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1.  Online Stimulus Optimization Rapidly Reveals Multidimensional Selectivity in Auditory Cortical Neurons 
The Journal of Neuroscience  2014;34(27):8963-8975.
Neurons in sensory brain regions shape our perception of the surrounding environment through two parallel operations: decomposition and integration. For example, auditory neurons decompose sounds by separately encoding their frequency, temporal modulation, intensity, and spatial location. Neurons also integrate across these various features to support a unified perceptual gestalt of an auditory object. At higher levels of a sensory pathway, neurons may select for a restricted region of feature space defined by the intersection of multiple, independent stimulus dimensions. To further characterize how auditory cortical neurons decompose and integrate multiple facets of an isolated sound, we developed an automated procedure that manipulated five fundamental acoustic properties in real time based on single-unit feedback in awake mice. Within several minutes, the online approach converged on regions of the multidimensional stimulus manifold that reliably drove neurons at significantly higher rates than predefined stimuli. Optimized stimuli were cross-validated against pure tone receptive fields and spectrotemporal receptive field estimates in the inferior colliculus and primary auditory cortex. We observed, from midbrain to cortex, increases in both level invariance and frequency selectivity, which may underlie equivalent sparseness of responses in the two areas. We found that onset and steady-state spike rates increased proportionately as the stimulus was tailored to the multidimensional receptive field. By separately evaluating the amount of leverage each sound feature exerted on the overall firing rate, these findings reveal interdependencies between stimulus features as well as hierarchical shifts in selectivity and invariance that may go unnoticed with traditional approaches.
PMCID: PMC4078078  PMID: 24990917
auditory cortex; closed-loop; genetic algorithm; online neural characterization; optimization algorithm; sparse coding
2.  Coding of Electric Pulse Trains Presented through Cochlear Implants in the Auditory Midbrain of Awake Rabbit: Comparison with Anesthetized Preparations 
The Journal of Neuroscience  2014;34(1):218-231.
Cochlear implant (CI) listeners show limits at high frequencies in tasks involving temporal processing such as rate pitch and interaural time difference discrimination. Similar limits have been observed in neural responses to electric stimulation in animals with CI; however, the upper limit of temporal coding of electric pulse train stimuli in the inferior colliculus (IC) of anesthetized animals is lower than the perceptual limit. We hypothesize that the upper limit of temporal neural coding has been underestimated in previous studies due to the confound of anesthesia. To test this hypothesis, we developed a chronic, awake rabbit preparation for single-unit studies of IC neurons with electric stimulation through CI. Stimuli were periodic trains of biphasic pulses with rates varying from 20 to 1280 pulses per second. We found that IC neurons in awake rabbits showed higher spontaneous activity and greater sustained responses, both excitatory and suppressive, at high pulse rates. Maximum pulse rates that elicited synchronized responses were approximately two times higher in awake rabbits than in earlier studies with anesthetized animals. Here, we demonstrate directly that anesthesia is a major factor underlying these differences by monitoring the responses of single units in one rabbit before and after injection of an ultra-short-acting barbiturate. In general, the physiological rate limits of IC neurons in the awake rabbit are more consistent with the psychophysical limits in human CI subjects compared with limits from anesthetized animals.
PMCID: PMC3866485  PMID: 24381283
anesthesia; cochlear implant; inferior colliculus; temporal coding
3.  Congenital and Prolonged Adult-Onset Deafness Cause Distinct Degradations in Neural ITD Coding with Bilateral Cochlear Implants 
Bilateral cochlear implant (CI) users perform poorly on tasks involving interaural time differences (ITD), which are critical for sound localization and speech reception in noise by normal-hearing listeners. ITD perception with bilateral CI is influenced by age at onset of deafness and duration of deafness. We previously showed that ITD coding in the auditory midbrain is degraded in congenitally deaf white cats (DWC) compared to acutely deafened cats (ADC) with normal auditory development (Hancock et al., J. Neurosci, 30:14068). To determine the relative importance of early onset of deafness and prolonged duration of deafness for abnormal ITD coding in DWC, we recorded from single units in the inferior colliculus of cats deafened as adults 6 months prior to experimentation (long-term deafened cats, LTDC) and compared neural ITD coding between the three deafness models. The incidence of ITD-sensitive neurons was similar in both groups with normal auditory development (LTDC and ADC), but significantly diminished in DWC. In contrast, both groups that experienced prolonged deafness (LTDC and DWC) had broad distributions of best ITDs around the midline, unlike the more focused distributions biased toward contralateral-leading ITDs present in both ADC and normal-hearing animals. The lack of contralateral bias in LTDC and DWC results in reduced sensitivity to changes in ITD within the natural range. The finding that early onset of deafness more severely degrades neural ITD coding than prolonged duration of deafness argues for the importance of fitting deaf children with sound processors that provide reliable ITD cues at an early age.
