Macaque Auditory Cortex Research Articles

Laminar pattern of sensory-evoked dynamic high-frequency oscillatory activity in the macaque auditory cortex.

High-frequency (>60Hz) neuroelectric signals likely have functional roles distinct from low-frequency (<30Hz) signals. While high-gamma activity (>60Hz) does not simply equate to neuronal spiking, they are highly correlated, having similar information encoding. High-gamma activity is typically considered broadband and poorly phase-locked to sensory stimuli and thus is typically analyzed after transformations into absolute amplitude or spectral power. However, those analyses discard signal polarity, compromising the interpretation of neuroelectric events that are essentially dipolar. In the spectrotemporal profiles of field potentials in auditory cortex, we show high-frequency spectral peaks not phase-locked to sound onset, which follow the broadband peak of phase-locked onset responses. Isolating the signal components comprising the high-frequency peaks reveals narrow-band high-frequency oscillatory events, whose instantaneous frequency changes rapidly from >150 to 60Hz, which may underlie broadband high-frequency spectral peaks in previous reports. The laminar amplitude distributions of the isolated activity had two peak positions, while the laminar phase patterns showed a counterphase relationship between those peaks, indicating the formation of dipoles. Our findings suggest that nonphase-locked HGA arises in part from oscillatory or recurring activity of supragranular-layer neuronal ensembles in auditory cortex.

The distribution and nature of responses to broadband sounds associated with pitch in the macaque auditory cortex

The organisation of pitch-perception mechanisms in the primate cortex is controversial, in that divergent results have been obtained, ranging from a single circumscribed ‘pitch centre’ to systems widely distributed across auditory cortex. Possible reasons for such discrepancies include different species, recording techniques, pitch stimuli, sampling of auditory fields, and the neural metrics recorded. In the present study, we sought to bridge some of these divisions by examining activity related to pitch in both neurons and neuronal ensembles within the auditory cortex of the rhesus macaque, a primate species with similar pitch perception and auditory cortical organisation to humans. We demonstrate similar responses, in primary and non-primary auditory cortex, to two different types of broadband pitch above the macaque lower limit in both neurons and local field potential (LFP) gamma oscillations. The majority of broadband pitch responses in neurons and LFP sites did not show equivalent tuning for sine tones.

Divergence in the functional organization of human and macaque auditory cortex revealed by fMRI responses to harmonic tones

We report a difference between humans and macaque monkeys in the functional organization of cortical regions implicated in pitch perception: humans but not macaques showed regions with a strong preference for harmonic sounds compared to noise, measured with both synthetic tones and macaque vocalizations. In contrast, frequency-selective tonotopic maps were similar between the two species. This species difference may be driven by the unique demands of speech and music perception in humans.

Signature Patterns for Top-Down and Bottom-Up Information Processing via Cross-Frequency Coupling in Macaque Auditory Cortex.

Predictive coding is a theoretical framework that provides a functional interpretation of top-down and bottom-up interactions in sensory processing. The theory suggests there are differences in message passing up versus down the cortical hierarchy. These differences result from the linear feedforward of prediction errors, and the nonlinear feedback of predictions. This implies that cross-frequency interactions should predominate top-down. But it remains unknown whether these differences are expressed in cross-frequency interactions in the brain. Here we examined bidirectional cross-frequency coupling across four sectors of the auditory hierarchy in the macaque. We computed two measures of cross-frequency coupling, phase–amplitude coupling (PAC) and amplitude–amplitude coupling (AAC). Our findings revealed distinct patterns for bottom-up and top-down information processing among cross-frequency interactions. Both top-down and bottom-up interactions made prominent use of low frequencies: low-to-low-frequency (theta, alpha, beta) and low-frequency-to-high- gamma couplings were predominant top-down, while low-frequency-to-low-gamma couplings were predominant bottom-up. These patterns were largely preserved across coupling types (PAC and AAC) and across stimulus types (natural and synthetic auditory stimuli), suggesting that they are a general feature of information processing in auditory cortex. Our findings suggest the modulatory effect of low frequencies on gamma-rhythms in distant regions is important for bidirectional information transfer. The finding of low-frequency-to-low-gamma interactions in the bottom-up direction suggest that nonlinearities may also play a role in feedforward message passing. Altogether, the patterns of cross-frequency interaction we observed across the auditory hierarchy are largely consistent with the predictive coding framework.

