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1.  Implants and Decoding for Intracortical Brain Computer Interfaces 
Intracortical brain computer interfaces (iBCIs) are being developed to enable a person to drive an output device, such as a computer cursor, directly from their neural activity. One goal of the technology is to help people with severe paralysis or limb loss. Key elements of an iBCI are the implanted sensor that records the neural signals and the software which decodes the user’s intended movement from those signals. Here, we focus on recent advances in these two areas, with special attention being placed on contributions that are or may soon be adopted by the iBCI research community. We discuss how these innovations increase the technology’s capability, accuracy, and longevity, all important steps that are expanding the range of possible future clinical applications.
doi:10.1146/annurev-bioeng-071910-124640
PMCID: PMC3985135  PMID: 23862678
brain machine interfaces; multielectrode arrays; signal processing; neural engineering
2.  A 32-channel fully implantable wireless neurosensor for simultaneous recording from two cortical regions 
We present a fully implantable, wireless, neurosensor for multiple-location neural interface applications. The device integrates two independent 16-channel intracortical microelectrode arrays and can simultaneously acquire 32 channels of broadband neural data from two separate cortical areas. The system-on-chip implantable sensor is built on a flexible Kapton polymer substrate and incorporates three very low power subunits: two cortical subunits connected to a common subcutaneous subunit. Each cortical subunit has an ultra-low power 16-channel preamplifier and multiplexer integrated onto a cortical microelectrode array. The subcutaneous epicranial unit has an inductively coupled power supply, two analog-to-digital converters, a low power digital controller chip, and microlaser-based infrared telemetry. The entire system is soft encapsulated with biocompatible flexible materials for in vivo applications. Broadband neural data is conditioned, amplified, and analog multiplexed by each of the cortical subunits and passed to the subcutaneous component, where it is digitized and combined with synchronization data and wirelessly transmitted transcutaneously using high speed infrared telemetry.
doi:10.1109/IEMBS.2011.6090579
PMCID: PMC3925433  PMID: 22254801
3.  Polymeric Packaging for Fully Implantable Wireless Neural Microsensors 
We present polymeric packaging methods used for subcutaneous, fully implantable, broadband, and wireless neurosensors. A new tool for accelerated testing and characterization of biocompatible polymeric packaging materials and processes is described along with specialized test units to simulate our fully implantable neurosensor components, materials and fabrication processes. A brief description of the implantable systems is presented along with their current encapsulation methods based on polydimethylsiloxane (PDMS). Results from in-vivo testing of multiple implanted neurosensors in swine and non-human primates are presented. Finally, a novel augmenting polymer thin film material to complement the currently employed PDMS is introduced. This thin layer coating material is based on the Plasma Enhanced Chemical Vapor Deposition (PECVD) process of Hexamethyldisiloxane (HMDSO) and Oxygen (O2).
doi:10.1109/EMBC.2012.6346038
PMCID: PMC3904293  PMID: 23365999
4.  A 100-Channel Hermetically Sealed Implantable Device for Chronic Wireless Neurosensing Applications 
A 100-channel fully implantable wireless broadband neural recording system was developed. It features 100 parallel broadband (0.1 Hz–7.8 kHz) neural recording channels, a medical grade 200 mAh Li-ion battery recharged inductively at 150 kHz, and data telemetry using 3.2 GHz to 3.8 GHz FSK modulated wireless link for 48 Mbps Manchester encoded data. All active electronics are hermetically sealed in a titanium enclosure with a sapphire window for electromagnetic transparency. A custom, high-density configuration of 100 individual hermetic feedthrough pins enable connection to an intracortical neural recording microelectrode array. A 100 MHz bandwidth custom receiver was built to remotely receive the FSK signal and achieved −77.7 dBm sensitivity with 10−8 BER at 48 Mbps data rate. ESD testing on all the electronic inputs and outputs has proven that the implantable device satisfies the HBM Class-1B ESD Standard. In addition, the evaluation of the worst-case charge density delivered to the tissue from each I/O pin verifies the patient safety of the device in the event of failure. Finally, the functionality and reliability of the complete device has been tested on-bench and further validated chronically in ongoing freely moving swine and monkey animal trials for more than one year to date.
doi:10.1109/TBCAS.2013.2255874
PMCID: PMC3904295  PMID: 23853294
Hermetical seal; implantable device; inductive power; neural recording; wireless transmission
5.  Nanotools for Neuroscience and Brain Activity Mapping 
ACS nano  2013;7(3):1850-1866.
