Provision of interaural time difference information in chronic intracochlear electrical stimulation enhances neural sensitivity to these differences in neonatally deafened cats.

Although performance with bilateral cochlear implants is superior to that with a unilateral implant, bilateral implantees have poor performance in sound localisation and in speech discrimination in noise compared to normal hearing subjects. Studies of the neural processing of interaural time differences (ITDs) in the inferior colliculus (IC) of long-term deaf animals, show substantial degradation compared to that in normal hearing animals. It is not known whether this degradation can be ameliorated by chronic cochlear electrical stimulation, but such amelioration is unlikely to be achieved using current clinical speech processors and cochlear implants, which do not provide good ITD cues. We therefore developed a custom sound processor to deliver salient ITDs for chronic bilateral intra-cochlear electrical stimulation in a cat model of neonatal deafness, to determine if long-term exposure to salient ITDs would prevent degradation of ITD processing. We compared the sensitivity to ITDs in cochlear electrical stimuli of neurons in the IC of cats chronically stimulated with our custom ITD-aware sound processor with sensitivity in acutely deafened cats with normal hearing development and in cats chronically stimulated with a clinical stimulator and sound processor. Animals that experienced stimulation with our custom ITD-aware sound processor had significantly higher neural sensitivity to ITDs than those that received stimulation from clinical sound processors. There was no significant difference between animals received no stimulation and those that received stimulation from clinical sound processors, consistent with findings from clinical cochlear implant users. This result suggests that development and use of clinical ITD-aware sound processing strategies from a young age may promote ITD sensitivity in the clinical population.

Auditory perceptual learning and changes in the conceptualization of auditory cortex.

Perceptual learning, improvement in discriminative ability as a consequence of training, is one of the forms of sensory system plasticity that has driven profound changes in our conceptualization of sensory cortical function. Psychophysical and neurophysiological studies of auditory perceptual learning have indicated that the characteristics of the learning, and by implication the nature of the underlying neural changes, are highly task specific. Some studies in animals have indicated that recruitment of neurons to the population responding to the training stimuli, and hence an increase in the so-called cortical "area of representation" of those stimuli, is the substrate of improved performance, but such changes have not been observed in other studies. A possible reconciliation of these conflicting results is provided by evidence that changes in area of representation constitute a transient stage in the processes underlying perceptual learning. This expansion - renormalization hypothesis is supported by evidence from studies of the learning of motor skills, another form of procedural learning, but leaves open the nature of the permanent neural substrate of improved performance. Other studies have suggested that the substrate might be reduced response variability - a decrease in internal noise. Neuroimaging studies in humans have also provided compelling evidence that training results in long-term changes in auditory cortical function and in the auditory brainstem frequency-following response. Musical training provides a valuable model, but the evidence it provides is qualified by the fact that most such training is multimodal and sensorimotor, and that few of the studies are experimental and allow control over confounding variables. More generally, the overwhelming majority of experimental studies of the various forms of auditory perceptual learning have established the co-occurrence of neural and perceptual changes, but have not established that the former are causally related to the latter. Important forms of perceptual learning in humans are those involved in language acquisition and in the improvement in speech perception performance of post-lingually deaf cochlear implantees over the months following implantation. The development of a range of auditory training programs has focused interest on the factors determining the extent to which perceptual learning is specific or generalises to tasks other than those used in training. The context specificity demonstrated in a number of studies of perceptual learning suggests a multiplexing model, in which learning relating to a particular stimulus attribute depends on a subset of the diverse inputs to a given cortical neuron being strengthened, and different subsets being gated by top-down influences. This hypothesis avoids the difficulty of balancing system stability with plasticity, which is a problem for recruitment hypotheses. The characteristics of auditory perceptual learning reflect the fact that auditory cortex forms part of distributed networks that integrate the representation of auditory stimuli with attention, decision, and reward processes.

Plasticity in the auditory system.

