Neural representation of vocalizations in the primate ventrolateral prefrontal cortex

In this study, we examined the role of the ventrolateral prefrontal cortex in encoding communication stimuli. Specifically, we recorded single-unit responses from the ventrolateral prefrontal cortext (vlPFC) in awake behaving rhesus macaques in response to species-specific vocalizations. We determined the selectivity of vlPFC cells for 10 types of rhesus vocalizations and also asked what types of vocalizations cluster together in the neuronal response. The data from the present study demonstrate that vlPFC auditory neurons respond to a variety of species-specific vocalizations from a previously characterized library. Most vlPFC neurons responded to two to five vocalizations, while a small percentage of cells responded either selectively to a particular vocalization type or nonselectively to most auditory stimuli tested. Use of information theoretic approaches to examine vocalization tuning indicates that on average, vlPFC neurons encode information about one or two vocalizations. Further analysis of the types of vocalizations that vlPFC cells typically respond to using hierarchical cluster analysis suggests that the responses of vlPFC cells to multiple vocalizations is not based strictly on the call's function or meaning but may be due to other features including acoustic morphology. These data are consistent with a role for the primate vlPFC in assessing distinctive acoustic features.     

Stimulus-related gamma oscillations in primate auditory cortex

With a multielectrode system, we explored neuronal activity in the gamma range (>40 Hz) in the primary and caudomedial auditory cortex of six anesthetized macaque monkeys. Stimuli were tone bursts of 100- to 500-ms duration that were presented at sound pressure levels of 40-60 dB and were varied over a wide range of frequencies. These stimuli induced gamma oscillations, not phase-locked to the onset of stimulation, in 465 of 616 multiunit clusters and at 321 of 422 sites at which field potentials were recorded. Occurrence of gamma activity was stimulus dependent. It was mostly seen when the stimulus was at the units' preferred frequency. The incidence of gamma activity decreased with increasing difference between stimulus frequency and preferred frequency. gamma activity emerged 100-900 ms after stimulus onset with highest incidence ~120 ms. Amplitudes of stimulus-induced gamma oscillations in field potentials were, on average, almost twice the amplitude of spontaneously occurring gamma oscillations. gamma activity at different sites within the primary and the caudomedial auditory field could be synchronized at near-zero phase. Synchrony depended on the spatial distance and on the receptive fields similarity of pairs of units. It decreased with increasing distance between recording sites and increased with similarity of preferred frequencies of the pairs of units. The results indicate that stimulus-induced gamma oscillations originate from sources in the auditory cortex. They further suggest that gamma oscillations may provide a mechanism utilized in many parts of the sensory cortex, including the auditory cortex, to integrate neurons according to the similarity of their receptive fields.     

Face-selective and auditory neurons in the primate orbitofrontal cortex

Neurons with responses selective for faces are described in the macaque orbitofrontal cortex. The neurons typically respond 2–13 times more to the best face than to the best non-face stimulus, and have response latencies which are typically in the range of 130–220 ms. Some of these face-selective neurons respond to identity, and others to facial expression. Some of the neurons do not have different responses to different views of a face, which is a useful property of neurons responding to face identity. Other neurons have view-dependent responses, and some respond to moving but not still heads. The neurons with face expression, face movement, or face view-dependent responses would all be useful as part of a system decoding and representing signals important in social interactions. The representation of face identity is also important in social interactions, for it provides some of the information needed in order to make different responses to different individuals. In addition, some orbitofrontal cortex neurons were shown to be tuned to auditory stimuli, including for some neurons, the sound of vocalizations. The findings are relevant to understanding the functions of the primate including human orbitofrontal cortex in normal behaviour, and to understanding the effects of damage to this region in humans.     

