The neural networks underlying auditory sensory gating.

One of the most consistent electrophysiological deficits reported in the schizophrenia literature is the failure to inhibit, or properly gate, the neuronal response to the second stimulus of an identical pair (i.e., sensory gating). Although animal and invasive human studies have consistently implicated the auditory cortex, prefrontal cortex and hippocampus in mediating the sensory gating response, localized activation in these structures has not always been reported during non-invasive imaging modalities. In the current experiment, event-related FMRI and a variant of the traditional gating paradigm were utilized to examine how the gating network differentially responded to the processing of pairs of identical and non-identical tones. Two single-tone conditions were also presented so that they could be used to estimate the HRF for paired stimuli, reconstructed based on actual hemodynamic responses, to serve as a control non-gating condition. Results supported an emerging theory that the gating response for both paired-tone conditions was primarily mediated by auditory and prefrontal cortex, with potential contributions from the thalamus. Results also indicated that the left auditory cortex may play a preferential role in determining the stimuli that should be inhibited (gated) or receive further processing due to novelty of information. In contrast, there was no evidence of hippocampal involvement, suggesting that future work is needed to determine what role it may play in the gating response.

Commonalities and differences among vectorized beamformers in electromagnetic source imaging.

A number of beamformers have been introduced to localize neuronal activity using magnetoencephalography (MEG) and electroencephalography (EEG). However, currently available information about the major aspects of existing beamformers is incomplete. In the present study, detailed analyses are performed to study the commonalities and differences among vectorized versions of existing beamformers in both theory and practice. In addition, a novel beamformer based on higher-order covariance analysis is introduced. Theoretical formulas are provided on all major aspects of each beamformer; to examine their performance, computer simulations with different levels of correlation and signal-to-noise ratio are studied. Then, an empirical data set of human MEG median-nerve responses with a large number of neuronal generators is analyzed using the different beamformers. The results show substantial differences among existing MEG/EEG beamformers in their ways of describing the spatial map of neuronal activity. Differences in performance are observed among existing beamformers in terms of their spatial resolution, false-positive background activity, and robustness to highly correlated signals. Superior performance is obtained using our novel beamformer with higher-order covariance analysis in simulated data. Excellent agreement is also found between the results of our beamformer and the known neurophysiology of the median-nerve MEG response.

Auditory sensory gating deficit and cortical thickness in schizophrenia.

Both an EEG P50 sensory gating deficit and abnormalities of the temporal lobe structure are considered characteristic of schizophrenia. The standard P50 sensory gating measure does not foster differential assessment of left- and right-hemisphere contributions, but its analogous MEG M50 component may be used to measure gating of distinct auditory source dipoles localizing to left- and right-hemisphere primary auditory cortex. The present study sought to determine how sensory gating ratio may relate to cortical thickness at the site of the auditory dipole localization. A standard auditory paired-click paradigm was used during MEG for patients (n=22) and normal controls (n=11). Sensory gating ratios were determined by measuring the strength of the 50 ms response to the second click divided by that of the first click (S2/S1). Cortical thickness was assessed by two reliable raters using 3D sMRI. Results showed that: (1) patients had a P50 and left M50 sensory gating deficit relative to controls; (2) cortex in both hemispheres was thicker in the control group; (3) in schizophrenia, poorer left-hemisphere M50 sensory gating correlated with thinner left-hemisphere auditory cortical thickness; and (4) poorer right-hemisphere M50 auditory sensory gating ratio correlated with thinner right-hemisphere auditory cortical thickness in patients. The MEG-assessed hemisphere-specific auditory sensory gating ratio may be driven by this structural abnormality in auditory cortex.

Predicting EEG responses using MEG sources in superior temporal gyrus reveals source asynchrony in patients with schizophrenia.

OBJECTIVE: An integrated analysis using Electroencephalography (EEG) and magnetoencephalography (MEG) is introduced to study abnormalities in early cortical responses to auditory stimuli in schizophrenia. METHODS: Auditory responses were recorded simultaneously using EEG and MEG from 20 patients with schizophrenia and 19 control subjects. Bilateral superior temporal gyrus (STG) sources and their time courses were obtained using MEG for the 30-100 ms post-stimulus interval. The MEG STG source time courses were used to predict the EEG signal at electrode Cz. RESULTS: In control subjects, the STG sources predicted the EEG Cz recording very well (97% variance explained). In schizophrenia patients, the STG sources accounted for substantially (86%) and significantly (P<0.0002) less variance. After MEG-derived STG activity was removed from the EEG Cz signal, the residual signal was dominated by 40 Hz activity, an indication that the remaining variance in EEG is probably contributed by other brain generators, rather than by random noise. CONCLUSIONS: Integrated MEG and EEG analysis can differentiate patients and controls, and suggests a basis for a well established abnormality in the cortical auditory response in schizophrenia, implicating a disorder of functional connectivity in the relationship between STG sources and other brain generators.

Effects of treatment protocols and subcutaneous implantation on bovine pericardium: a Raman spectroscopy study.

