A functional role for the ventrolateral prefrontal cortex in non-spatial auditory cognition.

Spatial and non-spatial sensory information is hypothesized to be evaluated in parallel pathways. In this study, we tested the spatial and non-spatial sensitivity of auditory neurons in the ventrolateral prefrontal cortex (vPFC), a cortical area in the non-spatial pathway. Activity was tested while non-human primates reported changes in an auditory stimulus' spatial or non-spatial features. We found that vPFC neurons were reliably modulated during a non-spatial auditory task but were not modulated during a spatial auditory task. The degree of modulation during the non-spatial task correlated positively with the monkeys' behavioral performance. These results are consistent with the hypotheses that the vPFC is part of a circuit involved in non-spatial auditory processing and that the vPFC plays a functional role in non-spatial auditory cognition.

Reaches to sounds encoded in an eye-centered reference frame.

A recent hypothesis suggests that neurons in the lateral intraparietal area (LIP) and the parietal reach region (PRR) encode movement plans in a common eye-centered reference frame. To test this hypothesis further, we examined how PRR neurons encode reach plans to auditory stimuli. We found that PRR activity was affected by eye and initial hand position. Population analyses, however, indicated that PRR neurons were affected more strongly by eye position than by initial hand position. These eye position effects were appropriate to maintain coding in eye coordinates. Indeed, a significant population of PRR neurons encoded reaches to auditory stimuli in an eye-centered reference frame. These results extend the hypothesis that, regardless of the modality of the sensory input or the eventual action, PRR and LIP neurons represent movement plans in a common, eye-centered representation.

Maps versus clusters: different representations of auditory space in the midbrain and forebrain.

The auditory system determines the location of stimuli based on the evaluation of specific cues. The analysis begins in the tonotopic pathway, where these cues are processed in parallel, frequency-specific channels. This frequency-specific information is processed further in the midbrain and in the forebrain by specialized, space-processing pathways that integrate information across frequency channels, creating high-order neurons tuned to specific locations in space. Remarkably, the results of this integrative step are represented very differently in the midbrain and forebrain: in the midbrain, space is represented in maps, whereas, in the forebrain, space is represented in clusters of similarly tuned neurons. We propose that these different representations reflect the different roles that these two brain areas have in guiding behavior.

Representation of binaural spatial cues in field L of the barn owl forebrain.

This study examined the representation of spatial information in the barn owl Field L, the first telencephalic processing stage of the classical auditory pathway. Field L units were recorded extracellularly, and their responses to dichotically presented interaural time differences (ITD) and interaural level differences (ILD) were tested. We observed a variety of tuning profiles in Field L. Some sites were not sensitive to ITD or ILD. Other sites, especially those in the high-frequency region, were highly selective for values of ITD and ILD. These sites had multipeaked (commonly called "phase ambiguous") ITD tuning profiles and were tuned for a single value of ILD. The tuning properties of these sites are similar to those seen in the lateral shell of the central nucleus of the inferior colliculus. Although the tuning properties of Field L sites were similar to those observed in the inferior colliculus, the functional organization of this spatial information was fundamentally different. Whereas in the inferior colliculus spatial information is organized into global topographics maps, in Field L spatial information is organized into local clusters, with sites having similar binaural tuning properties grouped together. The representation of binaural cues in Field L suggests that it is involved in auditory space processing but at a lower level of information processing than the auditory archistriatum, a forebrain area that is specialized for processing spatial information, and that the levels of information processing in the forebrain space processing pathway are remarkably similar to those in the well-known midbrain space processing pathway.

Forebrain pathway for auditory space processing in the barn owl.