Neuroscience is at a crossroads. Great effort is being invested into deciphering specific neural interactions and circuits. At the same time, there exist few general theories or principles that explain brain function. We attribute this disparity, in part, to limitations in current methodologies. Traditional neurophysiological approaches record the activities of one neuron or a few neurons at a time. Neurochemical approaches focus on single neurotransmitters. Yet, there is an increasing realization that neural circuits operate at emergent levels, where the interactions between hundreds or thousands of neurons, utilizing multiple chemical transmitters, generate functional states. Brains function at the nanoscale, so tools to study brains must ultimately operate at this scale, as well. Nanoscience and nanotechnology are poised to provide a rich toolkit of novel methods to explore brain function by enabling simultaneous measurement and manipulation of activity of thousands or even millions of neurons. We and others refer to this goal as the Brain Activity Mapping Project. In this Nano Focus, we discuss how recent developments in nanoscale analysis tools and in the design and synthesis of nanomaterials have generated optical, electrical, and chemical methods that can readily be adapted for use in neuroscience. These approaches represent exciting areas of technical development and research. Moreover, unique opportunities exist for nanoscientists, nanotechnologists, and other physical scientists and engineers to contribute to tackling the challenging problems involved in understanding the fundamentals of brain function.
doi:10.1021/nn4012847
PMCID: PMC3665747  PMID: 23514423
6.  An Implantable Neural Sensing Microsystem with Fiber-Optic Data Transmission and Power Delivery 
Sensors (Basel, Switzerland)  2013;13(5):6014-6031.
We have developed a prototype cortical neural sensing microsystem for brain implantable neuroengineering applications. Its key feature is that both the transmission of broadband, multichannel neural data and power required for the embedded microelectronics are provided by optical fiber access. The fiber-optic system is aimed at enabling neural recording from rodents and primates by converting cortical signals to a digital stream of infrared light pulses. In the full microsystem whose performance is summarized in this paper, an analog-to-digital converter and a low power digital controller IC have been integrated with a low threshold, semiconductor laser to extract the digitized neural signals optically from the implantable unit. The microsystem also acquires electrical power and synchronization clocks via optical fibers from an external laser by using a highly efficient photovoltaic cell on board. The implantable unit employs a flexible polymer substrate to integrate analog and digital microelectronics and on-chip optoelectronic components, while adapting to the anatomical and physiological constraints of the environment. A low power analog CMOS chip, which includes preamplifier and multiplexing circuitry, is directly flip-chip bonded to the microelectrode array to form the cortical neurosensor device.
doi:10.3390/s130506014
PMCID: PMC3690043  PMID: 23666130
brain machine interface; neural probe array; neuromotor prosthesis; optical telemetry; photovoltaic device
7.  Visual experience-dependent maturation of correlated neuronal activity patterns in a developing visual system 
The functional properties of neural circuits become increasingly robust over development. This allows circuits to optimize their output in response to a variety of input. However it is not clear whether this optimization is a function of hardwired circuit elements, or whether it requires neural experience in order to develop. Here we perform rapid in vivo imaging of calcium signals from bulk-labeled neurons in the Xenopus laevis optic tectum in order to resolve the rapid spatiotemporal response properties of populations of developing tectal neurons in response to visual stimuli. We find that during a critical time in tectal development, network activity becomes increasingly robust, more correlated and more synchronous. These developmental changes require normal visual input during development and are disrupted by NMDA receptor blockade. Our data show that visual activity and NMDAR activation are critical for the maturation of tectal network dynamics during visual system development.
