Auditory Research publications

Introduction: Competing noise in the environment negatively affects speech intelligibility, particularly when listening at a distance. This is especially true for children with hearing loss in classroom environments where the signal-to-noise ratio is often poor. Remote microphone technology has been shown to be highly beneficial at improving the signal-to-noise ratio in hearing device users. Children with bone conduction devices, however, often must rely on indirect transmission of the acoustic signal for commonly used classroom-based remote microphone listening (e.g., digital adaptive microphone) which may negatively affect speech intelligibility. There are no studies on the effectiveness of using a relay method of signal delivery using remote microphone technology to improve speech intelligibility in adverse listening environments in bone conduction device users. Methods: Nine children with irresolvable conductive hearing loss and 12 adult controls with normal hearing were included for study. Controls were bilaterally plugged to simulate conductive hearing loss. All testing was conducted using the Cochlear™ Baha® 5 standard processor coupled with either the Cochlear™ Mini Microphone 2+ digital remote microphone or the Phonak Roger™ adaptive digital remote microphone. Speech intelligibility in noise was evaluated in the (1) bone conduction device processor alone, (2) bone conduction device + personal remote microphone, and (3) bone conduction device + personal remote microphone + adaptive digital remote microphone listening conditions at −10 dB, 0 dB, and +5 dB signal-to-noise ratios. Results and Conclusions: Speech intelligibility in noise improved significantly in the bone conduction device + personal remote microphone condition over the bone conduction device alone, demonstrating significant benefit for listening at poor signal-to-noise ratios in children with conductive hearing loss using bone conduction devices with personal remote microphone use. Experimental findings demonstrate poor signal transparency when using the relay method. Coupling of the adaptive digital remote microphone technology to the personal remote microphone negatively affects signal transparency, and no hearing in noise improvements are observed. Significant gains in speech intelligibility are consistently observed for direct streaming methods and are confirmed in adult controls. Behavioral findings are supported by objective verification of the signal transparency between the remote microphone and the bone conduction device.

Objectives: Investigating the effect of metformin on peripheral nerve regeneration and the molecular mechanism. Methods: In this study, a rat model of sciatic nerve injury and an inflammatory bone marrow-derived macrophage (BMDM) cell model were established. We assessed the sensory and motor function of the hind limbs four weeks after sciatic nerve injury, immunofluorescence was used to detect axonal regeneration and myelin formation, as well as local macrophage subtypes. We investigated the polarizing effect of metformin on inflammatory macrophages, and western blotting was applied to detect the molecular mechanisms behind it. Results: Metformin treatment accelerated functional recovery, axon regeneration and remyelination, and promoted M2 macrophage polarization. In vivo, metformin transformed pro-inflammatory macrophages into pro-regeneration M2 macrophages. Protein expression levels of phosphorylated AMP-activated protein kinase (p-AMPK), proliferator-activated receptor-γ co-activator 1α (PGC-1α), and peroxisome proliferator-activated receptor-γ (PPAR-γ) increased upon metformin treatment. Moreover, inhibition of AMPK abolished the effects of metformin treatment on M2 polarization. Conclusion: Metformin promoted M2 macrophage polarization by activating the AMPK/PGC-1α/PPAR-γ signaling axis, thereby promoting peripheral nerve regeneration.

Considerable work suggests the dominant syllable rhythm of the acoustic envelope is remarkably similar across languages (∼4–5 Hz) and that oscillatory brain activity tracks these quasiperiodic rhythms to facilitate speech processing. However, whether this fundamental periodicity represents a common organizing principle in both auditory and motor systems involved in speech has not been explicitly tested. To evaluate relations between entrainment in the perceptual and production domains, we measured individuals’ (i) neuroacoustic tracking of the EEG to speech trains and their (ii) simultaneous and non-simultaneous productions synchronized to syllable rates between 2.5 and 8.5 Hz. Productions made without concurrent auditory presentation isolated motor speech functions more purely. We show that neural synchronization flexibly adapts to the heard stimuli in a rate-dependent manner, but that phase locking is boosted near ∼4.5 Hz, the purported dominant rate of speech. Cued speech productions (recruit sensorimotor interaction) were optimal between 2.5 and 4.5 Hz, suggesting a low-frequency constraint on motor output and/or sensorimotor integration. In contrast, “pure” motor productions (without concurrent sound cues) were most precisely generated at rates of 4.5 and 5.5 Hz, paralleling the neuroacoustic data. Correlations further revealed strong links between receptive (EEG) and production synchronization abilities; individuals with stronger auditory-perceptual entrainment better matched speech rhythms motorically. Together, our findings support an intimate link between exogenous and endogenous rhythmic processing that is optimized at 4–5 Hz in both auditory and motor systems. Parallels across modalities could result from dynamics of the speech motor system coupled with experience-dependent tuning of the perceptual system via the sensorimotor interface.

