The combination of in vivo extracellular recording and genetic-engineering-assisted optical stimulation is a powerful tool for the study of neuronal circuits. Precise analysis of complex neural circuits requires high-density integration of multiple cellular-size light sources and recording electrodes. However, high-density integration inevitably introduces stimulation artifact. We present minimal-stimulation-artifact (miniSTAR) μLED optoelectrodes that enable effective elimination of stimulation artifact. A multi-metal-layer structure with a shielding layer effectively suppresses capacitive coupling of stimulation signals. A heavily boron-doped silicon substrate silences the photovoltaic effect induced from LED illumination. With transient stimulation pulse shaping, we reduced stimulation artifact on miniSTAR μLED optoelectrodes to below 50 μVpp, much smaller than a typical spike detection threshold, at optical stimulation of >50 mW mm–2irradiance. We demonstrated high-temporal resolution (<1 ms) opto-electrophysiology without any artifact-induced signal quality degradation during in vivo experiments. MiniSTAR μLED optoelectrodes will facilitate functional mapping of local circuits and discoveries in the brain.
Dynamic interactions within and across brain areas underlie behavioral and cognitive functions. To understand the basis of these processes, the activities of distributed local circuits inside the brain of a behaving animal must be synchronously recorded while the inputs to these circuits are precisely manipulated. Even though recent technological advances have enabled such large‐scale recording capabilities, the development of the high‐spatiotemporal‐resolution and large‐scale modulation techniques to accompany those recordings has lagged. A novel neural probe is presented in this work that enables simultaneous electrical monitoring and optogenetic manipulation of deep neuronal circuits at large scales with a high spatiotemporal resolution. The “hectoSTAR” micro‐light‐emitting‐diode (μLED) optoelectrode features 256 recording electrodes and 128 stimulation μLEDs monolithically integrated on the surface of its four 30‐µm thick silicon micro‐needle shanks, covering a large volume with 1.3‐mm × 0.9‐mm cross‐sectional area located as deep as 6 mm inside the brain. The use of this device in behaving mice for dissecting long‐distance network interactions across cortical layers and hippocampal regions is demonstrated. The recording‐and‐stimulation capabilities hectoSTAR μLED optoelectrodes enables will open up new possibilities for the cellular and circuit‐based investigation of brain functions in behaving animals.
16 July 2018 in IEEE Transactions on Biomedical Circuits and Systems
This work presents a fully integrated neural interface system in a small form factor (1.9 g), consisting of a μLED silicon optoelectrode (12 μLEDs and 32 recording sites in a 4-shank configuration), an Intan 32-channel recording chip, and a custom optical stimulation chip for controlling 12 μLEDs. High-resolution optical stimulation with approximately 68.5 nW radiant flux resolution is achieved by a custom LED driver ASIC, which enables individual control of up to 48 channels with a current precision of 1 μA, a maximum current of 1.024 mA, and an update rate of >10 kHz. Recording is performed by an off-the-shelf 32-channel digitizing front-end ASIC from Intan. Two compact custom interface printed circuit boards were designed to link the headstage with a PC. The prototype system demonstrates precise current generation, sufficient optical radiant flux generation $({\Phi _e} > \text{0.16}\, \mu \text{W})$ , and fast turn-on of μLEDs $(t_{{\rm{rise}}} < \text{10}\, \mu \text{s})$ . Single animal in vivo experiments validated the headstage's capability to precisely modulate single neuronal activity and independently modulate activities of separate neuronal populations near neighboring optoelectrode shanks.
The minimal invasiveness of electrocorticography (ECoG) enabled its widespread use in clinical areas as well as in neuroscience research. However, most existing ECoG arrays require that the entire surface area of the brain that is to be recorded be exposed through a large craniotomy. We propose a device that overcomes this limitation, i.e., a minimally invasive, polyimide-based flexible array of electrodes that can enable the recording of ECoG signals in multiple regions of the brain with minimal exposure of the surface of the brain. Magnetic force-assisted positioning of a flexible electrode array enables recording from distant brain regions with a small cranial window. Also, a biodegradable organic compound used for attaching a magnet on the electrodes allows simple retrieval of the magnet. We demonstrate with an in vivo chronic recording that an implanted ECoG electrode array can record ECoG signals from the visual cortex and the motor cortex during a rat's free behavior. Our results indicate that the proposed device induced minimal damage to the animal. We expect the proposed device to be utilized for experiments for large-scale brain circuit analyses as well as clinical applications for intra-operative monitoring of epileptic activity.
We report an energy-efficient, cancellation-free, bit-wise time-division duplex (B-TDD) transceiver (TRX) for real-time closed-loop control of high channel count neural interfaces. The proposed B-TDD architecture consists of a duty-cycled ultra-wide band (UWB) transmitter (3.1−5 GHz) and a switching U-NII band (5.2 GHz) receiver. An energy-efficient duplex is realized in a single antenna without power-hungry self-interference cancellation circuits which are prevalently used in the conventional full-duplex, single antenna transceivers. To suppress the interference between up- and down-links and enhance the isolation between the two, we devised a fast-switching scheme in a low noise amplifier and used 5× oversampling with a built-in winner-take-all voting in the receiver. The B-TDD transceiver was fabricated in 65 nm CMOS RF process, achieving low energy consumption of 0.32 nJ/b at 10 Mbps in the receiver and 9.7 pJ/b at 200 Mbps in the transmitter, respectively. For validation, the B-TDD TRX has been integrated with a μLED optoelectrode and a custom analog frontend integrated circuit in a prototype wireless bidirectional neural interface system. Successful in-vivo operation for simultaneously recording broadband neural signals and optical stimulation was demonstrated in a transgenic rodent.