CAUTION: Investigational device. Limited by Federal (USA) law to investigational use – only being studied in the USA. Case Report Preliminary Observations of Device Efficacy There were no post-surgical complications which is supported by the continued ability to record neural activity. No adverse events or other study-related complications have been reported. Safety assessments include daily checks of connector, weekly nurse visits, and monthly physician exams including neurological and mental status exams. BrainGate Neural Interface System

17 SENSATION AND PERCEPTION | BRAIN FACTS SOCIETY FOR NEUROSCIENCE Although the process is not yet completely understood, recent findings suggest that visual signals are fed into at least three separate processing systems. One system appears to process information mainly about shape; a second, mainly about color; and a third, movement, location, and spatial organization. These findings of separate processing systems come from anatomical and physiological studies in monkeys. They are supported by human psychological studies showing that the perception of movement, depth, perspective, the relative size of objects, the relative movement of objects, shading, and gradations in texture all depend primarily on contrasts in light intensity rather than on color. Why movement and depth perception should be emphasized by one processing system may be explained by a school of thought called Gestalt psychology. Perception requires various elements to be organized so that related ones are grouped together. This stems from the brain’s ability to group the parts of an image together and also to separate images from one another and from their individual backgrounds. How do all these systems combine to produce the vivid images of solid objects that we perceive? This involves extracting biologically relevant information at each stage and associating firing patterns of neuron l populations with past experience. Vision studies also have led to better treatment for visual disorders. Information from research in cats and monkeys has improved the therapy for strabismus, or squint, a term for cross-eye or walleye. Children with strabismus initially have good vision in each eye. But because they cannot fuse the images in the two eyes, they tend to favor one eye and often lose useful vision in the other. Vision can be restored in such cases, but only during infancy or early childhood. Beyond the age of 6 or so, the blindness in one eye becomes permanent. Until a few decades ago, ophthalmologists waited until children reached the age of 4 before operating to align the eyes or prescribing exercises or an eye patch. Now strabismus is corrected very early in life — before age 4, when normal vision can still be restored.

Primary motor cortex (M1), a key region for voluntary motor control, has been considered a first choice as the source of neural signals to control prosthetic devices for humans with paralysis. Less is known about the potential for other areas of frontal cortex as prosthesis signal sources. The frontal cortex is widely engaged in voluntary behavior. Single-neuron recordings in monkey frontal cortex beyond M1 have readily identified activity related to planning and initiating movement direction, remembering movement instructions over delays, or mixtures of these features. Human functional imaging and lesion studies also support this role. Intraoperative mapping during deep brain stimulator placement in humans provides a unique opportunity to evaluate potential prosthesis control signals derived from nonprimary areas and to expand our understanding of frontal lobe function and its role in movement disorders. This study shows that recordings from small groups of human prefrontal/premotor cortex neurons can provide information about movement planning, production, and decision-making sufficient to decode the planned direction of movement. Thus, additional frontal areas, beyond M1, may be valuable signal sources for human neuromotor prostheses.

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.

Extracellular recordings of motor cortex (MI) neurons, using a chronically implanted multi-electrode array, promise to yield a high dimensional input signal to external devices such as a computer, exoskeleton or prosthetic arm. For the multi-electrode array to be used as a sensor for a neuromotor prosthesis (NMP), it is important that it continually record movement-related signals over long time periods. Recent studies have demonstrated that it is possible to continually record for up to 1.5 years from a sufficient number of MI neurons in monkeys to enable neural decoding of arm movement. Cyberkinetics Neurotechnology Systems Inc. has initiated an investigational device exemption (TOE) study investigating the safety and efficacy of the BrainGate/spl trade/ Neural Interface System, a medical device that combines this sensor with data acquisition and processing devices to decode movement intent. This device is currently being investigated as a means for a quadriplegic person to operate a range of assistive technologies. Preliminary results from this case study provide evidence that (1) MI neurons remain active more than 3 years after spinal cord injury, (2) units can be recorded 6 months after surgery. This technology may benefit quadriplegic people by providing a new output pathway from the cortex, to control their muscles.

An implanted neural interface system may eventually afford patients with severe motor impairment a new output signal from their central nervous systems. By deriving output signals directly from the cerebral cortex, the BrainGate Neural Interface may provide a signal that can function in patients with a broad range of motor impairments. Previous studies in non-human primates (Serruya et al., 2002 Nature 416:141) indicate that the neural activity of a small number of cortical neurons coupled to simple mathematical decoding algorithms can generate a behaviorally useful output signal. The system consists of an intracortical microelectrode array, an amplifier and signal conditioning system (processor module), a decoder and a patient computer interface. The sensor is based on the Cyberkinetics 100 channel silicon electrode array and is designed to be implanted into the cortex. In its current version the array is connected externally through a 100-contact percutaneous connector. This implant has been tested in non-human primates. Signal processing involves standard spike discrimination. The decoder is designed to build mathematical relations between desired actions and brain output. A clinical trial protocol has been developed and initial sites for clinical trials are being explored. The protocol includes measures designed to characterize the safety profile of this new device, and measures to assess the ability of patients to use the novel output to drive a variety of computer programs including assistive software and standard desktop interfaces.

Neural prosthetic devices for paralyzed patients based on implanted microelectrode arrays will require humans to use neural output to control devices. Previously we demonstrated that nonhuman primates could substitute the decoded output of motor cortex neurons for hand motion to perform visuomotor tasks (Serruya et al., 2002 Nature 416:141). As a next step we are examining whether cortical ensembles can be used in humans to achieve rapid, accurate control of external devices. Multielectrode recordings were performed intraoperatively in the premotor/prefrontal cortex of patients prior to mapping for implantation of a deep brain stimulator to treat movement disorders. Patients were mildly sedated, but sufficiently alert to participate in visually-guided arm movement tasks. Participants performed either a 4 direction center out task or a random-target step tracking task using planar arm movements; hand position and targets were displayed on a video monitor. A depth electrode system (5 electrode array) was introduced into the premotor/prefrontal cortex at the site where the DBS implant track was located. Up to 9 neurons have been simultaneously recorded in two patients. Tasks were performed either with hand or neural control of the position feedback cursor. The neural cursor was driven from a linear weighted sum of neural spiking, with filter coefficients determined from a few minutes of spiking during hand control. Patients tested so far could move the neural cursor towards targets, despite ambiguity in the recording location and the small number of neurons available. One patient reached the targets in 13/16 attempts lasting

There were no post-surgical complications which is supported by the continued ability to record neural activity. No adverse events or other study-related complications have been reported. Safety assessments include daily checks of connector, weekly nurse visits, and monthly physician exams including neurological and mental status exams.