Effect of Emotional Cues on Memory Recall and Response Time

Combining electroencephalography, the recording of the brain\u27s electrical activity, with other psychological research techniques allows the link between memory and emotion to be investigated. This study, which is currently in the pilot phase, investigates the effect of emotions on performance in a memory test. Subjects are shown written memory cues with or without accompanying photos of strong facially-expressed emotions and later prompted to recall the written cues. By monitoring brain activity and recall success rate, emotion\u27s effect on memory in this context can be determined, including what brain regions are stimulated by the emotion-memory link and the improvement or impairment of memory skills under the effect of outside emotional cues

Analysis of the Fabrication Conditions in Organic Field-Effect Transistors

Polymer-based organic field-effect transistors have raised substantial awareness because they enable low-cost, solution processing techniques, and have the potential to be implemented in flexible, disposable organic electronic devices. The performance of these devices is highly dependent on the processing conditions, as well as the intrinsic properties of the polymer. Processing conditions play an important role in semiconductor film formation and device performance. These factors may provide an important link between structure and performance. In this study, an empirical analysis tool, Process Scout, was applied to assess processing factors such as polymer concentration and silicon modification. This sanctioned the creation of a realistic optimization model because common variance was not assumed and the mobility was capably analyzed in the real space. After the analysis of the processing conditions, it was evident that further study on the effect of humidity on performance must be conducted to account for the variance between similarly fabricated devices. The developed process may be applied to expand the study of other organic semiconductors. This process is the first step in creating a standard fabrication protocol, allowing organic field-effect transistors to prosper

Maternal fluoxetine exposure alters cortical hemodynamic and calcium response of offspring to somatosensory stimuli

Epidemiological studies have found an increased incidence of neurodevelopmental disorders in populations prenatally exposed to selective serotonin reuptake inhibitors (SSRIs). Optical imaging provides a minimally invasive way to determine if perinatal SSRI exposure has long-term effects on cortical function. Herein we probed the functional neuroimaging effects of perinatal SSRI exposure in a fluoxetine (FLX)-exposed mouse model. While resting-state homotopic contralateral functional connectivity was unperturbed, the evoked cortical response to forepaw stimulation was altered in FLX mice. The stimulated cortex showed decreased activity for FLX versus controls, by both hemodynamic responses [oxyhemoglobin (Hb

Developmental hypomyelination in Wolfram syndrome: New insights from neuroimaging and gene expression analyses

Wolfram syndrome is a rare multisystem disorder caused by mutations in WFS1 or CISD2 genes leading to brain structural abnormalities and neurological symptoms. These abnormalities appear in early stages of the disease. The pathogenesis of Wolfram syndrome involves abnormalities in the endoplasmic reticulum (ER) and mitochondrial dynamics, which are common features in several other neurodegenerative disorders. Mutations in WFS1 are responsible for the majority of Wolfram syndrome cases. WFS1 encodes for an endoplasmic reticulum (ER) protein, wolframin. It is proposed that wolframin deficiency triggers the unfolded protein response (UPR) pathway resulting in an increased ER stress-mediated neuronal loss. Recent neuroimaging studies showed marked alteration in early brain development, primarily characterized by abnormal white matter myelination. Interestingly, ER stress and the UPR pathway are implicated in the pathogenesis of some inherited myelin disorders like Pelizaeus-Merzbacher disease, and Vanishing White Matter disease. In addition, exploratory gene-expression network-based analyses suggest that WFS1 expression occurs preferentially in oligodendrocytes during early brain development. Therefore, we propose that Wolfram syndrome could belong to a category of neurodevelopmental disorders characterized by ER stress-mediated myelination impairment. Further studies of myelination and oligodendrocyte function in Wolfram syndrome could provide new insights into the underlying mechanisms of the Wolfram syndrome-associated brain changes and identify potential connections between neurodevelopmental disorders and neurodegeneration

Shared developmental gait disruptions across two mouse models of neurodevelopmental disorders

