Responses of midbrain auditory neurons in rats to FM and AM tones presented simultaneously.

Speech and other communication signals contain components of frequency and amplitude modulations (FM, AM) that often occur together. Auditory midbrain (or inferior colliculus, IC) is an important center for coding time-varying features of sounds. It remains unclear how IC neurons respond when FM and AM stimuli are both presented. Here we studied IC neurons in the urethane-anesthetized rats when animals were simultaneously stimulated with FM and AM tones. Of 122 units that were sensitive to the dual stimuli, the responses could be grossly divided into two types: one that resembled the respective responses to FM or AM stimuli presented separately ("simple" sensitivity, 45% of units), and another that appeared markedly different from their respective responses to FM or AM tones ("complex" sensitivity, 55%). These types of combinational sensitivities were further correlated with individual cell's frequency tuning pattern (response area) and with their common response pattern to FM and AM sounds. Results suggested that such combinational sensitivity could reflect local synaptic interactions on IC neurons and that the neural mechanisms could underlie more developed sensitivities to acoustic combinations found at the auditory cortex.

Fine frequency-modulation trigger features of midbrain auditory neurons extracted by the progressive thresholding method--a preliminary study.

Spectro-temporal receptive fields (STRFs) are commonly used to characterize response properties of central auditory neurons and for visualizing 'trigger features'. However, trigger features in STRF maps typically have a blurry appearance. Therefore it is unclear what details could be embedded in them. To investigate this, we developed a new method called 'progressive thresholding' to resolve fine structures in the STRFs, and applied the method to FM responses recorded from single units at the auditory midbrain of anesthetized rats. Random FM tones of a narrow frequency range (approximately 0.5 octave) were first presented to evoked spike responses at the cell's best frequency. Perispike modulating time waveforms collected (50 msec long, n = 1500 to 4000 tracings) were used to generate STRF based on spike-triggered-averaging. After supra-threshold areas of pixel counts had been determined through a step of progressive thresholding in the map, those peri-spike modulating waveforms passing through each area were dejittered systematically. At what seemed to be an optimal threshold, multiple trigger features (up to a maximum of 4 fine bands) were extracted from the initially simple-looking STRF. Results show that fine FM trigger features are present in STRFs and that they can be resolved with the present method of analysis.

Functional connections between auditory cortical fields in humans revealed by Granger causality analysis of intra-cranial evoked potentials to sounds: comparison of two methods.

Knowledge of neural interactions amongst cortical sites is important for understanding higher brain function. We studied such interactions using Granger causality (GC) to analyze auditory event-related potentials (ERPs) recorded directly and simultaneously from two physiologically identified and functionally interconnected auditory areas of cerebral cortex in human neurosurgical patients. Two methods of GC analysis were used and the results compared. Both approaches involved adaptive autoregressive modeling but differed from each other in other ways. Results obtained by using the two methods also differed. Fewer false-positive results were obtained using the method that suppressed the ERP non-stationarity and that expressed the GC as the sum of model coefficients, which suggests that this is the more appropriate approach for analyzing ERPs recorded directly from the human cortex.

Multiple-band trigger features of midbrain auditory neurons revealed in composite spectro-temporal receptive fields.

Receptive fields of single units in the auditory midbrain of anesthetized rats were studied using random FM-tone stimuli of narrow frequency-ranges. Peri-spike averaging of the modulating waveform first produced a spectro-temporal receptive field (STRF). Combining STRFs obtained from the same unit at different frequency regions generated a composite receptive field covering a wider frequency range of 2 to 3 octaves. About 20% of the composite STRFs (26/122) showed a pattern of multiple-bands which were not clear in the non-composite maps. Multiple-bands in a given composite map were often oriented in the same direction (representing upward or downward FM ramp) separated at rather regular frequency intervals. They reflect multiple FM trigger features in the stimulus rather than repetitive firing to a single trigger feature. Results showed that the subcortical auditory pathways are capable of detecting multiple FM features and such sensitivity could be useful in detecting multiple-harmonic FM bands present in the vocalization sounds.