The environment noise may disturb animal behavior and echolocation via three potential mechanisms: acoustic masking, reduced attention and noise avoidance. Compared with the mechanisms of reduced attention and noise avoidance, acoustic masking is thought to occur only when the signal and background noise overlap spectrally and temporally. In this study, we investigated the effects of spectrally non-overlapping noise on echolocation pulses and electrophysiological responses of a constant frequency–frequency modulation (CF-FM) bat, Hipposideros pratti. We found that H. pratti called at higher intensities while keeping the CFs of their echolocation pulses consistent. Electrophysiological tests indicated that the noise could decrease auditory sensitivity and sharp intensity tuning, suggesting that spectrally non-overlapping noise imparts an acoustic masking effect. Because anthropogenic noises are usually concentrated at low frequencies and are spectrally non-overlapping with the bat’s echolocation pulses, our results provide further evidence of negative consequences of anthropogenic noise. On this basis, we sound a warning against noise in the foraging habitats of echolocating bats.

We examined the effect of neonatal deafening on frequency-specific pathways for processing of interaural time differences (ITDs) in cochlear-implant stimuli. Animal studies have demonstrated differences in neural ITD sensitivity in the inferior colliculus (IC) depending on the intracochlear location of intracochlear stimulating electrodes. We used neonatally deafened (ND) rats of both sexes and recorded the responses of single neurons in the IC to electrical stimuli with ITDs delivered to the apical or basal cochlea and compared them with acutely deafened (AD) rats of both sexes with normal hearing (NH) during development. We found that neonatal deafness significantly impacted the ITD sensitivity and the ITD tuning patterns restricted to apically driven IC neurons. In ND rats, the ITD sensitivity of apically driven neurons is reduced to values similar to basally driven neurons. The prevalence of ITD-sensitive apical neurons with a peak-shaped ITD tuning curve, which may reflect predominant input from the medial superior olivary (MSO) complex, in ND rats was diminished compared with that in AD rats (67%, AD vs 40%, ND). Conversely, monotonic-type responses rarely occurred in AD rats (14%) but were approximately equally as prevalent as peak-type tuning curves in ND rats (42%). Nevertheless, in ND rats, the ITD at the maximum slope of the ITD tuning curve was still more concentrated within the physiological ITD range in apically driven than in basally driven neurons. These results indicate that the development of high ITD sensitivity processed by low-frequency pathways depends on normal auditory experience and associated biases in ITD tuning strategies.

Many cochlear implant users with binaural residual (acoustic) hearing benefit from combining electric and acoustic stimulation (EAS) in the implanted ear with acoustic amplification in the other. These bimodal EAS listeners can potentially use low-frequency binaural cues to localize sounds. However, their hearing is generally asymmetric for mid- and high-frequency sounds, perturbing or even abolishing binaural cues. Here, we investigated the effect of a frequency-dependent binaural asymmetry in hearing thresholds on sound localization by seven bimodal EAS listeners. Frequency dependence was probed by presenting sounds with power in low-, mid-, high-, or mid-to-high-frequency bands. Frequency-dependent hearing asymmetry was present in the bimodal EAS listening condition (when using both devices) but was also induced by independently switching devices on or off. Using both devices, hearing was near symmetric for low frequencies, asymmetric for mid frequencies with better hearing thresholds in the implanted ear, and monaural for high frequencies with no hearing in the non-implanted ear. Results show that sound-localization performance was poor in general. Typically, localization was strongly biased toward the better hearing ear. We observed that hearing asymmetry was a good predictor for these biases. Notably, even when hearing was symmetric a preferential bias toward the ear using the hearing aid was revealed. We discuss how frequency dependence of any hearing asymmetry may lead to binaural cues that are spatially inconsistent as the spectrum of a sound changes. We speculate that this inconsistency may prevent accurate sound-localization even after long-term exposure to the hearing asymmetry.

