Hierarchical Organization of Frontotemporal Networks for the Prediction of Stimuli across Multiple Dimensions.

Brain function can be conceived as a hierarchy of generative models that optimizes predictions of sensory inputs and minimizes "surprise." Each level of the hierarchy makes predictions of neural events at a lower level in the hierarchy, which returns a prediction error when these expectations are violated. We tested the generalization of this hypothesis to multiple sequential deviations, and we identified the most likely organization of the network that accommodates deviations in temporal structure of stimuli. Magnetoencephalography of healthy human participants during an auditory paradigm identified prediction error responses in bilateral primary auditory cortex, superior temporal gyrus, and lateral prefrontal cortex for deviation by frequency, intensity, location, duration, and silent gap. We examined the connectivity between cortical sources using a set of 21 generative models that embedded alternate hypotheses of frontotemporal network dynamics. Bayesian model selection provided evidence for two new features of functional network organization. First, an expectancy signal provided input to the prefrontal cortex bilaterally, related to the temporal structure of stimuli. Second, there are functionally significant lateral connections between superior temporal and/or prefrontal cortex. The results support a predictive coding hypothesis but go beyond previous work in demonstrating the generalization to multiple concurrent stimulus dimensions and the evidence for a temporal expectancy input at the higher level of the frontotemporal hierarchy. We propose that this framework for studying the brain's response to unexpected events is not limited to simple sensory tasks but may also apply to the neurocognitive mechanisms of higher cognitive functions and their disorders.This work was supported by the Medical Research Council (Grant MC-A060-5PQ30 and a doctoral training award to H.N.P.), the Wellcome Trust (Grants 088324 and 103838 to J.B.R. and L.E.H., Biomedical Research Fellowship WT093811MA to T.A.B.), and the James F. McDonnell Foundation 21st Century Science Initiative: Understanding Human Cognition.This is the final version of the article. It first appeared from Society for Neuroscience via http://dx.doi.org/10.1523/JNEUROSCI.5095-14.201

Perseveration and choice in Parkinson's disease: the impact of progressive frontostriatal dysfunction on action decisions.

We have previously shown that patients with Parkinson's disease (PD) perseverate in their choice of action relative to healthy controls, and that this is affected by dopaminergic medication (Hughes LE, Barker RA, Owen AM, Rowe JB. 2010. Parkinson's disease and healthy aging: Independent and interacting effects on action selection. Hum Brain Mapp. 31:1886-1899). To understand further the neural basis of these phenomena, we used a new task that manipulated the options to repeat responses. Seventeen patients with idiopathic PD were studied both "on" and "off" dopaminergic medication and 18 healthy adults were scanned twice as controls. All subjects performed a right-handed 3-choice button press task, which controlled the availability of repeatable responses. The frequency of choosing to repeat a response (a form of perseveration) in patients was related to dopamine therapy and disease severity as a "U-shaped" function. For repetitive trials, this "U-shaped" relationship was also reflected in the BOLD response in the caudate nuclei and ventrolateral prefrontal cortex. Our results support a U-shaped model of optimized cortico-striatal circuit function and clearly demonstrate that flexibility in response choice is modulated by an interaction of dopamine and disease severity

The Effect of Epstein-Barr Virus Latent Membrane Protein 2 Expression on the Kinetics of Early B Cell Infection

Infection of human B cells with wild-type Epstein-Barr virus (EBV) in vitro leads to activation and proliferation that result in efficient production of lymphoblastoid cell lines (LCLs). Latent Membrane Protein 2 (LMP2) is expressed early after infection and previous research has suggested a possible role in this process. Therefore, we generated recombinant EBV with knockouts of either or both protein isoforms, LMP2A and LMP2B (Δ2A, Δ2B, Δ2A/Δ2B) to study the effect of LMP2 in early B cell infection. Infection of B cells with Δ2A and Δ2A/Δ2B viruses led to a marked decrease in activation and proliferation relative to wild-type (wt) viruses, and resulted in higher percentages of apoptotic B cells. Δ2B virus infection showed activation levels comparable to wt, but fewer numbers of proliferating B cells. Early B cell infection with wt, Δ2A and Δ2B viruses did not result in changes in latent gene expression, with the exception of elevated LMP2B transcript in Δ2A virus infection. Infection with Δ2A and Δ2B viruses did not affect viral latency, determined by changes in LMP1/Zebra expression following BCR stimulation. However, BCR stimulation of Δ2A/Δ2B cells resulted in decreased LMP1 expression, which suggests loss of stability in viral latency. Long-term outgrowth assays revealed that LMP2A, but not LMP2B, is critical for efficient long-term growth of B cells in vitro. The lowest levels of activation, proliferation, and LCL formation were observed when both isoforms were deleted. These results suggest that LMP2A appears to be critical for efficient activation, proliferation and survival of EBV-infected B cells at early times after infection, which impacts the efficient long-term growth of B cells in culture. In contrast, LMP2B did not appear to play a significant role in these processes, and long-term growth of infected B cells was not affected by the absence of this protein. © 2013 Wasil et al

