Maike Vollmer

Plasticity in central representations in the inferior colliculus induced by chronic single- vs. two-channel electrical stimulation by a cochlear implant after neonatal deafness.

The goal of this research is to examine the functional consequences of patterned electrical stimulation delivered by a cochlear implant in the deafened developing auditory system. In previous electrophysiological experiments conducted in the inferior colliculus (IC), we have demonstrated that the precise cochleotopic organization of the central nucleus (ICC) develops normally in neonatally deafened unstimulated cats and is unaltered despite the lack of normal auditory input during development. However, these studies also showed that chronic electrical stimulation delivered at a single intracochlear location by one bipolar channel of a cochlear implant induces significant expansion of the central representation of the stimulated cochlear sector and degrades the cochleotopic organization of the IC. This report presents additional data from a new experimental series of neonatally deafened cats that received chronic stimulation on two adjacent bipolar intracochlear channels of a cochlear implant. Results suggest that competing inputs elicited by electrical stimulation delivered by two adjacent channels can maintain the selective representations of each activated cochlear sector within the central auditory system and prevent the expansion seen after single-channel stimulation. Alternating stimulation of two channels and use of highly controlled electrical signals may be particularly effective in maintaining or even sharpening selectivity of central representations of stimulated cochlear sectors. In contrast, simultaneous stimulation using two channels of a model analog cochlear implant processor in one experimental animal failed to maintain channel selectivity and resulted in marked expansion and fusion of the central representations of the stimulated channels. This potentially important preliminary result suggests that under some conditions the central auditory system may be unable to discriminate simultaneous, overlapping inputs from adjacent cochlear implant channels as distinct.

The effects of chronic intracochlear electrical stimulation on inferior colliculus spatial representation in adult deafened cats.

Previous studies have shown that chronic electrical stimulation through a cochlear implant causes significant alterations in the central auditory system of neonatally deafened cats. The goal of this study was to investigate the effects of chronic stimulation in the mature auditory system. Normal hearing adult animals were deafened by ototoxic drugs and received daily electrical stimulation over periods of 4-6 months. In terminal physiology experiments, response thresholds to pulsatile and sinusoidal signals were recorded within the inferior colliculus (IC). Using previously established methods, spatial tuning curves (STCs; threshold vs. IC depth functions) were constructed, and their widths measured to infer spatial selectivity. The IC spatial representations were similar for pulsatile and sinusoidal stimulation when phase duration was taken into consideration. However, sinusoidal signals consistently elicited much lower thresholds than pulsatile signals, a difference not solely attributable to differences in charge/phase. The average STC width was significantly broader in the adult deafened/stimulated animals than in controls (adult deafened/unstimulated cats), suggesting that electrical stimulation can induce spatial expansion of the IC representation of the chronically stimulated cochlear sector. Further, results in these adult animals were not significantly different from results in neonatally deafened, early stimulated animals, suggesting that a similar degree of plasticity was induced within the auditory midbrains of mature animals.

Behavioral and Neurophysiological Thresholds for Electrical Cochlear Stimulation in the Deaf Cat

Psychophysical detection thresholds for unmodulated electrical pulse trains or for sinusoidally amplitude-modulated (SAM) pulse trains were estimated in deaf juvenile cats using a conditioned avoidance paradigm. Biphasic current pulses (0.2 ms/phase) were delivered by scala tympani electrodes consisting of 4–8 electrode contacts driven as bipolar pairs. Electrical auditory brainstem response (EABR) thresholds were obtained periodically, and at the conclusion of behavioral training, response thresholds were obtained for neurons in the inferior colliculus (IC) and the primary auditory cortex (A1) in acute physiological experiments in the same animals. The results of the study include: (1) detection thresholds for unmodulated pulse trains and for SAM pulse trains were virtually identical; (2) EABR thresholds and behavioral thresholds were significantly correlated, although EABR thresholds consistently overestimated behavioral thresholds; (3) the lowest thresholds in the IC and the A1 were significantly correlated with behavioral thresholds, and (4) mean lowest thresholds in the IC and the A1 were essentially the same as the mean psychophysical detection threshold in the trained deaf cats.

