Biomedical subjects

Christopher J Long

Publications and source records attributed to Christopher J Long.

10 recordsLinked to original sources

PubMed2007

Concurrent sound segregation in electric and acoustic hearing.

We investigated potential cues to sound segregation by cochlear implant (CI) and normal-hearing (NH) listeners. In each presentation interval of experiment 1a, CI listeners heard a mixture of four pulse trains applied concurrently to separate electrodes, preceded by a "probe" applied to a single electrode. In one of these two intervals, which the subject had to identify, the probe electrode was the same as a "target" electrode in the mixture. The pulse train on the target electrode had a higher level than the others in the mixture. Additionally, it could be presented either with a 200-ms onset delay, at a lower rate, or with an asynchrony produced by delaying each pulse by about 5 ms re those on the nontarget electrodes. Neither the rate difference nor the asynchrony aided performance over and above the level difference alone, but the onset delay produced a modest improvement. Experiment 1b showed that two subjects could perform the task using the onset delay alone, with no level difference. Experiment 2 used a method similar to that of experiment 1, but investigated the onset cue using NH listeners. In one condition, the mixture consisted of harmonics 5 to 40 of a 100-Hz fundamental, with the onset of either harmonics 13 to 17 or 26 to 30 delayed re the rest. Performance was modest in this condition, but could be improved markedly by using stimuli containing a spectral gap between the target and nontarget harmonics. The results suggest that (a) CI users are unlikely to use temporal pitch differences between adjacent channels to separate concurrent sounds, and that (b) they can use onset differences between channels, but the usefulness of this cue will be compromised by the spread of excitation along the nerve-fiber array. This deleterious effect of spread-of-excitation can also impair the use of onset cues by NH listeners.

Acoustic Stimulation↗

PubMed2006

Binaural unmasking with bilateral cochlear implants.

Nearly 100,000 deaf patients worldwide have had their hearing restored by a cochlear implant (CI) fitted to one ear. However, although many patients understand speech well in quiet, even the most successful experience difficulty in noisy situations. In contrast, normal-hearing (NH) listeners achieve improved speech understanding in noise by processing the differences between the waveforms reaching the two ears. Here we show that a form of binaural processing can be achieved by patients fitted with an implant in each ear, leading to substantial improvements in signal detection in the presence of competing sounds. The stimulus in each ear consisted of a narrowband noise masker, to which a tonal signal was sometimes added; this mixture was half-wave rectified, lowpass-filtered, and then used to modulate a 1000-pps biphasic pulse train. All four CI users tested showed significantly better signal detection when the signal was presented out of phase at the two ears than when it was in phase. This advantage occurred even though subjects only received information about the slowly varying sound envelope to be presented, contrary to previous reports that waveform fine structure dominates binaural processing. If this advantage generalizes to multichannel situations, it would demonstrate that envelope-based CI speech-processing strategies may allow patients to exploit binaural unmasking in order to improve speech understanding in noise. Furthermore, because the tested patients had been deprived of binaural hearing for eight or more years, our results show that some sensitivity to time-varying interaural cues can persist over extended periods of binaural deprivation.

Adult↗

PubMed2006

Substrate specificity of lipoprotein lipase and endothelial lipase: studies of lid chimeras.

The triglyceride (TG) lipase gene subfamily, consisting of LPL, HL, and endothelial lipase (EL), plays a central role in plasma lipoprotein metabolism. Compared with LPL and HL, EL is relatively more active as a phospholipase than as a TG lipase. The amino acid loop or "lid" covering the catalytic site has been implicated as the basis for the difference in substrate specificity between HL and LPL. To determine the role of the lid in the substrate specificity of EL, we studied EL in comparison with LPL by mutating specific residues of the EL lid and exchanging their lids. Mutation studies showed that amphipathic properties of the lid contribute to substrate specificity. Exchanging lids between LPL and EL only partially shifted the substrate specificity of the enzymes. Studies of a double chimera possessing both the lid and the C-terminal domain (C-domain) of EL in the LPL backbone showed that the role of the lid in determining substrate specificity does not depend on the nature of the C-domain of the lipase. Using a kinetic assay, we showed an additive effect of the EL lid on the apparent affinity for HDL(3) in the presence of the EL C-domain.

