Functional organization of spectral receptive fields in the primary auditory cortex of the owl monkey.

Recent experiments in the cat have demonstrated that several response parameters, including frequency tuning, intensity tuning, and FM selectivity, are spatially segregated across the isofrequency axis. To investigate whether a similar functional organization exists in the primate, we have studied the spatial distribution of pure-tone receptive field parameters across the primary auditory cortex (AI) in six owl monkeys (Aotus trivirgatus). The distributions of binaural interaction types and onset latency were also examined. Consistent with previous studies, the primary auditory cortex contained a clear cochleotopic organization. We demonstrate here that several other properties of the responses to tonal stimuli also showed nonrandom spatial distributions that were largely independent from each other. In particular, the sharpness of frequency tuning to pure tones, intensity tuning and sensitivity, response latency, and binaural interaction types all showed spatial variations that were independent from the representation of characteristic frequency and from each other. Statistical analysis confirmed that these organizations did not reflect random distributions. The overall organizational pattern of overlaying but independent functional maps that emerged was quite similar to that seen in AI of cats and, in general, appears to reflect a fundamental organization principle of primary sensory cortical fields.

Differential effect of near-threshold stimulus intensities on sound localization performance in azimuth and elevation in normal human subjects.

The ability of humans to localize sounds remains relatively constant across a range of intensities well above detection threshold, and increasing the spectral content of the stimulus results in an improvement in localization ability. For broadband stimuli, intensities near detection threshold result in fewer and weaker binaural cues used in azimuth localization because the stimulus energy at the high- and low-frequency ends of the audible spectrum fall below detection threshold. Thus, the ability to localize broadband sounds in azimuth is predicted to be degraded at audible but near threshold stimulus intensities. The spectral cues for elevation localization (spectral peaks and notches generated by the head-related transfer function) span a narrower frequency range than those for azimuth. As the stimulus intensity decreases, the ability to detect the stimulus frequencies corresponding to the spectral notches will be more strongly affected than the ability to detect frequencies outside the range where these spectral cues are useful. Consequently, decreasing the stimulus intensity should degrade localization in both azimuth and elevation and create a greater deficit in elevation localization due to the narrower band of audible frequencies containing elevation cues compared to azimuth cues. The present study measured the ability of 11 normal human subjects to localize broadband noise stimuli along the midsagittal plane and horizontal meridian at stimulus intensities of 14, 22, and 30 dB above the subject's detection threshold using a go/no-go behavioral paradigm. Localization ability decreased in both azimuth and elevation with decreasing stimulus intensity, and this effect was greater on localization in elevation than on localization in azimuth. The differential effects of stimulus intensity on sound localization in azimuth and elevation found in the present study may provide a valuable tool in investigating the neural correlates of sound location perception.

Temporal and spatial dependency of the ventriloquism effect.

The perception of the spatial location of an auditory stimulus can be captured by a spatially disparate visual stimulus, a phenomenon known as the ventriloquism effect. This study investigated the temporal and spatial dependency of this illusion. In the temporal domain, only disparities of 50-100 ms were perceived as simultaneous, and disparities where the visual stimulus occurred before the auditory stimulus were more effective in creating the illusion. In the spatial domain, the illusion was elicited most strongly at spatial disparities below spatial discrimination thresholds. There was also a significant interaction between temporal and spatial disparities. These results indicate that both temporal and spatial parameters are critical in the perception of real world objects in extrapersonal space.

Alterations in correlated activity parallel ICMS-induced representational plasticity.

We studied neural interactions by cross correlation analysis during representational plasticity induced by intracortical microstimulation (ICMS). Neuron pairs were simultaneously recorded in area 3b in adult New World monkeys, and in cortical field SI in adult rats. In normal animals, the degree of correlated spontaneous activity corresponded to the extent of receptive field overlap. After several hours of ICMS, the spatial extents of cortex over which correlated activity could be recorded was enlarged several-fold. Mapping experiments revealed that increased correlated activity was only recorded within that cortical sector that was representationally reorganized, indicating a close relationship between cortical reorganization and cooperative processes. Results support the hypothesis that discharge coincidence is crucial for the formation of functionally coupled neural groups, and implicate dynamically maintained groups in the genesis of postontogenetic plasticity.

Response profiles of auditory cortical neurons to tones and noise in behaving macaque monkeys.