PMCID: PMC3642270  PMID: 23462803
binaural hearing; congenital deafness; inferior colliculus; cochlear implants; ITD
4.  Neural coding of ITD with bilateral cochlear implants: Effects of congenital deafness 
Human bilateral cochlear implant users do poorly on tasks involving interaural time differences (ITD), a cue which provides important benefits to the normal hearing, especially in challenging acoustic environments. Yet the precision of neural ITD coding in acutely-deafened, bilaterally-implanted cats is essentially normal (Smith and Delgutte, J. Neurosci. 27:6740–6750). One explanation for this discrepancy is that the extended periods of binaural deprivation typically experienced by cochlear implant users degrades neural ITD sensitivity, either by impeding normal maturation of the neural circuitry or by altering it later in life. To test this hypothesis, we recorded from single units in inferior colliculus (IC) of two groups of bilaterally-implanted, anesthetized cats that contrast maximally in binaural experience: acutely-deafened cats, which had normal binaural hearing until experimentation, and congenitally deaf white cats, which received no auditory inputs until the experiment. Rate responses of only half as many neurons showed significant ITD sensitivity to low-rate pulse trains in congenitally deaf cats compared to acutely deafened cats. For neurons that were ITD sensitive, ITD tuning was broader and best ITDs were more variable in congenitally deaf cats, leading to poorer ITD coding within the naturally-occurring range. A signal detection model constrained by the observed physiology supports the idea that the degraded neural ITD coding resulting from deprivation of binaural experience contributes to poor ITD discrimination by human implantees.
PMCID: PMC3025489  PMID: 20962228
binaural hearing; electric stimulation; congenital deafness; cochlear implant; inferior colliculus; ITD
5.  Better Temporal Neural Coding with Cochlear Implants in Awake Animals 
Both the performance of cochlear implant (CI) listeners and the responses of auditory neurons show limits in temporal processing at high frequencies. However, the upper limit of temporal coding of pulse train stimuli in the inferior colliculus (IC) of anesthetized animals appears to be lower than that observed in corresponding perceptual tasks. We hypothesize that the neural rate limits have been underestimated due to the effect of anesthesia. To test this hypothesis, we developed a chronic, awake rabbit preparation for recording responses of single IC neurons to CI stimulation without the confound of anesthesia, and compared these data with earlier recordings from the IC of anesthetized cats. Stimuli were periodic trains of biphasic pulses with rates varying from 20 to 1280 pulses per second (pps). We found that the maximum pulse rates that elicited sustained firing and phase-locked responses were 2–3 times higher in the IC of awake rabbits than in anesthetized cats. Moreover, about 25% of IC neurons in awake rabbit showed sustained responses to periodic pulse trains at much higher pulse rates (> 1000 pps) than observed in anesthetized animals. Similar differences were observed in single units whose responses to pulse trains were monitored while the animal was given an injection of an ultra short-acting anesthetic. In general, the physiological rate limits of IC neurons in awake rabbit are more consistent with the psychophysical limits in human CI subjects compared to the data from anesthetized animals.
