The role of the human hippocampus in decision-making under uncertainty.

The role of the hippocampus in decision-making is beginning to be more understood. Because of its prospective and inferential functions, we hypothesized that it might be required specifically when decisions involve the evaluation of uncertain values. A group of individuals with autoimmune limbic encephalitis-a condition known to focally affect the hippocampus-were tested on how they evaluate reward against uncertainty compared to reward against another key attribute: physical effort. Across four experiments requiring participants to make trade-offs between reward, uncertainty and effort, patients with acute limbic encephalitis demonstrated blunted sensitivity to reward and effort whenever uncertainty was considered, despite demonstrating intact uncertainty sensitivity. By contrast, the valuation of these two attributes (reward and effort) was intact on uncertainty-free tasks. Reduced sensitivity to changes in reward under uncertainty correlated with the severity of hippocampal damage. Together, these findings provide evidence for a context-sensitive role of the hippocampus in value-based decision-making, apparent specifically under conditions of uncertainty.

Remote digital cognitive assessment reveals cognitive deficits related to hippocampal atrophy in autoimmune limbic encephalitis: a cross-sectional validation study.

Background: Autoimmune limbic encephalitis (ALE) is a neurological disease characterised by inflammation of the limbic regions of the brain, mediated by pathogenic autoantibodies. Because cognitive deficits persist following acute treatment of ALE, the accurate assessment of long-term cognitive outcomes is important for clinical assessments and trials. However, evaluating cognition is costly and an unmet need exists for validated digital methods. Methods: In this cross-sectional validation study, we investigated whether a remote digital platform could identify previously characterised cognitive impairments in patients with chronic ALE and whether digital metrics would correlate with standard neuropsychological assessment and hippocampal volume. Patients with ALE who had a chronic and stable presentation and received a clinical diagnosis of ALE were recruited for this study. The cognitive performance of 21 patients with ALE and 54 age-matched healthy controls - enrolled via the University of Oxford (UK) Cognitive Neurology Lab testing programme - was assessed with a battery of 12 cognitive tasks from the Cognitron online platform. The platform was optimised with National Institute for Health and Care Research (NIHR) support to be deliverable remotely to elderly and patient groups. The primary outcome measure was behavioural performance and corresponding neuroimaging and neuropsychological assessment metrics. Findings: Between February 15, 2021, and April 21, 2022, 21 patients with ALE (mean age 63.01 years, 14 males) and 54 healthy controls (mean age 65.56 years, 23 males) completed the digital cognitive assessment. Patients with ALE performed significantly worse in memory, visuospatial abilities, executive function, and language. No impairments in digit & spatial span, target detection (attention) and emotion discrimination were observed. The global score on the online cognitive tasks correlated significantly with the established Addenbrooke's Cognitive Examination III (ACE) pen-and-paper test. Deficits in visuospatial processing and language were identified in ALE compared to controls using remote digital testing but not using the ACE, highlighting higher sensitivity of computerised testing to residual cognitive impairment. Finally, the hippocampal volumes of patients with ALE and healthy controls correlated with online cognitive scores. Interpretation: These findings demonstrate that subtle cognitive deficits in patients with chronic ALE, who often show full recovery in measures of disability and dependence on daily activities, are detectable using a remote online platform, which also relates to hippocampal atrophy. Such methods may facilitate the characterisation of cognitive profiles in complex neurological diseases. Future longitudinal studies designed to assess the utility of such digital methods for further clinical characterisation are needed. Funding: The Wellcome Trust, Medical Research Council, National Institute for Health Research, Rhodes Scholarship, and the Berrow Foundation Scholarship.

Hyperreactivity to uncertainty is a key feature of subjective cognitive impairment.

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.

Assessment of apathy in neurological patients using the Apathy Motivation Index caregiver version.

