Topographic Spread of Inferior Colliculus Activation in Response to Acoustic and Intracochlear Electric Stimulation

The design of contemporary multichannel cochlear implants is predicated on the presumption that they activate multiple independent sectors of the auditory nerve array. The independence of these channels, however, is limited by the spread of activation from each intracochlear electrode across the auditory nerve array. In this study, we evaluated factors that influence intracochlear spread of activation using two types of intracochlear electrodes: (1) a clinical-type device consisting of a linear series of ring contacts positioned along a silicon elastomer carrier, and (2) a pair of visually placed (VP) ball electrodes that could be positioned independently relative to particular intracochlear structures, e.g., the spiral ganglion. Activation spread was estimated by recording multineuronal evoked activity along the cochleotopic axis of the central nucleus of the inferior colliculus (ICC). This activity was recorded using silicon-based single-shank, 16-site recording probes, which were fixed within the ICC at a depth defined by responses to acoustic tones. After deafening, electric stimuli consisting of single biphasic electric pulses were presented with each electrode type in various stimulation configurations (monopolar, bipolar, tripolar) and/or various electrode orientations (radial, off-radial, longitudinal). The results indicate that monopolar (MP) stimulation with either electrode type produced widepread excitation across the ICC. Bipolar (BP) stimulation with banded pairs of electrodes oriented longitudinally produced activation that was somewhat less broad than MP stimulation, and tripolar (TP) stimulation produced activation that was more restricted than MP or BP stimulation. Bipolar stimulation with radially oriented pairs of VP ball electrodes produced the most restricted activation. The activity patterns evoked by radial VP balls were comparable to those produced by pure tones in normal-hearing animals. Variations in distance between radially oriented VP balls had little effect on activation spread, although increases in interelectrode spacing tended to reduce thresholds. Bipolar stimulation with longitudinally oriented VP electrodes produced broad activation that tended to broaden as the separation between electrodes increased.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41383/1/10162_2004_Article_4026.pd

Reducing Channel Interaction Through Cochlear Implant Programming May Improve Speech Perception

Speech perception among cochlear implant (CI) listeners is highly variable. High degrees of channel interaction are associated with poorer speech understanding. Two methods for reducing channel interaction, focusing electrical fields, and deactivating subsets of channels were assessed by the change in vowel and consonant identification scores with different program settings. The main hypotheses were that (a) focused stimulation will improve phoneme recognition and (b) speech perception will improve when channels with high thresholds are deactivated. To select high-threshold channels for deactivation, subjects’ threshold profiles were processed to enhance the peaks and troughs, and then an exclusion or inclusion criterion based on the mean and standard deviation was used. Low-threshold channels were selected manually and matched in number and apex-to-base distribution. Nine ears in eight adult CI listeners with Advanced Bionics HiRes90k devices were tested with six experimental programs. Two, all-channel programs, (a) 14-channel partial tripolar (pTP) and (b) 14-channel monopolar (MP), and four variable-channel programs, derived from these two base programs, (c) pTP with high- and (d) low-threshold channels deactivated, and (e) MP with high- and (f) low-threshold channels deactivated, were created. Across subjects, performance was similar with pTP and MP programs. However, poorer performing subjects (scoring  2). These same subjects showed slightly more benefit with the reduced channel MP programs (5 and 6). Subjective ratings were consistent with performance. These finding suggest that reducing channel interaction may benefit poorer performing CI listeners

A Fast Method for Measuring Psychophysical Thresholds Across the Cochlear Implant Array

A rapid threshold measurement procedure, based on Bekesy tracking, is proposed and evaluated for use with cochlear implants (CIs). Fifteen postlingually deafened adult CI users participated. Absolute thresholds for 200-ms trains of biphasic pulses were measured using the new tracking procedure and were compared with thresholds obtained with a traditional forced-choice adaptive procedure under both monopolar and quadrupolar stimulation. Virtual spectral sweeps across the electrode array were implemented in the tracking procedure via current steering, which divides the current between two adjacent electrodes and varies the proportion of current directed to each electrode. Overall, no systematic differences were found between threshold estimates with the new channel sweep procedure and estimates using the adaptive forced-choice procedure. Test–retest reliability for the thresholds from the sweep procedure was somewhat poorer than for thresholds from the forced-choice procedure. However, the new method was about 4 times faster for the same number of repetitions. Overall the reliability and speed of the new tracking procedure provides it with the potential to estimate thresholds in a clinical setting. Rapid methods for estimating thresholds could be of particular clinical importance in combination with focused stimulation techniques that result in larger threshold variations between electrodes

Constitutive reductions in mTOR alter cell size, immune cell development, and antibody production

Mammalian TOR (mTOR) regulates cell growth, proliferation, and migration. Because mTOR knock-outs are embryonic lethal, we generated a viable hypomorphic mouse by neo-insertion that partially disrupts mTOR transcription and creates a potential physiologic model of mTORC1/TORC2 inhibition. Homozygous knock-in mice exhibited reductions in body, organ, and cell size. Although reductions in most organ sizes were proportional to decreased body weight, spleens were disproportionately smaller. Decreases in the total number of T cells, particularly memory cells, and reduced responses to chemokines suggested alterations in T-cell homing/homeostasis. T-cell receptor-stimulated T cells proliferated less, produced lower cytokine levels, and expressed FoxP3. Decreased neutrophil numbers were also observed in the spleen, despite normal development and migration in the bone marrow. However, B-cell effects were most pronounced, with a partial block in B-cell development in the bone marrow, altered splenic populations, and decreases in proliferation, antibody production, and migration to chemokines. Moreover, increased AKTSer473 phosphorylation was observed in activated B cells, reminiscent of cancers treated with rapamycin, and was reduced by a DNA-pk inhibitor. Thus, mTOR is required for the maturation and differentiation of multiple immune cell lineages. These mice provide a novel platform for studying the consequences of constitutively reduced mTORC1/TORC2 activity