Homology and Specificity of Natural Sound-Encoding in Human and Monkey Auditory Cortex.

Understanding homologies and differences in auditory cortical processing in human and nonhuman primates is an essential step in elucidating the neurobiology of speech and language. Using fMRI responses to natural sounds, we investigated the representation of multiple acoustic features in auditory cortex of awake macaques and humans. Comparative analyses revealed homologous large-scale topographies not only for frequency but also for temporal and spectral modulations. In both species, posterior regions preferably encoded relatively fast temporal and coarse spectral information, whereas anterior regions encoded slow temporal and fine spectral modulations. Conversely, we observed a striking interspecies difference in cortical sensitivity to temporal modulations: While decoding from macaque auditory cortex was most accurate at fast rates (> 30 Hz), humans had highest sensitivity to ~3 Hz, a relevant rate for speech analysis. These findings suggest that characteristic tuning of human auditory cortex to slow temporal modulations is unique and may have emerged as a critical step in the evolution of speech and language.

Age-Related Changes in Temporal Processing of Rapidly-Presented Sound Sequences in the Macaque Auditory Cortex.

The mammalian auditory cortex is necessary to resolve temporal features in rapidly-changing sound streams. This capability is crucial for speech comprehension in humans and declines with normal aging. Nonhuman primate studies have revealed detrimental effects of normal aging on the auditory nervous system, and yet the underlying influence on temporal processing remains less well-defined. Therefore, we recorded from the core and lateral belt areas of auditory cortex when awake young and old monkeys listened to tone-pip and noise-burst sound sequences. Elevated spontaneous and stimulus-driven activity were the hallmark characteristics in old monkeys. These old neurons showed isomorphic-like discharge patterns to stimulus envelopes, though their phase-locking was less precise. Functional preference in temporal coding between the core and belt existed in the young monkeys but was mostly absent in the old monkeys, in which old belt neurons showed core-like response profiles. Finally, the analysis of population activity patterns indicated that the aged auditory cortex demonstrated a homogenous, distributed coding strategy, compared to the selective, sparse coding strategy observed in the young monkeys. Degraded temporal fidelity and highly-responsive, broadly-tuned cortical responses could underlie how aged humans have difficulties to resolve and track dynamic sounds leading to speech processing deficits.

Primary Generators of Visually Evoked Field Potentials Recorded in the Macaque Auditory Cortex.

Prior studies have reported "local" field potential (LFP) responses to faces in the macaque auditory cortex and have suggested that such face-LFPs may be substrates of audiovisual integration. However, although field potentials (FPs) may reflect the synaptic currents of neurons near the recording electrode, due to the use of a distant reference electrode, they often reflect those of synaptic activity occurring in distant sites as well. Thus, FP recordings within a given brain region (e.g., auditory cortex) may be "contaminated" by activity generated elsewhere in the brain. To determine whether face responses are indeed generated within macaque auditory cortex, we recorded FPs and concomitant multiunit activity with linear array multielectrodes across auditory cortex in three macaques (one female), and applied current source density (CSD) analysis to the laminar FP profile. CSD analysis revealed no appreciable local generator contribution to the visual FP in auditory cortex, although we did note an increase in the amplitude of visual FP with cortical depth, suggesting that their generators are located below auditory cortex. In the underlying inferotemporal cortex, we found polarity inversions of the main visual FP components accompanied by robust CSD responses and large-amplitude multiunit activity. These results indicate that face-evoked FP responses in auditory cortex are not generated locally but are volume-conducted from other face-responsive regions. In broader terms, our results underscore the caution that, unless far-field contamination is removed, LFPs in general may reflect such "far-field" activity, in addition to, or in absence of, local synaptic responses.SIGNIFICANCE STATEMENT Field potentials (FPs) can index neuronal population activity that is not evident in action potentials. However, due to volume conduction, FPs may reflect activity in distant neurons superimposed upon that of neurons close to the recording electrode. This is problematic as the default assumption is that FPs originate from local activity, and thus are termed "local" (LFP). We examine this general problem in the context of previously reported face-evoked FPs in macaque auditory cortex. Our findings suggest that face-FPs are indeed generated in the underlying inferotemporal cortex and volume-conducted to the auditory cortex. The note of caution raised by these findings is of particular importance for studies that seek to assign FP/LFP recordings to specific cortical layers.