Apathy is a common, disabling neuropsychiatric syndrome that occurs across many brain disorders and may be associated with diminished motivation in behavioural, cognitive, emotional and social domains. Assessment is complicated by the variability of symptoms across apathy domains and self-report from patients, which can be misleading due to their lack of insight. Independent evaluation by clinicians also has limitations though if it has to be performed with limited time. Caregiver reports are a viable alternative, but current assessments for them either do not distinguish between different apathy domains or are interview-based and take long to administer. In this study, we developed a brief caregiver questionnaire version of the recently developed Apathy Motivation Index (AMI), which is a self-report tool. We confirmed three apathy factors in this new caregiver measure (AMI-CG) that were also present in the AMI: Behavioural Activation, Emotional Sensitivity and Social Motivation. Furthermore, we validated the scores against more extensive caregiver interviews using the established Lillle apathy rating scale as well as patient self-reports of apathy, measures of depression, anhedonia, cognition, activities of daily living and caregiver burden across four different neurological conditions: Parkinson's disease, Alzheimer's disease, subjective cognitive impairment and limbic encephalitis. The AMI-CG showed good internal reliability, external validity and diagnostic accuracy. It also uncovered cases of social apathy overlooked by traditional instruments. Crucially, patients who under-rated their apathy compared to informants were more likely to have difficulties performing everyday activities and to be a greater burden to caregivers. The findings provide evidence for a multidimensional conceptualization of apathy and an instrument for efficient detection of apathy based on caregiver reports for use in clinical practice.

Vividness of visual imagery questionnaire scores and their relationship to visual short-term memory performance.

Mechanisms underlying visual imagery, the ability to create vivid mental representations of a scene in the absence of sensory input, remain to be fully understood. Some previous studies have proposed that visual imagery might be related to visual short-term memory (STM), with a common mechanism involving retention of visual information over short periods of time. Other observations have shown a strong relationship between visual imagery and functional activity in the hippocampus and primary visual cortex, both regions also associated with visual STM. Here we examined the relationship of visual imagery to STM and hippocampal and primary visual cortex volumes, first in a large sample of healthy people across a large age range (N = 229 behavioural data; N = 56 MRI data in older participants) and then in patients with Alzheimer's disease and Parkinson's disease (N = 19 in each group compared to 19 age-matched healthy controls). We used a variant of the "What was where?" visual object-location binding task to assess the quality of remembered information over short delays. In healthy people, no evidence of a relationship between the vividness of visual imagery and any visual STM performance parameter was found. However, there was a significant positive correlation between visual imagery and the volumes of the hippocampus and primary visual cortex. Although visual STM performance was significantly impaired in patients with Alzheimer's disease, their vividness of visual imagery scores were comparable to those of age-matched elderly controls and patients with Parkinson's disease. Despite hippocampal volumes also being reduced in Alzheimer's patients, there appeared to be no impact on their self-reported visual imagery. In conclusion, visual imagery was not significantly related to visual STM performance, either in healthy controls or Alzheimer's or Parkinson's disease but it was related to hippocampal and visual cortex volume in healthy people.

The computational cost of active information sampling before decision-making under uncertainty.

Humans often seek information to minimize the pervasive effect of uncertainty on decisions. Current theories explain how much knowledge people should gather before a decision, based on the cost-benefit structure of the problem at hand. Here, we demonstrate that this framework omits a crucial agent-related factor: the cognitive effort expended while collecting information. Using an active sampling model, we unveil a speed-efficiency trade-off whereby more informative samples take longer to find. Crucially, under sufficient time pressure, humans can break this trade-off, sampling both faster and more efficiently. Computational modelling demonstrates the existence of a cost of cognitive effort which, when incorporated into theoretical models, provides a better account of people's behaviour and also relates to self-reported fatigue accumulated during active sampling. Thus, the way people seek knowledge to guide their decisions is shaped not only by task-related costs and benefits, but also crucially by the quantifiable computational costs incurred.

The relationship between apathy and impulsivity in large population samples.

Apathy and impulsivity are debilitating conditions associated with many neuropsychiatric conditions, and expressed to variable degrees in healthy people. While some theories suggest that they lie at different ends of a continuum, others suggest their possible co-existence. Surprisingly little is known, however, about their empirical association in the general population. Here, gathering data from six large studies ([Formula: see text]), we investigated the relationship between measures of apathy and impulsivity in young adults. The questionnaires included commonly used self-assessment tools-Apathy Evaluation Scale, Barratt Impulsiveness Scale (BIS-11) and UPPS-P Scale-as well as a more recent addition, the Apathy Motivation Index (AMI). Remarkably, across datasets and assessment tools, global measures of apathy and impulsivity correlated positively. However, analysis of sub-scale scores revealed a more complex relationship. Although most dimensions correlated positively with one another, there were two important exceptions revealed using the AMI scale. Social apathy was mostly negatively correlated with impulsive behaviour, and emotional apathy was orthogonal to all other sub-domains. These results suggest that at a global level, apathy and impulsivity do not exist at distinct ends of a continuum. Instead, paradoxically, they most often co-exist in young adults. Processes underlying social and emotional apathy, however, appear to be different and dissociable from behavioural apathy and impulsivity.