Over the last 30 years a wide range of manipulations of auditory input and experience have been shown to result in plasticity in auditory cortical and subcortical structures. The time course of plasticity ranges from very rapid stimulus-specific adaptation to longer-term changes associated with, for example, partial hearing loss or perceptual learning. Evidence for plasticity as a consequence of these and a range of other manipulations of auditory input and/or its significance is reviewed, with an emphasis on plasticity in adults and in the auditory cortex. The nature of the changes in auditory cortex associated with attention, memory and perceptual learning depend critically on task structure, reward contingencies, and learning strategy. Most forms of auditory system plasticity are adaptive, in that they serve to optimize auditory performance, prompting attempts to harness this plasticity for therapeutic purposes. However, plasticity associated with cochlear trauma and partial hearing loss appears to be maladaptive, and has been linked to tinnitus. Three important forms of human learning-related auditory system plasticity are those associated with language development, musical training, and improvement in performance with a cochlear implant. Almost all forms of plasticity involve changes in synaptic excitatory - inhibitory balance within existing patterns of connectivity. An attractive model applicable to a number of forms of learning-related plasticity is dynamic multiplexing by individual neurons, such that learning involving a particular stimulus attribute reflects a particular subset of the diverse inputs to a given neuron being gated by top-down influences. The plasticity evidence indicates that auditory cortex is a component of complex distributed networks that integrate the representation of auditory stimuli with attention, decision and reward processes.

Second spatial derivative analysis of cortical surface potentials recorded in cat primary auditory cortex using thin film surface arrays: Comparisons with multi-unit data.

BACKGROUND: Current source density analysis of recordings from penetrating electrode arrays has traditionally been used to examine the layer- specific cortical activation and plastic changes associated with changed afferent input. We report on a related analysis, the second spatial derivative (SSD) of surface local field potentials (LFPs) recorded using custom designed thin-film polyimide substrate arrays. RESULTS: SSD analysis of tone- evoked LFPs generated from the auditory cortex under the recording array demonstrated a stereotypical single local minimum, often flanked by maxima on both the caudal and rostral sides. In contrast, tone-pips at frequencies not represented in the region under the array, but known (on the basis of normal tonotopic organization) to be represented caudal to the recording array, had a more complex pattern of many sources and sinks. COMPARISON WITH EXISTING METHODS: Compared to traditional analysis of LFPs, SSD analysis produced a tonotopic map that was more similar to that obtained with multi-unit recordings in a normal-hearing animal. Additionally, the statistically significant decrease in the number of acoustically responsive cortical locations in partially deafened cats following 6 months of cochlear implant use compared to unstimulated cases observed with multi-unit data (p=0.04) was also observed with SSD analysis (p=0.02), but was not apparent using traditional analysis of LFPs (p=0.6). CONCLUSIONS: SSD analysis of surface LFPs from the thin-film array provides a rapid and robust method for examining the spatial distribution of cortical activity with improved spatial resolution compared to more traditional LFP recordings.

A model of synaptic vesicle-pool depletion and replenishment can account for the interspike interval distributions and nonrenewal properties of spontaneous spike trains of auditory-nerve fibers.

In mammalian auditory systems, the spiking characteristics of each primary afferent (type I auditory-nerve fiber; ANF) are mainly determined by a single ribbon synapse in a single receptor cell (inner hair cell; IHC). ANF spike trains therefore provide a window into the operation of these synapses and cells. It was demonstrated previously (Heil et al., 2007) that the distribution of interspike intervals (ISIs) of cat ANFs during spontaneous activity can be modeled as resulting from refractoriness operating on a non-Poisson stochastic point process of excitation (transmitter release events from the IHC). Here, we investigate nonrenewal properties of these cat-ANF spontaneous spike trains, manifest as negative serial ISI correlations and reduced spike-count variability over short timescales. A previously discussed excitatory process, the constrained failure of events from a homogeneous Poisson point process, can account for these properties, but does not offer a parsimonious explanation for certain trends in the data. We then investigate a three-parameter model of vesicle-pool depletion and replenishment and find that it accounts for all experimental observations, including the ISI distributions, with only the release probability varying between spike trains. The maximum number of units (single vesicles or groups of simultaneously released vesicles) in the readily releasable pool and their replenishment time constant can be assumed to be constant (∼4 and 13.5 ms, respectively). We suggest that the organization of the IHC ribbon synapses not only enables sustained release of neurotransmitter but also imposes temporal regularity on the release process, particularly when operating at high rates.

