Biomedical subjects
Publications and source records attributed to David R Moore.
Sounds that move towards us have a greater biological salience than those that move away. Recent studies in human and non-human primates have demonstrated a perceptual and behavioural priority for such looming sounds that is also reflected in an asymmetric pattern of cortical activation.
Otitis media with effusion (OME), a form of middle ear disease, is the most common reason for young children both to visit their family doctor and to have surgery. Almost all children have at least a single episode of OME before their first birthday and annual incidence rates exceed 50% in each of the first five years. For most children, OME occurs infrequently, but about 10-15% of children have OME during more than half of their first six years. Middle ear effusions attenuate and delay sound, causing conductive sound distortion during the crucial years for language acquisition. The many studies of OME effects on language and other indices of development have produced mixed results. However, a consensus is emerging of mild language impairment in the preschool years, with subsequent performance, emotional, and behavioral difficulties. In addition to the peripheral hearing loss produced directly by the disease, binaural and other central auditory deficits can outlive the OME. It has been unclear which children are at risk of central impairment following OME, since the children studied have generally been recruited from otolaryngology clinics. Consequently, a detailed prospective history of the middle ear status of participants has not been available. By studying six-year-old children with a lifetime known history of OME, we show in this study that only those children with a cumulative OME experience of more than about half the time during the first five years consistently have residual impaired binaural hearing.
Effects of conductive hearing loss on level and spectrum are well known. However, little is known about possible additional effects on temporal aspects of sound transmission. This study investigated effects of earplugs and middle ear effusions on amplitude and timing of cochlear microphonic (CM) responses in gerbils. Bilateral CM responses to pure tones (1-16 kHz) were monitored before and after (i). unilateral earplug insertion or (ii). injection of silicone oil, of various viscosities, into one middle ear. Earplugs produced flat hearing losses (mean 13 dB) and delayed CMs more at lower (mean 80 micros, 1-6 kHz) than at higher (20 micros, 8-16 kHz) frequencies. Effusions also produced flat hearing loss. On average, high viscosity effusions produced larger hearing losses (36 dB) than medium (25 dB) or low (20 dB) viscosity effusions. Low and medium viscosity effusions delayed responses to lower (mean 82 and 65 micros respectively, 1-6 kHz) more than to higher (mean 20 and 10 micros respectively, 8-16 kHz) frequencies. High viscosity effusions produced smaller delays across all frequencies (mean 31 micros, 1-16 kHz). In normal animals, CM responses were not delayed over a wide range of stimulus levels. Therefore, in addition to attenuation, conductive loss distorts acoustic temporal cues important for hearing.
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Polymerization of beta-butyrolactone (BBL) and beta-valerolactone (BVL) using the zinc alkoxide initiator (BDI-1)ZnO(i)()Pr [(BDI-1) = 2-((2,6-diisopropylphenyl)amido)-4-((2,6-diisopropylphenyl)imino)-2-pentene] proceeds very rapidly under mild conditions to produce poly(3-hydroxybutyrate) (PHB) and poly(3-hydroxyvalerate) (PHV), respectively. For the monomer-to-initiator ratio 200:1, PHB number-average molecular weights (M(n)) are proportional to conversion throughout the reaction and polydispersity indices (PDIs) are narrow, consistent with a living polymerization. Higher monomer-to-initiator ratios can be used to achieve high molecular weight PHB (M(n) > 100 000). End-group analysis verifies that the polymerization of BBL follows a coordination-insertion mechanism, where complexes of the form (BDI-1)ZnOCH(Me)CH(2)CO(2)R are the active species. Variable temperature NMR experiments show that (BDI-1)ZnO(i)()Pr is monomeric in benzene-d(6) solution. In contrast, (BDI-2)ZnO(i)()Pr [(BDI-2) = 2-((2,6-diethylphenyl)amido)-4-((2,6-diethylphenyl)imino)-2-pentene] is a poor initiator at room temperature because it prefers to form a bis-mu-isopropoxide dimer in solution. According to kinetic studies, propagation by (BDI-1)ZnO(i)()Pr is first order in both monomer as well as (BDI-1)ZnO(i)()Pr concentration. These results lead us to propose a monometallic active species. Several results suggest that elimination side reactions are slowly catalyzed by zinc alkoxides, leading to degradation of the polymer.
