Thalamic connections of the core auditory cortex and rostral supratemporal plane in the macaque monkey.

In the primate auditory cortex, information flows serially in the mediolateral dimension from core, to belt, to parabelt. In the caudorostral dimension, stepwise serial projections convey information through the primary, rostral, and rostrotemporal (AI, R, and RT) core areas on the supratemporal plane, continuing to the rostrotemporal polar area (RTp) and adjacent auditory-related areas of the rostral superior temporal gyrus (STGr) and temporal pole. In addition to this cascade of corticocortical connections, the auditory cortex receives parallel thalamocortical projections from the medial geniculate nucleus (MGN). Previous studies have examined the projections from MGN to auditory cortex, but most have focused on the caudal core areas AI and R. In this study, we investigated the full extent of connections between MGN and AI, R, RT, RTp, and STGr using retrograde and anterograde anatomical tracers. Both AI and R received nearly 90% of their thalamic inputs from the ventral subdivision of the MGN (MGv; the primary/lemniscal auditory pathway). By contrast, RT received only ∼45% from MGv, and an equal share from the dorsal subdivision (MGd). Area RTp received ∼25% of its inputs from MGv, but received additional inputs from multisensory areas outside the MGN (30% in RTp vs. 1-5% in core areas). The MGN input to RTp distinguished this rostral extension of auditory cortex from the adjacent auditory-related cortex of the STGr, which received 80% of its thalamic input from multisensory nuclei (primarily medial pulvinar). Anterograde tracers identified complementary descending connections by which highly processed auditory information may modulate thalamocortical inputs.

Intrinsic Connections of the Core Auditory Cortical Regions and Rostral Supratemporal Plane in the Macaque Monkey.

In the ventral stream of the primate auditory cortex, cortico-cortical projections emanate from the primary auditory cortex (AI) along 2 principal axes: one mediolateral, the other caudorostral. Connections in the mediolateral direction from core, to belt, to parabelt, have been well described, but less is known about the flow of information along the supratemporal plane (STP) in the caudorostral dimension. Neuroanatomical tracers were injected throughout the caudorostral extent of the auditory core and rostral STP by direct visualization of the cortical surface. Auditory cortical areas were distinguished by SMI-32 immunostaining for neurofilament, in addition to established cytoarchitectonic criteria. The results describe a pathway comprising step-wise projections from AI through the rostral and rostrotemporal fields of the core (R and RT), continuing to the recently identified rostrotemporal polar field (RTp) and the dorsal temporal pole. Each area was strongly and reciprocally connected with the areas immediately caudal and rostral to it, though deviations from strictly serial connectivity were observed. In RTp, inputs converged from core, belt, parabelt, and the auditory thalamus, as well as higher order cortical regions. The results support a rostrally directed flow of auditory information with complex and recurrent connections, similar to the ventral stream of macaque visual cortex.

Auditory short-term memory in the primate auditory cortex.

Sounds are fleeting, and assembling the sequence of inputs at the ear into a coherent percept requires auditory memory across various time scales. Auditory short-term memory comprises at least two components: an active ׳working memory' bolstered by rehearsal, and a sensory trace that may be passively retained. Working memory relies on representations recalled from long-term memory, and their rehearsal may require phonological mechanisms unique to humans. The sensory component, passive short-term memory (pSTM), is tractable to study in nonhuman primates, whose brain architecture and behavioral repertoire are comparable to our own. This review discusses recent advances in the behavioral and neurophysiological study of auditory memory with a focus on single-unit recordings from macaque monkeys performing delayed-match-to-sample (DMS) tasks. Monkeys appear to employ pSTM to solve these tasks, as evidenced by the impact of interfering stimuli on memory performance. In several regards, pSTM in monkeys resembles pitch memory in humans, and may engage similar neural mechanisms. Neural correlates of DMS performance have been observed throughout the auditory and prefrontal cortex, defining a network of areas supporting auditory STM with parallels to that supporting visual STM. These correlates include persistent neural firing, or a suppression of firing, during the delay period of the memory task, as well as suppression or (less commonly) enhancement of sensory responses when a sound is repeated as a ׳match' stimulus. Auditory STM is supported by a distributed temporo-frontal network in which sensitivity to stimulus history is an intrinsic feature of auditory processing. This article is part of a Special Issue entitled SI: Auditory working memory.

