Influence of Auditory Cues on the Neuronal Response to Naturalistic Visual Stimuli in a Virtual Reality Setting

Virtual reality environments offer great opportunities to study the performance of brain-computer interfaces (BCIs) in real-world contexts. As real-world stimuli are typically multimodal, their neuronal integration elicits complex response patterns. To investigate the effect of additional auditory cues on the processing of visual information, we used virtual reality to mimic safety-related events in an industrial environment while we concomitantly recorded electroencephalography (EEG) signals. We simulated a box traveling on a conveyor belt system where two types of stimuli – an exploding and a burning box – interrupt regular operation. The recordings from 16 subjects were divided into two subsets, a visual-only and an audio-visual experiment. In the visual-only experiment, the response patterns for both stimuli elicited a similar pattern – a visual evoked potential (VEP) followed by an event-related potential (ERP) over the occipital-parietal lobe. Moreover, we found the perceived severity of the event to be reflected in the signal amplitude. Interestingly, the additional auditory cues had a twofold effect on the previous findings: The P1 component was significantly suppressed in the case of the exploding box stimulus, whereas the N2c showed an enhancement for the burning box stimulus. This result highlights the impact of multisensory integration on the performance of realistic BCI applications. Indeed, we observed alterations in the offline classification accuracy for a detection task based on a mixed feature extraction (variance, power spectral density, and discrete wavelet transform) and a support vector machine classifier. In the case of the explosion, the accuracy slightly decreased by –1.64% p. in an audio-visual experiment compared to the visual-only. Contrarily, the classification accuracy for the burning box increased by 5.58% p. when additional auditory cues were present. Hence, we conclude, that especially in challenging detection tasks, it is favorable to consider the potential of multisensory integration when BCIs are supposed to operate under (multimodal) real-world conditions

Biocompatible, Flexible, and Oxygen-Permeable Silicone-Hydrogel Material for Stereolithographic Printing of Microfluidic Lab-On-A-Chip and Cell-Culture Devices

We present a photocurable, biocompatible, and flexible silicone-hydrogel hybrid material for stereolithographic (SLA) printing of biomedical devices. The silicone-hydrogel polymer is similar to mixtures used for contact lenses. It is flexible and stretchable with a Young’s modulus of 78 MPa and a maximum elongation at break of 51%, shows a low degree of swelling (<4% v/v) in water, and can be bonded easily to flat glass substrates via a surface-modification method. The in vitro cytotoxicity of the material is assessed with a WST-8 cell viability assay using five different cell lines: HT1080, L929, and Hs27 fibroblasts, cardiomyocyte-like HL-1 cells, and neuronal-phenotype PC-12 cells. On this account, the silicone-hydrogel polymer is compared to several other common SLA printing materials used for cell-culture applications and polydimethylsiloxane (PDMS). A simple extraction step in water is sufficient for reaching biocompatibility of the material with respect to the tested cell types. The oxygen permeability of the silicone-hydrogel material is investigated and compared to that of PDMS, Medicalprint clear—a commercial resin for medical products, and a short-chain hydrogel-based resin. As a proof of concept, we demonstrate a 3D-printed microfluidic device with integrated valves and mixers. Furthermore, we show a printed culture chamber for analyzing signal propagation in HL-1 cardiomyocyte cell networks. Ca2+ imaging is used to observe the signal propagation through the cardiac cell layers grown in the microchannels. The cells are shown to maintain normal electrophysiological activity within the printed chambers. Overall, the biocompatible silicone-hydrogel material will be an advancement for SLA printing in cell-culture and microfluidic lab-on-a-chip applications

Aerosol Jet-Printed High-Aspect Ratio Micro-Needle Electrode Arrays Applied for Human Cerebral Organoids and 3D Neurospheroid Networks

The human brain is a complex and poorly accessible organ. Thus, new tools are required for studying the neural function in a controllable environment that preserves multicellular interaction and neuronal wiring. In particular, high-throughput methods that alleviate the need for animal experiments are essential for future studies. Recent developments of induced pluripotent stem cell technologies have enabled in vitro modeling of the human brain by creating three-dimensional brain tissue mimic structures. To leverage these new technologies, a systematic and versatile approach for evaluating neuronal activity at larger tissue depths within the regime of tens to hundreds of micrometers is required. Here, we present an aerosol-jet- and inkjet-printing-based method to fabricate microelectrode arrays, equipped with high-aspect ratio μ-needle electrodes that penetrate 3D neural network assemblies. The arrays have been successfully applied for electrophysiological recordings on interconnected neurospheroids formed on an engineered substrate and on cerebral organoids, both derived from human induced pluripotent stem cells