Stimulus-dependent spatial patterns of response in SI cortex

BACKGROUND: Recently we reported that vibrotactile flutter stimulation of a skin locus at different amplitudes evokes an optical response confined to the same local region of the primary somatosensory cortex (SI), where its overall magnitude varies proportionally to the flutter amplitude. In this report, we characterize the impact of the flutter amplitude on the spatial patterns of activity evoked within the responding SI region. RESULTS: In order to characterize the spatial pattern of activity within the responding SI region, images of the flutter-evoked SI optical response were segmented and analyzed with spatial frequency analysis. The analysis revealed that: (1) dominant spatial frequencies in the optical intrinsic signal emerge within the responding SI region within 3–5 sec of stimulus onset; (2) the stimulus-evoked activity is spatially organized in a form of several roughly parallel, anterior-posteriorly extended waves, spaced 0.4–0.5 mm apart; (3) the waves themselves exhibit spatial periodicities along their long axis; and (4) depending on the flutter stimulus amplitude, these periodicities can range from fine 0.15 mm "ripples" at 50 μm amplitude to well-developed 0.5 mm fluctuations at the amplitude of 400 μm. CONCLUSION: The observed spatiointensive fractionation on a sub-macrocolumnar scale of the SI response to skin stimulation might be the product of local competitive interactions within the stimulus-activated SI region and may be a feature that could yield novel insights into the functional interactions that take place in SI cortex

Amplitude-dependency of response of SI cortex to flutter stimulation

BACKGROUND: It is established that increasing the amplitude of a flutter stimulus increases its perceived intensity. Although many studies have examined this phenomenon with regard to the responding afferent population, the way in which the intensity of a stimulus is coded in primary somatosensory cortex (SI) remains unclear. RESULTS: Optical intrinsic signal (OIS) imaging was used to study the evoked responses in SI of anesthetized squirrel monkeys by 25 Hz sinusoidal vertical skin displacement stimulation. Stimuli were 10 sec duration with a 50 sec inter-stimulus interval. Stimulus amplitude ranged from 50 to 400 microns and different amplitudes were interleaved. Control levels of activity were measured in the absence of stimulation, and used to compare with activation levels evoked by the different stimulus amplitudes. Stimulation of a discrete skin site on the forelimb evoked a prominent increase in absorbance within the forelimb representational region in cytoarchitectonic areas 3b and 1 of the contralateral hemisphere. An increase in stimulus amplitude led to a proportional increase in the magnitude of the absorbance increase in this region of areas 3b and 1 while surrounding cortex underwent a decrease in absorbance. Correlation maps revealed that as stimulus amplitude is increased, the spatial extent of the activated region in SI remains relatively constant, and the activity within this region increases progressively. Additionally, as stimulus amplitude is increased to suprathreshold levels, activity in the surround of the activated SI territory decreases, suggesting an increase in inhibition of neuronal activity within these regions. CONCLUSION: Increasing the amplitude of a flutter stimulus leads to a proportional increase in absorbance within the forelimb representational region of SI. This most likely reflects an increase in the firing rate of neurons in this region of SI. The relatively constant spatial extent of this stimulus-evoked increase in absorbance suggests that an increase in the amplitude of a 25 Hz skin stimulus does not evoke a larger area of SI neuronal activation due to an amplitude-dependent lateral inhibitory effect that spatially funnels the responding SI neuronal population

National Kriging Exposure Estimation: Liao et al. Respond

Szpiro et al. suggest that our findings Liao et al. (2006) do not adequately support using national-scale, log-normal ordinary kriging to estimate daily mean concentrations of PM10 (particulate matter with aerodynamic diameter ≤ 10 µm) at unmonitored locations in the contiguous United States. They posit that the absence of the cross-validation SE prevents evaluating the validity of kriging estimation, as we implemented in this context, and the comparability of both regionalversus national-scale kriging and manually modified versus semiautomated, defaultcalculated semivariograms

Determinants of patchy metabolic labeling in the somatosensory cortex of cats: a possible role for intrinsic inhibitory circuitry

Despite repeated experimental demonstration that somatic stimulation leads to an intermittent, "column-like" pattern of 2-deoxyglucose (2DG) label in the somatosensory cortex, the functional significance of this pattern remains uncertain. A number of recent studies have suggested that the putative inhibitory neurotransmitter GABA may play an influential role in the cortical processing of sensory information. To test the possibility that GABA-mediated inhibitory processes might participate in the formation of the 2DG patches, the 2DG pattern obtained under "normal" experimental conditions was compared with the pattern observed when cortical inhibition was modified by topical application of the GABA antagonist, bicuculline methiodide (BIC). Under "normal" experimental conditions, we found that somatic stimulation led to an intermittent, patch like distribution of 2DG uptake in cat somatosensory cortex, which exhibited consistent features in animals studied using the same stimulus and experimental condition. Reconstructions of the stimulus-evoked activity patterns revealed that the label was confined to territories known to receive input from the stimulated body region and was organized into elongated strips. Topical application of BIC to the somatosensory cortex dramatically altered the dimension of the metabolic patches, which were often embedded in a field of elevated 2DG uptake. In BIC-treated hemispheres the average width of 2DG patches was 1266 microns, whereas the average width of patches in the opposite untreated hemisphere (elicited by identical stimuli) was 713 microns. Unfolded maps of the labeling pattern revealed that in the BIC-treated hemispheres adjacent "strips" of 2DG label tended to fuse, leading to a less intermittent distribution than that observed in the untreated hemispheres. An important role for GABA in the formation of the normal cortical response to somatic stimulation is suggested