Cisplatin is a widely used and efficacious chemotherapeutic agent for treating solid tumors, yet it causes systemic end-organ damage that is often irreversible and detrimental to quality of life. This includes severe sensorineural hearing loss, hepatotoxicity, and renal injury. Based on the hard-soft acid-base theory, we recently developed two acetophenone-derived, enol-based compounds that directly interfere with the side effects of cisplatin. We investigated organ-specific and generalized toxicity in order to define dose-dependent responses in rodents injected with cisplatin with or without the protective compounds. All metrics that were used as indicators of toxicity showed retention of baseline or control measurements when animals were pre-treated with acetophenones prior to cisplatin administration, while animals injected with no protective compounds showed expected elevations in toxicity measurements or depressions in measurements of organ function. These data support the further investigation of novel acetophenone compounds for the prevention of cisplatin-induced end-organ toxicity.

Human cognitive abilities naturally vary along a spectrum, even among those we call "neurotypical". Individuals differ in their ability to selectively attend to goal-relevant auditory stimuli. We sought to characterize this variability in a cohort of people with diverse attentional functioning. We recruited both neurotypical (N = 20) and ADHD (N = 25) young adults, all with normal hearing. Participants listened to one of three concurrent, spatially separated speech streams and reported the order of the syllables in that stream while we recorded electroencephalography (EEG). We tested both the ability to sustain attentional focus on a single "Target" stream and the ability to monitor the Target but flexibly either ignore or switch attention to an unpredictable "Interrupter" stream from another direction that sometimes appeared. Although differences in both stimulus structure and task demands affected behavioral performance, ADHD status did not. In both groups, the Interrupter evoked larger neural responses when it was to be attended compared to when it was irrelevant, including for the P3a "reorienting" response previously described as involuntary. This attentional modulation was weaker in ADHD listeners, even though their behavioral performance was the same. Across the entire cohort, individual performance correlated with the degree of top-down modulation of neural responses. These results demonstrate that listeners differ in their ability to modulate neural representations of sound based on task goals, while suggesting that adults with ADHD may have weaker volitional control of attentional processes than their neurotypical counterparts.

RESUMO Objetivo analisar o efeito do mascaramento estável e modulado no Potencial Evocado Auditivo Cortical com estímulo de fala em adultos-jovens. Método participaram 14 indivíduos com idades entre 19 e 28 anos de ambos os sexos e sem perda auditiva. O exame de Potencial Evocado Auditivo Cortical foi realizado com estímulo de fala sintética /ba/ simultâneo ao ruído Speech Shaped Noise apresentado em três condições: ruído estável com intensidade de 30 dB NPSpe (ruído estável fraco), ruído estável com intensidade de 65 dB NPSpe (ruído estável forte) e ruído modulado em intensidade de 30 dB NPSpe e 65 dB NPSpe em 25Hz e com período de modulação de 40 ms. Resultados foram observadas maiores latências nos componentes corticais, exceto P2, na condição de ruído estável forte e medidas mais robustas de amplitude dos componentes corticais P1, N1 e P2 na condição de ruído modulado com diferença estatística significativa na comparação com a condição de ruído estável forte. Houve pior morfologia na condição de ruído estável forte, quando comparado aos demais registros. Os limiares eletrofisiológicos médios para as condições de ruído estável forte e ruído modulado foram 60 dB NPSpe e 49 dB NPSpe, respectivamente, mostrando 11,7 dB de diferença média. Conclusão podemos inferir que houve um menor efeito mascarante do ruído modulado, comparado à condição de ruído estável forte, nas medidas de amplitude dos componentes corticais e uma diferença média de 11,7 dB entre os limiares eletrofisiológicos (interpretado como a medida do Benefício do Mascaramento Modulado).

