High-density electrophysiological recordings in macaque using a chronically implanted 128-channel passive silicon probe.

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 µm 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.

A silicon-based neural probe with densely-packed low-impedance titanium nitride microelectrodes for ultrahigh-resolution in vivo recordings.

In this study, we developed and validated a single-shank silicon-based neural probe with 128 closely-packed microelectrodes suitable for high-resolution extracellular recordings. The 8-mm-long, 100-µm-wide and 50-µm-thick implantable shank of the probe fabricated using a 0.13-µm complementary metal-oxide-semiconductor (CMOS) metallization technology contains square-shaped (20 × 20 µm2), low-impedance (~ 50 kΩ at 1 kHz) recording sites made of rough and porous titanium nitride which are arranged in a 32 × 4 dense array with an inter-electrode pitch of 22.5 µm. The electrophysiological performance of the probe was tested in in vivo experiments by implanting it acutely into neocortical areas of anesthetized animals (rats, mice and cats). We recorded local field potentials, single- and multi-unit activity with superior quality from all layers of the neocortex of the three animal models, even after reusing the probe in multiple (> 10) experiments. The low-impedance electrodes monitored spiking activity with high signal-to-noise ratio; the peak-to-peak amplitude of extracellularly recorded action potentials of well-separable neurons ranged from 0.1 mV up to 1.1 mV. The high spatial sampling of neuronal activity made it possible to detect action potentials of the same neuron on multiple, adjacent recording sites, allowing a more reliable single unit isolation and the investigation of the spatiotemporal dynamics of extracellular action potential waveforms in greater detail. Moreover, the probe was developed with the specific goal to use it as a tool for the validation of electrophysiological data recorded with high-channel-count, high-density neural probes comprising integrated CMOS circuitry.

Fully integrated silicon probes for high-density recording of neural activity.

Sensory, motor and cognitive operations involve the coordinated action of large neuronal populations across multiple brain regions in both superficial and deep structures. Existing extracellular probes record neural activity with excellent spatial and temporal (sub-millisecond) resolution, but from only a few dozen neurons per shank. Optical Ca2+ imaging offers more coverage but lacks the temporal resolution needed to distinguish individual spikes reliably and does not measure local field potentials. Until now, no technology compatible with use in unrestrained animals has combined high spatiotemporal resolution with large volume coverage. Here we design, fabricate and test a new silicon probe known as Neuropixels to meet this need. Each probe has 384 recording channels that can programmably address 960 complementary metal-oxide-semiconductor (CMOS) processing-compatible low-impedance TiN sites that tile a single 10-mm long, 70 × 20-µm cross-section shank. The 6 × 9-mm probe base is fabricated with the shank on a single chip. Voltage signals are filtered, amplified, multiplexed and digitized on the base, allowing the direct transmission of noise-free digital data from the probe. The combination of dense recording sites and high channel count yielded well-isolated spiking activity from hundreds of neurons per probe implanted in mice and rats. Using two probes, more than 700 well-isolated single neurons were recorded simultaneously from five brain structures in an awake mouse. The fully integrated functionality and small size of Neuropixels probes allowed large populations of neurons from several brain structures to be recorded in freely moving animals. This combination of high-performance electrode technology and scalable chip fabrication methods opens a path towards recording of brain-wide neural activity during behaviour.