Amino Acid Sequence↗

PubMed2005

Effect of inter-phase gap on the sensitivity of cochlear implant users to electrical stimulation.

Human behavioral thresholds for trains of biphasic pulses applied to a single channel of Nucleus CI24 and LAURA cochlear implants were measured as a function of inter-phase gap (IPG). Experiment 1 used bipolar stimulation, a 100-pps pulse rate, and a 400-ms stimulus duration. In one condition, the two phases of each pulse had opposite polarity. Thresholds continued to drop by 9-10 dB as IPG was increased from near zero to the longest value tested (2900 micros for CI24, 4900 micros for LAURA). This time course is much longer than reported for single-cell recordings from animals. In a second condition, the two phases of each pulse had the same polarity, which alternated from pulse to pulse. Thresholds were independent of IPG, and similar to those in condition 1 at IPG=4900 micros. Experiment 2 used monopolar stimulation. One condition was similar to condition 1 of experiment 1, and thresholds also dropped up to the longest IPG studied (2900 micros). This also happened when the pulse rate was reduced to 20 pps, and when only a single pulse was presented on each trial. Keeping IPG constant at 8 micros and adding an extra biphasic pulse x ms into each period produced thresholds that were roughly independent of x, indicating that the effect of IPG in the other conditions was not due to a release from refractoriness at sites central to the auditory nerve. Experiment 3 measured thresholds at three IPGs, which were less than, equal to, and more than one half of the interval between successive pulses. Thresholds were lowest at the intermediate IPG. The results of all experiments could be fit by a linear model consisting of a lowpass filter based on the function relating threshold to the frequency of sinusoidal electrical stimulation. The data and model have implications for reducing the power consumption of cochlear implants.

Action Potentials↗

PubMed2005

Optimizing the clinical fit of auditory brain stem implants.

OBJECTIVE: To develop and implement a new audiological fitting procedure for auditory brain stem implants (ABIs), based on an efficient algorithm, and to compare it with two procedures presently used in clinical practice. DESIGN: First, the different procedures were compared by using computer models and simulations with normal-hearing subjects (N = 4). This allows for an analysis of the accuracy of the procedures in a way that is not possible when testing ABI users. The root-mean-square error between the order estimated by the procedure and the true order was calculated. In addition, ABI users (N = 2) were tested with the new procedure to see if it could be successfully applied in clinic. The degree of variability of their results across runs and sessions was analyzed. RESULTS: The tests of the normal-hearing subjects showed that our proposed procedure required significantly fewer trials (22 on average) than procedures presently used in clinic (with 76 and 234 trials on average for the two other procedures tested) to produce the same degree of accuracy. Computer modeling also demonstrated this advantage. Additional testing showed this advantage was maintained under a variety of conditions relevant to the clinic. The two patients tested were able to use this procedure with success, even though they were poor at discriminating the pitch of electrodes. The patients showed results consistent with having about 4 to 5 discriminable groups of electrodes with the 12 to 14 electrodes tested. CONCLUSIONS: The proposed procedure requires fewer trials to produce a clinically useful result and is well tolerated in the clinic. An additional advantage is that it allows testing to be broken down into several "blocks," each containing a small number of trials. If the variability between blocks is small, information can be combined across blocks to increase the accuracy of the result. If the variability is large, perhaps between blocks on different days, this may reflect a significant change in the percepts generated by the implant, and signal to the clinician that a significant alteration in the fitting is required. We recommend its use in ABI user fitting and in cochlear implant fitting when pitch ranking is problematic.

Adult↗

PubMed2004

Role of N-linked glycosylation in the secretion and activity of endothelial lipase.

