Basic Properties of Coordinated Neuronal Ensembles in the Auditory Thalamus.

Coordinated neuronal activity has been identified to play an important role in information processing and transmission in the brain. However, current research predominantly focuses on understanding the properties and functions of neuronal coordination in hippocampal and cortical areas, leaving subcortical regions relatively unexplored. In this study, we use single-unit recordings in female Sprague Dawley rats to investigate the properties and functions of groups of neurons exhibiting coordinated activity in the auditory thalamus-the medial geniculate body (MGB). We reliably identify coordinated neuronal ensembles (cNEs), which are groups of neurons that fire synchronously, in the MGB. cNEs are shown not to be the result of false-positive detections or by-products of slow-state oscillations in anesthetized animals. We demonstrate that cNEs in the MGB have enhanced information-encoding properties over individual neurons. Their neuronal composition is stable between spontaneous and evoked activity, suggesting limited stimulus-induced ensemble dynamics. These MGB cNE properties are similar to what is observed in cNEs in the primary auditory cortex (A1), suggesting that ensembles serve as a ubiquitous mechanism for organizing local networks and play a fundamental role in sensory processing within the brain.

Auditory training remodels hippocampus-related memory in adult rats.

Consequences of perceptual training, such as improvements in discriminative ability, are highly stimulus and task specific. Therefore, most studies on auditory training-induced plasticity in adult brain have focused on the sensory aspects, particularly on functional and structural effects in the auditory cortex. Auditory training often involves, other than auditory demands, significant cognitive components. Yet, how auditory training affects cognition-related brain regions, such as the hippocampus, remains unclear. Here, we found in female rats that auditory cue-based go/no-go training significantly improved the memory-guided behaviors associated with hippocampus. The long-term potentiations of the trained rats recorded in vivo in the hippocampus were also enhanced compared with the naïve rats. In parallel, the phosphorylation level of calcium/calmodulin-dependent protein kinase II and the expression of parvalbumin-positive interneurons in the hippocampus were both upregulated. These findings demonstrate that auditory training substantially remodels the processing and function of brain regions beyond the auditory system, which are associated with task demands.

Plasticity of Multidimensional Receptive Fields in Core Rat Auditory Cortex Directed by Sound Statistics.

Sensory cortical neurons can nonlinearly integrate a wide range of inputs. The outcome of this nonlinear process can be approximated by more than one receptive field component or filter to characterize the ensuing stimulus preference. The functional properties of multidimensional filters are, however, not well understood. Here we estimated two spectrotemporal receptive fields (STRFs) per neuron using maximally informative dimension analysis. We compared their temporal and spectral modulation properties and determined the stimulus information captured by the two STRFs in core rat auditory cortical fields, primary auditory cortex (A1) and ventral auditory field (VAF). The first STRF is the dominant filter and acts as a sound feature detector in both fields. The second STRF is less feature specific, preferred lower modulations, and had less spike information compared to the first STRF. The information jointly captured by the two STRFs was larger than that captured by the sum of the individual STRFs, reflecting nonlinear interactions of two filters. This information gain was larger in A1. We next determined how the acoustic environment affects the structure and relationship of these two STRFs. Rats were exposed to moderate levels of spectrotemporally modulated noise during development. Noise exposure strongly altered the spectrotemporal preference of the first STRF in both cortical fields. The interaction between the two STRFs was reduced by noise exposure in A1 but not in VAF. The results reveal new functional distinctions between A1 and VAF indicating that (i) A1 has stronger interactions of the two STRFs than VAF, (ii) noise exposure diminishes modulation parameter representation contained in the noise more strongly for the first STRF in both fields, and (iii) plasticity induced by noise exposure can affect the strength of filter interactions in A1. Taken together, ascertaining two STRFs per neuron enhances the understanding of cortical information processing and plasticity effects in core auditory cortex.

Information diversity in individual auditory cortical neurons is associated with functionally distinct coordinated neuronal ensembles.

