Adaptation of Binaural Processing in the Adult Brainstem Induced by Ambient Noise

Interaural differences in stimulus intensity and timing are major cues for sound localization. In mammals, these cues are first processed in the lateral and medial superior olive by interaction of excitatory and inhibitory synaptic inputs from ipsi- and contralateral cochlear nucleus neurons. To preserve sound localization acuity following changes in the acoustic environment, the processing of these binaural cues needs neuronal adaptation. Recent studies have shown that binaural sensitivity adapts to stimulation history within milliseconds, but the actual extent of binaural adaptation is unknown. In the current study, we investigated long-term effects on binaural sensitivity using extracellular in vivo recordings from single neurons in the dorsal nucleus of the lateral lemniscus that inherit their binaural properties directly from the lateral and medial superior olives. In contrast to most previous studies, we used a noninvasive approach to influence this processing. Adult gerbils were exposed for 2 weeks to moderate noise with no stable binaural cue. We found monaural response properties to be unaffected by this measure. However, neuronal sensitivity to binaural cues was reversibly altered for a few days. Computational models of sensitivity to interaural time and level differences suggest that upregulation of inhibition in the superior olivary complex can explain the electrophysiological data

Psychophysical and physiological evidence for fast binaural processing

The mammalian auditory system is the temporally most precise sensory modality: To localize low-frequency sounds in space, the binaural system can resolve time differences between the ears with microsecond precision. In contrast, the binaural system appears sluggish in tracking changing interaural time differences as they arise from a low-frequency sound source moving along the horizontal plane. For a combined psychophysical and electrophysiological approach, we created a binaural stimulus, called "Phasewarp," that can transmit rapid changes in interaural timing. Using this stimulus, the binaural performance in humans is significantly better than reported previously and comparable with the monaural performance revealed with amplitude-modulated stimuli. Parallel, electrophysiological recordings of binaural brainstem neurons in the gerbil show fast temporal processing of monaural and different types of binaural modulations. In a refined electrophysiological approach that was matched to the psychophysics, the seemingly faster binaural processing of the Phasewarp was confirmed. The current data provide both psychophysical and physiological evidence against a general, hard-wired binaural sluggishness and reconcile previous contradictions of electrophysiological and psychophysical estimates of temporal binaural performance

Novel approaches for the investigation of sound localization in mammals

The ability to localize sounds in space is important to mammals in terms of awareness of the environment and social contact with each other. In many mammals, and particularly in humans, localization of sound sources in the horizontal plane is achieved by an extraordinary sensitivity to interaural time differences (ITDs). Auditory signals from sound sources, which are not centrally located in front of the listener travel different distances to the ears and thereby generate ITDs. These ITDs are first processed by binaural sensitive neurons of the superior olivary complex (SOC) in the brainstem. Despite decades of research on this topic, the underlying mechanisms of ITD processing are still an issue of strong controversy and the processing of concurrent sounds for example is not well understood. Here I used in vivo extra-cellular single cell recordings in the dorsal nucleus of the lateral lemniscus (DNLL) to pursue three novel approaches for the investigation of ITD processing in gerbils, a well-established animal model for sound localization. The first study focuses on the ITD processing of static pure tones in the DNLL. I found that the low frequency neurons of the DNLL express an ITD sensitivity that closely resembles the one seen in the SOC. Tracer injections into the DNLL confirmed the strong direct inputs of the SOC to the DNLL. These findings support the population of DNLL neurons as a suitable novel approach to study the general mechanism of ITD processing, especially given the technical difficulties in recording from neurons in the SOC. The discharge rate of the ITD-sensitive DNLL neurons was strongly modulated over the physiological relevant range of ITDs. However, for the majority of these neurons the maximal discharge rates were clearly outside this range. These findings contradict the possible encoding of physiological relevant ITDs by the maximal discharge of single neurons. In contrast, these data support the more recent hypothesis that the discharge rate averaged over a population of ITD-sensitive neurons encodes the location of low frequency sounds. In the second study, I investigated the ITD processing of two concurrent sound sources, extending the classical approach of using only a single sound source. As concurrent sound sources a pure tone and background noise were chosen. The data show that concurrent white noise has a high impact on the response to tones and vice versa. The discharge rate to tones was mostly suppressed by the noise. The discharge rate to the noise was suppressed or enhanced by the tone depending on the ITD of the tone. Investigating the responses to monaural stimulation and to tone stimulation with concurrent spectrally filtered noise, I found that the ITD sensitivity of DNLL neurons strongly depends on the spectral compositions, the ITDs, and the levels of the concurrent sound sources. Two different mechanisms that mediate these findings were identified: monaural across-frequency interactions and temporal interactions at the level of the coincidence detector. Simulations of simple coincidence detector models (in cooperation with Christian Leibold) suggested this interpretation. In the third study of my thesis, the temporal resolution of binaural motion was analyzed. Particularly, it was investigated how fast the neuronal system can follow changes of the ITD. Here, psychophysical experiments in humans and electrophysiological recordings in the gerbil DNLL were performed using identical acoustic stimulation. Although the binaural system has previously been described as sluggish, the binaural response of ITD-sensitive DNLL neurons was found to follow fast changes of ITDs. Furthermore, in psychophysical experiments in humans, the binaural performance was better than expected when using a novel plausible motion stimulus. These data suggest that the binaural system can follow changes of the binaural cues much faster than previously reported and almost as fast as the monaural system, given a physiological useful stimulus. In summary, the results presented here establish the ITD-sensitive DNLL neurons as a novel approach for the investigation of ITD processing. In addition, the usage of more complex and naturalistic stimuli is a promising and necessary approach for opening the field for further studies regarding a better understanding of the hearing process

