Hypersensitivity to uncertainty in subjective cognitive decline

A behavioural and imaging study investigated the mechanisms of subjective cognitive decline (SCD) and its relation to depression and anxiety. It demonstrated that SCD patients have hypersensitivity to uncertainty, which is associated with strong insular-hippocampal connectivity.

In SCD, there is by definition no evidence of significant dysfunction. However, depression and anxiety are common, and the severity of SCD has often been found to correlate with the severity of this affective burden. Despite this correlation, the mechanisms behind this affective burden are not well understood, explained Dr Bahaaeddin Attaallah (University of Oxford, United Kingdom). The key factor underlying affective burden in SCD may be the processing of uncertainty. People prone to anxiety or depression may overact to uncertainty, i.e. gather more information than needed; likely due to an overestimation of uncertainty.

The presented study focused on the gathering of information (quantity and speed) when faced with uncertainty. A behavioural paradigm was used in which subjects were required to make decisions involving uncertainty and gather information before committing to these decisions. Participants were 27 SCD patients and 27 controls; mean age was 61 years. Participants also completed self-reported questionnaires of anxiety and depression. To investigate the brain networks involved, resting-state functional MRI was used.

Results showed that SCD patients require uncertainty to be lower; they do this by gathering more information prior to committing to a decision and doing this quicker than controls. However, no difference was observed in sampling efficiency. As expected, SCD patients were more depressed and more anxious. Affective burden was associated with rapid and extensive sampling.

In a network functional connectivity analysis, 40 regions of interest (ROIs) and 780 connections were analysed. These results showed that SCD patients, compared with controls, had specifically increased functional connectivity between the insular cortex and the hippocampus. Increased insular-hippocampal connectivity was also associated with overacting to uncertainty.

“Hyperreactivity to uncertainty mediates the association between increased insular-hippocampal connectivity and affective burden,” Dr Attaallah concluded. “This could be a key mechanism underlying psycho-cognitive manifestations in SCD and may be a possible treatment target.”

1. Attaallah B, et al. Hypersensitivity to uncertainty in subjective cognitive impairment. OPR-204, EAN 2021 Virtual Congress, 19–22 June.

 

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Posted on 18 August 202125 March 2024