Investigation of electro-vascular phase-amplitude coupling during an auditory task.

Multimodal neuroimaging using electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) provides complementary views of cortical processes, including those related to auditory processing. However, current multimodal approaches often overlook potential insights that can be gained from nonlinear interactions between electrical and hemodynamic signals. Here, we explore electro-vascular phase-amplitude coupling (PAC) between low-frequency hemodynamic and high-frequency electrical oscillations during an auditory task. We further apply a temporally embedded canonical correlation analysis (tCCA)-general linear model (GLM)-based correction approach to reduce the possible effect of systemic physiology on fNIRS recordings. Before correction, we observed significant PAC between fNIRS and broadband EEG in the frontal region (p ≪ 0.05), ß (p ≪ 0.05) and γ (p = 0.010) in the left temporal/temporoparietal (left auditory; LA) region, and γ (p = 0.032) in the right temporal/temporoparietal (right auditory; RA) region across the entire dataset. Significant differences in PAC across conditions (task versus silence) were observed in LA (p = 0.023) and RA (p = 0.049) γ sub-bands and in lower frequency (5-20 Hz) frontal activity (p = 0.005). After correction, significant fNIRS-γ-band PAC was observed in the frontal (p = 0.021) and LA (p = 0.025) regions, while fNIRS-α (p = 0.003) and fNIRS-ß (p = 0.041) PAC were observed in RA. Decreased frontal γ-band (p = 0.008) and increased ß-band (p ≪ 0.05) PAC were observed during the task. These outcomes represent the first characterization of electro-vascular PAC between fNIRS and EEG signals during an auditory task, providing insights into electro-vascular coupling in auditory processing.

Individual-specific characterization of event-related hemodynamic responses during an auditory task: An exploratory study.

Functional near-infrared spectroscopy (fNIRS) has been established as an informative modality for understanding the hemodynamic-metabolic correlates of cortical auditory processing. To date, such knowledge has shown broad clinical applications in the diagnosis, treatment, and intervention procedures in disorders affecting auditory processing; however, exploration of the hemodynamic response to auditory tasks is yet incomplete. This holds particularly true in the context of auditory event-related fNIRS experiments, where preliminary work has shown the presence of valid responses while leaving the need for more comprehensive explorations of the hemodynamic correlates of event-related auditory processing. In this study, we apply an individual-specific approach to characterize fNIRS-based hemodynamic changes during an auditory task in healthy adults. Oxygenated hemoglobin (HbO2) concentration change time courses were acquired from eight participants. Independent component analysis (ICA) was then applied to isolate individual-specific class discriminative spatial filters, which were then applied to HbO2 time courses to extract auditory-related hemodynamic features. While six of eight participants produced significant class discriminative features before ICA-based spatial filtering, the proposed method identified significant auditory hemodynamic features in all participants. Furthermore, ICA-based filtering improved correlation between trial labels and extracted features in every participant. For the first time, this study demonstrates hemodynamic features important in experiments exploring auditory processing as well as the utility of individual-specific ICA-based spatial filtering in fNIRS-based feature extraction techniques in auditory experiments. These outcomes provide insights for future studies exploring auditory hemodynamic characteristics and may eventually provide a baseline framework for better understanding auditory response dysfunctions in clinical populations.

Can future type I diabetes be predicted? A study in families of affected children.

This article examines the risk of type I (insulin-dependent) diabetes in siblings of affected children, in relation to HLA genotypes. The 288 available siblings of 160 diabetic probands were grouped according to the number of HLA haplotypes in common with their probands. HLA-identical siblings (both haplotypes in common) have an approximately 100 times greater risk of developing the disease than that in the general population, and this risk is significantly higher than that in haplo-identical siblings (one haplotype in common) P = 0.008). Thus, in Northern European populations, some 30% of HLA-identical siblings are expected to be diabetic by the age of 30 yr. The risk in nonidentical siblings (neither haplotype in common) is not significantly increased. These findings carry implications for genetic counseling and research.

Monoclonal antibodies defined abnormalities of T-lymphocytes in type I (insulin-dependent) diabetes.

