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Laminar termination patterns of thalamic, callosal, and association afferents in the primary auditory area of the rhesus monkey.

Thalamic, callosal, and association afferents to the primary auditory konicortex, area KA, were investigated in rhesus monkeys with the aid of anterograde tract tracing techniques (radioactively labeled amino acids, wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP), and the Fink-Heimer silver impregnation method). Different patterns of anterograde label in KA were produced by radioactively labeled amino acid injections in the contralateral primary auditory area, the ipsilateral medial geniculate body (MGB), or auditory association cortex of the superior temporal gyrus (STG). Thalamic afferents from the MGB were found throughout KA in layers IV and III where the density waxed and waned, forming regular patches of higher density label separated by areas of less dense label. Callosal afferents from the contralateral auditory cortices were found in layers IV, III, and II in larger, more spatially separated, and irregular patches. In contrast, association afferents from the auditory association cortex of the STG were found in a continuous band in layer I. To determine the extent to which the patches of callosal afferents overlap with or interdigitate between the high-density thalamic clusters, two types of double anterograde labeling experiments were undertaken. In one set of experiments isotope injections of the MGB were made in conjunction with transection of the corpus callosum in the same animal. In another set of experiments isotope injections of the MGB were made in one hemisphere and an injection of WGA-HRP was made in the opposite supratemporal plane, including KA, in the same animal. Both approaches demonstrate that the patches of callosal afferents in KA mainly occur between the high-density patches of thalamic afferents, although there is a variable degree of overlap at their periphery. Thus it seems that thalamic and callosal inputs to KA are organized in a largely complementary fashion while input from the lateral association cortex is continuous and overlaps both. When considered in light of pertinent anatomical and physiological studies in a variety of species, it appears that the areas mainly occupied by callosal or thalamic inputs may be differentially involved in frequency analysis and sound localization, respectively.

Animals↗

Distribution of calcium-binding protein immunoreactivities in the guinea pig auditory brainstem.

This study was intended to provide an overview of the distribution of calcium-binding proteins in the rodent auditory brainstem. We based our observations on immunohistochemical material obtained in the guinea pig, a species widely used in auditory research in which a mapping of calcium-binding proteins in the auditory brainstem is still missing. Differences in the amounts of these proteins throughout the auditory brainstem were further analyzed semiquantitatively. Parvalbumin was present in most neurons and their axon terminals throughout the ascending auditory brainstem. Nuclei that surround the main relay nuclei of the ascending auditory pathway lacked labeling. Calretinin staining was prominent in spherical and globular cells of the cochlear nucleus, in their axon terminals in the superior olivary complex, and in principal cells of the medial superior olive. Measures of optical densities showed that auditory neurons involved in sound localization had the highest calretinin labeling levels. Calbindin D-28k was present in cartwheel cells of the dorsal cochlear nucleus, in almost all neurons of the medial nucleus of the trapezoid body, and in globular cells in the ventral nucleus of the lateral lemniscus. The labeling patterns for calretinin and calbindin D-28k were non-overlapping throughout the auditory brainstem. This was also evident in the ventral nucleus of the lateral lemniscus where calbindin D-28k-immunoreactive terminals were found in the medial portion, while the calretinin-immunoreactive terminals were observed in the lateral portion. This study presents the first direct and comprehensive comparison of these three calcium-binding proteins in the auditory brainstem of a rodent. Each antibody yields a unique staining pattern that provides a basis for further defining neuronal populations. In addition, since their axons are also selectively stained, auditory nuclei can further be compartmentalized based on different terminal fields. These immunoreactivities have provided clues to the complex structure of the auditory brainstem.

Animals↗

Electrical responses of the auditory area of the cerebellar cortex to acoustic stimulation.

Single unit activity from the VI and VII lobuli of the cerebellar vermis cortex was studied following acoustical stimulation with sound signals of different parameters. Cerebellar neurons, as compared to those from the auditory system, showed low selectivity to sound frequency, intensity and duration. However, about 2/3 of the neurons were selectively sensitive to interaural time and intensity differences; about 1/3 of neurons showed a specific response to signals simulating sound motion in a definite direction. Thus, cerebellar neurons seem to be mainly responsive to those sound parameters which are essential for sound localization.

Acoustic Stimulation↗

Development of responses to acoustic interaural intensity differences in the car inferior colliculus.