Human endothelial lipase (EL), a member of the triglyceride lipase gene family, has five potential N-linked glycosylation sites, two of which are conserved in both lipoprotein lipase and hepatic lipase. Reduction in molecular mass of EL after treatment with glycosidases and after treatment of EL-expressing cells with the glycosylation inhibitor tunicamycin demonstrated that EL is a glycosylated protein. Each putative glycosylation site was examined by site-directed mutagenesis of the asparagine (Asn). Mutation of Asn-60 markedly reduced secretion and slightly increased specific activity. Mutation of Asn-116 did not influence secretion but increased specific activity. In both cases, this resulted from decreased apparent K(m) and increased apparent V(max). Mutation of Asn-373 did not influence secretion but significantly reduced specific activity, as a result of a decrease in apparent V(max). Mutation of Asn-471 resulted in no reduction in secretion or specific activity. Mutation of Asn-449 resulted in no change in secretion, activity, or molecular mass, indicating that the site is not utilized. The ability of mutants secreted at normal levels to mediate bridging between LDL and cell surfaces was examined. The Asn-373 mutant demonstrated a 3-fold decrease in bridging compared with wild-type EL, whereas Asn-116 and Asn-471 were similar to wild-type EL.

Adenoviridae↗

PubMed2003

Pitch of amplitude-modulated irregular-rate stimuli in acoustic and electric hearing.

The pitch of stimuli was studied under conditions where place-of-excitation was held constant, and where pitch was therefore derived from "purely temporal" cues. In experiment 1, the acoustical and electrical pulse trains consisted of pulses whose amplitudes alternated between a high and a low value, and whose interpulse intervals alternated between 4 and 6 ms. The attenuated pulses occurred after the 4-ms intervals in condition A, and after the 6-ms intervals in condition B. For both normal-hearing subjects and cochlear implantees, the period of an isochronous pulse train equal in pitch to this "4-6" stimulus increased from near 6 ms at the smallest modulation depth to nearly 10 ms at the largest depth. Additionally, the modulated pulse trains in condition A were perceived as being lower in pitch than those in condition B. Data are interpreted in terms of increased refractoriness in condition A, where the larger pulses are more closely followed by the smaller ones than in condition B. Consistent with this conclusion, the A-B difference was reduced at longer interpulse intervals. These findings provide a measure of supra-threshold effects of refractoriness on pitch perception, and increase our understanding of coding of temporal information in cochlear implant speech processing schemes.

Acoustic Stimulation↗

PubMed2003

Binaural sensitivity as a function of interaural electrode position with a bilateral cochlear implant user.

Experiments were conducted with a single, bilateral cochlear implant user to examine interaural level and time-delay cues that putatively underlie the design and efficacy of bilateral implant systems. The subject's two implants were of different types but custom equipment allowed presentation of controlled bilateral stimuli, particularly those with specified interaural time difference (ITD) and interaural level difference (ILD) cues. A lateralization task was used to measure the effect of these cues on the perceived location of the sensations elicited. For trains of fixed-amplitude, biphasic current pulses at 100 pps, the subject demonstrated sensitivity to an ITD of 300 micros, providing evidence of access to binaural information. The choice of bilateral electrode pair greatly influenced ITD sensitivity, suggesting that electrode pairings are likely to be an important consideration in the effort to provide binaural advantages. The selection of bilateral electrode pairs showing sensitivity to ITD was partially aided by comparisons of the pitch elicited by individual electrodes in each ear (when stimulated alone with fixed-amplitude current pulses at 813 pps): specifically, interaural electrodes with similar pitches were more likely (but not certain) to show ITD sensitivity. Significant changes in lateral position occurred with specific electrode pairs. With five bilateral electrode pairs of 14 tested, ITDs of 300 and 600 micros moved an auditory image significantly from right to left. With these same pairs, ILD changes of approximately 11% of the dynamic range (in microApp) moved an auditory image from the far left to the far right-significantly farther than the nine pairs not showing significant ITD sensitivity. However, even these nine pairs did show response changes as a function of the interaural (or confounding monaural) level cue. Overall, insofar as the access to bilateral cues demonstrated herein generalizes to other subjects, it provides hope that the normal binaural advantages for speech recognition and sound localization can be made available to bilateral implant users.