Peripheral T-lymphocytes subsets have been investigated in 36 patients with type I (insulin-dependent) diabetes of varying duration, 18 patients with type II (non-insulin-dependent) diabetes, and in 23 healthy subjects, using six different monoclonal antibodies. At the time of diagnosis of type I diabetes, there was evidence of an increase in cytotoxic T-lymphocytes, a decrease in suppressor T-lymphocytes, but a normal proportion of helper/inducer T-lymphocytes. In six of seven newly diagnosed cases studied, there was evidence of an increased number of activated T cells. An increase in activated T-cells was also found in 5 of 10 genetically susceptible islet cell antibody positive unaffected siblings in type I diabetic probands. In type I diabetes of long standing, the total T-cell population was decreased, largely due to a marked decrease in helper/inducer T-lymphocytes. Type II diabetic patients showed no abnormalities in T-lymphocyte subsets, making it unlikely that hyperglycemia was responsible for the changes observed. These results suggest that an imbalance of T-lymphocyte regulation is an important feature of type I diabetes and lend support for an immunologic role in its early pathogenesis.

Syntactic parsing preferences and their on-line revisions: a spatio-temporal analysis of event-related brain potentials.

The present study investigates the processes involved in the recovery from temporarily ambiguous garden-path sentences. Event-related brain potentials (ERP) were recorded while subjects read German subject-object ambiguous relative and complement clauses. As both clause types are initially analyzed as subject-first structures, object-first structures require a revision which is more difficult for complement than for relative clauses. The hypothesis is tested that the revision process consists of two sub-processes, namely diagnosis and actual reanalysis. Applying a spatio-temporal principal component analysis to the ERP data, distinct positive sub-components presumably reflecting different sub-processes could be identified in the time range of the P300 and P600. It will be argued that the P600 is not a monolithic component, and that different sub-processes may be involved at varying time points depending on the type of garden-path sentence.

Leaf position error during conformal dynamic arc and intensity modulated arc treatments.

Conformal dynamic arc (CD-ARC) and intensity modulated arc treatments (IMAT) are both treatment modalities where the multileaf collimator (MLC) can change leaf position dynamically during gantry rotation. These treatment techniques can be used to generate complex isodose distributions, similar to those used in fix-gantry intensity modulation. However, a beam-hold delay cannot be used during CD-ARC or IMAT treatments to reduce spatial error. Consequently, a certain amount of leaf position error will have to be accepted in order to make the treatment deliverable. Measurements of leaf position accuracy were taken with leaf velocities ranging from 0.3 to 3.0 cm/s. The average and maximum leaf position errors were measured, and a least-squares linear regression analysis was performed on the measured data to determine the MLC velocity error coefficient. The average position errors range from 0.03 to 0.21 cm, with the largest deviations occurring at the maximum achievable leaf velocity (3.0 cm/s). The measured MLC velocity error coefficient was 0.0674 s for a collimator rotation of 0 degrees and 0.0681 s for a collimator rotation of 90 degrees. The distribution in leaf position error between the 0 degrees and 90 degrees collimator rotations was within statistical uncertainty. A simple formula was developed based on these results for estimating the velocity-dependent dosimetric error. Using this technique, a dosimetric error index for plan evaluation can be calculated from the treatment time and the dynamic MLC leaf controller file.

Ionization chamber, electrometer, linear accelerator, field size, and energy dependence of the polarity effect in electron dosimetry.

Plane-parallel ionization chambers are the instrument of choice for use in electron calibration and dosimetry, but these chambers may exhibit large polarity effects. This study concentrates on measuring the dependence of the polarity error at various mean energies using different linear accelerator, field size, ion chamber, and electrometer combinations. The polarity error was shown to increase for all four ionization chambers as the mean energy at depth decreased, but was always less than one percent at d(max). Polarity error dependence was also observed for similar plane-parallel chambers, varying field sizes, and different linear accelerators, but no polarity error dependence was observed for similar cylindrical chambers and different electrometers. Measurements of the polarity error can be used to develop correction factors for future measurements that will help minimize the time spent performing electron dosimetry and calibrations. These correction factors can be used to calculate the correct reading without the need to reverse the chamber bias, thus reducing the number of measurements required.

Dosimetric verification of two commercially available three-dimensional treatment planning systems using the TG 23 test package.

