Representation of temporal memory retrieval in the human precuneus

Shared neural ensembles link distinct memories encoded close in time, thus events encoded within close temporal distance (TD) are more likely to be co-recalled than events encoded across more distant TD: here we identified the multivoxel response pattern reflecting this effect in human parietal cortex

Significance of Input Correlations in Striatal Function

The striatum is the main input station of the basal ganglia and is strongly associated with motor and cognitive functions. Anatomical evidence suggests that individual striatal neurons are unlikely to share their inputs from the cortex. Using a biologically realistic large-scale network model of striatum and cortico-striatal projections, we provide a functional interpretation of the special anatomical structure of these projections. Specifically, we show that weak pairwise correlation within the pool of inputs to individual striatal neurons enhances the saliency of signal representation in the striatum. By contrast, correlations among the input pools of different striatal neurons render the signal representation less distinct from background activity. We suggest that for the network architecture of the striatum, there is a preferred cortico-striatal input configuration for optimal signal representation. It is further enhanced by the low-rate asynchronous background activity in striatum, supported by the balance between feedforward and feedback inhibitions in the striatal network. Thus, an appropriate combination of rates and correlations in the striatal input sets the stage for action selection presumably implemented in the basal ganglia

Time spent on work-related activities, social activities and time pressure as intermediary determinants of health disparities among elderly women and men in 5 European countries: a structural equation model

Background Psychosocial factors shape the health of older adults through complex inter-relating pathways. Besides socioeconomic factors, time use activities may explain gender inequality in self-reported health. This study investigated the role of work-related and social time use activities as determinants of health in old age. Specifically, we analysed whether the impact of stress in terms of time pressure on health mediated the relationship between work-related time use activities (i.e. housework and paid work) on self-reported health. Methods We applied structural equation models and a maximum-likelihood function to estimate the direct and indirect effects of psychosocial factors on health using pooled data from the Multinational Time Use Study on 11,168 men and 14,295 women aged 65+ from Italy, Spain, UK, France and the Netherlands. Results The fit indices for the conceptual model indicated an acceptable fit for both men and women. The results showed that socioeconomic status (SES), demographic factors, stress and work-related time use activities after retirement had a significant direct influence on self-reported health among the elderly, but the magnitude of the effects varied by gender. Social activities had a positive impact on self-reported health but had no significant impact on stress among older men and women. The indirect standardized effects of work-related activities on self-reported health was statistically significant for housework (β = − 0.006; P  0.05 among women), which implied that the paths from paid work and housework on self-reported health via stress (mediator) was very weak because their indirect effects were close to zero. Conclusions Our findings suggest that although stress in terms of time pressure has a direct negative effect on health, it does not indirectly influence the positive effects of work-related time use activities on self-reported health among elderly men and women. The results support the time availability hypothesis that the elderly may not have the same time pressure as younger adults after retirement

Imaging biomarker roadmap for cancer studies.

Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthcare, by crossing 'translational gaps' through validation and qualification. Important differences exist between IBs and biospecimen-derived biomarkers and, therefore, the development of IBs requires a tailored 'roadmap'. Recognizing this need, Cancer Research UK (CRUK) and the European Organisation for Research and Treatment of Cancer (EORTC) assembled experts to review, debate and summarize the challenges of IB validation and qualification. This consensus group has produced 14 key recommendations for accelerating the clinical translation of IBs, which highlight the role of parallel (rather than sequential) tracks of technical (assay) validation, biological/clinical validation and assessment of cost-effectiveness; the need for IB standardization and accreditation systems; the need to continually revisit IB precision; an alternative framework for biological/clinical validation of IBs; and the essential requirements for multicentre studies to qualify IBs for clinical use.Development of this roadmap received support from Cancer Research UK and the Engineering and Physical Sciences Research Council (grant references A/15267, A/16463, A/16464, A/16465, A/16466 and A/18097), the EORTC Cancer Research Fund, and the Innovative Medicines Initiative Joint Undertaking (grant agreement number 115151), resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and European Federation of Pharmaceutical Industries and Associations (EFPIA) companies' in kind contribution

Impact of correlated inputs to neurons: modeling observations from in vivo intracellular recordings

In vivo recordings in rat somatosensory cortex suggest that excitatory and inhibitory inputs are often correlated during spontaneous and sensory-evoked activity. Using a computational approach, we study how the interplay of input correlations and timing observed in experiments controls the spiking probability of single neurons. Several correlation-based mechanisms are identified, which can effectively switch a neuron on and off. In addition, we investigate the transfer of input correlation to output correlation in pairs of neurons, at the spike train and the membrane potential levels, by considering spike-driving and non-spike-driving inputs separately. In particular, we propose a plausible explanation for the in vivo finding that membrane potentials in neighboring neurons are correlated, but the spike-triggered averages of membrane potentials preceding a spike are not: Neighboring neurons possibly receive an ongoing bombardment of correlated subthreshold background inputs, and occasionally uncorrelated spike-driving inputs

The role of microsatellite instability in cervical intraepithelial neoplasia and squamous cell carcinoma of the cervix

Objectives. This study was conducted to define the role of microsatellite instability (MSI) in cervical intraepithelial neoplasia (CIN) and squamous cell carcinoma (SCC) of the cervix. We also tested the validity of using markers recommended for MSI study in colonic carcinoma by the National Cancer Institute (NCI) for cervical neoplasm. Methods. Twenty normal cervical, 24 low-grade CIN (CIN-L), 59 high-grade CIN (CIN-H), and 93 SCC tissues were examined for MSI after microdissection. A polymerase chain reaction based MSI detection was performed using five markers recommended by the NCI for colonic cancer (panel one) as well as five other markers (panel two) found to be informative in earlier studies. High-frequency MSI (MSI-H) was defined as instability in ≥2 of 5 loci if one panel was used and ≥30% of loci when more than five loci were used. Low-frequency MSI (MSI-L) was diagnosed if instability was noted but did not meet the criteria of MSI-H. Findings were correlated with clinicopathologic information. Results. The combined use of panel one and two markers showed no MSI in normal cervical or CIN-L tissue, MSI-L in 1 CIN-H (1.7%), MSI-L in 16 (17.2%), and MSI-H in 11 (11.8%) SCC, respectively. The NCI-recommended panel alone detected 19 of 27 MSI-positive SCC. MSI-positive was not related to patient age, disease stage, and tumor grade. The overall survival of MSI-positive patients was significantly worse than that of microsatellite stable patients (P = 0.02). An increasing trend of MSI-H rate with higher disease stages was noted (P = 0.035) but MSI-H was not associated with poor prognosis. Conclusions. The NCI recommended panel of markers might not be useful in MSI study for SCC and using more than five markers improves the MSI detection. MSI is rare in cervical dysplasia but is present in a subset of SCC. The association between MSI-positivity and prognosis awaits future confirmation. © 2003 Elsevier Science (USA). All rights reserved.link_to_subscribed_fulltex