Alpha power during task performance predicts individual language comprehension.

Alpha power attenuation during cognitive task performing has been suggested to reflect a process of release of inhibition, increase of excitability, and thereby benefit the improvement of performance. Here, we hypothesized that changes in individual alpha power during the execution of a complex language comprehension task may correlate with the individual performance in that task. We tested this using magnetoencephalography (MEG) recorded during comprehension of German sentences of different syntactic complexity. Results showed that neither the frequency nor the power of the spontaneous oscillatory activity at rest were associated with the individual performance. However, during the execution of a sentences processing task, the individual alpha power attenuation did correlate with individual language comprehension performance. Source reconstruction localized these effects in left temporal-parietal brain regions known to be associated with language processing and their right-hemisphere homologues. Our results support the notion that in-task attenuation of individual alpha power is related to the essential mechanisms of the underlying cognitive processes, rather than merely to general phenomena like attention or vigilance.

Sources of synchronized induced Gamma-Band responses during a simple object recognition task: a replication study in human MEG.

Natural stimuli are compiled of numerous features, which are cortically represented in dispersed structures. Synchronized oscillations in the Gamma-Band (>30 Hz; induced Gamma-Band Responses, iGBRs), are regarded as a plausible mechanism to re-integrate these regions into a meaningful cortical object representation. Using electroencephalography (EEG) it was demonstrated that the generators of iGBRs can be localized to temporal, parietal, posterior, and frontal areas. The present magnetoencephalogram (MEG) study intended to replicate these findings in order contribute to the ongoing debate regarding the possible functional difference of high-frequency signals as measured by both techniques. During a standard object recognition task we found an augmentation of the iGBR after the presentation of meaningful as opposed to meaningless stimuli at approximately 160-440 ms after stimulus onset. This peak was localized to inferior temporal gyri, superior parietal lobules and the right middle frontal gyrus. Importantly, most of these brain structures were significantly phase-locked to each other. The implications of these results are twofold: (1) they present further evidence for the view that iGBRs signify neuronal activity in a broadly distributed network during object recognition. (2) MEG is well suited to detect induced high-frequency oscillations with a very similar morphology as revealed by EEG recordings, thereby eliminating known problems with electroencephalographical methods (e.g. reference confounds). In contrast to the iGBR, the localization of event-related fields (ERFs) and evoked Gamma-Band Response (eGBRs) revealed generators in focal visual areas, and thus, seem to mirror early sensory processing.

Rapidly induced changes in neuromagnetic fields following repetitive hand movements.

Sensory feedback plays a major role in movement execution and motor learning, particularly in motor rehabilitation. Whilst elaborating therapeutic strategies, it is of interest to visualize the effect of a therapeutic intervention at the moment of its application. We analyzed the effect of repeated execution of a simple extension and flexion movement of the wrist on the sensorimotor cortex of seven healthy subjects using magnetoencephalography. Spatial filtering based on current dipoles was used to quantify the strength of cortical activation. Our results showed an increase of cortical activation reflecting activity of efferent neurons, whereas the activity of proprioceptive afferent neurons was not affected. Since only efferent activity increased, it is suggested that this reflects phenomena of long-term potentiation.

Frequency specific impairment of automatic pitch change detection by fMRI acoustic noise: an MEG study.

The loud acoustic noise produced by the magnetic resonance scanner is a major source of interference in auditory fMRI research. Whole-head magnetoencephalography (MEG) was used to investigate the interaction between the frequency range of auditory stimulation and fMRI acoustic noise. Pure tones and 3-harmonic complexes varying between 240 and 1240 Hz in frequency were presented while participants attended to a silent subtitled film. Continuous fMRI acoustic noise was presented during half of the blocks. The activity in six regions of interest was analyzed in 100-200 and 200-300 ms time windows to evaluate the magnetic counterparts of the mismatch negativity (MMN) and P3a brain responses. The results suggested that fMRI noise significantly reduced the amplitude of these responses. The effect of the noise on the automatic processing of the tones was more prominent for the tones with frequencies higher than 500 Hz. It is recommended that in the MMN protocols using continuous fMRI acquisition the sound stimuli should be spectrally separated from the fMRI scanner noise spectrum.

The influence of volume conduction effects on the EEG/MEG reconstruction of the sources of the Early Left Anterior Negativity.