Real-time data-reusing adaptive learning of a radial basis function network for tracking evoked potentials.

Tracking variations in both the latency and amplitude of evoked potential (EP) is important in quantifying properties of the nervous system. Adaptive filtering is a powerful tool for tracking such variations. In this paper, a data-reusing non-linear adaptive filtering method, based on a radial basis function network (RBFN), is implemented to estimate EP. The RBFN consists of an input layer of source nodes, a single hidden layer of non-linear processing units and an output layer of linear weights. It has built-in nonlinear activation functions that allow learning of function mappings. Moreover, it produces satisfactory estimates of signals against a background noise without a priori knowledge of the signal, provided that the signal and noise are independent. In clinical situations where EP responses change rapidly, the convergence rate of the algorithm becomes a critical factor. A carefully designed data-reusing RBFN can accelerate the convergence rate markedly and, thus, enhance its performance. Both theoretical analysis and simulation results support the improved performance of our new algorithm.

Frequency discrimination in rats exposed to noise as juveniles.

Sound exposure during the early postnatal period can significantly influence the function of the auditory system in rats during adulthood. In the present study, rat pups (strain Long-Evans) were exposed to broad-band noise at 125dB SPL for 8, 12 or 25min on postnatal day 14 and then at the age of 3-5months their frequency discrimination at 4 and 16kHz was assessed using a modified method of the prepulse inhibition of the acoustic startle reflex. In all groups of exposed rats, an altered frequency discrimination of the tonal stimuli was observed, in comparison with controls, at 70dB SPL. A worsening of frequency discrimination was observed even in animals exposed for 8min, the auditory thresholds of which were almost identical to that of control animals. The individual auditory thresholds did not correlate with frequency discrimination. The difference in frequency discrimination between the exposed and control animals disappeared at 85-90dB SPL. Our data suggests that brief noise exposure during the critical period of development results in the altered frequency discrimination at moderate sound intensities in adult rats, which may appear even in individuals with normal hearing thresholds.

Evaluation of microvasculature at the auditory midbrain--the benefits of sectioning at a tangential angle.

Vascular remodeling in the brain occurs as a plastic change following neural over-activity. The auditory midbrain (or inferior colliculus, IC) is an ideal place to study sound-induced vascular changes because it is the brain's most vascularized structure and it is tonotopically organized. However, its micro-vascular pattern remains poorly understood. Since the IC is a sphere-like structure, the histological assessment of vasculature could depend on the angle of sectioning. Here, we studied the effects of cutting the IC at different angles on microvascular assessment, specifically: micro-vascular density and the shape of microvascular lumen. Photomicrographs were taken from 5 µm toluidine blue-stained histological sections obtained at two angles of sectioning: (a) the conventional coronal sectioning, and (b) a novel "tangential" sectioning (tangential to the dorso-medial surface of the IC). Results showed that the tangential sections, in comparison with the coronal sections, yielded (a) a higher count of micro-vascular density and (b) a higher proportion of round-shaped micro-vascular lumens. This discrepancy in results between two cut angles is likely related to the spatial pattern of blood vessels supplying the IC. We propose that the tangential sectioning should be adopted as standard for the accurate study of microvasculature in the IC.

Long-term changes of response in the inferior colliculus of senescence accelerated mice after early sound exposure.