Diverse cortical codes for scene segmentation in primate auditory cortex.

The temporal coherence of amplitude fluctuations is a critical cue for segmentation of complex auditory scenes. The auditory system must accurately demarcate the onsets and offsets of acoustic signals. We explored how and how well the timing of onsets and offsets of gated tones are encoded by auditory cortical neurons in awake rhesus macaques. Temporal features of this representation were isolated by presenting otherwise identical pure tones of differing durations. Cortical response patterns were diverse, including selective encoding of onset and offset transients, tonic firing, and sustained suppression. Spike train classification methods revealed that many neurons robustly encoded tone duration despite substantial diversity in the encoding process. Excellent discrimination performance was achieved by neurons whose responses were primarily phasic at tone offset and by those that responded robustly while the tone persisted. Although diverse cortical response patterns converged on effective duration discrimination, this diversity significantly constrained the utility of decoding models referenced to a spiking pattern averaged across all responses or averaged within the same response category. Using maximum likelihood-based decoding models, we demonstrated that the spike train recorded in a single trial could support direct estimation of stimulus onset and offset. Comparisons between different decoding models established the substantial contribution of bursts of activity at sound onset and offset to demarcating the temporal boundaries of gated tones. Our results indicate that relatively few neurons suffice to provide temporally precise estimates of such auditory "edges," particularly for models that assume and exploit the heterogeneity of neural responses in awake cortex.

Neural correlates of auditory short-term memory in rostral superior temporal cortex.

BACKGROUND: Auditory short-term memory (STM) in the monkey is less robust than visual STM and may depend on a retained sensory trace, which is likely to reside in the higher-order cortical areas of the auditory ventral stream. RESULTS: We recorded from the rostral superior temporal cortex as monkeys performed serial auditory delayed match-to-sample (DMS). A subset of neurons exhibited modulations of their firing rate during the delay between sounds, during the sensory response, or during both. This distributed subpopulation carried a predominantly sensory signal modulated by the mnemonic context of the stimulus. Excitatory and suppressive effects on match responses were dissociable in their timing and in their resistance to sounds intervening between the sample and match. CONCLUSIONS: Like the monkeys' behavioral performance, these neuronal effects differ from those reported in the same species during visual DMS, suggesting different neural mechanisms for retaining dynamic sounds and static images in STM.

The neural code for auditory space depends on sound frequency and head size in an optimal manner.

A major cue to the location of a sound source is the interaural time difference (ITD)-the difference in sound arrival time at the two ears. The neural representation of this auditory cue is unresolved. The classic model of ITD coding, dominant for a half-century, posits that the distribution of best ITDs (the ITD evoking a neuron's maximal response) is unimodal and largely within the range of ITDs permitted by head-size. This is often interpreted as a place code for source location. An alternative model, based on neurophysiology in small mammals, posits a bimodal distribution of best ITDs with exquisite sensitivity to ITDs generated by means of relative firing rates between the distributions. Recently, an optimal-coding model was proposed, unifying the disparate features of these two models under the framework of efficient coding by neural populations. The optimal-coding model predicts that distributions of best ITDs depend on head size and sound frequency: for high frequencies and large heads it resembles the classic model, for low frequencies and small head sizes it resembles the bimodal model. The optimal-coding model makes key, yet unobserved, predictions: for many species, including humans, both forms of neural representation are employed, depending on sound frequency. Furthermore, novel representations are predicted for intermediate frequencies. Here, we examine these predictions in neurophysiological data from five mammalian species: macaque, guinea pig, cat, gerbil and kangaroo rat. We present the first evidence supporting these untested predictions, and demonstrate that different representations appear to be employed at different sound frequencies in the same species.

Encoding frequency contrast in primate auditory cortex.

