Auditory Research publications

Interaural level differences (ILDs) are the dominant cue for localizing the sources of high frequency sounds that differ in azimuth. Neurons in the primary auditory cortex (A1) respond differentially to ILDs of simple stimuli such as tones and noise bands, but the extent to which this applies to complex natural sounds, such as vocalizations, is not known. In sufentanil/N2O anesthetized marmosets, we compared the responses of 76 A1 neurons to three vocalizations (Ock, Tsik, and Twitter) and pure tones at cells' characteristic frequency. Each stimulus was presented with ILDs ranging from 20 dB favoring the contralateral ear to 20 dB favoring the ipsilateral ear to cover most of the frontal azimuthal space. The response to each stimulus was tested at three average binaural levels (ABLs). Most neurons were sensitive to ILDs of vocalizations and pure tones. For all stimuli, the majority of cells had monotonic ILD sensitivity functions favoring the contralateral ear, but we also observed ILD sensitivity functions that peaked near the midline and functions favoring the ipsilateral ear. Representation of ILD in A1 was better for pure tones and the Ock vocalization in comparison to the Tsik and Twitter calls; this was reflected by higher discrimination indices and greater modulation ranges. ILD sensitivity was heavily dependent on ABL: changes in ABL by ±20 dB SPL from the optimal level for ILD sensitivity led to significant decreases in ILD sensitivity for all stimuli, although ILD sensitivity to pure tones and Ock calls was most robust to such ABL changes. Our results demonstrate differences in ILD coding for pure tones and vocalizations, showing that ILD sensitivity in A1 to complex sounds cannot be simply extrapolated from that to pure tones. They also show A1 neurons do not show level-invariant representation of ILD, suggesting that such a representation of auditory space is likely to require population coding, and further processing at subsequent hierarchical stages.

The kinase Akt is a key downstream mediator of the phosphoinositide-3-kinase signaling pathway and participates in a variety of cellular processes. Akt comprises three isoforms each encoded by a separate gene. There is evidence to indicate that Akt is involved in the survival and protection of auditory hair cells in vitro. However, little is known about the physiological role of Akt in the inner ear-especially in the intact animal. To elucidate this issue, we first analyzed the mRNA expression of the three Akt isoforms in the inner ear of C57/BL6 mice by real-time PCR. Next, we tested the susceptibility to gentamicin-induced auditory hair cell loss in isoform-specific Akt knockout mice compared to wild-types (C57/BL6) in vitro. To analyze the effect of gene deletion in vivo, hearing and cochlear microanatomy were evaluated in Akt isoform knockout animals. In this study, we found that all three Akt isoforms are expressed in the cochlea. Our results further indicate that Akt2 and Akt3 enhance hair cell resistance to ototoxicity, while Akt1 does not. Finally, we determined that untreated Akt1 and Akt2/Akt3 double knockout mice display significant hearing loss, indicating a role for these isoforms in normal hearing. Taken together, our results indicate that each of the Akt isoforms plays a distinct role in the mammalian inner ear.

A significant challenge in tinnitus research lies in explaining how acoustic insult leads to tinnitus in some individuals, but not others. One possibility is genetic variability in the expression and function of neuromodulators - components of neural signaling that alter the balance of excitation and inhibition in neural circuits. An example is nitric oxide (NO) - a free radical and potent neuromodulator in the mammalian brain - that regulates plasticity via both pre-synaptic and postsynaptic mechanisms. Changes in NO have previously been implicated in tinnitus generation, specifically in the ventral cochlear nucleus (VCN). Here, we examined nitric oxide synthase (NOS) - the enzyme responsible for NO production - in the guinea pig VCN following acoustic trauma. NOS was present in most cell types - including spherical and globular bushy cells, small, medium, and large multipolar cells, and octopus cells - spanning the entire extent of the VCN. The staining pattern was symmetrical in control animals. Unilateral acoustic over-exposure (AOE) resulted in marked asymmetries between ipsilateral and contralateral sides of the VCN in terms of the distribution of NOS across the cochlear nuclei in animals with behavioral evidence of tinnitus: fewer NOS-positive cells and a reduced level of NOS staining was present across the whole extent of the contralateral VCN, relative to the ipsilateral VCN. The asymmetric pattern of NOS-containing cells was observed as early as 1 day after AOE and was also present in some animals at 3, 7, and 21 days after AOE. However, it was not until 8 weeks after AOE, when tinnitus had developed, that asymmetries were significant overall, compared with control animals. Asymmetrical NOS expression was not correlated with shifts in the threshold hearing levels. Variability in NOS expression between animals may represent one underlying difference that can be linked to whether or not tinnitus develops after noise exposure.

