Construction of direction selectivity in V1: from simple to complex cells

Despite detailed knowledge about the anatomy and physiology of the primary visual cortex (V1), the immense number of feed-forward and recurrent connections onto a given V1 neuron make it difficult to understand how the physiological details relate to a given neuron’s functional properties. Here, we focus on a well-known functional property of many V1 complex cells: phase-invariant direction selectivity (DS). While the energy model explains its construction at the conceptual level, it remains unclear how the mathematical operations described in this model are implemented by cortical circuits. To understand how DS of complex cells is constructed in cortex, we apply a nonlinear modeling framework to extracellular data from macaque V1. We use a modification of spike-triggered covariance (STC) analysis to identify multiple biologically plausible "spatiotemporal features" that either excite or suppress a cell. We demonstrate that these features represent the true inputs to the neuron more accurately, and the resulting nonlinear model compactly describes how these inputs are combined to result in the functional properties of the cell. In a population of 59 neurons, we find that both simple and complex V1 cells are selective to combinations of excitatory and suppressive motion features. Because the strength of DS and simple/complex classification is well predicted by our models, we can use simulations with inputs matching thalamic and simple cells to assess how individual model components contribute to these measures. Our results unify experimental observations regarding the construction of DS from thalamic feed-forward inputs to V1: based on the differences between excitatory and inhibitory inputs, they suggest a connectivity diagram for simple and complex cells that sheds light on the mechanism underlying the DS of cortical cells. More generally, they illustrate how stage-wise nonlinear combination of multiple features gives rise to the processing of more abstract visual information

Tuberculosis and Poverty: Why Are the Poor at Greater Risk in India?

Background: Although poverty is widely recognized as an important risk factor for tuberculosis (TB) disease, the specific proximal risk factors that mediate this association are less clear. The objective of our study was to investigate the mechanisms by which poverty increases the risk of TB. Methods: Using individual level data from 198,754 people from the 2006 Demographic Health Survey (DHS) for India, we assessed self-reported TB status, TB determinants and household socioeconomic status. We used these data to calculate the population attributable fractions (PAF) for each key TB risk factor based on the prevalence of determinants and estimates of the effect of these risk factors derived from published sources. We conducted a mediation analysis using principal components analysis (PCA) and regression to demonstrate how the association between poverty and TB prevalence is mediated. Results: The prevalence of self-reported TB in the 2006 DHS for India was 545 per 100,000 and ranged from 201 in the highest quintile to 1100 in the lowest quintile. Among those in the poorest population, the PAFs for low body mass index (BMI) and indoor air pollution were 34.2% and 28.5% respectively. The PCA analysis also showed that low BMI had the strongest mediating effect on the association between poverty and prevalent TB (12%, p = 0.019). Conclusion: TB control strategies should be targeted to the poorest populations that are most at risk, and should address the most important determinants of disease—specifically low BMI and indoor air pollution

Analysis of auditory functions in grades one, two, and three.

Thesis (Ed.M.)--Boston Universit

Parasympathetic functions in children with sensory processing disorder.

The overall goal of this study was to determine if parasympathetic nervous system (PsNS) activity is a significant biomarker of sensory processing difficulties in children. Several studies have demonstrated that PsNS activity is an important regulator of reactivity in children, and thus, it is of interest to study whether PsNS activity is related to sensory reactivity in children who have a type of condition associated with sensory processing disorders termed sensory modulation dysfunction (SMD). If so, this will have important implications for understanding the mechanisms underlying sensory processing problems of children and for developing intervention strategies to address them. The primary aims of this project were: (1) to evaluate PsNS activity in children with SMD compared to typically developing (TYP) children, and (2) to determine if PsNS activity is a significant predictor of sensory behaviors and adaptive functions among children with SMD. We examine PsNS activity during the Sensory Challenge Protocol; which includes baseline, the administration of eight sequential stimuli in five sensory domains, recovery, and also evaluate response to a prolonged auditory stimulus. As a secondary aim we examined whether subgroups of children with specific physiological and behavioral sensory reactivity profiles can be identified. Results indicate that as a total group the children with severe SMD demonstrated a trend for low baseline PsNS activity, compared to TYP children, suggesting this may be a biomarker for SMD. In addition, children with SMD as a total group demonstrated significantly poorer adaptive behavior in the communication and daily living subdomains and in the overall Adaptive Behavior Composite of the Vineland than TYP children. Using latent class analysis, the subjects were grouped by severity and the severe SMD group had significantly lower PsNS activity at baseline, tones and prolonged auditory. These results provide preliminary evidence that children who demonstrate severe SMD may have physiological activity that is different from children without SMD, and that these physiological and behavioral manifestations of SMD may affect a child\u27s ability to engage in everyday social, communication, and daily living skills

Integrating modern business values and cloning: The legality, morality, and social responsibility of somatic cell nuclear transfer