To achieve a deeper understanding of language processing in the human brain, scientists and clinicians use Electroencephalography (EEG) and Magnetoencephalography (MEG) inverse methods to reconstruct sources of Event Related Potentials. There exists a persistent uncertainty regarding the influence of volume conduction effects such as the anisotropy of tissue conductivity of the skull and the white matter layers on the inverse results. In this paper, we will study the sensitivity to anisotropy of the source reconstruction of the Early Left Anterior Negativity (ELAN) component in language processing. For EEG, the presence of tissue anisotropy substantially compromises the restoration ability of an L1-norm current density approach. The centers of activity are strongly shifted along the Sylvian fissure in the anterior direction. In contrast, MEG in combination with the L1 norm approach is able to reconstruct the main features of the ELAN source distribution even in the presence of anisotropic conductivity.

The "fixed" charge of glomerular capillary wall as determinant of permselectivity.

The determinants of glomerular capillary wall (GCW) permeability to proteins have been subject of controversial discussion. To study this question we have developed a modified isolated perfused rat kidney model in which tubular transport processes are completely blocked by perfusion fixation with glutaraldehyde. This model allows to directly titrate the charge density of the GCW using albumin solutions buffered over a wide pH-range, a manipulation that cannot be performed in the intact kidney. Analyzing the results of these experiments helped to determine a fixed charge density of the GCW of 43 mEq/L. In the present work, we used the isolated perfused fixed rat kidney model to study the influence of this fixed charge on the transglomerular passage of proteins. To do this, the fixed kidney was perfused with albumin solutions containing different isoforms of horseradish peroxidase. The lowest sieving coefficient was obtained with the acidic isoform (0.035+/-0.008, n = 7), while the isoforms at pI 6.85 and 8.45 showed higher sieving coefficients (0.059+/-0.008, n = 7 and 0.090+/-0.008, n = 4, respectively). The highest sieving coefficient (0.59+/-0.031, n = 6) was observed in perfusion experiments of the fixed kidney with cationic HRP (pI > or = 9.30). However, when comparing the sieving coefficients, the highly cationic isoform was excluded because it has a lower molecular weight than the other isoforms. The sieving coefficients of the other isoforms were significantly different (p < 0.05. ANOVA, Scheffé test). In conclusion, the presence of a discrete (even if lower than previously thought) "fixed" charge on the GCW of 43 mEq/L restricts the transglomerular passage of isoforms of horseradish peroxidase by a factor 2-3. These results imply that the influence of charge selectivity has been overstated in the literature.

Musical syntax is processed in Broca's area: an MEG study.

The present experiment was designed to localize the neural substrates that process music-syntactic incongruities, using magnetoencephalography (MEG). Electrically, such processing has been proposed to be indicated by early right-anterior negativity (ERAN), which is elicited by harmonically inappropriate chords occurring within a major-minor tonal context. In the present experiment, such chords elicited an early effect, taken as the magnetic equivalent of the ERAN (termed mERAN). The source of mERAN activity was localized in Broca's area and its right-hemisphere homologue, areas involved in syntactic analysis during auditory language comprehension. We find that these areas are also responsible for an analysis of incoming harmonic sequences, indicating that these regions process syntactic information that is less language-specific than previously believed.

Localization of early syntactic processes in frontal and temporal cortical areas: a magnetoencephalographic study.

Previous electrophysiological studies had found an early anterior negativity often with a maximum over the left hemisphere to correlate with the early detection of an error in the syntactic structure of a sentence. In this paper, the cortical structures involved in such early syntactic parsing processes were localized using MEG. Subjects were presented with acoustic sentences and asked to judge their syntactic correctness. The subjects' brain responses to syntactic violations were recorded with a 148-channel whole-head magnetometer. Dipole source localization was performed using a realistically shaped standard volume conductor model with fMRI constraints. The results show that the early syntactic parsing processes are supported by temporal regions, possibly the planum polare, as well as by fronto-lateral regions. As indicated by the resultant dipole strengths, these regions are activated bilaterally with a dominance in the left hemisphere for four out of the five subjects. The contribution of the left temporal regions to the early syntactic processes seems to be larger than that of the left fronto-lateral regions.

Magnetic brain activity evoked and induced by visually presented words and nonverbal stimuli.