The primate auditory cortex is anatomically divided into several areas, but little is known about the functional differences between these areas. Similarly, although neurons in sub-cortical auditory areas of other species have been classified into distinct categories, these criteria have not been applied in primates. This study measured the responses of single neurons in the primary auditory cortex (AI) and the caudomedial field (CM) to tones and noise. Most neurons could be qualitatively classified as onset, sustained, or sustained-onset, but never as primary (VIII nerve)-like or chopper. Quantitative analysis showed a continuum of response types, from having only onset responses to responding throughout the stimulus period. AI neurons had higher firing rates that CM neurons, but CM neurons had higher firing rates to noise stimuli compared to tone stimuli, and a greater percentage of CM neurons had excitatory responses after stimulus offset. There were no differences in the percentage of neurons that had tonic or inhibitory responses. These results indicate that the responses of neurons in the primate auditory cortex are better described as a continuum rather than as discrete classes, and provide further evidence that auditory information is processed in series between AI and CM in the primate.

Regional and age-related differences in GAD67 expression of parvalbumin- and calbindin-expressing neurons in the rhesus macaque auditory midbrain and brainstem.

Neurons expressing the calcium binding proteins (CaBPs) parvalbumin (PV) and calbindin (CB) have shown age-related density changes throughout the ascending auditory system of both rodents and macaque monkeys. In the cerebral cortex, neurons expressing these CaBPs express markers of γ-aminobutyric acidergic neurotransmission, such as GAD67, and have well-understood physiological response properties. Recent evidence suggests that, in the rodent auditory brainstem, CaBP-containing cells do not express GAD67. It is unknown whether PV- and CB-containing cells in subcortical auditory structures of macaques similarly do not express GAD67, and a better understanding of the neurotransmission of neurons expressing these proteins is necessary for understanding the age-related changes in their density throughout the macaque auditory system. This was investigated with immunofluorescent double-labeling techniques to coregister PV- and CB-expressing neurons with GAD67 in the superior olivary complex and the inferior colliculus of young and aged rhesus macaques. The proportions of GAD67-expressing PV- and CB-positive neurons were computed with unbiased sampling techniques. Our results indicate that between 42% and 62% of PV- and CB-positive neurons in the auditory brainstem and midbrain express GAD67, which is significantly less than in the cerebrum. In general, fewer PV(+) neurons and more CB(+) neurons expressed GAD67 as a function of age. These results demonstrate that the inhibitory molecular profile of PV- and CB-expressing neurons can change with age in subcortical auditory structures and that these neurons are distinct from the well-described inhibitory interneurons that express these proteins in the cerebral cortex.

Single-neuron responses to rapidly presented temporal sequences in the primary auditory cortex of the awake macaque monkey.

One fundamental process of the auditory system is to process rapidly occurring acoustic stimuli, which are fundamental components of complex stimuli such as animal vocalizations and human speech. Although the auditory cortex is known to subserve the perception of acoustic temporal events, relatively little is currently understood about how single neurons respond to such stimuli. We recorded the responses of single neurons in the primary auditory cortex of alert monkeys performing an auditory task. The stimuli consisted of four tone pips with equal duration and interpip interval, with the first and last pip of the sequence being near the characteristic frequency of the neuron under study. We manipulated the rate of presentation, the frequency of the middle two tone pips, and the order by which they were presented. Our results indicate that single cortical neurons are ineffective at responding to the individual tone pips of the sequence for pip durations of <12 ms, but did begin to respond synchronously to each pip of the sequence at 18-ms durations. In addition, roughly 40% of the neurons tested were able to discriminate the order that the two middle tone pips were presented in at durations of > or =24 ms. These data place the primate primary auditory cortex at an early processing stage of temporal rate discrimination.

Spatial processing in the auditory cortex of the macaque monkey.

