Spatial Filtering of Electroencephalography Reduces Artifacts and Enhances Signals Related to Spinal Cord Stimulation (SCS).

OBJECTIVES: How spinal cord stimulation (SCS) in its different modes suppresses pain is poorly understood. Mechanisms of action may reside locally in the spinal cord, but also involve a larger network including subcortical and cortical brain structures. Tonic, burst, and high-frequency modes of SCS can, in principle, entrain distinct temporal activity patterns in this network, but finally have to yield specific effects on pain suppression. Here, we employ high-density electroencephalography (EEG) and recently developed spatial filtering techniques to reduce SCS artifacts and to enhance EEG signals specifically related to neuromodulation by SCS. MATERIALS AND METHODS: We recorded high-density resting-state EEGs in patients suffering from pain of various etiologies under different modes of SCS. We established a pipeline for the robust spectral analysis of oscillatory brain activity during SCS, which includes spatial filtering for attenuation of pulse artifacts and enhancement of brain activity potentially modulated by SCS. RESULTS: In sensor regions responsive to SCS, neuromodulation strongly reduced activity in the theta and low alpha range (6-10 Hz) in all SCS modes. Results were consistent in all patients, and in accordance with thalamocortical dysrhythmia hypothesis of pain. Only in the tonic mode showing paresthesia as side effect, SCS also consistently and strongly reduced high-gamma activity (>84 Hz). CONCLUSIONS: EEG spectral analysis combined with spatial filtering allows for a spatially and temporally specific assessment of SCS-related, neuromodulatory EEG activity, and may help to disentangle therapeutic and side effects of SCS.

Neighborhood urban form, social environment, and depression.

We examined whether neighborhood urban form, along with the social environment, was associated with depressive symptoms in a sample of Miami residents. Using a validated measure of depressive symptoms, we found that living in neighborhoods with higher housing density was associated with fewer symptoms. A larger acreage of green spaces was also linked to fewer depressive symptoms but did not reach significance in the full model. Our results suggest that how residents use the environment matters. Living in neighborhoods with a higher density of auto commuters relative to land area, an indicator of chronic noise exposure, was associated with more symptoms.

Putting the capital "E" environment into ecological models of health.

The recent public health reawakening to the role of the built environment has largely excluded consideration of the natural environment. This exclusion is despite the fact that land conservation, or green infrastructure, supports the most fundamental human needs and healthy lifestyles. Although the contemporary public health paradigm acknowledges the environment as an important construct in an "ecological" approach to health, environmental protection is not commonly viewed as an upstream approach to preventing disease. This guest commentary suggests that environmental health research and practice should consider green infrastructure as germane to a healthy human environment.

Greenspace redevelopment, pressure of displacement, and sleep quality among Black adults in Southwest Atlanta.

BACKGROUND: Little is known on how greenspace redevelopment-creating or improving existing parks and trails-targeted for low-income and/or majority Black neighborhoods could amplify existing social environmental stressors, increase residents' susceptibility to displacement, and impact their sleep quality. OBJECTIVE: To examine the relationship between social environmental stressors associated with displacement and sleep quality among Black adults. METHODS: Linear regression models were employed on survey data to investigate the association between social environmental stressors, independently and combined, on sleep quality among Black adults residing in block groups targeted for greenspace redevelopment (i.e., exposed) and matched with block groups that were not (i.e., unexposed). RESULTS: The independent associations between everyday discrimination, heightened vigilance, housing unaffordability, and subjective sleep quality were not modified by greenspace redevelopment, controlling for other factors. The association between financial strain and subjective sleep quality was different for exposed and unexposed participants with exposed participants having a poorer sleep quality. The combined model revealed that the association between financial strain and sleep quality persisted. However, for different financial strain categories exposed participants slept poorer and/or better than unexposed participants. SIGNIFICANCE: Our findings suggest a nuanced relationship between social environmental stressors, pressure of displacement related to greenspace redevelopment, and sleep quality among Black adults.

Development of skeletal muscle sodium and potassium currents in zebrafish sofa potato mutants.

In some cells, the development of voltage-gated channels requires synaptic input, while in others it does not. Here we investigate whether the sodium and potassium currents in the skeletal muscle of zebrafish sofa potato (sop(-/-)) mutants develop normally. Zebrafish sop(-/-) mutants do not express nicotinic acetylcholine receptors at neuromuscular junctions, and therefore do not exhibit synaptic activity in muscle. We find that in both red and white muscle fibers, sop(-/-) mutants are able to support normal potassium current development during early stages of development [1-3 days post fertilization (dpf)], but at 6 dpf the potassium current density is significantly smaller than that in their phenotypically wild-type siblings (sop(+/?)). In contrast, sodium current density is unaffected. The steady-state properties of potassium currents are unaltered in the sop(-/-) mutants, but there is a significant difference in the V(50) of inactivation of sodium currents. This is the first study in zebrafish to investigate activity-dependent mechanisms of ion channel development and our results indicate that some aspects of ion current development in skeletal muscle require synaptic activity, whereas others do not.

