Tonotopic organization of the sources of human auditory steady-state responses

Steady-state responses (SSRs) or steady-state fields (SSFs) show maximum amplitude when tone pulses are presented at repetition rates near 40 Hz. This result has led to the hypothesis that the SSR/SSF consists of superimposed transient 'middle latency' responses which display wave periods near 40 Hz and summate with one another when phase locked by 40 Hz steady-state stimulation. We evaluated this hypothesis by comparing the cortical sources of the 40 Hz auditory SSF with sources of the middle latency Pa wave which is prominent in electrical and magnetic recordings, and with the cortical sources of the familiar N1 wave, at different carrier frequencies between 250 and 4000 Hz. SSF sources determined for the different carrier frequencies were found to display a 'medial' tendency tonotopy resembling that of the N1m (sources for the higher frequencies represented more deeply within the supratemporal sulcus), opposite the 'lateral' tendency tonotopy of the middle latency Pam (sources for the higher frequencies situated more laterally). A medial SSF tonotopy was observed in each of the subjects investigated, including three subjects for whom Pam and N1m maps were also available. These findings suggest that the 40 Hz SSF may not consist of summated or entrained middle latency responses, as has previously been proposed. Alternative mechanisms for the SSR are discussed.     

Intrapulmonary steady-state concentrations of clarithromycin and azithromycin in healthy adult volunteers

The steady-state concentrations of clarithromycin and azithromycin in plasma were compared with concomitant concentrations in epithelial lining fluid (ELF) and alveolar macrophages (AM) obtained in intrapulmonary samples during bronchoscopy and bronchoalveolar lavage from 40 healthy, nonsmoking adult volunteers. Mean plasma clarithromycin, 14-(R)-hydroxyclarithromycin, and azithromycin concentrations were similar to those previously reported. Clarithromycin was extensively concentrated in ELF (range of mean +/- standard deviation concentrations, 34.4 +/- 29.3 microg/ml at 4 h to 4.6 +/- 3.7 microg/ml at 24 h) and AM (480 +/- 533 microg/ml at 4 h to 99 +/- 50 microg/ml at 24 h). The concentrations of azithromycin in ELF were 1.01 +/- 0.45 microg/ml at 4 h to 1.22 +/- 0.59 microg/ml at 24 h, and those in AM were 42.7 +/- 28.7 microg/ml at 4 h to 41.7 +/- 12.1 microg/ml at 24 h. The concentrations of 14-(R)-hydroxyclarithromycin in the AM ranged from 89.3 +/- 52.8 microg/ml at 4 h to 31.3 +/- 17.7 microg/ml at 24 h. During the period of 24 h after drug administration, azithromycin and clarithromycin achieved mean concentrations in ELF and AM higher than the concomitant concentrations in plasma.     

Frequency contribution to the click-evoked auditory brain-stem response in human adults and infants

The results of previous research reports have led some investigators to hypothesize that frequency contribution to the infant click-evoked auditory brain-stem response (ABR) is low-frequency dominated and derived primarily from the apical cochlea. This is in contrast to latency and morphology of the adult click-evoked ABR which reflects contributions from the basal cochlea. Recent research, however, has suggested that a simple low-frequency first model of development does not adequately describe the infant auditory brain-stem response. This experiment was conducted as a carefully controlled comparison of infant and adult click-evoked ABRs restricted to narrow frequency ranges with notched-noise masking. The primary objective of this experiment was to define frequency contribution to wave I and V click-evoked ABR latency and morphology in adults and 3-month-old infants. Results indicate that 3-month-old infants have adultlike latency shifts (re: unmasked latency) when the ABR is recorded in the presence of notched-noise masking with center frequencies ranging from 500-8000 Hz. With high-frequency centered notches, latency, and morphology change are similar to the unmasked response, while low-frequency centered notches induce an average latency shift of approximately 3.5 ms for wave I and V of both infant and adult subjects. These data suggest that by 3 months of age, in normal hearing infants, ABR latency and appearance are determined by high-frequency spectral components in the broadband click which activate the basal cochlea. The adultlike pattern of latency shift observed in the ABR of these infants suggests that relatively mature tonotopic organization is established by 3 months of age.     

