Preclinical safety study of a fully implantable, sub-scalp ring electrode array for long-term EEG recordings.

OBJECTIVE: Long-term electroencephalogram (EEG) recordings can aid diagnosis and management of various neurological conditions such as epilepsy. In this study we characterize the safety and stability of a clinical grade ring electrode arrays by analyzing EEG recordings, fluoroscopy, and computed tomography (CT) imaging with long-term implantation and histopathological tissue response. APPROACH: Seven animals were chronically implanted with EEG recording array consisting of four electrode contacts. Recordings were made bilaterally using a bipolar longitudinal montage. The array was connected to a fully implantable micro-processor controlled electronic device with two low-noise differential amplifiers and a transmitter-receiver coil. An external wearable was used to power, communicate with the implant via an inductive coil, and store the data. The sub-scalp electrode arrays were made using medical grade silicone and platinum. The electrode arrays were tunneled in the subgaleal cleavage plane between the periosteum and the overlying dermis. These were implanted for 3-7 months before euthanasia and histopathological assessment. EEG and impedance were recorded throughout the study. MAIN RESULTS: Impedance measurements remained low throughout the study for 11 of 12 channels over the recording period ranged from 3 to 5 months. There was also a steady amplitude of slow-wave EEG and chewing artifact (noise). The post-mortem CT and histopathology showed the electrodes remained in the subgaleal plane in 6 of 7 sheep. There was minimal inflammation with a thin fibrotic capsule that ranged from 4 to 101µm. There was a variable fibrosis in the subgaleal plane extending from 210 to 3617µm (S3-S7) due to surgical cleavage. One sheep had an inflammatory reaction due to electrode extrusion. The passive electrode array extraction force was around 1N. SIGNIFICANCE: Results show sub-scalp electrode placement was safe and stable for long term implantation. This is advantageous for diagnosis and management of neurological conditions where long-term, EEG monitoring is required.

Behavioral frequency discrimination ability of partially deafened cats using cochlear implants.

The aim of this study was to determine the effects of cochlear implant (CI) use on behavioral frequency discrimination ability in partially deafened cats. We hypothesized that the additional information provided by the CI would allow subjects to perform better on a frequency discrimination task. Four cats with a high frequency hearing loss induced by ototoxic drugs were first trained on a go/no-go, positive reinforcement, frequency discrimination task and reached asymptotic performance (measured by d' - detection theory). Reference frequencies (1, 4, and 7 kHz) were systematically rotated (Block design) every 9-11 days to cover the hearing range of the cats while avoiding bias arising from the order of testing. Animals were then implanted with an intracochlear electrode array connected to a CI and speech processor. They then underwent 6 months of continuous performance measurement with the CI turned on, except for one month when the stimulator was turned off. Overall, subjects performed the frequency discrimination task significantly better with their CI turned on than in the CI-off condition (3-way ANOVA, p < 0.001). The analysis showed no dependence on subject (3-way ANOVA, subject × on-off condition, p > 0.5); however, the CI only significantly improved performance for two (1 and 7 kHz) of the three reference frequencies. In this study we were able to show, for the first time, that cats can utilize information provided by a CI in performing a behavioral frequency discrimination task.

An automated psychoacoustic testing apparatus for use in cats.

Animal behavioral studies make a significant contribution to hearing research and provide vital information which is not available from human subjects. Animal psychoacoustics is usually extremely time consuming and labor intensive; in addition, animals may become stressed, especially if restraints or negative reinforcers such as electric shocks are used. We present a novel behavioral experimental system that was developed to allow efficient animal training in response to acoustic stimuli. Cats were required to perform a relatively simple task of moving toward and away from the device depending on whether the members of a tone pair were different or the same in frequency (go/no-go task). The experimental setup proved to be effective, with all animals (N = 7) performing at above 90% correct on an easy task. Animals were trained within 2-4 weeks and then generated a total of 150-200 trials per day, distributed within approximately 8 self initiated sessions. Data collected using this system were stable over 1 week and repeatable over long test periods (14 weeks). Measured frequency discrimination thresholds from 3 animals at 3 different reference frequencies were comparable with previously published results. The main advantages of the system are: relatively simple setup; large amounts of data can be generated without the need of researcher supervision; multiple animals can be tested simultaneously without removal from home pens; and no electric shocks or restraints are required.