Early sound exposure could alter auditory sensitivity in young animals. For example, the distribution of frequency tuning at the midbrain inferior colliculus (IC) is altered following early exposure to a tone at a moderate intensity level. Whether such neonatal change is still present in the old animals remains unknown. We studied the long-term effects of early sound exposure using a mutant strain of mice expressing accelerated senescence (SAM). Experimental animals were first exposed to a 9-kHz tone (53 dB sound pressure level (SPL)) for 30 days (10 h/day) after birth. Control animals received no tones. At the age of 15 months, responses of single IC units to sounds were studied electrophysiologically under urethane anesthesia. In the control group, we found an overall reduction in sensitivity to tones particularly at high frequencies, in comparison with normal non-senescent mice. Moreover, neurons exhibited increased spontaneous activities. These signs are consistent with accelerated senescence. Early sound exposure produced two effects in the experimental group. Firstly, IC units showed an apparent 'clustering' of best frequencies towards the frequency of the exposing tone (i.e., 9 kHz). Secondly, there was a further loss in sensitivity to tones particularly at high frequencies. Results suggest that early sound exposure has produced a long-lasting effect on frequency tuning of IC neurons. Acoustic overstimulation early in life may also accelerate the senescence of neurons or structures in the auditory system.

Adaptive filtering of evoked potentials with radial-basis-function neural network prefilter.

Evoked potentials (EPs) are time-varying signals typically buried in relatively large background noise. To extract the EP more effectively from noise, we had previously developed an approach using an adaptive signal enhancer (ASE) (Chen et al., 1995). ASE requires a proper reference input signal for its optimal performance. Ensemble- and moving window-averages were formerly used with good results. In this paper, we present a new method to provide even more effective reference inputs for the ASE. Specifically, a Gaussian radial basis function neural network (RBFNN) was used to preprocess raw EP signals before serving as the reference input. Since the RBFNN has built-in nonlinear activation functions that enable it to closely fit any function mapping, the output of RBFNN can effectively track the signal variations of EP. Results confirmed the superior performance of ASE with RBFNN over the previous method.

Prolonged sound exposure has different effects on increasing neuronal size in the auditory cortex and brainstem.

Tone at moderate levels presented to young rats at a stage (postnatal week-4) presumably that has passed the cortical critical period still can enlarge neurons in the auditory cortex. It remains unclear whether this delayed plastic change occurs only in the cortex, or reflects a change taking place in the auditory brainstem. Here we compared sound-exposure effects on neuronal size in the auditory cortex and the midbrain. Starting from postnatal day 22, young rats were exposed to a low-frequency tone (4 kHz at 65 dB SPL) for a period of 3 (postnatal day 22-25) or 7 (postnatal day 22-29) days before sacrifice. Neurons were analyzed morphometrically from 7 µm-thick histological sections. A marked increase in neuronal size (32%) was found at the cortex in the high-frequency region distant from the exposing tone. The increase in the midbrain was even larger (67%) and was found in both the low and high frequency regions. While cell enlargements were clear at day 29, only in the high frequency region of the cortex a slight enlargement was found at day 22, suggesting that the cortical and subcortical changes are synchronized, if not slightly preceded by the cortex. In contrast, no changes in neuronal size were found in the cochlear nucleus or the visual midbrain. Such differential effects of sound-exposure at the auditory centers across cortical and subcortical levels cannot be explained by a simple activity-driven change occurring earlier in the brainstem, and might involve function of other structures as for example the descending auditory system.

Modeling complex responses of FM-sensitive cells in the auditory midbrain using a committee machine.

Frequency modulation (FM) is an important building block of complex sounds that include speech signals. Exploring the neural mechanisms of FM coding with computer modeling could help understand how speech sounds are processed in the brain. Here, we modeled the single unit responses of auditory neurons recorded from the midbrain of anesthetized rats. These neurons displayed spectral temporal receptive fields (STRFs) that had multiple-trigger features, and were more complex than those with single-trigger features. Their responses have not been modeled satisfactorily with simple artificial neural networks, unlike neurons with simple-trigger features. To improve model performance, here we tested an approach with the committee machine. For a given neuron, the peri-stimulus time histogram (PSTH) was first generated in response to a repeated random FM tone, and peaks in the PSTH were segregated into groups based on the similarity of their pre-spike FM trigger features. Each group was then modeled using an artificial neural network with simple architecture, and, when necessary, by increasing the number of neurons in the hidden layer. After initial training, the artificial neural networks with their optimized weighting coefficients were pooled into a committee machine for training. Finally, the model performance was tested by prediction of the response of the same cell to a novel FM tone. The results showed improvement over simple artificial neural networks, supporting that trigger-feature-based modeling can be extended to cells with complex responses. This article is part of a Special Issue entitled Neural Coding 2012. This article is part of a Special Issue entitled Neural Coding 2012.

