Adaptive frequency-domain filtering for neural signal preprocessing.

Electrical interference from various sources is a common issue for experimental extracellular electrophysiology recordings collected using multi-electrode array neural recording systems. This interference deteriorates the signal-to-noise ratio (SNR) of the raw electrophysiology signals and hampers the accuracy of data post-processing using techniques such as spike-sorting. Traditional signal processing methods to digitally remove electrical interference during post-processing include bandpass filtering to limit the signal to the relevant spectral range of the biological data, e.g., the spikes band (300 Hz - 7 kHz), targeted notch filtering to remove power line interference from standard alternating current mains electricity and common reference removal to minimize noise common to all electrodes. These methods require a priori knowledge of the frequency of the interfering signal source to address the unique electromagnetic interference environment of each experimental setup. We discuss an adaptive method for automatically removing narrow-band electrical interference through a spectral peak detection and removal (SPDR) step that can be applied during post-processing of the recorded data, based on the intuition that tall, narrowband signals localized in the signal spectrum correspond to interference, rather than the activity of neurons. A spectral peak prominence (SPP) threshold is used to detect these peaks in the frequency domain, which will then be removed via notch filtering. We applied this method to simulated waveforms and also experimental electrophysiology data collected from cerebral organoids to demonstrate its effectiveness for removing unwanted interference without significantly distorting the neural signals. We discuss that proper selection of the SPP threshold is required to avoid over-filtering, which can result in distortion of the electrophysiology data. We also compare the firing-rate activity in the filtered electrophysiology with fluorescence calcium imaging, a secondary cellular activity marker, to quantify signal distortion and provide bounds on SNR-based optimization of the SPP threshold. The adaptive filtering technique demonstrated in this paper is a powerful method that can automatically detect and remove interband interference in recorded neural signals, potentially enabling data collection in more naturalistic settings where external interference signals are difficult to eliminate.

Bioelectrical interfaces with cortical spheroids in three-dimensions.

Objective.Three-dimensional (3D) neuronal spheroid culture serves as a powerful model system for the investigation of neurological disorders and drug discovery. The success of such a model system requires techniques that enable high-resolution functional readout across the entire spheroid. Conventional microelectrode arrays and implantable neural probes cannot monitor the electrophysiology (ephys) activity across the entire native 3D geometry of the cellular construct.Approach.Here, we demonstrate a 3D self-rolled biosensor array (3D-SR-BA) integrated with a 3D cortical spheroid culture for simultaneousin vitroephys recording, functional Ca2+imaging, while monitoring the effect of drugs. We have also developed a signal processing pipeline to detect neural firings with high spatiotemporal resolution from the ephys recordings based on established spike sorting methods.Main results.The 3D-SR-BAs cortical spheroid interface provides a stable, high sensitivity recording of neural action potentials (<50µV peak-to-peak amplitude). The 3D-SR-BA is demonstrated as a potential drug screening platform through the investigation of the neural response to the excitatory neurotransmitter glutamate. Upon addition of glutamate, the neural firing rates increased notably corresponding well with the functional Ca2+imaging.Significance.Our entire system, including the 3D-SR-BA integrated with neuronal spheroid culture, enables simultaneous ephys recording and functional Ca2+imaging with high spatiotemporal resolution in conjunction with chemical stimulation. We demonstrate a powerful toolset for future studies of tissue development, disease progression, and drug testing and screening, especially when combined with native spheroid cultures directly extracted from humans.