Neurotrophic effects of GM1 ganglioside and electrical stimulation on cochlear spiral ganglion neurons in cats deafened as neonates

Previous studies have shown that electrical stimulation of the cochlea by a cochlear implant promotes increased survival of spiral ganglion (SG) neurons in animals deafened early in life (Leake et al. [ 1999 ] J Comp Neurol 412:543–562). However, electrical stimulation only partially prevents SG degeneration after deafening and other neurotrophic agents that may be used along with an implant are of great interest. GM1 ganglioside is a glycosphingolipid that has been reported to be beneficial in treating stroke, spinal cord injuries, and Alzheimers disease. GM1 activates trkB signaling and potentiates neurotrophins, and exogenous administration of GM1 has been shown to reduce SG degeneration after hearing loss. In the present study, animals were deafened as neonates and received daily injections of GM1, beginning either at birth or after animals were deafened and continuing until the time of cochlear implantation. GM1‐treated and deafened control groups were examined at 7–8 weeks of age; additional GM1 and no‐GM1 deafened control groups received a cochlear implant at 7–8 weeks of age and at least 6 months of unilateral electrical stimulation. Electrical stimulation elicited a significant trophic effect in both the GM1 group and the no‐GM1 group as compared to the contralateral, nonstimulated ears. The results also demonstrated a modest initial improvement in SG density with GM1 treatment, which was maintained by and additive with the trophic effect of subsequent electrical stimulation. However, in the deafened ears contralateral to the implant SG soma size was severely reduced several months after withdrawal of GM1 in the absence of electrical activation. J. Comp. Neurol. 501:837–853, 2007.

Behavioral training restores temporal processing in auditory cortex of long-deaf cats

Temporal auditory processing is poor in prelingually hearing-impaired patients fitted with cochlear prostheses as adults. In an animal model of prelingual long-term deafness, we investigated the effects of behavioral training on temporal processing in the adult primary auditory cortex (AI). Neuronal responses to pulse trains of increasing frequencies were recorded in three groups of neonatally deafened cats that received a cochlear prosthesis after >3 yr of deafness: 1) acutely implanted animals that received no electric stimulation before study, 2) animals that received chronic-passive stimulation for several weeks to months before study, and 3) animals that received chronic-passive stimulation and additional behavioral training (signal detection). A fourth group of normal adult cats that was deafened acutely and implanted served as controls. The neuronal temporal response parameters of interest included the stimulus rate that evoked the maximum number of phase-locked spikes [best repetition rate (BRR)], the stimulus rate that produced 50% of the spike count at BRR (cutoff rate), the peak-response latency, and the first spike latency and timing-jitter. All long-deaf animals demonstrated a severe reduction in spiral ganglion cell density (mean, <6% of normal). Long-term deafness resulted in a significantly reduced temporal following capacity and spike-timing precision of cortical neurons in all parameters tested. Neurons in deaf animals that received only chronic-passive stimulation showed a gain in BRR but otherwise were similar to deaf cats that received no stimulation. In contrast, training with behaviorally relevant stimulation significantly enhanced all temporal processing parameters to normal levels with the exception of minimum latencies. These results demonstrate the high efficacy of learning-based remodeling of fundamental timing properties in cortical processing even in the adult, long-deaf auditory system, suggesting rehabilitative strategies for patients with long-term hearing loss.