Changes in amplitude and frequency jointly determine much of the communicative significance of complex acoustic signals, including human speech. We have previously described responses of neurons in the core auditory cortex of awake rhesus macaques to sinusoidal amplitude modulation (SAM) signals. Here we report a complementary study of sinusoidal frequency modulation (SFM) in the same neurons. Responses to SFM were analogous to SAM responses in that changes in multiple parameters defining SFM stimuli (e.g., modulation frequency, modulation depth, carrier frequency) were robustly encoded in the temporal dynamics of the spike trains. For example, changes in the carrier frequency produced highly reproducible changes in shapes of the modulation period histogram, consistent with the notion that the instantaneous probability of discharge mirrors the moment-by-moment spectrum at low modulation rates. The upper limit for phase locking was similar across SAM and SFM within neurons, suggesting shared biophysical constraints on temporal processing. Using spike train classification methods, we found that neural thresholds for modulation depth discrimination are typically far lower than would be predicted from frequency tuning to static tones. This "dynamic hyperacuity" suggests a substantial central enhancement of the neural representation of frequency changes relative to the auditory periphery. Spike timing information was superior to average rate information when discriminating among SFM signals, and even when discriminating among static tones varying in frequency. This finding held even when differences in total spike count across stimuli were normalized, indicating both the primacy and generality of temporal response dynamics in cortical auditory processing.

Effect of acoustic similarity on short-term auditory memory in the monkey.

Recent evidence suggests that the monkey's short-term memory in audition depends on a passively retained sensory trace as opposed to a trace reactivated from long-term memory for use in working memory. Reliance on a passive sensory trace could render memory particularly susceptible to confusion between sounds that are similar in some acoustic dimension. If so, then in delayed matching-to-sample, the monkey's performance should be predicted by the similarity in the salient acoustic dimension between the sample and subsequent test stimulus, even at very short delays. To test this prediction and isolate the acoustic features relevant to short-term memory, we examined the pattern of errors made by two rhesus monkeys performing a serial, auditory delayed match-to-sample task with interstimulus intervals of 1 s. The analysis revealed that false-alarm errors did indeed result from similarity-based confusion between the sample and the subsequent nonmatch stimuli. Manipulation of the stimuli showed that removal of spectral cues was more disruptive to matching behavior than removal of temporal cues. In addition, the effect of acoustic similarity on false-alarm response was stronger at the first nonmatch stimulus than at the second one. This pattern of errors would be expected if the first nonmatch stimulus overwrote the sample's trace, and suggests that the passively retained trace is not only vulnerable to similarity-based confusion but is also highly susceptible to overwriting.

Monkeys have a limited form of short-term memory in audition.

A stimulus trace may be temporarily retained either actively [i.e., in working memory (WM)] or by the weaker mnemonic process we will call passive short-term memory, in which a given stimulus trace is highly susceptible to "overwriting" by a subsequent stimulus. It has been suggested that WM is the more robust process because it exploits long-term memory (i.e., a current stimulus activates a stored representation of that stimulus, which can then be actively maintained). Recent studies have suggested that monkeys may be unable to store acoustic signals in long-term memory, raising the possibility that they may therefore also lack auditory WM. To explore this possibility, we tested rhesus monkeys on a serial delayed match-to-sample (DMS) task using a small set of sounds presented with ~1-s interstimulus delays. Performance was accurate whenever a match or a nonmatch stimulus followed the sample directly, but it fell precipitously if a single nonmatch stimulus intervened between sample and match. The steep drop in accuracy was found to be due not to passive decay of the sample's trace, but to retroactive interference from the intervening nonmatch stimulus. This "overwriting" effect was far greater than that observed previously in serial DMS with visual stimuli. The results, which accord with the notion that WM relies on long-term memory, indicate that monkeys perform serial DMS in audition remarkably poorly and that whatever success they had on this task depended largely, if not entirely, on the retention of stimulus traces in the passive form of short-term memory.

Transformation of temporal processing across auditory cortex of awake macaques.

The anatomy and connectivity of the primate auditory cortex has been modeled as a core region receiving direct thalamic input surrounded by a belt of secondary fields. The core contains multiple tonotopic fields (including the primary auditory cortex, AI, and the rostral field, R), but available data only partially address the degree to which those fields are functionally distinct. This report, based on single-unit recordings across four hemispheres in awake macaques, argues that the functional organization of auditory cortex is best understood in terms of temporal processing. Frequency tuning, response threshold, and strength of activation are similar between AI and R, validating their inclusion as a unified core, but the temporal properties of the fields clearly differ. Onset latencies to pure tones are longer in R (median, 33 ms) than in AI (20 ms); moreover, synchronization of spike discharges to dynamic modulations of stimulus amplitude and frequency, similar to those present in macaque and human vocalizations, suggest distinctly different windows of temporal integration in AI (20-30 ms) and R (100 ms). Incorporating data from the adjacent auditory belt reveals that the divergence of temporal properties within the core is in some cases greater than the temporal differences between core and belt.