Deactivation of the inferior colliculus by cooling demonstrates intercollicular modulation of neuronal activity.

The auditory pathways coursing through the brainstem are organized bilaterally in mirror image about the midline and at several levels the two sides are interconnected. One of the most prominent points of interconnection is the commissure of the inferior colliculus (CoIC). Anatomical studies have revealed that these fibers make reciprocal connections which follow the tonotopic organization of the inferior colliculus (IC), and that the commissure contains both excitatory and, albeit fewer, inhibitory fibers. The role of these connections in sound processing is largely unknown. Here we describe a method to address this question in the anaesthetized guinea pig. We used a cryoloop placed on one IC to produce reversible deactivation while recording electrophysiological responses to sounds in both ICs. We recorded single units, multi-unit clusters and local field potentials (LFPs) before, during and after cooling. The degree and spread of cooling was measured with a thermocouple placed in the IC and other auditory structures. Cooling sufficient to eliminate firing was restricted to the IC contacted by the cryoloop. The temperature of other auditory brainstem structures, including the contralateral IC and the cochlea were minimally affected. Cooling below 20°C reduced or eliminated the firing of action potentials in frequency laminae at depths corresponding to characteristic frequencies up to ~8 kHz. Modulation of neural activity also occurred in the un-cooled IC with changes in single unit firing and LFPs. Components of LFPs signaling lemniscal afferent input to the IC showed little change in amplitude or latency with cooling, whereas the later components, which likely reflect inter- and intra-collicular processing, showed marked changes in form and amplitude. We conclude that the cryoloop is an effective method of selectively deactivating one IC in guinea pig, and demonstrate that auditory processing in the IC is strongly influenced by the other.

Age-related changes in the acoustic startle reflex in Fischer 344 and Long Evans rats.

The behavioral consequences of age-related changes in the auditory system were studied in Fischer 344 (F344) rats as a model of fast aging and in Long Evans (LE) rats as a model of normal aging. Hearing thresholds, the strength of the acoustic startle responses (ASRs) to noise and tonal stimuli, and the efficiency of the prepulse inhibition (PPI) of ASR were assessed in young-adult, middle-aged, and aged rats of both strains. Compared with LE rats, F344 rats showed larger age-related hearing threshold shifts, and the amplitudes of their startle responses were mostly lower. Both rat strains demonstrated a significant decrease of startle reactivity during aging. For tonal stimuli, this decrease occurred at an earlier age in the F344 rats: middle-aged F344 animals expressed similar startle reactivity as aged F344 animals, whereas middle-aged LE animals had similar startle reactivity as young-adult LE animals. For noise stimuli, on the other hand, a similar progression of age-related ASR changes was found in both strains. No significant relationship between the hearing thresholds and the ASR amplitudes was found within any age group. Auditory PPI was less efficient in F344 rats than in LE rats. An age-related reduction of the PPI of ASR was observed in rats of both strains; however, a significant reduction of PPI occurred only in aged rats. The results indicate that the ASR may serve as an indicator of central presbycusis.

Modeling frequency modulated responses of midbrain auditory neurons based on trigger features and artificial neural networks.