Using Raman microspectroscopy, we have studied mineral deposition on bovine pericardia, fixed according to three different protocols and either implanted subcutaneously or not implanted (controls). A lightly carbonated apatitic phosphate mineral, similar to that found in bone tissue, was deposited on the surface of a glutaraldehyde-fixed, implanted pericardium. Implanted pericardia fixed in glutaraldehyde followed by treatment in either an 80% ethanol or a 5% octanol/40% ethanol solution did not mineralize on implantation. Collagen secondary structure changes were observed on glutaraldehyde fixation by monitoring the center of gravity of the amide I envelope. It is proposed that the decrease in the amide I center of gravity frequency for the glutaraldehyde-fixed tissue compared to the nonfixed tissue is due to an increase in nonreducible collagen cross-links (1660 cm(-1)) and a decrease in reducible cross-links (1690 cm(-1)). The amide I center of gravity in the glutaraldehyde/ethanol-fixed pericardium was higher than the glutaraldehyde-fixed tissue center of gravity. This increase in center of gravity could possibly be due to a decrease in hydrogen bonding within the collagen fibrils following the ethanol pretreatment. In addition, we found a secondary structure change to the pericardial collagen after implantation: an increase in the frequency of the center of gravity of amide I is indicative of an increase in cross-links.

Comparison of chemical treatments on the chain dynamics and thermal stability of bovine pericardium collagen.

A new approach for the replacement of heart valves consists of obtaining an acellular matrix from animal aortic valves that performs mechanically, is nonantigenic, and is free from calcification and fibroblast proliferation. Novel biochemical treatments must be developed for this purpose. In this work, we focus on the characterization of collagen in acellular bovine cardiovascular tissues, fresh or glutaraldehyde treated, and stored in different solutions [phosphate-buffered saline (PBS), ethanol, octanol, and glutaraldehyde], to determine whether the resulting fibrous material is structurally preserved. The preservation of the triple helical structure of collagen is checked by differential scanning calorimetry (DSC), which is a well suited technique to analyze thermal transitions in proteins, such as denaturation. To get insight into the molecular dynamics of collagen in the nanometric range, we used thermally stimulated currents, a dielectric technique running at low frequency, that measure the dipolar reorientations in proteins submitted to a static electrical field. The combined use of these two techniques allowed us to evaluate the physical structure and conformation of collagen after the different chemical treatments. We have found that the glutaraldehyde treatment followed by octanol storage preserves the triple helical conformation of the polypeptidic chains of collagen, contrary to the ethanol and PBS storage that induce drastic changes in the thermal and dielectric behavior of the protein. Moreover, this particular chemical treatment stabilizes the collagen structure (shift toward high temperature of the collagen denaturation and stiffening of the chains by a cross-linking action) when compared to the control sample, and so could provide interesting fibrous material for the conception of bioprosthetic heart valve.

The role of material surface chemistry in implant device calcification: a hypothesis.

We proposed that a similar mechanism for calcification exists for poly(ether)urethanes and glutaraldehyde stabilized tissue. The mechanism is based on the propensity of the polyether component of the materials to complex calcium and provide initiating sites for ultimate formation of calcific deposits. Data evaluating the role ether containing materials have on calcification demonstrate that the rate of mineralization of either tissue valves or polymer valves can be controlled by paying attention to the basic chemical mechanism of complexation occurring at the surface and within the bulk of the implant devices. The molecular models described above, point out that the driving force for complexation with either the polyethers of the polyurethane or the polyether of glutaraldehyde is very strong, therefore, controlling the driving force may lead to medical devices with longer term durability.

Biomedical applications of polyurethanes: implications of failure mechanisms.

Three mechanisms have been described which explain various observed interactions between polyurethane chemistry and body chemistry. These include calcification, environmental stress cracking, and chain scission. Each may result in implant device failure, and each appears to involve metal ion complexation as a key parameter. Continued expansion of polyurethane into implantable product applications will require further clarification of the effect of each of these interactions on long-term product performance. It is believed that design considerations and polymer modifications will help control the effects of each of the interactions and will result in new and improved polyurethane implant products.

Studies of poly(ether)urethane pacemaker lead insulation oxidation.

Published reports suggest that silver ions may catalyze the oxidation of poly(ether)urethane soft-segments resulting in the failure of urethane insulations of specific models of pacemaker leads. Attempted oxidation of soft-segment models, poly(tetra-methylene ether)glycols, by silver nitrate has shown that metal-ion catalyzed oxidative-reduction (MICOR) does not adequately explain observed failures unless antioxidants are removed in process. Such cracking can, however, be explained in terms of a metal ion enhanced environmental stress cracking.

Poly(ether) urethane reactivity with metal-ion in calcification and environmental stress cracking.

Since their introduction to the biomedical community in 1967, polyurethanes have been used in a number of biomedical applications. In chronic applications evidence is now available which suggests that polyurethanes may be subject to various cracking phenomena. Environmental stress cracking and calcification are two phenomena resulting in poly(ether)urethane cracking, which have been shown to be enhanced by ion complexation. Much evidence now exists which defines the ability of poly(ether)urethanes to selectively extract ions, especially calcium ion from solution. Metal ion binding appears to enhance environmental stress cracking and appears to be a first step in the process of calcification.