Optical Neural Recording Research Articles

Implantable graded-index fibers for neural-dynamics-resolving brain imaging in awake mice on an air-lifted platform.

We demonstrate a versatile framework for cellular brain imaging in awake mice based on suitably tailored segments of graded-index (GRIN) fiber. Closed-form solutions to ray-path equations for graded-index waveguides are shown to offer important insights into image-transmission properties of GRIN fibers, suggesting useful recipes for optimized GRIN-fiber-based deep-brain imaging. We show that the lengths of GRIN imaging components intended for deep-brain studies in freely moving rodents need to be chosen as a tradeoff among the spatial resolution, the targeted imaging depth and the degree of fiber-probe invasiveness. In the experimental setting that we present in this paper, the head of an awake mouse with a GRIN-fiber implant is fixed under a microscope objective, but the mouse is free to move around an in-house-built flat-floored air-lifted platform, exploring a predesigned environment, configured as an arena for one of standard cognitive tests. We show that cellular-resolution deep-brain imaging can be integrated in this setting with robust cell-specific optical neural recording to enable in vivo studies with minimal physical restraints on animal models. The enhancement of the information capacity of the fluorescence signal, achieved via a suitable filtering of the GRIN-fiber readout, is shown to open routes toward practical imaging modalities whereby the deep-brain neuronal dynamics and axonal connections underpinning the integrative functions of essential brain structures can be studied in awake rodent models.

Semi‐Transparent, Micrometer Resolution p‐NiO/n‐ZnO Heterojunction Diode Temperature Sensors with Ultrathin Metal Anode

AbstractVarious temperature sensitive biological mechanisms have been utilized for new biomedical engineering tools such as neuromodulation, cancer cell hyperthermia or photothermal therapy. Optically transparent and high spatio‐temporal resolution temperature sensors are needed to precisely analyze the biological effects that occur in response to the temperature changes. In this work, semi‐transparent p‐NiO/n‐ZnO heterojunction diode‐based temperature sensors with 100 µm‐diameter ultrathin transparent Au/Ag metal anodes is introduced. The fabricated diode temperature sensors accurately measure temperature changes from 25 to 80 °C, which is of significant interest in many biomedical engineering applications. The sensors also exhibit adequate transparency over the entire visible light spectrum for biomedical imaging including fluorescent microscopy. Low‐power operation of the temperature sensor (<0.2 nW) is achieved to avoid a self‐heating effect. The micro‐scale spatial resolution of the transparent temperature sensors is especially useful for cellular resolution bio‐imaging, optical neural recording, and optical bio‐modulation where transparency and high‐resolution temperature sensing are necessary.

A Mechanically Flexible, Implantable Neural Interface for Computational Imaging and Optogenetic Stimulation Over 5.4×5.4mm2 FoV.

Emerging optical functional imaging and optogenetics are among the most promising approaches in neuroscience to study neuronal circuits. Combining both methods into a single implantable device enables all-optical neural interrogation with immediate applications in freely-behaving animal studies. In this paper, we demonstrate such a device capable of optical neural recording and stimulation over large cortical areas. This implantable surface device exploits lens-less computational imaging and a novel packaging scheme to achieve an ultra-thin (250μm-thick), mechanically flexible form factor. The core of this device is a custom-designed CMOS integrated circuit containing a 160×160 array of time-gated single-photon avalanche photodiodes (SPAD) for low-light intensity imaging and an interspersed array of dual-color (blue and green) flip-chip bonded micro-LED (μLED) as light sources. We achieved 60μm lateral imaging resolution and 0.2mm3 volumetric precision for optogenetics over a 5.4×5.4mm2 field of view (FoV). The device achieves a 125-fps frame-rate and consumes 40 mW of total power.

Resolving neural states from optical neural response readout

We examine two types of information loss function encountered in optical neural recording—the uncertainty of neural states encoding an external stimulus and the incompleteness of information that laser-excited fluorescence can read out from these neural states. We show that, even though these uncertainties are of distinctly different nature, they can be treated on an equal footing against the Fisher information metric, revealing the fundamental information limits inherent in optical neural recording.

Light-induced uncertainty and information limits of optical neural recording

Cutting-edge methods of laser microscopy combined with fluorescent protein engineering and spectral analysis provide a unique resource for high-resolution neuroimaging, enabling a high-fidelity, high-contrast detection of fine structural details of neural cells and intracellular compartments. In addition to their extraordinary imaging abilities in real space, such methods can help resolve the neural states in a multidimensional space of neural responses whereby individual neurons and neural populations encode information on external stimuli. This study shows, however, that laser-induced biochemical processes in neural cells can give rise to an uncertainty of neural states, setting an upper bound on the information that optical measurements can provide on neural states, neural encodings, and neural dynamics. Comparison of absorbed laser power with the native biochemical energy budget of neuronal firing suggests that each readout photon in optical recording comes at a cost of precision of neural encoding and a loss of information encoded by the neural response. A quantitative measure for such a measurement-induced neural uncertainty can be defined, as this study shows, in terms of the Fisher information, relating the lower bound of this uncertainty to the loss of the Shannon information capacity of neural states.

Phase-sensitive optical neural recording of cerebellum tissue on a flexible interface

Knowing an increased number of patients suffering from mental disorders, neural signal recording and imaging have become highly prerequisite challenges for providing healing procedures. Despite the fact that novel optical techniques provide highly resolved imaging/recording of large neuron population, most of them suffer from insertion damage, tethering connection, labeling, and photobleaching deficiencies, among which plasmonic ellipsometry is a highly sensitive and label-free platform for detecting neural activity both quantitatively and qualitatively. In this paper, a flexible patterned plasmonic substrate is used as a sensing surface for phase-sensitive neural recording of a cerebellum tissue slice under electrical and chemical stimulations. Although the traditional reflection spectrum cannot represent the changes in neural activity with high precision, phase-sensitive neuroplasmonics can not only reveal the neural activity level but also distinguish different electrical and chemical stimulation types with a considerable phase splitting factor. This study can open up a new insight into label-free and flexible biological sensors with neuroscience applications.

