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Emerging applications in brain-machine interface systems require high-resolution, chronic multisite cortical recordings, which cannot be obtained with existing technologies due to high power consumption, high invasiveness, or inability to transmit data wirelessly. In this paper, we describe a microsystem based on electrocorticography (ECoG) that overcomes these difficulties, enabling chronic recording and wireless transmission of neural signals from the surface of the cerebral cortex. The device is comprised of a highly flexible, high-density, polymer-based 64-channel electrode array and a flexible antenna, bonded to 2.4 mm × 2.4 mm CMOS integrated circuit (IC) that performs 64-channel acquisition, wireless power and data transmission. The IC digitizes the signal from each electrode at 1 kS/s with 1.2 μV input referred noise, and transmits the serialized data using a 1 Mb/s backscattering modulator. A dual-mode power-receiving rectifier reduces data-dependent supply ripple, enabling the integration of small decoupling capacitors on chip and eliminating the need for external components. Design techniques in the wireless and baseband circuits result in over 16× reduction in die area with a simultaneous 3× improvement in power efficiency over the state of the art. The IC consumes 225 μW and can be powered by an external reader transmitting 12 mW at 300 MHz, which is over 3× lower than IEEE and FCC regulations.

losed-loop neuromodulation improves open-loop therapeutic electrical stimulation by providing adaptive, on-demand therapy, reducing side effects and extending battery life in wireless devices 1,2. Closing the loop requires low-latency extraction and accurate estimation of neural biomarkers 3-5 from recorded signals to automatically adjust when and how to administer stimulation as feedback to the brain. Recent studies have shown responsive stimulation to be a viable option for treating epilepsy 2,6 , and there is evidence that closed-loop strategies could improve deep brain stimulation (DBS) for treating Parkinson's disease and other motor disorders 7,8. However, there is presently no commercial device allowing closed-loop stimulation for DBS in patients with movement disorders, and strategies for implementing such stimulation are still under investigation. In fact, most attempts to close the loop for DBS treatments have been done only for short duration using systems that were not fully implantable 4,5,9-11. To enable advanced research in closed-loop neuromodulation, there is a need for a flexible research platform, for testing and implementing these various closed-loop paradigms, that is also wireless, compact, robust and safe. Designing such a device requires unification of multi-channel recording, biomarker detection and microstimulation technologies into a single unit with careful consideration of their interactions. Wireless, multi-channel recording-only devices capture activity from wide neuronal populations 12,13 , but do not have the built-in ability to immediately act on that information and deliver stimulation. Several complete closed-loop devices have been proposed and demonstrated, but are limited by low channel counts 14-17 and low wireless streaming bandwidth 14-18. Most recently, variations of the fully integrated and optimized closed-loop neuromodulation system-on-a-chip (SoC) have been presented, but full system functionality has not yet been adequately demonstrated in vivo 19-25. While future versions may be paired with miniaturized external battery packs and controllers, current systems built around these SoCs require large, stationary devices to deliver power inductively from a close range 19,21,23. This limits studies to using small, caged animals. Furthermore, any device for concurrent sensing and stimulation must be able to mitigate or remove stimulation artefactsthe large voltage transients resulting from stimulation that distort recorded signals and obscure neural biomarkers. Signals recorded concurrently with stimulation may contain relevant information for closed-loop algorithms or offline analysis, yet existing devices disregard these affected windows of data, or fail to reduce artefacts to an acceptable level for recovery of many potentially useful biomarker features. Effectively and efficiently cancelling artefacts requires careful co-design of the stimulators and signal acquisition chains. Additionally, computational reprogrammability is needed for application-dependent algorithm de...

Closed-loop and responsive neuromodulation systems improve open-loop neurostimulation by responding directly to measured neural activity and providing adaptive, on-demand therapy. To be effective, these systems must be able to simultaneously record and stimulate neural activity, a task made difficult by persistent stimulation artifacts that distort and obscure underlying biomarkers. To enable simultaneous stimulation and recording, several techniques have been proposed. These techniques involve artifact-preventing system configurations, resilient recording front-ends, and back-end signal processing for removing recorded artifacts. Co-designing and integrating these artifact cancellation techniques will be key to enabling neuromodulation systems to stimulate and record at the same time. Here, we review the state-of-the-art for these techniques and their role in achieving artifact-free neuromodulation.

A 0.8 mm 3 wireless, ultrasonically powered, freefloating neural recording implant is presented. The device is comprised only of a 0.25 mm 2 recording IC and a single piezoceramic resonator that is used for both power harvesting and data transmission. Uplink data transmission is performed by analog amplitude modulation of the ultrasound echo. Using a 1.78 MHz main carrier, >35 kbps/mote equivalent uplink data rate is achieved. A technique to linearize the echo amplitude modulation is introduced, resulting in <1.2% static nonlinearity of the received signal over a ±10 mV input range. The IC dissipates 37.7 µW, while the neural recording front-end consumes 4 µW and achieves a noise floor of 5.3 µVrms in a 5 kHz bandwidth. This work improves sub-mm recording mote depth by >2.5x, resulting in the highest measured depth/volume ratio by ∼3x. Orthogonal subcarrier modulation enables simultaneous operation of multiple implants, using a single-element ultrasound external transducer. Dual-mote simultaneous power up and data transmission is demonstrated at a rate of 7 kS/s at the depth of 50 mm.

We present an 180nm HV CMOS IC for concurrent neural stimulation and recording that combines 64 low-noise recording front-ends and 4 independent stimulators multiplexed to any of the 64 channels. The stimulators have 5mA peak current, 12V compliance and dynamic power management to maximize efficiency. Co-design of the stimulation and recording subsystems resulted in 100mV of recording linear range, 70nV/rtHz noise, and a rapid 1ms (single-sample) artifact recovery during stimulation.

We present a 6.5mm 3 , 10mg, wireless peripheral nerve stimulator. The stimulator is powered and controlled through ultrasound from an external transducer and utilizes a single 750x750x750µm 3 piezocrystal for downlink communication, powering, and readout, reducing implant volume and mass. An IC with 0.06mm 2 active circuit area, designed in TSMC 65nm LPCMOS process, converts harvested ultrasound to stimulation charge with a peak efficiency of 82%. A custom wireless protocol that does not require a clock or memory circuits reduces on-chip power to 4µW when not stimulating. The encapsulated stimulator was cuffed to the sciatic nerve of an anesthetized rodent and demonstrated full-scale nerve activation in vivo. We achieve a highly efficient and temporally precise wireless peripheral nerve stimulator that is the smallest and lightest to our knowledge.