Biomedical subjects

M Don

Publications and source records attributed to M Don.

At least 19 recordsLinked to original sources

PubMed2006

Alpha- and beta-secretase activity as a function of age and beta-amyloid in Down syndrome and normal brain.

Aged individuals with Down syndrome (DS) develop Alzheimer's disease (AD) neuropathology by the age of 40 years. The purpose of the current study was to measure age-associated changes in APP processing in 36 individuals with DS (5 months-69 years) and in 26 controls (5 months-100 years). Alpha-secretase significantly decreased with age in DS, particularly in cases over the age of 40 years and was stable in controls. The levels of C-terminal fragments of APP reflecting alpha-secretase processing (CTF-alpha) decreased with age in both groups. In both groups, there was significant increase in beta-secretase activity with age. CTF-beta remained constant with age in controls suggesting compensatory increases in turnover/clearance mechanisms. In DS, young individuals had the lowest CTF-beta levels that may reflect rapid conversion of beta-amyloid (Abeta) to soluble pools or efficient CTF-beta clearance mechanisms. Treatments to slow or prevent AD in the general population targeting secretase activity may be more efficacious in adults with DS if combined with approaches that enhance Abeta degradation and clearance.

Adolescent↗

PubMed2005

Nasal NO: normal values in children age 6 through to 17 years.

The present study is an assessment of normal values of nasal nitric oxide (nNO) in healthy children. Healthy children aged between 6-17 yrs were recruited from three schools in Rotterdam (The Netherlands). Breath was held for 10 s, while air was extracted from one nostril at 700 mL.min(-1). The mean nNO value at the response plateau after 7-10 s was recorded and the average of three measurements was used. In total, 340 children participated; the male:female ratio was 156:184. Three reliable measurements were available in 85% of the children. The nNO concentrations were distributed normally (mean 449 ppb, SD 115). They were not associated with sex, passive smoking or body mass index. In children aged <12 yrs nNO correlated positively with age, history of adenoidectomy and ambient NO. In children aged > or =12 yrs ambient NO was the only significant modifier. Prediction rules for nNO values in children were formulated. In conclusion, the current study presents normal values for nasal nitric oxide in children, which can be used to assess the value of nasal nitric oxide in respiratory illnesses.

Adolescent↗

PubMed2002

[Candida pneumonia in patients without definitive immunodeficiency].

The occurrence of community-acquired pneumonia due to yeast-like fungi of the genus Candida in patients without manifest immunodeficiency has previously been discounted. However, such pneumonias may indeed occur in patients with chronic parenchymal lung damage, e.g. from nicotine. Candida pneumonia can be triggered in these patients for example by trivial viral infections. Three corresponding cases are discussed.

Adult↗

PubMed2001

Plasticity in the adult human central auditory system: evidence from late-onset profound unilateral deafness.

Experience-related changes in central nervous system (CNS) activity have been observed in the adult brain of many mammalian species, including humans. In humans, late-onset profound unilateral deafness creates an opportunity to study plasticity in the adult CNS consequent to monaural auditory deprivation. CNS activity was assessed by measuring long-latency auditory evoked potentials (AEPs) recorded from teens and adults with late-onset (post-childhood) profound unilateral deafness. Compared to monaurally stimulated normal-hearing subjects, the AEPs recorded from central electrode sites located over auditory cortical areas showed significant increases in inter-hemispheric waveform cross-correlation coefficients, and in inter-hemispheric AEP peak amplitude correlations. These increases provide evidence of substantial changes from the normal pattern of asymmetrical (contralateral > ipsilateral amplitude) and asynchronous (contralateral earlier than ipsilateral) central auditory system activation in the normal-hearing population to a much more symmetrical and synchronous activation in the unilaterally deaf. These cross-sectional analyses of AEP data recorded from the unilaterally deaf also suggest that the changes in cortical activity occur gradually and continue for at least 2 years after the onset of hearing loss. Analyses of peak amplitude correlations suggest that the increased inter-hemispheric symmetry may be a consequence of changes in the generators producing the N (approximately 100 ms peak latency) potential. These experience-related changes in central auditory system activity following late-onset profound unilateral deafness thus provide evidence of the presence and the time course of auditory system plasticity in the adult brain.

Adolescent↗

PubMed2000

Maturation of human central auditory system activity: evidence from multi-channel evoked potentials.