Embryonic motor activity and implications for regulating motoneuron axonal pathfinding in zebrafish.

Zebrafish embryos exhibit spontaneous contractions of the musculature as early as 18-19 h post fertilization (hpf) when removed from their protective chorion. These movements are likely initiated by early embryonic central nervous system activity. We have made the observation that narrowminded mutant embryos (hereafter, nrd(-/-)) lack normal embryonic motor output upon dechorionation. However, these mutants can swim and respond to tactile stimulation by larval stages of development. nrd(-/-) embryos exhibit defects in neural crest development, slow muscle development and also lack spinal mechanosensory neurons known as Rohon-Beard (RB) neurons. At early developmental stages (i.e. 21-22 hpf) and while still in their chorions, nrd siblings (nrd(+/?)) exhibited contractions of the musculature at a rate similar to wild-type embryos. Anatomical analysis indicated that RB neurons were present in the motile embryos, but absent in the non-motile embryos, indicating that the non-motile embryos were nrd(-/-) embryos. Further anatomical analysis of nrd(-/-) embryos revealed errors in motoneuron axonal pathfinding that persisted into the larval stage of development. These errors were reversed when nrd(-/-) embryos were raised in high [K(+)] beginning at 21 hpf, indicating that the abnormal axonal phenotypes may be related to a lack of depolarizing activity early in development. When activity was blocked with tricaine in wild-type embryos, motoneuron phenotypes were similar to the motoneuron phenotypes in nrd(-/-) embryos. These results implicate early embryonic activity in conjunction with other factors as necessary for normal motoneuron development.

Differential expression of PKC isoforms in developing zebrafish.

Protein kinase C isozymes are a biologically diverse group of enzymes known to be involved in a wide variety of cellular processes. They fall into three families (conventional, novel and atypical) depending upon their mode of activation. Several classes of zebrafish neurons have been shown to express PKCalpha during development, but the expression of other isoforms remains unknown. In this study we performed immunohistochemistry to determine if zebrafish express various isoforms of PKC. We used antibodies to test for the presence of enzymes that are thought to be preferentially expressed in the nervous system (PKCgamma, betaII, delta, epsilon, theta and zeta). Here, we show that PKCgamma, epsilon, theta and zeta are expressed in the zebrafish CNS. Anti-PKCgamma labels Rohon-Beard sensory neurons and Mauthner cells. PKCepsilon and zeta staining is widespread in the CNS, and PKCtheta and betaII are expressed in skeletal muscle, especially at intersegmental boundaries. Immunoblot experiments confirm the specificity of the antibodies in zebrafish and indicate that the fish isoforms of PKCgamma, betaII, epsilon and zeta are similar to the mammalian isoforms. Interestingly, PKCtheta appears to be similar to PKCthetaII, which, to date, has been found exclusively in mouse testis, but not in the mammalian CNS. Overall, our findings indicate that several different PKC isoforms are expressed in zebrafish, and that Rohon-Beard, Mauthner cells and muscle fibers preferentially express some isoforms over others.

Behavioral-state modulation of inhibition is context-dependent and cell type specific in mouse visual cortex.

Cortical responses to sensory stimuli are modulated by behavioral state. In the primary visual cortex (V1), visual responses of pyramidal neurons increase during locomotion. This response gain was suggested to be mediated through inhibitory neurons, resulting in the disinhibition of pyramidal neurons. Using in vivo two-photon calcium imaging in layers 2/3 and 4 in mouse V1, we reveal that locomotion increases the activity of vasoactive intestinal peptide (VIP), somatostatin (SST) and parvalbumin (PV)-positive interneurons during visual stimulation, challenging the disinhibition model. In darkness, while most VIP and PV neurons remained locomotion responsive, SST and excitatory neurons were largely non-responsive. Context-dependent locomotion responses were found in each cell type, with the highest proportion among SST neurons. These findings establish that modulation of neuronal activity by locomotion is context-dependent and contest the generality of a disinhibitory circuit for gain control of sensory responses by behavioral state.

Green Infrastructure, Ecosystem Services, and Human Health.