Representation of speech categories in the primate auditory cortex

A "ventral" auditory pathway in nonhuman primates that originates in the core auditory cortex and ends in the prefrontal cortex is thought to be involved in components of nonspatial auditory processing. Previous work from our laboratory has indicated that neurons in the prefrontal cortex reflect monkeys' decisions during categorical judgments. Here, we tested the role of the superior temporal gyrus (STG), a region of the secondary auditory cortex that is part of this ventral pathway, during similar categorical judgments. While monkeys participated in a match-to-category task and reported whether two consecutive auditory stimuli belonged to the same category or to different categories, we recorded spiking activity from STG neurons. The auditory stimuli were morphs of two human-speech sounds (bad and dad). We found that STG neurons represented auditory categories. However, unlike activity in the prefrontal cortex, STG activity was not modulated by the monkeys' behavioral reports (choices). This finding is consistent with the anterolateral STG's role as a part of functional circuit involved in the coding, representation, and perception of the nonspatial features of an auditory stimulus.     

An auditory domain in primate prefrontal cortex.

Although neuroimaging studies confirm the frontal lobe's involvement in language processes and auditory working memory, the cellular and network basis of these functions is unclear. Physiological studies of the frontal lobe in non-human primates have focused on visual working memory and auditory spatial processing in dorsolateral prefrontal cortex (PFC), although the candidate PFC areas for non-spatial acoustic processing lie in the ventrolateral PFC (areas 12 and 45), which receives afferents from physiologically and anatomically defined auditory cortex. We recorded neuronal responses from ventrolateral PFC to auditory cues in awake monkeys under controlled conditions and report that the macaque ventrolateral PFC contains an auditory responsive domain in which neurons show responses to complex sounds, including animal and human vocalizations.     

Level dependence of spatial processing in the primate auditory cortex

Sound localization in both humans and monkeys is tolerant to changes in sound levels. The underlying neural mechanism, however, is not well understood. This study reports the level dependence of individual neurons' spatial receptive fields (SRFs) in the primary auditory cortex (A1) and the adjacent caudal field in awake marmoset monkeys. We found that most neurons' excitatory SRF components were spatially confined in response to broadband noise stimuli delivered from the upper frontal sound field. Approximately half the recorded neurons exhibited little change in spatial tuning width over a ~20-dB change in sound level, whereas the remaining neurons showed either expansion or contraction in their tuning widths. Increased sound levels did not alter the percent distribution of tuning width for neurons collected in either cortical field. The population-averaged responses remained tuned between 30- and 80-dB sound pressure levels for neuronal groups preferring contralateral, midline, and ipsilateral locations. We further investigated the spatial extent and level dependence of the suppressive component of SRFs using a pair of sequentially presented stimuli. Forward suppression was observed when the stimuli were delivered from "far" locations, distant to the excitatory center of an SRF. In contrast to spatially confined excitation, the strength of suppression typically increased with stimulus level at both the excitatory center and far regions of an SRF. These findings indicate that although the spatial tuning of individual neurons varied with stimulus levels, their ensemble responses were level tolerant. Widespread spatial suppression may play an important role in limiting the sizes of SRFs at high sound levels in the auditory cortex.     

Long-lasting modulation by stimulus context in primate auditory cortex

A sound embedded in an acoustic stream cannot be unambiguously segmented and identified without reference to its stimulus context. To understand the role of stimulus context in cortical processing, we investigated the responses of auditory cortical neurons to 2-sound sequences in awake marmosets, with a focus on stimulus properties other than carrier frequency. Both suppressive and facilitatory modulations of cortical responses were observed by using combinations of modulated tone and noise stimuli. The main findings are as follows. 1) Preceding stimuli could suppress or facilitate responses to succeeding stimuli for durations >1 s. These long-lasting effects were dependent on the duration, sound level, and modulation parameters of the preceding stimulus, in addition to the carrier frequency. They occurred regardless of whether the 2 stimuli were separated by a silent interval. 2) Suppression was often tuned such that preceding stimuli whose parameters were similar to succeeding stimuli produced the strongest suppression. However, the responses of many units could be suppressed, although often weaker, even when the 2 stimuli were dissimilar. In some cases, only a dissimilar preceding stimulus produced suppression in the responses to the succeeding stimulus. 3) In contrast to suppression, facilitation of responses to succeeding stimuli by the preceding stimulus was usually strongest when the 2 stimuli were dissimilar. 4) There was no clear correlation between the firing rate evoked by the preceding stimulus and the change in the firing rate evoked by the succeeding stimulus, indicating that the observed suppression was not simply a result of habituation or spike adaptation. These results demonstrate that persistent modulations of the responses of an auditory cortical neuron to a given stimulus can be induced by preceding stimuli. Decreases or increases of responses to the succeeding stimuli are dependent on the spectral, temporal, and intensity properties of the preceding stimulus. This indicates that cortical auditory responses to a sound are not static, but instead depend on the stimulus context in a stimulus-specific manner. The long-lasting impact of stimulus context and the prevalence of facilitation suggest that such cortical response properties are important for auditory processing beyond forward masking, such as for auditory streaming and segregation.     