The Task Group 23 (TG-23) radiation treatment planning dosimetry verification package was used to evaluate the dosimetric accuracy of two commercially available treatment planning systems. The TG-23 test package contains experimentally measured beam data for two x-ray beams (4 and 18 MV) that can be used as input for 3D-RTP (three-dimensional radiation treatment planning) systems. Once the beam data is entered and modeled, a series of test cases are performed that isolate different aspects of the dose computational process. The computed values from the 3D-RTP system are compared against the measured dosimetry data, included in the package, for a set of comparison points within each test case. Both of the treatment planning systems that were studied provided excellent agreement between computed and measured doses. The cumulative 4 and 18 MV TG-23 test results for the convolution/superposition based planning system indicates that 96% of the dosimetric test points are within +/-2%, and 98% are within +/-3% of the tabulated TG-23 values. The dosimetric TG-23 test results for the pencil beam kernel based planning system are similar, with 96% of the test points falling within +/-2%, and 99% falling within +/-3% of the TG-23 measurements.

The lateralized readiness potential: relationship between human data and response activation in a connectionist model.

Psychophysiological measures such as the lateralized readiness potential (LRP) have been used to study information processing in the Eriksen flankers task. The data provided by these measures are consistent with a continuous flow theory, which proposes that the output of stimulus evaluation is continuously available to the response channels. Cohen et al. (1992) realized this theory in a connectionist model and showed that its behavior corresponded to that of human subjects in the flankers task. We report here a modification of the model and an analysis of the degree to which simulated LRPs (based on the activation functions of the response units of the model) resemble the actual LRPs of human subjects in the same task. Across a variety of different experimental conditions and outcomes, there was a marked correspondence between the simulated and actual LRPs. These observations strengthen the propriety of the connectionist model and of the continuous flow theory on which it is based.

Poststimulus EEG spectral analysis and P300: attention, task, and probability.

Event-related potentials (ERPs) were elicited with auditory stimuli, and spectral analysis was performed on the poststimulus electroencephalographic (EEG) activity to assess how variables that influence the P300 affect spectral parameters of the resultant ERP. In Experiment 1, a no-stimulus condition was compared with a single repeated tone that was either ignored or counted. In Experiment 2, an auditory oddball paradigm was used in which the subject ignored all stimuli, counted only the target, or counted both the target and the standard stimuli in different conditions. In Experiment 3, stimulus probability was manipulated in separate conditions (.20, .50, .80), with the subject required to count the target stimulus. Delta and theta band spectral power increased whenever P300 amplitude increased. However, as the attentional requirements increased across tasks, alpha-1 and alpha-2 power and mean frequency increased. The findings indicate that auditory stimulus processing modulates the EEG more than just by adding ERP components to the epoch.

A componential analysis of the ERP elicited by novel events using a dense electrode array.

In this study, we examined the relationship between the novelty P3 and the P300 components of the brain event-related potential (ERP). Fifteen subjects responded manually to the rare stimuli embedded either in a classical auditory oddball series or in a series in which "novel" stimuli were inserted. The electroencephalogram (EEG) was recorded with a dense array of 129 electrodes. The data were analyzed by using spatial Principal Components Analysis (PCA) to identify a set of orthogonal scalp distributions, "virtual electrodes" that account for the spatial variance. The data were then expressed as ERPs measured at each of the virtual electrodes. These ERPs were analyzed using temporal PCA, yielding a set of "virtual epochs." Most of the temporal variance of the rare events was associated with a virtual electrode with a posterior topography, that is, with a classical P300, which was active during the virtual epoch associated with the P300. The novel stimuli were found to elicit both a classical P300 and a component focused on a virtual electrode with a frontal topography. We propose that the term Novelty P3 should be restricted to this frontal component.

Spatiotemporal analysis of the late ERP responses to deviant stimuli.

We used a novel application of principal components analysis (spatiotemporal PCA) to decompose the event-related brain potentials (ERPs) obtained with a dense electrode array, with the purpose of elucidating the late ERP components elicited by deviant stimuli under "attend" and "ignore" conditions. First, a "spatial" PCA was performed to identify a set of scalp distributions (spatial factors or "virtual electrodes") that accounted for the spatial variance in the data set. The data were expressed as spatial factor scores or "virtual ERPs" measured at each of the virtual electrodes. These virtual ERPs were submitted to a "temporal" PCA, yielding a set of temporal factors or "virtual epochs." Statistical analyses of the temporal factor scores found that (1) attended deviant stimuli elicited the P300 and Novelty P3 components, the latter being largest for highly salient nontargets: (2) "ignored" deviants elicited a small Novelty P3, and depending on the primary task, a small P300: and (3) the classical Slow Wave consisted of separate frontal-negative and posterior-positive components.