Contemporary ecological models of health prominently feature the natural environment as fundamental to the ecosystem services that support human life, health, and well-being. The natural environment encompasses and permeates all other spheres of influence on health. Reviews of the natural environment and health literature have tended, at times intentionally, to focus on a limited subset of ecosystem services as well as health benefits stemming from the presence, and access and exposure to, green infrastructure. The sweeping influence of green infrastructure on the myriad ecosystem services essential to health has therefore often been underrepresented. This survey of the literature aims to provide a more comprehensive picture-in the form of a primer-of the many simultaneously acting health co-benefits of green infrastructure. It is hoped that a more accurately exhaustive list of benefits will not only instigate further research into the health co-benefits of green infrastructure but also promote consilience in the many fields, including public health, that must be involved in the landscape conservation necessary to protect and improve health and well-being.

The portrayal of natural environment in the evolution of the ecological public health paradigm.

This paper explores the conceptualization of the natural environment in an evolving ecological public health paradigm. The natural environment has long been recognized as essential to supporting life, health, and wellbeing. Our understanding of the relationship between the natural environment and health has steadily evolved from one of an undynamic environment to a more sophisticated understanding of ecological interactions.  This evolution is reflected in a number of ecological public health models which demonstrate the many external and overlapping determinants of human health. Six models are presented here to demonstrate this evolution, each model reflecting an increasingly ecological appreciation for the fundamental role of the natural environment in supporting human health. We conclude that after decades of public health's acceptance of the ecological paradigm, we are only now beginning to assemble knowledge of sophisticated ecological interdependencies and apply this knowledge to the conceptualization and study of the relationship between the natural environment and the determinants of human health.

County-level effects of green space access on physical activity.

BACKGROUND: Parks and other forms of green space are among the key environmental supports for recreational physical activity. Measurements of green space access have provided mixed results as to the influence of green space access on physical activity. METHODS: This cross-sectional study uses a geographical information system (GIS) to examine the relationships between the amount of and distance to green space and county-level (n = 67) moderate and vigorous physical activity (MVPA) in the state of Florida. RESULTS: The gross amount of green space in a county (P < .05) and the amount of green space within defined distances of where people live (1/4 mile, P < .01; 1/2 mile, P < .05; 1 mile, P < .01) were positively associated with self-reported levels of MVPA. Distance to the nearest green space and the amount of green space furthest from where people live (10 miles) were not significantly associated with MVPA. All measures were weighted by the population living in census tracts. CONCLUSIONS: The results suggest that there is an association between the accessibility created by having more green space closer to home and MVPA, but this holds only for areas up to and including 1 mile from home.

Mechanisms underlying metabolic and neural defects in zebrafish and human multiple acyl-CoA dehydrogenase deficiency (MADD).

In humans, mutations in electron transfer flavoprotein (ETF) or electron transfer flavoprotein dehydrogenase (ETFDH) lead to MADD/glutaric aciduria type II, an autosomal recessively inherited disorder characterized by a broad spectrum of devastating neurological, systemic and metabolic symptoms. We show that a zebrafish mutant in ETFDH, xavier, and fibroblast cells from MADD patients demonstrate similar mitochondrial and metabolic abnormalities, including reduced oxidative phosphorylation, increased aerobic glycolysis, and upregulation of the PPARG-ERK pathway. This metabolic dysfunction is associated with aberrant neural proliferation in xav, in addition to other neural phenotypes and paralysis. Strikingly, a PPARG antagonist attenuates aberrant neural proliferation and alleviates paralysis in xav, while PPARG agonists increase neural proliferation in wild type embryos. These results show that mitochondrial dysfunction, leading to an increase in aerobic glycolysis, affects neurogenesis through the PPARG-ERK pathway, a potential target for therapeutic intervention.

Development of ionic currents of zebrafish slow and fast skeletal muscle fibers.

Voltage-gated Na+ and K+ channels play key roles in the excitability of skeletal muscle fibers. In this study we investigated the steady-state and kinetic properties of voltage-gated Na+ and K+ currents of slow and fast skeletal muscle fibers in zebrafish ranging in age from 1 day postfertilization (dpf) to 4-6 dpf. The inner white (fast) fibers possess an A-type inactivating K+ current that increases in peak current density and accelerates its rise and decay times during development. As the muscle matured, the V50s of activation and inactivation of the A-type current became more depolarized, and then hyperpolarized again in older animals. The activation kinetics of the delayed outward K+ current in red (slow) fibers accelerated within the first week of development. The tail currents of the outward K+ currents were too small to allow an accurate determination of the V50s of activation. Red fibers did not show any evidence of inward Na+ currents; however, white fibers expressed Na+ currents that increased their peak current density, accelerated their inactivation kinetics, and hyperpolarized their V50 of inactivation during development. The action potentials of white fibers exhibited significant changes in the threshold voltage and the half width. These findings indicate that there are significant differences in the ionic current profiles between the red and white fibers and that a number of changes occur in the steady-state and kinetic properties of Na+ and K+ currents of developing zebrafish skeletal muscle fibers, with the most dramatic changes occurring around the end of the first day following egg fertilization.