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Biomedical subjects

Joseph P Walton

Publications and source records attributed to Joseph P Walton.

7 recordsLinked to original sources

Age-related structural and functional changes in the cochlear nucleus.

Presbycusis - age-related hearing loss - is a key communication disorder and chronic medical condition of our aged population. The cochlear nucleus is the major site of projections from the auditory portion of the inner ear. Relative to other levels of the peripheral and central auditory systems, relatively few studies have been conducted examining age-related changes in the cochlear nucleus. The neurophysiological investigations suggest declines in glycine-mediated inhibition, reflected in increased firing rates in cochlear nucleus neurons from old animals relative to young adults. Biochemical investigations of glycine inhibition in the cochlear nucleus are consistent with the functional aging declines of this inhibitory neurotransmitter system that affect complex sound processing. Anatomical reductions in neurons of the cochlear nucleus and their output pathways can occur due to aging changes in the brain, as well as due to age-dependent plasticity of the cochlear nucleus in response to the age-related loss of inputs from the cochlea, particularly from the basal, high-frequency regions. Novel preventative and curative biomedical interventions in the future aimed at alleviating the hearing loss that comes with age, will likely emanate from increasing our knowledge and understanding of its neural and molecular bases. To the extent that this sensory deficit resides in the central auditory system, including the cochlear nucleus, future neural therapies will be able to improve hearing in the elderly.

Age Factors↗

Age reduces response latency of mouse inferior colliculus neurons to AM sounds.

Age and stimulus rise time (RT) effects on response latency were investigated for inferior colliculus (IC) neurons in young-adult and old CBA mice. Single-unit responses were recorded to unmodulated and sinusoidal amplitude modulated (SAM) broadband noise carriers, presented at 35 to 80 dB SPL. Data from 63 young-adult and 76 old phasic units were analyzed to identify the time interval between stimulus onset and driven-response onset (latency). When controlling for stimulus sound level and AM frequency, significant age-related changes in latency were identified. Absolute latency decreased with age at all stimulus AM frequencies, significantly so for equivalent rise times (RT) < or = 12.5 ms. The linear correlation of latency with AM stimulus RT was significant for both young-adult and old units, and increased significantly with age. It is likely that both the decrease in absolute latency and the increase in latency/RT correlation with age are consistent with a reduction of inhibitory drive with age in the IC. These latency changes will result in age-related timing variations in brainstem responses to stimulus onsets, and therefore affect the encoding of complex sounds.

Aging↗

Impaired gap encoding in aged mouse inferior colliculus at moderate but not high stimulus levels.

Age-related deterioration of auditory temporal acuity has been identified as a contributing factor in presbycusis. In the present study, the effects of aging and stimulus level on gap encoding and gap recovery functions were investigated by measuring near-field auditory evoked potentials in the inferior colliculus of eight 3 month old and eight 24 month old CBA/CaJ mice, in response to gap stimuli embedded in broadband noise (40, 60, and 80 dB SPL). Gap encoding was assessed by measuring latencies and amplitudes of peak features of the near-field response, and also with a procedure that calculated the root mean square of the response within specific time windows. The chief differences in gap encoding between young and old mice were longer gap thresholds, slower recovery functions, and longer response peak latencies for old mice at 60, but not 80 dB SPL, although the latency of the earliest measured peak remained delayed for this condition in the old compared with the young mice. These results demonstrate that age-related changes in temporal acuity may interact with stimulus level, and suggest that adequate amplification may be critically important for maintaining temporal acuity with advancing age.

Acoustic Stimulation↗

The relative detectability for mice of gaps having different ramp durations at their onset and offset boundaries.

The effect on gap detectability of varying noise fall time (FT) and rise time (RT) of the gap boundary ramps was examined in mice using reflex modification audiometry, measuring inhibition of acoustic startle reflexes by variously shaped gaps just preceding reflex expression. In experiment 1 (n = 12) inhibition increased up to near-asymptotic values with longer FT (0, 1, 2, 3, 5, or 10 ms) and QT (quiet time, 0 to 13 ms), with a 2:1 trade-off between FT and QT. In experiment 2 (n = 24) inhibition increased for any RT above 0 ms (2, 3, 5, or 7 ms) if QT= 1 ms, but diminished with increased RT when QT = 3 or 8 ms. Enhanced detectability for subthreshold gaps by longer ramps results from their extending the apparent gap duration. The negative effect of increased RT for threshold gaps suggests the importance for gap detection of the stronger neural responses to sharp edges at the end of the gap shown previously in the mouse inferior colliculus. These effects are specific to gaps: inhibition for fixed (70-dB SPL) or varied level pulses (30 to 60 dB) was unaffected by varying the ramped edges (experiments 3 and 4, n = 9).

