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.

The human hippocampus and its subfield volumes across age, sex and APOE e4 status.

Female sex, age and carriage of the apolipoprotein E e4 allele are the greatest risk factors for sporadic Alzheimer's disease. The hippocampus has a selective vulnerability to atrophy in ageing that may be accelerated in Alzheimer's disease, including in those with increased genetic risk of the disease, years before onset. Within the hippocampal complex, subfields represent cytoarchitectonic and connectivity based divisions. Variation in global hippocampal and subfield volume associated with sex, age and apolipoprotein E e4 status has the potential to provide a sensitive biomarker of future vulnerability to Alzheimer's disease. Here, we examined non-linear age, sex and apolipoprotein E effects, and their interactions, on hippocampal and subfield volumes across several decades spanning mid-life to old age in 36 653 healthy ageing individuals. FMRIB Software Library derived estimates of total hippocampal volume and Freesurfer derived estimates hippocampal subfield volume were estimated. A model-free, sliding-window approach was implemented that does not assume a linear relationship between age and subfield volume. The annualized percentage of subfield volume change was calculated to investigate associations with age, sex and apolipoprotein E e4 homozygosity. Hippocampal volume showed a marked reduction in apolipoprotein E e4/e4 female carriers after age 65. Volume was lower in homozygous e4 individuals in specific subfields including the presubiculum, subiculum head, cornu ammonis 1 body, cornu ammonis 3 head and cornu ammonis 4. Nearby brain structures in medial temporal and subcortical regions did not show the same age, sex and apolipoprotein E interactions, suggesting selective vulnerability of the hippocampus and its subfields. The findings demonstrate that in healthy ageing, two factors-female sex and apolipoprotein E e4 status-confer selective vulnerability of specific hippocampal subfields to volume loss.

Hippocampal volume across age: Nomograms derived from over 19,700 people in UK Biobank.

Measurement of hippocampal volume has proven useful to diagnose and track progression in several brain disorders, most notably in Alzheimer's disease (AD). For example, an objective evaluation of a patient's hippocampal volume status may provide important information that can assist diagnosis or risk stratification of AD. However, clinicians and researchers require access to age-related normative percentiles to reliably categorise a patient's hippocampal volume as being pathologically small. Here we analysed effects of age, sex, and hemisphere on the hippocampus and neighbouring temporal lobe volumes, in 19,793 generally healthy participants in the UK Biobank. A key finding of the current study is a significant acceleration in the rate of hippocampal volume loss in middle age, more pronounced in females than in males. In this report, we provide normative values for hippocampal and total grey matter volume as a function of age for reference in clinical and research settings. These normative values may be used in combination with our online, automated percentile estimation tool to provide a rapid, objective evaluation of an individual's hippocampal volume status. The data provide a large-scale normative database to facilitate easy age-adjusted determination of where an individual hippocampal and temporal lobe volume lies within the normal distribution.

Apathy in Alzheimer's disease.

Apathy is the most common neuropsychiatric symptom in patients with Alzheimer's disease (AD). The presence of apathy has been related to greater caregiver distress, decreased quality of life, and increased morbidity. Here we review the most recent studies on this neuropsychiatric syndrome, focusing on prevalence, impact on quality of life, behavioural and neuroimaging studies, and treatment options. The results of some investigations on the behavioural and neuroanatomical profile of apathy in AD point to a role of frontostriatal circuits, specifically involving the anterior cingulate cortex. However, small and heterogeneous samples, lack of control for disease severity, and non-specific apathy scales complicate interpretation of results. Future studies might benefit from studying multiple dimensions of apathy within conceptual frameworks which allow for a deconstruction of underlying mechanisms.

Relationships between activity and well-being in people with parkinson's disease.

Objectives: The complex symptomatology of Parkinson' disease (PD) usually goes along with reduced physical activity. Previous studies have indicated positive effects of activating therapies on patients' well-being. This study, therefore, examined how activity in daily life is related to patients' subjective condition. Materials and Methods: Twenty-one PD patients rated their condition every two hours during two routine days and documented the duration and type of their activities (based on the PRISCUS-Physical Activity Questionnaire) during the respective time intervals. They were furthermore assessed regarding motor and nonmotor symptoms, personality factors, and coping strategies. Results: Patients spent on average 8.59 ± 2.93 hr per day at physical rest and 5.47 ± 2.93 hr physically active. We found highly significant associations between positive condition ratings (such as happiness, motivation, and concentration) and the duration of subsequent physical activities (adj.r2  = .689) as well as between the duration of these activities and a subsequent improvement in the subjective condition (adj.r2  = .545). This was strongest in patients using active coping strategies and showing agreeable and conscientious personality traits (adj.r2  = .380). Nonmotor symptom severity was weakly inversely related to the daily amount of activities (adj.r2  = .273), whereas no significant association with motor symptom severity was found. Conclusions: The results suggest a feedback process between a positive subjective condition and physical activities in PD patients. This appears to depend on the use of active coping strategies and nonmotor symptoms rather than on motor symptom severity. The results should encourage physicians to address the importance of everyday physical activities and to provide patients with behavioral advice.

Theory of mind performance in Parkinson's disease is associated with motor and cognitive functions, but not with symptom lateralization.

Next to the typical motor signs, Parkinson's disease (PD) goes along with neuropsychiatric symptoms, amongst others affecting social cognition. Particularly, Theory of Mind (ToM) impairments have mostly been associated with right hemispherical brain dysfunction, so that it might prevail in patients with left dominant PD. Fourty-four PD patients, twenty-four with left and twenty with right dominant motor symptoms, engaged in the Reading the Mind in the Eyes (RME) and the Faux Pas Detection Test (FPD) to assess affective and cognitive ToM. The results were correlated with performance in further cognitive tests, and analyzed with respect to associations with the side of motor symptom dominance and severity of motor symptoms. No association of ToM performance with right hemispheric dysfunction was found. RME results were inversely correlated with motor symptom severity, while FPD performance was found to correlate with the performance in verbal fluency tasks and the overall cognitive evaluation. Affective ToM was found associated with motor symptom severity and cognitive ToM predominantly with executive function, but no effect of PD lateralization on this was identified. The results suggest that deficits in social cognition occur as a sequel of the general corticobasal pathology in PD, rather than as a result of hemisphere-specific dysfunction.