Neuronal activity in auditory cortex is often highly synchronous between neighboring neurons. Such coordinated activity is thought to be crucial for information processing. We determined the functional properties of coordinated neuronal ensembles (cNEs) within primary auditory cortical (AI) columns relative to the contributing neurons. Nearly half of AI cNEs showed robust spectro-temporal receptive fields whereas the remaining cNEs showed little or no acoustic feature selectivity. cNEs can therefore capture either specific, time-locked information of spectro-temporal stimulus features or reflect stimulus-unspecific, less-time specific processing aspects. By contrast, we show that individual neurons can represent both of those aspects through membership in multiple cNEs with either high or absent feature selectivity. These associations produce functionally heterogeneous spikes identifiable by instantaneous association with different cNEs. This demonstrates that single neuron spike trains can sequentially convey multiple aspects that contribute to cortical processing, including stimulus-specific and unspecific information.

Spectral plasticity in monkey primary auditory cortex limits performance generalization in a temporal discrimination task.

Auditory experience and behavioral training can modify perceptual performance. However, the consequences of temporal perceptual learning for temporal and spectral neural processing remain unclear. Specifically, the attributes of neural plasticity that underlie task generalization in behavioral performance remain uncertain. To assess the relationship between behavioral and neural plasticity, we evaluated neuronal temporal processing and spectral tuning in primary auditory cortex (AI) of anesthetized owl monkeys trained to discriminate increases in the envelope frequency (e.g., 4-Hz standard vs. >5-Hz targets) of sinusoidally amplitude-modulated (SAM) 1-kHz or 2-kHz carriers. Behavioral and neuronal performance generalization was evaluated for carriers ranging from 0.5 kHz to 8 kHz. Psychophysical thresholds revealed high SAM discrimination acuity for carriers from one octave below to ∼0.6 octave above the trained carrier frequency. However, generalization of SAM discrimination learning progressively declined for carrier frequencies >0.6 octave above the trained carrier frequency. Neural responses in AI showed that SAM discrimination training resulted in 1) increases in temporal modulation preference, especially at carriers close to the trained frequency, 2) narrowing of spectral tuning for neurons with characteristic frequencies near the trained carrier frequency, potentially limiting spectral generalization of temporal training effects, and 3) enhancement of firing-rate contrast for rewarded versus nonrewarded SAM frequencies, providing a potential cue for behavioral temporal discrimination near the trained carrier frequency. Our findings suggest that temporal training at a specific spectral location sharpens local frequency tuning, thus, confining the training effects to a narrow frequency range and limiting generalization of temporal discrimination learning across a wider frequency range.NEW & NOTEWORTHY Monkeys' ability to generalize amplitude modulation discrimination to nontrained carriers was limited to one octave below and 0.6 octave above the trained carrier frequency. Asymmetric generalization was paralleled by sharpening in cortical spectral tuning and enhanced firing-rate contrast between rewarded and nonrewarded SAM stimuli at carriers near the trained frequency. The spectral content of the training stimulus specified spectral and temporal plasticity that may provide a neural substrate for limitations in generalization of temporal discrimination learning.

Auditory Cortical Plasticity Dependent on Environmental Noise Statistics.

During critical periods, neural circuits develop to form receptive fields that adapt to the sensory environment and enable optimal performance of relevant tasks. We hypothesized that early exposure to background noise can improve signal-in-noise processing, and the resulting receptive field plasticity in the primary auditory cortex can reveal functional principles guiding that important task. We raised rat pups in different spectro-temporal noise statistics during their auditory critical period. As adults, they showed enhanced behavioral performance in detecting vocalizations in noise. Concomitantly, encoding of vocalizations in noise in the primary auditory cortex improves with noise-rearing. Significantly, spectro-temporal modulation plasticity shifts cortical preferences away from the exposed noise statistics, thus reducing noise interference with the foreground sound representation. Auditory cortical plasticity shapes receptive field preferences to optimally extract foreground information in noisy environments during noise-rearing. Early noise exposure induces cortical circuits to implement efficient coding in the joint spectral and temporal modulation domain.

