PT - JOURNAL ARTICLE AU - Bahaaeddin Attaallah AU - Pierre Petitet AU - Elista Slavkova AU - Vicky Turner AU - Youssuf Saleh AU - Sanjay G. Manohar AU - Masud Husain TI - Hypersensitivity to uncertainty is key feature of subjective cognitive impairment AID - 10.1101/2021.12.23.473986 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.12.23.473986 4099 - http://biorxiv.org/content/early/2021/12/24/2021.12.23.473986.short 4100 - http://biorxiv.org/content/early/2021/12/24/2021.12.23.473986.full AB - 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 hypersensitive 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. Hypersensitivity 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 both uncertainty hypersensitivity and affective burden were associated with stronger insular-hippocampal connectivity. 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.Competing Interest StatementThe authors have declared no competing interest.