Gene Electrotransfer via Conductivity-Clamped Electric Field Focusing Pivots Sensori-Motor DNA Therapeutics: "A Spoonful of Sugar Helps the Medicine Go Down".

Viral vectors and lipofection-based gene therapies have dispersion-dependent transduction/transfection profiles that thwart precise targeting. The study describes the development of focused close-field gene electrotransfer (GET) technology, refining spatial control of gene expression. Integration of fluidics for precise delivery of "naked" plasmid deoxyribonucleic acid (DNA) in sucrose carrier within the focused electric field enables negative biasing of near-field conductivity ("conductivity-clamping"-CC), increasing the efficiency of plasma membrane molecular translocation.

Comparisons of electrophysiological and psychophysical fitting methods for cochlear implants.

Objective: This study compared two different versions of an electrophysiology-based software-guided cochlear implant fitting method with a procedure employing standard clinical software. The two versions used electrically evoked compound action potential (ECAP) thresholds for either five or all twenty-two electrodes to determine sound processor stimulation level profiles. Objective and subjective performance results were compared between software-guided and clinical fittings.

Neurotrophin gene augmentation by electrotransfer to improve cochlear implant hearing outcomes.

This Review outlines the development of DNA-based therapeutics for treatment of hearing loss, and in particular, considers the potential to utilize the properties of recombinant neurotrophins to improve cochlear auditory (spiral ganglion) neuron survival and repair. This potential to reduce spiral ganglion neuron death and indeed re-grow the auditory nerve fibres has been the subject of considerable pre-clinical evaluation over decades with the view of improving the neural interface with cochlear implants. This provides the context for discussion about the development of a novel means of using cochlear implant electrode arrays for gene electrotransfer.

Sound localization with bilateral cochlear implants in noise: how much do head movements contribute to localization?

Bilateral cochlear implant (CI) users encounter difficulties in localizing sound sources in everyday environments, especially in the presence of background noise and reverberation. They tend to show large directional errors and front-back confusions compared to normal hearing (NH) subjects in the same conditions. In this study, the ability of bilateral CI users to use head movements to improve sound source localization was evaluated.

Neurophysiological evidence of impaired musical sound perception in cochlear-implant users.

Objective: Music perception with a cochlear implant (CI) can be unsatisfactory because current-day implants are primarily designed to enable speech discrimination. The present study aimed at evaluating electrophysiological correlates of musical sound perception in CI users to help achieve the long-term goal of improved restoration of hearing in those individuals.

Methods: Auditory discrimination accuracy in adult CI users (n=12) and matched normal-hearing controls (n=12) was measured by behavioral discrimination tasks and mismatch negativity (MMN) recordings.

Neural adaptation and the ECAP response threshold: a pilot study.

The electrically evoked compound action potential (ECAP) amplitude resulting from a train of pulses of finite duration (100 ms or 200 ms) was found to vary inversely to the stimulation rate (pulse rate), corroborating well with neural adaptation results from a previous study (Dillier et al., 2005). Amplitude growth functions based on these adapted responses yield thresholds (TNRT) that increase with increasing pulse rate, contrary to behavioural thresholds, which are known to vary inversely with the stimulation rate.