Fragile X Syndrome (FXS), a neurodevelopmental disorder, is the most prevalent single-gene cause of autism spectrum disorder. Autism has been associated with impaired auditory processing, abnormalities in the auditory brainstem response (ABR), and reduced cell number and size in the auditory brainstem nuclei. FXS is characterized by elevated cortical responses to sound stimuli, with some evidence for aberrant ABRs. Here, we assessed ABRs and auditory brainstem anatomy in Fmr1-/- mice, an animal model of FXS. We found that Fmr1-/- mice showed elevated response thresholds to both click and tone stimuli. Amplitudes of ABR responses were reduced in Fmr1-/- mice for early peaks of the ABR. The growth of the peak I response with sound intensity was less steep in mutants that in wild type mice. In contrast, amplitudes and response growth in peaks IV and V did not differ between these groups. We did not observe differences in peak latencies or in interpeak latencies. Cell size was reduced in Fmr1-/- mice in the ventral cochlear nucleus (VCN) and in the medial nucleus of the trapezoid body (MNTB). We quantified levels of inhibitory and excitatory synaptic inputs in these nuclei using markers for presynaptic proteins. We measured VGAT and VGLUT immunolabeling in VCN, MNTB, and the lateral superior olive (LSO). VGAT expression in MNTB was significantly greater in the Fmr1-/- mouse than in wild type mice. Together, these observations demonstrate that FXS affects peripheral and central aspects of hearing and alters the balance of excitation and inhibition in the auditory brainstem.

Autism Spectrum Disorders (ASD) are complex neurodevelopmental disorders characterized by repetitive behavior and impaired social communication and interactions. Apart from these core symptoms, a significant number of ASD individuals display higher levels of anxiety and some ASD individuals exhibit impaired emotional learning. We therefore sought to further examine anxiety and emotional learning in an environmentally induced animal model of ASD that utilizes the administration of the known teratogen, valproic acid (VPA) during gestation. Specifically we exposed dams to one of two different doses of VPA (500 and 600 mg/kg) or vehicle on day 12.5 of gestation and examined the resultant progeny. Our data indicate that animals exposed to VPA in utero exhibit enhanced anxiety in the open field test and normal object recognition memory compared to control animals. Animals exposed to 500 mg/kg of VPA displayed normal acquisition of auditory fear conditioning, and exhibited reduced extinction of fear memory and normal litter survival rates as compared to control animals. We observed that animals exposed to 600 mg/kg of VPA exhibited a significant reduction in the acquisition of fear conditioning, a significant reduction in social interaction and a significant reduction in litter survival rates as compared to control animals. VPA (600 mg/kg) exposed animals exhibited similar shock sensitivity and hearing as compared to control animals indicating the fear conditioning deficit observed in these animals was not likely due to sensory deficits, but rather due to deficits in learning or memory retrieval. In conclusion, considering that progeny from dams exposed to rather similar doses of VPA exhibit striking differences in emotional learning, the VPA model may serve as a useful tool to explore the molecular and cellular mechanisms that contribute to not only ASD, but also emotional learning.

The mechanism of loss of consciousness (LOC) under anesthesia is unknown. Because consciousness depends on activity in the cortico-thalamic network, anesthetic actions on this network are likely critical for LOC. Competing theories stress the importance of anesthetic actions on bottom-up "core" thalamo-cortical (TC) vs. top-down cortico-cortical (CC) and matrix TC connections. We tested these models using laminar recordings in rat auditory cortex in vivo and murine brain slices. We selectively activated bottom-up vs. top-down afferent pathways using sensory stimuli in vivo and electrical stimulation in brain slices, and compared effects of isoflurane on responses evoked via the two pathways. Auditory stimuli in vivo and core TC afferent stimulation in brain slices evoked short latency current sinks in middle layers, consistent with activation of core TC afferents. By contrast, visual stimuli in vivo and stimulation of CC and matrix TC afferents in brain slices evoked responses mainly in superficial and deep layers, consistent with projection patterns of top-down afferents that carry visual information to auditory cortex. Responses to auditory stimuli in vivo and core TC afferents in brain slices were significantly less affected by isoflurane compared to responses triggered by visual stimuli in vivo and CC/matrix TC afferents in slices. At a just-hypnotic dose in vivo, auditory responses were enhanced by isoflurane, whereas visual responses were dramatically reduced. At a comparable concentration in slices, isoflurane suppressed both core TC and CC/matrix TC responses, but the effect on the latter responses was far greater than on core TC responses, indicating that at least part of the differential effects observed in vivo were due to local actions of isoflurane in auditory cortex. These data support a model in which disruption of top-down connectivity contributes to anesthesia-induced LOC, and have implications for understanding the neural basis of consciousness.