Effect of organophosphorus compound intoxication on auditory brainstem response in mini pigs

Marketing analysis is a means of identifying consumer satisfaction, thus providing a means of exploiting weaknesses in competitors. As part of a graduate midwifery programme a small study was undertaken analysing marketing activities used by one competitor provider of maternity care services. The Marketing mix, Ansoff matrix and Gap analysis were the marketing tools used. Recommendations to midwifery service providers suggest using market research to identify consumer expectations and explore areas of both satisfaction and dissatisfaction.     

Effects of noise burst rise time and level on the human brainstem auditory evoked response

An experiment was conducted to examine the effects of noise burst rise time and level on the human BAER. Noise burst levels included 15, 30, 45 and 60 dB nHL, with linear rise times of 0, 0.5, 1.25 and 2.5 ms. With increasing noise burst level, there is a decrease in wave V latency and an increase in peak amplitude. With increasing noise burst rise time, there is an increase in wave V latency and a decrease in wave V amplitude. The slope of the latency/intensity function increases with increasing rise time. The slope of the latency/rise time function increases with decreasing noise burst level. The change in wave V latency associated with changing rise time is less than the change in rise time for all experimental conditions.     

Gender distinctions and lateral asymmetry in the low-level auditory brainstem response of the human neonate

Given the reported long-range cis-inactivating effect of the XIST gene in early embryonic development and the lack of requirement of X-chromosome-specific elements for propagating the inactive state, there exists the possibility of cis inactivation of autosomal material after de novo translocation to an inactive X chromosome (Xi) in differentiated cells. We have analyzed de novo radiation-induced translocations between the Xi and autosomes to study the maintenance and spreading of X-chromosome inactivation (X inactivation) in relation to the position of the X-inactivation center (XIC)/XIST in differentiated cells. Autosome/Xi translocations were detected by fluorescence in situ hybridization (FISH). The activation status of the chromosomes involved in the translocation was determined by simultaneous immunocytogenetic studies using antibodies against either BrdU incorporated at late S phase or acetylated histone H4. The position of XIC/XIST in the reciprocal products of the translocation was determined by XIST-specific FISH and computer enhancement. In other experiments, the Xq13 region carrying XIC/XIST was localized by computer enhancement of the DAPI banding pattern. Our study in differentiated cells provides a visual demonstration that physical separation from XIC/XIST does not result in reactivation of inactive X-chromosome material and that X inactivation is not spread to the translocated autosomes irrespective of the position of XIC/XIST. This observation suggests that physical linkage to XIC/XIST does not lead to de novo inactivation of autosomal material.     

Catnip and the alteration of human consciousness

Uncertainty exists regarding the ability of catnip (Nepeta cataria) to affect human consciousness. We report a case of a toddler exhibiting central nervous system depression after consuming a large quantity of catnip. His obtundation was not attributable to another cause. We review the published literature describing the alleged psychoactive capabilities of catnip and present our case as further information for use in this ongoing controversy.     

Low-level steady-state auditory evoked potentials: effects of rate and sedation on detectability

Steady-state auditory evoked potentials (SSAEPs) in alert adults are most detectable at stimulus or modulation rates of about 40 Hz. Sedation reduces the detectability of 40-Hz SSAEPs and increases it for higher rate SSAEPs. This study examined whether rates higher than 40 Hz would be preferable for detecting responses to low-intensity tones in sedated adults. Fourteen normal adults listened to 640-Hz tones at modulation rates (and toneburst rates) of 20-160 Hz, in 10-Hz steps, at levels of 38 and 58 dB peak equivalent sound-pressure level (peSPL) (20 and 40 dB normal hearing level (nHL) for amplitude-modulated (AM) tones), both alert and sedated (1-2 g chloral hydrate). Sedation reduced both signal (SSAEP) power and noise power at all rates, but noise power reduction was greater for higher rates. Detectability in the alert condition was always greatest at 40 Hz. Under sedation, a second detectability peak was present at 90 Hz for 58-dB peSPL tones, approximately equal to that seen at 40 Hz. At 38 dB peSPL (sedated), peak detectability moved from 40 to 50 Hz. These results suggest that presentation/modulation rates around 40 Hz may be optimal for SSAEP detectability at low levels in adults, whether alert or sedated.     