The cochlea’s ability to discriminate sound frequencies is facilitated by a special topography along its longitudinal axis known as tonotopy. Auditory hair cells located at the base of the cochlea respond to high-frequency sounds, whereas hair cells at the apex respond to lower frequencies. Gradual changes in morphological and physiological features along the length of the cochlea determine each region’s frequency selectivity, but it remains unclear how tonotopy is established during cochlear development. Recently, sonic hedgehog (SHH) was proposed to initiate the establishment of tonotopy by conferring regional identity to the primordial cochlea. Here, using mouse genetics, we provide in vivo evidence that regional identity in the embryonic cochlea acts as a framework upon which tonotopy-specific properties essential for frequency selectivity in the mature cochlea develop. We found that follistatin (FST) is required for the maintenance of apical cochlear identity, but dispensable for its initial induction. In a fate-mapping analysis, we found that FST promotes expansion of apical cochlear cells, contributing to the formation of the apical cochlear domain. SHH, in contrast, is required both for the induction and maintenance of apical identity. In the absence of FST or SHH, mice produce a short cochlea lacking its apical domain. This results in the loss of apex-specific anatomical and molecular properties and low-frequency-specific hearing loss.

Hearing loss is the most common sensory deficit, of which genetic etiologies are a frequent cause. Dominant and recessive mutations in TMC1 , a gene encoding the pore-forming subunit of the hair cell mechanotransduction channel, cause DFNA36 and DFNB7/11, respectively, accounting for ∼2% of genetic hearing loss. Previous work has established the efficacy of mutation-targeted RNAi in treatment of murine models of autosomal dominant non-syndromic deafness. However, application of such approaches is limited by the infeasibility of development and validation of novel constructs for each variant. We developed an allele-non-specific approach consisting of mutation-agnostic RNAi suppression of both mutant and WT alleles, co-delivered with a knockdown-resistant engineered WT allele with or without the use of woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) to augment transgene expression. This therapeutic construct was delivered into the mature murine model of DFNA36 with an AAV vector and achieved robust hair cell and auditory brainstem response preservation. However, WPRE-enhanced Tmc1 expression resulted in inferior outcomes, suggesting a role for gene dosage optimization in future TMC1 gene therapy development.

Hearing loss is a major health problem and psychological burden in humans. Mouse models offer a possibility to elucidate genes involved in the underlying developmental and pathophysiological mechanisms of hearing impairment. To this end, large-scale mouse phenotyping programs include auditory phenotyping of single-gene knockout mouse lines. Using the auditory brainstem response (ABR) procedure, the German Mouse Clinic and similar facilities worldwide have produced large, uniform data sets of averaged ABR raw data of mutant and wildtype mice. In the course of standard ABR analysis, hearing thresholds are assessed visually by trained staff from series of signal curves of increasing sound pressure level. This is time-consuming and prone to be biased by the reader as well as the graphical display quality and scale.In an attempt to reduce workload and improve quality and reproducibility, we developed and compared two methods for automated hearing threshold identification from averaged ABR raw data: a supervised approach involving two combined neural networks trained on human-generated labels and a self-supervised approach, which exploits the signal power spectrum and combines random forest sound level estimation with a piece-wise curve fitting algorithm for threshold finding.We show that both models work well and are suitable for fast, reliable, and unbiased hearing threshold detection and quality control. In a high-throughput mouse phenotyping environment, both methods perform well as part of an automated end-to-end screening pipeline to detect candidate genes for hearing involvement. Code for both models as well as data used for this work are freely available.

Inner ear gene therapy using adeno-associated viral vectors (AAVs) in neonatal mice can alleviate hearing loss in mouse models of deafness. However, efficient and safe transgene delivery to the adult mouse cochlea is critical for the effectiveness of AAV-mediated therapy. Here, we examined three gene delivery approaches including posterior semicircular canal (PSCC) canalostomy, round window membrane (RWM) injection, and tubing-RWM+PSCC (t-RP) in adult mice. Transduction rates and survival rates of cochlear hair cells were analyzed, hearing function was recorded, AAV distribution in the sagittal brain sections was evaluated, and cochlear histopathologic images were appraised. We found that an injection volume of 1 μL AAV through the PSCC is safe and highly efficient and does not impair hearing function in adult mice, but local injection allows AAV vectors to spread slightly into the brain. We then tested five AAV serotypes (PHP.eB, IE, Anc80L65, AAV2, and PHP.s) in parallel and observed the most robust eGFP expression in inner hair cells, outer hair cells, and spiral ganglion neurons throughout the cochlea after AAV-Anc80L65 injection. Thus, PSCC-injected Anc80L65 provides a foundation for gene therapy in the adult cochlea and will facilitate the development of inner ear gene therapy.