Stimulus dependent transformations between synaptic and spiking receptive fields in auditory cortex.

Auditory cortex neurons nonlinearly integrate synaptic inputs from the thalamus and cortex, and generate spiking outputs for simple and complex sounds. Directly comparing synaptic and spiking activity can determine whether this input-output transformation is stimulus-dependent. We employ in vivo whole-cell recordings in the mouse primary auditory cortex, using pure tones and broadband dynamic moving ripple stimuli, to examine properties of functional integration in tonal (TRFs) and spectrotemporal (STRFs) receptive fields. Spectral tuning in STRFs derived from synaptic, subthreshold and spiking responses proves to be substantially more selective than for TRFs. We describe diverse spectral and temporal modulation preferences and distinct nonlinearities, and their modifications between the input and output stages of neural processing. These results characterize specific processing differences at the level of synaptic convergence, integration and spike generation resulting in stimulus-dependent transformation patterns in the primary auditory cortex.

Distinct Manifestations of Cooperative, Multidimensional Stimulus Representations in Different Auditory Forebrain Stations.

Classic spectrotemporal receptive fields (STRFs) for auditory neurons are usually expressed as a single linear filter representing a single encoded stimulus feature. Multifilter STRF models represent the stimulus-response relationship of primary auditory cortex (A1) neurons more accurately because they can capture multiple stimulus features. To determine whether multifilter processing is unique to A1, we compared the utility of single-filter versus multifilter STRF models in the medial geniculate body (MGB), anterior auditory field (AAF), and A1 of ketamine-anesthetized cats. We estimated STRFs using both spike-triggered average (STA) and maximally informative dimension (MID) methods. Comparison of basic filter properties of first maximally informative dimension (MID1) and second maximally informative dimension (MID2) in the 3 stations revealed broader spectral integration of MID2s in MGBv and A1 as opposed to AAF. MID2 peak latency was substantially longer than for STAs and MID1s in all 3 stations. The 2-filter MID model captured more information and yielded better predictions in many neurons from all 3 areas but disproportionately more so in AAF and A1 compared with MGBv. Significantly, information-enhancing cooperation between the 2 MIDs was largely restricted to A1 neurons. This demonstrates significant differences in how these 3 forebrain stations process auditory information, as expressed in effective and synergistic multifilter processing.

Coordinated neuronal ensembles in primary auditory cortical columns.

The synchronous activity of groups of neurons is increasingly thought to be important in cortical information processing and transmission. However, most studies of processing in the primary auditory cortex (AI) have viewed neurons as independent filters; little is known about how coordinated AI neuronal activity is expressed throughout cortical columns and how it might enhance the processing of auditory information. To address this, we recorded from populations of neurons in AI cortical columns of anesthetized rats and, using dimensionality reduction techniques, identified multiple coordinated neuronal ensembles (cNEs), which are groups of neurons with reliable synchronous activity. We show that cNEs reflect local network configurations with enhanced information encoding properties that cannot be accounted for by stimulus-driven synchronization alone. Furthermore, similar cNEs were identified in both spontaneous and evoked activity, indicating that columnar cNEs are stable functional constructs that may represent principal units of information processing in AI.

A Critical Role of Inhibition in Temporal Processing Maturation in the Primary Auditory Cortex.

Faithful representation of sound envelopes in primary auditory cortex (A1) is vital for temporal processing and perception of natural sounds. However, the emergence of cortical temporal processing mechanisms during development remains poorly understood. Although cortical inhibition has been proposed to play an important role in this process, direct in-vivo evidence has been lacking. Using loose-patch recordings in rat A1 immediately after hearing onset, we found that stimulus-following ability in fast-spiking neurons was significantly better than in regular-spiking (RS) neurons. In-vivo whole-cell recordings of RS neurons revealed that inhibition in the developing A1 demonstrated much weaker adaptation to repetitive stimuli than in adult A1. Furthermore, inhibitory synaptic inputs were of longer duration than observed in vitro and in adults. Early in development, overlap of the prolonged inhibition evoked by 2 closely following stimuli disrupted the classical temporal sequence between excitation and inhibition, resulting in slower following capacity. During maturation, inhibitory duration gradually shortened accompanied by an improving temporal following ability of RS neurons. Both inhibitory duration and stimulus-following ability demonstrated exposure-based plasticity. These results demonstrate the role of inhibition in setting the pace for experience-dependent maturation of temporal processing in the auditory cortex.

