Douglas C. Fitzpatrick

A neuronal population code for sound localization

The accuracy with which listeners can locate sounds is much greater than the spatial sensitivity of single neurons. The broad spatial tuning of auditory neurons indicates that a code based on the responses of ensembles of neurons, a population code, must be used to determine the position of a sound in space. Here we show that the tuning of neurons to the most potent localization cue, the interaural time difference in low-frequency signals (<∼2 kHz; refs 4, 5), becomes sharper as the information ascends through the auditory system. We also show that this sharper tuning increases the efficiency of the population code, in the sense that fewer neurons are required to achieve a given acuity.

Transformations in processing interaural time differences between the superior olivary complex and inferior colliculus: beyond the Jeffress model

Interaural time differences (ITDs) are used to localize sounds and improve signal detection in noise. Encoding ITDs in neurons depends on specialized mechanisms for comparing inputs from the two ears. Most studies have emphasized how the responses of ITD-sensitive neurons are consistent with the tenets of the Jeffress model. The Jeffress model uses neuronal coincidence detectors that compare inputs from both sides and delay lines so that different neurons achieve coincidence at different ITDs. Although Jeffress-type models are successful at predicting sensitivity to ITDs in humans, in many respects they are a limited representation of the responses seen in neurons. In the superior olivary complex (SOC), ITD-sensitive neurons are distributed across both the medial (MSO) and lateral (LSO) superior olives. Similar response types are found in neurons sensitive to ITDs in two signal types: low-frequency sounds and envelopes of high-frequency sounds. Excitatory-excitatory interactions in the MSO are associated with peak-type responses, and excitatory-inhibitory interactions in the LSO are associated with trough-type responses. There are also neurons with responses intermediate between peak- and trough-type. In the inferior colliculus (IC), the same basic types remain, presumably due to inputs arising from the MSO and LSO. Using recordings from the SOC and IC, we describe how the response types can be described within a continuum that extends to very large values of ITD, and compare the functional organization at the two levels.

Detection of interaural correlation by neurons in the superior olivary complex, inferior colliculus and auditory cortex of the unanesthetized rabbit

A critical binaural cue important for sound localization and detection of signals in noise is the interaural time difference (ITD), or difference in the time of arrival of sounds at each ear. The ITD can be determined by cross-correlating the sounds at the two ears and finding the ITD where the correlation is maximal. The amount of interaural correlation is affected by properties of spaces and can therefore be used to assess spatial attributes. To examine the neural basis for sensitivity to the overall level of the interaural correlation, we identified subcollicular neurons and neurons in the inferior colliculus (IC) and auditory cortex of unanesthetized rabbits that were sensitive to ITDs and examined their responses as the interaural correlation was varied. Neurons at each brain level could show linear or non-linear responses to changes in interaural correlation. The direction of the non-linearities in most neurons was to increase the slope of the response change for correlations near 1.0. The proportion of neurons with non-linear responses was similar in subcollicular and IC neurons but increased in the auditory cortex. Non-linear response functions to interaural correlation were not related to the type of response as determined by the tuning to ITDs across frequencies. The responses to interaural correlation were also not related to the frequency tuning of the neuron, unlike the responses to ITD, which broadens for neurons tuned to lower frequencies. The neural discriminibility of the ITD using frozen noise in the best neurons was similar to the behavioral acuity in humans at a reference correlation of 1.0. However, for other reference ITDs the neural discriminibility was more linear and generally better than the human discriminibility of the interaural correlation, suggesting that stimulus rather than neural variability is the basis for the decline in human performance at lower levels of interaural correlation.

Intraoperative round window recordings to acoustic stimuli from cochlear implant patients.

Hypothesis Acoustically evoked neural and hair cell potentials can be measured from the round window (RW) intraoperatively in the general population of cochlear implant recipients. Background Cochlear implant performance varies greatly among patients. Improved methods to assess and monitor functional hair cell and neural substrate before and during implantation could potentially aid in enhanced nontraumatic intracochlear electrode placement and subsequent improved outcomes. Methods Subjects (1–80 yr) undergoing cochlear implantation were included. A monopolar probe was placed at the RW after surgical access was obtained. The cochlear microphonic (CM), summating potential (SP), compound action potential (CAP), and auditory nerve neurophonic (ANN) were recorded in response to tone bursts at frequencies of 0.25 to 4 kHz at various levels. Results Measurable hair cell/neural potentials were detected to 1 or more frequencies in 23 of 25 subjects. The greatest proportion and magnitude of cochlear responses were to low frequencies (<1,000 Hz). At these low frequencies, the ANN, when present, contributed to the ongoing response at the stimulus frequency. In many subjects, the ANN was small or absent, whereas hair cell responses remained. Conclusion In cochlear implant recipients, acoustically evoked cochlear potentials are detectable even if hearing is extremely limited. Sensitive measures of cochlear and neural status can characterize the state of hair cell and neural function before implantation. Whether this information correlates with speech performance outcomes or can help in tailoring electrode type, placement or audiometric fitting, can be determined in future studies.