OBJECTIVE: The purpose of this study was to evaluate central auditory system maturation based on detailed data from multi-electrode recordings of long-latency auditory evoked potentials (AEPs). METHODS: AEPs were measured at 30 scalp-electrode locations from 118 subjects between 5 and 20 years of age. Analyses focused on age-related latency and amplitude changes in the P1, N1b, P2, and N2 peaks of the AEPs generated by a brief train of clicks presented to the left ear. RESULTS: Substantial and unexpected changes that extend well into adolescence were found for both the amplitude and latency of the AEP components. While the maturational changes in latency followed a pattern of gradual change, amplitude changes tended to be more abrupt and step-like. Age-related latency decreases were largest for the P1 and N1b peaks. In contrast, P2 latency did not change significantly and the N2 peak increased in latency as a function of age. Abrupt changes in P1, P1-N1b, and N2 peak amplitude (also RMS amplitude) were observed around age 10 at the lateral electrode locations C3 and C4, but not at the midline electrodes Cz and Fz. These changes in amplitude coincided with a sharp increase and plateau in AEP peak and RMS amplitude variability from 9 to 11 years of age. CONCLUSIONS: These analyses demonstrated that the observed pattern of AEP maturation depends on the scalp location at which the responses are recorded. The distinct maturational time courses observed for individual AEP peaks support a model of AEP generation in which activity originates from two or more at least partly independent central nervous system pathways. A striking parallel was observed between previously reported maturational changes in auditory cortex synaptic density and, in particular, the age-related changes in P1 amplitude. The results indicate that some areas of the brain activated by sound stimulation have a maturational time course that extends into adolescence. Maturation of certain auditory processing skills such as speech recognition in noise also has a prolonged time course. This raises the possibility that the emergence of adult-like auditory processing skills may be governed by the same maturing neural processes that affect AEP latency and amplitude.

Adolescent↗

PubMed1999

Spatial mislocalization of EEG electrodes -- effects on accuracy of dipole estimation.

OBJECTIVE: The estimation of cortical current activity from scalp-recorded potentials is a complicated mathematical problem that requires fairly precise knowledge of the location of the scalp electrodes. It is expected that spatial mislocalization of electrodes will introduce errors in this estimation. The present study uses simulated and real data to quantify these errors for dipole current sources in a spherical head model. METHODS: A 3-dimensional digitizer was used to locate the positions of 31 scalp electrodes placed on the head according to the 10-20 system in 10 normal subjects. Dipole localizations were performed on auditory evoked potentials (AEPs) collected from these subjects. RESULTS: Computer simulations with several dipole source configurations suggest that errors in locations and orientations on the order of 5 mm and 5 degrees, respectively, are possible for electrode mislocalizations of about 5 degrees. In actual experimental settings, digitized electrode positions were typically mislocalized by an average of about 4 degrees from their standard 10-20 positions on a spherical model. These differences in electrode positions translated to mean differences of about 8 mm in dipole locations and 5 degrees in dipole orientations. CONCLUSIONS: Dipole estimation errors due to electrode mislocalizations are within the limits of errors due to other modeling approximations and noise.

Adult↗

PubMed1999

Activating separate ascending auditory pathways produces different human thalamic/cortical responses.

When auditory nerve function is lost due to surgical removal of bilateral acoustic tumors in cases of neurofibromatosis type 2, a sense of hearing may be restored by means of an auditory brainstem implant (ABI), which electrically stimulates the cochlear nucleus. Electrically evoked auditory brainstem responses recorded from ABI subjects exhibit a variety of waveforms due to the presence or absence of different components. Evidently, ABI stimulation activates different ascending auditory pathways in different individuals. This study examined whether such differences at the brainstem level are associated with corresponding differences at higher levels. Multichannel recordings of electrically evoked middle-latency and late auditory responses were obtained from two ABI subjects whose very different electrically evoked auditory brainstem responses represent distinct categories of waveform morphology. The waveforms of both types of response were qualitatively similar in that for each condition tested there were corresponding main peaks and troughs. Quantitatively, however, there were differences in the scalp distributions and magnitudes of all components present. One subject had distributions suggesting bilateral activation and an N1-P2 complex of large amplitude, whereas the other subject had distributions suggesting unilateral activation contralateral to the side of stimulation and an N1-P2 complex of small amplitude. The differences suggest that activation of different ascending pathways in the auditory system results in different spatial and temporal patterns of neural activity in the thalamic and/or cortical auditory areas.

Adult↗

PubMed1998

The effects of sensory hearing loss on cochlear filter times estimated from auditory brainstem response latencies.