The patterns of cortico-cortical and cortico-thalamic connections of auditory cortical areas in the rhesus monkey have led to the hypothesis that acoustic information is processed in series and in parallel in the primate auditory cortex. Recent physiological experiments in the behaving monkey indicate that the response properties of neurons in different cortical areas are both functionally distinct from each other, which is indicative of parallel processing, and functionally similar to each other, which is indicative of serial processing. Thus, auditory cortical processing may be similar to the serial and parallel "what" and "where" processing by the primate visual cortex. If "where" information is serially processed in the primate auditory cortex, neurons in cortical areas along this pathway should have progressively better spatial tuning properties. This prediction is supported by recent experiments that have shown that neurons in the caudomedial field have better spatial tuning properties than neurons in the primary auditory cortex. Neurons in the caudomedial field are also better than primary auditory cortex neurons at predicting the sound localization ability across different stimulus frequencies and bandwidths in both azimuth and elevation. These data support the hypothesis that the primate auditory cortex processes acoustic information in a serial and parallel manner and suggest that this may be a general cortical mechanism for sensory perception.

Rapidly induced auditory plasticity: the ventriloquism aftereffect.

Cortical representational plasticity has been well documented after peripheral and central injuries or improvements in perceptual and motor abilities. This has led to inferences that the changes in cortical representations parallel and account for the improvement in performance during the period of skill acquisition. There have also been several examples of rapidly induced changes in cortical neuronal response properties, for example, by intracortical microstimulation or by classical conditioning paradigms. This report describes similar rapidly induced changes in a cortically mediated perception in human subjects, the ventriloquism aftereffect, which presumably reflects a corresponding change in the cortical representation of acoustic space. The ventriloquism aftereffect describes an enduring shift in the perception of the spatial location of acoustic stimuli after a period of exposure of spatially disparate and simultaneously presented acoustic and visual stimuli. Exposure of a mismatch of 8 degrees for 20-30 min is sufficient to shift the perception of acoustic space by approximately the same amount across subjects and acoustic frequencies. Given that the cerebral cortex is necessary for the perception of acoustic space, it is likely that the ventriloquism aftereffect reflects a change in the cortical representation of acoustic space. Comparisons between the responses of single cortical neurons in the behaving macaque monkey and the stimulus parameters that give rise to the ventriloquism aftereffect suggest that the changes in the cortical representation of acoustic space may begin as early as the primary auditory cortex.

Spatial processing in the primate auditory cortex.

Spatial localization of auditory stimuli is dependent on the cerebral cortex, yet it remains unclear how cortical activity gives rise to spatial percepts. It has recently been proposed that spatial information is processed serially within the primate auditory cortex, initially in the primary auditory cortex (AI) through the auditory areas caudal to AI, particularly the caudomedial (CM) and caudolateral fields, and onward to the parietal lobe. The activity of single neurons in AI and CM supports this hypothesis, where a greater percentage of CM neurons are sensitive to the spatial location of acoustic stimuli than AI neurons, and the spatial sensitivity of CM neurons extends across a broader range of the stimulus spectrum compared to AI neurons. Further, populations of CM neurons are better able to predict sound localization ability than are populations of AI neurons. We have recently explored the effects of stimulus intensity on both sound localization performance and the spatial sensitivity of auditory cortical neurons. The preliminary results of these experiments again indicate that spatial information is serially processed between AI and the caudal fields. The effects of visual stimulation on auditory localization have also been investigated. Under the appropriate circumstances, visual stimuli can "capture" the spatial location of auditory stimuli in both humans and monkeys. This perceptual illusion suggests that there is a plastic shift in auditory spatial perception. Where the representation of this shift resides is unknown, although two likely candidates are the multimodal regions of the parietal lobe and the superior temporal sulcus.

Effects of attention on MT and MST neuronal activity during pursuit initiation.

The responses of neurons in monkey extrastriate areas MT (middle temporal) and MST (medial superior temporal), and the initial metrics of saccadic and pursuit eye movements, have previously been shown to be better predicted by vector averaging or winner-take-all models depending on the stimulus conditions. To investigate the potential influences of attention on the neuronal activity, we measured the responses of single MT and MST neurons under identical stimulus conditions when one of two moving stimuli was the target for a pursuit eye movement. We found the greatest attentional modulation across neurons when two stimuli moved through the receptive field (RF) of the neuron and the stimulus motion was initiated at least 450 ms before reaching the center of the RF. These conditions were the same as those in which a winner-take-all model better predicted both the eye movements and the underlying neuronal activity. The modulation was almost always an increase of activity, and it was about equally frequent in MT and MST. A modulation of >50% was observed in approximately 41% of MT neurons and 27% of MST neurons. Responses to all directions of motion were modulated so that the direction tuning curves in the attended and unattended conditions were similar. Changes in the background activity with target selection were small and unlikely to account for the observed attentional modulation. In contrast, there was little change in the neuronal response with attention when the stimulus reached the RF center 150 ms after motion onset, which was also the condition in which the vector average model better predicted the initial eye movements and the activity of the neurons. These results are consistent with a competition model of attention in which top-down attention acts on the activity of one of two competing populations of neurons activated by the bottom-up input from peripheral stimuli. They suggest that there is a minimal separation of the populations necessary before attention can act on one population, similar to that required to produce a winner-take-all mode of behavior in pursuit initiation. The present experiments also suggest that it takes several hundred milliseconds to develop this top-down attention effect.