The forebrain plays an important role in many aspects of sound localization behavior. Yet, the forebrain pathway that processes auditory spatial information is not known for any species. Using standard anatomic labeling techniques, we used a "top-down" approach to trace the flow of auditory spatial information from an output area of the forebrain sound localization pathway (the auditory archistriatum, AAr), back through the forebrain, and into the auditory midbrain. Previous work has demonstrated that AAr units are specialized for auditory space processing. The results presented here show that the AAr receives afferent input from Field L both directly and indirectly via the caudolateral neostriatum. Afferent input to Field L originates mainly in the auditory thalamus, nucleus ovoidalis, which, in turn, receives input from the central nucleus of the inferior colliculus. In addition, we confirmed previously reported projections of the AAr to the basal ganglia, the external nucleus of the inferior colliculus (ICX), the deep layers of the optic tectum, and various brain stem nuclei. A series of inactivation experiments demonstrated that the sharp tuning of AAr sites for binaural spatial cues depends on Field L input but not on input from the auditory space map in the midbrain ICX: pharmacological inactivation of Field L eliminated completely auditory responses in the AAr, whereas bilateral ablation of the midbrain ICX had no appreciable effect on AAr responses. We conclude, therefore, that the forebrain sound localization pathway can process auditory spatial information independently of the midbrain localization pathway.

Morphometric changes in the chick nucleus magnocellularis following acoustic overstimulation.

The present investigation considered the effects of cochlear damage caused by exposure to intense sound on the nucleus magnocellularis of the chick. Neonatal chicks exposed to intense sound were separated into four groups with post-exposure recovery durations of 0, 15, 27, and 43 days. Four age-matched, non-exposed control groups were also formed. At each recovery interval, the control and exposed birds were sacrificed and their brains prepared for paraffin embedding. The brain stem region containing the nucleus magnocellularis (NM) was serially sectioned in the coronal plane. All sections containing NM cells were identified and then coded in terms of their percentile distance from the most caudolateral section. Sections along the nucleus at the 15th, 30th, 50th, 65th, 80th, and 95th percentile positions were selected for evaluation, and the cross-sectional areas of individual NM cells in these sections were then measured. Cell areas were corrected for the bias introduced by eccentricity of the nucleus. The number of NM cells per 1,000 microm2 was also calculated at the 50th and 65th percentile positions. These procedures were repeated for the age-matched, non-exposed control animals. The cross-sectional cell area in exposed animals, immediately after the exposure, was reduced significantly at all positions, but returned to near normal by 43 days of recovery. However, the coronal area of NM in the sections at the 50th and 65th percentile position, as well as NM cell density, were unaffected by the exposure at all recovery intervals. The observation of structural recovery in NM cells at 43 days post-exposure was remarkable because it occurred at least 4 weeks after complete functional restoration of single-cell activity in the NM. The shrinkage in NM cell size throughout the nucleus may be due to a general reduction in spontaneous activity in the cochlear nerve fibers caused by the acoustic injury to the chick basilar papilla.

Posterior parietal areas specialized for eye movements (LIP) and reach (PRR) using a common coordinate frame.

The posterior parietal cortex (PPC) has long been considered a sensory area specialized for spatial awareness and the directing of attention. However, a new, far reaching concept is now emerging that this area is involved in integrating sensory information for the purpose of planning action. Moreover, experiments by our group and others over the last two decades indicate that PPC is in fact anatomically organized with respect to action. PPC also is an 'association' cortex which must combine different sensory modalities which are coded in different coordinate frames. We have found, at least for two different cortical areas within PPC, that different sensory signals are brought into a common coordinate frame. This coordinate frame codes locations with respect to the eye, but also gain modulates the activity by eye and body position signals. An interesting feature of this coordinate representation at the population level is that it codes concurrently target locations in multiple coordinate frames (eye, head, body and world). Depending on how this population of neurons is sampled, different coordinate transformations can be accomplished by the same population of neurons.

Representation of frequency in the primary auditory field of the barn owl forebrain.