Effects of deafness and cochlear implant use on temporal response characteristics in cat primary auditory cortex.

We have previously shown that neonatal deafness of 7-13 months duration leads to loss of cochleotopy in the primary auditory cortex (AI) that can be reversed by cochlear implant use. Here we describe the effects of a similar duration of deafness and cochlear implant use on temporal processing. Specifically, we compared the temporal resolution of neurons in AI of young adult normal-hearing cats that were acutely deafened and implanted immediately prior to recording with that in three groups of neonatally deafened cats. One group of neonatally deafened cats received no chronic stimulation. The other two groups received up to 8 months of either low- or high-rate (50 or 500 pulses per second per electrode, respectively) stimulation from a clinical cochlear implant, initiated at 10 weeks of age. Deafness of 7-13 months duration had no effect on the duration of post-onset response suppression, latency, latency jitter, or the stimulus repetition rate at which units responded maximally (best repetition rate), but resulted in a statistically significant reduction in the ability of units to respond to every stimulus in a train (maximum following rate). None of the temporal response characteristics of the low-rate group differed from those in acutely deafened controls. In contrast, high-rate stimulation had diverse effects: it resulted in decreased suppression duration, longer latency and greater jitter relative to all other groups, and an increase in best repetition rate and cut-off rate relative to acutely deafened controls. The minimal effects of moderate-duration deafness on temporal processing in the present study are in contrast to its previously-reported pronounced effects on cochleotopy. Much longer periods of deafness have been reported to result in significant changes in temporal processing, in accord with the fact that duration of deafness is a major factor influencing outcome in human cochlear implantees.

Effects of chronic cochlear electrical stimulation after an extended period of profound deafness on primary auditory cortex organization in cats.

Extended periods of deafness have profound effects on central auditory system function and organization. Neonatal deafening results in loss of the normal cochleotopic organization of the primary auditory cortex (AI), but environmentally-derived intracochlear electrical stimulation, via a cochlear implant, initiated shortly after deafening, can prevent this loss. We investigated whether such stimulation initiated after an extended period of deafness can restore cochleotopy. In two groups of neonatally-deafened cats, a multi-channel intracochlear electrode array was implanted at 8 weeks of age. One group received only minimal stimulation, associated with brief recordings at 4-6-week intervals, over the following 6 months to check the efficacy of the implant. In the other group, this 6-month period was followed by 6 months of near-continuous intracochlear electrical stimulation from a modified clinical cochlear implant system. We recorded multi-unit clusters in the auditory cortex and used two different methods to define the region of interest in the putative AI. There was no evidence of cochleotopy in any of the minimally stimulated animals, confirming our earlier finding. In three of six chronically stimulated cats there was clear evidence of AI cochleotopy, and in a fourth cat in which the majority of penetrations were in the anterior auditory field there was clear evidence of cochleotopy in that field. The finding that chronic intracochlear electrical stimulation after an extended period of deafness is able to restore cochleotopy in some (but not all) cases has implications for the performance of patients implanted after an extended period of deafness.

A probabilistic model of absolute auditory thresholds and its possible physiological basis.

