Neuroprosthetic devices based on brain-machine interface technology hold promise for the restoration of body mobility in patients suffering from devastating motor deficits caused by brain injury, neurologic diseases and limb loss. During the last decade, considerable progress has been achieved in this multidisciplinary research, mainly in the brain-machine interface that enacts upper-limb functionality. However, a considerable number of problems need to be resolved before fully functional limb neuroprostheses can be built. To move towards developing neuroprosthetic devices for humans, brain-machine interface research has to address a number of issues related to improving the quality of neuronal recordings, achieving stable, long-term performance, and extending the brain-machine interface approach to a broad range of motor and sensory functions. Here, we review the future steps that are part of the strategic plan of the Duke University Center for Neuroengineering, and its partners, the Brazilian National Institute of Brain-Machine Interfaces and the École Polytechnique Fédérale de Lausanne (EPFL) Center for Neuroprosthetics, to bring this new technology to clinical fruition.

The brain representation of the body, called the body schema, is susceptible to plasticity. For instance, subjects experiencing a rubber hand illusion develop a sense of ownership of a mannequin hand when they view it being touched while tactile stimuli are simultaneously applied to their own hand. Here, the cortical basis of such an embodiment was investigated through concurrent recordings from primary somatosensory (i.e., S1) and motor (i.e., M1) cortical neuronal ensembles while two monkeys observed an avatar arm being touched by a virtual ball. Following a period when virtual touches occurred synchronously with physical brushes of the monkeys' arms, neurons in S1 and M1 started to respond to virtual touches applied alone. Responses to virtual touch occurred 50 to 70 ms later than to physical touch, consistent with the involvement of polysynaptic pathways linking the visual cortex to S1 and M1. We propose that S1 and M1 contribute to the rubber hand illusion and that, by taking advantage of plasticity in these areas, patients may assimilate neuroprosthetic limbs as parts of their body schema.multielectrode recordings | cortical plasticity I n the early 1900s, Head and Holmes coined the concept of the "body schema" to describe the spatial model of the body that the brain builds based on sensory inputs from the skin, joints, and muscles, as well as visual and auditory signals (1). Numerous studies since then have explored different aspects of the body schema (2-6), particularly the role of cortical areas (7,8). The accumulated literature indicates that the body schema is plastic and can even incorporate artificial tools (5, 9, 10). A striking example of body schema plasticity is provided by the rubber hand illusion (RHI), in which subjects start to perceive a mannequin hand as their own after their real hand, hidden from sight, and the mannequin hand are repeatedly touched simultaneously (11-13). Subjects do not perceive a third limb, but report a shift in position sense from the real arm to the fake one (11-14), and there is even a decrease in skin temperature of the real arm (15). Incorporation of artificial limbs into the body schema began to be further explored with the advancement of brain machine interfaces (BMIs), hybrid systems that connect the brain with external devices (16)(17)(18)(19). Here, we recorded cortical ensemble activity in monkeys exposed to the paradigm that elicits RHI in humans (11)(12)(13)(14)20). ResultsMonkeys M and N were chronically implanted with microwire arrays in the primary motor (i.e., M1) and somatosensory (i.e., S1) cortical neuronal ensembles. They observed a 3D image of a virtual arm (i.e., an avatar arm) being touched by a virtual ball on an LCD screen while a robot slid a physical brush through the skin of their real arms ( Fig. 1 A and B). The virtual touch (V) and physical touch (P) were synchronous or asynchronous (Fig. 1C). In a subset of trials, virtual brushing occurred alone (i.e., Vonly).Excitatory and Inhibitory Responses to Physical Touch. Experiments with mon...