Differential representation of species-specific primate vocalizations in the auditory cortices of marmoset and cat.

A number of studies in various species have demonstrated that natural vocalizations generally produce stronger neural responses than do their time-reversed versions. The majority of neurons in the primary auditory cortex (A1) of marmoset monkeys responds more strongly to natural marmoset vocalizations than to the time-reversed vocalizations. However, it was unclear whether such differences in neural responses were simply due to the difference between the acoustic structures of natural and time-reversed vocalizations or whether they also resulted from the difference in behavioral relevance of both types of the stimuli. To address this issue, we have compared neural responses to natural and time-reversed marmoset twitter calls in A1 of cats with those obtained from A1 of marmosets using identical stimuli. It was found that the preference for natural marmoset twitter calls demonstrated in marmoset A1 was absent in cat A1. While both cortices responded approximately equally to time-reversed twitter calls, marmoset A1 responded much more strongly to natural twitter calls than did cat A1. This differential representation of marmoset vocalizations in two cortices suggests that experience-dependent and possibly species-specific mechanisms are involved in cortical processing of communication sounds.     

Timing and laminar profile of eye-position effects on auditory responses in primate auditory cortex

We examined effects of eye position on auditory cortical responses in macaques. Laminar current-source density (CSD) and multiunit activity (MUA) profiles were sampled with linear array multielectrodes. Eye position significantly modulated auditory-evoked CSD amplitude in 24/29 penetrations (83%), across A1 and belt regions; 4/24 cases also showed significant MUA AM. Eye-position effects occurred mainly in the supragranular laminae and lagged the co-located auditory response by, on average, 38 ms. Effects in A1 and belt regions were indistinguishable in amplitude, laminar profile, and latency. The timing and laminar profile of the eye-position effects suggest that they are not combined with auditory signals at a subcortical stage of the lemniscal auditory pathways and simply "fed-forward" into cortex. Rather, these effects may be conveyed to auditory cortex by feedback projections from parietal or frontal cortices, or alternatively, they may be conveyed by nonclassical feedforward projections through auditory koniocellular (calbindin positive) neurons.     

Binaural interaction revisited in the cat primary auditory cortex

The binaural interactions of neurons were studied in the primary auditory cortex (AI) of barbiturate-anesthetized cats with a matrix of binaural tonal stimuli varying in both interaural level differences (ILD) and average binaural level (ABL). The purpose of this study was to determine: 1) the distribution of preferred binaural combinations (PBCs) of a large population of neurons and its relationships with binaural interactions and binaural monotonicity; 2) whether monaural responses are predictive of binaural responses; and 3) whether there is a restricted set of representative binaural stimulus configurations that could effectively classify the binaural interactions. Binaural interactions were often diverse in the matrix and dependent on both ABL and ILD. Compared with previous studies, a higher proportion of mixed binaural interaction type and a lower proportion of EO/I type were found. No monaural neurons were found. Binaural responses often differed from monaural responses in the number of spikes and/or the form of the response functions. The PBCs of the majority of EO and PB neurons were in the contralateral field and midline, respectively. However, the PBCs of EE units were evenly distributed across the contralateral and ipsilateral fields. The majority of the nonmonotonic neurons responded most strongly to lower ABLs, whereas the majority of monotonic neurons responded most strongly to higher ABLs. This study demonstrated that in AI a restricted set of binaural stimulus configurations is not sufficient to reveal the binaural responses properties. Also, monaural responses are not predictive of binaural responses.     