Detection thresholds for auditory stimuli, specified in terms of their -amplitude or level, depend on the stimulus temporal envelope and decrease with increasing stimulus duration. The neural mechanisms underlying these fundamental across-species observations are not fully understood. Here, we present a "continuous look" model, according to which the stimulus gives rise to stochastic neural detection events whose probability of occurrence is proportional to the 3rd power of the low-pass filtered, time-varying stimulus amplitude. Threshold is reached when a criterion number of events have occurred (probability summation). No long-term integration is required. We apply the model to an extensive set of thresholds measured in humans for tones of different envelopes and durations and find it to fit well. Subtle differences at long durations may be due to limited attention resources. We confirm the probabilistic nature of the detection events by analyses of simple reaction times and verify the exponent of 3 by validating model predictions for binaural thresholds from monaural thresholds. The exponent originates in the auditory periphery, possibly in the intrinsic Ca(2+) cooperativity of the Ca(2+) sensor involved in exocytosis from inner hair cells. It results in growth of the spike rate of auditory-nerve fibers (ANFs) with the 3rd power of the stimulus amplitude before saturating (Heil et al., J Neurosci 31:15424-15437, 2011), rather than with its square (i.e., with stimulus intensity), as is commonly assumed. Our work therefore suggests a link between detection thresholds and a key biochemical reaction in the receptor cells.

An improved model for the rate-level functions of auditory-nerve fibers.

Acoustic information is conveyed to the brain by the spike patterns in auditory-nerve fibers (ANFs). In mammals, each ANF is excited via a single ribbon synapse in a single inner hair cell (IHC), and the spike patterns therefore also provide valuable information about those intriguing synapses. Here we reexamine and model a key property of ANFs, the dependence of their spike rates on the sound pressure level of acoustic stimuli (rate-level functions). We build upon the seminal model of Sachs and Abbas (1974), which provides good fits to experimental data but has limited utility for defining physiological mechanisms. We present an improved, physiologically plausible model according to which the spike rate follows a Hill equation and spontaneous activity and its experimentally observed tight correlation with ANF sensitivity are emergent properties. We apply it to 156 cat ANF rate-level functions using frequencies where the mechanics are linear and find that a single Hill coefficient of 3 can account for the population of functions. We also demonstrate a tight correspondence between ANF rate-level functions and the Ca(2+) dependence of exocytosis from IHCs, and derive estimates of the effective intracellular Ca(2+) concentrations at the individual active zones of IHCs. We argue that the Hill coefficient might reflect the intrinsic, biochemical Ca(2+) cooperativity of the Ca(2+) sensor involved in exocytosis from the IHC. The model also links ANF properties with properties of psychophysical absolute thresholds.

A dual-process account of auditory change detection.

Listeners can be "deaf" to a substantial change in a scene comprising multiple auditory objects unless their attention has been directed to the changed object. It is unclear whether auditory change detection relies on identification of the objects in pre- and post-change scenes. We compared the rates at which listeners correctly identify changed objects with those predicted by change-detection models based on signal detection theory (SDT) and high-threshold theory (HTT). Detected changes were not identified as accurately as predicted by models based on either theory, suggesting that some changes are detected by a process that does not support change identification. Undetected changes were identified as accurately as predicted by the HTT model but much less accurately than predicted by the SDT models. The process underlying change detection was investigated further by determining receiver-operating characteristics (ROCs). ROCs did not conform to those predicted by either a SDT or a HTT model but were well modeled by a dual-process that incorporated HTT and SDT components. The dual-process model also accurately predicted the rates at which detected and undetected changes were correctly identified.

Effects of prismatic adaptation on spatial gradients in unilateral neglect: A comparison of visual and auditory target detection with central attentional load.

