Fully bioresorbable hybrid opto-electronic neural implant system for simultaneous electrophysiological recording and optogenetic stimulation.

Bioresorbable neural implants based on emerging classes of biodegradable materials offer a promising solution to the challenges of secondary surgeries for removal of implanted devices required for existing neural implants. In this study, we introduce a fully bioresorbable flexible hybrid opto-electronic system for simultaneous electrophysiological recording and optogenetic stimulation. The flexible and soft device, composed of biodegradable materials, has a direct optical and electrical interface with the curved cerebral cortex surface while exhibiting excellent biocompatibility. Optimized to minimize light transmission losses and photoelectric artifact interference, the device was chronically implanted in the brain of transgenic mice and performed to photo-stimulate the somatosensory area while recording local field potentials. Thus, the presented hybrid neural implant system, comprising biodegradable materials, promises to provide monitoring and therapy modalities for versatile applications in biomedicine.

HectoSTAR µLED Optoelectrodes for Large-Scale, High-Precision In Vivo Opto-Electrophysiology.

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.

A 3.1-5.2GHz, Energy-Efficient Single Antenna, Cancellation-Free, Bitwise Time-Division Duplex Transceiver for High Channel Count Optogenetic Neural Interface.

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.

A Multimodal Multi-Shank Fluorescence Neural Probe for Cell-Type-Specific Electrophysiology in Multiple Regions across a Neural Circuit.

Cell-type-specific, activity-dependent electrophysiology can allow in-depth analysis of functional connectivity inside complex neural circuits composed of various cell types. To date, optics-based fluorescence recording devices enable monitoring cell-type-specific activities. However, the monitoring is typically limited to a single brain region, and the temporal resolution is significantly low. Herein, a multimodal multi-shank fluorescence neural probe that allows cell-type-specific electrophysiology from multiple deep-brain regions at a high spatiotemporal resolution is presented. A photodiode and an electrode-array pair are monolithically integrated on each tip of a minimal-form-factor silicon device. Both fluorescence and electrical signals are successfully measured simultaneously in GCaMP6f expressing mice, and the cell type from sorted neural spikes is identified. The probe's capability of combined electro-optical recordings for cell-type-specific electrophysiology at multiple brain regions within a neural circuit is demonstrated. The new experimental paradigm to enable the precise investigation of functional connectivity inside and across complex neural circuits composed of various cell types is expected.

Bimodal neural probe for highly co-localized chemical and electrical monitoring of neural activities in vivo.

Investigation of the chemical and electrical signals of cells in vivo is critical for studying functional connectivity and brain diseases. Most previous studies have observed either the electrical signals or the chemical signals of cells because recording electrical signals and neurochemicals are done by fundamentally different methods. Herein, we present a bimodal MEMS neural probe that is monolithically integrated with an array of microelectrodes for recording electrical activity, microfluidic channels for sampling extracellular fluid, and a microfluidic interface chip for multiple drug delivery and sample isolation from the localized region at the cellular level. In this work, we successfully demonstrated the functionality of our probe by monitoring and modulating bimodal (electrical and chemical) neural activities through the delivery of chemicals in a co-localized brain region in vivo. We expect our bimodal probe to provide opportunities for a variety of in-depth studies of brain functions as well as for the investigation of neural circuits related to brain diseases.

A minimally invasive flexible electrode array for simultaneous recording of ECoG signals from multiple brain regions.

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.

Preexisting hippocampal network dynamics constrain optogenetically induced place fields.

Memory models often emphasize the need to encode novel patterns of neural activity imposed by sensory drive. Prior learning and innate architecture likely restrict neural plasticity, however. Here, we test how the incorporation of synthetic hippocampal signals is constrained by preexisting circuit dynamics. We optogenetically stimulated small groups of CA1 neurons as mice traversed a chosen segment of a linear track, mimicking the emergence of place fields. Stimulation induced persistent place field remapping in stimulated and non-stimulated neurons. The emergence of place fields could be predicted from sporadic firing in the new place field location and the temporal relationship to peer neurons before the optogenetic perturbation. Circuit modification was reflected by altered spike transmission between connected pyramidal cells and inhibitory interneurons, which persisted during post-experience sleep. We hypothesize that optogenetic perturbation unmasked sub-threshold place fields. Plasticity in recurrent/lateral inhibition may drive learning through the rapid association of existing states.

Artifact-free and high-temporal-resolution in vivo opto-electrophysiology with microLED optoelectrodes.

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-2 irradiance. 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.

A High-Resolution Opto-Electrophysiology System With a Miniature Integrated Headstage.

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 , and fast turn-on of µLEDs . 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.

Pyramidal Cell-Interneuron Circuit Architecture and Dynamics in Hippocampal Networks.

Excitatory control of inhibitory neurons is poorly understood due to the difficulty of studying synaptic connectivity in vivo. We inferred such connectivity through analysis of spike timing and validated this inference using juxtacellular and optogenetic control of presynaptic spikes in behaving mice. We observed that neighboring CA1 neurons had stronger connections and that superficial pyramidal cells projected more to deep interneurons. Connection probability and strength were skewed, with a minority of highly connected hubs. Divergent presynaptic connections led to synchrony between interneurons. Synchrony of convergent presynaptic inputs boosted postsynaptic drive. Presynaptic firing frequency was read out by postsynaptic neurons through short-term depression and facilitation, with individual pyramidal cells and interneurons displaying a diversity of spike transmission filters. Additionally, spike transmission was strongly modulated by prior spike timing of the postsynaptic cell. These results bridge anatomical structure with physiological function.

Heat engine driven by purely quantum information.

The key question of this Letter is whether work can be extracted from a heat engine by using purely quantum mechanical information. If the answer is yes, what is its mathematical formula? First, by using a bipartite memory we show that the work extractable from a heat engine is bounded not only by the free energy change and the sum of the entropy change of an individual memory but also by the change of quantum mutual information contained inside the memory. We then find that the engine can be driven by purely quantum information, expressed as the so-called quantum discord, forming a part of the quantum mutual information. To confirm it, as a physical example we present the Szilard engine containing a diatomic molecule with a semipermeable wall.

Information from time-forward and time-backward processes in Szilard engines.

We derive the work performed in the Szilard engine (SZE) by using the dissipative work formula of nonequilibrium thermodynamics developed by Kawai et al. [Phys. Rev. Lett. 98, 080602 (2007)]. The work is described as the difference of probability distributions of measurement outcomes of the time-forward and the time-backward process.