Relationship between white matter alteration and encoding related brain activation in connected brain regions

Knaupp, Hedwig Maria (2022): Relationship between white matter alteration and encoding related brain activation in connected brain regions: a DTI-fMRI-study. Dissertation, LMU München: Medizinische Fakultät

Abstract

Background: Aging is associated with alterations of white matter and brain activation. Functional MRI studies in elderly subjects showed changes in encoding related brain activation such as hyperactivation in frontal areas and hypoactivation in occipital gyrus in comparison to a younger control group. A contributing factor could be alterations of white matter integrity, resulting from age-related small vessel disease (SVD), a pathology that effects the small vessels of the brain or Wallerian Degeneration (WD) that explains axonal degeneration distal of an injury. These processes lead to changes such as white matter hyperintensities (WMH) detected by MRI or microstructural change assessed by the diffusion tensor imaging (DTI), marker mean diffusivity (MD) or peak width (PW). It was hypothesized that the directionality of the structure-function relationship of the brain is dependent on the investigated brain region. We aim to verify this assumption. Other studies focused on frontal brain regions. Instead we implemented a whole-brain analysis of the structure-function relationship. Therefore, the goal of this study was to investigate changes in white matter as a predictor of changed encoding-related brain activation in anatomically connected brain regions in cognitively normal performing older subjects. Furthermore, there are different theories that try to explain the changed brain activation in association with white matter change, such as compensatory mechanisms, dedifferentiation theory or inefficient neuronal processes. To gain a better understanding we examined the association between decreased brain activation respectively increased white matter changes in relation to cognitive performance of the subjects. Methods: Cognitively healthy elderly subjects (N = 35) performed a face-name matching paradigm within the fMRI scanner with the encoding phase being relevant in the present study. The integrity of white matter was determined with measurement of WMH volume and DTI based markers such as MD and PW. We performed ANOVAs with DTI-markers as dependent and activation as the independent variable. Furthermore, we performed ANOVAs with white matter change or brain activation as dependent variable and cognitive performance as independent variable. Since we assumed that there are local differences of white matter change we created boxplots for the chosen MD, PW and WMH-ratio within the chosen fiber tracts and global MD, PW and WMH-ratio. Additionally, we computed a correlation matrix between tract-specific MD or PW for a comparison of these two markers. Results: We could demonstrate a significant positive association between PW in the inferior fronto-occipital fasciculus left (IFOF L) and the activation in the left frontal gyrus as well as PW in the inferior longitudinal fasciculus right (ILF R) and activation in the occipital gyrus. Furthermore, the data revealed no significant result for the relationship between white matter change and cognition or brain activation and cognition. The boxplot showed a significant difference between the white matter tracts when using MD and PW as marker. Because of its low burden we had to exclude WMH-ratio as a marker for white matter change. The correlation-matrix revealed that PW within the tracts correlated less with each other than MD. Conclusion: These results suggest that microstructural changes lead to increased brain activation due to decreased white matter connectivity and reduced fidelity of data transmission. Additionally, the subjects' cognitive performance appears not to benefit from the increased brain activation. Thus, the negative structure-function relationship seems not to be based on a compensatory mechanism or dedifferentiation theory but most likely on an inefficient neuronal response. White matter change can be considered as regionally variable as revealed by the boxplots and the correlation matrix. However, the structure-function relation seems not be dependent on brain region, because the whole brain analysis showed a consistent directionality of the structure-function relationship.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Keywords: fMRI, DTI, encoding, healthy aging
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften ; 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Fakultäten: Medizinische Fakultät
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 7. Dezember 2022
• 1. Bericht­erstatter:in: Ewers, Michael