Intra and intersubject variability in auditory steady-state response amplitude with high modulation rates to 1000 Hz amplitude modulated and tone pip stimuli

Abstract

Objective: This study set out to provide further information on how high modulation/stimulus rates affect the auditory steady-state response (ASSR) amplitude for a 1000-Hz tone, and how this effect varies between individuals. Both sinusoidal amplitude modulated tones and tone pip stimuli were investigated. Design: Modulation/stimulus rates were 70, 80, and 90 Hz and the peak to peak stimulus levels were matched for the two different types of stimuli, at 90.5 dBSPLppe. Study sample: The study was carried out on fourteen normally-hearing adults (9 males and 5 females) Results: Overall the ASSR amplitude to the two types of stimuli was similar. In general there was an increasing response amplitude between rates of 70 and 90 Hz; The relationship between the amplitude of the response and the modulation /stimulus rate varied considerably between subjects. Conclusions: Optimum stimulus rates based on group data may not give the best rate in a significant proportion of subjects. Currently tone pip ABR is the primary method used in assessing hearing in babies. Finding a way of avoiding suboptimal stimulus rates for ‘80-Hz’ ASSR in babies will improve the likelihood of ASSR being seen as an alternative.     

STATISTICAL INFERENCE FOR RELATIVE POTENCY IN BIVARIATE DOSE-RESPONSE ASSAYS WITH CORRELATED RESPONSES

ABSTRACT

The analysis of dose-response assays measuring two correlated responses is considered. Attention is given to statistical inference for the potency ratio. Results from a simulation study suggest that a post hoc adjustment for the correlation in parameter estimates obtained from univariate fits provides nearly as much power to detect differences in potency as a bivariate response model fit.     

GROUNDHOG DAY: CAUSE AND EFFECT AND THE PRIMARY IMPORTANCE OF THE FINITE POPULATION INDUCED BY RANDOMIZATION

The logical structure that enables randomized clinical trials to establish cause and effect is reviewed. Statisticians have a major role to define this structure clearly and to help clinicians apply statistical inference in ways directly related to their trials. Scientific importance of establishing limited cause and effect should be accented rather than inferences to generalized populations beyond the scope of a trial's actual random sampling. Authors of clinical reports should clearly define the randomization-induced populations to which their inferences apply. Careful attention to identifying this population of inference can lead to resolution of some issues commonly debated in the analysis of clinical trials. If formal inferences to generalized populations are attempted, these populations should also be carefully described, the assumed random sampling process should be carefully defined, and appropriate methods should be used that correspond with the assumed random sampling process.     

On-Line Computer Scoring of the Auditory Brainstem Response for Estimation of Hearing Threshold

Auditory brainstem responses (ABRs) to click stimuli have become established as a useful indicator of hearing thresholds in infants and young children. Although the investigation is objective in so far as the patient is concerned, a subjective element remains in the decision by the operator as to whether or not an ABR is present in an averaged waveform. A simple on-line computer detection technique is described which removes some of the reliance placed upon the operator. The technique employs a scanning window for correlation and amplitude analysis of pairs of averaged ABR waveforms.

The reliability and accuracy of computer and operator scoring of 25 thresholds in normally hearing adults and 50 thresholds in infants and young children with suspected hearing impairment have been investigated. In the adult group, 96% of computer estimates of the threshold were within ± 10 dB of the subjective hearing threshold, compared with 92% for operator scoring. There were 92% of computer and operator scores within ± 10 dB of each other. In the patient group there was equally good agreement between computer and operator scoring with 90% of the thresholds within ± 10 dB of each other; the incidence of possible false-positive thresholds was also lower with computer scoring.

This on-line scoring technique, therefore, offers useful assistance to the operator; requires only limited computing power, and is suitable for use in a routine clinical environment.     

Screening and appraisal for immunological adjuvant-active fractions from Platycodon grandiflorum total saponins

In this study, the total saponins from the root of Platycodon grandiflorum (PGS_t) was subjected to D101 macroreticular resin column chromatography to afford four fractions (PGS₃₀, PGS₅₀, PGS₇₅ and PGS₉₅). PGS_t and its four fractions were evaluated and compared for the haemolytic activities and adjuvant potentials on the specific cellular and humoral immune responses of ICR mice against recombinant hepatitis B surface antigen (HBsAg). PGS_t, PGS₃₀, PGS₅₀, PGS₇₅, and PGS₇₅ showed a slight haemolytic effect, with their concentration inducing 50% of the maximum haemolysis (HD₅₀) being 16.13?±?0.81, >200, 17.53?±?0.24, 20.16?±?0.76, 76.31?±?2.20?μg/mL against 0.5% rabbit red blood cell, respectively. PGS_t, PGS₅₀, and PGS₇₅ significantly not only enhanced the Con A-, lipopolysaccharide-, and HBsAg-induced splenocyte proliferation, but promoted the killing activities of natural killer (NK) cells from splenocytes in HBsAg-immunized mice (P?<?0.01 or P?<?0.001). HBsAg-specific IgG, IgG1, IgG2a, and IgG2b antibody levels in serum were also significantly enhanced by PGS_t, PGS₅₀, and PGS₇₅ compared with HBsAg control group (P?<?0.05, P?<?0.01, or P?<?0.001). Moreover, the adjuvant effects of PGS₅₀ and PGS₇₅ on the cellular immune responses and HBsAg-specific IgG2a and IgG2b antibody responses were more significant than those of Alum, PGS₃₀, and PGS₉₅. The results indicated that PGS₅₀ and PGS₇₅ could improve both cellular and humoral immune responses, and elicit a balanced Th1/Th2 response to HBsAg in mice, and that PGS₇₅ may be developed as an ideal candidate adjuvant for hepatitis B vaccine.     