BACKGROUND: Motor deficits such as abnormal gait are an underappreciated yet characteristic phenotype of many neurodevelopmental disorders (NDDs), including Williams Syndrome (WS) and Neurofibromatosis Type 1 (NF1). Compared to cognitive phenotypes, gait phenotypes are readily and comparably assessed in both humans and model organisms and are controlled by well-defined CNS circuits. Discovery of a common gait phenotype between NDDs might suggest shared cellular and molecular deficits and highlight simple outcome variables to potentially quantify longitudinal treatment efficacy in NDDs. METHODS: We characterized gait using the DigiGait assay in two different murine NDD models: the complete deletion (CD) mouse, which models hemizygous loss of the complete WS locus, and the Nf1 RESULTS: Compared to wildtype littermate controls, both models displayed markedly similar spatial, temporal, and postural gait abnormalities during development. Developing CD mice also displayed significant decreases in variability metrics. Multiple gait abnormalities observed across development in the Nf1 CONCLUSIONS: These findings suggest that the subcomponents of gait affected in NDDs show overlap between disorders as well as some disorder-specific features, which may change over the course of development. Our incorporation of spatial, temporal, and postural gait measures also provides a template for gait characterization in other NDD models and a platform to examining circuits or longitudinal therapeutics

Pharmacokinetics of esomeprazole in goats (Capra aegagrus hircus) after intravenous and subcutaneous administration

Background: Stressed and hospitalized goats are at risk of developing abomasal (gastric) ulceration, but there is a paucity of pharmacokinetic studies for proton pump inhibiting drugs, such as, esomeprazole in goats. Objectives: The objectives for this study were to estimate plasma pharmacokinetic parameters for esomeprazole in adult goats after intravenous (IV) and subcutaneous (SQ) administration. A secondary objective was to describe the plasma kinetics of the metabolite esomeprazole sulfone after IV and SC administration in goats. Materials and methods: Esomeprazole was administered to 5 adult goats in a crossover study at doses of 1 mg/kg IV or 2 mg/kg SC. Plasma samples were collected over 36 h and analyzed via reverse phase HPLC to determine concentrations of esomeprazole and esomeprazole sulfone. Pharmacokinetic parameters were derived via non-compartmental analysis. Results: Following IV administration, mean values for plasma clearance (Cl), elimination half-life [T1/2 (λz)], C0, and volume of distribution (Vz) of esomeprazole were estimated at 24.9 mL/min/kg, 6 min, 2.324 μg/mL, and 0.23 L/kg, respectively. After SC administration elimination half-life, maximum concentration (Cmax) and time to maximum concentration (Tmax) of esomeprazole were estimated at 29 min, 1.038 μg/mL, and 22 minutes respectively. Maximum concentrations of the sulfone metabolite were 32 and 18 ng/mL after IV and SC administration. Conclusion: Esomeprazole was rapidly eliminated from plasma after both IV and SC injection in goats. The elimination half-life in goats appears to be shorter than reported in dogs, as well as less than that reported for pantoprazole in goats. The sulfone metabolite was detected and also rapidly eliminated from the plasma after both IV and SC administration. Additional pharmacodynamic investigations are needed to determine the efficacy of esomeprazole on abomasal (gastric) acid suppression in goats and could include larger doses or additional routes of administration