Dlx1 and Dlx2 Promote Interneuron GABA Synthesis, Synaptogenesis, and Dendritogenesis.

The postnatal functions of the Dlx1&2 transcription factors in cortical interneurons (CINs) are unknown. Here, using conditional Dlx1, Dlx2, and Dlx1&2 knockouts (CKOs), we defined their roles in specific CINs. The CKOs had dendritic, synaptic, and survival defects, affecting even PV+ CINs. We provide evidence that DLX2 directly drives Gad1, Gad2, and Vgat expression, and show that mutants had reduced mIPSC amplitude. In addition, the mutants formed fewer GABAergic synapses on excitatory neurons and had reduced mIPSC frequency. Furthermore, Dlx1/2 CKO had hypoplastic dendrites, fewer excitatory synapses, and reduced excitatory input. We provide evidence that some of these phenotypes were due to reduced expression of GRIN2B (a subunit of the NMDA receptor), a high confidence Autism gene. Thus, Dlx1&2 coordinate key components of CIN postnatal development by promoting their excitability, inhibitory output, and survival.

Cortical Interneurons Differentially Regulate the Effects of Acoustic Context.

Both behavioral and neural responses to sounds are generally modified by the acoustic context in which they are encountered. As an example, in the auditory cortex, preceding sounds can powerfully suppress responses to later, spectrally similar sounds-a phenomenon called forward suppression (FWS). Whether cortical inhibitory networks shape such suppression or whether it is wholly regulated by common mechanisms such as synaptic depression or spike frequency adaptation is controversial. Here, we show that optogenetically suppressing somatostatin-positive (Sst+) interneurons weakens forward suppression, often revealing facilitation in neurons that are normally forward-suppressed. In contrast, inactivating parvalbumin-positive (Pvalb+) interneurons strengthens forward suppression and alters its frequency dependence. In a simple network model, we show that these effects can be accounted for by differences in short-term synaptic dynamics of inputs onto Pvalb+ and Sst+ interneurons. These results demonstrate separate roles for somatostatin and parvalbumin interneurons in regulating the context dependence of auditory processing.

Diverse effects of stimulus history in waking mouse auditory cortex.

Responses to auditory stimuli are often strongly influenced by recent stimulus history. For example, in a paradigm called forward suppression, brief sounds can suppress the perception of, and the neural responses to, a subsequent sound, with the magnitude of this suppression depending on both the spectral and temporal distances between the sounds. As a step towards understanding the mechanisms that generate these adaptive representations in awake animals, we quantitatively characterize responses to two-tone sequences in the auditory cortex of waking mice. We find that cortical responses in a forward suppression paradigm are more diverse in waking mice than previously appreciated, that these responses vary between cells with different firing characteristics and waveform shapes, but that the variability in these responses is not substantially related to cortical depth or columnar location. Moreover, responses to the first tone in the sequence are often not linearly related to the suppression of the second tone response, suggesting that spike-frequency adaptation of cortical cells is not a large contributor to forward suppression or its variability. Instead, we use a simple multilayered model to show that cell-to-cell differences in the balance of intracortical inhibition and excitation will naturally produce such a diversity of forward interactions. We propose that diverse inhibitory connectivity allows the cortex to encode spectro-temporally fluctuating stimuli in multiple parallel ways.NEW & NOTEWORTHY Behavioral and neural responses to auditory stimuli are profoundly influenced by recent sounds, yet how this occurs is not known. Here, the authors show in the auditory cortex of awake mice that the quality of history-dependent effects is diverse and related to cell type, response latency, firing rates, and receptive field bandwidth. In a cortical model, differences in excitatory-inhibitory balance can produce this diversity, providing the cortex with multiple ways of representing temporally complex information.