Effect of a subanesthetic minimum alveolar concentration of isoflurane on two tests of the hypoxic ventilatory response

BACKGROUND: These experiments were designed to study the effect of 0.1 minimum alveolar concentration isoflurane on the hypoxic ventilatory response as measured by two common methods of hypoxic testing: when normocapnic hypoxia was induced abruptly and when it was induced gradually. We hypothesized that any disparity in results would be due to an isoflurane effect that was manifested differently in the two tests. METHODS: After 20 min for uptake and equilibration of 0.1 minimum alveolar concentration end-tidal isoflurane or carrier gas in hyperoxia, isocapnic hypoxia was induced either abruptly over 60-80 s ("step" test) or gradually over 10 min ("ramp" test), followed by 20 min of isocapnic hypoxia at 45 mmHg end-tidal oxygen. Control of the hypoxic and isocapnic stimuli was accomplished accurately by a computer-controlled dynamic end-tidal forcing system. Eight subjects performed each test in the presence and absence of isoflurane. RESULTS: For both step tests and ramp tests, 0.1 minimum alveolar concentration isoflurane had no effect on minute ventilation during the defined periods of hypoxia. With isoflurane, delta VE45, the acute change in ventilation from hyperoxia to hypoxia, was 97 +/- 20% (mean +/- SEM) of the control response for step tests and 100 +/- 25% of the control response for ramp tests. The step tests produced significantly larger acute hypoxic responses than did the ramp tests, but by the end of 20 min of hypoxia, ventilation was similar for both tests. CONCLUSIONS: Neither method of hypoxic testing demonstrated the level of isoflurane effect reported by others. A comparison of the two methods of hypoxic testing suggests that ramp tests, as commonly performed, do not allow adequate time for full expression of the acute hypoxic ventilatory response. Step tests also better separated the opposing hypoxic effects of carotid body stimulation and central ventilatory depression.     

Measurements of the temporal fMRI response of the human auditory cortex to trains of tones

Averaged single trials (AST) allowed the functional magnetic resonance imaging (fMRI) response to auditory stimuli to be measured at high temporal (1 s) and spatial (0.1 cm3) resolution. Using this paradigm we investigated the transient signal response to 100-ms tone bursts in trains of between 100 ms and 25.5 s in total duration. We have demonstrated that the fMRI response to such auditory stimuli is approximately linear for trains of 6 s and longer, but that shorter stimuli produce signals that are larger than might be expected from the response to the longer stimuli. This nonlinear behavior can be modeled if an adaptive response to each stimulus is assumed. A study using a novel paradigm was also performed in order to study the influence of scanner noise during fMRI experiments on the auditory system response to tones. This study demonstrated that the temporal response to 700-ms tone stimuli is modified when performed in the presence of scanner gradient noise, the modification being a small but significant increase (P < 0.05) in the magnitude of the response. Finally the ability to measure the onset of functional activation using the AST method was examined. It was found, with the aid of computer simulation that a sampling rate of one image per second is adequate to distinguish temporal responses. Using the data acquired in this study, onset times were calculated for the auditory cortex, and these results are consistent with current models of functional activation.     

Effect of isoflurane and sevoflurane on evoked potentials and EEG

Evoked potentials and EEG are used to monitor the central nervous system and the depth of anesthesia in anesthetized patients. In this study, we examined EEG, VEP, SEP and ABR at various concentrations of isoflurane or sevoflurane, and evaluated the influence of volatile agents and their usefulness for the monitoring of the depth of anesthesia. With increasing concentrations of isoflurane and sevoflurane, AE (frequency which account for 80% of total voltage) showed dose-related reduction and EEG showed a trend toward a slower wave and higher amplitude. With increasing concentrations of isoflurane and sevoflurane, P100 of VEP showed a significant dose-related reduction in its amplitude and increase in its latency. So we could not record P100 at the level of the anesthesia of 1.0 MAC with 66% N2O. N20 of SEP can be easily recorded at any depth of anesthesia. And the trend showed consistent dose-related changes in amplitude and latency. With increasing concentrations of isoflurane and sevoflurane, wave III and V of ABR increased significantly in latency, but the changes were very small. In conclusion, the effect of isoflurane and that of sevoflurane on evoked potentials and EEG are similar with each other and with other volatile agents. SEP is the most consistent and reliable factor to monitor the depth of anesthesia neurophysiologically.     