Animals↗

Background noise improves gap detection in tonically inhibited inferior colliculus neurons.

Single units in the inferior colliculus (IC) in the C57Bl/6 inbred mouse strain were tested for their temporal processing ability as measured by their minimum gap threshold (MGT), the shortest silent interval in an ongoing white-noise stimulus which a unit could encode. After ascertaining the MGT in quiet, units were re-tested in various levels of background noise. The focus of this report is on two types of tonically responding units found in the IC. Tonically inhibited (TI) units encoded gaps poorly in quiet and low levels of background noise as compared with tonically excited (TE) units. In quiet, the MGTs of TI units were about an order of magnitude longer than the MGTs typical of TE units. Paradoxically, gap encoding was improved in high levels of background noise for TI units. This result is unexpected from the traditional viewpoint that noise necessarily degrades signal processing and is inconsistent with psychophysical observations of diminished speech and gap detection processing in noisy environments. We believe the improved feature detection described here is produced by the adaptation of inhibitory input. Continuous background noise would diminish the inhibitory efficacy of the gap stimulus by increasing the latency to the onset of inhibition and decreasing its duration. This would allow more spontaneous activity to "bleed through" the silent gap, thus signaling its presence. Improved feature detection in background noise resulting from inhibitory adaptation would seem an efficient neural mechanism and one that might be generally useful in other signal detection tasks.

Acoustic Stimulation↗

Age-related alterations in the neural coding of envelope periodicities.

This research was guided by the working hypothesis that the aging auditory system progressively loses its ability to process rapid acoustic transients efficiently, and in elderly listeners, this results in difficulties in speech perception. Neural correlates of age-related deficits in temporal processing were investigated by recording from inferior colliculus (IC) neurons from young adult and old CBA mice. Single-unit responses were recorded to sinusoidally amplitude-modulated (SAM) noise carriers, presented at 65-80 dB SPL, having modulation frequencies (MFs) that ranged from 10 to 800 Hz. Because phasic-type temporal response patterns dominate responses to tone and noise in mammalian IC, we limited our analyses to only phasic units. Modulation transfer functions (MTF) for both rate (rMTF) and synchronization (sMTF) measures were used to derive respective best modulation frequencies (rBMF and sBMF). The main age-related finding was that there was an overall increase in response rate to SAM noise carriers and a decrease in the median upper cutoff frequency in units from old mice. At rBMF, the median spike count from units from old animals was 1.63 times greater, and at the sBMF, the median spike count was 2.29 times greater than the young adult sample. We explored whether the increase in driven activity was due to a change in the transient (first cycle response) or periodic (remaining response) component of the response to SAM noise. Median spike counts of the transient component decreased with increasing MF for both young adult and old units, with median counts consistently greater in the old sample as compared with young. Median spike counts for the periodic response remained relatively constant as a function of MF; however, there was a significantly greater (3 times) response for older units in a restricted range of MFs. The greater median spike counts found for the transient and periodic response was also evident when we analyzed the cycle-by-cycle response. The magnitude of the differences between the young adult and the old spike median responses was greatest at low MFs and then declined as MF increased. Finally, the young adult distribution of rBMFs extends to higher MFs than the old, with 36.0% of units having rBMFs >100 Hz as compared with only 12.5% of the old unit sample. We postulate that this age-related difference in rate coding of SAM noise carriers is consistent with a loss, or imbalance, of excitatory and inhibitory neural mechanisms known to shape encoding of envelope periodicities in the IC.

Acoustic Stimulation↗

Behavioral and neural measures of auditory temporal acuity in aging humans and mice.

Three experiments compared auditory temporal acuity in humans and in the behavior and single cells in the inferior colliculus (IC) of mice, to establish the comparability of aging effects on temporal acuity across species, and to suggest a neural foundation. The thresholds for silent gaps placed in white noise (MGTs) were similar in young mice and young humans, and increased in some but not all old humans and old mice. Neural MGT in the most sensitive cells of both young and old mice was comparable to behavioral MGT in the young of both species, but older mice had more cells with very high MGT. Human listeners were selected to have minimal absolute hearing loss. Older mice had significant hearing loss that was correlated with MGT in behavioral, but not in neural, measures. Some old mice and some old IC cells, however, had low MGTs coupled with elevated absolute hearing thresholds. Age-related changes in temporal acuity appear comparable in humans and mice. The data suggest a common deficit in neural mechanisms.

Acoustic Stimulation↗