Acoustic Stimulation↗

PubMed2002

Identification of genetic variants in endothelial lipase in persons with elevated high-density lipoprotein cholesterol.

BACKGROUND: Elevated high-density lipoprotein cholesterol (HDL-C) is associated with reduced risk of cardiovascular disease, and variation in HDL-C levels has been shown to be approximately 50% heritable. Overexpression of endothelial lipase (EL), a member of the lipoprotein lipase gene family, markedly reduces HDL-C levels in mouse models. We hypothesized that genetic variation in EL might be associated with elevated HDL-C. METHODS AND RESULTS: All exons and 1.2 kilobase of promoter of the EL gene were sequenced in 20 unrelated human subjects with high HDL-C levels. A total of 17 variants were identified. Six of these were potentially functional and were confirmed by restriction enzyme analysis. Four variants result in amino acid changes (Gly26Ser, Thr111Ile, Thr298Ser, and Asn396Ser,) and 2 variants were in the promoter (-303A/C and -410C/G). The genotype frequencies of each variant were determined in 176 black controls, 165 white controls, and 123 whites with high HDL-C. The Thr111Ile variant was the most common, with an allele frequency of 10.3% in blacks, 31.2% in white controls, and 32.6% in the high HDL-C group. The remaining variants all had allele frequencies <5.0% but differed in frequency among the 3 groups. Interestingly, Gly26Ser, Thr298Ser, and -303A/C were found in the black and high HDL-C white cohorts but were absent in the control white group. CONCLUSIONS: Six new potentially functional variants in EL were discovered through sequencing of the EL gene in subjects with high HDL-C levels. Differences in allele frequencies exist between blacks and whites and between control subjects and those with high HDL-C levels.

Black People↗

PubMed2002

Temporal pitch mechanisms in acoustic and electric hearing.

Two experiments investigated pitch perception for stimuli where the place of excitation was held constant. Experiment 1 used pulse trains in which the interpulse interval alternated between 4 and 6 ms. In experiment 1a these "4-6" pulse trains were bandpass filtered between 3900 and 5300 Hz and presented acoustically against a noise background to normal listeners. The rate of an isochronous pulse train (in which all the interpulse intervals were equal) was adjusted so that its pitch matched that of the "4-6" stimulus. The pitch matches were distributed unimodally, had a mean of 5.7 ms, and never corresponded to either 4 or to 10 ms (the period of the stimulus). In experiment 1b the pulse trains were presented both acoustically to normal listeners and electrically to users of the LAURA cochlear implant, via a single channel of their device. A forced-choice procedure was used to measure psychometric functions, in which subjects judged whether the 4-6 stimulus was higher or lower in pitch than isochronous pulse trains having periods of 3, 4, 5, 6, or 7 ms. For both groups of listeners, the point of subjective equality corresponded to a period of 5.6 to 5.7 ms. Experiment 1c confirmed that these psychometric functions were monotonic over the range 4-12 ms. In experiment 2, normal listeners adjusted the rate of an isochronous filtered pulse train to match the pitch of mixtures of pulse trains having rates of F1 and F2 Hz, passed through the same bandpass filter (3900-5400 Hz). The ratio F2/F1 was 1.29 and F1 was either 70, 92, 109, or 124 Hz. Matches were always close to F2 Hz. It is concluded that the results of both experiments are inconsistent with models of pitch perception which rely on higher-order intervals. Together with those of other published data on purely temporal pitch perception, the data are consistent with a model in which only first-order interpulse intervals contribute to pitch, and in which, over the range 0-12 ms, longer intervals receive higher weights than short intervals.

Adult↗