Effects of insulin and hypoglycemia on the auditory brain stem response in humans

1. This study aimed to differentiate effects of insulin and hypoglycemia on sensory brain stem functions in humans. Auditory brain stem responses (ABR) were examined in 30 healthy men during euglycemia and after 20 and 50 min of steady-state hypoglycemia of 2.6 mM induced with human insulin (HI) in one session and porcine insulin (PI) in another session. 2. Levels of blood glucose and serum insulin were identical in both sessions during HI and PI infusion. 3. Hypoglycemia increased interpeak latencies III-V (+71 microseconds; P < 0.001) and I-V (+123 microseconds; P < 0.001), whereas changes in the latency of wave I were not significant. 4. After 20 min of constant hypoglycemia, increases in the interpeak latencies I-V and III-V were significantly more pronounced during infusion of PI than HI. These differences disappeared with time spent in hypoglycemia, i.e., after 50 min of hypoglycemia. 5. Apart from the delaying effect of hypoglycemia on neuronal transmission within the sensory brain stem, the results provide evidence for a separate influence of insulin on these functions.     

Inhibition of neutrophil apoptosis and modulation of the inflammatory response by granulocyte colony-stimulating factor in healthy and ethanol-treated human volunteers

Nitrogen dioxide levels were measured in 80 homes in the Latrobe Valley, Victoria, Australia, using passive samplers. Some 148 children between 7 and 14 yr of age were recruited as study participants, 53 of whom had asthma. Health outcomes for the children were studied using a respiratory questionnaire, skin prick tests, and peak flow measurements. Nitrogen dioxide concentrations were low, with an indoor median of 11.6 microgram/m3 (6.0 ppb), and a maximum of 246 microgram/m3 (128 ppb). Respiratory symptoms were more common in children exposed to a gas stove (odds ratio 2.3 [95% CI 1. 0-5.2], adjusted for parental allergy, parental asthma, and sex). Nitrogen dioxide exposure was a marginal risk factor for respiratory symptoms, with a dose-response association present (p = 0.09). Gas stove exposure was a significant risk factor for respiratory symptoms even after adjusting for nitrogen dioxide levels (odds ratio 2.2 [1.0-4.8]), suggesting an additional risk apart from the average nitrogen dioxide exposure associated with gas stove use. Atopic children tended to have a greater risk of respiratory symptoms compared with nonatopic children with exposure to gas stoves or nitrogen dioxide, but the difference was not significant.     

Neurotological auditory brain stem response findings in human immunodeficiency virus-positive patients without neurologic manifestations

Neurologic manifestations of human immunodeficiency virus (HIV) infection, rather than being a late complication of the disease, are principally correlated with the early central nervous system (CNS) localization of HIV. The CNS may be infected in the early stages of acquired immunodeficiency syndrome (AIDS) without evidence of neurologic disorders. Evoked potentials (visual, auditory, and somatosensory) and electronystagmographic test batteries have proven to be very sensitive in showing subclinical CNS disorders due to HIV. In this study, auditory brain stem response (ABR) and electronystagmographic test battery findings (smooth pursuit, saccades, caloric test) were performed in 29 neurologically asymptomatic, HIV-positive subjects at different stages of the disease. Compared to results of a control group, the ABR latencies of waves V, I, and III and interpeaks I-V and III-V were significantly increased in HIV patients. The same parameters did not differ significantly among the stages of the disease. In HIV-positive subjects, the accuracy of saccades was significantly reduced, while latency was normal. The velocity and the gain of pursuit were significantly reduced in HIV-positive patients, and 15 of 29 patients showed corrective saccades. Caloric tests revealed qualitative nystagmus abnormalities in 82% of HIV patients, while quantitative parameters were normal. The present results confirm that CNS involvement by HIV occurs early in the course of the disease. In particular, HIV does not seem to affect the labyrinth or the eighth cranial nerve, as demonstrated by the normality of the I-III value of the ABR and of the quantitative parameters of the caloric responses, but it does appear to involve the brain stem acoustic pathways, pontocerebellar pathways, and supratentorial areas.     

The automated prediction of hearing thresholds in sleeping subjects using auditory steady-state evoked potentials

OBJECTIVE: To examine the relationship between auditory steady-state evoked potentials (SSEPs) and behavioral thresholds in sleeping subjects. DESIGN: 60 adults and children with hearing thresholds ranging from normal to profound were selected on the basis of appropriate audiograms. Behavioral audiograms were determined at the octave frequencies 250-4000 Hz. These behavioral thresholds were then compared with the SSEP thresholds obtained during natural sleep for adults, or natural or sedated sleep for children. RESULTS: A strong relationship between behavioral and SSEP thresholds was observed. The strength of the relationship increased with increasing frequency and increasing degree of the loss. On the basis of these data, the prediction of behavioral thresholds from SSEP levels was determined. It was found that the standard deviation of the error in this prediction decreased with increasing frequency and increasing degree of the loss. There was no significant age effect in the results obtained at any of the frequencies. CONCLUSION: The results suggest the SSEP technique can be used as a predictor of behavioral threshold in adults and children at the frequencies 250-4000 Hz.     

