5 research outputs found
Cortisol, cognition and the ageing prefrontal cortex
The structural and functional decline of the ageing human brain varies by brain
region, cognitive function and individual. The underlying biological mechanisms are
poorly understood. One potentially important mechanism is exposure to
glucocorticoids (GCs; cortisol in humans); GC production is increasingly varied with
age in humans, and chronic exposure to high levels is hypothesised to result in
cognitive decline via cerebral remodelling. However, studies of GC exposure in
humans are scarce and methodological differences confound cross-study comparison.
Furthermore, there has been little focus on the effects of GCs on the frontal lobes and
key white matter tracts in the ageing brain. This thesis therefore examines
relationships among cortisol levels, structural brain measures and cognitive
performance in 90 healthy, elderly community-dwelling males from the Lothian
Birth Cohort 1936. Salivary cortisol samples characterised diurnal (morning and
evening) and reactive profiles (before and after a cognitive test battery). Structural
variables comprised Diffusion Tensor Imaging measures of major brain tracts and a
novel manual parcellation method for the frontal lobes. The latter was based on a
systematic review of current manual methods in the context of putative function and
cytoarchitecture. Manual frontal lobe brain parcellation conferred greater spatial and
volumetric accuracy when compared to both single- and multi-atlas parcellation at
the lobar level. Cognitive ability was assessed via tests of general cognitive ability,
and neuropsychological tests thought to show differential sensitivity to the integrity
of frontal lobe sub-regions. The majority of, but not all frontal lobe test scores shared
considerable overlap with general cognitive ability, and cognitive scores correlated
most consistently with the volumes of the anterior cingulate. This is discussed in
light of the diverse connective profile of the cingulate and a need to integrate
information over more diffuse cognitive networks according to proposed de-differentiation
or compensation in ageing. Individuals with higher morning, evening
or pre-test cortisol levels showed consistently negative relationships with specific
regional volumes and tract integrity. Participants whose cortisol levels increased
between the start and end of cognitive testing showed selectively larger regional
volumes and lower tract diffusivity (correlation magnitudes <.44). The significant
relationships between cortisol levels and cognition indicated that flatter diurnal
slopes or higher pre-test levels related to poorer test performance. In contrast, higher
levels in the morning generally correlated with better scores (correlation magnitudes
<.25). Interpretation of all findings was moderated by sensitivity to type I error,
given the large number of comparisons conducted. Though there were limited
candidates for mediation analysis, cortisol-function relationships were partially
mediated by tract integrity (but not sub-regional frontal volumes) for memory and
post-error slowing. This thesis offers a novel perspective on the complex interplay
among glucocorticoids, cognition and the structure of the ageing brain. The findings
suggest some role for cortisol exposure in determining age-related decline in
complex cognition, mediated via brain structure
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Associations between pattern separation and hippocampal subfield structure and function vary along the lifespan: A 7 T imaging study.
Pattern separation (PS) describes the process by which the brain discriminates similar stimuli from previously encoded stimuli. This fundamental process requires the intact processing by specific subfields in the hippocampus and can be examined using mnemonic discrimination tasks. Previous studies reported different patterns for younger and older individuals between mnemonic discrimination performance and hippocampal subfield activation. Here, we investigated the relationship between the lure discrimination index (LDI) and hippocampal subfield volume and activity across the adult lifespan (20-70 years old). Using ultra-high field functional and structural magnetic resonance imaging at 7 T, we found that lower DG volume and higher CA3 activation was associated with worse LDI performance in individuals (>60 years), suggesting that this higher activation may be an indication of aberrant neurodegenerative-related processes. In fact, higher activation in the CA1 and DG was associated with lower volumes in these subfields. For individuals around 40-50 years old, we observed that greater left and right DG volume, and greater activity in the CA3 was associated with lower LDI performance. Taken together, these results suggest that the relationship between memory and hippocampal subfield structure or function varies nonlinearly and possibly reciprocally with age, with midlife being a critically vulnerable period in life
Default mode network connectivity as a function of familial and environmental risk for psychotic disorder
Research suggests that altered interregional connectivity in specific networks, such as the default mode network (DMN), is associated with cognitive and psychotic symptoms in schizophrenia. In addition, frontal and limbic connectivity alterations have been associated with trauma, drug use and urban upbringing, though these environmental exposures have never been examined in relation to DMN functional connectivity in psychotic disorder.status: publishe