Large-scale multielectrode recording and stimulation of neural activity

Large circuits of neurons are employed by the brain to encode and process information. How this encoding and processing is carried out is one of the central questions in neuroscience. Since individual neurons communicate with each other through electrical signals (action potentials), the recording of neural activity with arrays of extracellular electrodes is uniquely suited for the investigation of this question. Such recordings provide the combination of the best spatial (individual neurons) and temporal (individual action-potentials) resolutions compared to other large-scale imaging methods. Electrical stimulation of neural activity in turn has two very important applications: it enhances our understanding of neural circuits by allowing active interactions with them, and it is a basis for a large variety of neural prosthetic devices. Until recently, the state-of-the-art in neural activity recording systems consisted of several dozen electrodes with inter-electrode spacing ranging from tens to hundreds of microns. Using silicon microstrip detector expertise acquired in the field of high-energy physics, we created a unique neural activity readout and stimulation framework that consists of high-density electrode arrays, multi-channel custom-designed integrated circuits, a data acquisition system, and data-processing software. Using this framework we developed a number of neural readout and stimulation systems: (1) a 512-electrode system for recording the simultaneous activity of as many as hundreds of neurons, (2) a 61-electrode system for electrical stimulation and readout of neural activity in retinas and brain-tissue slices, and (3) a system with telemetry capabilities for recording neural activity in the intact brain of awake, naturally behaving animals. We will report on these systems, their various applications to the field of neurobiology, and novel scientific results obtained with some of them. We will also outline future directions

Active C4 electrodes for local field potential recording applications

Extracellular neural recording, with multi-electrode arrays (MEAs), is a powerful method used to study neural function at the network level. However, in a high density array, it can be costly and time consuming to integrate the active circuit with the expensive electrodes. In this paper, we present a 4 mm × 4 mm neural recording integrated circuit (IC) chip, utilizing IBM C4 bumps as recording electrodes, which enable a seamless active chip and electrode integration. The IC chip was designed and fabricated in a 0.13 μm BiCMOS process for both in vitro and in vivo applications. It has an input-referred noise of 4.6 μV rms for the bandwidth of 10 Hz to 10 kHz and a power dissipation of 11.25 mW at 2.5 V, or 43.9 μW per input channel. This prototype is scalable for implementing larger number and higher density electrode arrays. To validate the functionality of the chip, electrical testing results and acute in vivo recordings from a rat barrel cortex are presented.R01 NS072385 - NINDS NIH HHS; 1R01 NS072385 - NINDS NIH HH

Chronic neural probe for simultaneous recording of single-unit, multi-unit, and local field potential activity from multiple brain sites

Drug resistant focal epilepsy can be treated by resecting the epileptic focus requiring a precise focus localization using stereoelectroencephalography (SEEG) probes. As commercial SEEG probes offer only a limited spatial resolution, probes of higher channel count and design freedom enabling the incorporation of macro and microelectrodes would help increasing spatial resolution and thus open new perspectives for investigating mechanisms underlying focal epilepsy and its treatment. This work describes a new fabrication process for SEEG probes with materials and dimensions similar to clinical probes enabling recording single neuron activity at high spatial resolution. Polyimide is used as a biocompatible flexible substrate into which platinum electrodes and leads are... The resulting probe features match those of clinically approved devices. Tests in saline solution confirmed the probe stability and functionality. Probes were implanted into the brain of one monkey (Macaca mulatta), trained to perform different motor tasks. Suitable configurations including up to 128 electrode sites allow the recording of task-related neuronal signals. Probes with 32 and 64 electrode sites were implanted in the posterior parietal cortex. Local field potentials and multi-unit activity were recorded as early as one hour after implantation. Stable single-unit activity was achieved for up to 26 days after implantation of a 64-channel probe. All recorded signals showed modulation during task execution. With the novel probes it is possible to record stable biologically relevant data over a time span exceeding the usual time needed for epileptic focus localization in human patients. This is the first time that single units are recorded along cylindrical polyimide probes chronically implanted 22 mm deep into the brain of a monkey, which suggests the potential usefulness of this probe for human applications

Bioresorbable silicon electronics for transient spatiotemporal mapping of electrical activity from the cerebral cortex.