Despite recent advances regarding catalysts for CO2/epoxide copolymerization, the development of high-activity catalysts for alternating polymerization of CO2 and commodity epoxides, such as propylene oxide, remains a challenge. A new class of unsymmetrically substituted beta-diiminate zinc complexes is reported that exhibits unprecedented activity for CO2/propylene oxide copolymerization. The polymers formed are of high molecular weight (Mn approximately 35 kg/mol) and have narrow polydispersities (PDI approximately 1.1), consistent with a living polymerization.
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This study investigated the long-term effects of unilateral hearing loss on the structure of synapses within the gerbil medial superior olivary (MSO) nuclei. Five animals had complete (surgical) left cochlear ablation at postnatal day 18. Previous studies have shown this to produce, within 3 days, significant transneuronal atrophy in the left dendritic field of both MSOs. Electron micrographs from sagittal ultrathin sections through the MSOs of the cochlear-ablated animals were compared to those from unoperated normals. Qualitatively, the ultrastructural features were similar. Most of the axodendritic terminals were R-type (round-type vesicles, putative excitatory) whereas, in the central part of the nucleus, predominated by neuron soma profiles, terminals of P- and F-type (pleomorphic- and flattened-type vesicles, putative inhibitory) were present in equal numbers with R-type terminals. F-type terminals were infrequent and occurred most around lateral parts of the MSO somata. These three types of terminals seen around the somata and proximal dendrites all had extended profiles with multiple, discontinuous appositions. Quantitative analysis revealed that R-type axodendritic terminals became smaller and less densely populated with vesicles where they synapsed onto the remaining dendrites arrayed towards the ablated side of both MSOs, and axosomatic P-type afferent terminals were smaller in the contralateral nuclei. A significant reduction in the number of terminals and synapses occurred in the central, somatic, region of the ipsilateral MSO. However, the terminal vesicle concentration in the remaining terminals increased. The results indicate that cochlear ablation can induce transynaptic reduction in the size of afferent axon terminals within the MSO, and alter their vesicle concentration. These changes are likely to affect the probability of transmitter release and thus influence their signaling power within the nucleus.
The human ear is functionally mature shortly after birth, but the central auditory system continues to develop for at least the first decade of life. Current interest focuses on the relation between the very late developing aspects of hearing and other aspects of cognition and behaviour. While active neural input to the brain is essential during the very early stages of development, auditory experience is now thought to be a powerful influence on central function throughout an individual's lifespan. Studies of sound localization and hearing with two ears have shown the capacity of the auditory system to adapt to altered environmental cues, even into adulthood. This environmental influence may either be harmful, as during conductive deafness, or beneficial, as evidenced by the positive outcomes of auditory training.
The "temporal processing hypothesis" suggests that individuals with specific language impairments (SLIs) and dyslexia have severe deficits in processing rapidly presented or brief sensory information, both within the auditory and visual domains. This hypothesis has been supported through evidence that language-impaired individuals have excess auditory backward masking. This paper presents an analysis of masking results from several studies in terms of a model of temporal resolution. Results from this modeling suggest that the masking results can be better explained by an "auditory efficiency" hypothesis. If impaired or immature listeners have a normal temporal window, but require a higher signal-to-noise level (poor processing efficiency), this hypothesis predicts the observed small deficits in the simultaneous masking task, and the much larger deficits in backward and forward masking tasks amongst those listeners. The difference in performance on these masking tasks is predictable from the compressive nonlinearity of the basilar membrane. The model also correctly predicts that backward masking (i) is more prone to training effects, (ii) has greater inter- and intrasubject variability, and (iii) increases less with masker level than do other masking tasks. These findings provide a new perspective on the mechanisms underlying communication disorders and auditory masking.
This paper describes optical imaging of the auditory cortex in the anesthetized ferret, particularly addressing optimization of narrowband stimuli. The types of sound stimuli used were tone-pip trains and sinusoidal frequency and amplitude modulated (SFM and SAM) tones. By employing short illumination wavelengths (546 nm), we have successfully characterized the tonotopic arrangement, in agreement with the well-established electrophysiological tonotopic maps of the ferret auditory primary field (AI). The magnitude of the optical signal increased with sound level, was maximal for a modulation frequency (MF) of 2-4 Hz, and was larger for tone-pip trains and SFM sounds than for SAM sounds. Accordingly, an optimal narrowband stimulus was defined. Thus optical imaging can be used successfully to obtain frequency maps in auditory cortex by an appropriate choice of stimulus parameters. In addition, background noise consisting of 0.1-Hz oscillations could be reduced by introduction of blood pressure enhancing drugs. The optical maps were largely independent of 1) the type of narrowband stimulus, 2) the sound level, and 3) the MF. This stability of the optical maps was not predicted from the electrophysiological literature.
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