Lability in the responses of cells in the auditory cortex of squirrel monkeys to species-specific vocalizations

Summary The activity of 28 cells located mainly in the secondary auditory cortex (A II) of awake squirrel-monkeys, was extracellularly recorded for periods of up to 6 h. Seven different species-specific vocalizations, which were repeatedly presented to the monkey, were used as auditory stimuli. Twenty-six cells responded, at least once, to one or more vocalizations; 22 cells revealed some change in their response (pattern or strength) to at least one vocalization (change in response). Twenty-one cells exhibited a change in the number and/or type of vocalization to which they responded during the recording period (change in selectivity). At some time during the recording period all the responding cells exhibited a change in response and/or a change in selectivity (change in responsiveness). A change in response of a cell to a vocalization did not necessarily exclude a change in selectivity, associated with the same vocalization, later in time and vice-versa. A change in responsiveness to one vocalization was not necessarily correlated with changes in responsiveness to other vocalizations.     

Differential neural coding of acoustic flutter within primate auditory cortex

A sequence of acoustic events is perceived either as one continuous sound or as a stream of temporally discrete sounds (acoustic flutter), depending on the rate at which the acoustic events repeat. Acoustic flutter is perceived at repetition rates near or below the lower limit for perceiving pitch, and is akin to the discrete percepts of visual flicker and tactile flutter caused by the slow repetition of sensory stimulation. It has been shown that slowly repeating acoustic events are represented explicitly by stimulus-synchronized neuronal firing patterns in primary auditory cortex (AI). Here we show that a second neural code for acoustic flutter exists in the auditory cortex of marmoset monkeys (Callithrix jacchus), in which the firing rate of a neuron is a monotonic function of an acoustic event's repetition rate. Whereas many neurons in AI encode acoustic flutter using a dual temporal/rate representation, we find that neurons in cortical fields rostral to AI predominantly use a monotonic rate code and lack stimulus-synchronized discharges. These findings indicate that the neural representation of acoustic flutter is transformed along the caudal-to-rostral axis of auditory cortex.     

Dual streams of auditory afferents target multiple domains in the primate prefrontal cortex

'What' and 'where' visual streams define ventrolateral object and dorsolateral spatial processing domains in the prefrontal cortex of nonhuman primates. We looked for similar streams for auditory-prefrontal connections in rhesus macaques by combining microelectrode recording with anatomical tract-tracing. Injection of multiple tracers into physiologically mapped regions AL, ML and CL of the auditory belt cortex revealed that anterior belt cortex was reciprocally connected with the frontal pole (area 10), rostral principal sulcus (area 46) and ventral prefrontal regions (areas 12 and 45), whereas the caudal belt was mainly connected with the caudal principal sulcus (area 46) and frontal eye fields (area 8a). Thus separate auditory streams originate in caudal and rostral auditory cortex and target spatial and non-spatial domains of the frontal lobe, respectively.     

Representation of spectral and temporal envelope of twitter vocalizations in common marmoset primary auditory cortex

