Brian J. Malone

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.

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.

The Operating Point of the Cortex: Neurons as Large Deviation Detectors

Spiking neurons translate analog intracellular variables into a sequence of action potentials. A simplified model of this transformation is one in which an underlying “generator potential,” representing a measure of overall neuronal drive, is passed through a static nonlinearity to produce an instantaneous firing rate. An important question is how adaptive mechanisms adjust the mean and SD of the generator potential to define an “operating point” that controls spike generation. In early sensory pathways adaptation has been shown to rescale the generator potential to maximize the amount of transmitted information. In contrast, we demonstrate that the operating point in the cortex is tuned so that cells respond only when the generator potential executes a large excursion above its mean value. The distance from the mean of the generator potential to spike threshold is, on average, 1 SD of the ongoing activity. Signals above threshold are amplified linearly and do not reach saturation. The operating point is adjusted dynamically so that it remains relatively invariant despite changes in stimulus contrast. We conclude that the operating regimen of the cortex is suitable for the detection of signals in background noise and for enhancing the selectivity of spike responses relative to those of the generator potential (the so-called “iceberg effect”), but not to maximize the transmission of total information.

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.

Dynamics of tuning in the Fourier domain.

Neurons in primary visual cortex (area V1) are jointly tuned to the orientation and spatial frequency of sinusoidal stimuli (the Fourier domain). The role that suppressive mechanisms play in shaping the tuning and dynamics of cortical responses remains the subject of debate. Here we used subspace reverse correlation to study the relationship between suppression by nonoptimal stimuli, the spectral-temporal separability of the responses, and their persistence in time. Two clear relationships emerged from our data. First, cells with inseparable responses were often accompanied by suppression to nonpreferred stimuli, while separable responses showed mostly enhancement by their preferred stimuli. Second, inseparable responses were characterized by a longer persistence in time compared with those with separable dynamics. A parametric model that assumes the additive combination of separable enhancement and suppression signals, with suppression constrained to be low-pass in spatial frequency and untuned for orientation, explained the data well. These new findings, in addition to an established correlation between selectivity and suppression for nonoptimal stimuli, clarify how the dynamics and selectivity of cortical responses are shaped by suppressive signals and how their interplay generates the large diversity of responses observed in primary visual cortex.