Apathy and effort-based decision-making in Alzheimer's disease and subjective cognitive impairment.

INTRODUCTION: Apathy is a significant feature in Alzheimer's disease (AD) and subjective cognitive impairment (SCI), though its mechanisms are not well established. METHODS: An effort-based decision-making (EBDM) framework was applied to investigate apathy in 30 AD patients, 41 SCI participants, and 55 healthy controls (HC). Data were analyzed using a drift-diffusion model (DDM) to uncover latent psychological processes. RESULTS: SCI participants reported higher apathy than AD patients and HC. However, informant reports of apathy in AD patients were higher than self-reports and indicated significant apathy compared to HC. Both the AD and SCI groups showed reduced sensitivity to effort changes, linked to executive dysfunction in AD and apathy in SCI. Increased resting functional cortical connectivity with the nucleus accumbens (NA) was associated with higher apathy in SCI. DISCUSSION: These results highlight a similar disruption of EBDM in AD and SCI, differentially related to executive functioning in AD and apathy in SCI. Highlights: This is the first study investigating apathy using an effort-based decision-making (EBDM) framework in Alzheimer's disease (AD) and subjective cognitive impairment (SCI).Self-reports underestimate apathy in AD patients when compared to informant reports and healthy controls (HC). SCI participants, in whom self and informant reports were more concordant, also showed higher degrees of apathy.Both AD and SCI groups showed reduced sensitivity to effort.Reduced sensitivity to effort correlates with executive dysfunction in AD and apathy, but not depression, in SCI.Increased nucleus accumbens (ventral striatum) connectivity with the frontoparietal network was associated with higher apathy scores in SCI.The results thus suggest that while AD and SCI can have similar deficits in EBDM, these deficits correlate with distinct clinical manifestations: executive dysfunction in AD and apathy in SCI.

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.

Role of serotonin in modulation of decision-making in Parkinson's disease.

BACKGROUND: Dysfunction of dopaminergic pathways has been considered to play a pivotal role in Parkinson's disease (PD), affecting the processing of emotional and rewarding information, and potentially leading to symptoms of depression or apathy. However, some aspects of motivation in PD might be affected by non-dopaminergic mechanisms. AIM AND METHOD: The objective of this experimental medicine study was to investigate the contribution of serotonergic modulation via administration of citalopram (20 mg) for 7 days on motivated decision-making in twenty PD patients, measured using several different computerised tasks and clinical questionnaires that probe different aspects of decision-making. Twenty healthy controls were additionally tested without medication to assess any baseline differences between the two groups. RESULTS: Results indicated that PD patients were overall less motivated than controls on an effort- and reward-based decision-making task. Citalopram increased or decreased willingness to exert effort for reward, depending on whether baseline motivation was high or low, respectively. A task assessing decision-making under risk revealed higher levels of risk aversion for potential losses in PD patients, which neither serotonin nor the patient's regular dopaminergic medication seemed to restore. However, citalopram in PD was associated with more risk-seeking choices for gains, although patients and controls did not differ on this at baseline. CONCLUSION: The results provide evidence for a role of the serotonergic system in influencing some aspects of motivated decision-making in PD processes.

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.

Impact of processing demands at encoding, maintenance and retrieval in visual working memory.

There has been surprisingly little examination of how recall performance is affected by processing demands induced by retrieval cues, how manipulations at encoding interact with processing demands during maintenance or due to the retrieval cue, and how these are affected with aging. Here, we investigate these relationships by examining the fidelity of working memory recall across two delayed reproduction tasks with a continuous measure of report across the adult lifespan. Participants were asked to remember and subsequently reproduce from memory the identity and location of a probed item from the encoding display. In Experiment 1, we examined the effect of filtering irrelevant information at encoding and the impact of filtering distracting information at retrieval simultaneously. In Experiment 2, we tested how ignoring distracting information during maintenance or updating current contents with new information during this period affects recall. The results reveal that manipulating processing requirements induced by retrieval cues (by altering the nature of the retrieval foil) had a significant impact on memory recall: the presence of two previously viewed features from the encoding display in the retrieval foil led to a decrease in identification accuracy. Although irrelevant information can be filtered out well at encoding, both ignoring irrelevant information and updating the contents of memory during the maintenance delay had a detrimental effect on recall. These effects were similar across the lifespan, but older individuals were particularly affected by manipulations of processing demands at encoding as well as increasing set size of information to be retained in memory. Finally, analyses revealed that there were no systematic relationships between filtering performance at encoding, maintenance and retrieval suggesting that these processing demands are independent of each other. Rather than filtering being a single, monolithic entity, the data suggest that it is better accounted for as distinctly dissociable cognitive processes that engage and articulate with different phases of working memory.

Dopamine affects short-term memory corruption over time in Parkinson's disease.

Cognitive deficits are a recognised component of Parkinson's disease (PD). However, particularly within the domain of short-term memory, it is unclear whether these impairments are masked, or caused, by patients' dopaminergic medication. The effect of medication on pure maintenance in PD patients has rarely been explored, with most assessments examining maintenance intercalated between other executive tasks. Moreover, few studies have utilised methods that can measure the quality of mental representations, which can enable the decomposition of recall errors into their underlying neurocognitive components. Here, we fill this gap by examining pure maintenance in PD patients in high and low dopaminergic states. Participants had to encode the orientation of two stimuli and reproduce these orientations after a short (2 s) or long (8 s) delay. In addition, we also examined the performance of healthy, age-matched older adults to contextualise these effects and determine whether PD represents an exacerbation of the normal ageing process. Patients showed improved recall OFF compared to ON their dopaminergic medication, but only for long-duration trials. Moreover, PD patients OFF their medication actually performed at a level superior to age-matched controls, indicative of a paradoxical enhancement of memory in the low dopaminergic state. The application of a probabilistic model of response selection suggested that PD patients made fewer misbinding errors in the low, compared with high, dopaminergic state for longer-delay trials. Thus, unexpectedly, the mechanisms that prevent memoranda from being corrupted by misbinding over time appear to be enhanced in PD patients OFF dopaminergic medication. Possible explanations for this paradoxical effect are discussed.