Derived-band auditory brainstem responses (ABRs) were obtained in 43 normal-hearing and 80 cochlear hearing-impaired individuals using clicks and high-pass noise masking. The response times across the cochlea [the latency difference between wave V's of the 5.7- and 1.4-kHz center frequency (CF) derived bands] were calculated for five levels of click stimulation ranging from 53 to 93 dB p.-p.e. SPL (23 to 63 dB nHL) in 10-dB steps. Cochlear response times appeared to shorten significantly with hearing loss, especially when the average pure tone (1 to 8 kHz) hearing loss exceeded 30 dB. Examination of derived-band latencies indicates that this shortening is due to a dramatic decrease of wave V latency in the lower CF derived band. Estimates of cochlear filter times in terms of the number of periods to maximum response (Nmax) were calculated from derived-band latencies corrected for gender-dependent cochlear transport and neural conduction times. Nmax decreased as a function of hearing loss, especially for the low CF derived bands. The functions were similar for both males and females. These results are consistent with broader cochlear tuning due to peripheral hearing loss. Estimating filter response times from ABR latencies enhances objective noninvasive diagnosis and allows delineation of the differential effects of pathology on the underlying cochlear mechanisms involved in cochlear transport and filter build-up times.

Acoustic Stimulation↗

PubMed1997

Integrated mismatch negativity (MMNi): a noise-free representation of evoked responses allowing single-point distribution-free statistical tests.

If the repeated presentation of a single (standard) auditory stimulus is randomly interspersed with a second acoustically different (deviant) stimulus, the cortical activity evoked by the deviant stimulus can contain a negative component known as the mismatch negativity (MMN). The MMN is derived by subtracting the averaged response evoked by the standard stimulus from that evoked by the deviant stimulus. When the magnitude of the response is small or the signal-to-noise ratio is poor, it is difficult to judge the presence or absence of the MMN simply by visual inspection, and statistical detection techniques become necessary. A method of analysis is proposed to quantify the magnitude and statistically evaluate the presence of the MMN based on time-integrated evoked responses. This paper demonstrates the use of this integrated mismatch negativity (MMNi) analysis to detect the MMN evoked by stimulus contrasts near the perceptual threshold of two subjects. The MMNi, by virtue of being equivalent to a low-pass filtered response, presents an almost noise-free estimate of MMN magnitude. A single measure of the integrated evoked response at a fixed time point is used in a distribution-free statistic that compares the magnitude of the averaged response evoked by the deviant stimulus with a magnitude distribution derived from 200 subaveraged responses to the standard stimulus (with the number of sweeps per average equal to that of the deviant stimulus). This allows a calculation of the exact probability for the null hypothesis that the negative magnitude of the response evoked by the deviant stimulus is drawn from the magnitude distribution of responses evoked by the standard stimulus. Rejection of this hypothesis provides objective evidence of the presence of the MMN.

Acoustic Stimulation↗

PubMed1997

Spatio-temporal EEG source localization using simulated annealing.

The estimation of multiple dipole parameters in spatio-temporal source modeling (STSM) of electroencephalographic (EEG) data is a difficult nonlinear optimization problem due to multiple local minima in the cost function. A straightforward iterative optimization approach to such a problem is very susceptible to being trapped in a local minimum, thereby resulting in incorrect estimates of the dipole parameters. In this paper, we present and evaluate a more robust optimization approach based on the simulated annealing algorithm. The complexity of this approach for the STSM problem was reduced by separating the dipole parameters into linear (moment) and nonlinear (location) components. The effectiveness of the proposed method and its superiority over the traditional nonlinear simplex technique in escaping local minima were tested and demonstrated through computer simulations. The annealing algorithm and its implementation for multidipole estimation are also discussed. We found the simulated annealing approach to be 7-31% more effective than the simplex method at converging to the true global minimum for a number of different kinds of three-dipole problems simulated in this work. In addition, the computational cost of the proposed approach was only marginally higher than its simplex counterpart. The annealing method also yielded similar solutions irrespective of the initial guesses used. The proposed simulated annealing method is an attractive alternative to the simplex method that is currently more common in dipole estimation applications.

Algorithms↗

PubMed1997

Maturational delays in cortical evoked potentials in cochlear implant users.

We studied the effects of prolonged auditory deprivation in children in whom auditory stimulation was restored by a cochlear implant. The latency of the P1 component of the late cortical potential was used as the indicator of auditory system maturation. For normal-hearing children there is a gradual evolution of evoked potential features that extends through adolescence with P1 latency becoming adult-like at about age 15. It appears that maturation of P1 latency in normal and implanted children occurs at the same rate, but the time to maturity in implanted subjects is delayed by an amount approximately equal to the duration of deafness.