Responses of single neurones in the inferior colliculus of anesthetized adult cats and kittens were studied using best-frequency stimuli of varying interaural intensity differences (IID). Two broad classes of neurone, distinguished by the predominant type of input from each ear, were examined. One class of cells received predominantly excitatory input from each er (EE cells). The other class were excited by monaural stimulation of the contralateral ear and showed no response to monaural stimulation of the ipsilateral ear, but inhibition of the excitatory response by simultaneous ipsilateral stimulation (EI cells). Fourteen of the 18 adult EI cells showed marked changes in discharge rate with variation in IID. Adult EI cells showed low response variability and were insensitive to changes in average binaural intensity. In all cases of IID sensitivity, the onset component of the response was less sensitive to IID than the sustained component. Eight out of ten EE cells were insensitive to IID over the range tested. Cells of high best-frequency in kittens younger than 28 days showed irregular changes in discharge rate with variation in IID and wide response variability. Some low-frequency EI cells in young kittens showed sensitivity to IID, but it is unlikely that these could be involved in sound localization as their frequency response was inappropriate. Many cells in kittens aged 31-40 days showed monotonic, adult-like IID functions, but the response variability of these cells remained higher than that of adult cat neurones. These data provide evidence for a developmental change of binaural interaction in the cat.

Aging↗

Changing-loudness aftereffects: slope of response functions and spectral dependence.

Aftereffects of azimuthal auditory motion may have two components. A sensory component is inferred from strong aftereffects, because they are spectrally dependent and have shallower response functions than those for non-adaptation. Neither property applies to weak aftereffects, suggesting a cognitive component. Two experiments determined whether changing-loudness aftereffects (CLA) might be understood similarly. In a single-interval forced-choice procedure, listeners responded "growing softer" or "growing louder" to test stimuli changing in intensity. In Exp. 1, adapting and test stimuli were diotic and had the same 1-kHz sinusoidal carrier. Although response functions following adaptation were displaced from response functions for non-adaptation-indicating CLA-their slopes were broadly similar. In Exp. 2, stimuli were monotic; adapting frequency was 1 kHz and test frequencies were between 0.5 and 2.0 kHz. CLA was present in most adaptation conditions, but was strongest when the test frequency was 1.0 kHz; functions' slopes again evinced no systematic variation. The two-component hypothesis for CLA is supported by spectral dependence alone. It is argued that the slope of response functions is due to the nulling procedures for measuring auditory aftereffects. The slope depends on whether the adapted property is processed by "direct" and "indirect" mechanisms; aftereffects tap "direct" mechanisms alone, which may affect sensitivity during measurement.

Adult↗

Inhibitory control of eye movements during oculomotor countermanding in adults with attention-deficit hyperactivity disorder.

Children with attention-deficit hyperactivity disorder (ADHD) are impulsive, and that impulsiveness can be measured using a countermanding task. Although the overt behaviors of ADHD attenuate with age, it is not clear how well impulsiveness is controlled in adults with ADHD. We tested ADHD adults with an oculomotor countermanding task. The task included two conditions: on 75% of the trials, participants viewed a central fixation marker and then looked to an eccentric target that appeared simultaneous with the disappearance of the fixation marker; on 25% of the trials, a signal was presented at variable delays after target appearance. The signal instructed subjects to stop, or countermand, an eye movement to the target. A correct movement in this case would be to hold gaze at the central fixation location. We expected ADHD participants to be impulsive in their countermanding performance. Additionally, we expected that a visual stop signal at the central fixation location would assist oculomotor countermanding because the signal is presented in the "stop" location, at fixation. To test whether a central stop signal positively biased countermanding, we used a three types of stop signal to instruct the stop: a central visual marker, a peripheral visual signal, and a non-localized sound. All subjects performed best with the central visual stop signal. Subjects with ADHD were less able to countermand eye movements and were influenced more negatively by the non-central signals. Oculomotor countermanding may be useful for quantifying impulsive dysfunction in adults with ADHD especially if a non-central stop signal is applied.

Acoustic Stimulation↗

The effect of temporal structure on rustling-sound detection in the gleaning bat, Megaderma lyra.

For a gleaning bat hunting prey from the ground, rustling sounds generated by prey movements are essential to invoke a hunting behaviour. The detection of prey-generated rustling sounds may depend heavily on the time structure of the prey-generated and the masking sounds due to their spectral similarity. Here, we systematically investigate the effect of the temporal structure on psychophysical rustling-sound detection in the gleaning bat, Megaderma lyra. A recorded rustling sound serves as the signal; the maskers are either Gaussian noise or broadband noise with various degrees of envelope fluctuations. Exploratory experiments indicate that the selective manipulation of the temporal structure of the rustling sound does not influence its detection in a Gaussian-noise masker. The results of the main experiment show, however, that the temporal structure of the masker has a strong and systematic effect on rustling-sound detection: When the width of irregularly spaced gaps in the masker exceeded about 0.3 ms, rustling-sound detection improved monotonically with increasing gap duration. Computer simulations of this experiment reveal that a combined detection strategy of spectral and temporal analysis underlies rustling-sound detection with fluctuating masking sounds.