Echolocating bats use the delay between their sonar emissions and the reflected echoes to measure target range, a crucial parameter for avoiding collisions or capturing prey. In many bat species, target range is represented as an orderly organized map of echo delay in the auditory cortex. Here we show that the map of target range in bats is dynamically modified by the continuously changing flow of acoustic information perceived during flight ('echo-acoustic flow'). Combining dynamic acoustic stimulation in virtual space with extracellular recordings, we found that neurons in the auditory cortex of the bat Phyllostomus discolor encode echo-acoustic flow information on the geometric relation between targets and the bat's flight trajectory, rather than echo delay per se. Specifically, the cortical representation of close-range targets is enlarged when the lateral passing distance of the target decreases. This flow-dependent enlargement of target representation may trigger adaptive behaviours such as vocal control or flight manoeuvres.

Children with autism often have language impairments and degraded cortical responses to speech. Extensive behavioral interventions can improve language outcomes and cortical responses. Prenatal exposure to the antiepileptic drug valproic acid (VPA) increases the risk for autism and language impairment. Prenatal exposure to VPA also causes weaker and delayed auditory cortex responses in rats. In this study, we document speech sound discrimination ability in VPA exposed rats and document the effect of extensive speech training on auditory cortex responses. VPA exposed rats were significantly impaired at consonant, but not vowel, discrimination. Extensive speech training resulted in both stronger and faster anterior auditory field (AAF) responses compared to untrained VPA exposed rats, and restored responses to control levels. This neural response improvement generalized to non-trained sounds. The rodent VPA model of autism may be used to improve the understanding of speech processing in autism and contribute to improving language outcomes.

The primary auditory cortex (AI) modulates the sound information processing in the lemniscal subcortical nuclei, including the anteroventral cochlear nucleus (AVCN), in a frequency-specific manner. The dorsal cochlear nucleus (DCN) is a non-lemniscal subcortical nucleus but it is tonotopically organized like the AVCN. However, it remains unclear how the AI modulates the sound information processing in the DCN. This study examined the impact of focal electrical stimulation of AI on the auditory responses of the DCN neurons in mice. We found that the electrical stimulation induced significant changes in the best frequency (BF) of DCN neurons. The changes in the BFs were highly specific to the BF differences between the stimulated AI neurons and the recorded DCN neurons. The DCN BFs shifted higher when the AI BFs were higher than the DCN BFs and the DCN BFs shifted lower when the AI BFs were lower than the DCN BFs. The DCN BFs showed no change when the AI and DCN BFs were similar. Moreover, the BF shifts were linearly correlated to the BF differences. Thus, our data suggest that corticofugal modulation of the DCN is also highly specific to frequency information, similar to the corticofugal modulation of the AVCN. The frequency-specificity of corticofugal modulation does not appear limited to the lemniscal ascending pathway.

Animal models of tinnitus allow us to study the relationship between changes in neural activity and the tinnitus percept. Here, guinea pigs were subjected to unilateral noise trauma and tested behaviourally for tinnitus 8 weeks later. By comparing animals with tinnitus with those without, all of which were noise‐exposed, we were able to identify changes unique to the tinnitus group. Three physiological markers known to change following noise exposure were examined: spontaneous firing rates ( SFR s) and burst firing in the inferior colliculus ( IC ), evoked auditory brainstem responses ( ABR s), and the number of neurons in the cochlear nucleus containing nitric oxide synthase ( NOS ). We obtained behavioural evidence of tinnitus in 12 of 16 (75%) animals. Both SFR s and incidences of burst firing were elevated in the IC of all noise‐exposed animals, but there were no differences between tinnitus and no‐tinnitus animals. There were significant decreases in ipsilateral ABR latencies in tinnitus animals, contrary to what might be expected with a small hearing loss. Furthermore, there was an ipsilateral–contralateral asymmetry in NOS staining in the ventral cochlear nucleus ( VCN ) that was only apparent in tinnitus animals. Tinnitus animals had a significantly greater number of NOS ‐containing neurons on the noise‐exposed side, whereas no‐tinnitus animals did not. These data suggest that measuring NOS in the VCN and recording ABR s supplement behavioural methods for confirming tinnitus in animals, and that nitric oxide is involved in plastic neural changes associated with tinnitus.

