The very large electrode array for retinal stimulation (VLARS)-A concept study.

OBJECTIVE: The restoration of vision in blind patients suffering from degenerative retinal diseases like retinitis pigmentosa may be obtained by local electrical stimulation with retinal implants. In this study, a very large electrode array for retinal stimulation (VLARS) was introduced and tested regarding its safety in implantation and biocompatibility. Further, the array's stimulation capabilities were tested in an acute setting. APPROACH: The polyimide-based implants have a diameter of 12 mm, cover approximately 110 mm2 of the retinal surface and carrying 250 iridium oxide coated gold electrodes. The implantation surgery was established in cadaveric porcine eyes. To analyze biocompatibility, ten rabbits were implanted with the VLARS device, and observed for 12 weeks using slit lamp examination, fundus photography, optical coherence tomography (OCT) as well as ultrasound imaging. After enucleation, histological examinations were performed. In acute stimulation experiments, electrodes recorded cortical field potentials upon retinal stimulation in the visual cortex in rabbits. MAIN RESULTS: Implantation studies in rabbits showed that the implantation surgery is safe but difficult. Retinal detachment induced by retinal tears was observed in five animals in varying severity. In five cases, corneal edema reduced the quality of the follow-up examinations. Findings in OCT-imaging and funduscopy suggested that peripheral fixation was insufficient in various animals. Results of the acute stimulation demonstrated the array's ability to elicit cortical responses. SIGNIFICANCE: Overall, it was possible to implant very large epiretinal arrays. On retinal stimulation with the VLARS responses in the visual cortex were recorded. The VLARS device offers the opportunity to restore a much larger field of visual perception when compared to current available retinal implants.

Attention Modulates the Auditory Cortical Processing of Spatial and Category Cues in Naturalistic Auditory Scenes.

This combined fMRI and MEG study investigated brain activations during listening and attending to natural auditory scenes. We first recorded, using in-ear microphones, vocal non-speech sounds, and environmental sounds that were mixed to construct auditory scenes containing two concurrent sound streams. During the brain measurements, subjects attended to one of the streams while spatial acoustic information of the scene was either preserved (stereophonic sounds) or removed (monophonic sounds). Compared to monophonic sounds, stereophonic sounds evoked larger blood-oxygenation-level-dependent (BOLD) fMRI responses in the bilateral posterior superior temporal areas, independent of which stimulus attribute the subject was attending to. This finding is consistent with the functional role of these regions in the (automatic) processing of auditory spatial cues. Additionally, significant differences in the cortical activation patterns depending on the target of attention were observed. Bilateral planum temporale and inferior frontal gyrus were preferentially activated when attending to stereophonic environmental sounds, whereas when subjects attended to stereophonic voice sounds, the BOLD responses were larger at the bilateral middle superior temporal gyrus and sulcus, previously reported to show voice sensitivity. In contrast, the time-resolved MEG responses were stronger for mono- than stereophonic sounds in the bilateral auditory cortices at ~360 ms after the stimulus onset when attending to the voice excerpts within the combined sounds. The observed effects suggest that during the segregation of auditory objects from the auditory background, spatial sound cues together with other relevant temporal and spectral cues are processed in an attention-dependent manner at the cortical locations generally involved in sound recognition. More synchronous neuronal activation during monophonic than stereophonic sound processing, as well as (local) neuronal inhibitory mechanisms in the auditory cortex, may explain the simultaneous increase of BOLD responses and decrease of MEG responses. These findings highlight the complimentary role of electrophysiological and hemodynamic measures in addressing brain processing of complex stimuli.

Altered resonance properties of somatosensory responses in mice deficient for the schizophrenia risk gene Neuregulin 1.

To reveal the neuronal underpinnings of sensory processing deficits in patients with schizophrenia, previous studies have investigated brain activity in response to sustained sensory stimulation at various frequencies. This paradigm evoked neural activity at the stimulation frequency and harmonics thereof. During visual and auditory stimulation that elicited enhanced or 'resonant' responses in healthy controls, patients with schizophrenia displayed reduced activity. The present study sought to elucidate the cellular basis of disease-related deficits in sensory resonance properties using mice heterozygous for the schizophrenia susceptibility gene Neuregulin 1 (NRG1). We applied repetitive whisker stimulation at 1-15 Hz, a range relevant to whisking behavior in mice, and measured cellular activity in the primary somatosensory cortex. At frequencies where control mice displayed enhancements in measures of response magnitude and precision, NRG1 (+/-) mutants showed reductions. Our results demonstrate for the first time a link between a mutation of a schizophrenia risk gene and altered neuronal resonance properties in sensory cortex.

Sensory encoding in Neuregulin 1 mutants.

Schizophrenic patients show altered sensory perception as well as changes in electrical and magnetic brain responses to sustained, frequency-modulated sensory stimulation. Both the amplitude and temporal precision of the neural responses differ in patients as compared to control subjects, and these changes are most pronounced for stimulation at gamma frequencies (20-40 Hz). In addition, patients display enhanced spontaneous gamma oscillations, which has been interpreted as 'neural noise' that may interfere with normal stimulus processing. To investigate electrophysiological markers of aberrant sensory processing in a model of schizophrenia, we recorded neuronal activity in primary somatosensory cortex of mice heterozygous for the schizophrenia susceptibility gene Neuregulin 1. Sensory responses to sustained 20-70 Hz whisker stimulation were analyzed with respect to firing rates, spike precision (phase locking) and gamma oscillations, and compared to baseline conditions. The mutants displayed elevated spontaneous firing rates, a reduced gain in sensory-evoked spiking and gamma activity, and reduced spike precision of 20-40 Hz responses. These findings present the first in vivo evidence of the linkage between a genetic marker and altered stimulus encoding, thus suggesting a novel electrophysiological endophenotype of schizophrenia.