On the search for the neurophysiological manifestation of recollective experience.

M.E. Smith (1993) obtained event-related brain potentials (ERPs) from subjects performing a recognition memory task using "remember" (R) and "know" (K) judgments, and reported observing in the ERP a "neurophysiological manifestation of recollective experience" as a difference between the positive waveforms elicited by stimuli that yielded R and K judgments. We replicated his experiment and examined the componential structure of the R > K effect in two ways. First, we found that correction for P300 latency jitter eliminated the effect reported by Smith. Second, the application of principal component analysis indicated that the positive waveform elicited by the words in the test list was a P300. These analyses do not support the hypothesis that there is a new component (the "memory-evoked shift") that is a specific manifestation of recollection.

The mental prosthesis: assessing the speed of a P300-based brain-computer interface.

We describe a study designed to assess a brain-computer interface (BCI), originally described by Farwell and Donchin [9] in 1988. The system utilizes the fact that the rare events in the oddball paradigm elicit the P300 component of the event-related potential (ERP). The BCI presents the user with a matrix of 6 by 6 cells, each containing one letter of the alphabet. The user focuses attention on the cell containing the letter to be communicated while the rows and the columns of the matrix are intensified. Each intensification is an event in the oddball sequence, the row and the column containing the attended cell are "rare" items and, therefore, only these events elicit a P300. The computer thus detects the transmitted character by determining which row and which column elicited the P300. We report an assessment, using a boot-strapping approach, which indicates that an off line version of the system can communicate at the rate of 7.8 characters a minute and achieve 80% accuracy. The system's performance in real time was also assessed. Our data indicate that a P300-based BCI is feasible and practical. However, these conclusions are based on tests using healthy individuals.

The genetic susceptibility to type 1 (insulin-dependent) diabetes: analysis of the HLA-DR association.

HLA-DR and MT1, MT2, MT3 genotypes have been investigated in 123 Type 1 (insulin-dependent) diabetic subjects and their families. Ninety-eight percent of probands possessed either DR3 (relative risk = 5.0), or DR4 (relative risk = 6.8) or both antigens (relative risk = 14.3), emphasizing the strong association of the disease with these two antigens. Almost 51% of the probands were DR3, DR4 heterozygotes. The DR antigen combinations of the parents leading to DR3, DR4 heterozygous and to DR3 and DR4 homozygous offspring were analysed. There was a marked increase in DR3, DR4 heterozygosity, but no increase in homozygosity for these antigens compared with the expected frequencies. These results are compatible with the existence of two susceptibility genes operating at a locus or at loci closely linked to that of HLA-DR. There was a striking reduction of DR7 (relative risk = 0.1) and only five probands possessed DR2 (relative risk = 0.1). In each case, the other inherited allele was DR3 or DR4. Linkage disequilibrium between B7 and DR2 was much lower in the haplotypes of the probands than in the 'non-diabetic' parental haplotype. In contrast, the association of BW62 with DR4 was more pronounced in the haplotypes of the probands. There was no increase in recombination frequency in these families and no strong effect of HLA-DR on age of onset could be demonstrated. There was a significant shift towards DR identity compared with identity for the whole HLA haplotype (A, B, C and DR) in both healthy and diabetic siblings (p less than 0.025).

Surface-enhanced raman detection of 2,4-dinitrotoluene impurity vapor as a marker to locate landmines.

Time, cost, and casualties associated with demining efforts underscore the need for improved detection techniques. Reduction in the number of false positives by directly detecting the explosive material, rather than casing material, is desirable. The desired field sensor must, at a minimum, demonstrate reproducibility, the necessary level of sensitivity, portability, instrumental stability, and fast system response times. Ideally, vibrational spectroscopic techniques have the potential to remove false positives, since every chemical has a unique bond structure. Herein, we demonstrate the capabilities of surface-enhanced Raman spectroscopy to detect the chemical vapor signature emanating from buried TNT-based landmines. We present reproducible results obtained from blind tests controlled by the Defense Advanced Research Projects Agency (DARPA) that demonstrate vapor detection of 2,4-dinitrotoluene at concentration levels of 5 ppb or less. The results presented used acquisition times of 30 s on a fieldable system and showed that SERS can be a significant improvement over current landmine detection methods.