Shift in smooth pursuit initiation and MT and MST neuronal activity under different stimulus conditions.

The activity of neurons in extrastriate middle temporal (MT) and medial superior temporal (MST) areas were studied during the initiation of pursuit eye movements in macaque monkeys. The intersecting motion of two stimuli was used to test hypotheses about how these direction- and speed-sensitive neurons contribute to the generation of pursuit. The amplitude and direction of the initial saccade to the target and the initial speed and direction of pursuit were best predicted by a vector-average model of the underlying neuronal activity with relatively short time and spatial separation before a visual pursuit target and a distracter stimulus crossed in the visual field. The resulting eye movements were best described by a winner-take-all model when the time and spatial separation between the two stimuli was increased before the stimuli crossed. Neurons in MT and MST also shifted their activity from that best described by a vector average to a winner-take-all model under the same stimulus conditions. The changes in activity of neurons in both areas were generally similar to each other during these changes in pursuit initiation. Thus a slight alteration in the target motion produced a concurrent shift in both the neuronal processing and the movement execution. We propose that the differences in the oculomotor behavior can be accounted for by shifts in the overlap of active neuronal populations within MT and MST.

Expansion of the cortical representation of a specific skin field in primary somatosensory cortex by intracortical microstimulation.

Intracortical microstimulation (ICMS) was applied to a single site in the middle cortical layers (III-IV) in the koniocortical somatosensory fields of sodium pentobarbital-anesthetized rats (Sml) and new world monkeys (area 3b). Low-threshold cutaneous receptive fields were defined in the cortical region surrounding the stimulation site prior to and following 2-6 hr of 5 microA ICMS stimulation. ICMS stimulation did not usually affect the receptive field location, size, or responsiveness to tactile stimulation of neurons at the stimulation site. However, the number of cortical neurons surrounding the stimulation site with a receptive field that overlapped with the ICMS-site receptive field increased in all studied animals, resulting in an enlarged cortical representation of a restricted skin region spanning several hundred microns. The mean size of receptive fields changed in some but not all cases. These results provide evidence that the responses of cortical neurons are subject to change by the introduction of locally coincident inputs into a single location, and demonstrate a capacity for representational plasticity in the neocortex in the absence of peripheral stimulation. These experimental observations are consistent with hypotheses that the cerebral cortex comprises radially oriented populations of neurons that share a common input, and that these inputs are shaped by coincident activity (see Edelman, 1978, 1987; Merzenich, 1987; Merzenich et al., 1990; von der Malsburg and Singer, 1988).

Plasticity in the frequency representation of primary auditory cortex following discrimination training in adult owl monkeys.

Previous studies have shown that the tonotopic organization of primary auditory cortex is altered subsequent to restricted cochlear lesions (Robertson and Irvine, 1989) and that the topographic reorganization of the primary somatosensory cortex is correlated with changes in the perceptual acuity of the animal (Recanzone et al., 1992a-d). Here we report an increase in the cortical area of representation of a restricted frequency range in primary auditory cortex of adult owl monkeys that is correlated with the animal's performance at a frequency discrimination task. Monkeys trained for several weeks to discriminate small differences in the frequency of sequentially presented tonal stimuli revealed a progressive improvement in performance with training. At the end of the training period, the tonotopic organization of Al was defined by recording multiple-unit responses at 70-258 cortical locations. These responses were compared to those derived from three normal monkeys and from two monkeys that received the same auditory stimuli but that were engaged in a tactile discrimination task. The cortical representation, the sharpness of tuning, and the latency of the response were greater for the behaviorally relevant frequencies of trained monkeys when compared to the same frequencies of control monkeys. The cortical area of representation was the only studied parameter that was correlated with behavioral performance. These results demonstrate that attended natural stimulation can modify the tonotopic organization of Al in the adult primate, and that this alteration is correlated with changes in perceptual acuity.