1. The primary auditory field (PAF) constitutes the first telencephalic stage of auditory information processing in the classical auditory pathway. In this study we investigated the frequency representation in the PAF of the barn owl, a species with a broad frequency range of hearing and a highly advanced auditory system. 2. Single- and multiunit sites were recorded extracellularly in ketamine-anesthetized owls. The frequency response properties of PAF sites were assessed with the use of digitally synthesized dichotic stimuli. PAF sites (n = 442) either were unresponsive to tonal stimulation (but responsive to noise stimuli), were tuned for frequency, or had multipeaked frequency response profiles. Tuned sites responded best to frequencies between 0.2 and 8.8 kHz, a range that encompasses nearly the entire hearing range of the barn owl. Most sites responding best to frequencies < 4 kHz had relatively broad frequency tuning, whereas sites responding best to higher frequencies had either broad or narrow frequency tuning. Sites with multipeaked frequency response profiles typically had two response peaks. The first peak was usually between 1 and 3 kHz and the second was usually between 5 and 8 kHz; there was no systematic relationship between the two peak frequencies. 3. In dorsoventral electrode penetrations that contained sites with tuned and/or multipeaked response profiles, a "common frequency" was identified that elicited a maximal response from all of the sites in the penetration. 4. The PAF contains a single tonotopic field. Units tuned to low frequencies are located caudomedially, whereas units tuned to high frequencies are located rostrolaterally. Compared with the frequency representation along the basilar papilla and in other auditory structures, the PAF overrepresents low frequencies (< 4 kHz) that are important for barn owl vocalizations. Conversely, high frequencies (> or = 4 kHz), which are necessary for precise sound localization, are underrepresented relative to these more peripheral auditory structures. 5. There was considerable interindividual variability both in the relative magnification of different frequency ranges and in the orientation of the tonotopic map in the brain. 6. These results suggest that the barn owl PAF, like the mammalian primary auditory cortex, is a general processor of auditory information that is involved in the analysis of both the meaning (such as species-specific vocalizations) and the location of auditory stimuli. In addition, the high degree of interindividual variability in the representation of frequency information suggests that the barn owl PAF, like the mammalian auditory cortex, is subject to modification by sensory experience.

Characterization of a forebrain gaze field in the archistriatum of the barn owl: microstimulation and anatomical connections.

We present evidence that the archistriatum in the forebrain of the barn owl participates in gaze control, that it can mediate gaze changes independently of the optic tectum (OT), and that it projects in parallel to both the OT and to saccade-generating circuitry in the brainstem tegmentum. These properties are similar to those of the frontal eye fields (FEF) in the prefrontal cortex of primates. The forebrain was surveyed for sites where electrical microstimulation would induce head saccades. Head (and eye) saccades were elicited from the anterior 70% of the archistriatum, a region that we refer to as the archistriatal gaze fields (AGF). At single stimulation sites in the AGF, saccade amplitude tended to vary as a function of stimulation parameters (current strength, pulse frequency, and train duration) and starting head position. In contrast, saccade direction was largely independent of these parameters. Saccade direction did vary over a wide range of primarily contraversive directions with the site of stimulation in the AGF. Using anatomical pathway tracing techniques, we found that the archistriatum projects strongly and in parallel to the deep layers of the OT and to nuclei in the midline brainstem tegmentum. Previous work has shown that electrical microstimulation of either of these brainstem regions evokes saccadic movements of the head and/or eyes (du Lac and Knudsen, 1990; Masino and Knudsen, 1992b). Inactivation of the OT with lidocaine reduced the size but did not eliminate (or change the direction of) the saccades evoked by AGF stimulation. The direct anatomical pathway from the archistriatum to the midline tegmental nuclei can account for saccades that persist following OT inactivation. The similarities between the AGF in barn owls and the FEF in primates suggest that the same general plan of anatomical and functional organization supports the contribution of the forebrain to gaze control in a wide variety of species.

Binaural tuning of auditory units in the forebrain archistriatal gaze fields of the barn owl: local organization but no space map.

