Abstract
In this study we investigated effects of the APOE ε4 allele (which confers an enhanced risk of poorer cognitive ageing, and Alzheimer’s Disease) on sustained attention (vigilance) performance in young adults using the Rapid Visual Information Processing (RVIP) task and event-related fMRI. Previous fMRI work with this task has used block designs: this study is the first to image an extended (6-minute) RVIP task. Participants were 26 carriers of the APOE ε4 allele, and 26 non carriers (aged 18–28). Pupil diameter was measured throughout, as an index of cognitive effort. We compared activity to RVIP task hits to hits on a control task (with similar visual parameters and response requirements but no working memory load): this contrast showed activity in medial frontal, inferior and superior parietal, temporal and visual cortices, consistent with previous work, demonstrating that meaningful neural data can be extracted from the RVIP task over an extended interval and using an event-related design. Behavioural performance was not affected by genotype; however, a genotype by condition (experimental task/control task) interaction on pupil diameter suggested that ε4 carriers deployed more effort to the experimental compared to the control task. fMRI results showed a condition by genotype interaction in the right hippocampal formation: only ε4 carriers showed downregulation of this region to experimental task hits versus control task hits. Experimental task beta values were correlated against hit rate: parietal correlations were seen in ε4 carriers only, frontal correlations in non-carriers only. The data indicate that, in the absence of behavioural differences, young adult ε4 carriers already show a different linkage between functional brain activity and behaviour, as well as aberrant hippocampal recruitment patterns. This may have relevance for genotype differences in cognitive ageing trajectories.
Highlights
In this study we investigated effects of the Apolipoprotein E (APOE) ε4 allele on sustained attention performance in young adults using the Rapid Visual Information Processing (RVIP) task and event-related fMRI
In this study we investigated cognitive performance and neural activation differences in young adult carriers of the Apolipoprotein E (APOE) ε4 allele using the rapid visual information processing (RVIP) task [1], a paradigm frequently used to measure sustained attention
For the purposes of this study, it was important that we examine sustained attention over an extended task interval for consistency with previous behavioural investigations showing that young adult e4+ sustain a higher level of performance over a 6-minute task epoch [4, 5], with some evidence of a time by genotype interaction [4]
Summary
In this study we investigated cognitive performance and neural activation differences in young adult carriers of the Apolipoprotein E (APOE) ε4 allele using the rapid visual information processing (RVIP) task [1], a paradigm frequently used to measure sustained attention. A small number of studies have examined its neural underpinnings using fMRI [10, 11]; others have combined fMRI with a nicotine manipulation [6, 12]: importantly, these studies have used block designs which constrains the epoch over which the task can be run These studies contrasted RVIP task blocks against interleaved control task blocks (employing the same stimuli but with the last digit of each target sequence replaced by a ‘0’: participants are instructed to respond to the ‘0’, eliminating the working memory requirement). Commonalities (task>control) were observed in bilateral frontal, left parietal, thalamus and cerebellum; and (control>task) in occipital lobe This was the first time an event-related approach had been tried: previously, authors had reservations about whether an event-related analysis could capture the neural activity reflecting the sustained nature of the vigilance requirements. Neale et al.’s findings suggest that vigilance-related activity can be extracted in an analysis that only models hits
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