Video gaming and digital competence among elementary school students

Engagement with video games can potentially advance student digital competence however, there is a digital skills gap by the time young people progress into adolescence. This current research explores how elementary school students’ digital self-efficacy might relate to experiences in video game environments to influence perceptions of digital competence. We examine the differential impact of sex, self-efficacy, and socioeconomic status (SES) on 7–10-year-old students’ (N = 613) perceptions of video gaming and their digital skills. Analysis revealed the unexpected finding that SES was inversely related to enjoyment for gaming and digital technology, with students in the lower-SES category responding more positively compared to students in higher SES categories. As expected, boys self-reported digital skills higher than girls across all SES categories. We argue for the use of gaming pedagogies to support learning in classrooms that accounts for nuances in students’ digital self-efficacy moderated by gender and SES

Combined use of the Consolidated Framework for Implementation Research (CFIR) and the Theoretical Domains Framework (TDF): A systematic review

Background: Over 60 implementation frameworks exist. Using multiple frameworks may help researchers to address multiple study purposes, levels, and degrees of theoretical heritage and operationalizability; however, using multiple frameworks may result in unnecessary complexity and redundancy if doing so does not address study needs. The Consolidated Framework for Implementation Research (CFIR) and the Theoretical Domains Framework (TDF) are both well-operationalized, multi-level implementation determinant frameworks derived from theory. As such, the rationale for using the frameworks in combination (i.e., CFIR + TDF) is unclear. The objective of this systematic review was to elucidate the rationale for using CFIR + TDF by (1) describing studies that have used CFIR + TDF, (2) how they used CFIR + TDF, and (2) their stated rationale for using CFIR + TDF. Methods: We undertook a systematic review to identify studies that mentioned both the CFIR and the TDF, were written in English, were peer-reviewed, and reported either a protocol or results of an empirical study in MEDLINE/PubMed, PsycInfo, Web of Science, or Google Scholar. We then abstracted data into a matrix and analyzed it qualitatively, identifying salient themes. Findings: We identified five protocols and seven completed studies that used CFIR + TDF. CFIR + TDF was applied to studies in several countries, to a range of healthcare interventions, and at multiple intervention phases; used many designs, methods, and units of analysis; and assessed a variety of outcomes. Three studies indicated that using CFIR + TDF addressed multiple study purposes. Six studies indicated that using CFIR + TDF addressed multiple conceptual levels. Four studies did not explicitly state their rationale for using CFIR + TDF. Conclusions: Differences in the purposes that authors of the CFIR (e.g., comprehensive set of implementation determinants) and the TDF (e.g., intervention development) propose help to justify the use of CFIR + TDF. Given that the CFIR and the TDF are both multi-level frameworks, the rationale that using CFIR + TDF is needed to address multiple conceptual levels may reflect potentially misleading conventional wisdom. On the other hand, using CFIR + TDF may more fully define the multi-level nature of implementation. To avoid concerns about unnecessary complexity and redundancy, scholars who use CFIR + TDF and combinations of other frameworks should specify how the frameworks contribute to their study. Trial registration: PROSPERO CRD4201502761

Arkansas Range Extensions of the Eastern Small-Footed Bat (Myotis leibii) and Northern Long-Eared Bat (Myotisseptentrionalis) and Additional County Records for the Silver-Haired Bat (Lasionycteris noctivagans), Hoary Bat (Lasiurus cinereus), Southeastern Bat (Myotis austroriparius), and Rafinesque\u27s Big-Eared Bat (Plecotus rafinesquii)

We continued field studies of bats in non-cave regions of Arkansas from 1989 to present and utilized specimens submitted to the Arkansas Department of Health Rabies Laboratory to establish Arkansas range extensions for the eastern smallfooted bat (Myotis leibii) and northern long-eared bat (Myotisseptentrionalis). In addition, we documented additional county records for the silver-haired bat (Lasionycteris noctivagans), hoary bat (Lasiurus cinereus), southeastern bat (Myotis austroriparius), and Rafinesque\u27s big-eared bat (Plecotus rafinesquii)

Women and healthcare providers' perceptions of a midwife-led unit in a Swiss university hospital: a qualitative study.