Frequency discrimination training engaging a restricted skin surface results in an emergence of a cutaneous response zone in cortical area 3a.

1. The responses of cortical neurons evoked by cutaneous stimulation were investigated in the hand representation of cortical area 3a in adult owl monkeys that had been trained in a tactile frequency discrimination task. Cortical representations of the hands in these experimental hemispheres were compared with those representing the opposite, untrained hand, as well as with those representing a passively stimulated hand in a second class of control monkeys. 2. A large cutaneous representation of the hairy and glabrous skin surfaces of the hand emerged in area 3a in each trained hemisphere. 3. With the emergence of cutaneous responses recorded for neurons at many area 3a locations, the normally recorded deep receptor inputs were no longer evident at most of these locations. 4. There was a greater territory of representation of the small area of skin that was stimulated in the behavioral task in trained monkeys, when compared with the representations of corresponding skin sites in the opposite hemisphere of the same monkeys, or to the representations of equivalent skin sites stimulated in passively stimulated control monkeys. 5. There was great variability in the receptive-field properties of neurons responsive to cutaneous inputs among trained monkeys. In most recording sites within the representations of the behaviorally engaged hands, the cutaneous receptive fields were large, extending over a significant part of the glabrous or hairy surfaces of the hand. However, in one monkey, very small, topographically ordered cutaneous receptive fields were recorded over a wide zone of area 3a. 6. The physiologically defined borders between areas 3a and 3b were in register with the cytoarchitectonically defined borders between these two cortical areas in trained and in control monkeys. 7. This study demonstrates that there is a reorganization of the cutaneous and "deep" representation of hand in cortical area 3a, with the main change being an emergence of a large cutaneous representation and the parallel disappearance of a large part of the normal deep representation in this field. These changes are discussed in light of the possible functional roles of cortical area 3a.

Changes in the distributed temporal response properties of SI cortical neurons reflect improvements in performance on a temporally based tactile discrimination task.

1. Temporal response characteristics of neurons were sampled in fine spatial grain throughout the hand representations in cortical areas 3a and 3b in adult owl monkeys. These monkeys had been trained to detect small differences in tactile stimulus frequencies in the range of 20-30 Hz. Stimuli were presented to an invariant, restricted spot on a single digit. 2. The absolute numbers of cortical locations and the cortical area over which neurons showed entrained frequency-following responses to behaviorally important stimuli were significantly greater when stimulation was applied to the trained skin, as compared with stimulation on an adjacent control digit, or at corresponding skin sites in passively stimulated control animals. 3. Representational maps defined with sinusoidal stimuli were not identical to maps defined with just-visible tapping stimuli. Receptive-field/frequency-following response site mismatches were recorded in every trained monkey. Mismatches were less frequently recorded in the representations of control skin surfaces. 4. At cortical locations with entrained responses, neither the absolute firing rates of neurons nor the degree of the entrainment of the response were correlated with behavioral discrimination performance. 5. All area 3b cortical locations with entrained responses evoked by stimulation at trained or untrained skin sites were combined to create population peristimulus time and cycle histograms. In all cases, stimulation of the trained skin resulted in 1) larger-amplitude responses, 2) peak responses earlier in the stimulus cycle, and 3) temporally sharper responses, than did stimulation applied to control skin sites. 6. The sharpening of the response of cortical area 3b neurons relative to the period of the stimulus could be accounted for by a large subpopulation of neurons that had highly coherent responses. 7. Analysis of cycle histograms for area 3b neuron responses revealed that the decreased variance in the representation of each stimulus cycle could account for behaviorally measured frequency discrimination performance. A strong correlation between these temporal response distributions and the discriminative performances for stimuli applied at all studied skin surfaces was even stronger (r = 0.98) if only the rising phases of cycle histogram were considered in the analysis. 8. The responses of neurons in area 3a could not account for measured differences in frequency discrimination performance. 9. These representational changes did not occur in monkeys that were stimulated on the same schedule but were performing an auditory discrimination task during skin stimulation. 10. It is concluded that by behaviorally training adult owl monkeys to discriminate the temporal features of a tactile stimulus, distributed spatial and temporal response properties of cortical neurons are altered.(ABSTRACT TRUNCATED AT 400 WORDS)

Frequency and intensity response properties of single neurons in the auditory cortex of the behaving macaque monkey.