Widespread and Opponent fMRI Signals Represent Sound Location in Macaque Auditory Cortex

In primates, posterior auditory cortical areas are thought to be part of a dorsal auditory pathway that processes spatial information. But how posterior (and other) auditory areas represent acoustic space remains a matter of debate. Here we provide new evidence based on functional magnetic resonance imaging (fMRI) of the macaque indicating that space is predominantly represented by a distributed hemifield code rather than by a local spatial topography. Hemifield tuning in cortical and subcortical regions emerges from an opponent hemispheric pattern of activation and deactivation that depends on the availability of interaural delay cues. Importantly, these opponent signals allow responses in posterior regions to segregate space similarly to a hemifield code representation. Taken together, our results reconcile seemingly contradictory views by showing that the representation of space follows closely a hemifield code and suggest that enhanced posterior-dorsal spatial specificity in primates might emerge from this form of coding.

The Relationship of Tuning and Noise Correlations in Macaque Auditory Cortex.

All neurons are noisy, but some neurons are more noisy than others, [Downer and colleagues (2015)][1] report in a recent issue of The Journal of Neuroscience . Sources of biological noise are plenty: from the stochastic nature of presynaptic neurotransmitter release and postsynaptic ion channel

Generation of field potentials and modulation of their dynamics through volume integration of cortical activity.

Field potentials (FPs) recorded within the brain, often called "local field potentials" (LFPs), are useful measures of net synaptic activity in a neuronal ensemble. However, due to volume conduction, FPs spread beyond regions of underlying synaptic activity, and thus an "LFP" signal may not accurately reflect the temporal patterns of synaptic activity in the immediately surrounding neuron population. To better understand the physiological processes reflected in FPs, we explored the relationship between the FP and its membrane current generators using current source density (CSD) analysis in conjunction with a volume conductor model. The model provides a quantitative description of the spatiotemporal summation of immediate local and more distant membrane currents to produce the FP. By applying the model to FPs in the macaque auditory cortex, we have investigated a critical issue that has broad implications for FP research. We have shown that FP responses in particular cortical layers are differentially susceptible to activity in other layers. Activity in the supragranular layers has the strongest contribution to FPs in other cortical layers, and infragranular FPs are most susceptible to contributions from other layers. To define the physiological processes generating FPs recorded in loci of relatively weak synaptic activity, strong effects produced by synaptic events in the vicinity have to be taken into account. While outlining limitations and caveats inherent to FP measurements, our results also suggest specific peak and frequency band components of FPs can be related to activity in specific cortical layers. These results may help improving the interpretability of FPs.

Processing of harmonics in the lateral belt of macaque auditory cortex.

Many speech sounds and animal vocalizations contain components, referred to as complex tones, that consist of a fundamental frequency (F0) and higher harmonics. In this study we examined single-unit activity recorded in the core (A1) and lateral belt (LB) areas of auditory cortex in two rhesus monkeys as they listened to pure tones and pitch-shifted conspecific vocalizations (“coos”). The latter consisted of complex-tone segments in which F0 was matched to a corresponding pure-tone stimulus. In both animals, neuronal latencies to pure-tone stimuli at the best frequency (BF) were ~10 to 15 ms longer in LB than in A1. This might be expected, since LB is considered to be at a hierarchically higher level than A1. On the other hand, the latency of LB responses to coos was ~10 to 20 ms shorter than to the corresponding pure-tone BF, suggesting facilitation in LB by the harmonics. This latency reduction by coos was not observed in A1, resulting in similar coo latencies in A1 and LB. Multi-peaked neurons were present in both A1 and LB; however, harmonically-related peaks were observed in LB for both early and late response components, whereas in A1 they were observed only for late components. Our results suggest that harmonic features, such as relationships between specific frequency intervals of communication calls, are processed at relatively early stages of the auditory cortical pathway, but preferentially in LB.

