Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer's disease.

Apolipoprotein (apo) E4 is the major genetic risk factor for Alzheimer's disease (AD), increasing risk and decreasing age of disease onset. Many studies have demonstrated the detrimental effects of apoE4 in varying cellular contexts. However, the underlying mechanisms explaining how apoE4 leads to cognitive decline are not fully understood. Recently, the combination of human induced pluripotent stem cell (hiPSC) modeling of neurological diseases in vitro and electrophysiological studies in vivo have begun to unravel the intersection between apoE4, neuronal subtype dysfunction or loss, subsequent network deficits, and eventual cognitive decline. In this review, we provide an overview of the literature describing apoE4's detrimental effects in the central nervous system (CNS), specifically focusing on its contribution to neuronal subtype dysfunction or loss. We focus on γ-aminobutyric acid (GABA)-expressing interneurons in the hippocampus, which are selectively vulnerable to apoE4-mediated neurotoxicity. Additionally, we discuss the importance of the GABAergic inhibitory network to proper cognitive function and how dysfunction of this network manifests in AD. Finally, we examine how apoE4-mediated GABAergic interneuron loss can lead to inhibitory network deficits and how this deficit results in cognitive decline. We propose the following working model: Aging and/or stress induces neuronal expression of apoE. GABAergic interneurons are selectively vulnerable to intracellularly produced apoE4, through a tau dependent mechanism, which leads to their dysfunction and eventual death. In turn, GABAergic interneuron loss causes hyperexcitability and dysregulation of neural networks in the hippocampus and cortex. This dysfunction results in learning, memory, and other cognitive deficits that are the central features of AD

Peripheral Intravenous Infiltrates: Engaging Staff to Increase Reporting

A large free standing children’s academic hospital aimed to improve patient safety and outcomes by decreasing the overall severity of peripheral intravenous infiltration and extravasations (PIVIEs). A care bundle was developed by creating a PIVIE measurement tool within the electronic medical record (EMR) and integrating the tool into standardized daily practice for nurses. The care bundle included creating a team of clinical leaders consisting of empowered bedside nurses acting as mobilized resources embedded into each unit. The initiative resulted in a large scale increase in reported PIVIEs system-wide within 1 month of education dissemination to bedside RN staff. The QI interventions captured a realistic interpretation allowing for a more global and accurate reflection of the number and severity of PIVIE events system-wide, while creating documentation for the PIVIE tool in the EMR and a clinical leader model. The results reflected a dramatic rise in the number of reported PIVIE events, increase in staff awareness of PIVIEs, increased peripheral intravenous line assessments, and decreased severity of PIVIEs that do occur

From Cow Pasture to Cul-de-sac: The Intersection of Rural Values, Memory, and Nostalgia amidst Suburban Development in the American South

How do residents of a once small farming community react to rapid suburbanization? By examining rhetoric on growth, progress, and rurality, this thesis argues a complex landscape forms where longtime residents weave among pragmatism, disaffection, and nostalgia, with efforts to preserve memories of the past for themselves and future generations

Hemorrhagic Disease in Montana’s Wild Ruminants

Epizootic hemorrhagic disease and bluetongue virus have been documented in Montana for decades.  Montana has experienced localized and variable population declines in wild cervids when these outbreaks occur.  Transmission is seasonal in North America, with infection occurring in the late summer and fall.  In northern states, transmission ends once adult vectors cease activity with the onset of winter.  Montana is in an epidemic zone where outbreaks appear periodically and mortality events can be significant.  Montana Fish, Wildlife and Parks wildlife health lab has tested samples from suspected outbreak events, research captures and opportunistically for detection of EHD and BTV.  Environmental factors and virus-vector-host interactions are knowledge gaps that need to be addressed to improve our understanding of these orbivirus dynamics.  Enhanced reporting, surveillance, and research efforts are potential tools that may improve our understanding of the role these viruses play in wild ruminant populations across the state

2015 Wildlife Disease Retrospective

Montana Fish, Wildlife and Parks is developing a Wildlife Health Program.  One of the functions of the program is to integrate disease surveillance, population health monitoring, and wildlife health diagnostic services to provide information to the public and wildlife professionals on the dynamics, risk, and impacts of disease in Montana’s wildlife.   The knowledge gained from this program is aimed at improving conservation efforts and the safety of both humans and domestic animals.  The Wildlife Health Laboratory is a statewide lab that receives hundreds to thousands of biological samples each year for disease surveillance projects, epidemiologic and morbidity investigations, and forensics.  An overview of notable zoonotic and non-zoonotic diseases detected from 2015 laboratory submissions will be discussed, providing relevance, repercussions and general background or recent history of the diseases in Montana

