Brain weight differences associated with induced focal microgyria

BACKGROUND: Disrupting neural migration with bilateral focal freezing necrosis on postnatal day 1 (P1) results in the formation of 4-layered microgyria. This developmental injury triggers a pervasive neural reorganization, which is evident at the electrophysiological, behavioral, and anatomical levels. In this experiment, we investigated changes in brain weight as an index of global disruption of neural systems caused by focal damage to the developing cortical plate. RESULTS: We found a dramatic reduction in overall brain weight in microgyric subjects. This reduction in brain weight among animals with microgyria is reflected in decreased total brain volume, with a disproportionate decrease in neocortical volume. This effect is so robust that it is seen across varied environments, at variable ages, and across the sexes. CONCLUSIONS: This finding supports previous work suggesting that substantial reorganization of the brain is triggered by the induction of bilateral freezing damage. These results have critical implications for the profound re-organizational effects of relatively small focal injuries early in development to distributed systems throughout the brain, and particularly in the cerebral cortex

Coexisting cryptic species of the Litoditis marina complex (Nematoda) show differential resource use and have distinct microbiomes with high intraspecific variability

Differences in resource use or in tolerances to abiotic conditions are often invoked as potential mechanisms underlying the sympatric distribution of cryptic species. Additionally, the microbiome can provide physiological adaptations of the host to environmental conditions. We determined the intra-and interspecific variability of the microbiomes of three cryptic nematode species of the Litoditis marina species complex that co-occur, but show differences in abiotic tolerances. Roche 454 pyrosequencing of the microbial 16S rRNA gene revealed distinct bacterial communities characterized by a substantial diversity (85-513 OTUs) and many rare OTUs. The core microbiome of each species contained only very few OTUs (2-6), and four OTUs were identified as potentially generating tolerance to abiotic conditions. A controlled experiment in which nematodes from two cryptic species (Pm1 and Pm3) were fed with either an E. coli suspension or a bacterial mix was performed, and the 16S rRNA gene was sequenced using the MiSeq technology. OTU richness was 10-fold higher compared to the 454 data set and ranged between 1118 and 7864. This experiment confirmed the existence of species-specific microbiomes, a core microbiome with few OTUs, and high interindividual variability. The offered food source affected the bacterial community and illustrated different feeding behaviour between the cryptic species, with Pm3 exhibiting a higher degree of selective feeding than Pm1. Morphologically similar species belonging to the same feeding guild (bacterivores) can thus have substantial differences in their associated microbiomes and feeding strategy, which in turn may have important ramifications for biodiversity-ecosystem functioning relationships

Review of Major Crop and Animal Arthropod Pests of South Texas

The Lower Rio Grande Valley is an area in Texas that consists of the four southern-most counties. This area contains a diverse range of agriculture and land-use including vegetable, row-crop and livestock production. The year-around cool to hot subtropical climate means that green vegetation is continually present, including many crops. Geographically, it shares an international border, making it a region vulnerable to new invasive species and the re-introduction of pests that have been previously eliminated in the United States. These combined factors lead to an array of arthropod pests that may have serious impacts on the crops, animals, and people in the region. This review focuses on arthropod pests that have historically, currently, or have the potential to significantly impact vegetables, row-crops, livestock, and humans in the LRGV. This is not an all-inclusive re-view but aims to focus on many of the arthropods that have been significant in the last 20 years

Impact of Quantitative Information and a Nudge on Attitudes toward Colorectal Cancer Screening

Research in behavioral economics suggests that individuals facing complex decisions benefit from being given a “nudge” towards one option, especially in situations where making any choice, as opposed to none, is preferred. Decisions about colorectal cancer (CRC) screening are of this type, since several tests are recommended by guidelines, including colonoscopy, sigmoidoscopy, and stool testing. No studies have examined the use of a nudge in the context of CRC screening. In this study, we compared the effects of two different approaches to providing quantitative information about CRC risk and benefits of screening, one with and one without a nudge towards fecal immunochemical testing (FIT) (a stool test)

