The nervous system serves as the primary communication system in animals. Neurons, the fundamental structural and functional units of this system, communicate through a combination of electrical and chemical signals. Deciphering and comprehending diverse neural activities and circuit functions are of paramount importance in the realms of fundamental brain science, the diagnosis and treatment of neurological disorders, and brain-computer interface applications. Integrating optogenetics and electrophysiology into an optoelectric neural interface offers a synergistic approach to studying complex brain circuits and unraveling their intricate dynamics, enabling researchers to observe and modulate neuronal activity with precision. This capability opens new avenues for investigating fundamental questions about how different brain regions communicate and contribute to behavior. By combining optogenetics and electrophysiology to create advanced optoelectric neural interfaces, researchers can gain unprecedented insights into brain functions.

An optogenetic stimulation system was integrated with an electrophysiological recording system to measure photoelectric artifacts. A 473 nm fiber-coupled laser served as the light source for optogenetic stimulation, with a pulse generator employed to control the laser pulses. Electrophysiological signals were recorded using an Intan 1024-channel electrophysiological recording system. The optoelectrodes were fabricated using tapered optical fibers and ultra-flexible electrodes, which were then implanted into either the mouse brain or an agarose gel phantom to capture photoelectric artifacts in vivo or in vitro. The ultra-flexible neural electrode was fabricated using planar semiconductor technology, incorporating a polyimide insulation layer and a gold wire layer, as described in our previous publications. In addition, the electrode surface was modified with PEDOT∶PSS to enhance electrophysiological recording performance. The tapered optical fiber, supplied by Optogenix, featured a numerical aperture (NA) of 0.39, core size of 200 μm, and an active length of 2.5 mm. The optoelectrode probe was assembled by temporarily bonding the optical fiber to the ultra-flexible electrode using polyethylene glycol (PEG, m_PEG=400000 u). The optical performance of the fabricated optoelectrode was characterized through theoretical calculations using LightSpread software, as well as experimental verification in vitro and in vivo. In the in vitro measurements, powdered milk, agarose, and sodium fluorescein were used to simulate tissue scattering and assess the light-field distribution of both tapered and flat port fibers in a scattering medium. For the in vivo demonstrations, optoelectrodes were implanted into the mouse CA1 brain region to perform concurrent optogenetic stimulation and electrical recording. Electrophysiological signals were filtered and analyzed using MATLAB software. The peak value of the photoelectric artifact was defined as the maximum absolute voltage observed during the optical pulse. The power spectral density (PSD) of the local field potentials during optical stimulation was obtained using a short-time Fourier transform, and the Mountainsort4 algorithm was employed for peak potential cluster analysis to isolate the waveform and timestamp of the action potentials.

We designed and fabricated a novel optoelectrode that combines a tapered fiber with an ultra-flexible electrode (Fig. 1). The tapered fibers exhibit an extended illumination range and a more uniform intensity distribution compared to flat-port fibers in a scattering medium (Fig. 2). In vitro experiments reveal variations in photoelectric artifacts across different channels, optical powers, and media types, with the peak values of photoelectric artifacts increasing alongside higher concentrations of milk powder and laser power. Power spectral density analysis indicates that photoelectric artifacts predominantly occur within the frequency range below 10 Hz (Fig. 3). During in vivo experiments, we analyzed the impact of light stimulation on the frequency bands of local field potentials (LFP), ranging from 0 to 300 Hz, and action potentials (AP), ranging from 300 to 7500 Hz. Our findings indicate that photoelectric artifacts primarily affect the LFP signals. Additionally, we longitudinally assessed the impedance evolution of the optoelectrode post-implantation and observed a gradual increase in average impedance during the first week, followed by stabilization over the subsequent three weeks. The peak value of photoelectric artifacts initially increases during the first two weeks, followed by a gradual decline over the next two weeks. Power spectral density analysis reveals that light stimulation predominantly influenced electrophysiological signals below 10 Hz, consistent with the in vitro testing results (Fig. 4). Finally, we validated the capabilities of optogenetic stimulation and synchronous electrophysiological recordings using the optoelectrode.

In this study, we present the design and fabrication of a novel optoelectrode that combines a tapered fiber with an ultra-flexible neural electrode. A comparative analysis of the optical power density and optical field distributions in a scattering medium was conducted between the tapered flat-port fibers, revealing the superior optogenetic stimulation performance of the tapered fiber. Moreover, we investigated the impact of photoelectric artifacts from the optoelectrode on electrophysiological recordings. The in vitro test results reveal variations in photoelectric artifacts across different electrode channels, environmental conditions, and laser powers. In vivo experiments demonstrate that optical stimulation primarily influences the LFP band, whereas the electrochemical impedance of the optoelectrode gradually increases and eventually stabilizes over time. The peak value of photoelectric artifacts varies depending on the duration of implantation. Photoelectric artifacts primarily induce interference within the frequency range below 10 Hz. To mitigate these artifacts, future studies could explore the utilization of coating materials such as PBK, PGO, and Pt-Black/PEDOT-GO. In addition, incorporating principal component analysis or machine learning techniques during data processing, employing a longer-wavelength excitation light source, or adjusting the electrode distance from the light source are all avenues worth investigating.