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Biomedical subjects

W Ritter

Publications and source records attributed to W Ritter.

At least 19 recordsLinked to original sources

Endogenous event-related potentials as indices of dementia in multiple sclerosis patients.

Auditory event-related potentials (ERPs) were recorded in a "double oddball" paradigm requiring an easy and a hard pitch discrimination from multiple sclerosis (MS) patients with and without dementia, and a group of age and sex matched normal subjects. Cognitive function was assessed by a short battery of neuropsychologic (NP) tests, and the two groups of MS patients were selected on the basis of substantial non-overlapping degrees of cognitive deficit in the demented as compared to the non-demented group. The N100, P200 and P300 ERP components were longer in latency in the demented patients, and the N100-P300 interval was prolonged as well, compared to the non-demented patients, whose ERP latencies did not differ from those of the normal subjects. Increased P300 latency was associated with poorer performance on the NP tests, especially those sensitive to impairment of learning and retrieval from memory. The reaction times of both patient groups were prolonged as compared to the controls, whereas the accuracy of the demented patients was significantly poorer than that of the non-demented patients.

Adult

Event-related potentials to repetition and change of auditory stimuli.

The major intent of this study was to compare the role of stimulus repetition and change in the elicitation of the MMN, an ERP component specific to stimulus change, and N2b, usually partially overlapping the MMN when stimuli are attended. Event-related potentials were recorded in one set of conditions where subjects ignored the stimuli and read a book, and in another set of conditions where subjects counted stimuli designated as targets. Stimuli were delivered in 4 ways, the common feature between all these conditions being the occurrence of infrequent events at a probability of 0.20: (1) an oddball paradigm with 1 deviant, (2) an oddball paradigm with 2 deviants, each with a probability of 0.10, (3) a regular alternation of tones of 2 pitches where either of the 2 tones infrequently repeated (P = 0.20), and (4) a random presentation of tones of 5 different pitches, where any of the 5 tones infrequently repeated (P = 0.20). In the count conditions, the infrequent events were designated as targets. It was found that the MMN was elicited by stimulus change and not stimulus repetition in the ignore and count conditions, whereas the N2b was elicited by both stimulus changes and repetitions in the count conditions. It was also possible, in the count conditions, to disentangle the part of the late positive complex which is related to stimulus deviation and the part which is related to stimulus significance (target).

Acoustic Stimulation

Mismatch detection and the latency of temporal judgements.

Event-related potentials were recorded in two auditory tasks involving the discrimination of pitch or duration of binaurally presented tones. Frequently-presented nontarget tones, when compared to the same tones in a simple reaction time task, elicited two negative peaks, NA1 and NA2, followed by a positive peak, nontarget positivity. Infrequently-presented target tones, when compared to the nontargets, elicited mismatch negativity (MMN), followed by N2 and P3b. The peak latencies of NA1 and NA2 did not differ between the pitch and duration tasks, but the duration of NA1 and the peak latencies of mismatch negativity, N2, and P3b, as well as reaction time, increased in parallel for the duration task. It is proposed that the NA1-nontarget positivity sequence reflects the initiation, maintenance, and termination of an attention-modulated process, which is required for the performance of an auditory discrimination task, and that the MMN-N2-P3b sequence reflects a process elicited by infrequently-presented targets, which is the main determinant of reaction time under these testing conditions.

Adult

The chronometry of attention-modulated processing and automatic mismatch detection.

Event-related potentials were recorded from normal subjects in an auditory selective attention task. Targets were rare longer (170-ms) tones of a designated pitch, embedded in a sequence of 100-ms standard tones. The effects of attention-modulated processing were evident in the event-related potentials elicited by the standards. Those to relevant standards were similar for easy (1000 Hz vs. 2000 Hz) and hard (1000 Hz vs. 1030 Hz) pitch separations, and were more negative frontocentrally than those to irrelevant standards. Difference waveforms (attended minus unattended standards) revealed Nd, a negative deflection that was earlier in latency for the easy task (onset, 120 ms; peak, 250 ms) than for the hard task (onset, 250 ms; peak, 350 ms). The speed of detection of the deviant longer tones was insensitive to the attention-modulated processes indexed by Nd. Median reaction time did not differ between tasks, although there were more misses and false alarms in the hard task (and nearly all of the latter were to the irrelevant longer tones). Neither direction of attention nor task difficulty affected the latency of mismatch negativity, N2, or P3 (as identified in difference waveforms: attended or unattended longer tones minus their respective standards). The data suggest that performance was guided by two independent but converging processes, automatic mismatch detection of the longer tone and attention-modulated processing of pitch, followed by selection of response.

Adult

A developmental event-related potential study of picture matching in children, adolescents, and young adults: a replication and extension.

