Psychophysical measures of tonotopic selectivity in cats and humans

Sound spectra are represented by patterns of activity along the tonotopic axis ofthe cochlea. Cochlear implants can transmit spectra by stimulating tonotopicallyappropriate electrodes, but fidelity is limited by intracochlear spread of excitation. We aim to better evaluate present-day experimental stimulation procedures and, potentially, to improve transmission of spectra with novel stimulation modalities. As a first step, we are developing non-invasive measures of tonotopic spread of excitation that can be compared between normal-hearing cats and humans. These measures include psychophysics in the present study and scalp-recorded electrophysiology in a companion study (Guérit et al., 2021). Cats and humans detected pure-tone probes presented in continuous 1/8- and 1-oct noise-band maskers. Masker bandwidths were readily discernable in both species by the dependence of masked thresholds on probe frequencies. Thresholds were largely constant across the bandwidth of the 1-oct masker, whereas thresholds dropped markedly at frequencies away from the center of the 1/8-oct masker. Cats and humans differed in that the feline auditory filter centered on 8 kHz, which we measured using a notched-noise procedure, was 22% wider than published values for humans at the same center frequency. Also, thresholds for the cats in the 1-octmasker condition consistently were 1.0 to 3.2 dB higher than expected based on the estimated masker power in the feline auditory filter. The present psychophysical results parallel those in our companion electrophysiological study, thereby providing perceptual validation for that study. These psychophysical and electrophysiological methods will be valuable for future investigations of novel approaches for auditory prosthesis.

Clinical Pharmacology and Therapeutics of Antiepileptic Drugs

This article describes clinical antiepileptic drugs (AEDs) that are available for treatment of epilepsy. Epilepsy is characterized by repeated occurrence of seizures. Epileptic seizures are classified into focal onset (partial) and generalized onset (generalized) types. Around two-dozen AEDs are available for treating epilepsy. AEDs act on diverse molecular targets to selectively modify the abnormal excitability of neurons by reducing the focal seizure discharges or preventing spread of excitation. AEDs suppress seizures by blocking the voltage-gated sodium channels (phenytoin, carbamazepine, valproate, lamotrigine, oxcarbazepine, topiramate), voltage-activated calcium channels (ethosuximide, gabapentin), potentiation of GABA inhibition (barbiturates, benzodiazepines, tiagabine), and reduction of glutamate excitation (felbamate, parampanel). Carbamazepine, phenytoin, and valproate are the first-line agents for partial onset seizures and generalized onset seizures. Ethosuximide is the drug of choice for absence seizures. AEDs are orally-active and show unique PK features. Some AEDs cause enzyme induction and hence produce drug-drug interactions. Newer AEDs such as gabapentin, levetiracetam, tiagabine, and pregabalin do not cause enzyme induction. Despite many advances in AEDs, nearly 30% of people with epilepsy have drug-resistant or intractable seizures. Presently, there is no cure for epilepsy. Thus, newer and better AEDs that can better prevent refractory seizures and modify the disease are needed for curing epilepsy.

Electrical Vestibular Stimulation in Humans: A Narrative Review

Background: In patients with bilateral vestibulopathy, the regular treatment options, such as medication, surgery, and/or vestibular rehabilitation, do not always suffice. Therefore, the focus in this field of vestibular research shifted to electrical vestibular stimulation (EVS) and the development of a system capable of artificially restoring the vestibular function. Key Message: Currently, three approaches are being investigated: vestibular co-stimulation with a cochlear implant (CI), EVS with a vestibular implant (VI), and galvanic vestibular stimulation (GVS). All three applications show promising results but due to conceptual differences and the experimental state, a consensus on which application is the most ideal for which type of patient is still missing. Summary: Vestibular co-stimulation with a CI is based on “spread of excitation,” which is a phenomenon that occurs when the currents from the CI spread to the surrounding structures and stimulate them. It has been shown that CI activation can indeed result in stimulation of the vestibular structures. Therefore, the question was raised whether vestibular co-stimulation can be functionally used in patients with bilateral vestibulopathy. A more direct vestibular stimulation method can be accomplished by implantation and activation of a VI. The concept of the VI is based on the technology and principles of the CI. Different VI prototypes are currently being evaluated regarding feasibility and functionality. So far, all of them were capable of activating different types of vestibular reflexes. A third stimulation method is GVS, which requires the use of surface electrodes instead of an implanted electrode array. However, as the currents are sent through the skull from one mastoid to the other, GVS is rather unspecific. It should be mentioned though, that the reported spread of excitation in both CI and VI use also seems to induce a more unspecific stimulation. Although all three applications of EVS were shown to be effective, it has yet to be defined which option is more desirable based on applicability and efficiency. It is possible and even likely that there is a place for all three approaches, given the diversity of the patient population who serves to gain from such technologies.