Anisomorphic cortical reorganization in asymmetric sensorineural hearing loss.

Acoustic trauma or inner ear disease may predominantly injure one ear, causing asymmetric sensorineural hearing loss (SNHL). While characteristic frequency (CF) map plasticity of primary auditory cortex (AI) contralateral to the injured ear has been detailed, there is no study that also evaluates ipsilateral AI to compare cortical reorganization across both hemispheres. We assess whether the normal isomorphic mirror-image relationship between the two hemispheres is maintained or disrupted in mild-to-moderate asymmetric SNHL of adult squirrel monkeys. At week 24 after induction of acoustic injury to the right ear, functional organization of the two hemispheres differs in direction and magnitude of interaural CF difference, percentage of recording sites with spectrally nonoverlapping binaural activation, and the concurrence of peripheral and central activation thresholds. The emergence of this anisomorphic cortical reorganization of the two hemispheres is replicated by simulation based on spike timing-dependent plasticity, where 1) AI input from the contralateral ear is dominant, 2) reestablishment of relatively shorter contralateral ear input timing drives reorganization, and 3) only AI contralateral to the injured ear undergoes major realignment of interaural frequency maps that evolve over months. Asymmetric SNHL disrupts isomorphic organization between the two hemispheres and results in relative local hemispheric autonomy, potentially impairing performance of tasks that require binaural input alignment or interhemispheric processing.NEW & NOTEWORTHY Mild-to-moderate hearing loss in one ear and essentially normal hearing in the other triggers cortical reorganization that is different in the two hemispheres. Asymmetry of cochlea sensitivities does not simply propagate to the two auditory cortices in mirror-image fashion. The resulting anisomorphic cortical reorganization may be a neurophysiological basis of clinical deficits in asymmetric hearing loss, such as difficulty with hearing in noise, impaired spatial hearing, and accelerated decline of the poorer ear.

Background noise exerts diverse effects on the cortical encoding of foreground sounds.

In natural listening conditions, many sounds must be detected and identified in the context of competing sound sources, which function as background noise. Traditionally, noise is thought to degrade the cortical representation of sounds by suppressing responses and increasing response variability. However, recent studies of neural network models and brain slices have shown that background synaptic noise can improve the detection of signals. Because acoustic noise affects the synaptic background activity of cortical networks, it may improve the cortical responses to signals. We used spike train decoding techniques to determine the functional effects of a continuous white noise background on the responses of clusters of neurons in auditory cortex to foreground signals, specifically frequency-modulated sweeps (FMs) of different velocities, directions, and amplitudes. Whereas the addition of noise progressively suppressed the FM responses of some cortical sites in the core fields with decreasing signal-to-noise ratios (SNRs), the stimulus representation remained robust or was even significantly enhanced at specific SNRs in many others. Even though the background noise level was typically not explicitly encoded in cortical responses, significant information about noise context could be decoded from cortical responses on the basis of how the neural representation of the foreground sweeps was affected. These findings demonstrate significant diversity in signal in noise processing even within the core auditory fields that could support noise-robust hearing across a wide range of listening conditions.NEW & NOTEWORTHY The ability to detect and discriminate sounds in background noise is critical for our ability to communicate. The neural basis of robust perceptual performance in noise is not well understood. We identified neuronal populations in core auditory cortex of squirrel monkeys that differ in how they process foreground signals in background noise and that may contribute to robust signal representation and discrimination in acoustic environments with prominent background noise.

Passive stimulation and behavioral training differentially transform temporal processing in the inferior colliculus and primary auditory cortex.

