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We present a wireless electro-optic headstage that uses a 0.13- μm CMOS custom integrated circuit (IC) implementing a digital neural decoder (ND-IC) for enabling real-time closed-loop (CL) optogenetics. The ND-IC processes the neural activity data using three digital cores: 1) the detector core detects and extracts the action potential (AP) of individual neurons by using an adaptive threshold; 2) the data compression core compresses the detected AP by using an efficient Symmlet-2 discrete wavelet transform (DWT) processor for decreasing the amount of data to be transmitted by the low-power wireless link; and 3) the classification core sorts the compressed AP into separated clusters on the fly according to their wave shapes. The ND-IC encompasses several innovations: 1) the compression core decreases the complexity from O(n 2 ) to O(n · log(n)) compared to the previous solutions, while using two times less memory, thanks to the use of a new coefficient sorting tree; and 2) the AP classification core reuses both the compressed DWT coefficients to perform implicit dimensionality reduction, which allows for performing intensive signal processing on-chip, while increasing power and hardware efficiency. This core also reuses the signal standard deviation already computed by the AP detector core as threshold for performing automatic AP sorting. The headstage also introduces innovations by enabling a new wireless CL scheme between the neural data acquisition module and the optical stimulator. Our CL scheme uses the AP sorting and timing information produced by the ND-IC for detecting complex firing patterns within the brain. The headstage is also smaller (1.13 cm 3 ), lighter (3.0 g with a 40 mAh battery) and less invasive than the previous solutions, while providing a measured autonomy of 2h40, with the ND-IC. The whole system and the ND-IC are first validated in vivo in the LD thalamus of a Long-Evans rat, and then in freely-moving CL experiments involving a mouse virally expressing ChR2-mCherry in inhibitory neurons of the prelimbic cortex, and the results show that our system works well within an in vivo experimental setting with a freely moving mouse.

Fluorescence biophotometry measurements require wide dynamic range (DR) and high-sensitivity laboratory apparatus. Indeed, it is often very challenging to accurately resolve the small fluorescence variations in presence of noise and high-background tissue autofluorescence. There is a great need for smaller detectors combining high linearity, high sensitivity, and high-energy efficiency. This paper presents a new biophotometry sensor merging two individual building blocks, namely a low-noise sensing front-end and a order continuous-time modulator (CTSDM), into a single module for enabling high-sensitivity and high energy-efficiency photo-sensing. In particular, a differential CMOS photodetector associated with a differential capacitive transimpedance amplifier-based sensing front-end is merged with an incremental order 1-bit CTSDM to achieve a large DR, low hardware complexity, and high-energy efficiency. The sensor leverages a hardware sharing strategy to simplify the implementation and reduce power consumption. The proposed CMOS biosensor is integrated within a miniature wireless head mountable prototype for enabling biophotometry with a single implantable fiber in the brain of live mice. The proposed biophotometry sensor is implemented in a 0.18- CMOS technology, consuming from a 1.8- supply voltage, while achieving a peak dynamic range of over a 50- input bandwidth, a sensitivity of 24 mV/nW, and a minimum detectable current of 2.46- at a 20- sampling rate.

Studying brain activity in vivo requires collecting bioelectrical signals from several microelectrodes simultaneously in order to capture neuron interactions. In this work, we present a new current-reuse analog front-end (AFE), which is scalable to very large numbers of recording channels, thanks to its small implementation silicon area and its low-power consumption. This current-reuse AFE, which is including a low-noise amplifier (LNA) and a programmable gain amplifier (PGA), employs a new fully differential current-mirror topology using fewer transistors, and improving several design parameters, such as power consumption and noise, over previous current-reuse amplifier circuit implementations. We show that the proposed current-reuse amplifier can provide a theoretical noise efficiency factor (NEF) as low as 1.01, which is the lowest reported theoretical NEF provided by an LNA topology. A foue-channel current-reuse AFE implemented in a CMOS 0.18-μm technology is presented as a proof-of-concept. T-network capacitive circuits are used to decrease the size of input capacitors and to increase the gain accuracy in the AFE. The measured performance of the whole AFE is presented. The total power consumption per channel, including the LNA and the PGA stage, is 9 μW (4.5 μW for LNA and 4.5 μW for PGA), for an input referred noise of 3.2 μV rms , achieving a measured NEF of 1.94. The entire AFE presents three selectable gains of 35.04, 43.1, and 49.5 dB, and occupies a die area of 0.072 mm 2 per channel. The implemented circuit has a measured inter-channel rejection ratio of 54 dB. In vivo recording results obtained with the proposed AFE are reported. It successfully allows collecting low-amplitude extracellular action potential signals from a tungsten wire microelectrode implanted in the hippocampus of a laboratory mouse.

This paper presents a wireless headstage with real-time spike detection and data compression for combined optogenetics and multichannel electrophysiological recording. The proposed headstage, which is intended to perform both optical stimulation and electrophysiological recordings simultaneously in freely moving transgenic rodents, is entirely built with commercial off-the-shelf components, and includes 32 recording channels and 32 optical stimulation channels. It can detect, compress and transmit full action potential waveforms over 32 channels in parallel and in real time using an embedded digital signal processor based on a low-power field programmable gate array and a Microblaze microprocessor softcore. Such a processor implements a complete digital spike detector featuring a novel adaptive threshold based on a Sigma-delta control loop, and a wavelet data compression module using a new dynamic coefficient re-quantization technique achieving large compression ratios with higher signal quality. Simultaneous optical stimulation and recording have been performed in-vivo using an optrode featuring 8 microelectrodes and 1 implantable fiber coupled to a 465-nm LED, in the somatosensory cortex and the Hippocampus of a transgenic mouse expressing ChannelRhodospin (Thy1::ChR2-YFP line 4) under anesthetized conditions. Experimental results show that the proposed headstage can trigger neuron activity while collecting, detecting and compressing single cell microvolt amplitude activity from multiple channels in parallel while achieving overall compression ratios above 500. This is the first reported high-channel count wireless optogenetic device providing simultaneous optical stimulation and recording. Measured characteristics show that the proposed headstage can achieve up to 100% of true positive detection rate for signal-to-noise ratio (SNR) down to 15 dB, while achieving up to 97.28% at SNR as low as 5 dB. The implemented prototype features a lifespan of up to 105 minutes, and uses a lightweight (2.8 g) and compact [Formula: see text] rigid-flex printed circuit board.