Prismatic adaptation is increasingly recognised as an effective procedure for rehabilitating symptoms of unilateral spatial neglect--producing relatively long-lasting improvements on a variety of spatial attention tasks. The mechanisms by which the aftereffects of adaptation change neglect patients' performance on these tasks remain controversial. It is not clear, for example, whether adaptation directly influences the pathological ipsilesional attention bias that underlies neglect, or whether it simply changes exploratory motor behaviour. Here we used visual and auditory versions of a target detection task with a secondary task at fixation. Under these conditions, patients with neglect demonstrated a spatial gradient in their ability to orient to the brief, peripheral visual or auditory targets. Following prism adaptation, we found that overall performance on both the auditory and visual task improved, however, most patients in our sample did not show changes in their visual or auditory spatial gradient of attention, despite adequate aftereffects of adaptation and significant improvement in neglect on visual cancellation. Although there were individual cases that suggested prism-induced changes in visual target detection, and even reversal of the visual spatial gradient, such cases were not evident for the auditory modality. The findings indicate that spatial gradients in stimulus-driven attention may be less responsive to the effects of prism adaptation than neglect symptoms in voluntary orienting and exploratory behaviour. Individual factors such as lesion site and symptom severity may also determine the expression of prism effects on spatial neglect.

Neural prostheses and brain plasticity.

The success of modern neural prostheses is dependent on a complex interplay between the devices' hardware and software and the dynamic environment in which the devices operate: the patient's body or 'wetware'. Over 120 000 severe/profoundly deaf individuals presently receive information enabling auditory awareness and speech perception from cochlear implants. The cochlear implant therefore provides a useful case study for a review of the complex interactions between hardware, software and wetware, and of the important role of the dynamic nature of wetware. In the case of neural prostheses, the most critical component of that wetware is the central nervous system. This paper will examine the evidence of changes in the central auditory system that contribute to changes in performance with a cochlear implant, and discuss how these changes relate to electrophysiological and functional imaging studies in humans. The relationship between the human data and evidence from animals of the remarkable capacity for plastic change of the central auditory system, even into adulthood, will then be examined. Finally, we will discuss the role of brain plasticity in neural prostheses in general.

Effects of neonatal partial deafness and chronic intracochlear electrical stimulation on auditory and electrical response characteristics in primary auditory cortex.

The use of cochlear implants in patients with severe hearing losses but residual low-frequency hearing raises questions concerning the effects of chronic intracochlear electrical stimulation (ICES) on cortical responses to auditory and electrical stimuli. We investigated these questions by studying responses to tonal and electrical stimuli in primary auditory cortex (AI) of two groups of neonatally deafened cats with residual high-threshold, low-frequency hearing. One group were implanted with a multi-channel intracochlear electrode at 8 weeks of age, and received chronic ICES for up to 9 months before cortical recording. Cats in the other group were implanted immediately prior to cortical recording as adults. In all cats in both groups, multi-neuron responses throughout the rostro-caudal extent of AI had low characteristic frequencies (CFs), in the frequency range of the residual hearing, and high-thresholds. Threshold and minimum latency at CF did not differ between the groups, but in the chronic ICES animals there was a higher proportion of electrically but not acoustically excited recording sites. Electrical response thresholds were higher and latencies shorter in the chronically stimulated animals. Thus, chronic implantation and ICES affected the extent of AI that could be activated by acoustic stimuli and resulted in changes in electrical response characteristics.

Effects of restricted basilar papillar lesions and hair cell regeneration on auditory forebrain frequency organization in adult European starlings.

The frequency organization of neurons in the forebrain Field L complex (FLC) of adult starlings was investigated to determine the effects of hair cell (HC) destruction in the basal portion of the basilar papilla (BP) and of subsequent HC regeneration. Conventional microelectrode mapping techniques were used in normal starlings and in lesioned starlings either 2 d or 6-10 weeks after aminoglycoside treatment. Histological examination of the BP and recordings of auditory brainstem evoked responses confirmed massive loss of HCs in the basal portion of the BP and hearing losses at frequencies >2 kHz in starlings tested 2 d after aminoglycoside treatment. In these birds, all neurons in the region of the FLC in which characteristic frequencies (CFs) normally increase from 2 to 6 kHz had CF in the range of 2-4 kHz. The significantly elevated thresholds of responses in this region of altered tonotopic organization indicated that they were the residue of prelesion responses and did not reflect CNS plasticity. In the long-term recovery birds, there was histological evidence of substantial HC regeneration. The tonotopic organization of the high-frequency region of the FLC did not differ from that in normal starlings, but the mean threshold at CF in this frequency range was intermediate between the values in the normal and lesioned short-recovery groups. The recovery of normal tonotopicity indicates considerable stability of the topography of neuronal connections in the avian auditory system, but the residual loss of sensitivity suggests deficiencies in high-frequency HC function.