doi:10.1523/JNEUROSCI.5802-10.2011
PMCID: PMC3169172  PMID: 21632924
Optic tectum; visual system; development; activity dependent; calcium imaging; Xenopus
8.  Listening to Brain Microcircuits for Interfacing With External World—Progress in Wireless Implantable Microelectronic Neuroengineering Devices 
Acquiring neural signals at high spatial and temporal resolution directly from brain microcircuits and decoding their activity to interpret commands and/or prior planning activity, such as motion of an arm or a leg, is a prime goal of modern neurotechnology. Its practical aims include assistive devices for subjects whose normal neural information pathways are not functioning due to physical damage or disease. On the fundamental side, researchers are striving to decipher the code of multiple neural microcircuits which collectively make up nature’s amazing computing machine, the brain. By implanting biocompatible neural sensor probes directly into the brain, in the form of microelectrode arrays, it is now possible to extract information from interacting populations of neural cells with spatial and temporal resolution at the single cell level. With parallel advances in application of statistical and mathematical techniques tools for deciphering the neural code, extracted populations or correlated neurons, significant understanding has been achieved of those brain commands that control, e.g., the motion of an arm in a primate (monkey or a human subject). These developments are accelerating the work on neural prosthetics where brain derived signals may be employed to bypass, e.g., an injured spinal cord. One key element in achieving the goals for practical and versatile neural prostheses is the development of fully implantable wireless microelectronic “brain-interfaces” within the body, a point of special emphasis of this paper.
doi:10.1109/JPROC.2009.2038949
PMCID: PMC3108264  PMID: 21654935
Biomedical devices; brain science; neural engineering; neural signal recording
9.  Pathway-specific feedforward circuits between thalamus and neocortex revealed by selective optical stimulation of axons 
Neuron  2010;65(2):230-245.
Thalamocortical and corticothalamic pathways mediate bidirectional communication between the thalamus and neocortex. These pathways are entwined, making their study challenging. Here we used lentiviruses to express channelrhodopsin-2 (ChR2), a light-sensitive cation channel, in either thalamocortical or corticothalamic projection cells. Infection occurred only locally but efferent axons and their terminals expressed ChR2 strongly, allowing selective optical activation of each pathway. Laser stimulation of ChR2-expressing thalamocortical axons/terminals evoked robust synaptic responses in cortical excitatory cells and fast-spiking (FS) inhibitory interneurons, but only weak responses in somatostatin-containing interneurons. Strong FS cell activation led to feedforward inhibition in all cortical neuron types, including FS cells. Corticothalamic stimulation excited thalamic relay cells and inhibitory neurons of the thalamic reticular nucleus (TRN). TRN activation triggered inhibition in relay cells but not in TRN neurons. Thus, a major difference between thalamocortical and corticothalamic processing was the extent to which feedforward inhibitory neurons were themselves engaged by feedforward inhibition.
doi:10.1016/j.neuron.2009.12.025
PMCID: PMC2826223  PMID: 20152129
10.  Integrated device for optical stimulation and spatiotemporal electrical recording of neural activity in light-sensitized brain tissue 
Journal of neural engineering  2009;6(5):055007.
Neural stimulation with high spatial and temporal precision is desirable both for studying the real-time dynamics of neural networks and for prospective clinical treatment of neurological diseases. Optical stimulation of genetically targeted neurons expressing the light sensitive channel protein Channelrhodopsin (ChR2) has recently been reported as a means for millisecond temporal control of neuronal spiking activities with cell-type selectivity. This offers the prospect of enabling local delivery of optical stimulation and the simultaneous monitoring of the neural activity by electrophysiological means, both in the vicinity of and distant to the stimulation site. We report here a novel dual-modality hybrid device, which consists of a tapered coaxial optical waveguide (‘optrode’) integrated into a 100 element intra-cortical multi-electrode recording array. We first demonstrate the dual optical delivery and electrical recording capability of the single optrode in in vitro preparations of mouse retina, photo-stimulating the native retinal photoreceptors while recording light-responsive activities from ganglion cells. The dual-modality array device was then used in ChR2 transfected mouse brain slices. Specifically, epileptiform events were reliably optically triggered by the optrode and their spatiotemporal patterns were simultaneously recorded by the multi-electrode array.
doi:10.1088/1741-2560/6/5/055007
PMCID: PMC2921864  PMID: 19721185

Results 1-10 (10)