Sleep does not influence schema-facilitated motor memory consolidation.

STUDY OBJECTIVES: Novel information is rapidly learned when it is compatible with previous knowledge. This "schema" effect, initially described for declarative memories, was recently extended to the motor memory domain. Importantly, this beneficial effect was only observed 24 hours-but not immediately-following motor schema acquisition. Given the established role of sleep in memory consolidation, we hypothesized that sleep following the initial learning of a schema is necessary for the subsequent rapid integration of novel motor information. METHODS: Two experiments were conducted to investigate the effect of diurnal and nocturnal sleep on schema-mediated motor sequence memory consolidation. In Experiment 1, participants first learned an 8-element motor sequence through repeated practice (Session 1). They were then afforded a 90-minute nap opportunity (N = 25) or remained awake (N = 25) before learning a second motor sequence (Session 2) which was highly compatible with that learned prior to the sleep/wake interval. Experiment 2 was similar; however, Sessions 1 and 2 were separated by a 12-hour interval that included nocturnal sleep (N = 28) or only wakefulness (N = 29). RESULTS: For both experiments, we found no group differences in motor sequence performance (reaction time and accuracy) following the sleep/wake interval. Furthermore, in Experiment 1, we found no correlation between sleep features (non-REM sleep duration, spindle and slow wave activity) and post-sleep behavioral performance. CONCLUSIONS: The results of this research suggest that integration of novel motor information into a cognitive-motor schema does not specifically benefit from post-learning sleep.

Somatosensory targeted memory reactivation enhances motor performance via hippocampal-mediated plasticity.

Increasing evidence suggests that reactivation of newly acquired memory traces during postlearning wakefulness plays an important role in memory consolidation. Here, we sought to boost the reactivation of a motor memory trace during postlearning wakefulness (quiet rest) immediately following learning using somatosensory targeted memory reactivation (TMR). Using functional magnetic resonance imaging, we examined the neural correlates of the reactivation process as well as the effect of the TMR intervention on brain responses elicited by task practice on 24 healthy young adults. Behavioral data of the post-TMR retest session showed a faster learning rate for the motor sequence that was reactivated as compared to the not-reactivated sequence. Brain imaging data revealed that motor, parietal, frontal, and cerebellar brain regions, which were recruited during initial motor learning, were specifically reactivated during the TMR episode and that hippocampo-frontal connectivity was modulated by the reactivation process. Importantly, the TMR-induced behavioral advantage was paralleled by dynamical changes in hippocampal activity and hippocampo-motor connectivity during task practice. Altogether, the present results suggest that somatosensory TMR during postlearning quiet rest can enhance motor performance via the modulation of hippocampo-cortical responses.

Inhibition, Shifting and Updating: Inter and intra-domain commonalities and differences from an executive functions activation likelihood estimation meta-analysis.

Executive functions are higher-order mental processes that support goal-directed behavior. Among these processes, Inhibition, Updating, and Shifting have been considered core executive domains. In this meta-analysis, we comprehensively investigate the neural networks of these executive domains and we synthesize for the first time the neural convergences and divergences among the most frequently used executive paradigms within those domains. A systematic search yielded 1055 published neuroimaging studies (including 26,191 participants in total). Our study revealed that a fronto-parietal network was shared by the three main domains. Furthermore, we executed conjunction analyses among the paradigms of the same domain to extract the core distinctive components of the main executive domains. This approach showed that Inhibition and Shifting are characterized by a strongly lateralized neural activation in the right and left hemisphere, respectively. In addition, both networks overlapped with the Updating network but not with each other. Remarkably, our study detected heterogeneity among the paradigms from the same domain. More specifically, analysis of Inhibition tasks revealed differing activations for Response Inhibition compared to Interference Control paradigms, suggesting that Inhibition encompasses relatively heterogeneous sub-functions. Shifting analyses revealed a bilateral overlap of the Wisconsin Card Sorting Task with the Updating network, but this pattern was absent for Rule Switching and Dual Task paradigms. Moreover, our Updating meta-analyses revealed the neural signatures associated with the specific modules of the Working Memory model from Baddeley and Hitch. To our knowledge, this is the most comprehensive meta-analysis of executive functions to date. Its paradigm-driven analyses provide a unique contribution to a better understanding of the neural convergences and divergences among executive processes that are relevant for clinical applications, such as cognitive enhancement and neurorehabilitation interventions.