Accuracy of commercial geocoding: assessment and implications

BACKGROUND: Published studies of geocoding accuracy often focus on a single geographic area, address source or vendor, do not adjust accuracy measures for address characteristics, and do not examine effects of inaccuracy on exposure measures. We addressed these issues in a Women's Health Initiative ancillary study, the Environmental Epidemiology of Arrhythmogenesis in WHI. RESULTS: Addresses in 49 U.S. states (n = 3,615) with established coordinates were geocoded by four vendors (A-D). There were important differences among vendors in address match rate (98%; 82%; 81%; 30%), concordance between established and vendor-assigned census tracts (85%; 88%; 87%; 98%) and distance between established and vendor-assigned coordinates (mean ρ [meters]: 1809; 748; 704; 228). Mean ρ was lowest among street-matched, complete, zip-coded, unedited and urban addresses, and addresses with North American Datum of 1983 or World Geodetic System of 1984 coordinates. In mixed models restricted to vendors with minimally acceptable match rates (A-C) and adjusted for address characteristics, within-address correlation, and among-vendor heteroscedasticity of ρ, differences in mean ρ were small for street-type matches (280; 268; 275), i.e. likely to bias results relying on them about equally for most applications. In contrast, differences between centroid-type matches were substantial in some vendor contrasts, but not others (5497; 4303; 4210) p(interaction )< 10(-4), i.e. more likely to bias results differently in many applications. The adjusted odds of an address match was higher for vendor A versus C (odds ratio = 66, 95% confidence interval: 47, 93), but not B versus C (OR = 1.1, 95% CI: 0.9, 1.3). That of census tract concordance was no higher for vendor A versus C (OR = 1.0, 95% CI: 0.9, 1.2) or B versus C (OR = 1.1, 95% CI: 0.9, 1.3). Misclassification of a related exposure measure – distance to the nearest highway – increased with mean ρ and in the absence of confounding, non-differential misclassification of this distance biased its hypothetical association with coronary heart disease mortality toward the null. CONCLUSION: Geocoding error depends on measures used to evaluate it, address characteristics and vendor. Vendor selection presents a trade-off between potential for missing data and error in estimating spatially defined attributes. Informed selection is needed to control the trade-off and adjust analyses for its effects

Leveraging Case Study Research: A Mechanism to Measure Teaching Effectiveness

This article shares findings from a descriptive, multiple case study assessing graduate outcomes 2.5 years after the completion of a teacher education program. Case study was used as an alternative to value-added measures to holistically examine complex attributes of effective teaching. Mixed methods data collection included graduate and supervisor surveys, self and supervisor evaluation of skills and dispositions, interviews, and classroom observations. Results indicated participants effectively applied the knowledge, skills, and dispositions the program was designed to achieve in the areas of Learner and Learning, Content, Instructional Practice, and Professional Responsibility. Three major recommendations emerged: 1) the necessity to develop established proficiency levels for new teachers related to diverse learners, 2) the need for shared responsibility of outcomes and targeted induction support, and 3) support for supervisor evaluation as a viable mechanism for education program accountability of teaching effectiveness of graduates

Maternal residential proximity to major roadways, birth weight, and placental DNA methylation

Exposure to traffic pollution during fetal development has been associated with reduced fetal growth, and there is evidence to suggest that epigenetic mechanisms in the placenta in the form of variant DNA methylation may be a potential mechanism of this effect

Comparison of study designs used to detect and characterize pharmacogenomic interactions in nonexperimental studies: a simulation study

Adverse drug reactions are common, serious, difficult to predict, and may be influenced by genetics, prompting the increasing popularity of pharmacogenomic studies. Many pharmacogenomic studies are conducted in non-experimental settings, yet little is known about the influence of confounding by contraindication. We therefore compared the two designs (the overall population (OPD) and the treated-only (TOD) design) by simulating a pharmacogenomic study of the electrocardiographic QT interval (QT)

Use of alternative time scales in Cox proportional hazard models: implications for time-varying environmental exposures

Issues surrounding choice of time scales in Cox proportional hazard regression models have received limited attention in the literature. Although the choice between time on study and ‘attained’ age time scales has been examined, the calendar time scale may be of interest when modeling health effects of environmental exposures with noteworthy secular trends such as ambient particulate matter air pollution in large epidemiological cohort studies. The authors use simulation studies to examine performance (bias, mean squared error, coverage probabilities, and power) of models using all three time scales when the primary exposure of interest depends on calendar time. Results show that performance of models fit to the calendar time scale varies inversely with the strength of the linear association between the time-varying primary exposure and calendar time. Although models fit to attained age and time on study that do not adjust for calendar time were relatively robust, the authors conclude that care should be exercised when using time scales that are highly correlated with exposures of interest

Vibrotactile adaptation fails to enhance spatial localization in adults with autism

A recent study (Tannan et al., 2006) showed that pre-exposure of a skin region to a 5 sec 25 Hz flutter stimulus (“adaptation”) results in an approximately 2-fold improvement in the ability of neurologically healthy human adults to localize mechanical stimulation delivered to the same skin region that received the adapting stimulation. Tannan et al. (Tannan et al., 2006) proposed that tactile spatial discriminative performance is improved following adaptation because adaptation is accompanied by an increase in the spatial contrast in the response of contralateral primary somatosensory cortex (SI) to mechanical skin stimulation – an effect identified in previous imaging studies of SI cortex in anesthetized non-human primates (e.g., Simons et al., 2005; Tommerdahl et al., 2002; Whitsel et al., 1989)