Temporal codes for amplitude contrast in auditory cortex.

The encoding of sound level is fundamental to auditory signal processing, and the temporal information present in amplitude modulation is crucial to the complex signals used for communication sounds, including human speech. The modulation transfer function, which measures the minimum detectable modulation depth across modulation frequency, has been shown to predict speech intelligibility performance in a range of adverse listening conditions and hearing impairments, and even for users of cochlear implants. We presented sinusoidal amplitude modulation (SAM) tones of varying modulation depths to awake macaque monkeys while measuring the responses of neurons in the auditory core. Using spike train classification methods, we found that thresholds for modulation depth detection and discrimination in the most sensitive units are comparable to psychophysical thresholds when precise temporal discharge patterns rather than average firing rates are considered. Moreover, spike timing information was also superior to average rate information when discriminating static pure tones varying in level but with similar envelopes. The limited utility of average firing rate information in many units also limited the utility of standard measures of sound level tuning, such as the rate level function (RLF), in predicting cortical responses to dynamic signals like SAM. Response modulation typically exceeded that predicted by the slope of the RLF by large factors. The decoupling of the cortical encoding of SAM and static tones indicates that enhancing the representation of acoustic contrast is a cardinal feature of the ascending auditory pathway.

Representation of dynamic interaural phase difference in auditory cortex of awake rhesus macaques.

Neurons in auditory cortex of awake primates are selective for the spatial location of a sound source, yet the neural representation of the binaural cues that underlie this tuning remains undefined. We examined this representation in 283 single neurons across the low-frequency auditory core in alert macaques, trained to discriminate binaural cues for sound azimuth. In response to binaural beat stimuli, which mimic acoustic motion by modulating the relative phase of a tone at the two ears, these neurons robustly modulate their discharge rate in response to this directional cue. In accordance with prior studies, the preferred interaural phase difference (IPD) of these neurons typically corresponds to azimuthal locations contralateral to the recorded hemisphere. Whereas binaural beats evoke only transient discharges in anesthetized cortex, neurons in awake cortex respond throughout the IPD cycle. In this regard, responses are consistent with observations at earlier stations of the auditory pathway. Discharge rate is a band-pass function of the frequency of IPD modulation in most neurons (73%), but both discharge rate and temporal synchrony are independent of the direction of phase modulation. When subjected to a receiver operator characteristic analysis, the responses of individual neurons are insufficient to account for the perceptual acuity of these macaques in an IPD discrimination task, suggesting the need for neural pooling at the cortical level.

Dynamic amplitude coding in the auditory cortex of awake rhesus macaques.

In many animals, the information most important for processing communication sounds, including speech, consists of temporal envelope cues below approximately 20 Hz. Physiological studies, however, have typically emphasized the upper limits of modulation encoding. Responses to sinusoidal AM (SAM) are generally summarized by modulation transfer functions (MTFs), which emphasize tuning to modulation frequency rather than the representation of the instantaneous stimulus amplitude. Unfortunately, MTFs fail to capture important but nonlinear aspects of amplitude coding in the central auditory system. We focus on an alternative data representation, the modulation period histogram (MPH), which depicts the spike train folded on the modulation period of the SAM stimulus. At low modulation frequencies, the fluctuations of stimulus amplitude in decibels are robustly encoded by the cycle-by-cycle response dynamics evident in the MPH. We show that all of the parameters that define a SAM stimulus--carrier frequency, carrier level, modulation frequency, and modulation depth--are reflected in the shape of cortical MPHs. In many neurons that are nonmonotonically tuned for sound amplitude, the representation of modulation frequency is typically sacrificed to preserve the mapping between the instantaneous discharge rate and the instantaneous stimulus amplitude, resulting in two response modes per modulation cycle. This behavior, as well as the relatively poor tuning of cortical MTFs, suggests that auditory cortical neurons are not well suited for operating as a "modulation filterbank." Instead, our results suggest that <20 Hz, the processing of modulated signals is better described as envelope shape discrimination rather than modulation frequency extraction.

Effect of behavioral context on representation of a spatial cue in core auditory cortex of awake macaques.

