Reinforcement learning in populations of spiking neurons

Population coding is widely regarded as a key mechanism for achieving reliable behavioral responses in the face of neuronal variability. But in standard reinforcement learning a flip-side becomes apparent. Learning slows down with increasing population size since the global reinforcement becomes less and less related to the performance of any single neuron. We show that, in contrast, learning speeds up with increasing population size if feedback about the populationresponse modulates synaptic plasticity in addition to global reinforcement. The two feedback signals (reinforcement and population-response signal) can be encoded by ambient neurotransmitter concentrations which vary slowly, yielding a fully online plasticity rule where the learning of a stimulus is interleaved with the processing of the subsequent one. The assumption of a single additional feedback mechanism therefore reconciles biological plausibility with efficient learning

Spontaneous adaptation explains why people act faster when being imitated

The human ability to perform joint actions is often attributed to high-level cognitive processes. For example, the finding that action leaders act faster when imitated by their partners has been interpreted as evidence for anticipation of the other’s actions (Pfister, Dignath, Hommel, & Kunde, 2013). In two experiments, we showed that a low-level mechanism can account for this finding. Action leaders were faster when imitated than when counterimitated, but only if they could observe their partner’s actions (Exp. 1). Crucially, when due to our manipulation the partner’s imitative actions became slower than the counterimitative actions, leaders also became slower when they were imitated, and faster when counterimitated (Exp. 2). Our results suggest that spontaneous temporal adaptation is a key mechanism in joint action tasks. We argue for a reconsideration of other phenomena that have traditionally been attributed solely to high-level processes

Clinical registry of dental outcomes in head and neck cancer patients (OraRad): rationale, methods, and recruitment considerations

Background Most head and neck (H&N) cancer patients receive high-dose external beam radiation therapy (RT), often in combination with surgery and/or chemotherapy. Unfortunately, high-dose RT has significant adverse effects on the oral and maxillofacial tissues, some of which persist for the life of the patient. However, dental management of these patients is based largely on individual and expert opinion, as few studies have followed patients prospectively to determine factors that predict adverse oral sequelae. In addition, many previous studies were conducted before wide-spread adoption of intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy. The objective of this multi-center study is to systematically evaluate the oral health of subjects for 2 years after commencement of RT, with the goal of identifying risk factors that predict adverse oral outcomes post-RT. Methods This is a prospective multi-center longitudinal cohort study of H&N cancer patients who receive high-dose RT with curative intent. Planned enrollment is 756 subjects at 6 primary clinical sites (and their affiliated sites) in the USA. A baseline visit is conducted prior to the beginning of RT. Follow-up visits are conducted at 6, 12, 18 and 24 months from the start of RT. The primary outcome measure is the 2-year rate of tooth loss in patients who have received at least one session of external beam RT for H&N cancer. Secondary outcome measures include the incidence of exposed intraoral bone; incidence of post-extraction complications; change in Decayed Missing and Filled Surfaces (DMFS); change in periodontal measures; change in stimulated whole salivary flow rates; change in mouth opening; topical fluoride utilization; chronic oral mucositis incidence; changes in RT-specific quality of life measures; and change in oral pain scores. Discussion This study will contribute to a better understanding of the dental complications experienced by these patients. It will also enable identification of risk factors associated with adverse outcomes such as tooth loss and osteoradionecrosis. These findings will support the development of evidence-based guidelines and inform the planning of future interventional studies, with the goal of advancing improvements in patient care and outcomes. Trial registration ClinicalTrials.gov Identifier NCT02057510 , registered 5 February 2014

Adult Cardiac Progenitor Cell Aggregates Exhibit Survival Benefit Both In Vitro and In Vivo

Background: A major hurdle in the use of exogenous stems cells for therapeutic regeneration of injured myocardium remains the poor survival of implanted cells. To date, the delivery of stem cells into myocardium has largely focused on implantation of cell suspensions. Methodology and Principal Findings: We hypothesize that delivering progenitor cells in an aggregate form would serve to mimic the endogenous state with proper cell-cell contact, and may aid the survival of implanted cells. Microwell methodologies allow for the culture of homogenous 3D cell aggregates, thereby allowing cell-cell contact. In this study, we find that the culture of cardiac progenitor cells in a 3D cell aggregate augments cell survival and protects against cellular toxins and stressors, including hydrogen peroxide and anoxia/reoxygenation induced cell death. Moreover, using a murine model of cardiac ischemia-reperfusion injury, we find that delivery of cardiac progenitor cells in the form of 3D aggregates improved in vivo survival of implanted cells. Conclusion: Collectively, our data support the notion that growth in 3D cellular systems and maintenance of cell-cell contact improves exogenous cell survival following delivery into myocardium. These approaches may serve as a strategy to improve cardiovascular cell-based therapies

