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Brain Microstructure Across the Lifespan: Cognitive Links, Network Architecture, and Clinical Implications

Grydeland, Håkon
Doctoral thesis
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460_Grydeland_materie-DUO.pdf (11.13Mb)
Year
2014
Permanent link
http://urn.nb.no/URN:NBN:no-44594

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  • Psykologisk institutt [2921]
Abstract
Assessment of brain microstructure by way of magnetic resonance imaging-derived signal intensity putatively reflecting myelin i) increased detection accuracy of Alzheimer’s disease, ii) revealed age-related differences in myelin grade and myelin network organization across the lifespan, and iii) was related to cognitive functioning as measured by an attention task. The findings implicate myelin as an underlying neurobiological factor to brain alterations in normal development and aging, with cognitive links, as well as suggesting a clinical application in dementia.

The human brain undergoes large structural changes through life with contemporaneous alterations in most cognitive functions. Diseases such as Alzheimer’s dementia are characterized by deviations from these normal age-related change patterns. The advent of modern neuroimaging has yielded important new knowledge concerning brain development and aging, its aberrant path in disease, and its relation to cognition. Based on magnetic resonance imaging (MRI) for instance, structural measures such as volume and cortical thickness can be derived. A plethora of studies demonstrate that these measures show age-related differences, correlate with memory, attention and other cognitive functions, and demonstrate significant atrophy in specific regions in Alzheimer’s dementia. Still, both volume and thickness lack specificity regarding the underlying neurobiological mechanisms. Interestingly, studies demonstrate that, by using signal intensity derived from T1- and T2-weighted MRI scans, more information about underlying neurobiological processes can be obtained. For instance, a recent report shows how increased sensitivity to myelin could be obtained by dividing the T1w signal by a co-registered T2w image, enabling the opportunity to putatively assess myelin in vivo. The present thesis aims to assess myelin structure across the lifespan using signal intensity, and test for cognitive links to intracortical myelin maturation and senescence. In addition, we probe the ability to increase detection of Alzheimer’s dementia to potentially show clinical relevance.
List of papers
Paper I: Grydeland H, Westlye LT, Walhovd KB, Fjell AM. (2013). Improved Prediction of Alzheimer’s Disease with Longitudinal White Matter/Gray Matter Contrast Changes. Human Brain Mapping, 34, 2775-2785. The paper is removed from the thesis in DUO due to publisher restrictions. The published version is available at: https://doi.org/10.1002/hbm.22103
Paper II: Intracortical Myelin Links with Performance Variability Across the Human Lifespan – Results From T1- and T2-weighted MRI Myelin Mapping and Diffusion Tensor Imaging. Grydeland H, Walhovd KB, Tamnes CK, Westlye LT, Fjell AM. (2013). The Journal of Neuroscience, 33, 18618-30. The published version of this paper is available at: https://doi.org/10.1523/JNEUROSCI.2811-13.2013
Paper III: Altered Rich Club Organization Across the Human Lifespan – Structural Covariance Networks From T1- and T2-weighted MRI Myelin Mapping. Grydeland H, Bullmore ET, Vértes P, Patel AX, Tamnes CK, Westlye LT, Walhovd KB, Fjell AM. The paper is removed from the thesis in DUO due to publisher restrictions.
 
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