Close-Packed Silicon Microelectrodes for Scalable Spatially Oversampled Neural Recording

Objective: Neural recording electrodes are important tools for understanding neural codes and brain dynamics. Neural electrodes that are closely packed, such as in tetrodes, enable spatial oversampling of neural activity, which facilitates data analysis. Here we present the design and implementation of close-packed silicon microelectrodes to enable spatially oversampled recording of neural activity in a scalable fashion. Methods: Our probes are fabricated in a hybrid lithography process, resulting in a dense array of recording sites connected to submicron dimension wiring. Results: We demonstrate an implementation of a probe comprising 1000 electrode pads, each 9 × 9 μm, at a pitch of 11 μm. We introduce design automation and packaging methods that allow us to readily create a large variety of different designs. Significance: We perform neural recordings with such probes in the live mammalian brain that illustrate the spatial oversampling potential of closely packed electrode sites.Massachusetts Institute of Technology. Simons Center for the Social BrainNational Institutes of Health (U.S.) (NIH Director’s Pioneer Award DP1NS087724)National Institutes of Health (U.S.) (NIH Grant R01NS067199)National Institutes of Health (U.S.) (NIH grant Grant 2R44NS070453- 03A1)National Institutes of Health (U.S.) (NIH Grant R01DA029639)National Science Foundation (U.S.) (Cognitive Rhythms Collaborative, NSF DMS 1042134)Institution of Engineering and Technology (IET) (Harvey Prize)New York Stem Cell FoundationNational Institutes of Health (U.S.) (NIH grant CBET 1053233)United States. Defense Advanced Research Projects Agency (DARPA Grant HR0011-14-2-0004)Paul G. Allen Family Foundatio

A wirelessly powered and controlled device for optical neural control of freely-behaving animals

Optogenetics, the ability to use light to activate and silence specific neuron types within neural networks in vivo and in vitro, is revolutionizing neuroscientists' capacity to understand how defined neural circuit elements contribute to normal and pathological brain functions. Typically, awake behaving experiments are conducted by inserting an optical fiber into the brain, tethered to a remote laser, or by utilizing an implanted light-emitting diode (LED), tethered to a remote power source. A fully wireless system would enable chronic or longitudinal experiments where long duration tethering is impractical, and would also support high-throughput experimentation. However, the high power requirements of light sources (LEDs, lasers), especially in the context of the extended illumination periods often desired in experiments, precludes battery-powered approaches from being widely applicable. We have developed a headborne device weighing 2 g capable of wirelessly receiving power using a resonant RF power link and storing the energy in an adaptive supercapacitor circuit, which can algorithmically control one or more headborne LEDs via a microcontroller. The device can deliver approximately 2 W of power to the LEDs in steady state, and 4.3 W in bursts. We also present an optional radio transceiver module (1 g) which, when added to the base headborne device, enables real-time updating of light delivery protocols; dozens of devices can be controlled simultaneously from one computer. We demonstrate use of the technology to wirelessly drive cortical control of movement in mice. These devices may serve as prototypes for clinical ultra-precise neural prosthetics that use light as the modality of biological control.National Institutes of Health (U.S.) (NIH Director’s New Innovator Award (DP2OD002002))National Institutes of Health (U.S.) (Grant 1R01DA029639)National Institutes of Health (U.S.) (Grant 1RC1MH088182)National Institutes of Health (U.S.) (Grant 1RC2DE020919)National Institutes of Health (U.S.) (Grant 1R01NS067199)National Institutes of Health (U.S.) (Grant 1R43NS070453)National Science Foundation (U.S.) (CAREER award)National Science Foundation (U.S.) (NSF Grant DMS 1042134)National Science Foundation (U.S.) (NSF Grant DMS 0848804)National Science Foundation (U.S.) (NSF Grant EFRI 0835878)Benesse FoundationGoogle (Firm)Dr. Gerald Burnett and Marjorie BurnettUnited States. Dept. of Defense (CDMRP PTSD Program)Massachusetts Institute of TechnologyBrain & Behavior Research FoundationAlfred P. Sloan FoundationSociety for NeuroscienceMassachusetts Institute of Technology. Media LaboratoryMcGovern Institute for Brain Research at MITWallace H. Coulter Foundatio

The association between impulsivity and alcohol/drug use among prison inmates

Background: Few studies have examined the relation between impulsivity and drug involvement with prison inmates, in spite of their heavy drug use. Among this small body of work, most studies look at clinically relevant drug dependence, rather than drug use specifically. Method: N = 242 adult inmates (34.8% female, 52% White) with an average age of 35.58 (SD = 9.19) completed a modified version of the 15-item Barratt Impulsiveness Scale (BIS) and measures assessing lifetime alcohol, opiate, benzodiazepine, cocaine, cannabis, hallucinogen, and polysubstance use. Lifetime users also reported the frequency of use for the 30 days prior to incarceration. Results: Impulsivity was higher among lifetime users (versus never users) of all substances other than cannabis. Thirty day drug use frequency was only related to impulsivity for opiates and alcohol. Discussion: This study extends prior work, by showing that a lifetime history of non-clinical substance use is positively associated with impulsivity among prison inmates. Implications for drug interventions are considered for this population, which is characterized by high rates of substance use and elevated impulsivity