Economic-demographic interactions in long-run growth

Cliometrics confirms that Malthus’ model of the pre-industrial economy, in which increases in productivity raise population but higher population drives down wages, is a good description for much of demographic/economic history. A contributor to the Malthusian equilibrium was the Western European Marriage Pattern, the late age of female first marriage, which promised to retard the fall of living standards by restricting fertility. The demographic transition and the transition from Malthusian economies to modern economic growth attracted many Cliometric models surveyed here. A popular model component is that lower levels of mortality over many centuries increased the returns to, or preference for, human capital investment so that technical progress eventually accelerated. This initially boosted birth rates and population growth accelerated. Fertility decline was earliest and most striking in late eighteenth century France. By the 1830s the fall in French marital fertility is consistent with a response to the rising opportunity cost of children. The rest of Europe did not begin to follow until end of the nineteenth century. Interactions between the economy and migration have been modelled with Cliometric structures closely related to those of natural increase and the economy. Wages were driven up by emigration from Europe and reduced in the economies receiving immigrants

Proteomic analysis of the Plasmodium male gamete reveals the key role for glycolysis in flagellar motility.

BACKGROUND: Gametogenesis and fertilization play crucial roles in malaria transmission. While male gametes are thought to be amongst the simplest eukaryotic cells and are proven targets of transmission blocking immunity, little is known about their molecular organization. For example, the pathway of energy metabolism that power motility, a feature that facilitates gamete encounter and fertilization, is unknown. METHODS: Plasmodium berghei microgametes were purified and analysed by whole-cell proteomic analysis for the first time. Data are available via ProteomeXchange with identifier PXD001163. RESULTS: 615 proteins were recovered, they included all male gamete proteins described thus far. Amongst them were the 11 enzymes of the glycolytic pathway. The hexose transporter was localized to the gamete plasma membrane and it was shown that microgamete motility can be suppressed effectively by inhibitors of this transporter and of the glycolytic pathway. CONCLUSIONS: This study describes the first whole-cell proteomic analysis of the malaria male gamete. It identifies glycolysis as the likely exclusive source of energy for flagellar beat, and provides new insights in original features of Plasmodium flagellar organization

Regional differences in psychiatric disorders in Chile

BACKGROUND: Psychiatric epidemiological surveys in developing countries are rare and are frequently conducted in regions that are not necessarily representative of the entire country. In addition, in large countries with dispersed populations national rates may have low value for estimating the need for mental health services and programs. METHODS: The Chile Psychiatric Prevalence Study using the Composite International Diagnostic Interview was conducted in four distinct regions of the country on a stratified random sample of 2,978 people. Lifetime and 12-month prevalence and service utilization rates were estimated. RESULTS: Significant differences in the rates of major depressive disorder, substance abuse disorders, non-affective psychosis, and service utilization were found across the regions. The differential prevalence rates could not be accounted by socio-demographic differences between sites. CONCLUSIONS: Regional differences across countries may exist that have both implications for prevalence rates and service utilization. Planning mental health services for population centers that span wide geographical areas based on studies conducted in a single region may be misleading, and may result in areas with high need being underserved

Tag-Trigger-Consolidation: A Model of Early and Late Long-Term-Potentiation and Depression

Changes in synaptic efficacies need to be long-lasting in order to serve as a substrate for memory. Experimentally, synaptic plasticity exhibits phases covering the induction of long-term potentiation and depression (LTP/LTD) during the early phase of synaptic plasticity, the setting of synaptic tags, a trigger process for protein synthesis, and a slow transition leading to synaptic consolidation during the late phase of synaptic plasticity. We present a mathematical model that describes these different phases of synaptic plasticity. The model explains a large body of experimental data on synaptic tagging and capture, cross-tagging, and the late phases of LTP and LTD. Moreover, the model accounts for the dependence of LTP and LTD induction on voltage and presynaptic stimulation frequency. The stabilization of potentiated synapses during the transition from early to late LTP occurs by protein synthesis dynamics that are shared by groups of synapses. The functional consequence of this shared process is that previously stabilized patterns of strong or weak synapses onto the same postsynaptic neuron are well protected against later changes induced by LTP/LTD protocols at individual synapses