Response of SI cortex to ipsilateral, contralateral and bilateral flutter stimulation in the cat

BACKGROUND: While SII cortex is considered to be the first cortical stage of the pathway that integrates tactile information arising from both sides of the body, SI cortex is generally not considered as a region in which neuronal response is modulated by simultaneous stimulation of bilateral (and mirror-image) skin sites. RESULTS: Optical intrinsic signal imaging was used to evaluate the response of SI and SII in the same hemisphere to 25 Hz sinusoidal vertical skin displacement stimulation ("skin flutter") applied contralaterally, ipsilaterally, and bilaterally (simultaneously) to the central pads of the forepaws. A localized increase in absorbance in both SI and SII occurred in response to both contralateral and bilateral flutter stimulation. Ipsilateral flutter stimulation evoked a localized increase in absorbance in SII, but little or no change in SI absorbance. In the forepaw representational region of SI, however, bilateral stimulation of the central pads evoked a response substantially smaller (approximately 30–35% smaller) than the response to flutter stimulation of the contralateral central pad. CONCLUSION: The finding that the response of SI cortex to bilateral central pad flutter stimulation is substantially smaller than the response evoked by a contralateral flutter stimulus, together with the recently published observation that a region located posteriorly in SII responds with a substantially larger response to a bilateral flutter stimulus than the response evoked from the contralateral central pad, lead us to propose that the SI activity evoked by contralateral skin stimulation is suppressed/inhibited (via corticocortical connections between SII and SI in the same hemisphere) by the activity a simultaneous ipsilateral skin stimulus evokes in posterior SII

Response of SII cortex to ipsilateral, contralateral and bilateral flutter stimulation in the cat

BACKGROUND: A distinctive property of SII is that it is the first cortical stage of the somatosensory projection pathway that integrates information arising from both sides of the body. However, there is very little known about how inputs across the body mid-line are processed within SII. RESULTS: Optical intrinsic signal imaging was used to evaluate the response of primary somatosensory cortex (SI and SII in the same hemisphere) to 25 Hz sinusoidal vertical skin displacement stimulation ("skin flutter") applied contralaterally, ipsilaterally, and bilaterally to the central pads of the forepaws. A localized increase in absorbance in both SI and SII was evoked by both contralateral and bilateral flutter stimulation. Ipsilateral flutter stimulation evoked a localized increase in absorbance in SII, but not in SI. The SII region that responded with an increase in absorbance to ipsilateral stimulation was posterior to the region in which absorbance increased maximally in response to stimulation of the contralateral central pad. Additionally, in the posterior SII region that responded maximally to ipsilateral stimulation of the central pad, bilateral central pad stimulation approximated a linear summation of the SII responses to independent stimulation of the contralateral and ipsilateral central pads. Conversely, in anterior SII (the region that responded maximally to contralateral stimulation), bilateral stimulation was consistently less than the response evoked from the contralateral central pad. CONCLUSIONS: The results indicate that two regions located at neighboring, but distinctly different A-P levels of the anterior ectosylvian gyrus process input from opposite sides of the body midline in very different ways. The results suggest that the SII cortex, in the cat, can be subdivided into at least two functionally distinct regions and that these functionally distinct regions demonstrate a laterality preference within SII

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

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

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)

Ipsilateral Input Modifies the Primary Somatosensory Cortex Response to Contralateral Skin Flutter

We recorded the optical intrinsic signal response of squirrel monkey primary somatosensory cortex (SI) to 25 Hz vibrotactile ("flutter") stimulation applied independently to the thenar eminence on each hand and also to bilateral (simultaneous) stimulation of both thenars. The following observations were obtained in every subject (n = 5). (1) Ipsilateral stimulation was accompanied by an increase in absorbance within the SI hand region substantially smaller than the absorbance increase evoked by contralateral stimulation. (2) The absorbance increase evoked by simultaneous bilateral stimulation was smaller (by approximately 30%) than that evoked by contralateral stimulation. (3) The spatiointensive pattern of the SI response to bilateral flutter was distinctly different than the pattern that accompanied contralateral flutter stimulation: with contralateral flutter, the center of the responding region of SI underwent a large increase in absorbance, whereas absorbance decreased in the surrounding region; in contrast, during bilateral flutter, absorbance decreased (relative to that evoked by contralateral flutter) in the central region of SI but increased in the surround. The results raise the possibility that somatosensory perceptual experiences specific to bimanual tactile object exploration derive, at least in part, from the unique spatiointensive activity pattern evoked in SI when the stimulus makes contact with both hands. It is suggested that modulatory influences evoked by ipsilateral thenar flutter stimulation reach SI via a two-stage pathway involving interhemispheric (callosal) connections between information processing levels higher than SI and subsequently via intrahemispheric (corticocortical) projections to the SI hand region

Nociceptive Afferent Activity Alters the SI RA Neuron Response to Mechanical Skin Stimulation