Adolescent↗

PubMed1997

Successful detection of small acoustic tumors using the stacked derived-band auditory brain stem response amplitude.

HYPOTHESIS: The aim of this study was to show that a new auditory brain stem response (ABR) measure, the stacked derived-band ABR amplitude, can detect small acoustic intracanalicular tumors missed by standard ABR measures. BACKGROUND: Recent studies clearly have shown that standard ABR latency measures have inadequate sensitivity to detection of small intracanalicular acoustic tumors. Consequently, despite its relatively low cost and wide availability, the standard ABR test has been replaced as a diagnostic screening tool by magnetic resonance imaging (MRI) with gadolinium (GdDTPA) contrast. However, screening with MRIs can be problematic because of their high cost, limited availability, and impact on patient comfort. Thus, an ABR method capable of detecting small tumors with good specificity would be an invaluable cost-effective screening tool for reducing the number of patients without tumor imaged. METHODS: Derived-band ABRs were obtained to 63-dB normal hearing level (nHL) clicks using high-pass noise-masking procedures. The new measure is the wave V amplitude of a stacked ABR constructed by temporally aligning wave V of each derived-band ABR and then summing the time-shifted responses. RESULTS: In a series of 25 tumor cases, 5 small (< or = 1 cm) intracanalicular tumors, missed by standard ABR latency measures, were detected by this new stacked ABR method. The stacked wave V ABR amplitudes in all five cases were significantly lower than those obtained in a group of normal-hearing individuals without tumors. CONCLUSIONS: A new ABR measure, the stacked derived-band ABR amplitude, is sensitive to the presence of small intracanalicular tumors in patients and has excellent specificity for the absence of tumors in normal-hearing individuals. This method, in combination with standard ABR measures, appears promising both as a cost-effective approach to reducing the number of patients without tumors imaged and as a method for acoustic tumor screening when MRI scans: 1) are unavailable; 2) are not appropriate because of patient comfort; and 3) need to be justified because of their cost.

Evoked Potentials, Auditory, Brain Stem↗

PubMed1996

Auditory system plasticity in children after long periods of complete deafness.

Deaf children fitted with a cochlear implant provide a unique opportunity to examine the effects of auditory deprivation on the maturation of the human auditory system. We compared cortical evoked potentials recorded in implanted and normal-hearing children and found that age-dependent latency changes for the P1 component, fitted to a decaying exponential curve, showed the same rate of maturation. For implanted children, however, maturational delays for P1 latency approximated the period of auditory deprivation prior to implantation. This indicates the auditory system does not mature without stimulation. Nonetheless, the auditory system retains its plasticity during the period of deafness since the re-introduction of stimulation by the cochlear implant resumes the normal maturational sequence.

Acoustic Stimulation↗

PubMed1996

Maturation of human cortical auditory function: differences between normal-hearing children and children with cochlear implants.

OBJECTIVE: We investigated maturation of cortical auditory function in normal-hearing children and in children who receive stimulation of their auditory system through a cochlear implant. DESIGN: As a measure of cortical auditory function, auditory evoked responses (AERs) were recorded from normal-hearing children and adults as well as from children and adults fitted with a cochlear implant. Morphological and latency changes for evoked responses recorded at electrode Cz are reported. RESULTS: For normal-hearing children, there is a gradual evolution of AER features that extends through adolescence, with P1 latency becoming adult-like in the late teens. Latency changes for P1 occur at the same rate for implanted children, but the overall maturation sequence is delayed. By extrapolation from the existing data, the age at which P1 latency becomes adult-like is delayed by approximately 5 yr for the implanted population. Other typical features of the AER, namely N1 and P2, are either delayed in developing or absent in the implanted children. CONCLUSIONS: These preliminary findings suggest both similarities and differences in cortical auditory maturation for normal-hearing and implanted children. For implanted children, the 5 yr delay for maturation of P1 latency roughly corresponds to the average 4.5 yr interval between the onset of deafness and the time of implantation. These findings suggest that during the period of deafness, maturation of cortical auditory function does not progress. However, some, if not all, maturational processes resume after stimulation is reintroduced.

Adult↗

PubMed1996

Use of quantitative measures of auditory brain-stem response peak amplitude and residual background noise in the decision to stop averaging.