Response properties of auditory cortical neurons measured in anesthetized preparations have provided important information on the physiological differences between neurons in different auditory cortical areas. Studies in the awake animal, however, have been much less common, and the physiological differences noted may reflect differences in the influence of anesthetics on neurons in different cortical areas. Because the behaving monkey is gaining popularity as an animal model in studies exploring auditory cortical function, it has become critical to physiologically define the response properties of auditory cortical neurons in this preparation. This study documents the response properties of single cortical neurons in the primary and surrounding auditory cortical fields in monkeys performing an auditory discrimination task. We found that neurons with the shortest latencies were located in the primary auditory cortex (AI). Neurons in the rostral field had the longest latencies and the narrowest intensity and frequency tuning, neurons in the caudomedial field had the broadest frequency tuning, and neurons in the lateral field had the most monotonic rate/level functions of the four cortical areas studied. These trends were revealed by comparing response properties across the population of studied neurons, but there was considerable variability between neurons for each response parameter other than characteristic frequency (CF) in each cortical area. Although the neuronal CFs showed a systematic spatial organization across AI, no such systematic organization was apparent for any other response property in AI or the adjacent cortical areas. The results of this study indicate that there are physiological differences between auditory cortical fields in the behaving monkey consistent with previous studies in the anesthetized animal and provide insights into the functional role of these cortical areas in processing acoustic information.

Responses of MT and MST neurons to one and two moving objects in the receptive field.

To test the effects of complex visual motion stimuli on the responses of single neurons in the middle temporal visual area (MT) and the medial superior temporal area (MST) of the macaque monkey, we compared the response elicited by one object in motion through the receptive field with the response of two simultaneously presented objects moving in different directions through the receptive field. There was an increased response to a stimulus moving in a direction other than the best direction when it was paired with a stimulus moving in the best direction. This increase was significant for all directions of motion of the non-best stimulus and the magnitude of the difference increased as the difference in the directions of the two stimuli increased. Similarly, there was a decreased response to a stimulus moving in a non-null direction when it was paired with a stimulus moving in the null direction. This decreased response in MT did not reach significance unless the second stimulus added to the null direction moved in the best direction, whereas in MST the decrease was significant when the second stimulus direction differed from the null by 90 degrees or more. Further analysis showed that the two-object responses were better predicted by taking the averaged response of the neuron to the two single-object stimuli than by summation, multiplication, or vector addition of the responses to each of the two single-object stimuli. Neurons in MST showed larger modulations than did neurons in MT with stimuli moving in both the best direction and in the null direction and the average better predicted the two-object response in area MST than in area MT. This indicates that areas MT and MST probably use a similar integrative mechanisms to create their responses to complex moving visual stimuli, but that this mechanism is further refined in MST. These experiments show that neurons in both MT and MST integrate the motion of all directions in their responses to complex moving stimuli. These results with the motion of objects were in sound agreement with those previously reported with the use of random dot patterns for the study of transparent motion in MT and suggest that these neurons use similar computational mechanisms in the processing of object and global motion stimuli.

Comparison of relative and absolute sound localization ability in humans.

Sound localization ability has traditionally been studied using either a relative localization task, where thresholds to determine a difference in sound source location is approximately 1-10 degrees, or an absolute localization task, where the range of estimates of the source of a sound are 4-30 degrees. In order to directly relate these two psychophysical methods, we compared the psychometric functions from a relative localization task in a human subject to the same subject's performance on an absolute localization task using three different acoustic stimuli: Gaussian noise, 1-kHz tones, and 4-kHz tones. The results showed that the relative localization threshold was a poor indicator of the range of estimates of the same stimulus in absolute space, however, the width of the relative localization psychometric functions was well correlated with the width of the distribution of estimates made in the absolute localization task. It is concluded that the relative localization psychometric functions, but not threshold, provides a reliable estimate of absolute spatial localization ability in human subjects, and suggested that the same neuronal mechanisms can underlie the psychophysical data using both methods.