Wolbers, Thomas

Morris, Richard

Wood, Emma

Harris, Mathew Alan

Biotechnology and Biological Sciences Research Council (BBSRC)

2015-04-17T15:28:55Z

2015-04-17T15:28:55Z

2014-11-28

With advancing age, many cognitive faculties deteriorate, and navigation abilities may be among those most affected. The majority of previous work investigating navigation impairments in ageing has focused on allocentric processing, attributing deficits to hippocampal dysfunction. However, real-world navigation is dependent upon numerous different strategies, as well as the ability to flexibly switch between them. Outside the context of navigation, it has been demonstrated that strategy switching, thought to be coordinated by regions of prefrontal cortex and the locus coeruleus-noradrenergic system, is also susceptible to the effects of ageing. Deficits in navigational strategy switching, and prefrontal or noradrenergic dysfunction, are therefore also likely to contribute to age-related navigation impairments. The work presented in this thesis aimed to explore age-related impairments in strategy switching within the context of navigation, and the underlying neural mechanisms in terms of a prefrontal-noradrenergic model of switching. The studies presented in Chapter Three assessed the use of allocentric and egocentric navigational strategies by young and older people. Older participants tended to use an egocentric strategy where an allocentric strategy was required, possibly due to a difficulty in switching to the appropriate allocentric strategy. In Chapter Four, I provide an account of two studies directly assessing navigational strategy switching, using two different tasks based in virtual reality. The first study utilised a virtual adaptation of the plus maze task, involving switching between an allocentric place strategy and an egocentric response strategy, and demonstrated that older participants were specifically impaired at switching to the place strategy. The second study used a more realistic task set in a virtual town environment, which involved switching from an egocentric route-following strategy to an allocentric wayfinding strategy, and also demonstrated an age-related deficit in switching to an allocentric strategy. In Chapter Five, I begin to explore the mechanisms underlying impaired navigational strategy switching in ageing. Firstly, I describe a further behavioural study that used variants of the virtual plus maze and a navigational gambling task to demonstrate a contribution of impaired decision making to the deficit in switching to an allocentric strategy. This indicates that the deficit can be attributed, at least in part, to prefrontal dysfunction. A second study presented in the same chapter demonstrated that practising orienteering does not protect against decline in navigational strategy switching ability with ageing. Chapter Six provides an account of my direct assessment of the neural bases of navigational strategy switching using functional magnetic resonance imaging. In young subjects, I found some evidence in support of the roles of prefrontal regions in navigational strategy switching. However, I was unable to complete development of a task suitable for assessing age differences in functional activation of brain regions involved in navigational strategy switching. The final experimental study, included in Chapter Seven, assessed pupil size and heart rate as physiological correlates of noradrenergic activity during performance of the virtual plus maze. Both young and old participants demonstrated a noradrenergic response to all strategy changes, suggesting that impairments are more likely attributable to dysfunction of prefrontal cortex than of the locus coeruleus, although some subtle effects suggested that noradrenergic dysfunction does have some effect on navigational strategy switching deficits. In the same chapter, I report the results of a meta-analysis of data from five of the preceding studies, suggesting that deficits in both strategy switching and allocentric processing combine to produce a greater impairment in switching to an allocentric strategy. The main finding of this series of studies is that navigational strategy switching is impaired in ageing, which may contribute to the more widely reported difficulties that older people have with navigation. My work also provides evidence in support of a prefrontal-noradrenergic model of navigational strategy switching, and suggests that dysfunction of prefrontal cortex and, to a lesser extent, the locus coeruleus-noradrenergic system is responsible for decline in navigational strategy switching ability with ageing. In conclusion, this thesis draws attention to the important role of deficient executive processing and dysfunction of extra-hippocampal brain regions in age-related navigation impairments.

http://hdl.handle.net/1842/10066

en

The University of Edinburgh

Harris, M.A., Wiener, J.M. & Wolbers, T. (2012). Aging specifically impairs switching to an allocentric navigational strategy. Frontiers in Aging Neuroscience, 4: 29.

Wiener, J.M., de Condappa, O., Harris, M.A. & Wolbers, T. (2013). Maladaptive bias for extrahippocampal navigation strategies in aging humans. Journal of Neuroscience, 33: 6012-6017.

Harris, M.A. & Wolbers, T. (2014). How age-related strategy switching deficits affect wayfinding in complex environments. Neurobiology of Aging, 35: 1095-1102.

navigation

ageing

strategy switching

age-related impairment

prefrontal cortex

Navigational strategy switching in ageing

Thesis or Dissertation

Doctoral

PhD Doctor of Philosophy