Distinguishing between impairments of working memory and inhibitory control in cases of early dementia

Dementia (most notably, Alzheimer’s Disease) is often associated with impairments of both working memory and inhibitory control. However, it is unclear whether these are functionally distinct impairments. We addressed the issue of whether working memory and inhibitory control can be dissociated, using data from a sample of patients who were recruited in a longitudinal study (Crawford et al. 2013, 2015). The first case revealed a preserved working memory capacity together with poor inhibitory control in the anti-saccade task. A longitudinal follow-up revealed that the defective inhibitory control emerged 12-months before the dementia was evident on the mini-mental state examination assessment. A second case revealed a poor working memory together with a well-preserved level of inhibitory control. The dissociation of working memory and inhibitory control was confirmed statistically in 7 additional cases. These findings yield converging evidence that working memory and inhibitory control are distinct cognitive operations and challenges the Kimberg and Farah (2000) cognitive model of working memory

A third-person perspective on co-speech action gestures in Parkinson's disease

A combination of impaired motor and cognitive function in Parkinson’s disease (PD) can impact on language and communication, with patients exhibiting a particular difficulty processing action verbs. Co-speech gestures embody a link between action and language and contribute significantly to communication in healthy people. Here, we investigated how co-speech gestures depicting actions are affected in PD, in particular with respect to the visual perspective—or the viewpoint – they depict. Gestures are closely related to mental imagery and motor simulations, but people with PD may be impaired in the way they simulate actions from a first-person perspective and may compensate for this by relying more on third-person visual features. We analysed the action-depicting gestures produced by mild-moderate PD patients and age-matched controls on an action description task and examined the relationship between gesture-viewpoint, action-naming, and performance on an action observation task (weight judgement). Healthy controls produced the majority of their action-gestures from a first person perspective, whereas PD patients produced a greater proportion of gestures produced from a third person perspective. We propose that this reflects a compensatory reliance on third-person visual features in the simulation of actions in PD. Performance was also impaired in action-naming and weight judgement, although this was unrelated to gesture viewpoint. Our findings provide a more comprehensive understanding of how action-language impairments in PD impact on action communication, on the cognitive underpinnings of this impairment, as well as elucidating the role of action simulation in gesture production

Eye gaze and Ageing:Selective and combined effects of working memory and inhibitory control

Eye-tracking is increasingly studied as a cognitive and biological marker for the early signs of neuropsychological and psychiatric disorders. However, in order to make further progress a more comprehensive understanding of the age-related effects on eye-tracking is essential. The antisaccade task requires participants to make saccadic eye movements away from a prepotent stimulus. Speculation on the cause of the observed age-related differences in the antisaccade task largely centres around two sources of cognitive dysfunction: inhibitory control and working memory. The inhibitory control account views cognitive slowing and task errors as a direct result of the decline of inhibitory cognitive mechanisms. An alternative theory considers that a deterioration of working memory is the cause of these age-related effects on behaviour. The current study assessed inhibitory control and working memory processes underpinning saccadic eye movements in young and older participants. This was achieved with three experimental conditions that systematically varied the extent to which working memory and inhibitory control were taxed in the antisaccade task; a memory-guided task was used to explore the effect of increasing the working memory load; a Go/No-go task was used to explore the effect of increasing the inhibitory load; a ‘standard’ antisaccade task retained the standard working memory and inhibitory loads. Saccadic eye movements were also examined in control condition: the standard prosaccade task where the load or working memory and inhibitory control was minimal or absent. Saccade latencies, error rates and the spatial accuracy of saccades of older participants were compared to the same measures in healthy young controls across the conditions. The results revealed that ageing is associated with changes in both inhibitory control and working memory. Increasing the inhibitory load was associated with increased reaction times in the older group, whilst the increased working memory load and the inhibitory load contributed to an increase in the anti-saccade errors. These results reveal that ageing is associated with changes in both inhibitory control and working memory

Combined action observation and motor imagery influences hand movement amplitude in Parkinson's disease

Background: Action observation (AO) activates the motor system, influencing movement and increasing learning, and has been shown to improve speed and timing of movement in people with Parkinson's disease (PD). Importantly, however, effects on movement amplitude have not been quantitatively demonstrated. Additionally, motor imagery (MI) can increase behavioural and neural effects of AO, but the combined effects of AO+MI have never previously been explored in PD. The aim of this study was to investigate imitation of hand movement amplitude in people with PD following (i) AO and (ii) combined AO+MI. Methods: Twenty-four participants with mild to moderate PD and 24 healthy older adults observed and imitated videos showing a human hand moving between horizontal positions. Kinematics were recorded and modulation of vertical amplitude when replicating elevated vs. direct movements provided an index of imitation. After an initial set of AO trials, participants were instructed to engage in MI during observation for the remaining trials (AO+MI), emphasizing kinaesthetic (sensory) imagery. Results: Movement amplitude was imitated (modulated) for elevated vs. direct stimuli by both groups, and this imitation increased following MI instructions. Conclusions: These results demonstrate quantitatively for the first time that people with PD are able to modulate the amplitude of their hand movements following action observation, and that combining AO and MI increases imitation in PD. The effects parallel findings in healthy young participants, and indicate that combined action observation and motor imagery could be a promising therapeutic approach for PD