Procedures that reliably evoke cutaneous pain in humans (i.e., 5–7 s skin contact with a 47–51 °C probe, intradermal algogen injection) are shown to decrease the mean spike firing rate (MFR) and degree to which the rapidly adapting (RA) neurons in areas 3b/1 of squirrel monkey primary somatosensory cortex (SI) entrain to a 25-Hz stimulus to the receptive field center (RFcenter) when stimulus amplitude is “near-threshold” (i.e., 10–50 μm). In contrast, RA neuron MFR and entrainment are either unaffected or enhanced by 47–51 °C contact or intradermal algogen injection when the amplitude of 25-Hz stimulation is 100–200 μm (suprathreshold). The results are attributed to an “activity dependence” of γ-aminobutyric acid (GABA) action on the GABAA receptors of RA neurons. The nociceptive afferent drive triggered by skin contact with a 47–51 °C probe or intradermal algogen is proposed to activate nociresponsive neurons in area 3a which, via corticocortical connections, leads to the release of GABA in areas 3b/1. It is hypothesized that GABA is hyperpolarizing/inhibitory and suppresses stimulus-evoked RA neuron MFR and entrainment whenever RA neuron activity is low (as when the RFcenter stimulus is weak/near-threshold) but is depolarizing/excitatory and augments MFR and entrainment when RA neuron activity is high (when the stimulus is strong/suprathreshold)

A proteomic approach for investigating the pleiotropic effects of statins in the atherosclerosis risk in communities (ARIC) study

Background: Statins are prescribed to reduce LDL-c and risk of CVD. Statins have pleiotropic effects, affecting pathophysiological functions beyond LDL-c reduction. We compared the proteome of statin users and nonusers (controls). We hypothesized that statin use is associated with proteins unrelated to lipid metabolism. Methods: Among 10,902 participants attending ARIC visit 3 (1993–95), plasma concentrations of 4955 proteins were determined using SOMAlogic's DNA aptamer-based capture array. 379 participants initiated statins within the 2 years prior. Propensity scores (PS) were calculated based on visit 2 (1990–92) LDL-c levels and visit 3 demographic/clinical characteristics. 360 statin users were PS matched to controls. Log2-transformed and standardized protein levels were compared using t-tests, with false discovery rate (FDR) adjustment for multiple comparisons. Analyses were replicated in visit 2. Results: Covariates were balanced after PS matching, except for higher visit 3 LDL-c levels among controls (125.70 vs 147.65 mg/dL; p < 0.0001). Statin users had 11 enriched and 11 depleted protein levels after FDR adjustment (q < 0.05). Proteins related and unrelated to lipid metabolism differed between groups. Results were largely replicated in visit 2. Conclusion: Proteins unrelated to lipid metabolism differed by statin use. Pending external validation, exploring their biological functions could elucidate pleiotropic effects of statins. Significance: Statins are the primary pharmacotherapy for lowering low-density lipoprotein (LDL) cholesterol and preventing cardiovascular disease. Their primary mechanism of action is through inhibiting the protein 3hydroxy-3-methylglutaryl CoA reductase (HMGCR) in the mevalonate pathway of LDL cholesterol synthesis. However, statins have pleiotropic effects and may affect other biological processes directly or indirectly, with hypothesized negative and positive effects. The present study contributes to identifying these pathways by comparing the proteome of stain users and nonusers with propensity score matching. Our findings highlight potential biological mechanisms underlying statin pleiotropy, informing future efforts to identify statin users at risk of rare nonatherosclerotic outcomes and identify health benefits of statin use independent of LDL-C reduction

Fine Particulate air Pollution is Associated with Higher Vulnerability to Atrial Fibrillation—The APACR Study

The acute effects and the time course of fine particulate pollution (PM2.5) on atrial fibrillation/flutter (AF) predictors, including P-wave duration, PR interval duration, and P-wave complexity, were investigated in a community-dwelling sample of 106 nonsmokers. Individual-level 24-h beat-to-beat electrocardiogram (ECG) data were visually examined. After identifying and removing artifacts and arrhythmic beats, the 30-min averages of the AF predictors were calculated. A personal PM2.5 monitor was used to measure individual-level, real-time PM2.5 exposures during the same 24-h period, and corresponding 30-min average PM2.5 concentration were calculated. Under a linear mixed-effects modeling framework, distributed lag models were used to estimate regression coefficients (βs) associating PM2.5 with AF predictors. Most of the adverse effects on AF predictors occurred within 1.5–2 h after PM2.5 exposure. The multivariable adjusted βs per 10-µg/m3 rise in PM2.5 at lag 1 and lag 2 were significantly associated with P-wave complexity. PM2.5 exposure was also significantly associated with prolonged PR duration at lag 3 and lag 4. Higher PM2.5 was found to be associated with increases in P-wave complexity and PR duration. Maximal effects were observed within 2 h. These findings suggest that PM2.5 adversely affects AF predictors; thus, PM2.5 may be indicative of greater susceptibility to AF

Leveraging case study research: A mechanism for measuring 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