BACKGROUND: The development of medical-led care in obstetrics over the past decades has contributed to improving outcomes for both mother and child. Although efficiency has improved in complex situations, unnecessary interventions are still practiced in low-risk pregnancies, contrary to international recommendations. A shift to a less interventionist model of care has encouraged many countries to review their policies on maternal health care and develop models such as the "midwife-led unit" (MLU) where the midwife plays a predominant role with a minimum of routine intervention. Existing research has provided convincing evidence that MLUs lead to better maternal and neonatal outcomes when compared to traditional models. They not only improve the level of satisfaction amongst women, but are also associated with reduced healthcare costs. This study aimed to explore the perceptions of women and healthcare providers regarding the creation of an MLU in a Swiss university hospital. METHODS: A descriptive research study using qualitative methods was conducted among pregnant women and new mothers in a Swiss maternity unit, including also midwives and medical staff. Data collection was carried out through one-to-one interviews, focus groups, and telephone interviews (n = 63). After transcription, thematic analysis was performed. RESULTS: The triangulation of perceptions of women and healthcare providers indicated support for the implementation of an MLU to promote physiological delivery. Most women welcomed the idea of an MLU, in particular how it could help in offering continuity of care. Healthcare providers were optimistic about the implementation of an MLU and recognised the need for some women to have access to a less interventionist approach. From the women's perspective, barriers concerned the lack of awareness of midwives' full scope of practice, while barriers for midwives and obstetricians were related to the challenge to develop a good interprofessional collaboration. CONCLUSION: Alternative models to provide maternity care for low-risk women have been developed and evaluated widely in several countries outside Switzerland. This study showed that women and healthcare providers were favourable towards the development of a new care model, while taking into account the specific expectations and barriers raised by participants

The Gut Microbiota of Wild Mice

The gut microbiota profoundly affects the biology of its host. The composition of the microbiota is dynamic and is affected by both host genetic and many environmental effects. The gut microbiota of laboratory mice has been studied extensively, which has uncovered many of the effects that the microbiota can have. This work has also shown that the environments of different research institutions can affect the mouse microbiota. There has been relatively limited study of the microbiota of wild mice, but this has shown that it typically differs from that of laboratory mice (and that maintaining wild caught mice in the laboratory can quite quickly alter the microbiota). There is also inter-individual variation in the microbiota of wild mice, with this principally explained by geographical location. In this study we have characterised the gut (both the caecum and rectum) microbiota of wild caught Mus musculus domesticus at three UK sites and have investigated how the microbiota varies depending on host location and host characteristics. We find that the microbiota of these mice are generally consistent with those described from other wild mice. The rectal and caecal microbiotas of individual mice are generally more similar to each other, than they are to the microbiota of other individuals. We found significant differences in the diversity of the microbiotas among mice from different sample sites. There were significant correlations of microbiota diversity and body weight, a measure of age, body-mass index, serum concentration of leptin, and virus, nematode and mite infection

Activity and Connectivity Differences Underlying Inhibitory Control Across the Adult Life Span.

Inhibitory control requires precise regulation of activity and connectivity within multiple brain networks. Previous studies have typically evaluated age-related changes in regional activity or changes in interregional interactions. Instead, we test the hypothesis that activity and connectivity make distinct, complementary contributions to performance across the life span and the maintenance of successful inhibitory control systems. A representative sample of healthy human adults in a large, population-based life span cohort performed an integrated Stop-Signal (SS)/No-Go task during functional magnetic resonance imaging (n = 119; age range, 18-88 years). Individual differences in inhibitory control were measured in terms of the SS reaction time (SSRT), using the blocked integration method. Linear models and independent components analysis revealed that individual differences in SSRT correlated with both activity and connectivity in a distributed inhibition network, comprising prefrontal, premotor, and motor regions. Importantly, this pattern was moderated by age, such that the association between inhibitory control and connectivity, but not activity, differed with age. Multivariate statistics and out-of-sample validation tests of multifactorial functional organization identified differential roles of activity and connectivity in determining an individual's SSRT across the life span. We propose that age-related differences in adaptive cognitive control are best characterized by the joint consideration of multifocal activity and connectivity within distributed brain networks. These insights may facilitate the development of new strategies to support cognitive ability in old age.SIGNIFICANCE STATEMENT The preservation of cognitive and motor control is crucial for maintaining well being across the life span. We show that such control is determined by both activity and connectivity within distributed brain networks. In a large, population-based cohort, we used a novel whole-brain multivariate approach to estimate the functional components of inhibitory control, in terms of their activity and connectivity. Both activity and connectivity in the inhibition network changed with age. But only the association between performance and connectivity, not activity, differed with age. The results suggest that adaptive control is best characterized by the joint consideration of multifocal activity and connectivity. These insights may facilitate the development of new strategies to maintain cognitive ability across the life span in health and disease