Hochberg, L. R. et al. Neuronal ensemble control of prosthetic devices by a human with tetraplegia. Nature 442, 164-171

Department of Neurology, Massachusetts General Hospital, Brigham and Women's Hospital, and Spaulding Rehabilitation Hospital, Harvard Medical School, 55 Fruit Street, Boston, Massachusetts 02114, USA.
Nature (Impact Factor: 41.46). 08/2006; 442(7099):164-71. DOI: 10.1038/nature04970
Source: PubMed


Neuromotor prostheses (NMPs) aim to replace or restore lost motor functions in paralysed humans by routeing movement-related signals from the brain, around damaged parts of the nervous system, to external effectors. To translate preclinical results from intact animals to a clinically useful NMP, movement signals must persist in cortex after spinal cord injury and be engaged by movement intent when sensory inputs and limb movement are long absent. Furthermore, NMPs would require that intention-driven neuronal activity be converted into a control signal that enables useful tasks. Here we show initial results for a tetraplegic human (MN) using a pilot NMP. Neuronal ensemble activity recorded through a 96-microelectrode array implanted in primary motor cortex demonstrated that intended hand motion modulates cortical spiking patterns three years after spinal cord injury. Decoders were created, providing a 'neural cursor' with which MN opened simulated e-mail and operated devices such as a television, even while conversing. Furthermore, MN used neural control to open and close a prosthetic hand, and perform rudimentary actions with a multi-jointed robotic arm. These early results suggest that NMPs based upon intracortical neuronal ensemble spiking activity could provide a valuable new neurotechnology to restore independence for humans with paralysis.

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    • "I. INTRODUCTION Wireless multi-channel neural recording systems are highly demanded in neuroscience experiments with laboratory animals to study the complex brain behavior. They are also critical components in brain-controlled neural prostheses, to restore limb movement [1]. In neuroscience, their adoption improves animal freedom of movements and reduces motion artifacts and tethering effects. "
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    ABSTRACT: This paper presents a 64-channel neural recordingsystem-on-chip (SoC) with a 20-Mbps wireless telemetry. Eachchannel of the analog front-end consists of a low-noise band-pass amplifier, featuring a NEF of 3.11 with an input-referrednoise of 5.6μVrms in a 0.001-10 kHz band, and a 31.25-kSps6-fJ/conversion-step 10-bit SAR A/D converter. The recordedsignals are multiplexed in the digital domain and transmittedvia a 11.7%-efficiency pulse-period-modulation UWB transmitter(TX), reaching a transmission range in excess of 7.5m. The chiphas been fabricated in 130-nm CMOS process, measures 25mm2and dissipates 965μW from a 0.5-V supply. This SoC features thelowest power-per-channel (15μW-per-channel) among state-of-the-art wireless neural recording systems with a number of chan-nels larger than 32 and the widest transmission range withoutperforming any data compression or loosing vital information,such as local field potentials (LFPs).
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    • "Over recent years photo-or thermal-assisted grafting of vinylfunctionalized (1-alkene) biomolecules onto hydrogen-terminated silicon surfaces H Si(1 1 1) via hydrosilylation has been successfully undertaken, resulting in many biological applications [1] [2] [3]. This reaction, which generates a covalent Si C bond, is currently used in the modification of silicon substrates with organic molecules for specific interactions with biological targets, and for the production of silicon-based bioelectrical sensors and devices [4] [5], nanoparticle probes [6] [7], photonic devices [8] [9], and siliconneuron interfaces [10] [11]. The hydrosilylation reaction has been performed on H-terminated Si(1 1 1) [12] [13] [14], Si(1 0 0) surfaces and on porous silicon.[15] "
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    ABSTRACT: In this work we grafted vinyl- and azido-terminated tetrahydroisoquinolines (compounds 1 and 2, respectively) onto H-Si(1 1 1) silicon wafers obtaining highly stable modified surfaces. A double bond was incorporated into the tetrahydroisoquinoline structure of 1 to be immobilized by a light induced hydrosilylation reaction on hydrogen-terminated Si(1 11). The best results were obtained employing a polar solvent (DMSO), rather than a non-polar solvent (toluene). The azide derivative 2 was grafted onto alkenyl-terminated silicon substrates with copper-catalyzed azide-alkyne cycloaddition (CuAAC). Atomic force microscopy (AFM), contact angle goniometry (CA) and X-ray photoemission spectroscopy (XPS) were used to demonstrate the incorporation of 1 and 2 into the surfaces, study the morphology of the modified surfaces and to calculate the yield of grafting and surface coverage. CA measurements showed the increase in the surface hydrophobicity when 1 or 2 were incorporated into the surface. Moreover, compounds 1 and 2 were prepared starting from 1-(p-nitrophenyl)tetrahydroisoquinoline 3 under smooth conditions and in good yields. The structures of 1 and 2 were designed with a reduced A-ring, two substituents at positions C-6 and C-7, an N-methyl group and a phenyl moiety at C-1 in order to provide a high affinity against dopaminergic receptors. Moreover, O-demethylation of 1 was carried out once it was adsorbed onto the surface by treatment with BBr3. The method presented constitutes a simple, easily reproducible and high yielding approach for grafting complex organic biomolecules with dopaminergic properties onto silicon surfaces.
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    • "The first strategy aims at bypassing nonfunctional cortico-spinal pathways to allow for continuous and permanent control of robotic devices (Collinger et al., 2013) or functional electric stimulation (FES) of paralyzed muscles (Moritz et al., 2008; Pohlmeyer et al., 2009; Ethier et al., 2012; McGie et al., in press; Pfurtscheller et al., 2003). By substituting for lost motor functions, such assistive BMIs have demonstrated recovery of versatile motor control in daily life activities (Hochberg et al., 2006; Collinger et al., 2013). The second strategy aims at facilitation of neuroplasticity and motor learning to enhance motor recovery (rehabilitative BMIs) (Dobkin, 2007; Soekadar et al., 2011a) (Fig. 1a). "

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