Neuromodulation technologies are progressing from pacemaking and sensory operations to full closed-loop control. In particular, optogenetics-the genetic modification of light sensitivity into neural tissue allows for simultaneous optical stimulation and electronic recording. This paper presents a neural interface application-specified integrated circuit (ASIC) for intelligent optoelectronic probes. The architecture is designed to enable simultaneous optical neural stimulation and electronic recording. It provides four low noise (2.08  μV) recording channels optimized for recording local field potentials (LFPs) (0.1-300 Hz bandwidth, 5 mV range, sampled 10-bit@4 kHz), which are more stable for chronic applications. For stimulation, it provides six independently addressable optical driver circuits, which can provide both intensity (8-bit resolution across a 1.1 mA range) and pulse-width modulation for high-radiance light emitting diodes (LEDs). The system includes a fully digital interface using a serial peripheral interface (SPI) protocol to allow for use with embedded controllers. The SPI interface is embedded within a finite state machine (FSM), which implements a command interpreter that can send out LFP data whilst receiving instructions to control LED emission. The circuit has been implemented in a commercially available 0.35  μm CMOS technology occupying a 1.95 mm 1.10 mm footprint for mounting onto the head of a silicon probe. Measured results are given for a variety of bench-top, in vitro and in vivo experiments, quantifying system performance and also demonstrating concurrent recording and stimulation within relevant experimental models.

The coming years may see the advent of distributed implantable devices to support bioelectronic medicinal treatments. Communication between implantable components and between deep implants and the outside world can be challenging. Percutaneous wired connectivity is undesirable and both radiofrequency and optical methods are limited by tissue absorption and power safety limits. As such, there is a significant potential niche for ultrasound communications in this domain. In this paper, we present the design and testing of a reliable and efficient ultrasonic communication telemetry scheme using piezoelectric transducers that operate at 320 kHz frequency.A key challenge results from the multi-propagation path effect. Therefore, we present a method, using short pulse sequences with relaxation intervals. To counter an increasing bit, and thus packet, error rate with distance, we have incorporated an error correction encoding scheme. We then demonstrate how the communication scheme can scale to a network of implantable devices. We demonstrate that we can achieve an effective, error-free, data rate of 0.6 kbps, which is sufficient for low data rate bioelectronic medicine applications. Transmission can be achieved at an energy cost of 642 nJ per bit data packet using on/off power cycling in the electronics. achieve therapy. However, an important development is to progress from open-loop, pacemaker type, stimuli to closed-loop control methodologies which modify therapeutic stimuli according to need. Such systems will therefore also need sensors from perhaps downstream organs which can provide physiological information. Examples include blood oxygen and glucose levels, heart rate, chemical sensing, mechanical motion, and bioelectronic activity [7,8].Bioelectronic therapies would need to comprise an active implant (Active Implantable Medical Device or AIMD) which can gather information, perform processing and determine stimulus. As downstream organs are geographically separated by tens of centimeters, a possible architecture is for a central implant unit together with satellite units called bioelectronic nodes (BeNs) which provide sensing and perhaps stimulation. This configuration can be seen in Figure 1. Ideally, such bioelectronic nodes would be injected to their target locations rather than be surgically inserted. As such, the devices would need to be in the mm size range. Such devices would have small batteries and thus be limited in operation. i.e., duty cycles would be for a few milliseconds each hour or day. However, such operation is sufficient for bioelectronic therapies which only need to infrequently monitor physiological responses.

Neuromodulation is an established treatment for numerous neurological conditions, but to expand the therapeutic scope there is a need to improve the spatial, temporal and cell-type specificity of stimulation. Optogenetics is a promising area of current research, enabling optical stimulation of genetically-defined cell types without interfering with concurrent electrical recording for closed-loop control of neural activity. We are developing an open-source system to provide a platform for closed-loop optogenetic neuromodulation, incorporating custom integrated circuitry for recording and stimulation, real-time closed-loop algorithms running on a microcontroller and experimental control via a PC interface. We include commercial components to validate performance, with the ultimate aim of translating this approach to humans. In the meantime our system is flexible and expandable for use in a variety of preclinical neuroscientific applications. The platform consists of a Controlling Abnormal Network Dynamics using Optogenetics (CANDO) Control System (CS) that interfaces with up to four CANDO headstages responsible for electrical recording and optical stimulation through custom CANDO LED optrodes. Control of the hardware, inbuilt algorithms and data acquisition is enabled via the CANDO GUI (Graphical User Interface). Here we describe the design and implementation of this system, and demonstrate how it can be used to modulate neuronal oscillations in vitro and in vivo.

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