An objective quantitative approach to the decision of when to stop averaging sweeps in auditory brain-stem response (ABR) testing is presented. This decision is based on (1) the knowledge of the amplitude distributions of wave V in the ABRs of normal hearing individuals for varying stimulus levels, (2) calculated estimates of the residual background noise in the average, and (3) use of a quantitative statistical detector of an evoked potential. Several reasons for terminating an average are presented along with a specific protocol for each of the reasons. These protocols provide a general but consistent framework to address the issue of when to stop averaging and should improve the efficiency of ABR testing. Furthermore, it is quite possible to automate the procedure and the decision process.

Acoustic Stimulation↗

PubMed1996

Variable effects of click polarity on auditory brain-stem response latencies: analyses of narrow-band ABRs suggest possible explanations.

The auditory brain-stem responses (ABRs) to rarefaction and condensation clicks were obtained for 12 normal-hearing subjects in quiet, and high-pass masking at 8, 4, 2, 1, and 0.5 kHz. Derived narrow-band wave V latency differences were analyzed with respect to (1) stimulus polarity, (2) absolute differences irrespective of polarity. The analyses revealed no significant stimulus polarity effects on latency for the derived bands. Absolute latency differences regardless of polarity tended to be greater for those derived bands having lower characteristic frequencies (CFs). However, these differences were smaller than the expected half-period of the theoretical CF. Further analyses in three additional subjects using repeated runs of the same polarity indicate that this increase in absolute latency difference with lower derived band CF does not reflect a simple half-period change owing to polarity, but rather to the increase variability in measuring the peak latency of the lower CF derived bands. The variability is consistent with variability of eighth nerve PST histograms behavior observed in animal work [Kiang et al., "Discharge patterns of single fibers in the cat's auditory nerve," Research Monograph No. 35 (MIT, Cambridge, MA, 1965)]. Thus claimed polarity effects observed in other ABR work using absolute values may have been affected by this variability. It appears from these current data that half-period latency shifts of wave V owing to stimulus polarity differences are not observed in derived bands responses initiated from frequency specific regions of the cochlea.

Adolescent↗

PubMed1995

The mismatch negativity in cochlear implant users.

For individuals with severe or profound hearing loss, electrical stimulation of surviving neural elements by a cochlear implant may partly restore a sensation of hearing. Determining the extent of restoration based on behavioral measures may be difficult, particularly when evaluating young children or individuals who have little or no experience with normal hearing. In normal-hearing individuals, an objective measure of sound discrimination may be obtained by studying the mismatch negativity (MMN) component of the auditory evoked potential. The MMN may be evoked by a number of physical differences in acoustic stimuli including duration and pitch. For cochlear implant users, analogous stimulus differences may be produced by changing the length of a stimulus pulse train or by changing the pair of activated electrodes along a multi-electrode implant array. This paper will provide an overview of our current results, comparing evoked response data recorded from both normal-hearing individuals and cochlear implant users. In both normal-hearing individuals and cochlear implant users, MMNs were evoked by differences in stimulus train duration and pitch (or electrode pair activation in cochlear implant users). These findings suggest that the MMN may be a useful method for assessing the discriminability of electrical stimulation patterns produced by a cochlear implant. Eventually, information gained by MMN testing may yield important information for developing rehabilitation programs for the individual user.

Adult↗

PubMed1994

Auditory brainstem response (ABR) peak amplitude variability reflects individual differences in cochlear response times.

Previously, it was shown [Don et al., J. Acoust. Soc. Am. 94, 2135-2148 (1993)] that cochlear response times are gender specific and about 13% shorter in females than in males. It is also suggested that one of the possible reasons click-evoked auditory brainstem response (ABR) waveforms recorded from females are better defined and have larger amplitudes than those of males is due to a sex difference in cochlear response times leading to better synchronization of the cochlear output across the frequency regions. Variability in cochlear response times would also lead to variability in click evoked ABR amplitudes. The high-pass noise masking derived ABR technique was used to investigate the effect of normalizing the individual temporal variability at the neural and cochlear levels. This involved adjusting for differences in neural conduction time (I-V delay) by a compression or expansion of the derived ABR waveforms and by adjusting for differences in cochlear response times by a shift of the derived ABR waveforms. A summation of the compressed and shifted ABRs results in a normalized unmasked ABR waveform that can then be compared for amplitude variability with the unprocessed unmasked ABRs. Compensation for the neutral I-V variability had little effect while compensation for cochlear response times, particularly the delay between the 5.7- and 2.8-kHz regions, greatly affected the amplitude of wave V of the compounded ABR. This work provides a better understanding of the significant relationship between cochlear response times and variability of the ABR peak amplitudes.

Adolescent↗