Round window electrocochleography just before cochlear implantation: relationship to word recognition outcomes in adults.

Hypotheses Electrocochleography (ECoG) to acoustic stimuli can differentiate relative degrees of cochlear responsiveness across the population of cochlear implant recipients. The magnitude of the ongoing portion of the ECoG, which includes both hair cell and neural contributions, will correlate with speech outcomes as measured by results on CNC word score tests. Background Postoperative speech outcomes with cochlear implants vary from almost no benefit to near normal comprehension. A factor expected to have a high predictive value is the degree of neural survival. However, speech performance with the implant does not correlate with the number and distribution of surviving ganglion cells when measured postmortem. We will investigate whether ECoG can provide an estimate of cochlear function that helps predict postoperative speech outcomes. Methods An electrode was placed at the round window of the ear about to be implanted during implant surgery. Tone bursts were delivered through an insert earphone. Subjects included children (n = 52, 1–18 yr) and postlingually hearing impaired adults (n = 32). Word scores at 6 months were available from 21 adult subjects. Results Significant responses to sound were recorded from almost all subjects (80/84 or 95%). The ECoG magnitudes spanned more than 50 dB in both children and adults. The distributions of ECoG magnitudes and frequencies were similar between children and adults. The correlation between the ECoG magnitude and word score accounted for 47% of the variance. Conclusion ECoGs with high signal-to-noise ratios can be recorded from almost all implant candidates, including both adult and pediatric populations. In postlingual adults, the ECoG magnitude is more predictive of implant outcomes than other nonsurgical variables such as duration of deafness or degree of residual hearing.

Distinguishing hair cell from neural potentials recorded at the round window

Almost all patients who receive cochlear implants have some acoustic hearing prior to surgery. Electrocochleography (ECoG), or electrophysiological measures of cochlear response to sound, can identify remaining auditory nerve activity that is the basis for this residual hearing and can record potentials from hair cells that are no longer functionally connected to nerve fibers. The ECoG signal is therefore complex, being composed of both hair cell and neural signals. To identify signatures of different sources in the recorded potentials, we collected ECoG data across frequency and intensity from the round window of gerbils before and after treatment with kainic acid, a neurotoxin. Distortions in the recorded waveforms were produced by different sources over different ranges of frequency and intensity. In response to tones at low frequencies and low-to-moderate intensities, the major source of distortion was from neural phase-locking that was sensitive to kainic acid. At high intensities at all frequencies, the distortion was not sensitive to kainic acid and was consistent with asymmetric saturation of the hair cell transducer current. In addition to loss of phase-locking, changes in the envelope after kainic acid treatment indicate that sustained neural firing combines with receptor potentials from hair cells to produce the envelope of the response to tones. These results provide baseline data to interpret comparable recordings from human cochlear implant recipients.

Detection of intracochlear damage with cochlear implantation in a gerbil model of hearing loss.

Hypothesis: Cochlear trauma due to electrode insertion can be detected in acoustic responses to low frequencies in an animal model with a hearing condition similar to patients using electroacoustic stimulation. Background: Clinical evidence suggests that intracochlear damage during cochlear implantation negatively affects residual hearing. Recently, we demonstrated the usefulness of acoustically evoked potentials to detect cochlear trauma in normal-hearing gerbils. Here, gerbils with noise-induced hearing loss were used to investigate the effects of remote trauma on residual hearing. Methods: Gerbils underwent high-pass (4-kHz cutoff) noise exposure to produce sloping hearing loss. After 1 month of recovery, each animals hearing loss was determined from auditory brainstem responses and baseline intracochlear recording of the cochlear microphonic and compound action potential (CAP) obtained at the round window. Subsequently, electrode insertions were performed to produce basal trauma, whereas the acoustically generated potentials to a 1-kHz tone-burst were recorded after each step of electrode advancement. Hair cell counts were made to characterize the noise damage, and cochlear whole mounts were used to identify cochlear trauma due to the electrode. Results: The noise exposure paradigm produced a pattern of hair cell, auditory brainstem response, and intracochlear potential losses that closely mimicked that of electrical and acoustic stimulation patients. Trauma in the basal turn, in the 15- to 30-kHz portion of the deafened region, remote from preserved hair cells, induced a decline in intracochlear acoustic responses to the hearing preserved frequency of 1 kHz. Conclusion: The results indicate that a recording algorithm based on physiological markers to low-frequency acoustic stimuli can identify cochlear trauma during implantation. Future work will focus on translating these results for use with current cochlear implant technology in humans.