Frequency modulation (FM) is an important building block of communication signals for animals and human. Attempts to predict the response of central neurons to FM sounds have not been very successful, though achieving successful results could bring insights regarding the underlying neural mechanisms. Here we proposed a new method to predict responses of FM-sensitive neurons in the auditory midbrain. First we recorded single unit responses in anesthetized rats using a random FM tone to construct their spectro-temporal receptive fields (STRFs). Training of neurons in the artificial neural network to respond to a second random FM tone was based on the temporal information derived from the STRF. Specifically, the time window covered by the presumed trigger feature and its delay time to spike occurrence were used to train a finite impulse response neural network (FIRNN) to respond to this random FM. Finally we tested the model performance in predicting the response to another similar FM stimuli (third random FM tone). We found good performance in predicting the time of responses if not also the response magnitudes. Furthermore, the weighting function of the FIRNN showed temporal 'bumps' suggesting temporal integration of synaptic inputs from different frequency laminae. This article is part of a Special Issue entitled: Neural Coding.

Should spikes be treated with equal weightings in the generation of spectro-temporal receptive fields?

Knowledge on the trigger features of central auditory neurons is important in the understanding of speech processing. Spectro-temporal receptive fields (STRFs) obtained using random stimuli and spike-triggered averaging allow visualization of trigger features which often appear blurry in the time-versus-frequency plot. For a clearer visualization we have previously developed a dejittering algorithm to sharpen trigger features in the STRF of FM-sensitive cells. Here we extended this algorithm to segregate spikes, based on their dejitter values, into two groups: normal and outlying, and to construct their STRF separately. We found that while the STRF of the normal jitter group resembled full trigger feature in the original STRF, those of the outlying jitter group resembled a different or partial trigger feature. This algorithm allowed the extraction of other weaker trigger features. Due to the presence of different trigger features in a given cell, we proposed that in the generation of STRF, the evoked spikes should not be treated indiscriminately with equal weightings.

Early postnatal sound exposure induces lasting neuronal changes in the inferior colliculus of senescence accelerated mice (SAMP8): a morphometric study on GABAergic neurons and NMDA expression.

Senescence-acceleration-prone mice (SAMP8) provide a model to study the influence of early postnatal sound exposure upon the aging auditory midbrain. SAMP8 were exposed to a 9-kHz monotone of either 53- or 65-dB sound pressure level during the first 30 postnatal days, the neurons in the auditory midbrain responding selectively to 9 kHz were localized by c-fos immunohistochemistry and the following parameters were compared to control SAMP8 not exposed to sound: mortality after sound exposure, dendritic spine density, and quantitative neurochemical alterations in this 9-kHz isofrequency lamina. For morphometric analysis, animals were examined at 1, 4, and 8 months of age. Serial sections of the inferior colliculus were Golgi impregnated or stained immunohistochemically for the expression of epsilon1 subunit of NMDA receptor or GABA. Mortality after exposure to 53 dB was the same as in controls, but was markedly increased from 7 months of age onward after postnatal exposure to 65 dB. No gross morphological alterations were observed in the auditory midbrain after sound exposure. However, sound exposure to 53 or 65 dB significantly reduced dendritic spine density by 11% at 4 months or by 11-17% both at 1 and 4 months of age, respectively. The effect of sound exposure upon neurons expressing the NMDAepsilon1 subunit was dose-dependent. Increasing with age until 4 months in control mice and remaining essentially stable thereafter, the percentage of NMDAepsilon1-immunoreactive neurons was significantly elevated by 40-66% in 1- and 8-month-old SAMP8 exposed to 53 dB, whereas no significant effect of 65 dB was apparent. The proportion of GABAergic cells declined with age in controls. It was significantly decreased at 1 month after 53 and 65 dB sound exposure. In contrast, it was elevated at later stages, being significantly increased at 4 months after exposure to 53 dB and at 8 months after exposure to 65 dB. The total cell number in the 9-kHz isofrequency lamina of SAMP8 decreased with age, but was not affected by exposure to either 53 or 65 dB. The present results indicate that early postnatal exposure to a monotone of mild intensity has long-term effects upon the aging auditory brain stem. Some of the changes induced by sound exposure, e.g., decline in spine density, are interpreted as accelerations of the normal aging process, whereas other effects, e.g., increased NMDAepsilon1 expression after 53 dB and elevated GABA expression after both 53 and 65 dB, are not merely explicable by accelerated aging.