SaccadeMachine:Software for Analyzing Saccade Tests (Anti-Saccade and Pro-saccade)

Various types of saccadic paradigms, in particular, Prosaccade and Antisaccade tests are widely used in Pathophysiology and Psychology. Despite been widely used, there has not been a standard tool for processing and analyzing the eye tracking data obtained from saccade tests. We describe an open-source software for extracting and analyzing the eye movement data of different types of saccade tests that can be used to extract and compare participants' performance and various task-related measures across participants. We further demonstrate the utility of the software by using it to analyze the data from an antisaccade, and a recent distractor experiment

PSOVIS:An interactive tool for extracting post-saccadic oscillations from eye movement data

Post-microsaccadic eye movements recorded by high frame-rate pupil-based eye trackers reflect movements of different ocular structures such as deformation of the iris and pupil- eyeball relative movement as well as the dynamic overshoot of the eye globe at the end of each saccade. These Post-Saccadic Oscillations (PSO) exhibit a high degree of reproducibility across saccades and within participants. Therefore in order to study the characteristics of the post-saccadic eye movements, it is often desirable to extract the post-saccadic parts of the recorded saccades and to look at the ending part of all saccades. In order to ease the study- ing of PSO eye movements, a simple tool for extracting PSO signals from the eye movement recordings has been developed. The software application implements functions for extracting, aligning, visualising and finally exporting the PSO signals from eye movement recordings, to be used for post-processing. The code which is written in Python can be download from https://github.com/dmardanbeigi/PSOVIS.gi

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Hospital admission and emergency care attendance risk for SARS-CoV-2 delta (B.1.617.2) compared with alpha (B.1.1.7) variants of concern: a cohort study

Background: The SARS-CoV-2 delta (B.1.617.2) variant was first detected in England in March, 2021. It has since rapidly become the predominant lineage, owing to high transmissibility. It is suspected that the delta variant is associated with more severe disease than the previously dominant alpha (B.1.1.7) variant. We aimed to characterise the severity of the delta variant compared with the alpha variant by determining the relative risk of hospital attendance outcomes. Methods: This cohort study was done among all patients with COVID-19 in England between March 29 and May 23, 2021, who were identified as being infected with either the alpha or delta SARS-CoV-2 variant through whole-genome sequencing. Individual-level data on these patients were linked to routine health-care datasets on vaccination, emergency care attendance, hospital admission, and mortality (data from Public Health England's Second Generation Surveillance System and COVID-19-associated deaths dataset; the National Immunisation Management System; and NHS Digital Secondary Uses Services and Emergency Care Data Set). The risk for hospital admission and emergency care attendance were compared between patients with sequencing-confirmed delta and alpha variants for the whole cohort and by vaccination status subgroups. Stratified Cox regression was used to adjust for age, sex, ethnicity, deprivation, recent international travel, area of residence, calendar week, and vaccination status. Findings: Individual-level data on 43 338 COVID-19-positive patients (8682 with the delta variant, 34 656 with the alpha variant; median age 31 years [IQR 17–43]) were included in our analysis. 196 (2·3%) patients with the delta variant versus 764 (2·2%) patients with the alpha variant were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2·26 [95% CI 1·32–3·89]). 498 (5·7%) patients with the delta variant versus 1448 (4·2%) patients with the alpha variant were admitted to hospital or attended emergency care within 14 days (adjusted HR 1·45 [1·08–1·95]). Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients with the delta variant versus the alpha variant (adjusted HR for hospital admission 1·94 [95% CI 0·47–8·05] and for hospital admission or emergency care attendance 1·58 [0·69–3·61]) were similar to the HRs for unvaccinated patients (2·32 [1·29–4·16] and 1·43 [1·04–1·97]; p=0·82 for both) but the precision for the vaccinated subgroup was low. Interpretation: This large national study found a higher hospital admission or emergency care attendance risk for patients with COVID-19 infected with the delta variant compared with the alpha variant. Results suggest that outbreaks of the delta variant in unvaccinated populations might lead to a greater burden on health-care services than the alpha variant. Funding: Medical Research Council; UK Research and Innovation; Department of Health and Social Care; and National Institute for Health Research