We identified a region in the archistriatum of the barn owl forebrain that contains neurons sensitive to auditory stimuli. Nearly all of these neurons are tuned for binaural localization cues. The archistriatum is known to be the primary source of motor-related output from the avian forebrain and, in barn owls, contributes to the control of gaze, much like the frontal eye fields in monkeys. The auditory region is located in the medial portion of the archistriatum, at the level of the anterior commissure, and is within the region of the archistriatum from which head saccades can be elicited by electrical microstimulation (see preceding companion article, Knudsen et al., 1995). Free-field measurements revealed that auditory sites have large, spatial receptive fields. However, within these large receptive fields, responses are tuned sharply for sound source location. Dichotic measurements showed that auditory sites are tuned broadly for frequency and that the majority are tuned to particular values of interaural time differences and interaural level differences, the principal cues used by barn owls for sound localization. The tuning of sites to these binaural cues is essentially independent of sound level. The auditory properties of units in the medial archistriatum are similar to those of units in the optic tectum, a structure that also contributes to gaze control. Unlike the optic tectum, however, the auditory region of the archistriatum does not contain a single, continuous auditory map of space. Instead, it is organized into dorsoventral clusters of sites with similar binaural (spatial) tuning. The different representations of auditory space in closely related structures in the forebrain (archistriatum) and midbrain (optic tectum) probably reflect the fact that the forebrain contributes to a wide variety of sensorimotor tasks more complicated than gaze control.

The effect of acoustic overexposure on the tonotopic organization of the nucleus magnocellularis.

We assessed the effect a sound-induced cochlear lesion had on the tonotopic organization of the nucleus magnocellularis (NM) immediately after acoustic overexposure and following a twelve day recovery period. The acoustic overexposure was a 0.9 kHz tone at 120 dB sound pressure level (SPL) for 48 h. Initially after the acoustic overexposure, the tonotopic organization of the NM was statistically different from that of age-matched controls. Specifically, it appeared that the center frequencies of units in the frequency region of the NM associated with the acoustic overexposure had higher center frequencies than their control counterparts. Following a twelve day recovery period, when threshold sensitivity and frequency selectivity were operating normally, the tonotopic organization of the NM was not statistically different from age-matched controls. We suggest that the sound-induced changes in the tonotopic organization of the NM reflect peripheral damage in the basilar papilla. It has been well documented that similar exposure paradigms produce a loss of short hair cells and a degeneration of the tectorial membrane in the region of the basilar membrane associated with the overexposure. We postulate that the loss of these structures alters the micromechanics and tuning of the basilar membrane which is reflected in the observed changes in NM tonotopy. Following the recovery period, when those structures destroyed by the overexposure had regenerated and basilar membrane micromechanics were operating normally, the tonotopic organization of the NM returned to normal.

Auditory tuning for spatial cues in the barn owl basal ganglia.

1. The basal ganglia are known to contribute to spatially guided behavior. In this study, we investigated the auditory response properties of neurons in the barn owl paleostriatum augmentum (PA), the homologue of the mammalian striatum. The data suggest that the barn owl PA is specialized to process spatial cues and, like the mammalian striatum, is involved in spatial behavior. 2. Single- and multiunit sites were recorded extracellularly in ketamine-anesthetized owls. Spatial receptive fields were measured with a free-field sound source, and tuning for frequency and interaural differences in timing (ITD) and level (ILD) was assessed using digitally synthesized dichotic stimuli. 3. Spatial receptive fields measured at nine multiunit sites were tuned to restricted regions of space: tuning widths at half-maximum response averaged 22 +/- 9.6 degrees (mean +/- SD) in azimuth and 54 +/- 22 degrees in elevation. 4. PA sites responded strongly to broadband sounds. When frequency tuning could be measured (n = 145/201 sites), tuning was broad, averaging 2.7 kHz at half-maximum response, and tended to be centered near the high end of the owl's audible range. The mean best frequency was 6.2 kHz. 5. All PA sites (n = 201) were selective for both ITD and ILD. ITD tuning curves typically exhibited a single, large "primary" peak and often smaller, "secondary" peaks at ITDs ipsilateral and/or contralateral to the primary peak. Three indices quantified the selectivity of PA sites for ITD. The first index, which was the percent difference between the minimum and maximum response as a function of ITD, averaged 100 +/- 29%. The second index, which represented the size of the largest secondary peak relative to that of the primary peak, averaged 49 +/- 23%. The third index, which was the width of the primary ITD peak at half-maximum response, averaged only 66 +/- 35 microseconds. 6. The majority (96%; n = 192/201) of PA sites were tuned to a single "best" value of ILD. The widths of ILD tuning curves at half-maximum response averaged 24 +/- 9 dB. 7. On average, sound level had no effect on a site's best ITD or best ILD nor did it affect ITD tuning widths. ILD tuning widths did, however, tend to increase slightly with sound level (average effect was 0.1 dB ILD/dB). 8. Most PA sites responded best to contralateral-ear leading ITDs with a majority being tuned to ITDs near 0 microsecond (corresponding to sound-source locations just contralateral to the midline).(ABSTRACT TRUNCATED AT 400 WORDS)

