Investigation of the Stimulation Capabilities of a High-Resolution Neurorecording Probe for the Application of Closed-Loop Deep Brain Stimulation.

Deep brain stimulation is an established surgical treatment for several neurological and movement disorders, such as Parkinson's disease, in which electrostimulation is applied to targeted deep nuclei in the basal ganglia through implanted electrode leads. Recent technological improvements in the field have focused on the theoretical advantage of current steering and adaptive (closed-loop) deep brain stimulation. Current steering between several active electrodes would allow for improved accuracy when targeting the desired brain structures. This has the additional benefit of avoiding undesired stimulation of neural tracts that are related to side effects, e.g., internal capsule fibres of passage in subthalamic nucleus deep brain stimulation. Closed-loop deep brain stimulation is based on the premise of continuous recording of a proxy for pathological neural activity (such as beta-band power of measured local field potentials in patients with Parkinson's disease) and accordingly adapting the used stimulus parameters. In this study, we investigate the suitability of an existing highresolution neurorecording probe for high-precision neurostimulation. If a subset of the probe's recording electrodes can be used for stimulation, then the probe would be a suitable candidate for closed-loop deep brain stimulation. A finiteelement model is used to calculate the electric potential, induced by current injection through the high-resolution probe, for different sets of active electrodes. Volumes of activated tissue are calculated and a comparison is made between the highresolution probe and a conventional stimulation lead. We investigate the capability of the probe to shift the volume of activated tissue by steering currents to different sets of active electrodes. Finally, safety limits for the injected current are used to determine the size of the volume in which neurons can be activated with the relatively small electrodes patches on the highresolution 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.