Cochlear implant use following neonatal deafness influences the cochleotopic organization of the primary auditory cortex in cats.

Electrical stimulation of spiral ganglion neurons in a deafened cochlea, via a cochlear implant, provides a means of investigating the effects of the removal and subsequent restoration of afferent input on the functional organization of the primary auditory cortex (AI). We neonatally deafened 17 cats before the onset of hearing, thereby abolishing virtually all afferent input from the auditory periphery. In seven animals the auditory pathway was chronically reactivated with environmentally derived electrical stimuli presented via a multichannel intracochlear electrode array implanted at 8 weeks of age. Electrical stimulation was provided by a clinical cochlear implant that was used continuously for periods of up to 7 months. In 10 long-term deafened cats and three age-matched normal-hearing controls, an intracochlear electrode array was implanted immediately prior to cortical recording. We recorded from a total of 812 single unit and multiunit clusters in AI of all cats as adults using a combination of single tungsten and multichannel silicon electrode arrays. The absence of afferent activity in the long-term deafened animals had little effect on the basic response properties of AI neurons but resulted in complete loss of the normal cochleotopic organization of AI. This effect was almost completely reversed by chronic reactivation of the auditory pathway via the cochlear implant. We hypothesize that maintenance or reestablishment of a cochleotopically organized AI by activation of a restricted sector of the cochlea, as demonstrated in the present study, contributes to the remarkable clinical performance observed among human patients implanted at a young age.

The role of spatial location in auditory search.

The majority of research findings to date indicate that spatial cues play a minor role in enhancing listeners' ability to parse and detect a sound of interest when it is presented in a complex auditory scene comprising multiple simultaneous sounds. Frequency and temporal differences between sound streams provide more reliable cues for scene analysis as well as for directing attention to relevant auditory 'objects' in complex displays. The present study used naturalistic sounds with varying spectro-temporal profiles to examine whether spatial separation of sound sources can enhance target detection in an auditory search paradigm. The arrays of sounds were presented in virtual auditory space over headphones. The results of Experiment 1 suggest that target detection is enhanced when sound sources are spatially separated relative to when they are presented at the same location. Experiment 2 demonstrated that this effect is most prominent within the first 250 ms of exposure to the array of sounds. These findings suggest that spatial cues may be effective for enhancing early processes such as stream segregation, rather than simply directing attention to objects that have already been segmented.

Towards a unifying basis of auditory thresholds: distributions of the first-spike latencies of auditory-nerve fibers.

Detecting sounds in quiet is the simplest task performed by the auditory system, but the neural mechanisms underlying perceptual detection thresholds for sounds in quiet are still not understood. Heil and Neubauer [Heil, P., Neubauer, H., 2003. A unifying basis of auditory thresholds based on temporal summation. Proc. Natl. Acad. Sci. USA 100, 6151-6156] have provided evidence for a simple probabilistic model according to which the stimulus, at any point in time, has a certain probability of exceeding threshold and being detected. Consequently, as stimulus duration increases, the cumulative probability of detection events increases, performance improves, and threshold amplitude decreases. The origin of these processes was traced to the first synapse in the auditory system, between the inner hair cell and the afferent auditory-nerve fiber (ANF). Here we provide further support for this probabilistic "continuous-look" model. It is derived from analyses of the distributions of the latencies of the first spikes of cat ANFs with very low spontaneous discharge rates to tones of different amplitudes. The first spikes in these fibers can be considered detection events. We show that, as predicted, the distributions can be explained by the joint probability of the occurrence of three independent sub-events, where the probability of each of those occurring is proportional to the low-pass filtered stimulus amplitude. The "temporal integration" functions of individual ANFs, derived from their first-spike latencies, are remarkably similar in shape to "temporal integration" functions, which relate threshold sound pressure level at the perceptual level to stimulus duration. This further supports a close link between the mechanisms determining the timing of the first (and other) evoked spikes at the level of the auditory nerve and detection thresholds at the perceptual level. The possible origin and some functional consequences of the expansive power-law non-linearity are discussed.