Neural correlates of hearing in noise in macaque auditory cortex

The perception of sound in a noisy environment is a critical function of the auditory system. Here, we describe results from our study into the link between neural activity in the auditory cortex and the hearing-in-noise tasks described above. We recorded neural activity from single neurons in the core auditory cortex (i.e., A1) while monkeys were participating in these tasks. Neural recordings were conducted with tetrodes, and the frequency of the target matched the best frequency of the recorded auditory neuron. We found that the relative intensity of the target tone in the presence of the noise masker significantly modulated the response of A1 neurons. In contrast, the presentation of the target sound alone did not elicit a significant response from A1 neurons. This suggests a task-relevant contextual modulation of A1 responses during hearing in noise. Additionally we found no correlation between the monkey's behavioral choices—as assessed by their responses on choice trials—and A1 activity. Our results suggest that the encoding of a sound of interest in the presence of a noise masker is an active process, providing new insights into the neural basis for hearing in noise in the auditory system.

Differential Coding of Conspecific Vocalizations in the Ventral Auditory Cortical Stream

The mammalian auditory cortex integrates spectral and temporal acoustic features to support the perception of complex sounds, including conspecific vocalizations. Here we investigate coding of vocal stimuli in different subfields in macaque auditory cortex. We simultaneously measured auditory evoked potentials over a large swath of primary and higher order auditory cortex along the supratemporal plane in three animals chronically using high-density microelectrocorticographic arrays. To evaluate the capacity of neural activity to discriminate individual stimuli in these high-dimensional datasets, we applied a regularized multivariate classifier to evoked potentials to conspecific vocalizations. We found a gradual decrease in the level of overall classification performance along the caudal to rostral axis. Furthermore, the performance in the caudal sectors was similar across individual stimuli, whereas the performance in the rostral sectors significantly differed for different stimuli. Moreover, the information about vocalizations in the caudal sectors was similar to the information about synthetic stimuli that contained only the spectral or temporal features of the original vocalizations. In the rostral sectors, however, the classification for vocalizations was significantly better than that for the synthetic stimuli, suggesting that conjoined spectral and temporal features were necessary to explain differential coding of vocalizations in the rostral areas. We also found that this coding in the rostral sector was carried primarily in the theta frequency band of the response. These findings illustrate a progression in neural coding of conspecific vocalizations along the ventral auditory pathway.

Neural latencies across auditory cortex of macaque support a dorsal stream supramodal timing advantage in primates

Sensory systems across the brain are specialized for their input, yet some principles of neural organization are conserved across modalities. The pattern of anatomical connections from the primate auditory cortex to the temporal, parietal, and prefrontal lobes suggests a possible division into dorsal and ventral auditory processing streams, with the dorsal stream originating from more caudal areas of the auditory cortex, and the ventral stream originating from more rostral areas. These streams are hypothesized to be analogous to the well-established dorsal and ventral streams of visual processing. In the visual system, the dorsal processing stream shows substantially faster neural response latencies than does the ventral stream. However, the relative timing of putative dorsal and ventral stream processing has yet to be explored in other sensory modalities. Here, we compare distributions of neural response latencies from 10 different areas of macaque auditory cortex, confirmed by individual anatomical reconstructions, to determine whether a similar timing advantage is found for the hypothesized dorsal auditory stream. Across three varieties of auditory stimuli (clicks, noise, and pure tones), we find that latencies increase with hierarchical level, as predicted by anatomical connectivity. Critically, we also find a pronounced timing differential along the caudal-to-rostral axis within the same hierarchical level, with caudal (dorsal stream) latencies being faster than rostral (ventral stream) latencies. This observed timing differential mirrors that found for the dorsal stream of the visual system, suggestive of a common timing advantage for the dorsal stream across sensory modalities.

The Signs of Silence

How does auditory cortex respond to silence? In this issue of Neuron, show that activity in macaque auditory cortex is highly structured even in the absence of sensory stimuli. These data reveal a close link between spontaneous neural activity and the functional organization of auditory cortex.

Spontaneous High-Gamma Band Activity Reflects Functional Organization of Auditory Cortex in the Awake Macaque

In the absence of sensory stimuli, spontaneous activity in the brain has been shown to exhibit organization at multiple spatiotemporal scales. In the macaque auditory cortex, responses to acoustic stimuli are tonotopically organized within multiple, adjacent frequency maps aligned in a caudorostral direction on the supratemporal plane (STP) of the lateral sulcus. Here, we used chronic microelectrocorticography to investigate the correspondence between sensory maps and spontaneous neural fluctuations in the auditory cortex. We first mapped tonotopic organization across 96 electrodes spanning approximately two centimeters along the primary and higher auditory cortex. In separate sessions, we then observed that spontaneous activity at the same sites exhibited spatial covariation that reflected the tonotopic map of the STP. This observation demonstrates a close relationship between functional organization and spontaneous neural activity in the sensory cortex of the awake monkey.

