortex. Our results suggest a direct relationship between the structural and functional connectivity measures of the default mode network and contribute to the understanding of default mode network connectivity.

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“…To address this, DTI scans were acquired on a different cohort of aged monkeys. Analysis of FA changes revealed a significant age-related loss of FA in subcortical WM, including the areas like the corpus callosum, and cingulum bundle known to exhibit ultrastructual evidence of myelin damage (Makris et al 2007). This loss of FA likely reflects the increased frequency of fluid and cytoplasm filled inclusions in WM as well as a generalized loss of myelinated fibers confirming the vulnerability of forebrain WM to agerelated pathology, independent of loss of GM.…”

Section: Ultrastructural Observations Of Non-human Primate Cortex Witmentioning

confidence: 99%

Age-related changes in human and non-human primate white matter: from myelination disturbances to cognitive decline

Kohama

Rosene

Sherman

2011

AGE

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107

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The cognitive decline associated with normal aging was long believed to be due primarily to decreased synaptic density and neuron loss. Recent studies in both humans and non-human primates have challenged this idea, pointing instead to disturbances in white matter (WM) including myelin damage. Here, we review both cross-sectional and longitudinal studies in humans and non-human primates that collectively support the hypothesis that WM disturbances increase with age starting at middle age in humans, that these disturbances contribute to age-related cognitive decline, and that age-related WM changes may occur as a result of free radical damage, degenerative changes in cells in the oligodendrocyte lineage, and changes in microenvironments within WM.

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Frontal connections and cognitive changes in normal aging rhesus monkeys: A DTI study

Cited by 103 publications

References 76 publications

Quantitative fiber tracking of lateral and interhemispheric white matter systems in normal aging: Relations to timed performance

Quantitative fiber tracking of lateral and interhemispheric white matter systems in normal aging: Relations to timed performance

Microstructural Organization of the Cingulum Tract and the Level of Default Mode Functional Connectivity

Age-related changes in human and non-human primate white matter: from myelination disturbances to cognitive decline

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