Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Linortner, P.
Changes of brain structure associated with age-related white matter hyperintensities and their relationship to gait disturbances
PhD-Studium (Doctor of Philosophy); Humanmedizin; [ Dissertation ] Graz Medical University; 2015. pp. 145
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- Autor*innen der Med Uni Graz:
- Linortner Patricia
- Betreuer*innen:
- Enzinger Christian
- Fazekas Franz
- Ropele Stefan
- Altmetrics:
- Abstract:
- The PhD thesis consists of three separate yet interlinking neuroimaging studies dealing with the interplay of age, cerebral white matter hyperintensities (WMH), and gait (i.e. walking). The studies provide fundamentals for subsequent follow-up fMRI training studies in individuals with WMH but also stand for their own. In a consecutive series of investigations, we were first interested in the effects of age on brain response elicited by fMRI ankle movements, second, potential relationships between WMH and cortical microstructural changes and third, the development of a novel fMRI “walking” paradigm. Based on limited previous research, study 1 investigated potential functional changes in the central motor control of lower limb movements with age, using a big sample approach and two analysis techniques. Two regions turned out to be increasingly activated with higher age, i.e., the cerebellum and the precuneus. Study 2 then focused on the relationship of WMH and (regional) grey matter volume changes, using voxel based morphometry and a novel lesion masking approach. Apart from previously described behavioural, functional and structural white matter changes in individuals with WMH, WMH were associated with grey matter volume decreases in several brain area associated with motor, cognitive and visual functions. Finally, in study 3, the development of a novel fMRI “walking” paradigm including motor, cognitive and visual domains in a single experiment was realized. As a corollary (and unexpected) finding, sex influenced the brain’s response to motor imagery, with men showing stronger activation in frontal, parietal and premotor regions than women. The results yield several new important insights. Given that task performance did not vary with age, study 1 suggests the noted functional changes with age to be at least partially compensatory for other age-related changes in the sensorimotor network responsible for the control of limb function. The structural volume decreases in people with pronounced WMH in study 2 may be attributed to disconnection of fronto-cortico networks in the context of WMH in proximity to the corticospinal tract. Finally, the sex differences in the motor-imagery condition of the newly developed fMRI paradigm of study 3 suggest a different processing of movement-based mental imagery tasks in men than women. The current PhD project met the objective of developing and implementing a refined and stable fMRI “walking” paradigm, tested in healthy people, for future use in individuals with WMH. Further, the findings demonstrate the necessity to correct for potential age-effects and sex differences, esp. in mental-based motor trainings in WMH. These observations gain importance in light of future interventional studies (i.e., movement-related training in the motor and cognitive domain) in people with pronounced WMH, aiming to ameliorate existing deficits or even postpone structural changes.