Primary auditory cortex plays a crucial role in spatially directed behavior, but little is known about the effect of behavioral state on the neural representation of spatial cues. Macaques were trained to discriminate binaural cues to sound localization, eventually allowing measurement of thresholds comparable to human hearing. During behavior and passive listening, single units in low-frequency auditory cortex showed robust and consistent tuning to interaural phase difference (IPD). In most neurons, behavior exerted an effect on peak discharge rate (58% increased, 13% decreased), but this was not accompanied by a detectable shift in the best IPD of any cell. Neurometric analysis revealed a difference in discriminability between the behaving and passive condition in half of the sample (52%), but steepening of the neurometric function (29%) was only slightly more common than flattening (23%). This suggests that performance of a discrimination task does not necessarily confer an advantage in understanding the representation of the spatial cue in primary auditory cortex but nevertheless revealed some physiological effects. These results suggest that responses observed during passive listening provide a valid representation of neuronal response properties in core auditory cortex.

Cortical mechanisms in hearing.

Current understanding of neural processing in the auditory cortex has been shaped by a variety of experimental approaches in animals and humans. It remains a daunting challenge to reconcile data as diverse as synaptic properties recorded in a rodent brain slice and functional images of auditory cortex in a behaving human. Nevertheless, the gaps are narrowing through a renewed focus on humans and other primates, a continuing interest in evidence for functional pathways, a broader application of modern imaging techniques, a growing awareness of cortical sensitivity to dynamic features of sounds, and an improved understanding of auditory cortical circuitry.

A comparison of pursuit eye movement and perceptual performance in speed discrimination.

Currently there is considerable debate as to the nature of the pathways that are responsible for the perception and motor performance. We have studied the relationship between perceived speed, which is the experiential representation of a moving stimulus, and the speed of smooth pursuit eye movements, the motor action. We determined psychophysical thresholds for detecting small perturbations in the speed of moving patterns, and then by an ideal observer analysis computed analogous "oculometric" thresholds from the eye movement traces elicited by the same stimuli on the same trials. Our results confirm those of previous studies that show a remarkable agreement between perceptual judgments for speed discrimination and the fine gradations in eye movement speed. We analyzed the initial pursuit period of long duration (1000 ms) and short (200 ms) duration perturbations. When we compared the errors for perception and pursuit on a trial-by-trial basis there was no correlation between perceptual errors and eye movement errors. The observation that both oculometric and psychometric performance were similar, with Weber fractions in the normal range, but that there is no correlation in the errors suggests that the motor system and perception share the same constraints in their analysis of motion signals, but act independently and have different noise sources. We simulated noise in two models of perceptual and eye movement performance. In the first model we postulate an initial common source for the perceptual and eye movement signals. In that case about ten times the observed noise is required to produce no correlation in trial-by-trial performance. In the second model we postulate that the perceptual signal is a combination of a reafferent eye velocity signal plus the perturbation signal while the pursuit signal is derived from the oculomotor plant plus the perturbation signal. In this model about three times the noise level in the independent signals will mask any correlation due to the common perturbation signal.

Context-dependent adaptive coding of interaural phase disparity in the auditory cortex of awake macaques.

In the ascending auditory pathway, the context in which a particular stimulus occurs can influence the character of the responses that encode it. Here we demonstrate that the cortical representation of a binaural cue to sound source location is profoundly context-dependent: spike rates elicited by a 0 degrees interaural phase disparity (IPD) were very different when preceded by 90 degrees versus -90 degrees IPD. The changes in firing rate associated with equivalent stimuli occurring in different contexts are comparable to changes in discharge rate that establish cortical tuning to the cue itself. Single-unit responses to trapezoidally modulated IPD stimuli were recorded in the auditory cortices of awake rhesus monkeys. Each trapezoidal stimulus consisted of linear modulations of IPD between two steady-state IPDs differing by 90 degrees. The stimulus set was constructed so that identical IPDs and sweeps through identical IPD ranges recurred as elements of disparate sequences. We routinely observed orderly context-induced shifts in IPD tuning. These shifts reflected an underlying enhancement of the contrast in the discharge rate representation of different IPDs. This process is subserved by sensitivity to stimulus events in the recent past, involving multiple adaptive mechanisms operating on timescales ranging from tens of milliseconds to seconds. These findings suggest that the cortical processing of dynamic acoustic signals is dominated by an adaptive coding strategy that prioritizes the representation of stimulus changes over actual stimulus values. We show how cortical selectivity for motion direction in real space could emerge as a consequence of this general coding principle.