PMCID: PMC3726256  PMID: 23716241
cochlear implants; temporal coding; inferior colliculus; anesthesia
6.  A Physiologically Based Model of Interaural Time Difference Discrimination 
Interaural time difference (ITD) is a cue to the location of sounds containing low frequencies and is represented in the inferior colliculus (IC) by cells that respond maximally at a particular best delay (BD). Previous studies have demonstrated that single ITD-sensitive cells contain sufficient information in their discharge patterns to account for ITD acuity on the midline (ITD = 0). If ITD discrimination were based on the activity of the most sensitive cell available (“lower envelope hypothesis”), then ITD acuity should be relatively constant as a function of ITD. In response to broadband noise, however, the ITD acuity of human listeners degrades as ITD increases. To account for these results, we hypothesize that pooling of information across neurons is an essential component of ITD discrimination. This report describes a neural pooling model of ITD discrimination based on the response properties of ITD-sensitive cells in the IC of anesthetized cats.
Rate versus ITD curves were fit with a cross-correlation model of ITD sensitivity, and the parameters were used to constrain a population model of ITD discrimination. The model accurately predicts ITD acuity as a function of ITD for broadband noise stimuli when responses are pooled across best frequency (BF). Furthermore, ITD tuning based solely on a system of internal delays is not sufficient to predict ITD acuity in response to 500 Hz tones, suggesting that acuity is likely refined by additional mechanisms. The physiological data confirms evidence from the guinea pig that BD varies systematically with BF, generalizing the observation across species.
PMCID: PMC2041891  PMID: 15306644
auditory; binaural; hearing; inferior colliculus; localization; psychophysics
7.  Sound-Evoked Olivocochlear Activation in Unanesthetized Mice 
Genetic tools available for the mouse make it a powerful model to study the modulation of cochlear function by descending control systems. Suppression of distortion product otoacoustic emission (DPOAE) amplitude by contralateral acoustic stimulation (CAS) provides a robust tool for noninvasively monitoring the strength of descending modulation, yet investigations in mice have been performed infrequently and only under anesthesia, a condition likely to reduce olivocochlear activation. Here, we characterize the contralateral olivocochlear reflex in the alert, unanesthetized mouse. Head-fixed mice were restrained between two closed acoustic systems, while an artifact rejection protocol minimized contamination from self-generated sounds and movements. In mice anesthetized with pentobarbital, ketamine or urethane, CAS at 80 dB SPL evoked, on average, a <1-dB change in DPOAE amplitude. In contrast, the mean CAS-induced DPOAE suppression in unanesthetized mice was nearly 8 dB. Experiments in mice with targeted deletion of the α9 subunit of the nicotinic acetylcholine receptor confirmed the contribution of the medial olivocochlear efferents to this phenomenon. These findings demonstrate the utility of the CAS assay in the unanesthetized mouse and highlight the adverse effects of anesthesia when probing the functional status of descending control pathways within the auditory system.
PMCID: PMC3298614  PMID: 22160753
olivocochlear; corticofugal; arousal; attention; anesthesia; contralateral reflex; outer hair cell
8.  Robustness of cortical topography across fields, laminae, anesthetic states, and neurophysiological signal types 
The Journal of Neuroscience  2012;32(27):9159-9172.
Topographically organized maps of the sensory receptor epithelia are regarded as cornerstones of cortical organization as well as valuable readouts of diverse biological processes ranging from evolution to neural plasticity. However, maps are most often derived from multiunit activity recorded in the thalamic input layers of anesthetized animals using near-threshold stimuli. Less distinct topography has been described by studies that deviated from the formula above, which brings into question the generality of the principle. Here, we explicitly compared the strength of tonotopic organization at various depths within core and belt regions of the auditory cortex using electrophysiological measurements ranging from single units to delta-band local field potentials (LFP) in the awake and anesthetized mouse. Unit recordings in the middle cortical layers revealed a precise tonotopic organization in core, but not belt, regions of auditory cortex that was similarly robust in awake and anesthetized conditions. In core fields, tonotopy was degraded outside the middle layers or when LFP signals were substituted for unit activity, due to an increasing proportion of recording sites with irregular tuning for pure tones. However, restricting our analysis to clearly defined receptive fields revealed an equivalent tonotopic organization in all layers of the cortical column and for LFP activity ranging from gamma to theta bands. Thus, core fields represent a transition between topographically organized simple receptive field arrangements that extend throughout all layers of the cortical column and the emergence of non-tonotopic representations outside the input layers that are further elaborated in the belt fields.
PMCID: PMC3402176  PMID: 22764225

Results 1-8 (8)