EEG Phase Patterns Reflect the Selectivity of Neural Firing

Oscillations are pervasive in encephalographic signals and supposedly reflect cognitive processes and sensory representations. While the relation between oscillation amplitude (power) and sensory-cognitive variables has been extensively studied, recent work reveals that the dynamic oscillation signature (phase pattern) can carry information about such processes to a greater degree than amplitude. To elucidate the neural correlates of oscillatory phase patterns, we compared the stimulus selectivity of neural firing rates and auditory-driven electroencephalogram (EEG) oscillations. We employed the same naturalistic sound stimuli in 2 experiments, one recording scalp EEGs in humans and one recording intracortical local field potentials (LFPs) and single neurons in macaque auditory cortex. Using stimulus decoding techniques, we show that stimulus selective firing patterns imprint on the phase rather than the amplitude of slow (theta band) oscillations in LFPs and EEG. In particular, we find that stimuli which can be discriminated by firing rates can also be discriminated by phase patterns but not by oscillation amplitude and that stimulus-specific phase patterns also persist in the absence of increases of oscillation power. These findings support a neural basis for stimulus selective and entrained EEG phase patterns and reveal a level of interrelation between encephalographic signals and neural firing beyond simple amplitude covariations in both signals.

How Local Is the Local Field Potential?

Local field potentials (LFPs) are of growing importance in neurophysiological investigations. LFPs supplement action potential recordings by indexing activity relevant to EEG, magnetoencephalographic, and hemodynamic (fMRI) signals. Recent reports suggest that LFPs reflect activity within very small domains of several hundred micrometers. We examined this conclusion by comparing LFP, current source density (CSD), and multiunit activity (MUA) signals in macaque auditory cortex. Estimated by frequency tuning bandwidths, these signals' "listening areas" differ systematically with an order of MUA< CSD< LFP. Computational analyses confirm that observed LFPs receive local contributions. Direct measurements indicate passive spread of LFPs to sites more than a centimeter from their origins. These findings appear to be independent of the frequency content of the LFP. Our results challenge the idea that LFP recordings typically integrate over extremely circumscribed local domains. Rather, LFPs appear as a mixture of local potentials with "volume conducted" potentials from distant sites.

Eye Movement-Related Activity in and below the Macaque Auditory Cortex

Eye Movement-Related Activity in and below the Macaque Auditory Cortex

Regional and laminar distribution of the vesicular glutamate transporter, VGluT2, in the macaque monkey auditory cortex

The auditory cortex of primates contains 13 areas distributed among 3 hierarchically connected regions: core, belt, and parabelt. Thalamocortical inputs arise in parallel from four divisions of the medial geniculate complex (MGC), which have regionally distinct projection patterns. These inputs terminate in layers IIIb and/or IV, and are assumed to be glutamatergic, although this has not been verified. In the present study, immunoreactivity (-ir) for the vesicular glutamate transporter, VGluT2, was used to estimate the regional and laminar distribution of the glutamatergic thalamocortical projection in the macaque auditory cortex. Coronal sections containing auditory cortex were processed for VGluT2 and other markers concentrated in the thalamorecipient layers: cytochrome oxidase, acetylcholinesterase, and parvalbumin. Marker expression was studied with wide field and confocal microscopy. The main findings were: (1) VGluT2-ir was highest in the core, intermediate in the belt, and sparse in the parabelt; (2) VGluT2-ir was concentrated in the neuropil of layers IIIb/IV in the core and layer IIIb in the belt; (3) VGluT2-ir matched regional and laminar expression of the other chemoarchitectonic markers. The results indicate that the glutamatergic thalamic projection to auditory cortex, as indexed by VGluT2-ir, varies along the core–belt–parabelt axis in a manner that matches the gradients of other markers. These chemoarchitectonic features are likely to subserve regional differences in neuronal activity between regions of auditory cortex.