Using event-related fMRI to examine sustained attention processes and effects of APOE ε4 in young adults

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.

Responses to executive demand in young adulthood differ by APOE genotype

“…Furthermore, both genotype groups showed a decline in target detection (after accounting for response bias) from conditions of low to high executive demand, although robust analyses suggest this result should be interpreted with caution. Notably, an imaging study using the same sustained attention paradigm as the current study also reported no genotype behavioural differences in correct hits or target detection in young adults but instead saw different patterns of activation and cognitive effort indexed through pupillometry, suggestive of different cognitive strategies across genotypes [67].…”

TTLL11 gene is associated with sustained attention performance and brain networks: A genome‐wide association study of a healthy Chinese sample

“…On the other hand, imaging studies of ADHD also confirmed that DAN and VAN were involved in inattention, while SMN and DMN were involved in hyperactivity 35 . However, only a few studies have explored genetic effects on these brain regions when performing attention tasks 9,36,37 . We thus expected that genes associated with sustained attention might also be associated with functional connectivity of these networks.…”

“…35 However, only a few studies have explored genetic effects on these brain regions when performing attention tasks. 9,36,37 We thus expected that genes associated with sustained attention might also be associated with functional connectivity of these networks.…”

Mid age APOE ε4 carriers show memory-related functional differences and disrupted structure-function relationships in hippocampal regions

“…fMRI. The fMRI acquisition and preprocessing protocol has been described previously 67 : fMRI datasets were acquired using a T2* -weighted 2D-EPI sequence. To minimise signal artefacts originating from the sinuses, axial slices were tilted 30° from inter-commissural plane.…”