The neural substrate for the perception of vocalizations is relatively well described, but how their timing and specificity are tightly coupled with accompanying physiological changes and context-appropriate behaviors remains unresolved. We hypothesized that temporally integrated vocal and emotive responses, especially the expression of fear, vigilance and aggression, originate within the amygdala. To test this hypothesis, we performed electrical microstimulation at 461 highly restricted loci within the basal and central amygdala in awake mustached bats. At a subset of these sites, high frequency stimulation with weak constant current pulses presented at near-threshold levels triggered vocalization of either echolocation pulses or social calls. At the vast majority of locations, microstimulation produced a constellation of changes in autonomic and somatomotor outputs. These changes included widespread co-activation of significant tachycardia and hyperventilation and/or rhythmic ear pinna movements (PMs). In a few locations, responses were constrained to vocalization and/or PMs despite increases in the intensity of stimulation. The probability of eliciting echolocation pulses vs. social calls decreased in a medial-posterior to anterolateral direction within the centrobasal amygdala. Microinjections of kainic acid (KA) at stimulation sites confirmed the contribution of cellular activity rather than fibers-of-passage in the control of multimodal outputs. The results suggest that localized clusters of neurons may simultaneously modulate the activity of multiple central pattern generators (CPGs) present within the brainstem.

Previous studies have shown that sodium salicylate (SS) activates not only central auditory structures, but also nonauditory regions associated with emotion and memory. To identify electrophysiological changes in the nonauditory regions, we recorded sound-evoked local field potentials and multiunit discharges from the striatum, amygdala, hippocampus, and cingulate cortex after SS-treatment. The SS-treatment produced behavioral evidence of tinnitus and hyperacusis. Physiologically, the treatment significantly enhanced sound-evoked neural activity in the striatum, amygdala, and hippocampus, but not in the cingulate. The enhanced sound evoked response could be linked to the hyperacusis-like behavior. Further analysis showed that the enhancement of sound-evoked activity occurred predominantly at the midfrequencies, likely reflecting shifts of neurons towards the midfrequency range after SS-treatment as observed in our previous studies in the auditory cortex and amygdala. The increased number of midfrequency neurons would lead to a relative higher number of total spontaneous discharges in the midfrequency region, even though the mean discharge rate of each neuron may not increase. The tonotopical overactivity in the midfrequency region in quiet may potentially lead to tonal sensation of midfrequency (the tinnitus). The neural changes in the amygdala and hippocampus may also contribute to the negative effect that patients associate with their tinnitus.

Mitogen-activated protein kinases (MAP kinases) are intracellular signaling kinases activated by phosphorylation in response to a variety of extracellular stimuli. Mammalian MAP kinase pathways are composed of three major pathways: MEK1 (mitogen-activated protein kinase kinase 1)/ERK 1/2 (extracellular signal-regulated kinases 1/2)/p90 RSK (p90 ribosomal S6 kinase), JNK (c-Jun amino (N)-terminal kinase)/c-Jun, and p38 MAPK pathways. These pathways coordinately mediate physiological processes such as cell survival, protein synthesis, cell proliferation, growth, migration, and apoptosis. The involvement of MAP kinase in noise-induced hearing loss (NIHL) has been implicated in the cochlea; however, it is unknown how expression levels of MAP kinase change after the onset of NIHL and whether they are regulated by transient phosphorylation or protein synthesis. CBA/J mice were exposed to 120-dB octave band noise for 2 h. Auditory brainstem response confirmed a component of temporary threshold shift within 0-24 h and significant permanent threshold shift at 14 days after noise exposure. Levels and localizations of phospho- and total- MEK1/ERK1/2/p90 RSK, JNK/c-Jun, and p38 MAPK were comprehensively analyzed by the Bio-Plex® Suspension Array System and immunohistochemistry at 0, 3, 6, 12, 24 and 48 h after noise exposure. The phospho-MEK1/ERK1/2/p90 RSK signaling pathway was activated in the spiral ligament and the sensory and supporting cells of the organ of Corti, with peaks at 3-6 h and independently of regulations of total-MEK1/ERK1/2/p90 RSK. The expression of phospho-JNK and p38 MAPK showed late upregulation in spiral neurons at 48 h, in addition to early upregulations with peaks at 3 h after noise trauma. Phospho-p38 MAPK activation was dependent on upregulation of total-p38 MAPK. At present, comprehensive data on MAP kinase expression provide significant insight into understanding the molecular mechanism of NIHL, and for developing therapeutic models for acute sensorineural hearing loss.