Acoustic Stimulation↗

Can two streams of auditory information be processed simultaneously? Evidence from the gleaning bat Antrozous pallidus.

A tenet of auditory scene analysis is that we can fully process only one stream of auditory information at a time. We tested this assumption in a gleaning bat, the pallid bat (Antrozous pallidus) because this bat uses echolocation for general orientation, and relies heavily on prey-generated sounds to detect and locate its prey. It may therefore encounter situations in which the echolocation and passive listening streams temporally overlap. Pallid bats were trained to a dual task in which they had to negotiate a wire array, using echolocation, and land on one of 15 speakers emitting a brief noise burst in order to obtain a food reward. They were forced to process both streams within a narrow 300 to 500 ms time window by having the noise burst triggered by the bats' initial echolocation pulses as it approached the wire array. Relative to single task controls, echolocation and passive sound localization performance was slightly, but significantly, degraded. The bats also increased echolocation interpulse intervals during the dual task, as though attempting to reduce temporal overlap between the signals. These results suggest that the bats, like humans, have difficulty in processing more than one stream of information at a time.

Acoustic Stimulation↗

Temporal and directional processing by an identified interneuron, ON1, compared in cricket species that sing with different tempos.

We compare the temporal and directional processing properties of an identified auditory interneuron, ON1, between species with calling songs containing relatively low and high pulse rates (Teleogryllus oceanicus and Gryllus texensis, respectively). Using information theory, we find that the ON1 of G. texensis encodes higher amplitude-modulation frequencies than that of T. oceanicus. Bilateral differences in ON1 responses are also more pronounced in G. texensis, particularly for rapid, G. texensis-like stimuli. We show that brief silent intervals in a pulse train, such as those that occur in the natural calling song of G. texensis, enhance the representation of the stimulus pulse pattern as well as bilateral differences in activity. Our results suggest that the characteristics of an identified neuron vary, across cricket species, in accordance with the temporal structures of their communication signals.

Acoustic Stimulation↗

Behavioral guides for sensory neurophysiology.

The study of natural behavior is important for understanding the coding schemes of sensory systems. The jamming avoidance response of the weakly electric fish Eigenmannia is an excellent example of a bottom-up approach, in which behavioral analyses guided neurophysiological studies. These studies started from the electroreceptive sense organs to the motor output consisting of pacemaker neurons. Going in the opposite direction, from the central nervous system to lower centers, is the characteristic of the top-down approach. Although this approach is perhaps more difficult than the bottom-up approach, it was successfully employed in the neuroethological analysis of sound localization in the barn owl. In the latter studies, high-order neurons selective for complex natural stimuli led to the discovery of neural pathways and networks responsible for the genesis of the stimulus selectivity. Comparison of Eigenmannia and barn owls, and their neural systems, has revealed similarities in network designs, such as parallel pathways and their convergence to produce stimulus selectivity necessary for detection of natural stimuli.

Animals↗

FM signals produce robust paradoxical latency shifts in the bat's inferior colliculus.

Previous studies in echolocating bats, Myotis lucifugus, showed that paradoxical latency shift (PLS) is essential for neural computation of target range and that a number of neurons in the inferior colliculus (IC) exhibit unit-specific PLS (characterized by longer first-spike latency at higher sound levels) in response to tone pulses at the unit's best frequency. The present study investigated whether or not frequency-modulated (FM) pulses that mimic the bat's echolocation sonar signals were equally effective in eliciting PLS. For two-thirds of PLS neurons in the IC, both FM and tone pulses could elicit PLS, but only FM pulses consistently produced unit-specific PLS. For the remainder of PLS neurons, only FM pulses effectively elicited PLS; these cells showed either no PLS or no response, to tone pulses. PLS neurons generally showed more pronounced PLS in response to narrow-band FM (each sweeping 20 kHz in 2 ms) pulse that contained the unit's best frequency. In addition, almost all PLS neurons showed duration-independent PLS to FM pulses, but the same units exhibited duration-dependent PLS to tone pulses. Taken together, when compared to tone pulses, FM stimuli can provide more reliable estimates of target range.