Event-related potentials were recorded in a developmental study of picture matching using an adaptation of Posner's (1978) letter-matching tasks. Subjects ranging in age from 6-39 were asked to decide whether two line drawings, presented sequentially, were the same or different on the basis of physical (physical identity), nominal (name identity), or categorical (category identity) criteria. The amplitude of a negativity at 400 ms (Neg400) increased as the number of dimensions on which the two line drawings differed increased. This effect held for all age groups, and was interpreted as reflecting the degree of semantic and/or physical relationship between the two pictures. However, one finding for Neg400 did suggest a qualitative difference in processing mode between the younger and older subjects. Both Neg400 and P3b latencies showed highly significant linear age trends, decreasing with increasing age. These age-related changes were interpreted as demonstrating quantitative speed of processing differences among age groups. The latencies of both Neg400 and P3b increased as the matching criteria became more complex. Moreover, P3b latency increased as the number of dimensions on which the two pictures differed increased, and this did not interact with age. Although both Neg400 and P3b showed age-related changes in scalp distribution, the fact that each was related to the experimental variables in similar fashion in all age groups suggested that they were homologous components across the age range studied. Taken as a whole, the data support continuity of information processing during these tasks across a wide age range.

Adolescent

A brain event related to the making of a sensory discrimination.

Event-related potentials associated with detected targets in a vigilance task were analyzed in two ways: (i) by sorting the potentials in terms of sequential reaction time bins of 50 milliseconds and (ii) by examining the single trial waveforms. A negative component (N2) covaried in latency with reaction time. These results support the hypothesis that N2 reflects a decision process which controls behavioral responses in sensory discrimination tasks.

Behavior

Efficacy of propranolol in the control of exercise-induced or augmented ventricular ectopic activity.

The effect of propranolol on exercise-induced or augmented ventricular ectopy was studied in sixteen male patients, six of whom had documented coronary artery disease. Fifteen patients were exercised after two weeks of oral therapy, fourteen after single oral therapy and eight patients after intravenous therapy. Propranolol dosage was titrated to produce maximal beta-adrenergic blockade. Effective reduction of exercise-induced ventricular ectopy occurred in ten of fifteen patients (P less than 0.001), and in five of six patients with coronary disease (P less than 0.02). Propranolol therapy abolished ventricular couplets in eight of twelve patients and ventricular tachycardia in four of the patients. Single oral and intravenous therapy had similar or greater effects. Plasma propranolol levels following different routes of administration did not correlate with exercise-induced maximal heart rates or percent reduction in ventricular ectopy. When compared to exercise in eleven patients, ambulatory monitoring underestimated the severity, particularly the highest grades, of ventricular ectopy.

Adult

Comparison of the pharmacodynamic effects of furosemide and BAY g 2821 and correlation of the pharmacodynamics and pharmacokinetics of BAY g 2821 (muzolimine).

In a biometrically planned, double-blind study on 12 Oedema-free male patients the saluretic effect of muzolimine 30 mg was compared with furosemide 40 mg. The plasma level of muzolimine was determined and correlated with its pharmacodynamics. In terms of excretion during the 12-hour observation period muzolimine 30 mg had as great a cumulative effect as furosemide 40 mg. There was a significant difference in the time-response curve. During the first gwo hours furosemide 40 mg had more saluretic effect than muzolimine 30 mg. Between two and four hours there was no significant difference between the two substances. Between four and six hours, however, muzolimine was somewhat more effective than furosemide, although the difference did not reach the level of significance. After 6 h there was no longer any difference between the two compounds. The half-life of the fall in concentration of muzolimine in plasma was 3.7 up to 10 h after its administration. The time-response curve of the increased urine excretion correlated well with the time course of the concentration of muzolimine in plasma.

Adult

Thin-layer densitometric determination of muzolimine (BAY g 2821), a structurally new diuretic drug, at the nanogram level in biological fluids.

A sensitive and specific thin-layer densitometric method was developed for the determination of muzolimine (BAY g 2821), a structurally new diuretic drug of the pyrazolinone type. For detection of the drug on thin-layer chromatographic plates, a colour reaction with 4-dimethylaminocinnamaldehyde is carried out. The detection limit was 50 pg per spot on commercially available silica gel 60 plates. A nearly linear relationship between integrated peak area and amount per spot was obtained in the range from 100 pg to 1 mug per spot. For quantitative determination in biological fluids, a recovery of about 100% is achieved by a single extraction with dichloromethane, and the extract is spotted directly on to the plate. The detection limit of muzolimine in plasma and urine was 1 ng/ml, and inaccuracy in the nanogram range was found to be 5-8%. The assay was applied to pharmacokinetic studies and can be recommended for monitoring plasma levels of muzolimine in patients.

Chromatography, Thin Layer

The scalp topography of potentials in auditory and visual discrimination tasks.

Averaged event-related cortical potentials (ERPs) were obtained from an array of scalp electrodes overlying the left hemicranium in response to regularly presented visual or auditory stimuli (non-signals)and to infrequent random replacements by different stimuli (signals) in the same modality. A motor response was required to the signals. Non-signal ERPs were subtracted from signal ERPs and the topographic distributions of the negative (N2 delta) and positive (P3 delta) components were plotted as isopotential maps. N2 delta distributions differed for the auditory and visual modalities, whereas P3delta was modality unspecific. These topographic data were compared to those from the previous study of missing stimulus potentials (Simson et al. 1976) using maps representing the contributions from unilateral cerebral sources. The N2 delta and negative missing stimulus potential distributions ascribed to cortical activity within the secondary auditory and visual regions, whereas the late positive component (positive missing stimulus potential or P3 delta) were considered to derive principally from inferior parietal association cortex.