Functional Optical Imaging of the Developing Mouse Cortex in Health and Disease

Neurodevelopmental disorders (NDDs) are a heterogeneous family of disorders characterized by the presence of abnormal developmental trajectories. Functional connectivity (FC) neuroimaging provides a minimally-invasive method by which to investigate the progression of these disorders and identify potential biomarkers of disease-related dysfunction for use in therapeutics’ development. My thesis work therefore took several approaches to the question of how the functional connectome reflects developmental change as well as system-wide perturbations from environmental or genetic factors. I explored the use of optical fluorescence and intrinsic signal imaging to characterize FC and stimulation-derived responses in a NDD model of perinatal exposure to selective serotonin reuptake inhibitor, reporting an altered cortical calcium and hemodynamic response to somatosensory stimulation in adulthood (Chapter 2). To provide a template of healthy FC development, I also characterized longitudinal calcium FC between postnatal day 15 (P15) and P60 in the Thy1/GCaMP6f mouse (Chapter 3) using an awake imaging paradigm. I discovered that cortical FC displayed widespread dynamic change during this period, with a region-dependence to the shape of the developmental trajectory across time. Finally, I documented the sex-specific perturbations present in the Mecp2 mouse model of Rett Syndrome, both during development (P35) and at an adult time point proximal to symptom onset and decline for each sex (Chapter 4). I found that Mecp2 males display a strong FC phenotype in both development and adulthood, while Mecp2 females display more subtle variation. These sex-specific differences in FC phenotype reflect the symptomatology present in the Mecp2 animal model and the underlying X-linked genetics of Rett Syndrome. The observed Mecp2 FC phenotypes appeared at P35, consistent with male symptom progression but earlier than females typically display symptom onset, suggesting promise as a presymptomatic biomarker. Altogether, I discovered that FC phenotypes are present and specific to each NDD model, and that there exists a diversity of temporal and spatial changes in FC during development in the healthy mouse cortex. These results suggest that functional connectivity techniques will provide a wealth of opportunities for studies aimed at understanding how the developmental trajectory of various NDDs deviates from typical FC development

Pharmacokinetics of esomeprazole in goats (Capra aegagrus hircus) after intravenous and subcutaneous administration

Background: Stressed and hospitalized goats are at risk of developing abomasal (gastric) ulceration, but there is a paucity of pharmacokinetic studies for proton pump inhibiting drugs, such as, esomeprazole in goats. Objectives: The objectives for this study were to estimate plasma pharmacokinetic parameters for esomeprazole in adult goats after intravenous (IV) and subcutaneous (SQ) administration. A secondary objective was to describe the plasma kinetics of the metabolite esomeprazole sulfone after IV and SC administration in goats. Materials and methods: Esomeprazole was administered to 5 adult goats in a crossover study at doses of 1 mg/kg IV or 2 mg/kg SC. Plasma samples were collected over 36 h and analyzed via reverse phase HPLC to determine concentrations of esomeprazole and esomeprazole sulfone. Pharmacokinetic parameters were derived via non-compartmental analysis. Results: Following IV administration, mean values for plasma clearance (Cl), elimination half-life [T1/2 (λz)], C0, and volume of distribution (Vz) of esomeprazole were estimated at 24.9 mL/min/kg, 6 min, 2.324 μg/mL, and 0.23 L/kg, respectively. After SC administration elimination half-life, maximum concentration (Cmax) and time to maximum concentration (Tmax) of esomeprazole were estimated at 29 min, 1.038 μg/mL, and 22 minutes respectively. Maximum concentrations of the sulfone metabolite were 32 and 18 ng/mL after IV and SC administration. Conclusion: Esomeprazole was rapidly eliminated from plasma after both IV and SC injection in goats. The elimination half-life in goats appears to be shorter than reported in dogs, as well as less than that reported for pantoprazole in goats. The sulfone metabolite was detected and also rapidly eliminated from the plasma after both IV and SC administration. Additional pharmacodynamic investigations are needed to determine the efficacy of esomeprazole on abomasal (gastric) acid suppression in goats and could include larger doses or additional routes of administration.This article is published as Fladung R, Smith JS, Hines MT, Soto-Gonzalez WM, Fayne B, Rahn RR, Escher OG, Harvill L, Bergman J, Garcia JD, Kreuder AJ and Cox S (2022) Pharmacokinetics of esomeprazole in goats (Capra aegagrus hircus) after intravenous and subcutaneous administration. Front. Vet. Sci. 9:968973. DOI: 10.3389/fvets.2022.968973. Copyright 2022 Fladung, Smith, Hines, Soto-Gonzalez, Fayne, Rahn, Escher, Harvill, Bergman, Garcia, Kreuder and Cox. Attribution 4.0 International (CC BY 4.0). Posted with permission