A direct-to-drive neural data acquisition system

Driven by the increasing channel count of neural probes, there is much effort being directed to creating increasingly scalable electrophysiology data acquisition (DAQ) systems. However, all such systems still rely on personal computers for data storage, and thus are limited by the bandwidth and cost of the computers, especially as the scale of recording increases. Here we present a novel architecture in which a digital processor receives data from an analog-to-digital converter, and writes that data directly to hard drives, without the need for a personal computer to serve as an intermediary in the DAQ process. This minimalist architecture may support exceptionally high data throughput, without incurring costs to support unnecessary hardware and overhead associated with personal computers, thus facilitating scaling of electrophysiological recording in the future.National Institutes of Health (U.S.) (Grant 1DP1NS087724)National Institutes of Health (U.S.) (Grant 1R01DA029639)National Institutes of Health (U.S.) (Grant 1R01NS067199)National Institutes of Health (U.S.) (Grant 2R44NS070453)National Institutes of Health (U.S.) (Grant R43MH101943)New York Stem Cell FoundationPaul Allen FoundationMassachusetts Institute of Technology. Media LaboratoryGoogle (Firm)United States. Defense Advanced Research Projects Agency (HR0011-14-2-0004)Hertz Foundation (Myhrvold Family Fellowship

Antigenic Complementarity in the Origins of Autoimmunity: A General Theory Illustrated With a Case Study of Idiopathic Thrombocytopenia Purpura

We describe a novel, testable theory of autoimmunity, outline novel predictions made by the theory, and illustrate its application to unravelling the possible causes of idiopathic thrombocytopenia purpura (ITP). Pairs of stereochemically complementary antigens induce complementary immune responses (antibody or T-cell) that create loss of regulation and civil war within the immune system itself. Antibodies attack antibodies creating circulating immune complexes; T-cells attack T-cells creating perivascular cuffing. This immunological civil war abrogates the self-nonself distinction. If at least one of the complementary antigens mimics a self antigen, then this unregulated immune response will target host tissues as well. Data demonstrating that complementary antigens are found in some animal models of autoimmunity and may be present in various human diseases, especially ITP, are reviewed. Specific mechanisms for preventing autoimmunity or suppressing existing autoimmunity are derived from the theory, and critical tests proposed. Finally, we argue that Koch's postulates are inadequate for establishing disease causation for multiple-antigen diseases and discuss the possibility that current research has failed to elucidate the causes of human autoimmune diseases because we are using the wrong criteria

Millisecond-Timescale Optical Control of Neural Dynamics in the Nonhuman Primate Brain

To understand how brain states and behaviors are generated by neural circuits, it would be useful to be able to perturb precisely the activity of specific cell types and pathways in the nonhuman primate nervous system. We used lentivirus to target the light-activated cation channel channelrhodopsin-2 (ChR2) specifically to excitatory neurons of the macaque frontal cortex. Using a laser-coupled optical fiber in conjunction with a recording microelectrode, we showed that activation of excitatory neurons resulted in well-timed excitatory and suppressive influences on neocortical neural networks. ChR2 was safely expressed, and could mediate optical neuromodulation, in primate neocortex over many months. These findings highlight a methodology for investigating the causal role of specific cell types in nonhuman primate neural computation, cognition, and behavior, and open up the possibility of a new generation of ultraprecise neurological and psychiatric therapeutics via cell-type-specific optical neural control prosthetics.Helen Hay Whitney Foundation (Fellowship)National Institutes of Health (U.S.) (NIH-EY002621-31)McGovern Institute for Brain Research at MIT (Neurotechnology Award)National Institutes of Health (U.S.) (Grant NIH-EY12848)National Institutes of Health (U.S.) (Grant NIH-EY017292)National Institutes of Health (U.S.) (NIH Director's New Innovator Award (DP2 OD002002-01))Brain & Behavior Research FoundationUnited States. Dept. of DefenseNational Science Foundation (U.S.)Alfred P. Sloan FoundationDr. Gerald Burnett and Marjorie BurnettSFN Research Award for Innovation in NeuroscienceMassachusetts Institute of Technology. Media LaboratoryBenesse FoundationWallace H. Coulter Foundatio

Feed-Forward Microprocessing and Splicing Activities at a MicroRNA–Containing Intron

The majority of mammalian microRNA (miRNA) genes reside within introns of protein-encoding and non-coding genes, yet the mechanisms coordinating primary transcript processing into both mature miRNA and spliced mRNA are poorly understood. Analysis of melanoma invasion suppressor miR-211 expressed from intron 6 of melastatin revealed that microprocessing of miR-211 promotes splicing of the exon 6–exon 7 junction of melastatin by a mechanism requiring the RNase III activity of Drosha. Additionally, mutations in the 5′ splice site (5′SS), but not in the 3′SS, branch point, or polypyrimidine tract of intron 6 reduced miR-211 biogenesis and Drosha recruitment to intron 6, indicating that 5′SS recognition by the spliceosome promotes microprocessing of miR-211. Globally, knockdown of U1 splicing factors reduced intronic miRNA expression. Our data demonstrate novel mutually-cooperative microprocessing and splicing activities at an intronic miRNA locus and suggest that the initiation of spliceosome assembly may promote microprocessing of intronic miRNAs