High-density silicon probes have transformed neuroscience by enabling large-scale neural recordings at single-cell resolution. However, existing technologies have provided limited functionality in nonhuman primates (NHPs) such as macaques. In the present report, we describe the design, fabrication and performance of Neuropixels 1.0 NHP, a high-channel electrode array designed to enable large-scale acute recording throughout large animal brains. The probe features 4,416 recording sites distributed along a 45-mm shank. Experimenters can programmably select 384 recording channels, enabling simultaneous multi-area recording from thousands of neurons with single or multiple probes. This technology substantially increases scalability and recording access relative to existing technologies and enables new classes of experiments that involve electrophysiological mapping of brain areas at single-neuron and single-spike resolution, measurement of spike–spike correlations between cells and simultaneous brain-wide recordings at scale.
23 September 2019 in IEEE Transactions on Biomedical Circuits and Systems
Although CMOS fabrication has enabled a quick evolution in the design of high-density neural probes and neural-recording chips, the scaling and miniaturization of the complete data-acquisition systems has happened at a slower pace. This is mainly due to the complexity and the many requirements that change depending on the specific experimental settings. In essence, the fundamental challenge of a neural-recording system is getting the signals describing the largest possible set of neurons out of the brain and down to data storage for analysis. This requires a complete system optimization that considers the physical, electrical, thermal and signal-processing requirements, while accounting for available technology, manufacturing constraints and budget. Here we present a scalable and open-standards-based open-source data-acquisition system capable of recording from over 10,000 channels of raw neural data simultaneously. The components and their interfaces have been optimized to ensure robustness and minimum invasiveness in small-rodent electrophysiology.
High-density, integrated silicon electrodes have begun to transform systems neuroscience, by enabling large-scale neural population recordings with single cell resolution. Existing technologies, however, have provided limited functionality in nonhuman primate species such as macaques, which offer close models of human cognition and behavior. Here, we report the design, fabrication, and performance of Neuropixels 1.0-NHP, a high channel count linear electrode array designed to enable large-scale simultaneous recording in superficial and deep structures within the macaque or other large animal brain. These devices were fabricated in two versions: 4416 electrodes along a 45 mm shank, and 2496 along a 25 mm shank. For both versions, users can programmatically select 384 channels, enabling simultaneous multi-area recording with a single probe. We demonstrate recording from over 3000 single neurons within a session, and simultaneous recordings from over 1000 neurons using multiple probes. This technology represents a significant increase in recording access and scalability relative to existing technologies, and enables new classes of experiments involving fine-grained electrophysiological characterization of brain areas, functional connectivity between cells, and simultaneous brain-wide recording at scale.
To understand the neural basis of behavior, it is essential to sensitively and accurately measure neural activity at single neuron and single spike resolution. Extracellular electrophysiology delivers this, but it has biases in the neurons it detects and it imperfectly resolves their action potentials. To minimize these limitations, we developed a silicon probe with much smaller and denser recording sites than previous designs, called Neuropixels Ultra (NP Ultra). This device samples neuronal activity at ultra-high spatial density (~10 times higher than previous probes) with low noise levels, while trading off recording span. NP Ultra is effectively an implantable voltage-sensing camera that captures a planar image of a neuron's electrical field. We use a spike sorting algorithm optimized for these probes to demonstrate that the yield of visually-responsive neurons in recordings from mouse visual cortex improves up to ~3-fold. We show that NP Ultra can record from small neuronal structures including axons and dendrites. Recordings across multiple brain regions and four species revealed a subset of extracellular action potentials with unexpectedly small spatial spread and axon-like features. We share a large-scale dataset of these brain-wide recordings in mice as a resource for studies of neuronal biophysics. Finally, using ground-truth identification of three major inhibitory cortical cell types, we found that these cell types were discriminable with approximately 75% success, a significant improvement over lower-resolution recordings. NP Ultra improves spike sorting performance, detection of subcellular compartments, and cell type classification to enable more powerful dissection of neural circuit activity during behavior.
20 October 2020 in IEEE Solid-State Circuits Letters
In a normally functioning eye, the iris controls the pupil diameter to regulate the amount of light reaching the retina. Various iris deficiencies exist, manifesting as defects in the iris or an absence of one which result in too much light reaching the retina. Some iris deficiencies such as aniridia or leiomyoma can be mitigated with fixed or adaptive artificial irises 1. As an alternative, adaptive transparency glasses may also alleviate this situation, however both solutions do not mimic the other normal functionality of the natural iris: adaptive aperture. To address this, we developed a fully encapsulated, self-contained artificial iris embedded in a smart contact lens. The control ASIC of the contact lens is developed in 0.18 μm 16 V BCD TSMC and has a typical power consumption of 1.9 μW from a 3 V supply voltage at office light condition.
Objective . The analysis of interactions among local populations of neurons in the cerebral cortex (e.g. within cortical microcolumns) requires high resolution and high channel count recordings from chronically implanted laminar microelectrode arrays. The request for high-density recordings of a large number of recording sites can presently only be accomplished by probes realized using complementary metal-oxide-semiconductor (CMOS) technology. In preparation for their use in non-human primates, we aimed for neural probe validation in a head-fixed approach analyzing the long-term recording capability. Approach . We examined chronically implanted silicon-based laminar probes, realized using a CMOS technology in combination with micromachining, to record from the primary visual cortex (V1) of a monkey. We used a passive CMOS probe that had 128 electrodes arranged at a pitch of 22.5 µ m in four columns and 32 rows on a slender shank. In order to validate the performance of a dedicated microdrive, the overall dimensions of probe and interface boards were chosen to be compatible with the final active CMOS probe comprising integrated circuitry. Main results . Using the passive probe, we recorded simultaneously local field potentials (LFP) and spiking multiunit activity (MUA) in V1 of an awake behaving macaque monkey. We found that an insertion through the dura and subsequent readjustments of the chronically implanted neural probe was possible and allowed us to record stable LFPs for more than five months. The quality of MUA degraded within the first month but remained sufficiently high to permit mapping of receptive fields during the full recording period. Significance . We conclude that the passive silicon probe enables semi-chronic recordings of high quality of LFP and MUA for a time span exceeding five months. The new microdrive compatible with a commercial recording chamber successfully demonstrated the readjustment of the probe position while the implemented plug structure effectively reduced brain tissue movement relative to the probe.