Science and technology have catapulted the possibilities of cloning into reality. Over the past few decades, cloning has given rise to aggressive research and business opportunities that have transformed society's views on the scientific andcommercial uses, as well as abuses, of cloning. The advent of cloning, therefore, has engendered a multitude of implications and consequences that our society, legal system, religious, and scientific communities continue to struggle with. How does the public embrace, laws protect, religion condone, and morality support the research, science, and implementation of cloning? The worldwide involvement in cloning, moreover, is an indication that this practice has secured widespread recognition and influence. This paper will explore the science of cloning, the companies involved, the laws that affect it, the ethics that guide it, and the social responsibility of its participants and presence in our global society's future

fMRI Randomized Study of Mental and Motor Task Performance and Cortisol Levels to Potentiate Cortisol as a New Diagnostic Biomarker.

Cortisol is an important hormone in the protective stress response system, the Hypothalamus-Pituitary-Adrenal (HPA axis). It becomes especially salient in immune suppression syndromes such as multiple sclerosis and Cushing’s disease. Fatigue is a common symptom and mental and motor tasks are difficult and labored. The role of cortisol is mental and motor tasks and the recruitment of key brain regions in completion of these tasks is explored together with functional magnetic resonance imaging in healthy participants. Cortisol levels were found to be higher and had greater reduction in levels during mental versus motor tasks. Recruitment of brain stem and hypothalamus regions, important in cortisol activity, was affected differently. At low cortisol levels, mental task participants had less activity in the regions than their physical task counterparts. When cortisol levels were higher, widerspread recruitment of these brain regions was seen in the mental task participants, and for the physical task participants, the spread was at comparative low levels of cortisol. It is concluded that cortisol is implicated in these brain regions supporting the Thompson Cortisol Hypothesis and that brain region recruitment is likely to be dependent upon factors including cortisol levels as well as perception of stress in the task. It is suggested that mental tasks are perceived more stressful than physical but demand higher cortisol levels to promote wider spread brain region activity. Implication for neurological disease includes the use of cortisol in the proposed development of a potential new diagnostic biomarker for early detection of neurological sequelae

Population Health Impact and Cost-Effectiveness of Tuberculosis Diagnosis with Xpert MTB/RIF: A Dynamic Simulation and Economic Evaluation

Background: The Xpert MTB/RIF test enables rapid detection of tuberculosis (TB) and rifampicin resistance. The World Health Organization recommends Xpert for initial diagnosis in individuals suspected of having multidrug-resistant TB (MDR-TB) or HIV-associated TB, and many countries are moving quickly toward adopting Xpert. As roll-out proceeds, it is essential to understand the potential health impact and cost-effectiveness of diagnostic strategies based on Xpert. Methods and findings: We evaluated potential health and economic consequences of implementing Xpert in five southern African countries—Botswana, Lesotho, Namibia, South Africa, and Swaziland—where drug resistance and TB-HIV coinfection are prevalent. Using a calibrated, dynamic mathematical model, we compared the status quo diagnostic algorithm, emphasizing sputum smear, against an algorithm incorporating Xpert for initial diagnosis. Results were projected over 10- and 20-y time periods starting from 2012. Compared to status quo, implementation of Xpert would avert 132,000 (95% CI: 55,000–284,000) TB cases and 182,000 (97,000–302,000) TB deaths in southern Africa over the 10 y following introduction, and would reduce prevalence by 28% (14%–40%) by 2022, with more modest reductions in incidence. Health system costs are projected to increase substantially with Xpert, by US$460 million (294–699 million) over 10 y. Antiretroviral therapy for HIV represents a substantial fraction of these additional costs, because of improved survival in TB/HIV-infected populations through better TB case-finding and treatment. Costs for treating MDR-TB are also expected to rise significantly with Xpert scale-up. Relative to status quo, Xpert has an estimated cost-effectiveness of US$959 (633–1,485) per disability-adjusted life-year averted over 10 y. Across countries, cost-effectiveness ratios ranged from US$792 (482–1,785) in Swaziland to US$1,257 (767–2,276) in Botswana. Assessing outcomes over a 10-y period focuses on the near-term consequences of Xpert adoption, but the cost-effectiveness results are conservative, with cost-effectiveness ratios assessed over a 20-y time horizon approximately 20% lower than the 10-y values. Conclusions: Introduction of Xpert could substantially change TB morbidity and mortality through improved case-finding and treatment, with more limited impact on long-term transmission dynamics. Despite extant uncertainty about TB natural history and intervention impact in southern Africa, adoption of Xpert evidently offers reasonable value for its cost, based on conventional benchmarks for cost-effectiveness. However, the additional financial burden would be substantial, including significant increases in costs for treating HIV and MDR-TB. Given the fundamental influence of HIV on TB dynamics and intervention costs, care should be taken when interpreting the results of this analysis outside of settings with high HIV prevalence. Please see later in the article for the Editors' Summar