In profoundly deaf cats, behavioral training with intracochlear electric stimulation (ICES) can improve temporal processing in the primary auditory cortex (AI). To investigate whether similar effects are manifest in the auditory midbrain, ICES was initiated in neonatally deafened cats either during development after short durations of deafness (8 wk of age) or in adulthood after long durations of deafness (≥3.5 yr). All of these animals received behaviorally meaningless, "passive" ICES. Some animals also received behavioral training with ICES. Two long-deaf cats received no ICES prior to acute electrophysiological recording. After several months of passive ICES and behavioral training, animals were anesthetized, and neuronal responses to pulse trains of increasing rates were recorded in the central (ICC) and external (ICX) nuclei of the inferior colliculus. Neuronal temporal response patterns (repetition rate coding, minimum latencies, response precision) were compared with results from recordings made in the AI of the same animals (Beitel RE, Vollmer M, Raggio MW, Schreiner CE. J Neurophysiol 106: 944-959, 2011; Vollmer M, Beitel RE. J Neurophysiol 106: 2423-2436, 2011). Passive ICES in long-deaf cats remediated severely degraded temporal processing in the ICC and had no effects in the ICX. In contrast to observations in the AI, behaviorally relevant ICES had no effects on temporal processing in the ICC or ICX, with the single exception of shorter latencies in the ICC in short-deaf cats. The results suggest that independent of deafness duration passive stimulation and behavioral training differentially transform temporal processing in auditory midbrain and cortex, and primary auditory cortex emerges as a pivotal site for behaviorally driven neuronal temporal plasticity in the deaf cat. NEW & NOTEWORTHY: Behaviorally relevant vs. passive electric stimulation of the auditory nerve differentially affects neuronal temporal processing in the central nucleus of the inferior colliculus (ICC) and the primary auditory cortex (AI) in profoundly short-deaf and long-deaf cats. Temporal plasticity in the ICC depends on a critical amount of electric stimulation, independent of its behavioral relevance. In contrast, the AI emerges as a pivotal site for behaviorally driven neuronal temporal plasticity in the deaf auditory system.

Synchrony, connectivity, and functional similarity in auditory midbrain local circuits.

The central nucleus of the inferior colliculus (ICC) contains a laminar structure that functions as an organizing substrate of ascending inputs and local processing. While topographic distributions of ICC response parameters within and across laminae have been reported, the functional micro-organization of the ICC is less well understood. For pairs of neighboring ICC neurons, we examined the nature of functional connectivity and receptive field preferences to gain a better understanding of the structure and function of local circuits. By recording from pairs of adjacent neurons and presenting pure-tone and dynamic broad-band stimulation, we estimated functional connectivity and local differences in frequency response areas (FRAs), spectrotemporal receptive fields (STRFs), nonlinear input/output functions, and single-spike information. From the cross-covariance functions we identified putative unidirectional as well as bidirectional excitatory/inhibitory interactions. STRFs of neighboring neurons strongly conserve best frequency, and moderately agree in STRF similarity, bandwidth, temporal response type, best modulation frequency, nonlinearity structure, and degree of information processing. Excitatory connectivity was stronger and temporally more precise than for inhibitory connections. Neither connection strength nor degree of synchrony correlated with receptive field parameters. The functional similarity of local pairs of ICC neurons was substantially less than for local pairs in the granular layers of primary auditory cortex (AI). These results imply that while the ICC is an obligatory nexus of ascending information, local neurons are comparatively weakly connected and exhibit considerable receptive field variability, potentially reflecting the heterogeneity of converging inputs to ICC functional zones.

Effects of Signal-to-Noise Ratio on Auditory Cortical Frequency Processing.