Adult

Pharmacokinetics of Bay g 2821 in the dog and in man.

The pharmacokinetics of Bay g 2821, a new diuretic agent, were studied in dogs, healthy volunteers and in patients with renal insufficiency. The drug was rapidly absorbed after oral administration, peak plasma levels (approx. 0.4 microgram/ml) occurring within 1 hour. Elimination of the unchanged drug from plasma was biphasic - an initial rapid decline with a half-life of about 3 hours, followed by a longer second phase with a half-life of 13 to 17 hours. Results were similar in healthy volunteers and in patients with renal insufficiency. It is assumed that the drug is mainly eliminated in bile, probably after biotransformation, and elimination in the urine is a minor pathway.

Animals

The scalp topography of potentials associated with missing visual or auditory stimuli.

Averaged potentials time-locked to regularly presented visual and auditory stimuli and to the occasional random deletion of a stimulus were recorded from a scalp electrode array overlying the left hemicranium. The major components of visual and auditory evoked potentials and of the potentials associated with missing stimuli (MSP) were measured and their amplitude distributions depicted in the form of isopotential maps. The N1 components of the VEP and AEP had distributions compatible with sources in and near the respective primary cortical projection areas. The P2 components were more widely distributed and could be attributed in part to generators within modality specific association areas. The MSP comprised two main components, an initial negativity (NMSP) and a later positive wave (PMSP). The NMSP distributions were different in the visual and auditory modalities, and were similar to the respective EP topographies. The NMSP appeared to reflect a more powerful contribution of association areas than did the evoked responses. The PMSP topography was modality unspecific with distributions which were maximal over the parietal region. The possible functional significance of the NMSP and PMSP was considered in the light of their timing and topography.

Adult

On the independence of the CNV and the P300 components of the human averaged evoked potential.

We report an experiment designed to assess the interactions between the CNV and the P300 components of human event-related potential. Eight subjects were each presented with series of experimental trials on all of which either a 1200 c/sec or an 800 c/sec tone was presented. There were three independent variables: (a) The presence or absence of a warning flash 1000 msec prior to the tone. (b) The task assigned to the subject--that is subjects were either to make a discriminative response to the tone or, on half the series, to predict prior to the tiral which of the two tones would be presented. (c) The predictability of the tone frequency. On half the series high and low tones alternated from trial to trial. On the other series, tones were chosen randomly on each trial. The data show that the amplitude of the P300 component is not affected by the presence or absence of a warning stimulus. Furthermore, the distributions of P300 and the CNV over the scalp are quite different. These conclusions are supported by a principal component and a discriminant analysis of the data. We conclude that the CNV and the P300 reflect the activity of functionally distinct cortical mechanisms.

Analysis of Variance

Cortical evoked potentials elicited by real speech words and human sounds.

Averaged evoked potentials were recorded from PZ and left and right temporo-parietal electodes to real speech words and human sounds in 8 right-handed subjects. Stimuli were presented in a "no task" condition where the subject was instructed to listen attentively, and a vigilance condition where the subject responded to a particular word or sound during a run of such stimuli. The vigilance condition produced two classes of stimuli:signals and non-signals. Evoked potentials to physically identical words or sounds were examined when they were "no task", non-signal and signal stimuli. P300 amplitude increased significantly as a function of increasing task demands going from "no task" to non-signal to signal. When a strict statistical criterion for multiple comparisons (Bonferroni test) was applied in looking for asymmetries between hemispheres, only 2 isolated left greater than right differences turned out to be significant. Review of the literature concerning evoked potential correlates of differential hemispheric processing pointed up flaws in design, statistical technique, and inconsistencies in reported findings which suggested that while evoked potentials may sometimes reflect differences in hemispheric functioning, this effect is marginal at best.

Adult

The late positive component (P300) and information processing in sentences.

Averaged visual evoked potentials to sequentially flashed words comprising a sentence were recorded from vertex and left and right temporoparietal electrodes in 8 right-handed subjects. In condition 1 the sentence took the form: The -eel is on the shoe, in which the first grapheme was omitted from the second word, so that the subject did not know the meaning of the second word until he viewed the last word. In condition 2, the sentence took the form: The heel is on the shoe, in which the second word was given and the last word provided no further information. P300 latency to words which delivered information (last word of condition 1, second word of condition 2) were significantly longer than P300 latency to any of the other words in the sentence, as well as to the same position word in the other condition. Comparisons of P300 latencies to redundant words (the, is, on) within and between conditions showed no significant differences. P300 amplitude to the last word was significantly larger than P300 amplitude to any of the other words within the sentence, even in condition 2 where the second word delivered information. The major effect of information delivery was on P300 latency, while "syntactic closure" had its major effect on P300 amplitude. The fact that evoked potentials to all words had P300 components was attributed to the engagement of the P300 system whenever task-related language stimuli are used.

Adolescent