Background: In recent years, structural magnetic resonance imaging (MRI) studies have shown dramatic age-associated changes in grey matter volume, density and cortical thickness. Calibrated functional magnetic resonance (fMRI) has become a recognized technique for quantifying both the cerebral blood flow (CBF) and oxygen metabolism (CMR02) changes associated with neural activation. It has been used as an advanced approach for examining the physiological effects of age-related changes in the brain, which may be difficult to interpret if measured by the blood oxygen level dependent (BOLD) signal alone. fMRI studies of aging have revealed increased BOLD response to tasks of executive' function with advancing age, which is generally interpreted as increased neural activity. However, changes in the cerebrovascular system with age can alter the BOLD/signal, complicating this interpretation. Arterial spin labeling (ASL) allows simultaneous acquisition of BOLD and CBF information and can be used to quantify the component parts of the BOLD signal. Aims: Hyperoxia calibration was applied during fMRI to study neurovascular alterations and correlations with age. We aimed: (1) address if age-related differences in the BOLD signal develop from age-related neural plasticity or age-related cerebrovascular changes during a cognitive Stroop task. (2) Understand the underlying physiology of the BOLD signal change that is seen with aging. (3) Determine regional variation in physiological changes with age. (4) Determine regional changes in grey matter density and cortical thickness with increasing age. (5) Assess the impact of this structural change on physiological change. Methods: We used calibrated fMRI approach in 55 healthy participants over an age range of 18-71 years to determine the relative vascular and neuronal contributions to the age-related BOLD changes in response to a Stroop task. We analysed the structural data with the new VBM-DARTEL technique. The cortical thicknesses were analysed using the FreeSurfer tools. Results: The BOLD response increased significantly with increasing age but the CBF response did not alter, such that the BOLD increase is attributed to a significant reduction in CMRO2 response with increasing age. Hence, in this study, the BOLD increase with age should be interpreted as a reduction in neural activity, which would be consistent with neurodegeneration. The greatest BOLD increases with age were found in left and right medial frontal gyri and primary motor cortex and were again linked to a reduction in CMRO2• Age-related decline in grey matter density and cortical thickness were widespread, but the frontal regions, in general, exhibit greater thickness changes than parietal, temporal and occipital. The strongest correlations between age and (BOLD activations, grey matter density, cortical thickness) were found mainly in the frontal cortices. The cortical structure-function relationships are different for each sex. Finally, better performance had been observed to be associated with larger frontal grey matter density and thicker cortex on some executive tasks, and increased frontal CMRO2 response. Conclusions: This study demonstrates the relationship between structure, function, and cognition, as well as the need to take into account alterations in vascular-metabolic coupling and resting blood volume when interpreting changes in the BOLD response with aging. It also highlights the added benefit that calibrated fMRI offers in terms of interpreting the underlying physiological changes that give rise to the measured BOLD response.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:569546 |
| Date | January 2011 |
| Creators | Mohtasib, Rafat Saeed |
| Publisher | University of Liverpool |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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