Cortical sensitivity in representations of behaviorally relevant complex input signals was examined in recordings from primary auditory cortical neurons (AI) in adult, barbiturate-anesthetized common marmoset monkeys (Callithrix jacchus). We studied the robustness of distributed responses to natural and degraded forms of twitter calls, social contact vocalizations comprising several quasi-periodic phrases of frequency and AM. We recorded neuronal responses to a monkey's own twitter call (MOC), degraded forms of their twitter call, and sinusoidal amplitude modulated (SAM) tones with modulation rates similar to those of twitter calls. In spectral envelope degradation, calls with narrowband channels of varying bandwidths had the same temporal envelope as a natural call. However, the carrier phase was randomized within each narrowband channel. In temporal envelope degradation, the temporal envelope within narrowband channels was filtered while the carrier frequencies and phases remained unchanged. In a third form of degradation, noise was added to the natural calls. Spatiotemporal discharge patterns in AI both within and across frequency bands encoded spectrotemporal acoustic features in the call although the encoded response is an abstract version of the call. The average temporal response pattern in AI, however, was significantly correlated with the average temporal envelope for each phrase of a call. Response entrainment to MOC was significantly correlated with entrainment to SAM stimuli at comparable modulation frequencies. Sensitivity of the response patterns to MOC was substantially greater for temporal envelope than for spectral envelope degradations. The distributed responses in AI were robust to additive continuous noise at signal-to-noise ratios > or =10 dB. Neurophysiological data reflecting response sensitivity in AI to these forms of degradation closely parallel human psychophysical results on the intelligibility of degraded speech in quiet and noisy conditions.     

Synapses are lost during aging in the primate prefrontal cortex

An electron microscopic analysis has been carried out on the effects of age on the numerical density of both excitatory (asymmetric) and inhibitory (symmetric) synapses in the neuropil of layers 2/3 and of layer 5 in area 46 from the frontal cortex of behaviorally tested rhesus monkeys. There is no change in the lengths of synaptic junctions with age or in the percentage distribution of synapses relative to the postsynaptic spines and dendritic shafts. However, in layers 2/3 there is an overall loss of about 30% of synapses from 5 to 30 years of age, and both asymmetric and symmetric synapses are lost at the same rate. In layer 5 the situation is different; the overall loss of synapses is only 20% and this is almost entirely due to a loss of asymmetric synapses, since there is no significant loss of symmetric synapses from this layer with age. When the synapse data are correlated with the overall cognitive impairment shown by the monkeys, it is found that there is a strong correlation between the numerical density of asymmetric synapses in layers 2/3 and cognitive impairment, with a weaker correlation between symmetric synapse loss and cognitive impairment. In layer 5 on the other hand there is no correlation between synapse loss and cognitive impairment. However synapse loss is not the only factor causing cognitive impairment, since in previous studies of area 46 we have found that age-related alteration in myelin in this frontal area also significantly contributes to cognitive decline. The synapse loss is also considered in light of earlier studies, which show that the frequency of spontaneous excitatory synaptic responses is reduced with age in layers 2/3 neurons.     

Spatial representation of neural responses to natural and altered conspecific vocalizations in cat auditory cortex

This study shows the neural representation of cat vocalizations, natural and altered with respect to carrier and envelope, as well as time-reversed, in four different areas of the auditory cortex. Multiunit activity recorded in primary auditory cortex (AI) of anesthetized cats mainly occurred at onsets (<200-ms latency) and at subsequent major peaks of the vocalization envelope and was significantly inhibited during the stationary course of the stimuli. The first 200 ms of processing appears crucial for discrimination of a vocalization in AI. The dorsal and ventral parts of AI appear to have different roles in coding vocalizations. The dorsal part potentially discriminated carrier-altered meows, whereas the ventral part showed differences primarily in its response to natural and time-reversed meows. In the posterior auditory field, the different temporal response types of neurons, as determined by their poststimulus time histograms, showed discrimination for carrier alterations in the meow. Sustained firing neurons in the posterior ectosylvian gyrus (EP) could discriminate, among others, by neural synchrony, temporal envelope alterations of the meow, and time reversion thereof. These findings suggest an important role of EP in the detection of information conveyed by the alterations of vocalizations. Discrimination of the neural responses to different alterations of vocalizations could be based on either firing rate, type of temporal response, or neural synchrony, suggesting that all these are likely simultaneously used in processing of natural and altered conspecific vocalizations.     