Bioresorbable silicon electronics technology offers unprecedented opportunities to deploy advanced implantable monitoring systems that eliminate risks, cost and discomfort associated with surgical extraction. Applications include postoperative monitoring and transient physiologic recording after percutaneous or minimally invasive placement of vascular, cardiac, orthopaedic, neural or other devices. We present an embodiment of these materials in both passive and actively addressed arrays of bioresorbable silicon electrodes with multiplexing capabilities, which record in vivo electrophysiological signals from the cortical surface and the subgaleal space. The devices detect normal physiologic and epileptiform activity, both in acute and chronic recordings. Comparative studies show sensor performance comparable to standard clinical systems and reduced tissue reactivity relative to conventional clinical electrocorticography (ECoG) electrodes. This technology offers general applicability in neural interfaces, with additional potential utility in treatment of disorders where transient monitoring and modulation of physiologic function, implant integrity and tissue recovery or regeneration are required

Multiplexed, High Density Electrophysiology with Nanofabricated Neural Probes

Extracellular electrode arrays can reveal the neuronal network correlates of behavior with single-cell, single-spike, and sub-millisecond resolution. However, implantable electrodes are inherently invasive, and efforts to scale up the number and density of recording sites must compromise on device size in order to connect the electrodes. Here, we report on silicon-based neural probes employing nanofabricated, high-density electrical leads. Furthermore, we address the challenge of reading out multichannel data with an application-specific integrated circuit (ASIC) performing signal amplification, band-pass filtering, and multiplexing functions. We demonstrate high spatial resolution extracellular measurements with a fully integrated, low noise 64-channel system weighing just 330 mg. The on-chip multiplexers make possible recordings with substantially fewer external wires than the number of input channels. By combining nanofabricated probes with ASICs we have implemented a system for performing large-scale, high-density electrophysiology in small, freely behaving animals that is both minimally invasive and highly scalable

Neuronal and astroglial correlates underlying spatiotemporal Intrinsic Optical Signal in the rat hippocampal slice

Widely used for mapping afferent activated brain areas in vivo, the label-free intrinsic optical signal (IOS) is mainly ascribed to blood volume changes subsequent to glial glutamate uptake. By contrast, IOS imaged in vitro is generally attributed to neuronal and glial cell swelling, however the relative contribution of different cell types and molecular players remained largely unknown. We characterized IOS to Schaffer collateral stimulation in the rat hippocampal slice using a 464-element photodiode-array device that enables IOS monitoring at 0.6 ms time-resolution in combination with simultaneous field potential recordings. We used brief half-maximal stimuli by applying a medium intensity 50 Volt-stimulus train within 50 ms (20 Hz). IOS was primarily observed in the str. pyramidale and proximal region of the str. radiatum of the hippocampus. It was eliminated by tetrodotoxin blockade of voltage-gated Na+ channels and was significantly enhanced by suppressing inhibitory signaling with gamma-aminobutyric acid(A) receptor antagonist picrotoxin. We found that IOS was predominantly initiated by postsynaptic Glu receptor activation and progressed by the activation of astroglial Glu transporters and Mg2+-independent astroglial N-methyl-D-aspartate receptors. Under control conditions, role for neuronal K+/Cl- cotransporter KCC2, but not for glial Na+/K+/Cl- cotransporter NKCC1 was observed. Slight enhancement and inhibition of IOS through non-specific Cl- and volume-regulated anion channels, respectively, were also depicted. High-frequency IOS imaging, evoked by brief afferent stimulation in brain slices provide a new paradigm for studying mechanisms underlying IOS genesis. Major players disclosed this way imply that spatiotemporal IOS reflects glutamatergic neuronal activation and astroglial response, as observed within the hippocampus. Our model may help to better interpret in vivo IOS and support diagnosis in the future