Stefan J. Mauger

An in vivo investigation of first spike latencies in the inferior colliculus in response to multichannel penetrating auditory brainstem implant stimulation

The cochlear nucleus (CN) is the first auditory processing site within the brain and the target location of the auditory brainstem implant (ABI), which provides speech perception to patients who cannot benefit from a cochlear implant (CI). Although there is variance between ABI recipient speech performance outcomes, performance is typically low compared to CI recipients. Temporal aspects of neural firing such as first spike latency (FSL) are thought to code for many speech features; however, no studies have investigated FSL from CN stimulation. Consequently, ABIs currently do not incorporate CN-specific temporal information. We therefore systematically investigated inferior colliculus (IC) neurons FSL response to frequency-specific electrical stimulation of the CN in rats. The range of FSLs from electrical stimulation of many neurons indicates that both monosynaptic and polysynaptic pathways were activated, suggesting initial activation of multiple CN neuron types. Electrical FSLs for a single neuron did not change irrespective of the CN frequency region stimulated, indicating highly segregated projections from the CN to the IC. These results present the first evidence of temporal responses to frequency-specific CN electrical stimulation. Understanding the auditory systems temporal response to electrical stimulation will help in future ABI designs and stimulation strategies.

Acute Cochlear Nucleus Compression Alters Tuning Properties of Inferior Colliculus Neurons

Auditory brainstem implants (ABI) have been used in neurofibromatosis type 2 (NF2) patients in an attempt to restore hearing sensation, with limited clinical success. Factors associated with poor clinical outcomes for NF2 ABI patients include larger tumour size, longer duration of hearing loss, and brainstem distortion and/or deformation caused by tumours that compress the brainstem. The present study investigated changes in tuning properties of inferior colliculus (IC) neurons following compression of the contralateral cochlear nucleus (CN). The left CN in adult rats (n = 8) was exposed and a 32-channel acute recording probe inserted along the tonotopic gradient of the right IC. In 4 animals, an ethylene vinyl acetate bead was applied to the exposed CN. Three recordings were made corresponding to T1 = 0 min (before compression), T2 = 45 min (during compression) and T3 = 225 min (following bead removal/recovery). Recordings consisted of a response area protocol using pure tones of various frequencies and intensities (1–44 kHz; 10–70 dB SPL) to determine the characteristic frequency for each probe site. Compression of the CN led to sharpened tuning curves, decreased spike rate, and increased threshold and characteristic frequency in the IC. Reversal of compression enabled these variables, excluding threshold, to recover to baseline. NF2 patients may have poorer ABI performance due to damage to the physical structure of the CN, resulting in alterations to the tonotopic organisation of the auditory pathway which may complicate ABI implantation and activation.

Inferior colliculus responses to dual-site intralamina stimulation in the ventral cochlear nucleus.

A major limitation of the present auditory brainstem implant (ABI) is its inability to access the tonotopic organization of the ventral cochlear nucleus (VCN). A previous study by our group indicated that stimulation of single sites within a given VCN frequency region did not always elicit frequency‐specific responses within the central nucleus of the inferior colliculus (CIC) and in some cases did not elicit a response at all. For this study, we hypothesized that sequential stimulation (with a short interpulse delay of 320 μsec) of two VCN sites in similar frequency regions would enhance responsiveness in CIC neurons. Multiunit neural recordings in response to pure tones were obtained at 58 VCN and 164 CIC sites in anesthetized rats. Among the 58 VCN sites, 39 pairs of sites with similar characteristic frequencies were chosen for electrical stimulation. Each member of a VCN pair was electrically stimulated individually, followed by sequential stimulation of the pair, while recording CIC responses. On average, CIC sites were found to respond to dual‐site VCN stimulation with significantly lower thresholds, wider dynamic ranges, a greater extent of activation with increasing current levels, and a higher degree of frequency specificity compared with single‐site stimulation. Although these effects were positive for the most part, in some cases dual‐site stimulation resulted in increased CIC thresholds and decreased dynamic ranges, extent of activation, and frequency specificity. The results suggest that multisite stimulation within VCN isofrequency laminae using penetrating electrodes could significantly improve ABI stimulation strategies and implant performance. J. Comp. Neurol. 518:4226–4242, 2010.

Neural synchrony in ventral cochlear nucleus neuron populations is not mediated by intrinsic processes but is stimulus induced: implications for auditory brainstem implants.

The aim of this investigation was to elucidate if neural synchrony forms part of the spike time-based theory for coding of sound information in the ventral cochlear nucleus (VCN) of the auditory brainstem. Previous research attempts to quantify the degree of neural synchrony at higher levels of the central auditory system have indicated that synchronized firing of neurons during presentation of an acoustic stimulus could play an important role in coding complex sound features. However, it is unknown whether this synchrony could in fact arise from the VCN as it is the first station in the central auditory pathway. Cross-correlation analysis was conducted on 499 pairs of multiunit clusters recorded in the urethane-anesthetized rat VCN in response to pure tones and combinations of two tones to determine the presence of neural synchrony. The shift predictor correlogram was used as a measure for determining the synchrony owing to the effects of the stimulus. Without subtraction of the shift predictor, over 65% of the pairs of multiunit clusters exhibited significant correlation in neural firing when the frequencies of the tones presented matched their characteristic frequencies (CFs). In addition, this stimulus-evoked neural synchrony was dependent on the physical distance between electrode sites, and the CF difference between multiunit clusters as the number of correlated pairs dropped significantly for electrode sites greater than 800 microm apart and for multiunit cluster pairs with a CF difference greater than 0.5 octaves. However, subtraction of the shift predictor correlograms from the raw correlograms resulted in no remaining correlation between all VCN pairs. These results suggest that while neural synchrony may be a feature of sound coding in the VCN, it is stimulus induced and not due to intrinsic neural interactions within the nucleus. These data provide important implications for stimulation strategies for the auditory brainstem implant, which is used to provide functional hearing to the profoundly deaf through electrical stimulation of the VCN.

An in vivo investigation of inferior colliculus single neuron responses to cochlear nucleus pulse train stimulation

The auditory brain stem implant (ABI) is being used clinically to restore hearing to patients unable to benefit from a cochlear implant (CI). Speech perception outcomes for ABI users are typically poor compared with most CI users. The ABI is implanted either on the surface of or penetrating through the cochlear nucleus in the auditory brain stem and uses stimulation strategies developed for auditory nerve stimulation with a CI. Although the stimulus rate may affect speech perception outcomes with current stimulation strategies, no studies have systematically investigated the effect of stimulus rate electrophysiologically or clinically. We therefore investigated rate response properties and temporal response properties of single inferior colliculus (IC) neurons from penetrating ABI stimulation using stimulus rates ranging from 100 to 1,600 pulses/s in the rat. We found that the stimulus rate affected the proportion of response types, thresholds, and dynamic ranges of IC activation. The stimulus rate was also found to affect the temporal properties of IC responses, with higher rates providing more temporally similar responses to acoustic stimulation. Suppression of neural firing and inhibition in IC neurons was also found, with response properties varying with the stimulus rate. This study demonstrated that changes in the ABI stimulus rate results in significant differences in IC neuron response properties. Due to electrophysiological differences, the stimulus rate may also change perceptual properties. We suggest that clinical evaluation of the ABI stimulus rate should be performed.