Inhibiting the inhibition

The precedence effect describes the phenomenon whereby echoes are spatially fused to the location of an initial sound by selectively suppressing the directional information of lagging sounds (echo suppression). Echo suppression is a prerequisite for faithful sound localization in natural environments but can break down depending on the behavioral context. To date, the neural mechanisms that suppress echo directional information without suppressing the perception of echoes themselves are not understood. We performed in vivo recordings in Mongolian gerbils of neurons of the dorsal nucleus of the lateral lemniscus (DNLL), a GABAergic brainstem nucleus that targets the auditory midbrain, and show that these DNLL neurons exhibit inhibition that persists tens of milliseconds beyond the stimulus offset, so-called persistent inhibition (PI). Using in vitro recordings, we demonstrate that PI stems from GABAergic projections from the opposite DNLL. Furthermore, these recordings show that PI is attributable to intrinsic features of this GABAergic innervation. Implementation of these physiological findings into a neuronal model of the auditory brainstem demonstrates that, on a circuit level, PI creates an enhancement of responsiveness to lagging sounds in auditory midbrain cells. Moreover, the model revealed that such response enhancement is a sufficient cue for an ideal observer to identify echoes and to exhibit echo suppression, which agrees closely with the percepts of human subjects

A Temporal Filter for Binaural Hearing Is Dynamically Adjusted by Sound Pressure Level

In natural environments our auditory system is exposed to multiple and diverse signals of fluctuating amplitudes. Therefore, to detect, localize, and single out individual sounds the auditory system has to process and filter spectral and temporal information from both ears. It is known that the overall sound pressure level affects sensory signal transduction and therefore the temporal response pattern of auditory neurons. We hypothesize that the mammalian binaural system utilizes a dynamic mechanism to adjust the temporal filters in neuronal circuits to different overall sound pressure levels. Previous studies proposed an inhibitory mechanism generated by the reciprocally coupled dorsal nuclei of the lateral lemniscus (DNLL) as a temporal neuronal-network filter that suppresses rapid binaural fluctuations. Here we investigated the consequence of different sound levels on this filter during binaural processing. Our in vivo and in vitro electrophysiology in Mongolian gerbils shows that the integration of ascending excitation and contralateral inhibition defines the temporal properties of this inhibitory filter. The time course of this filter depends on the synaptic drive, which is modulated by the overall sound pressure level and N-methyl-D-aspartate receptor (NMDAR) signaling. In psychophysical experiments we tested the temporal perception of humans and show that detection and localization of two subsequent tones changes with the sound pressure level consistent with our physiological results. Together our data support the hypothesis that mammals dynamically adjust their time window for sound detection and localization within the binaural system in a sound level dependent manner

Frequency-Invariant Representation of Interaural Time Differences in Mammals

Interaural time differences (ITDs) are the major cue for localizing low-frequency sounds. The activity of neuronal populations in the brainstem encodes ITDs with an exquisite temporal acuity of about . The response of single neurons, however, also changes with other stimulus properties like the spectral composition of sound. The influence of stimulus frequency is very different across neurons and thus it is unclear how ITDs are encoded independently of stimulus frequency by populations of neurons. Here we fitted a statistical model to single-cell rate responses of the dorsal nucleus of the lateral lemniscus. The model was used to evaluate the impact of single-cell response characteristics on the frequency-invariant mutual information between rate response and ITD. We found a rough correspondence between the measured cell characteristics and those predicted by computing mutual information. Furthermore, we studied two readout mechanisms, a linear classifier and a two-channel rate difference decoder. The latter turned out to be better suited to decode the population patterns obtained from the fitted model

A Temporal Filter for Binaural Hearing Is Dynamically Adjusted by Sound Pressure Level

In natural environments our auditory system is exposed to multiple and diverse signals of fluctuating amplitudes. Therefore, to detect, localize, and single out individual sounds the auditory system has to process and filter spectral and temporal information from both ears. It is known that the overall sound pressure level affects sensory signal transduction and therefore the temporal response pattern of auditory neurons. We hypothesize that the mammalian binaural system utilizes a dynamic mechanism to adjust the temporal filters in neuronal circuits to different overall sound pressure levels. Previous studies proposed an inhibitory mechanism generated by the reciprocally coupled dorsal nuclei of the lateral lemniscus (DNLL) as a temporal neuronal-network filter that suppresses rapid binaural fluctuations. Here we investigated the consequence of different sound levels on this filter during binaural processing. Our in vivo and in vitro electrophysiology in Mongolian gerbils shows that the integration of ascending excitation and contralateral inhibition defines the temporal properties of this inhibitory filter. The time course of this filter depends on the synaptic drive, which is modulated by the overall sound pressure level and N-methyl-D-aspartate receptor (NMDAR) signaling. In psychophysical experiments we tested the temporal perception of humans and show that detection and localization of two subsequent tones changes with the sound pressure level consistent with our physiological results. Together our data support the hypothesis that mammals dynamically adjust their time window for sound detection and localization within the binaural system in a sound level dependent manner