To improve the performance of cochlear implants, we have integrated a microdevice into a model of the auditory periphery with the goal of creating a microprocessor. We constructed an artificial peripheral auditory system using a hybrid model in which polyvinylidene difluoride was used as a piezoelectric sensor to convert mechanical stimuli into electric signals. To produce frequency selectivity, the slit on a stainless steel base plate was designed such that the local resonance frequency of the membrane over the slit reflected the transfer function. In the acoustic sensor, electric signals were generated based on the piezoelectric effect from local stress in the membrane. The electrodes on the resonating plate produced relatively large electric output signals. The signals were fed into a computer model that mimicked some functions of inner hair cells, inner hair cell-auditory nerve synapses, and auditory nerve fibers. In general, the responses of the model to pure-tone burst and complex stimuli accurately represented the discharge rates of high-spontaneous-rate auditory nerve fibers across a range of frequencies greater than 1 kHz and middle to high sound pressure levels. Thus, the model provides a tool to understand information processing in the peripheral auditory system and a basic design for connecting artificial acoustic sensors to the peripheral auditory nervous system. Finally, we discuss the need for stimulus control with an appropriate model of the auditory periphery based on auditory brainstem responses that were electrically evoked by different temporal pulse patterns with the same pulse number.

It was recently shown that rhythmic entrainment, long considered a human-specific mechanism, can be demonstrated in a selected group of bird species, and, somewhat surprisingly, not in more closely related species such as nonhuman primates. This observation supports the vocal learning hypothesis that suggests rhythmic entrainment to be a by-product of the vocal learning mechanisms that are shared by several bird and mammal species, including humans, but that are only weakly developed, or missing entirely, in nonhuman primates. To test this hypothesis we measured auditory event-related potentials (ERPs) in two rhesus monkeys (Macaca mulatta), probing a well-documented component in humans, the mismatch negativity (MMN) to study rhythmic expectation. We demonstrate for the first time in rhesus monkeys that, in response to infrequent deviants in pitch that were presented in a continuous sound stream using an oddball paradigm, a comparable ERP component can be detected with negative deflections in early latencies (Experiment 1). Subsequently we tested whether rhesus monkeys can detect gaps (omissions at random positions in the sound stream; Experiment 2) and, using more complex stimuli, also the beat (omissions at the first position of a musical unit, i.e. the 'downbeat'; Experiment 3). In contrast to what has been shown in human adults and newborns (using identical stimuli and experimental paradigm), the results suggest that rhesus monkeys are not able to detect the beat in music. These findings are in support of the hypothesis that beat induction (the cognitive mechanism that supports the perception of a regular pulse from a varying rhythm) is species-specific and absent in nonhuman primates. In addition, the findings support the auditory timing dissociation hypothesis, with rhesus monkeys being sensitive to rhythmic grouping (detecting the start of a rhythmic group), but not to the induced beat (detecting a regularity from a varying rhythm).

Recent studies in humans and monkeys have reported that acoustic stimulation influences visual responses in the primary visual cortex (V1). Such influences can be generated in V1, either by direct auditory projections or by feedback projections from extrastriate cortices. To test these hypotheses, cortical activities were recorded using optical imaging at a high spatiotemporal resolution from multiple areas of the guinea pig visual cortex, to visual and/or acoustic stimulations. Visuo-auditory interactions were evaluated according to differences between responses evoked by combined auditory and visual stimulation, and the sum of responses evoked by separate visual and auditory stimulations. Simultaneous presentation of visual and acoustic stimulations resulted in significant interactions in V1, which occurred earlier than in other visual areas. When acoustic stimulation preceded visual stimulation, significant visuo-auditory interactions were detected only in V1. These results suggest that V1 is a cortical origin of visuo-auditory interaction.