Outcome-based reimbursement in Central-Eastern Europe and Middle-East.

Outcome-based reimbursement models can effectively reduce the financial risk to health care payers in cases when there is important uncertainty or heterogeneity regarding the clinical value of health technologies. Still, health care payers in lower income countries rely mainly on financial based agreements to manage uncertainties associated with new therapies. We performed a survey, an exploratory literature review and an iterative brainstorming in parallel about potential barriers and solutions to outcome-based agreements in Central and Eastern Europe (CEE) and in the Middle East (ME). A draft list of recommendations deriving from these steps was validated in a follow-up workshop with payer experts from these regions. 20 different barriers were identified in five groups, including transaction costs and administrative burden, measurement issues, information technology and data infrastructure, governance, and perverse policy outcomes. Though implementing outcome-based reimbursement models is challenging, especially in lower income countries, those challenges can be mitigated by conducting pilot agreements and preparing for predictable barriers. Our guidance paper provides an initial step in this process. The generalizability of our recommendations can be improved by monitoring experiences from pilot reimbursement models in CEE and ME countries and continuing the multistakeholder dialogue at national levels.

Manufacturers' views on outcome-based agreements.

INTRODUCTION: Outcome-based agreements (OBAs) are occasionally deployed to relieve the burden of high drug prices on healthcare budgets. However, it is not clear when manufacturers are willing to collaborate in establishing such agreements. Therefore, we explored the feasibility of OBAs from the manufacturer's point of view. METHODS: Dutch market-access experts from eight major pharmaceutical companies, globally active in the field of oncology, were interviewed. Opinions were compiled, and interviewees and their colleagues were then given the chance to review the manuscript for additional comments. RESULTS: Most interviewees believe that OBAs can be useful in providing access to off-label use of authorised medicines, especially when no alternative treatment is available for seriously ill patients. For the licenced indications, manufacturers seem to be more inclined to collaborate when there is a potential incentive to improve market-access (e.g., if the product is not used because of concerns regarding its effectiveness). However, manufacturers are less likely to collaborate when there are greater financial risks for the company. Further concerns were definition of outcome or performance, the impact of compliance on the effectiveness of a drug, administrative burden, uncertainty regarding revenue recognition and the challenges of reimbursing combination therapies. DISCUSSION: Market-access interviewees were generally positive about OBAs, however they were more reluctant towards OBAs for registered indications with low response-rate. The definition of performance or outcome and its clinical relevance and validity, the feasibility of OBAs and their administrative burden are relevant aspects that need to be addressed in advance. Ideally, countries should collaborate to share the outline of OBAs and create shared databases to accumulate evidence.

Home confinement during the COVID-19: day-to-day associations of sleep quality with rumination, psychotic-like experiences, and somatic symptoms.

Due to the coronavirus disease 2019 (COVID-19) pandemic, populations from many countries have been confined at home for extended periods of time in stressful environmental and media conditions. Cross-sectional studies already evidence deleterious psychological consequences, with poor sleep as a risk factor for impaired mental health. However, limitations of cross-sectional assessments are response bias tendencies and the inability to track daily fluctuations in specific subjective experiences in extended confinement conditions. In a prospective study conducted across three European countries, we queried participants (N = 166) twice a day through an online interface about their sleep quality and their negative psychological experiences for two consecutive weeks. The focus was set on between- and within-person associations of subjective sleep quality with daytime experiences, such as rumination, psychotic-like experiences, and somatic complaints about the typical symptoms of the coronavirus. The results show that daily reports of country-specific COVID-19 deaths predicted increased negative mood, psychotic-like experiences, and somatic complaints during the same day and decreased subjective sleep quality the following night. Disrupted sleep was globally associated with negative psychological outcomes during the study period, and a relatively poorer night of sleep predicted increased rumination, psychotic-like experiences, and somatic complaints the following day. This temporal association was not paralleled by daytime mental complaints predicting relatively poorer sleep quality on the following night. Our findings show that night-to-night changes in sleep quality predict how individuals cope the next day with daily challenges induced by home confinement.