CLINICS 2011;66(S1):25-32 10.1590/S1807-59322011001300004 Future developments in brain-machine interface research Mikhail A. Lebedev,I Andrew J. Tate,I,II Timothy L. Hanson,I,II Zheng Li,I,II Joseph E. O’Doherty,I,II Jesse A. Winans,I Peter J. Ifft,I Katie Z. Zhuang,I Nathan A. Fitzsimmons,I David A. Schwarz,I Andrew M. Fuller,I Je Hi An,I Miguel A. L. NicolelisI,III I Neurobiology,Duke University, Durham, NC, USA. II Duke University Center for Neuroengineering, Duke University, Durham, NC, USA. III Edmond and Lily Safra International Institute of Neuroscience of Natal 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 E´cole Polytechnique F e´de´ rale de Lausanne (EPFL) Center for Neuroprosthetics, to bring this new technology to clinical fruition. KEYWORDS: Brain-machine interface; Neuroprosthetic; Primate; Bipedal locomotion; Intracortical microstimulation; Sensory substitution. Lebedev MA, Tate AJ, Hanson TL, Li Z, O’Doherty JE, Winans JA, Ifft PJ, Zhuang KZ, Fitzsimmons NA, Schwarz DA, Fuller AM, An JH, Nicolelis MAL. Future developments in brain-machine interface research. Clinics. 2011;66(S1):25-32. Received for publication on January 28, 2011; Accepted for publicaiton on January 30, 2011 E-mail: nicoleli@neuro.duke.edu Tel.: 919 684 4580 INTRODUCTION Millions of people worldwide suffer from sensorimotor deficits caused by neurologic injuries, diseases or limb loss. According to recent data reported in Medical News Today, five million people in the USA alone currently suffer from some type of severe body paralysis.1 Currently, there is no cure for such devastating cases of paralysis, for example complete spinal cord injury (SCI).2 Meanwhile, treatment is only partially effective in less severe cases.3 Neural prosthetic devices based on brain-machine interfaces (BMIs) hold promise to restore both partial and full body mobility in paralyzed patients.4–10 BMIs bypass the site of the neural lesion and connect the remaining healthy motor areas of the brain, particularly the motor cortex, directly to assistive and prosthetic devices that can take the shape of, for example, robotic limbs or a full body exoskeleton. The main idea behind BMIs is to employ the activity of healthy motor brain areas, which in many cases of paralysis remain capable of generating motor commands despite being disconnected from the body effectors,11 to control artificial tools that restore the patient’s mobility. Copyright 2011 CLINICS – This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http:// creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non- commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 25 During the last decade, the field of BMIs has experienced an explosive development.7,9 Hence, it has generated high expectations among neuroscientists, physicians and patients alike, regarding its potential clinical applications. A number of BMI systems have been studied in rodents12 and nonhuman primates.13–17 BMI technology also entered human clinical research where both non-invasive EEG- based systems5,18,19 and invasive BMIs based on brain implants20–22 have been tested. Notwithstanding the success of these pioneering experiments, a number of issues need to be resolved before a fully functional practical neuropros- thetic for long-term use can be built.7 These include: implant biocompatibility issues;23 increasing the number of neural channels of the recording system; improving BMI decoding algorithms; building fully implantable systems; sensorizing neuroprosthetic limbs; and extending the BMI approach to a broader range of motor control tasks, especially tasks that require lower limb control: bipedal walking24 and upright posture control.25 The Duke University Center for Neuroengineering (DUCN) has been at the forefront of BMI research on cortical prosthetic devices for motor rehabilitation since this field emerged about 12 years ago. At the DUCN, we have developed pioneering BMI systems that enact a wide range of motor functions, from arm reaching and grasping 13,17,26 to bipedal locomotion24,27 in a variety of artificial actuators. DUCN researchers were also the first to incorporate artificial somatic sensation in BMIs.28,29 Here, we review the most recent findings of the BMI initiative at the DUCN and discuss