A Brief Measure of Fidelity for Mindfulness Programs: Development and Evaluation of the Concise Fidelity for Mindfulness-Based Interventions Tool

BackgroundMindfulness research and clinical programs are widespread, and it is important that mindfulness-based interventions are delivered with fidelity, or as intended, across settings. The MBI:TAC is a comprehensive system for assessing teacher competence, yet it can be complex to implement. A standardized, simple fidelity/engagement tool to address treatment delivery is needed.ObjectiveWe describe the development, evaluation, and outcomes of a brief, practical tool for assessing fidelity and engagement in online mindfulness-based programs. The tool contains questions about session elements such as meditation guidance and group discussion, and questions about participant engagement and technology-based barriers to engagement.MethodsThe fidelity rating tool was developed and tested in OPTIMUM, Optimizing Pain Treatment in Medical settings Using Mindfulness. The OPTIMUM study is a 3-site pragmatic randomized trial of group medical visits and adapted mindfulness-based stress reduction for primary care patients with chronic low back pain, delivered online. Two trained study personnel independently rated 26 recorded OPTIMUM sessions to determine inter-rater reliability of the Concise Fidelity for Mindfulness-Based Interventions (CoFi-MBI) tool. Trained raters also completed the CoFi-MBI for 105 sessions. Raters provided qualitative data via optional open text fields within the tool.ResultsInter-rater agreement was 77-100% for presence of key session components, and 69-88% for Likert ratings of participant engagement and challenges related to technology, with discrepancies only occurring within 2 categories: ‘very much’ and ‘quite a bit’. Key session components occurred as intended in 94-100% of the 105 sessions, and participant engagement was rated as ‘very much’ or ‘quite a bit’ in 95% of the sessions. Qualitative analysis of rater comments revealed themes related to engagement challenges and technology failures.ConclusionThe CoFi-MBI provides a practical way to assess basic adherence to online delivery of mindfulness session elements, participant engagement, and extent of technology obstacles. Optional text can guide strategies to improve engagement and reduce technology barriers

GABA-ergic Dynamics in Human Frontotemporal Networks Confirmed by Pharmaco-Magnetoencephalography.

To bridge the gap between preclinical cellular models of disease and in vivo imaging of human cognitive network dynamics, there is a pressing need for informative biophysical models. Here we assess dynamic causal models (DCM) of cortical network responses, as generative models of magnetoencephalographic observations during an auditory oddball roving paradigm in healthy adults. This paradigm induces robust perturbations that permeate frontotemporal networks, including an evoked 'mismatch negativity' response and transiently induced oscillations. Here, we probe GABAergic influences in the networks using double-blind placebo-controlled randomized-crossover administration of the GABA reuptake inhibitor, tiagabine (oral, 10 mg) in healthy older adults. We demonstrate the facility of conductance-based neural mass mean-field models, incorporating local synaptic connectivity, to investigate laminar-specific and GABAergic mechanisms of the auditory response. The neuronal model accurately recapitulated the observed magnetoencephalographic data. Using parametric empirical Bayes for optimal model inversion across both drug sessions, we identify the effect of tiagabine on GABAergic modulation of deep pyramidal and interneuronal cell populations. We found a transition of the main GABAergic drug effects from auditory cortex in standard trials to prefrontal cortex in deviant trials. The successful integration of pharmaco- magnetoencephalography with dynamic causal models of frontotemporal networks provides a potential platform on which to evaluate the effects of disease and pharmacological interventions.SIGNIFICANCE STATEMENT Understanding human brain function and developing new treatments require good models of brain function. We tested a detailed generative model of cortical microcircuits that accurately reproduced human magnetoencephalography, to quantify network dynamics and connectivity in frontotemporal cortex. This approach identified the effect of a test drug (GABA-reuptake inhibitor, tiagabine) on neuronal function (GABA-ergic dynamics), opening the way for psychopharmacological studies in health and disease with the mechanistic precision afforded by generative models of the brain