Behavioral training enhances cortical temporal processing in neonatally deafened juvenile cats

Deaf humans implanted with a cochlear prosthesis depend largely on temporal cues for speech recognition because spectral information processing is severely impaired. Training with a cochlear prosthesis is typically required before speech perception shows improvement, suggesting that relevant experience modifies temporal processing in the central auditory system. We tested this hypothesis in neonatally deafened cats by comparing temporal processing in the primary auditory cortex (AI) of cats that received only chronic passive intracochlear electric stimulation (ICES) with cats that were also trained with ICES to detect temporally challenging trains of electric pulses. After months of chronic passive stimulation and several weeks of detection training in behaviorally trained cats, multineuronal AI responses evoked by temporally modulated ICES were recorded in anesthetized animals. The stimulus repetition rates that produced the maximum number of phase-locked spikes (best repetition rate) and 50% cutoff rate were significantly higher in behaviorally trained cats than the corresponding rates in cats that received only chronic passive ICES. Behavioral training restored neuronal temporal following ability to levels comparable with those recorded in naïve prior normal-hearing adult deafened animals. Importantly, best repetitition rates and cutoff rates were highest for neuronal clusters activated by the electrode configuration used in behavioral training. These results suggest that neuroplasticity in the AI is induced by behavioral training and perceptual learning in animals deprived of ordinary auditory experience during development and indicate that behavioral training can ameliorate or restore temporal processing in the AI of profoundly deaf animals.

Spectral Context Affects Temporal Processing in Awake Auditory Cortex

Amplitude modulation encoding is critical for human speech perception and complex sound processing in general. The modulation transfer function (MTF) is a staple of auditory psychophysics, and has been shown to predict speech intelligibility performance in a range of adverse listening conditions and hearing impairments, including cochlear implant-supported hearing. Although both tonal and broadband carriers have been used in psychophysical studies of modulation detection and discrimination, relatively little is known about differences in the cortical representation of such signals. We obtained MTFs in response to sinusoidal amplitude modulation (SAM) for both narrowband tonal carriers and two-octave bandwidth noise carriers in the auditory core of awake squirrel monkeys. MTFs spanning modulation frequencies from 4 to 512 Hz were obtained using 16 channel linear recording arrays sampling across all cortical laminae. Carrier frequency for tonal SAM and center frequency for noise SAM was set at the estimated BF for each penetration. Changes in carrier type affected both rate and temporal MTFs in many neurons. Using spike discrimination techniques, we found that discrimination of modulation frequency was significantly better for tonal SAM than for noise SAM, though the differences were modest at the population level. Moreover, spike trains elicited by tonal and noise SAM could be readily discriminated in most cases. Collectively, our results reveal remarkable sensitivity to the spectral content of modulated signals, and indicate substantial interdependence between temporal and spectral processing in neurons of the core auditory cortex.

Modulation-Frequency-Specific Adaptation in Awake Auditory Cortex

Amplitude modulations are fundamental features of natural signals, including human speech and nonhuman primate vocalizations. Because natural signals frequently occur in the context of other competing signals, we used a forward-masking paradigm to investigate how the modulation context of a prior signal affects cortical responses to subsequent modulated sounds. Psychophysical “modulation masking,” in which the presentation of a modulated “masker” signal elevates the threshold for detecting the modulation of a subsequent stimulus, has been interpreted as evidence of a central modulation filterbank and modeled accordingly. Whether cortical modulation tuning is compatible with such models remains unknown. By recording responses to pairs of sinusoidally amplitude modulated (SAM) tones in the auditory cortex of awake squirrel monkeys, we show that the prior presentation of the SAM masker elicited persistent and tuned suppression of the firing rate to subsequent SAM signals. Population averages of these effects are compatible with adaptation in broadly tuned modulation channels. In contrast, modulation context had little effect on the synchrony of the cortical representation of the second SAM stimuli and the tuning of such effects did not match that observed for firing rate. Our results suggest that, although the temporal representation of modulated signals is more robust to changes in stimulus context than representations based on average firing rate, this representation is not fully exploited and psychophysical modulation masking more closely mirrors physiological rate suppression and that rate tuning for a given stimulus feature in a given neurons signal pathway appears sufficient to engender context-sensitive cortical adaptation.