Middle-ear development. IV. Umbo motion in neonatal mice.

Laser interferometry was used to measure umbo velocity in the developing BALB/c mouse middle ear at 133 pure-tone frequencies between 2.0 kHz and 40.0 kHz, all at a constant 100 dB sound pressure level. Umbo velocities increased with age across the entire frequency range, and reached adult-like levels by about 19 days between 2.0 and 22.0 kHz. Velocities at 28.0 and 34.0 kHz took 27 and 52 days respectively to reach adult-like levels. A simple middle-ear model utilizing compliance, resistance, and inertia elements matched the general trends of our velocity results and provided an indication of the anatomical basis for the growth in umbo velocity. The model suggested that velocity development at the lowest frequencies may be attributed to increases in tympanic membrane compliance. The model also indicated that both the frictional resistance of the middle ear and the inertia of the tympanic membrane and ossicles decreased during the growth period. At frequencies below 20.0 kHz, age-related increases in umbo velocity coincided with improvements in N1 thresholds recorded from the round window and evoked potential thresholds obtained from the cochlear nucleus. These results indicated that the functional development of the middle-ear plays a major role in the development of hearing in the mouse.

The contribution of middle-ear sound conduction to auditory development.

1. This presentation summarizes recent research concerning the maturation of sound transmission through the middle-ear conducting system of various vertebrate species. 2. In this review the structural and functional aspects of middle-ear development are presented, as well as the relationships between these events. 3. Functional changes in middle-ear transmission demonstrated that the efficiency of sound conduction improved dramatically during the period of development. 4. The functional development of the middle ear was then compared with the maturation of auditory sensitivity measured from more central locations in the auditory system. 5. The results indicated that conductive development in some species determined the rate of sensitivity development. 6. These findings add an important dimension to our understanding of the underlying processes of hearing maturation.

Middle-ear development. V: Development of umbo sensitivity in the gerbil.

PURPOSE: The development of the umbo response in the gerbil was studied in order to further elucidate the contribution of the middle ear to the development of auditory function. MATERIALS AND METHODS: Laser interferometry was used to study the development of umbo velocity in Mongolian gerbils between 10 days after birth and maturity. RESULTS: Before 15 days after birth, immaturities in the middle ear prevented any reliable measures of middle-ear motion. However, between 15 and 20 days after birth, a 10 dB improvement in umbo velocity was noted in the low-frequency (0.5 to 2.0 kHz) region of the umbo response. This improvement in sensitivity was correlated to an increased admittance due to an expanding bulla volume. Interestingly, umbo velocity remained relatively constant in the mid- and high-frequency regions of the response curve between 15 and 42 days after birth. The umbo response in the adult gerbil was decidedly different when compared with the response at 42 days after birth. CONCLUSION: We speculate that a decrease in bulla volume along with increased ossicular mass contributed to the changes in the adult umbo response. When the maturation of the umbo response was compared with more central ontogenetic measures, it became apparent that structures more central to the middle ear continued to develop well past the time the middle ear was structurally and functionally mature.