Evoked neural responses to sensory stimuli have been extensively investigated in humans and animal models both to enhance our understanding of brain function and to aid in clinical diagnosis of neurological and neuropsychiatric conditions. Recording and imaging techniques such as electroencephalography (EEG), magnetoencephalography (MEG), local field potentials (LFPs), and calcium imaging provide complementary information about different aspects of brain activity at different spatial and temporal scales. Modeling and simulations provide a way to integrate these different types of information to clarify underlying neural mechanisms. In this study, we aimed to shed light on the neural dynamics underlying auditory evoked responses by fitting a rate-based model to LFPs recorded via multi-contact electrodes which simultaneously sampled neural activity across cortical laminae. Recordings included neural population responses to best-frequency (BF) and non-BF tones at four representative sites in primary auditory cortex (A1) of awake monkeys. The model considered major neural populations of excitatory, parvalbumin-expressing (PV), and somatostatin-expressing (SOM) neurons across layers 2/3, 4, and 5/6. Unknown parameters, including the connection strength between the populations, were fitted to the data. Our results revealed similar population dynamics, fitted model parameters, predicted equivalent current dipoles (ECD), tuning curves, and lateral inhibition profiles across recording sites and animals, in spite of quite different extracellular current distributions. We found that PV firing rates were higher in BF than in non-BF responses, mainly due to different strengths of tonotopic thalamic input, whereas SOM firing rates were higher in non-BF than in BF responses due to lateral inhibition. In conclusion, we demonstrate the feasibility of the model-fitting approach in identifying the contributions of cell-type specific population activity to stimulus-evoked LFPs across cortical laminae, providing a foundation for further investigations into the dynamics of neural circuits underlying cortical sensory processing.

Cochlear implants (CIs) are neuroprosthetic devices that can provide hearing to deaf people1. Despite the benefits offered by CIs, the time taken for hearing to be restored and perceptual accuracy after long-term CI use remain highly variable2,3. CI use is believed to require neuroplasticity in the central auditory system, and differential engagement of neuroplastic mechanisms might contribute to the variability in outcomes4-7. Despite extensive studies on how CIs activate the auditory system4,8-12, the understanding of CI-related neuroplasticity remains limited. One potent factor enabling plasticity is the neuromodulator noradrenaline from the brainstem locus coeruleus (LC). Here we examine behavioural responses and neural activity in LC and auditory cortex of deafened rats fitted with multi-channel CIs. The rats were trained on a reward-based auditory task, and showed considerable individual differences of learning rates and maximum performance. LC photometry predicted when CI subjects began responding to sounds and longer-term perceptual accuracy. Optogenetic LC stimulation produced faster learning and higher long-term accuracy. Auditory cortical responses to CI stimulation reflected behavioural performance, with enhanced responses to rewarded stimuli and decreased distinction between unrewarded stimuli. Adequate engagement of central neuromodulatory systems is thus a potential clinically relevant target for optimizing neuroprosthetic device use.

The medial nucleus of the trapezoid body (MNTB) is an integral component of the auditory brainstem circuitry involved in sound localization. The giant presynaptic nerve terminal with multiple active zones, the calyx of Held (CH), is a hallmark of this nucleus, which mediates fast and synchronized glutamatergic synaptic transmission. To delineate how these synaptic structures adapt to reduced auditory afferents due to aging, we acquired and reconstructed circuitry-level volumes of mouse MNTB at different ages (3 weeks, 6, 18, and 24 months) using serial block-face electron microscopy. We used C57BL/6J, the most widely inbred mouse strain used for transgenic lines, which displays a type of age-related hearing loss. We found that MNTB neurons reduce in density with age. Surprisingly we observed an average of approximately 10% of poly-innervated MNTB neurons along the mouse lifespan, with prevalence in the low frequency region. Moreover, a tonotopy-dependent heterogeneity in CH morphology was observed in young but not in older mice. In conclusion, our data support the notion that age-related hearing impairments can be in part a direct consequence of several structural alterations and circuit remodeling in the brainstem.