Artefact Recognition And Diazepam In Electric Response Audiometry

In measurements near auditory threshold, the influence of nonstationary artifacts (movement, swallowing, muscle activity, etc.) leads to response-like averaged results which should be further evaluated before determining the objective threshold. It is pointed out that, especially in recording VIII-nerve compound action potentials, as well as cortical potentials near threshold, the difference-amplitude histogram is a helpful procedure for identifying real neural responses.

Diazepam-induced reducation of amplitude of the averaged result observed in a few adults with relative weak response amplitudes leads to the conclusion that this was caused by a further increase of latency variability. It is also mentioned that a complex interplay exists between the influence of diazepam upon amplitude and latency variability of the single response, which sometimes may result in a peculiar response of the average (e.g., increase of both may result in no change of the average).     

Proprioceptive neck influences modify the information about tilt direction coded by the cerebellar anterior vermis

Objective To verify whether the direction of head tilt coded by the population response of Purkinje (P) cells located in the cerebellar anterior vermis is modified by the relative position of the body with respect to the head.

Material and Methods In decerebrate cats, the responses of P cells to wobble of the whole animal were analyzed in order to compute the response vectors of the same cells to the labyrinthine input. These response vectors were used to evaluate the population response (vector) of all the recorded neurons to head tilt in specific directions.

Results When the head was aligned with the body, the direction of the population vector closely corresponded to that of head tilt. A 30° body-to-head rotation to the left or right around a C1–C2 vertical axis modified the response vectors of most of the recorded neurons, leading to reciprocal deviations of the population vector from the direction of head tilt of ≈30°.

Conclusion We propose that information from neck receptors regulates the convergence of labyrinthine signals with different spatial and temporal properties on corticocerebellar units, thus allowing the P-cell population to code the direction of body tilt.     

Elevated CD8 T cell responses in type 1 diabetes patients to a 13 amino acid coeliac‐active peptide from α‐gliadin

Some type 1 diabetes (T1D) patients have been reported to exhibit T cell reactivity to wheat gluten. We tested the hypothesis that this T cell reactivity could be abolished by using prolyl‐endopeptidase (PEP), an enzyme that cleaves peptide bonds after proline. Peripheral blood mononuclear cells (PBMCs) were isolated from T1D patients and healthy controls. PBMCs were stimulated with a peptic–tryptic digest of wheat gluten; a peptic–tryptic‐PEP digest of wheat gluten; and a 13 amino acid peptide from wheat gluten. Fluorescent‐labelled antibodies to CD3, CD4 and CD8 cell marker proteins were utilized to determine proliferative responses of CD3, CD4 and CD8 T cells. There were no significant differences in proliferative responses of CD3 or CD4 T cells to the wheat gluten antigens. A significantly higher proportion of CD8⁺ T cells from T1D patients proliferated in the presence of the 13 amino acid peptide than when challenged with the peptic–tryptic or the peptic–tryptic–PEP digests of wheat gluten. PEP treatment had no significant effect on CD8 T cell reactivity to the peptic–trytic digest of wheat gluten. Our results suggest that wheat gluten‐derived peptides, containing ≤ 13 amino acids, may evoke T cell responses in T1D patients.     

A time-frequency feature extraction scheme for the automated detection of binaural interaction in auditory brainstem responses

The binaural interaction component (BIC), the difference between the summed monaurally evoked potentials of each ear and the binaurally evoked brainstem potentials, has been shown to be related to directional hearing. However, the detection of the ß-peak as the most consistent part of the BIC is often difficult. Furthermore, there is no clearly defined signal feature characterizing the difference between the monaurally and the binaurally evoked brainstem responses. A closer look at the signals shows that amplitude differences as well as latency differences and variations in wave V slopes could be the reason for the formation of a ß-peak. Using a time-scale feature extraction scheme, we were able to define a signal feature (morphological local discriminant bases ( MLDB) coefficient 1) that accounts for the difference between the sum of the monaurally and binaurally evoked brainstem potentials. With use of this signal feature, reliable automated detection of differences between monaurally and binaurally evoked potentials is possible. As coefficient 1 replicates the behaviour of subjective measurements as well as of the BIC measurements, it can also be seen as a correlate of binaural interaction. With use of this signal feature, it is possible to judge from a given binaurally evoked potential whether it contains information on binaural interaction or not, without comparing it to the sum of the monaurally evoked brainstem responses. Consequently, binaural interaction can be assessed by one, instead of three, measurements by using the method described in this paper.     

Effects of Intensity Variations on Auditory Processing in Aphasia I. Equal Intensities at Each Ear

Clinical observations have led several authors to suggest that talking louder improves auditory comprehension for the aphasic patient, while others suggest that it does nothing to help comprehension. To clarify these observations under experimental conditions, four measures of auditory processing (cortical-evoked responses, nonverbal intensity sequencing, phoneme in word discrimination and sequencing, and a semantic-syntactic measure of comprehension) were used in diotic presentation of stimuli to 10 aphasic subjects with left temporal lobe damage. The stimuli were presented at 70, 85, and 100 dB SPL. Results suggest that a simple diotic (true binaural) increase of stimulus intensity is not a potent variable for influencing auditory processing in patients with aphasia. Although a few subjects improved their performances on selected levels when stimulus intensity was increased, the performances of others decreased. Auditory-evoked response (AER) latencies and amplitudes generally were not significantly different between the damaged and intact hemispheres. The time-intensity trading function was demonstrated with the AER, particularly for the N₂ component. The ear with the greatest advantage on dichotic listening was contralateral to the lesion and was contralateral to the hemisphere that had the shorter P₁ latencies, longer N₂ latencies, and smaller AER amplitudes.