Auditory cortical plasticity can be induced through various approaches. The medial geniculate body (MGB) of the auditory thalamus gates the ascending auditory inputs to the cortex. The thalamocortical system has been proposed to play a critical role in the responses of the auditory cortex (AC). In the present study, we investigated the cellular mechanism of the cortical activity, adopting an in vivo intracellular recording technique, recording from the primary auditory cortex (AI) while presenting an acoustic stimulus to the rat and electrically stimulating its MGB. We found that low-frequency stimuli enhanced the amplitudes of sound-evoked excitatory postsynaptic potentials (EPSPs) in AI neurons, whereas high-frequency stimuli depressed these auditory responses. The degree of this modulation depended on the intensities of the train stimuli as well as the intervals between the electrical stimulations and their paired sound stimulations. These findings may have implications regarding the basic mechanisms of MGB activation of auditory cortical plasticity and cortical signal processing.

Animal models of ototoxicity represent an elementary tool in otolaryngologic research. Such models are usually created via the consecutive injection of ototoxic drugs or the co-administration of ethacrynic acid and low-dose ototoxic drugs. Injection via the round window membrane (RWM) is one approach that allows for local drug delivery into the inner ear. In this study, 47 guinea pigs received an injection of varying doses of cisplatin via the RWM, and data concerning the animals' auditory brainstem responses, hair cells, and spiral ganglion neurons were analyzed. Our results indicate the high efficiency and generally small reaction of the subjects, suggesting that the application of cisplatin via the RWM is an effective animal model for ototoxicity research.

Acoustic communication has an important role in the reproductive behaviour of anurans. Although males of the concave-eared frog (Odorrana tormota) have shown an ultrasonic communication capacity adapted to the intense, predominately low-frequency ambient noise from local streams, whether the females communicate with ultrasound remains unclear. Here we present evidence that females exhibit no ultrasonic sensitivity. Acoustic playback experiments show that the calls from male evoke phonotaxis and vocal responses from gravid females, whereas the ultrasonic components (frequencies above 20 kHz) of the calls do not elicit any phonotaxis or vocalization in the females. Electrophysiological recordings from the auditory midbrain reveal an upper frequency limit at 16 kHz in females. Laser Doppler vibrometer measurements show that the velocity amplitude of the tympanic membranes peaks at 5 kHz in females and at ∼7 kHz in males. The auditory sex differences in O. tormota imply that ultrasonic hearing has evolved only in male anurans.

Multi-electrode array recordings of spike and local field potential (LFP) activity were made from primary auditory cortex of 12 normal hearing, ketamine-anesthetized cats. We evaluated 259 spectro-temporal receptive fields (STRFs) and 492 frequency-tuning curves (FTCs) based on LFPs and spikes simultaneously recorded on the same electrode. We compared their characteristic frequency (CF) gradients and their cross-correlation distances. The CF gradient for spike-based FTCs was about twice that for 2-40 Hz-filtered LFP-based FTCs, indicating greatly reduced frequency selectivity for LFPs. We also present comparisons for LFPs band-pass filtered between 4-8 Hz, 8-16 Hz and 16-40 Hz, with spike-based STRFs, on the basis of their marginal frequency distributions. We find on average a significantly larger correlation between the spike based marginal frequency distributions and those based on the 16-40 Hz filtered LFP, compared to those based on the 4-8 Hz, 8-16 Hz and 2-40 Hz filtered LFP. This suggests greater frequency specificity for the 16-40 Hz LFPs compared to those of lower frequency content. For spontaneous LFP and spike activity we evaluated 1373 pair correlations for pairs with >200 spikes in 900 s per electrode. Peak correlation-coefficient space constants were similar for the 2-40 Hz filtered LFP (5.5 mm) and the 16-40 Hz LFP (7.4 mm), whereas for spike-pair correlations it was about half that, at 3.2 mm. Comparing spike-pairs with 2-40 Hz (and 16-40 Hz) LFP-pair correlations showed that about 16% (9%) of the variance in the spike-pair correlations could be explained from LFP-pair correlations recorded on the same electrodes within the same electrode array. This larger correlation distance combined with the reduced CF gradient and much broader frequency selectivity suggests that LFPs are not a substitute for spike activity in primary auditory cortex.