Tropomodulin’s Actin-Binding Abilities Are Required to Modulate Dendrite Development

There are many unanswered questions about the roles of the actin pointed end capping and actin nucleation by tropomodulins (Tmod) in regulating neural morphology. Previous studies indicate that Tmod1 and Tmod2 regulate morphology of the dendritic arbor and spines. Tmod3, which is expressed in the brain, had only a minor influence on morphology. Although these studies established a defined role of Tmod in regulating dendritic and synaptic morphology, the mechanisms by which Tmods exert these effects are unknown. Here, we overexpressed a series of mutated forms of Tmod1 and Tmod2 with disrupted actin-binding sites in hippocampal neurons and found that Tmod1 and Tmod2 require both of their actin-binding sites to regulate dendritic morphology and dendritic spine shape. Proximity ligation assays (PLAs) indicate that these mutations impact the interaction of Tmod1 and Tmod2 with tropomyosins Tpm3.1 and Tpm3.2. This impact on Tmod/Tpm interaction may contribute to the morphological changes observed. Finally, we use molecular dynamics simulations (MDS) to characterize the structural changes, caused by mutations in the C-terminal helix of the leucine-rich repeat (LRR) domain of Tmod1 and Tmod2 alone and when bound onto actin monomers. Our results expand our understanding of how neurons utilize the different Tmod isoforms in development

GABAergic cortical network physiology in frontotemporal lobar degeneration.

The clinical syndromes caused by frontotemporal lobar degeneration are heterogeneous, including the behavioural variant frontotemporal dementia (bvFTD) and progressive supranuclear palsy. Although pathologically distinct, they share many behavioural, cognitive and physiological features, which may in part arise from common deficits of major neurotransmitters such as γ-aminobutyric acid (GABA). Here, we quantify the GABAergic impairment and its restoration with dynamic causal modelling of a double-blind placebo-controlled crossover pharmaco-magnetoencephalography study. We analysed 17 patients with bvFTD, 15 patients with progressive supranuclear palsy, and 20 healthy age- and gender-matched controls. In addition to neuropsychological assessment and structural MRI, participants undertook two magnetoencephalography sessions using a roving auditory oddball paradigm: once on placebo and once on 10 mg of the oral GABA reuptake inhibitor tiagabine. A subgroup underwent ultrahigh-field magnetic resonance spectroscopy measurement of GABA concentration, which was reduced among patients. We identified deficits in frontotemporal processing using conductance-based biophysical models of local and global neuronal networks. The clinical relevance of this physiological deficit is indicated by the correlation between top-down connectivity from frontal to temporal cortex and clinical measures of cognitive and behavioural change. A critical validation of the biophysical modelling approach was evidence from parametric empirical Bayes analysis that GABA levels in patients, measured by spectroscopy, were related to posterior estimates of patients' GABAergic synaptic connectivity. Further evidence for the role of GABA in frontotemporal lobar degeneration came from confirmation that the effects of tiagabine on local circuits depended not only on participant group, but also on individual baseline GABA levels. Specifically, the phasic inhibition of deep cortico-cortical pyramidal neurons following tiagabine, but not placebo, was a function of GABA concentration. The study provides proof-of-concept for the potential of dynamic causal modelling to elucidate mechanisms of human neurodegenerative disease, and explains the variation in response to candidate therapies among patients. The laminar- and neurotransmitter-specific features of the modelling framework, can be used to study other treatment approaches and disorders. In the context of frontotemporal lobar degeneration, we suggest that neurophysiological restoration in selected patients, by targeting neurotransmitter deficits, could be used to bridge between clinical and preclinical models of disease, and inform the personalized selection of drugs and stratification of patients for future clinical trials