Neural recording and stimulation using wireless networks of microimplants

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.

Neuromotor prostheses (NMPs) aim to replace or restore lost motor functions in paralysed humans by routeing movement-related signals from the brain, around damaged parts of the nervous system, to external effectors. To translate preclinical results from intact animals to a clinically useful NMP, movement signals must persist in cortex after spinal cord injury and be engaged by movement intent when sensory inputs and limb movement are long absent. Furthermore, NMPs would require that intention-driven neuronal activity be converted into a control signal that enables useful tasks. Here we show initial results for a tetraplegic human (MN) using a pilot NMP. Neuronal ensemble activity recorded through a 96-microelectrode array implanted in primary motor cortex demonstrated that intended hand motion modulates cortical spiking patterns three years after spinal cord injury. Decoders were created, providing a 'neural cursor' with which MN opened simulated e-mail and operated devices such as a television, even while conversing. Furthermore, MN used neural control to open and close a prosthetic hand, and perform rudimentary actions with a multi-jointed robotic arm. These early results suggest that NMPs based upon intracortical neuronal ensemble spiking activity could provide a valuable new neurotechnology to restore independence for humans with paralysis.

1. An array of radio receivers, connected to electrodes in contact with the occipital pole of the right cerebral hemisphere, has been implanted into a 52-year-old blind patient. By giving appropriate radio signals, the patient can be caused to experience sensations of light (;phosphenes') in the left half of the visual field.2. The sensation caused by stimulation through a single electrode is commonly a single very small spot of white light at a constant position in the visual field; but for some electrodes it is two or several such spots, or a small cloud.3. For weak stimuli the map of the visual field on the cortex agrees roughly with the classical maps of Holmes and others derived from war wounds. With stronger stimuli, additional phosphenes appear; these follow a map that is roughly the classical map inverted about the horizontal meridian.4. The phosphenes produced by stimulation through electrodes 2.4 mm apart can be easily distinguished. By stimulation through several electrodes simultaneously, the patient can be caused to see predictable simple patterns.5. The effects of the duration and frequency of stimulating pulses on the threshold have been explored.6. For cortical phosphenes there is no sharp flicker fusion frequency, and probably no flicker fusion frequency at all.7. During voluntary eye movements, the phosphenes move with the eyes. During vestibular reflex eye movements they remain fixed in space.8. Phosphenes ordinarily cease immediately when stimulation ceases, but after strong stimulation they sometimes persist for up to 2 min.9. Our findings strongly suggest that it will be possible, by improving our prototype, to make a useful prosthesis.