Acoustic Stimulation↗

Minicolumnar abnormalities in autism.

Autism is characterized by qualitative abnormalities in behavior and higher order cognitive functions. Minicolumnar irregularities observed in autism provide a neurologically sound localization to observed clinical and anatomical abnormalities. This study corroborates the initial reports of a minicolumnopathy in autism within an independent sample. The patient population consisted of six age-matched pairs of patients (DSM-IV-TR and ADI-R diagnosed) and controls. Digital micrographs were taken from cortical areas S1, 4, 9, and 17. The image analysis produced estimates of minicolumnar width (CW), mean interneuronal distance, variability in CW (V (CW)), cross section of Nissl-stained somata, boundary length of stained somata per unit area, and the planar convexity. On average CW was 27.2 microm in controls and 25.7 microm in autistic patients (P = 0.0234). Mean neuron and nucleolar cross sections were found to be smaller in autistic cases compared to controls, while neuron density in autism exceeded the comparison group by 23%. Analysis of inter- and intracluster distances of a Delaunay triangulation suggests that the increased cell density is the result of a greater number of minicolumns, otherwise the number of cells per minicolumns appears normal. A reduction in both somatic and nucleolar cross sections could reflect a bias towards shorter connecting fibers, which favors local computation at the expense of inter-areal and callosal connectivity.

Adolescent↗

How synapses in the auditory system wax and wane: theoretical perspectives.

Spike-timing-dependent synaptic plasticity has recently provided an account of both the acuity of sound localization and the development of temporal-feature maps in the avian auditory system. The dynamics of the resulting learning equation, which describes the evolution of the synaptic weights, is governed by an unstable fixed point. We outline the derivation of the learning equation for both the Poisson neuron model and the leaky integrate-and-fire neuron with conductance synapses. The asymptotic solutions of the learning equation can be described by a spectral representation based on a biorthogonal expansion.

Action Potentials↗

Subthreshold outward currents enhance temporal integration in auditory neurons.

Many auditory neurons possess low-threshold potassium currents ( I(KLT)) that enhance their responsiveness to rapid and coincident inputs. We present recordings from gerbil medial superior olivary (MSO) neurons in vitro and modeling results that illustrate how I(KLT) improves the detection of brief signals, of weak signals in noise, and of the coincidence of signals (as needed for sound localization). We quantify the enhancing effect of I(KLT) on temporal processing with several measures: signal-to-noise ratio (SNR), reverse correlation or spike-triggered averaging of input currents, and interaural time difference (ITD) tuning curves. To characterize how I(KLT), which activates below spike threshold, influences a neuron's voltage rise toward threshold, i.e., how it filters the inputs, we focus first on the response to weak and noisy signals. Cells and models were stimulated with a computer-generated steady barrage of random inputs, mimicking weak synaptic conductance transients (the "noise"), together with a larger but still subthreshold postsynaptic conductance, EPSG (the "signal"). Reduction of I(KLT) decreased the SNR, mainly due to an increase in spontaneous firing (more "false positive"). The spike-triggered reverse correlation indicated that I(KLT) shortened the integration time for spike generation. I(KLT) also heightened the model's timing selectivity for coincidence detection of simulated binaural inputs. Further, ITD tuning is shifted in favor of a slope code rather than a place code by precise and rapid inhibition onto MSO cells (Brand et al. 2002). In several ways, low-threshold outward currents are seen to shape integration of weak and strong signals in auditory neurons.

Animals↗

Computational model of response maps in the dorsal cochlear nucleus.

The neurons in the mammalian (gerbil, cat) dorsal cochlear nucleus (DCN) have responses to tones and noise that have been used to classify them into unit types. These types (I-V) are based on excitatory and inhibitory responses to tones organized into plots called response maps (RMs). Type I units show purely excitatory responses, while type V units are primarily inhibited. A computational model of the neural circuitry of the mammalian DCN, based on the MacGregor neuromime, was used to investigate RMs of the principal cells (P-cells) that represent the fusiform and giant cells. In gerbils, fusiform cells have been shown to have primarily type III unit response properties; however, fusiform cells in the cat DCN are thought to have type IV unit response properties. The DCN model is based on a previous computational model of the cat (Hancock and Voigt Ann Biomed Eng 27: 73-87, 1999) and gerbil (Zheng and Voigt Ann Biomed Eng 34: 697-708, 2006) DCN. The basic model for both species is architecturally the same, and to get either type III unit RMs or type IV unit RMs, connection parameters were adjusted. Interestingly, regardless of the RM type, these units in gerbils and cats show spectral notch sensitivity and are thought to play a role in sound localization in the median plane. In this study, further parameter adjustments were made to systematically explore their effect on P-cell RMs. Significantly, type I, type III, type III-i, type IV, type IV-T and type V unit RMs can be created for the modeled P-cells. Thus major RMs observed in the cat and gerbil DCN are recreated by the model. These results suggest that RMs of individual DCN projection neurons are the result of specific assortment of excitatory and inhibitory inputs to that neuron and that subtle differences in the complement of inputs can result in different RM types. Modulation of the efficacy of certain synapses suggests that RM type may change dynamically.