Monaural and binaural processing in the ventral nucleus of the lateral lemniscus: a major source of inhibition to the inferior colliculus

The ventral nucleus of the lateral lemniscus (VNLL) is a major source of input to the inferior colliculus. This paper reviews recent studies of neural responses in the VNLL of the unanesthetized rabbit. The VNLL has generally been viewed as a monaural nucleus, with its neurons responding primarily to stimulation of the contralateral ear. In the rabbit, the VNLL is divided into a medial division (VNLLm) comprising neurons intercalated in the medial limb of the lemniscus, a compact lateral division (VNLLl), and a dorsal division. The VNLLm contains an abundance of neurons sensitive to interaural temporal disparities (ITDs), one of the major binaural cues for sound localization. These neurons respond only at the onset of tones, and therefore appear to encode the ITDs of transients. Even in the VNLLl, many neurons are sensitive to binaural stimulation. The VNLLl contains a variety of neurons with different discharge patterns, the two most common of which are sustained and onset. The discharge patterns, frequency-tuning and dynamic ranges of VNLLl neurons indicate that this division is able to supply the inferior colliculus with a variety of inputs, each serving a different function in the analysis of sound.

Correlation of early auditory potentials and intracochlear electrode insertion properties: an animal model featuring near real-time monitoring.

Objective: The goal of this work was to assess electrophysiologic response changes to acoustic stimuli as an intracochlear electrode impacted cochlear structures in an animal model of hearing preservation cochlear implantation. The ultimate goal is to develop efficient procedures for assessing the status of cochlear physiology for intraoperative use. Methods: Sixteen gerbils and 18 ears were tested. A rigid electrode was inserted through a basal turn cochleostomy and directed toward the basilar membrane/osseous spiral lamina complex. We recorded acoustically evoked early auditory potentials including cochlear microphonics (CMs) and compound action potentials (CAPs) to a short stimulation sequence consisting of one stimulus frequency and intensity as the electrode was advanced. A microendoscope was used to visualize the electrode insertion progress and to identify the site of electrode impact. After each experiment, the site of intracochlear trauma was confirmed using whole mount preparations. Results: Electrophysiologic changes correlated well with the degree and location of trauma. We observed four distinct patterns. In addition, the endoscope in conjunction with the short recording sequence allowed for the detection of response changes that were reversible when the electrode was retracted. These cases were associated with less than full-thickness damage on histology. Conclusion: The short recording sequence to obtain acoustically evoked intracochlear potentials and the microendoscope allowed us to detect various levels of cochlear trauma including minor and reversible damage. Recordings of this type are potentially available using current implant technology. Future improvements in the measurements can be expected to improve the efficiency of the recording paradigm to produce a clinically useful tool.

Processing Temporal Modulations in Binaural and Monaural Auditory Stimuli by Neurons in the Inferior Colliculus and Auditory Cortex

Processing dynamic changes in the stimulus stream is a major task for sensory systems. In the auditory system, an increase in the temporal integration window between the inferior colliculus (IC) and auditory cortex is well known for monaural signals such as amplitude modulation, but a similar increase with binaural signals has not been demonstrated. To examine the limits of binaural temporal processing at these brain levels, we used the binaural beat stimulus, which causes a fluctuating interaural phase difference, while recording from neurons in the unanesthetized rabbit. We found that the cutoff frequency for neural synchronization to the binaural beat frequency (BBF) decreased between the IC and auditory cortex, and that this decrease was associated with an increase in the group delay. These features indicate that there is an increased temporal integration window in the cortex compared to the IC, complementing that seen with monaural signals. Comparable measurements of responses to amplitude modulation showed that the monaural and binaural temporal integration windows at the cortical level were quantitatively as well as qualitatively similar, suggesting that intrinsic membrane properties and afferent synapses to the cortical neurons govern the dynamic processing. The upper limits of synchronization to the BBF and the band-pass tuning characteristics of cortical neurons are a close match to human psychophysics.