The neural mechanisms that support the robust processing of acoustic signals in the presence of background noise in the auditory system remain largely unresolved. Psychophysical experiments have shown that signal detection is influenced by the signal-to-noise ratio (SNR) and the overall stimulus level, but this relationship has not been fully characterized. We evaluated the neural representation of frequency in rat primary auditory cortex by constructing tonal frequency response areas (FRAs) in primary auditory cortex for different SNRs, tone levels, and noise levels. We show that response strength and selectivity for frequency and sound level depend on interactions between SNRs and tone levels. At low SNRs, jointly increasing the tone and noise levels reduced firing rates and narrowed FRA bandwidths; at higher SNRs, however, increasing the tone and noise levels increased firing rates and expanded bandwidths, as is usually seen for FRAs obtained without background noise. These changes in frequency and intensity tuning decreased tone level and tone frequency discriminability at low SNRs. By contrast, neither response onset latencies nor noise-driven steady-state firing rates meaningfully interacted with SNRs or overall sound levels. Speech detection performance in humans was also shown to depend on the interaction between overall sound level and SNR. Together, these results indicate that signal processing difficulties imposed by high noise levels are quite general and suggest that the neurophysiological changes we see for simple sounds generalize to more complex stimuli. SIGNIFICANCE STATEMENT: Effective processing of sounds in background noise is an important feature of the mammalian auditory system and a necessary feature for successful hearing in many listening conditions. Even mild hearing loss strongly affects this ability in humans, seriously degrading the ability to communicate. The mechanisms involved in achieving high performance in background noise are not well understood. We investigated the effects of SNR and overall stimulus level on the frequency tuning of neurons in rat primary auditory cortex. We found that the effects of noise on frequency selectivity are not determined solely by the SNR but depend also on the levels of the foreground tones and background noise. These observations can lead to improvement in therapeutic approaches for hearing-impaired patients.

Human Superior Temporal Gyrus Organization of Spectrotemporal Modulation Tuning Derived from Speech Stimuli.

The human superior temporal gyrus (STG) is critical for speech perception, yet the organization of spectrotemporal processing of speech within the STG is not well understood. Here, to characterize the spatial organization of spectrotemporal processing of speech across human STG, we use high-density cortical surface field potential recordings while participants listened to natural continuous speech. While synthetic broad-band stimuli did not yield sustained activation of the STG, spectrotemporal receptive fields could be reconstructed from vigorous responses to speech stimuli. We find that the human STG displays a robust anterior-posterior spatial distribution of spectrotemporal tuning in which the posterior STG is tuned for temporally fast varying speech sounds that have relatively constant energy across the frequency axis (low spectral modulation) while the anterior STG is tuned for temporally slow varying speech sounds that have a high degree of spectral variation across the frequency axis (high spectral modulation). This work illustrates organization of spectrotemporal processing in the human STG, and illuminates processing of ethologically relevant speech signals in a region of the brain specialized for speech perception. SIGNIFICANCE STATEMENT: Considerable evidence has implicated the human superior temporal gyrus (STG) in speech processing. However, the gross organization of spectrotemporal processing of speech within the STG is not well characterized. Here we use natural speech stimuli and advanced receptive field characterization methods to show that spectrotemporal features within speech are well organized along the posterior-to-anterior axis of the human STG. These findings demonstrate robust functional organization based on spectrotemporal modulation content, and illustrate that much of the encoded information in the STG represents the physical acoustic properties of speech stimuli.

Perceptual Training Restores Impaired Cortical Temporal Processing Due to Lead Exposure.

Low-level lead exposure is a risk factor for cognitive and learning disabilities in children and has been specifically associated with deficits in auditory temporal processing that impair aural language and reading abilities. Here, we show that rats exposed to low levels of lead in early life display a significant behavioral impairment in an auditory temporal rate discrimination task. Lead exposure also results in a degradation of the neuronal repetition-rate following capacity and response synchronization in primary auditory cortex. A modified go/no-go repetition-rate discrimination task applied in adult animals for ∼50 days nearly restores to normal these lead-induced deficits in cortical temporal fidelity. Cortical expressions of parvalbumin, brain-derived neurotrophic factor, and NMDA receptor subunits NR2a and NR2b, which are down-regulated in lead-exposed animals, are also partially reversed with training. These studies in an animal model identify the primary auditory cortex as a novel target for low-level lead exposure and demonstrate that perceptual training can ameliorate lead-induced deficits in cortical discrimination between sound sequences.