Hyperreactivity to uncertainty is a key feature of subjective cognitive impairment

Abstract

With an increasingly ageing global population, more people are presenting with concerns about their cognitive function, but not all have an underlying neurodegenerative diagnosis. Subjective cognitive impairment (SCI) is a common condition describing self-reported deficits in cognition without objective evidence of cognitive impairment. Many individuals with SCI suffer from depression and anxiety, which have been hypothesised to account for their cognitive complaints. Despite this association between SCI and affective features, the cognitive and brain mechanisms underlying SCI are poorly understood. Here, we show that people with SCI are hyperreactive to uncertainty and that this might be a key mechanism accounting for their affective burden. Twenty-seven individuals with SCI performed an information sampling task, where they could actively gather information prior to decisions. Across different conditions, SCI participants sampled faster and obtained more information than matched controls to resolve uncertainty. Remarkably, despite their 'urgent' sampling behaviour, SCI participants were able to maintain their efficiency. Hyperreactivity to uncertainty indexed by this sampling behaviour correlated with the severity of affective burden including depression and anxiety. Analysis of MRI resting functional connectivity revealed that SCI participants had stronger insular-hippocampal connectivity compared to controls, which also correlated with faster sampling. These results suggest that altered uncertainty processing is a key mechanism underlying the psycho-cognitive manifestations in SCI and implicate a specific brain network target for future treatment.

Data availability

Anonymised data and code for replicating the main results in the manuscript have been deposited on the Open Science Framework platform: https://osf.io/7ysqu/.

The following data sets were generated

Article and author information

Author details

  1. Bahaaeddin Attaallah

    Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
    For correspondence
    Bahaaeddin.Attaallah@ndcn.ox.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7842-7974
  2. Pierre Petitet

    Department of Experimental Psychology, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1422-5326
  3. Elista Slavkova

    Department of Experimental Psychology, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Vicky Turner

    Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Youssuf Saleh

    Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Sanjay G Manohar

    Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Masud Husain

    Department of Experimental Psychology, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

Funding

Wellcome Trust (206330/Z/17/Z)

  • Masud Husain

Rhodes Scholarships

  • Bahaaeddin Attaallah

Medical Research Council (MR/P00878/X)

  • Sanjay G Manohar

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: All participants gave written consent to take part in the study. The study was approved by the University of Oxford ethics committee (RAS ID: 248379, Ethics Approval Reference: 18/SC/0448).

Copyright

© 2022, Attaallah et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,542
    views
  • 261
    downloads
  • 6
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Bahaaeddin Attaallah
  2. Pierre Petitet
  3. Elista Slavkova
  4. Vicky Turner
  5. Youssuf Saleh
  6. Sanjay G Manohar
  7. Masud Husain
(2022)
Hyperreactivity to uncertainty is a key feature of subjective cognitive impairment
eLife 11:e75834.
https://doi.org/10.7554/eLife.75834

Share this article

https://doi.org/10.7554/eLife.75834

Further reading

    1. Neuroscience
    Raven Star Wallace, Bronte Mckeown ... Jonathan Smallwood
    Research Article

    Movie-watching is a central aspect of our lives and an important paradigm for understanding the brain mechanisms behind cognition as it occurs in daily life. Contemporary views of ongoing thought argue that the ability to make sense of events in the ‘here and now’ depend on the neural processing of incoming sensory information by auditory and visual cortex, which are kept in check by systems in association cortex. However, we currently lack an understanding of how patterns of ongoing thoughts map onto the different brain systems when we watch a film, partly because methods of sampling experience disrupt the dynamics of brain activity and the experience of movie-watching. Our study established a novel method for mapping thought patterns onto the brain activity that occurs at different moments of a film, which does not disrupt the time course of brain activity or the movie-watching experience. We found moments when experience sampling highlighted engagement with multi-sensory features of the film or highlighted thoughts with episodic features, regions of sensory cortex were more active and subsequent memory for events in the movie was better—on the other hand, periods of intrusive distraction emerged when activity in regions of association cortex within the frontoparietal system was reduced. These results highlight the critical role sensory systems play in the multi-modal experience of movie-watching and provide evidence for the role of association cortex in reducing distraction when we watch films.

    1. Neuroscience
    Ankur Sinha, Padraig Gleeson ... Robin Angus Silver
    Tools and Resources

    Data-driven models of neurons and circuits are important for understanding how the properties of membrane conductances, synapses, dendrites, and the anatomical connectivity between neurons generate the complex dynamical behaviors of brain circuits in health and disease. However, the inherent complexity of these biological processes makes the construction and reuse of biologically detailed models challenging. A wide range of tools have been developed to aid their construction and simulation, but differences in design and internal representation act as technical barriers to those who wish to use data-driven models in their research workflows. NeuroML, a model description language for computational neuroscience, was developed to address this fragmentation in modeling tools. Since its inception, NeuroML has evolved into a mature community standard that encompasses a wide range of model types and approaches in computational neuroscience. It has enabled the development of a large ecosystem of interoperable open-source software tools for the creation, visualization, validation, and simulation of data-driven models. Here, we describe how the NeuroML ecosystem can be incorporated into research workflows to simplify the construction, testing, and analysis of standardized models of neural systems, and supports the FAIR (Findability, Accessibility, Interoperability, and Reusability) principles, thus promoting open, transparent and reproducible science.