Effect of unilateral and bilateral auditory cortex lesions on the discrimination of vocalizations by Japanese macaques

Ten Japanese macaques were trained to discriminate between two types of Japanese macaque coo vocalizations before and after auditory cortex ablation. Five of the animals were tested following left unilateral ablation, whereas the other five were tested following right unilateral ablation. After postoperative testing, symmetrical lesions were made in the remaining hemisphere in two animals from each group and the effect of bilateral lesions was assessed. The animals were tested using a shock avoidance procedure. Unilateral ablation of left auditory cortex consistently resulted in an initial impairment in the ability to discriminate between the vocalizations with the animals regaining normal performance in 5-15 sessions. In contrast, right unilateral ablation had no detectable effect on the discrimination. Bilateral auditory cortex ablation rendered the animals permanently unable to discriminate between the coos. Although the monkeys could learn to discriminate the coos from noise and from 2- and 4-kHz tones, they had great difficulty in discriminating between the coos and tones in the same frequency range as the coos (i.e., 500 Hz and 1 kHz). The initial impairment following left unilateral lesions indicates that the ability to perceive species-specific vocalizations is lateralized to the left hemisphere. The observation that bilateral lesions abolish the discrimination indicates that the recovery in the left lesion cases was the result of the right hemisphere mediating the discrimination.     

Fine-tuning of auditory cortex during speech production

The cortex suppresses sensory information when it is the result of a self-produced motor act, including the motor act of speaking. The specificity of the auditory cortical suppression to self-produced speech, a prediction derived from the posited operation of a precise forward model system, has not been established. We examined the auditory N100 component of the event-related brain potential elicited during speech production. While subjects uttered a vowel, they heard real-time feedback of their unaltered voice, their pitch-shifted voice, or an alien voice substituted for their own. The subjects' own unaltered voice feedback elicited a dampened auditory N100 response relative to the N100 elicited by altered or alien auditory feedback. This is consistent with the operation of a precise forward model modulating the auditory cortical response to self-generated speech and allowing immediate distinction of self and externally generated auditory stimuli.     

Sensory-motor mechanisms in human parietal cortex underlie arbitrary visual decisions

The neural mechanism underlying simple perceptual decision-making in monkeys has been recently conceptualized as an integrative process in which sensory evidence supporting different response options accumulates gradually over time. For example, intraparietal neurons accumulate motion information in favor of a specific oculomotor choice over time. It is unclear, however, whether this mechanism generalizes to more complex decisions that are based on arbitrary stimulus-response associations. In a task requiring arbitrary association of visual stimuli (faces or places) with different actions (eye or hand-pointing movements), we found that activity of effector-specific regions in human posterior parietal cortex reflected the 'strength' of the sensory evidence in favor of the preferred response. These regions did not respond to sensory stimuli per se but integrated sensory evidence toward the decision outcome. We conclude that even arbitrary decisions can be mediated by sensory-motor mechanisms that are completely triggered by contextual stimulus-response associations.     

The role of auditory feedback in the vocalizations of cats

Summary The vocalizations of deaf cats were compared with those of littermate hearing controls at 30 days, 50 days, 1 year and 3 years of age. At all ages, deaf cats called more loudly than hearing animals. At 30 days, 50 days, and 3 years, deaf cats called about twice as loudly as hearing animals while at 1 year the calls of the deaf animals were approximately 6 times louder than those of the hearing littermates. Analysis of variance revealed significant differences in call loudness between deaf and hearing animals at 30 days, 1, and 3 years. Deaf and hearing animals did not differ in rate of calling or in the duration of individual vocalizations at 30 days, 50 days, and 1 year. At 3 years, the calls of the deaf animal were shorter than those of the hearing control. The calls of deaf animals were less variable than those of hearing animals at 30 days, 50 days, and 3 years. There was a tendency for the fundamental frequency of the calls of deaf animals to be higher than that of hearing animals at 30 days, 50 days, and 1 year. These results document the importance of auditory feedback in the regulation of feline vocalization.