Evoked and induced magnetic brain activity measured over the left hemisphere were tested for their specificity to language-related processing. Induced activity refers to oscillatory alterations time locked but not phase locked to the stimulus. Words, false font stimuli, and two types of nonverbal patterns were presented visually while subjects performed a nonlinguistic visual feature detection task. The comparison of evoked and induced brain activity around 200 ms after stimulus onset revealed differential sensitivity to the stimuli. The M180 component of the evoked magnetic field was larger at the processing of words and false font stimuli compared with nonverbal stimuli. The induced magnetic brain activity in the 60-Hz band at a compatible latency range was correlated with the familiarity of the visual Gestalt. Sensitivity to language-specific information processing can be concluded if a parameter differentiates the word condition from the nonlexical conditions. Such a difference was observed at sensors located over the frontal-temporal scalp regions for induced but not evoked magnetic brain activity. Thus, evoked and induced magnetic brain activity revealed a differential sensitivity to elements of cognitive processing during the given task.

Noise affects auditory and linguistic processing differently: an MEG study.

We investigated the influence of noise on brain responses to spoken sentences in MEG. Sixteen subjects had to listen to acoustically presented sentences and judge their syntactic correctness. Sentences were either presented on a silent background or with noise. Noise had differential effects on early auditory and syntactic processes. While noise affected early auditory processes only in the right hemisphere, noise had a general effect on syntactical processes. The evoked responses to syntactic violations compared with correct sentences, namely an early left anterior negativity, were significantly suppressed when noise was present The noise suppression effect, however, was not lateralized.

Comparative study of the acute nephrotoxicity from standard dose cisplatin +/- ifosfamide and high-dose chemotherapy with carboplatin and ifosfamide.

The nephrotoxic effects of different platinum compounds based combination chemotherapies were compared. Chemotherapy consisted of either cisplatin fractionated over 5 days (5 x 20 mg/m2) or given as a single-day infusion (1 x 50 mg/m2) plus ifosfamide (4 g/m2) or high-dose chemotherapy was applied including carboplatin (3 x 500 mg/m2) and ifosfamide (3 x 4 g/m2) fractionated over three consecutive days. Conventional parameters such as serum creatinine and glomerular filtration rate (GFR), as well as urinary protein excretion of N-acetyl-beta-D-glucosaminidase (NAG)) and alpha 1-micro-globulin were assessed in 52 patients. Fractionation over 5 days without adding other nephrotoxic agents, i.e. ifosfamide, prevented decreases in GFR following cisplatin, whereas the combination of conventional dose cisplatin and ifosfamide, given as a single-day infusion, and high-dose carboplatin/ifosfamide yielded a pronounced fall of GFR. All groups showed increases in the urinary excretion levels of serum derived proteins and NAG, but with significant differences; about 2 to 3-fold for 5-days cisplatin, 3 to 5-fold for single-day cisplatin/ifosfamide, and 20 to 35-fold for high-dose chemotherapy. Thus, conventional approaches can reduce but not prevent the nephrotoxicity of cisplatin-based chemotherapy. In particular, high-dose chemotherapy regimens including carboplatin and ifosfamide are associated with comparable or even higher nephrotoxicity to single-day cisplatin/ifosfamide. In the light of the long-term consequences of persistent renal damage prevention of nephrotoxicity should be further improved.

Processing of syntactic information monitored by brain surface current density mapping based on MEG.

The cortical network subserving language processing is likely to exhibit a high spatial and temporal complexity. Studies using brain imaging methods, like fMRI or PET, succeeded in identifying a number of brain structures that seem to contribute to the processing of syntactic structures, while their dynamic interaction remains unclear due to the low temporal resolution of the methods. On the other hand, ERP studies have revealed a great deal of the temporal dimension of language processing without being able to provide more than very coarse information on the localisation of the underlying generators. MEG has a temporal resolution similar to EEG combined with a better spatial resolution. In this paper, Brain Surface Current Density (BSCD) mapping in a standard brain model was used to identify statistically significant differences between the activity of certain brain regions due to syntactically correct and incorrect auditory language input. The results show that the activity in the first 600 ms after violation onset is mainly concentrated in the temporal cortex and the adjacent frontal and parietal areas of both hemispheres. The statistical analysis reveals significantly different activity mainly in both frontal and temporal cortices. For longer latencies above 250 ms, the differential activity is more prominent in the right hemisphere. These findings confirm other recent results that suggest right hemisphere involvement in auditory language processing. One interpretation might be that right hemisphere regions play an important role in repair and re-analysis processes in order to free the specialised left hemisphere language areas for processing further input.

Magnetic field tomography analysis of continuous speech.