The effects of sound overexposure on the spectral response patterns of nucleus magnocellularis in the neonatal chick.

Spectral response plots from single cells in the chick nucleus magnocellularis were obtained following a 48 h exposure to a 0.9 kHz pure tone at 120 dB sound pressure level and after a recovery period of 12 days. Immediately after removal from the exposure, a variety of changes in the spectral response patterns of nucleus magnocellularis cells were noted. In particular, at recovery day 0, there was a significant decrease in spontaneous rate; a substantial loss of threshold sensitivity and frequency selectivity; and alterations in both the slope and dynamic range of the rate-intensity function. Interestingly, the maximum discharge rate appeared unaffected by the intense sound. Twelve days after removal from overstimulation, auditory function appeared to be operating at normal levels of efficacy as spontaneous rate, threshold sensitivity, frequency selectivity, and the dynamic range of the rate-intensity function were statistically identical to similar measures in nonexposed control birds. The loss and restoration of auditory function is correlated to structural damage and repair of the avian basilar papilla.

Middle ear development. III: Morphometric changes in the conducting apparatus of the Mongolian gerbil.

Middle-ear structural ontogeny was examined in 12 age groups of Mongolian gerbils between 2 and 42 days after birth. Measurements of tympanic membrane surface area; depth of the tympanic membrane cone; the lengths of the malleus and incus long processes; and stapes footplate, annular space, and oval window areas were obtained using video micrographs and computer digitization techniques. The incus long process matured first at 3.5 days after birth, while the pars flaccida surface area was the last middle-ear variable studied to reach adult size (26 days after birth). The incus long process increased its length by 30% from 0.5 mm to 0.65 mm. The malleus long process, however, demonstrated much more relative growth (47%). Pars tensa area expanded from 6.35 mm2 at two days after birth to its adult size of 16.9 mm2 and the stapes footplate expanded by 50%. The developmental changes observed in middle-ear anatomy are then discussed with regard to their contribution to the functional maturation of both the middle ear and more central auditory function.

Middle-ear development: II. Morphometric changes in the conducting apparatus of the chick.

The ontogeny of various middle-ear structures was examined in 11 groups of chicks between 10 days embryonic and adult. Measurements of the tympanic membrane surface area and height, columella length, and that of the columella footplate, annular ligament, and oval window area were obtained using video micrographs and computer digitization techniques. The oval window matures first at 53 days post-hatching, whereas the columella achieves adult size at 74 days. The tympanic membrane surface area is the last middle-ear variable studied to reach adult size (79 days post-hatch). The columella increases its length from 0.63 mm (10 days embryonic) to 2.73 mm in the adult. The tympanic membrane area expands by 280% whereas the columellar footplate area increases by 11x. As a result, the pressure amplification of the middle ear due to the tympanic membrane/columellar footplate area ratio improves by over 400%. These data further contribute to our understanding of the functional development of the middle ear.

Middle ear development. I: Extra-stapedius response in the neonatal chick.

A laser interferometry system was used to study the ontogeny of tympanic membrane mechanical responses to sound as measured at the tip of the extra-stapedius (ES) in chicks. The ES velocity and phase responses in the frequency range between 0.2 and 10.0 kHz were measured in animals ranging from 3 days of age to adult. The slope of the low frequency response remained constant with age while the ES low frequency sensitivity increased by 11 dB. The sensitivity improvement indicated an increase in low frequency middle-ear admittance. However, there was no consistent developmental improvement in high frequency ES sensitivity. Comparisons between the growth of low frequency ES velocity, the development of admittance magnitude, and evoked potential threshold sensitivity developmental data indicated no clear relation between these measures.