title: Disrupted neural activity patterns to novelty and effort in young adultAPOE-e4 carriers performing a subsequent memory task.
abstract: The APOE e4 allele has been linked to poorer cognitive aging and enhanced dementia risk. Previous imaging studies have used subsequent memory paradigms to probe hippocampal function in e4 carriers across the age range, and evidence suggests a pattern of hippocampal overactivation in young adult e4 carriers.
  
  
  
  In this study, we employed a word-based subsequent memory task under fMRI; pupillometry data were also acquired as an index of cognitive effort. Participants (26 non-e4 carriers and 28 e4 carriers) performed an incidental encoding task (presented as word categorization), followed by a surprise old/new recognition task after a 40 minute delay.
  
  
  
  In e4 carriers only, subsequently remembered words were linked to increased hippocampal activity. Across all participants, increased pupil diameter differentiated subsequently remembered from forgotten words, and neural activity covaried with pupil diameter in cuneus and precuneus. These effects were weaker in e4 carriers, and e4 carriers did not show greater pupil diameter to remembered words. In the recognition phase, genotype status also modulated hippocampal activity: here, however, e4 carriers failed to show the conventional pattern of greater hippocampal activity to novel words.
  
  
  
  Overall, neural activity changes were unstable in e4 carriers, failed to respond to novelty, and did not link strongly to cognitive effort, as indexed by pupil diameter. This provides further evidence of abnormal hippocampal recruitment in young adult e4 carriers, manifesting as both up and downregulation of neural activity, in the absence of behavioral performance differences.
authors.affiliation: School of Psychology University of Sussex Brighton East Sussex UK; School of Psychology University of Surrey Guildford Surrey UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Evans
authors.affiliation: Brighton and Sussex Medical School (BSMS) Brighton East Sussex UK.
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Dowell
authors.affiliation: Brighton and Sussex Medical School (BSMS) Brighton East Sussex UK.
authors.forename: Naji
authors.initials: N
authors.lastname: Tabet
authors.affiliation: School of Psychology University of Sussex Brighton East Sussex UK.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: King
authors.affiliation: School of Psychology University of Sussex Brighton East Sussex UK.
authors.forename: Samuel B
authors.initials: SB
authors.lastname: Hutton
authors.affiliation: School of Psychology University of Sussex Brighton East Sussex UK.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Rusted
mesh_terms: D000293:Adolescent; D000328:Adult; D053327:Apolipoprotein E4 / Q000235:genetics*; D005260:Female; D059907:Functional Neuroimaging / Q000379:methods*; D006579:Heterozygote; D006624:Hippocampus / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009778:Occipital Lobe / Q000503:physiopathology*; D010296:Parietal Lobe / Q000503:physiopathology*; D011680:Pupil / Q000502:physiology*; D021641:Recognition, Psychology / Q000502:physiology*; D055815:Young Adult
chemical_list: D053327:Apolipoprotein E4
keywords: APOE; fMRI; hippocampus; memory; pupillary; reflex