High-Yield Passive Si Photodiode Array Towards Optical Neural Recording

Emerging fluorescent protein-based sensors allow researchers to monitor neural activities via optical recording of the fluorescence signals. This optical method is able to monitor multiple cell signals with ease in identifying individual cells in dense neurocircuitry. To this end, we demonstrate a high-yield passive Si photodiode array, aiming to establish a miniaturized optical recording device toward in-vivo use. Our fabricated array features a high yield (>90%), low detection limit (32 $\mu {\text{W}}$ /cm2), and high speed (1000 frames per second for scanning up to 100 pixels). Using a fast I–V measurement setup, we examined the device performance in terms of detection limit and speed. A mapping of the light intensity on the entire array manifests its promise as an on-chip fluorescence imager for optical neural recording. The array routinely consumes sub- $10~\mu {\text{W}}$ power, which is suitable for chronic in vivo use.

Bioinspired Polarization Imaging Sensors: From Circuits and Optics to Signal Processing Algorithms and Biomedical Applications: Analysis at the focal plane emulates nature's method in sensors to image and diagnose with polarized light.

In this paper, we present recent work on bioinspired polarization imaging sensors and their applications in biomedicine. In particular, we focus on three different aspects of these sensors. First, we describe the electro-optical challenges in realizing a bioinspired polarization imager, and in particular, we provide a detailed description of a recent low-power complementary metal-oxide-semiconductor (CMOS) polarization imager. Second, we focus on signal processing algorithms tailored for this new class of bioinspired polarization imaging sensors, such as calibration and interpolation. Third, the emergence of these sensors has enabled rapid progress in characterizing polarization signals and environmental parameters in nature, as well as several biomedical areas, such as label-free optical neural recording, dynamic tissue strength analysis, and early diagnosis of flat cancerous lesions in a murine colorectal tumor model. We highlight results obtained from these three areas and discuss future applications for these sensors.

In-vivo Optical Measurement of Neural Activity in the Brain

The optical neural recording techniques are promising tools in recent years. Compared to the traditional electrophysiological recording, the optical means offer several advantages including no inclusion of electrical noise, simultaneous imaging of a large number of neurons, or selective recording from genetically-targeted neurons. Overall the optical neural recording technique comprises the intrinsic and the extrinsic optical recordings. The methods for intrinsic neural recording employ the change of optical properties in brains such as blood flow/oxygenation, cellular volume change, or refractive index change without addition of external indicators. Those properties can be detected using various optical techniques including laser Doppler flowmetry (LDF), near-infrared (NIR) spectrometer, functional optical coherence tomography (fOCT), and surface plasmon resonance (SPR). The extrinsic monitoring techniques use fluorescence signals reflecting neuronal activity via chemical or genetic modification of the neuronal cells. Two most popular activity-dependent fluorescent probes, calcium indicators and voltage-sensitive fluorescent proteins will be examined in this review. The principles, the instrumentations and in vivo applications of those optical signal measurements are described.

In vivo optical neural recording using fiber-based surface plasmon resonance

We propose an intrinsic optical method for in vivo neural recording using optic fiber-based surface plasmon resonance (SPR) phenomena. The fiber-based SPR method is electrical artifact free, labeling free, and feasible for a portable system compared with conventional in vivo neural recording systems. We simultaneously detected SPR signals and electrical neural activity from the rat somatosensory cortex evoked by electrical stimulation on the forepaw. Pharmacological analysis using a voltage-gated sodium channel blocker confirmed the neural origins of the optical signals. This fiber-based SPR system promises the enhanced ability to record in vivo neural activity for the investigation of neurons and their networks.

Head-mountable high speed camera for optical neural recording

We report a head-mountable CMOS camera for recording rapid neuronal activity in freely moving rodents using fluorescent activity reporters. This small, lightweight camera is capable of detecting small changes in light intensity (0.2% Δ I/ I) at 500 fps. The camera has a resolution of 32 × 32, sensitivity of 0.62 V/lx s, conversion gain of 0.52 μV/e − and well capacity of 2.1 Me −. The camera, containing intensity offset subtraction circuitry within the imaging chip, is part of a miniaturized epi-fluorescent microscope and represents a first generation, mobile scientific-grade, physiology imaging camera.

In vitro and in vivo noise analysis for optical neural recording

Laser diodes (LD) are commonly used for optical neural recordings in chronically recorded animals and humans, primarily due to their brightness and small size. However, noise introduced by LDs may counteract the benefits of brightness when compared to low-noise light-emitting diodes (LEDs). To understand noise sources in optical recordings, we systematically compared instrument and physiological noise profiles in two recording paradigms. A better understanding of noise sources can help improve optical recordings and make them more practical with fewer averages. We stimulated lobster nerves and a rat cortex, then compared the root mean square (RMS) noise and signal-to-noise ratios (SNRs) of data obtained with LED, superluminescent diode (SLD), and LD illumination for different numbers of averages. The LED data exhibited significantly higher SNRs in fewer averages than LD data in all recordings. In the absence of tissue, LED noise increased linearly with intensity, while LD noise increased sharply in the transition to lasing and settled to noise levels significantly higher than the LED's, suggesting that speckle noise contributed to the LD's higher noise and lower SNRs. Our data recommend low coherence and portable light sources for in vivo chronic neural recording applications.