Dataset Information

Disrupted neural activity patterns to novelty and effort in young adult APOE-e4 carriers performing a subsequent memory task.

ABSTRACT: INTRODUCTION: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. METHODS: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. RESULTS: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. CONCLUSIONS: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.

SUBMITTER: Evans S

PROVIDER: S-EPMC5318365 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Disrupted neural activity patterns to novelty and effort in young adult <i>APOE</i>-e4 carriers performing a subsequent memory task.

Evans Simon S Dowell Nicholas G NG Tabet Naji N King Sarah L SL Hutton Samuel B SB Rusted Jennifer M JM

Brain and behavior 20170105 2

<h4>Introduction</h4>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.<h4>Methods</h4>In this study, we employed a word-based subsequent memory task under fMRI; pupillometry data were also acquired as an index of cognitive effort. Participan ...[more]

PMID: 28239522

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Project description:Alzheimer's disease (AD) is the most common form of dementia and the leading risk factor, after age, is possession of the apolipoprotein E epsilon 4 allele (APOE4). Approximately 50% of AD patients carry one or two copies of APOE4 but the mechanisms by which it confers risk are still unknown. APOE4 carriers are reported to demonstrate changes in brain structure, cognition, and neuropathology, but findings have been inconsistent across studies. In the present study, we used multi-modal data to characterise the effects of APOE4 on the brain, to investigate whether AD pathology manifests differently in APOE4 carriers, and to determine if AD pathomechanisms are different between carriers and non-carriers. Brain structural differences in APOE4 carriers were characterised by applying machine learning to over 2000 brain MRI measurements from 33,384 non-demented UK biobank study participants. APOE4 carriers showed brain changes consistent with vascular dysfunction, such as reduced white matter integrity in posterior brain regions. The relationship between APOE4 and AD pathology was explored among the 1260 individuals from the Religious Orders Study and Memory and Aging Project (ROSMAP). APOE4 status had a greater effect on amyloid than tau load, particularly amyloid in the posterior cortical regions. APOE status was also highly correlated with cerebral amyloid angiopathy (CAA). Bulk tissue brain transcriptomic data from ROSMAP and a similar dataset from the Mount Sinai Brain Bank showed that differentially expressed genes between the dementia and non-dementia groups were enriched for vascular-related processes (e.g., "angiogenesis") in APOE4 carriers only. Immune-related transcripts were more strongly correlated with AD pathology in APOE4 carriers with some transcripts such as TREM2 and positively correlated with pathology severity in APOE4 carriers, but negatively in non-carriers. Overall, cumulative evidence from the largest neuroimaging, pathology, and transcriptomic studies available suggests that vascular dysfunction is key to the development of AD in APOE4 carriers. However, further studies are required to tease out non-APOE4-specific mechanisms.

Project description:Recent research has demonstrated that pupillometry is a robust measure for quantifying listening effort. However, pupillary responses in listening situations where multiple cognitive functions are engaged and sustained over a period of time remain hard to interpret. This limits our conceptualisation and understanding of listening effort in realistic situations, because rarely in everyday life are people challenged by one task at a time. Therefore, the purpose of this experiment was to reveal the dynamics of listening effort in a sustained listening condition using a word repeat and recall task. Words were presented in quiet and speech-shaped noise at different signal-to-noise ratios (SNR): 0dB, 7dB, 14dB and quiet. Participants were presented with lists of 10 words, and required to repeat each word after its presentation. At the end of the list, participants either recalled as many words as possible or moved on to the next list. Simultaneously, their pupil dilation was recorded throughout the whole experiment. When only word repeating was required, peak pupil dilation (PPD) was bigger in 0dB versus other conditions; whereas when recall was required, PPD showed no difference among SNR levels and PPD in 0dB was smaller than repeat-only condition. Baseline pupil diameter and PPD followed different variation patterns across the 10 serial positions within a block for conditions requiring recall: baseline pupil diameter built up progressively and plateaued in the later positions (but shot up when listeners were recalling the previously heard words from memory); PPD decreased at a pace quicker than in repeat-only condition. The current findings demonstrate that additional cognitive load during a speech intelligibility task could disturb the well-established relation between pupillary response and listening effort. Both the magnitude and temporal pattern of task-evoked pupillary response differ greatly in complex listening conditions, urging for more listening effort studies in complex and realistic listening situations.

Dataset Information

Disrupted neural activity patterns to novelty and effort in young adult APOE-e4 carriers performing a subsequent memory task.

Publications

Disrupted neural activity patterns to novelty and effort in young adult <i>APOE</i>-e4 carriers performing a subsequent memory task.

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