Animals↗

Using evoked potentials to match interaural electrode pairs with bilateral cochlear implants.

Bilateral cochlear implantation seeks to restore the advantages of binaural hearing to the profoundly deaf by providing binaural cues normally important for accurate sound localization and speech reception in noise. Psychophysical observations suggest that a key issue for the implementation of a successful binaural prosthesis is the ability to match the cochlear positions of stimulation channels in each ear. We used a cat model of bilateral cochlear implants with eight-electrode arrays implanted in each cochlea to develop and test a noninvasive method based on evoked potentials for matching interaural electrodes. The arrays allowed the cochlear location of stimulation to be independently varied in each ear. The binaural interaction component (BIC) of the electrically evoked auditory brainstem response (EABR) was used as an assay of binaural processing. BIC amplitude peaked for interaural electrode pairs at the same relative cochlear position and dropped with increasing cochlear separation in either direction. To test the hypothesis that BIC amplitude peaks when electrodes from the two sides activate maximally overlapping neural populations, we measured multiunit neural activity along the tonotopic gradient of the inferior colliculus (IC) with 16-channel recording probes and determined the spatial pattern of IC activation for each stimulating electrode. We found that the interaural electrode pairings that produced the best aligned IC activation patterns were also those that yielded maximum BIC amplitude. These results suggest that EABR measurements may provide a method for assigning frequency-channel mappings in bilateral implant recipients, such as pediatric patients, for which psychophysical measures of pitch ranking or binaural fusion are unavailable.

Animals↗

Tonotopic projections of the auditory nerve to the cochlear nucleus angularis in the barn owl.

The nucleus angularis (NA), one of the two cochlear nuclei of birds, plays an important role in the processing of sound intensity. To begin investigating the NA in detail in the barn owl, which is a popular animal model for neural mechanisms of sound localization, a frequency map for this nucleus is presented here. Focal injections of horseradish peroxidase or neurobiotin were placed either in the NA or in the cochlear nucleus magnocellularis, labeling small groups of auditory nerve fibers of known characteristic frequency (CF) from 0.25 to 9.6 kHz. The courses of their axonal branches were used to construct a composite average map of the tonotopic frequency representation in the nucleus angularis. Nucleus angularis in the barn owl, as seen in frontal sections, resembles a sheet of cells bent approximately into an S shape. The lowest frequencies were found represented at the ventromedial extreme. The representation of increasingly higher frequencies then followed the S shape, with the highest frequencies located at the ventrolateral tip. Auditory nerve fibers of a given CF always entered the nucleus angularis within a well-restricted area and then traveled along their isofrequency band within the NA while branching off terminals. The isofrequency bands were typically slanted from caudo-ventro-medial to rostro-dorso-lateral. The basic tonotopic organization is comparable to that found in other birds, the major differences being the large size and unusual shape of the barn owl's nucleus angularis.

Animals↗

Auditory cortex lesions and discrimination of spatial location by the rat.

Five normal rats and four rats with bilateral lesions of auditory cortex were tested by the conditioned suppression procedure to determine their abilities to discriminate between spatially separated sound sources. The discrimination involved detection of a change in location of a train of clicks from a speaker on the animals' left to a speaker on the right. The separation between speakers was varied from 180 degrees to 90 degrees, 45 degrees, 22 degrees, 12 degrees, 6 degrees, and psychophysical functions were obtained using a method of descending limits. Both normal and brain-damaged animals were capable of discriminating left from right clicks and psychophysical curves were similar for the two groups. Histological analysis indicated that the lesions in each of the four brain-damaged rats destroyed primary auditory cortex as well as surrounding belt areas. Therefore, for the rat, auditory cortex was not found to be essential for discrimination of the spatial locations of auditory stimuli. The results are discussed in light of impairments in sound localization following lesions of auditory cortex in other mammalian species.

Acoustic Stimulation↗