Cochlear implants and brain plasticity.

Cochlear implants have been implanted in over 110,000 deaf adults and children worldwide and provide these patients with important auditory cues necessary for auditory awareness and speech perception via electrical stimulation of the auditory nerve (AN). In 1942, Woolsey and Walzl presented the first report of cortical responses to localised electrical stimulation of different sectors of the AN in normal hearing cats, and established the cochleotopic organization of the projections to primary auditory cortex. Subsequently, individual cortical neurons in normal hearing animals have been shown to have well characterized input-output functions for electrical stimulation and decreasing response latencies with increasing stimulus strength. However, the central auditory system is not immutable, and has a remarkable capacity for plastic change, even into adulthood, as a result of changes in afferent input. This capacity for change is likely to contribute to the ongoing clinical improvements observed in speech perception for cochlear implant users. This review examines the evidence for changes of the response properties of neurons in, and consequently the functional organization of, the central auditory system produced by chronic, behaviourally relevant, electrical stimulation of the AN in profoundly deaf humans and animals.

Spontaneous activity of auditory-nerve fibers: insights into stochastic processes at ribbon synapses.

In several sensory systems, the conversion of the representation of stimuli from graded membrane potentials into stochastic spike trains is performed by ribbon synapses. In the mammalian auditory system, the spiking characteristics of the vast majority of primary afferent auditory-nerve (AN) fibers are determined primarily by a single ribbon synapse in a single inner hair cell (IHC), and thus provide a unique window into the operation of the synapse. Here, we examine the distributions of interspike intervals (ISIs) of cat AN fibers under conditions when the IHC membrane potential can be considered constant and the processes generating AN fiber activity can be considered stationary, namely in the absence of auditory stimulation. Such spontaneous activity is commonly thought to result from an excitatory Poisson point process modified by the refractory properties of the fiber, but here we show that this cannot be the case. Rather, the ISI distributions are one to two orders of magnitude better and very accurately described as a result of a homogeneous stochastic process of excitation (transmitter release events) in which the distribution of interevent times is a mixture of an exponential and a gamma distribution with shape factor 2, both with the same scale parameter. Whereas the scale parameter varies across fibers, the proportions of exponentially and gamma distributed intervals in the mixture, and the refractory properties, can be considered constant. This suggests that all of the ribbon synapses operate in a similar manner, possibly just at different rates. Our findings also constitute an essential step toward a better understanding of the spike-train representation of time-varying stimuli initiated at this synapse, and thus of the fundamentals of temporal coding in the auditory pathway.

Association between auditory and visual symptoms of unilateral spatial neglect.

Unilateral spatial neglect due to right brain damage (RBD) can occur in several different sensory modalities in the same patient. Previous studies of the association between auditory and visual neglect have yielded conflicting outcomes. Most such studies have compared performance on relatively simple clinical measures of visual neglect, such as target cancellation, with that on more sophisticated measures of auditory perception. This is problematic because such tasks are typically not matched for the cognitive processes they exercise. We overcame this limitation by using equivalent visual and auditory versions of extinction and temporal-order judgment (TOJ) tasks. RBD patients demonstrated lateralized deficits on both visual and auditory tasks when compared with same-aged, healthy controls. Critically, a significant association between the severity of visual and auditory deficits was apparent on the TOJ task but not the extinction task, suggesting that even when task demands are matched across modalities, dissociations between visual and auditory neglect can be apparent. Across the auditory tasks, patients showed more pronounced deficits for verbal stimuli than for non-verbal stimuli. These findings have implications for recent models proposed to explain the role of spatial attention in multimodal perception.