In this article we investigate MEG correlates of syntactic violations in continuous speech. An early left anterior negativity (ELAN) has been reported in previous EEG studies and has been related to syntactic processing. We used Magnetic Field Tomography (MFT) to extract a 3D estimate of the current density distribution J, from MEG data recorded while subjects listened to continuous speech. Separate estimates were obtained from the activity associated with the first word of the sentence, and the last words of the sentence which signified syntactic violation, semantic violation or correct sentences. In each case independent 3D MFT estimates of activity were obtained 2 ms apart. After converting the solutions into a PET-like format we perform a statistical analysis on a voxel-by-voxel basis. Visual inspection of the power of J at the time of the ELAN component and the statistical maps overlaid on the individual anatomical MRI suggests generators in the vicinity of the auditory cortex and in left frontal regions. Directional activation curves are computed to show the variation of activity as a function of time, from well circumscribed areas. The activation curve for the auditory cortex has a characteristic pattern consisting of three peaks, seen in the average time-locked to the onset of the first word, and the critical word of the syntactic violation. The left auditory cortex shows a delay of about 30 ms in the syntactic violation condition compared to the first word condition. No such delay is seen in the right auditory cortex.

A MEG analysis of the P300 in visual discrimination tasks.

Based on recent research that indicated that P300 scalp topography varies as a function of task and/or information to be processed, this study examined scalp-recorded magnetic fields correlated with the P300 by means of whole-head magnetoencephalography. Subjects performed two discrimination tasks, in which targets, defined on either object or spatial characteristics of the same visual stimuli, had to be discriminated. Based on the across-subject root mean square (RMS) functions a sequence of 4 components could be identified in both tasks, N1m, P3m, and two later components, which, based on their estimated neuronal sources, were classified as representing motor processes during and following the manual responses to target stimuli. Reliable between-task differences in source localization were obtained for the P3m component, but not for the other components. Inferior-medial sources were found for the P3m evoked by both spatial and object targets, with these sources being located about 3.5 cm more anterior for object targets. These results suggest that different neuronal sources, possibly located in subcortical regions in the vicinity of the thalamus, contribute to the P3m evoked by target stimuli defined by either object or spatial stimulus characteristics.

Oscillatory neuromagnetic activity induced by language and non-language stimuli.

Event-related oscillatory brain activity during language perception differs from activity occurring during the processing of comparable non-language stimuli. This fact became apparent in the observation of changes in the normalized spectral power of magnetoencephalographic (MEG) signals during the subject's processing of these stimuli. MEG was recorded over the left and right hemispheres of 12 right-handed subjects. During the experimental session, bisyllablic content words and physically similar non-language stimuli were presented with equal probability in a randomized order in either the visual or auditory modality. Approximately 15% of these stimuli were marked and the subject's task was to detect these marked stimuli. As a major characteristic of language vs. non-language processing, we obtained an enhancement of the normalized spectral power around 240 ins in the 60-65-Hz band over the left hemisphere for the language condition and over the right hemisphere for the non-language condition, independent of the modality of stimulus presentation. Starting at approximately the same latency but in lower-frequency bands (15-45-Hz), an extended (250-600 ms) reduction of normalized spectral power was observed. This reduction, although it generally confirmed previous results, differed in the no hemisphere-specific reduction was found for the processing of words. A domain-specific enhancement of normalized spectral power was also evident around 800-1200 ms in the 15-30-Hz band. In the auditory condition, this enhancement of the normalized spectral power was larger after the presentation of language stimuli whereas in the visual condition a larger enhancement of the normalized spectral power was obtained after presentation of non-language stimuli. As this latter effect appears relatively late after the stimulus onset and differs in expression for both modalities of stimulus presentation, a simple relationship between language perception and oscillatory brain dynamics can be excluded for this enhancement. In contrast, the left hemispheric enhancement of the normalized spectral power present around 240 ms in the 60-65-Hz band seems to reflect oscillatory pattern specific to the processing of words.

Species and strain differences in urinary protein excretion.

The physiological excretion of urinary protein is subject to great variation influenced not only by environmental and hormonal factors but also by genetics. The present study demonstrates that there is not only variation in respect to the excretion of plasma proteins but also of other types of proteins which are specific urinary proteins. There is a close relation between body weight and total protein excretion. However, male rats and mice do not fit the allometric line calculated for the other species studied. This is of special importance since these two species are often used in kidney research. The reason for this divergence in total protein is the excretion of sex-dependent low molecular weight proteins. The excretion of albumin, which is a marker of glomerular permeability and tubular reabsorption as well, shows a marked genetic variation between different rat strains. The data presented in this study demonstrate the general admissibility of transferring data from one species to the other but also the limitations in respect especially to the sex-dependent proteins which are excreted by some species.