The role of synaptic junctions in the identification of human consciousness

BACKGROUND: Elevated serum lipoprotein(a) [Lp(a)] levels are associated with the development of native coronary atherosclerosis. The association between increased levels of Lp(a) and the development of accelerated cardiac allograft vasculopathy (ACAV) in patients who have undergone orthotopic heart transplantation has not been firmly established. METHODS AND RESULTS: We studied 74 consecutive heart transplant recipients with at least 1 year survival to determine the relation between Lp(a) and the presence of ACAV. Recipient and donor clinical and laboratory parameters, including mean serum Lp(a) levels, were obtained. ACAV was defined angiographically as > or =30% stenosis in one or more epicardial arteries. ACAV 1 year after heart transplantation was angiographically present in 26 (35%) patients. Mean donor age (36 +/- 13 years [ACAV (+)] vs 28 +/- 10 years, [ACAV (-)]; p = 0.004) and mean serum triglyceride levels 6 months after transplantation (286 +/- 275 mg/dl [ACAV (+)] vs 169 +/- 85 mg/dl [ACAV (-)]; p = 0.025) were univariate predictors of ACAV. No significant difference in mean serum Lp(a) levels was observed (20 +/- 19 mg/dl [ACAV (+)] vs 30 +/- 30 mg/dl [ACAV (-)]; p = NS). Donor age was the single greatest independent predictor of ACAV by multivariate logistic regression (p = 0.02). CONCLUSIONS: Lp(a) does not appear to be a risk factor for the development of ACAV 1 year after heart transplantation. Further studies are needed to define the influence of serum Lp(a) on the development of cardiovascular disease after orthotopic heart transplantation.     

Effects of acute brainstem compression on auditory brainstem response in the guinea pig

BACKGROUND: The purpose of this study was to establish the norm for parameters of auditory brainstem response (ABR) in the guinea pig and to investigate if acute brainstem compression results in significant changes to these parameters. METHODS: Thirty-six guinea pigs with positive Preyer's reflex were anesthetized. A craniectomy was performed to remove the right occipital bone and the dura mater was opened to expose the brain, cerebellum and cerebellopontine angle (CPA). A small inflatable balloon was placed into the CPA precisely and slowly. ABR was recorded before incision of the skin as a baseline value, after placement and after inflation of the balloon with water at 0.1-ml intervals. RESULTS: Five stable peaks were recorded in 27 experimental animals. When the balloon was inflated with 0.1 ml water, the absolute latency (AL) of peaks IV and V and the interpeak latency (IPL) of peaks III and IV, and IV and V were prolonged. The amplitude ratios (AR) of peaks II, III, IV and V to peak I decreased. Inflation of the balloon with 0.2 ml of water caused further elongation of ALs of peaks IV and V and decreases in each AR. When the balloon volume increased to 0.3 ml, peak V became unrecognizable and peaks III and IV showed significant elongation of AL; peaks I and II did not show significant change in ALs. Further increase of the balloon volume to 0.4 ml resulted in disappearance of peaks III, IV and V; AL of peak II was also elongated. However, the amplitude and AL of peak I remained unchanged. Similar changes were observed in IPLs. CONCLUSIONS: This study establishes the norm of parameters of ABR in guinea pigs and demonstrates that acute brainstem compression causes elongation of ALs and IPLs of peaks II, III, IV and V. This suggests that peaks II, III, IV and V come from the brainstem and that peak I is not generated from the brainstem in the guinea pig.     

Effect of terbinafine on theophylline pharmacokinetics in healthy volunteers

Twelve healthy volunteers were enrolled in an open-label, randomized, crossover study. Subjects received single doses of theophylline (5 mg/kg) with and without multiple-dose terbinafine, and 11 blood samples were collected over 24 h. The study phases were separated by a 4-week washout period. Theophylline serum data were modeled via noncompartmental analysis. When the control phase (i.e., no terbinafine) was compared to the treatment phase (terbinafine), theophylline exposure (the area under the serum concentration-time curve from time zero to infinity) increased by 16% (P = 0.03), oral clearance decreased by 14% (P = 0.04), and half-life increased by 24% (P = 0.002). No significant changes in other theophylline pharmacokinetic parameters were evident.