The influence of facial signals on the automatic imitation on hand actions

Imitation and facial signals are fundamental social cues that guide interactions with others, but little is known regarding the relationship between these behaviors. It is clear that during expression detection, we imitate observed expressions by engaging similar facial muscles. It is proposed that a cognitive system, which matches observed and performed actions, controls imitation and contributes to emotion understanding. However, there is little known regarding the consequences of recognizing affective states for other forms of imitation, which are not inherently tied to the observed emotion. The current study investigated the hypothesis that facial cue valence would modulate automatic imitation of hand actions. To test this hypothesis, we paired different types of facial cue with an automatic imitation task. Experiments 1 and 2 demonstrated that a smile prompted greater automatic imitation than angry and neutral expressions. Additionally, a meta-analysis of this and previous studies suggests that both happy and angry expressions increase imitation compared to neutral expressions. By contrast, Experiments 3 and 4 demonstrated that invariant facial cues, which signal trait-levels of agreeableness, had no impact on imitation. Despite readily identifying trait-based facial signals, levels of agreeableness did not differentially modulate automatic imitation. Further, a Bayesian analysis showed that the null effect was between 2 and 5 times more likely than the experimental effect. Therefore, we show that imitation systems are more sensitive to prosocial facial signals that indicate “in the moment” states than enduring traits. These data support the view that a smile primes multiple forms of imitation including the copying actions that are not inherently affective. The influence of expression detection on wider forms of imitation may contribute to facilitating interactions between individuals, such as building rapport and affiliation

Observing Action Sequences Elicits Sequence-Specific Neural Representations in Frontoparietal Brain Regions.

Learning new skills by watching others is important for social and motor development throughout the lifespan. Prior research has suggested that observational learning shares common substrates with physical practice at both cognitive and brain levels. In addition, neuroimaging studies have used multivariate analysis techniques to understand neural representations in a variety of domains, including vision, audition, memory, and action, but few studies have investigated neural plasticity in representational space. Therefore, although movement sequences can be learned by observing other people's actions, a largely unanswered question in neuroscience is how experience shapes the representational space of neural systems. Here, across a sample of male and female participants, we combined pretraining and posttraining fMRI sessions with 6 d of observational practice to determine whether the observation of action sequences elicits sequence-specific representations in human frontoparietal brain regions and the extent to which these representations become more distinct with observational practice. Our results showed that observed action sequences are modeled by distinct patterns of activity in frontoparietal cortex and that such representations largely generalize to very similar, but untrained, sequences. These findings advance our understanding of what is modeled during observational learning (sequence-specific information), as well as how it is modeled (reorganization of frontoparietal cortex is similar to that previously shown following physical practice). Therefore, on a more fine-grained neural level than demonstrated previously, our findings reveal how the representational structure of frontoparietal cortex maps visual information onto motor circuits in order to enhance motor performance.SIGNIFICANCE STATEMENT Learning by watching others is a cornerstone in the development of expertise and skilled behavior. However, it remains unclear how visual signals are mapped onto motor circuits for such learning to occur. Here, we show that observed action sequences are modeled by distinct patterns of activity in frontoparietal cortex and that such representations largely generalize to very similar, but untrained, sequences. These findings advance our understanding of what is modeled during observational learning (sequence-specific information), as well as how it is modeled (reorganization of frontoparietal cortex is similar to that previously shown following physical practice). More generally, these findings demonstrate how motor circuit involvement in the perception of action sequences shows high fidelity to prior work, which focused on physical performance of action sequences

Anodal tDCS over Primary Motor Cortex Provides No Advantage to Learning Motor Sequences via Observation.

When learning a new motor skill, we benefit from watching others. It has been suggested that observation of others' actions can build a motor representation in the observer, and as such, physical and observational learning might share a similar neural basis. If physical and observational learning share a similar neural basis, then motor cortex stimulation during observational practice should similarly enhance learning by observation as it does through physical practice. Here, we used transcranial direct-current stimulation (tDCS) to address whether anodal stimulation to M1 during observational training facilitates skill acquisition. Participants learned keypress sequences across four consecutive days of observational practice while receiving active or sham stimulation over M1. The results demonstrated that active stimulation provided no advantage to skill learning over sham stimulation. Further, Bayesian analyses revealed evidence in favour of the null hypothesis across our dependent measures. Our findings therefore provide no support for the hypothesis that excitatory M1 stimulation can enhance observational learning in a similar manner to physical learning. More generally, the results add to a growing literature that suggests that the effects of tDCS tend to be small, inconsistent, and hard to replicate. Future tDCS research should consider these factors when designing experimental procedures.This work was supported by the Ministry of Defence of the United Kingdom Defence Science and Technology Laboratory (Grant no. DSTLX-1000083177 to Emily S. Cross and Richard Ramsey), the Economic and Social Research Council (Grant no. ES/K001884/1 to Richard Ramsey and ES/K001892/1 to Emily S. Cross), and the funding from the European Commission to Emily S. Cross (CIG11- 2012-322256 and ERC-2015-STG-677270)