Spatially Distinct Functional Output Regions within the Central Nucleus of the Inferior Colliculus: Implications for an Auditory Midbrain Implant

Abstract

The inferior colliculus central nucleus (ICC) has potential as a new site for an auditory prosthesis [i.e., auditory midbrain implant (AMI)]for deaf patients who cannot benefit from cochlear implants (CIs). We have previously shown that ICC stimulation achieves lower thresholds, greater dynamic ranges, and more localized, frequency-specific primary auditory cortex (A1) activation than CI stimulation. However, we also observed that stimulation location along the caudorostral (isofrequency) dimension of the ICC affects thresholds and frequency specificity in A1, suggesting possible differences in functional (output) organization within the ICC. In this study, we electrically stimulated different regions along the isofrequency laminas of the ICC and recorded the corresponding A1 activity in ketamineanesthetized guinea pigs using multisite probes to systematically assess ICC stimulation location effects. Our results indicate that stimulation of more rostral and somewhat ventral regions within an ICC lamina achieves lower thresholds, smaller discriminable level steps, and larger evoked potentials in A1. We also observed longer first spike latencies, which correlated with reduced spiking precision, when stimulating in more caudal and dorsal ICC regions. These findings suggest that at least two spatially distinct functional output regions exist along an ICC lamina: a caudal-dorsal region and a rostral-ventral region. The AMI will be implanted along the tonotopic axis of the ICC to achieve frequency-specific activation. However, stimulation location along the ICC laminas affects response properties that have shown to be important for speech perception performance, and needs to be considered when implanting future AMI patients.

Electrical Stimulation of the Midbrain for Hearing Restoration: Insight into the Functional Organization of the Human Central Auditory System

“…However, AMI thresholds (only for AMI-3 whose sites are in the ICC) are 6 -12 nC (5-10 C/cm 2 ), and dynamic ranges are 7-9 dB, which are similar to those of the CI [5-20 nC (ϳ1-5 C/cm 2 ) and 5-10 dB, respectively, using approximately similar stimuli] (Shannon, 1985;Pfingst et al, 1997). It is possible, as shown in guinea pigs (Lim and Anderson, 2007), that stimulation of more caudal and dorsal regions along the ICC laminas, in which the array is located in AMI-3, requires higher current levels for auditory cortical activation than stimulation of more rostral and ventral regions (Ͼ17 dB at the extreme edges). However, this then raises the question as to why stimulation of a caudodorsal ICC region would require higher current levels when sites are in close contact to neurons.…”

“…However, it is also possible that the sites for AMI-1 and AMI-3 are just located in regions of low temporal resolution. In guinea pigs, stimulation of more caudal and dorsal regions along an ICC lamina, in which AMI-3 is implanted, elicits auditory cortical activity with longer latencies and greater spiking jitter (Lim and Anderson, 2007). Both explanations emphasize the need for appropriate placement and/or more complex spatial stimuli within the ICC to achieve enhanced coding of temporal features.…”

“…The questions remain as to what are "appropriate" stimuli and if simultaneous stimulation across different frequency and isofrequency regions within the ICC and even other subregions of the IC are required to elicit the desired percepts. At least based on animal studies, we believe that stimulation of more rostral and ventrolateral regions within the ICC may provide additional improvements in performance (Lim and Anderson, 2007), and this may be sufficient to restore open-set speech perception. However, if we are going to take advantage of the enormous amount of information passing through the IC, which receives almost all projections from lower brainstem nuclei (Casseday et al, 2002), and considering that we observed different perceptual effects depending on stimulation location as discussed above, then we will likely need to develop a threedimensional array that sufficiently spans and activates the IC.…”

Response features across the auditory midbrain reveal an organization consistent with a dual lemniscal pathway

“…The dual lemniscal projections from the ICC up to the ACC are further supported by electrophysiological studies suggesting that a "caudal" pathway exhibits weaker and less temporally precise activation than a "rostral" pathway. In the guinea pig, electrical stimulation of the caudal-and-medial regions compared with the rostral-and-lateral regions along an isofrequency lamina of the ICC (note that hyphens refer to locations along an ICC lamina) required higher current levels for activating A1 and elicited weaker spiking and local field potential (LFP) magnitudes, longer latencies, greater spiking jitter, and larger discriminable level steps (Lim and Anderson 2007). In the cat, neurons responding to acoustic stimuli in caudal MGV compared with rostral MGV exhibited weaker excitatory activation, less precise time-locking to click trains, longer latencies, greater spiking jitter, and less strict tonotopic organization with wider tuning curves (Rodrigues-Dagaeff et al 1989).…”

Psychophysical assessment of stimulation sites in auditory prosthesis electrode arrays

“…However, there is evidence that there are anatomical differences along the rostral-caudal axis of frequency lamina in the inferior colliculus central nucleus that could contribute to differences in performance (Lim and Anderson, 2007). Psychophysical assessment can potentially make a significant contribution to identifying the best stimulation sites in a multiprobe implant at this location.…”