Introduction Ménière’s disease (MD), a common disease in the inner ear, is characterized by an increase in endolymph in the cochlear duct and vestibular labyrinth. The pathophysiology of the condition appears to be the immune response. Studies have shown that basal levels of the IL-1β increased in some MD patients. Methods Here, we used a murine model of endolymphatic hydrops (EH) to study the effect of anakinra on auditory and vestibular function. Mice were intraperitoneal injected with anakinra or saline before LPS by postauricular injection. Weight and disease severity were measured, histologic changes in auditory were assessed, and inflammation state was evaluated. Results We found that anakinra therapy reduced LPS-induced EH, alleviated LPS-induced hearing loss and vestibular dysfunction, and inhibited the expression of the inflammatory cytokines and macrophage infiltration in the cochlea of mice. We further demonstrated that anakinra ameliorated the disorganization and degeneration of myelin sheath, and reduced the neuron damage in cochlea of EH mice. Discussion Consequently, anakinra contributes to a promising therapeutic approach to MD, by restricting EH, alleviating auditory and vestibular function, inhibiting inflammation of the inner ear and protecting the cochlear nerve. Further investigations are needed to assess the potential therapeutic benefits of anakinra in patients with MD.

The temporal structure of sensory inputs contains essential information for their interpretation by the brain 1–9 . Sensory systems represent these temporal cues through two codes: the temporal sequences of neuronal activity and the spatial patterns of neuronal firing rate 3,7,10–20 . However, it is still unknown which of these two coexisting codes causally drives sensory decisions 3,10,20,21 . To separate their contributions, we designed an optogenetic stimulation paradigm in the mouse auditory cortex to generate neuronal activity patterns differing exclusively along their temporal or spatial dimensions. Training mice to discriminate these patterns shows that they efficiently learn to discriminate spatial but not temporal patterns, indicating that spatial representations are necessary for sensory learning. In line with this result, we observed, based on large-scale neuronal recordings of the auditory system, that the auditory cortex is the first region in which spatial patterns efficiently represent temporal auditory cues varying over several hundred milliseconds. This feature is shared by the deep layers of neural networks trained to categorise time-varying sounds. Therefore, the emergence of a spatial code for temporal sensory cues is a necessary condition to associate temporally structured stimuli to decisions. We expect this constraint to be crucial for re-engineering perception by cortical stimulation.

In the cochlear auditory epithelia, sensory hair and supporting cells are arranged in a checkerboard-like mosaic pattern, which is conserved across a wide range of species. The cell adhesion molecules nectin-1 and nectin-3 are required for this pattern formation. The checkerboard-like pattern is thought to be necessary for auditory function, but has never been examined. Here, we showed the significance of checkerboard-like cellular pattern in the survival and function of sensory hair cells in the cochlear auditory epithelia of nectin-3 knockout (KO) mice. Nectin-3 KO mice showed progressive hearing loss associated with degeneration of aberrantly attached hair cells via apoptosis. Apoptotic hair cell death was due to the disorganization of tight junctions between the hair cells. Our study revealed that the checkerboard-like cellular pattern in the auditory epithelium provides a structural basis for ensuring the survival of cochlear hair cells and hearing function.

To obtain combined behavioural and electrophysiological measures of pitch perception, we presented harmonic complexes, bandpass filtered to contain only high-numbered harmonics, to normal-hearing listeners. These stimuli resemble bandlimited pulse trains and convey pitch using a purely temporal code. A core set of conditions consisted of six stimuli with baseline pulse rates of 94, 188 and 280 pps, filtered into a HIGH (3365–4755 Hz) or VHIGH (7800–10,800 Hz) region, alternating with a 36% higher pulse rate. Brainstem and cortical processing were measured using the frequency following response (FFR) and auditory change complex (ACC), respectively. Behavioural rate change difference limens (DLs) were measured by requiring participants to discriminate between a stimulus that changed rate twice (up-down or down-up) during its 750-ms presentation from a constant-rate pulse train. FFRs revealed robust brainstem phase locking whose amplitude decreased with increasing rate. Moderate-sized but reliable ACCs were obtained in response to changes in purely temporal pitch and, like the psychophysical DLs, did not depend consistently on the direction of rate change or on the pulse rate for baseline rates between 94 and 280 pps. ACCs were larger and DLs lower for stimuli in the HIGH than in the VHGH region. We argue that the ACC may be a useful surrogate for behavioural measures of rate discrimination, both for normal-hearing listeners and for cochlear-implant users. We also showed that rate DLs increased markedly when the baseline rate was reduced to 48 pps, and compared the behavioural and electrophysiological findings to recent cat data obtained with similar stimuli and methods.