Cell-mediated immunity in the aetiopathogenesis of insulin-dependent (type I) diabetes mellitus.

We have investigated lymphocyte subpopulation levels with monoclonal antibodies in newly diagnosed insulin-dependent (type I) diabetics and in unaffected siblings of type I diabetic probands with islet cell antibodies. Our data show that in newly diagnosed diabetics there is 1) a decrease in T cells with suppressor phenotype, 2) an increase of T cells with cytotoxic phenotype and 3) the presence of "activated" T cells. The latter have also been found in some unaffected siblings with islet cell antibodies. These results suggest that cellular immune alterations are present, not only at diagnosis, but also in normal but "susceptible" individuals. "Activated" T cells could be a "disease" marker, but their better definition in terms of specificity should be established.

Analytical determination of enantiomeric purity using Raman optical activity.

Increased restrictions on the enantiomeric purity of pharmaceuticals underscore the need for improved analytical techniques to quantitate chiral purity. The method of scattered circularly polarized Raman optical activity (SCP ROA) is examined as a potentially useful analytical technique. Preliminary studies revealed SCP ROA measurements were reproducible to within current experimental noise limits and displayed the expected linear decrease in SCP ROA with increasing racemization of the enantiomeric mixtures. Minimal interference in SCP ROA signal was observed when either an achiral or another chiral entity was present in a mixture. The advantages of spectral subtraction techniques were demonstrated for separation of SCP ROA signals when multiple chiral entities are present. SCP ROA has been shown to be capable of quantitative analysis and is capable of simultaneous identification of multiple enantiomeric species. This is significant since traditional optical activity measurements, such as polarimetry and circular dichroism, are of limited value on mixtures where the impurities are not quantitatively defined.

The effects of hemispheric differences on feature perturbations.

Hemispheric differences for feature perturbations were investigated in two experiments. Stimulus displays consisting of five small squares arranged in a single row were presented tachistoscopically, with the subject instructed to state in which square a horizontal tick mark was located. Ticks could occur in any of the three middle squares, with half of the ticks presented on the inside and half presented on the outside of the square in relation to the fovea. Experiment 1 presented each array of five squares to the right or left of fixation at one of three distances from the fovea. Experiment 2 manipulated the distance between the squares and kept foveal distance constant. In each experiment, fewer errors were made when stimuli were presented to the left visual field/right hemisphere than when they were presented to the right visual field/left hemisphere, when ticks migrated toward the fovea. Experiment 1 found that increasing the distance from the fovea increased the error rate, but did not change the hemispheric differences. Experiment 2 found that increasing the distance between the squares did not change hemispheric effects reliably. The data imply that hemispheric differences for perceptual processing begin very early during sensory analysis.

In vitro inhibition of insulin release mediated by sera with complement-fixing islet cell antibodies belonging to normal first degree relatives of patients with type 1 diabetes.

Islet cell antibodies (ICA) are present in the sera of most patients with Type 1 diabetes at diagnosis and in some of their genetically susceptible, but otherwise normal, first degree relatives. In this study we have investigated basal and stimulated insulin release by mouse islets following preincubation with human sera (with or without the addition of guinea pig complement) belonging to: 15 normal first degree relatives of diabetic probands; 7 patients with Type 1 diabetes; 7 control subjects with no history of diabetes. All sera had been previously screened for conventional (IgG), complement fixing (CF) and surface (S) ICA. Basal insulin release was not altered by any of the sera. The response to stimulus after incubation with ICA negative and IgG-ICA positive (but CF-ICA negative) sera was similar whether complement was present or not. Stimulated insulin release was significantly inhibited by complement and sera from 2 relatives and 3 diabetic patients. These sera were CF-ICA positive, the sera of the 2 relatives being also ICSA positive. One relative developed Type 1 diabetes 14 months later. This study demonstrates for the first time that sera containing CF-ICA and belonging to individuals susceptible to Type 1 diabetes, can impair insulin release in vitro. It is therefore likely that antibody-dependent, complement-mediated mechanisms are involved in the pathogenesis of Type 1 diabetes.