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The feasibility of implanting an array of penetrating electrodes into peripheral nerves is studied in acute experiments in the cat sciatic nerve. A novel, silicon-based array of microelectrodes, the Utah Electrode Array, was used, which contains 25 or 100 1-mm long electrodes that project out from a silicon substrate. Electrode arrays of this complexity, when inserted in the peripheral nerve, could cause significant compression of the nerve and block the conduction of action potentials. Using a high velocity insertion technique, the electrode array was implanted into the sciatic nerve. Compound action potentials were evoked by and recorded with cuff electrodes. Compound action potentials recorded 1 h after insertion were only slightly altered from those recorded before insertion. Single units were readily extracted from evoked multiunit neural recordings in response to cutaneous stimulation and limb rotation around joints. Current injections into the nerve through the electrodes evoked muscle twitches with currents in the 10 microA range. Recording and stimulation stability were demonstrated for periods of up to 60 h. We have shown that high density arrays of electrodes can be inserted into the peripheral nerve and can provide a stable recording and stimulating interface to individual peripheral nerve axons. Such an array may be useful in future neuroscience research and potential neuroprosthetic applications.

The authors report the use of dense two-dimensional microelectrode array recordings to characterize fine resolution electrocortical activity ("microEEG") in epileptogenic human cortex. A 16-mm(2) 96 microelectrode array with 400-mum interelectrode spacing was implanted in five patients undergoing invasive EEG monitoring for medically refractory epilepsy. High spatial resolution data from the array were analyzed in conjunction with simultaneously acquired data from standard intracranial electrode grids and strips. microEEG recorded from within the epileptogenic zone demonstrates discharges resembling both interictal epileptiform activity ("microdischarges") and electrographic seizures ("microseizures") but confined to cortical regions as small as 200 microm(2). In two patients, this activity appeared to be involved in the initiation or propagation of electrographic seizures. The authors hypothesize that microdischarges and microseizures are generated by small cortical domains that form the substrate of epileptogenic cortex and play important roles in seizure initiation and propagation.

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. The cover shows Matt Nagle, first participant in the BrainGate pilot clinical trial. He is unable to move his arms or legs following cervical spinal cord injury. Researchers at the Department of Neuroscience at Brown University, working with biotech company Cyberkinetics and 3 other institutions, demonstrate that movement-related signals can be relayed from the brain via an implanted BrainGate chip, allowing the patient to drive a computer screen cursor and activate simple robotic devices. Such neuromotor prostheses could pave the way towards systems to replace or restore lost motor function in paralysed humans. Prior to this advance, this type of work has been performed chiefly in monkeys. The latest example of such research has achieved a large increase in speed over current devices, enhancing the prospects for clinically viable brain-machine interfaces.

The restoration of graceful, yet powerful movements in paralyzed regions of the body has not been achieved in humans. The problems are manifold and each is quite complex. Normal motions around a single joint are typically produced by coordinated activation of many muscles. Further, graded force generation in a single muscle is achieved by successively recruiting more and more motoneurons that innervate the target muscle. Finally, normal physiological movements are often achieved without excessive fatigue, a condition difficult to replicate with conventional cuff-type, epimysial, or surface electrodes. We have conducted experiments using intrafascicular multielectrodc stimulation (IFMS) in the cat sciatic nerve that address many of these problems by D. McDonnall, et al. (2004). We have implanted Utah slanted electrode arrays (USEA's) in the sciatic nerve of cat, and have been able to selectively stimulate small, independent subpopulations of motoneurons that innervate the muscles of the lower leg. The USEA consists of a 10 /spl times/ 10 grid of graded-length microelectrodes separated by 400 microns. We have shown that motoneuron stimulation via the USEA is highly selective and that stimulation via specific electrodes can evoke a maximal force in each of these muscles without producing substantive forces in the others. Further, because different electrodes excite different motoneurons innervating a particular muscle, we have been able to interleave low-frequency stimulation through these electrodes to produce ripple-free, fatigue-resistant forces over a large range of forces. These experiments demonstrate that IFMS can be achieved with high-count penetrating electrode arrays with a slanted architecture. Such arrays, when inserted into the nerves of the peripheral nervous system, could be used to recreate graceful, yet powerful, fatigue-resistant motions in the musculo-skeletal system of paralyzed subjects. The large number of muscles that can be activated via the 100 electrodes in a single USCA implantation, together with the relative ease of surgical implantation of these devices, offers a promising approach to reanimation of paralyzed limbs.

We studied the consequences of long-term implantation of a penetrating microelectrode array in peripheral nerve over the time course of 4-6 mo. Electrode arrays without lead wires were implanted to test the ability of different containment systems to protect the array and nerve during contractions of surrounding muscles. Treadmill walking was monitored and the animals showed no functional deficits as a result of implantation. In a different set of experiments, electrodes with lead wires were implanted for up to 7 mo and the animals were tested at 2-4 week intervals at which time stimulation thresholds and recorded sensory activity were monitored for every electrode. It was shown that surgical technique highly affected the long-term stimulation results. Results between measurement sessions were compared, and in the best case, the stimulation properties stabilized in 80% of the electrodes over the course of the experiment (162 days). The recorded sensory signals, however, were not stable over time. A histological analysis performed on all implanted tissues indicated that the morphology and fiber density of the nerve around the electrodes were normal.

The recording capability of a microelectrode array in the cat dorsal root ganglion (DRG) was studied in 11 acute experiments, 373 single, discriminable sensory units were recorded on 587 electrodes (0.64 units/electrode). Sensory action potentials as large as 1750 microV were obtained (mean=132 microV). These were comparable to literature reports of the best DRG extracellular recordings made with conventional electrodes. We were able simultaneously to activate and record over 50 discriminable, time-varying units from L6 and L7 DRGs during a cyclic ankle displacement. We also successfully recorded stable, phase dependent multiple sensory units with very little artifact or electromyographic (EMG) contamination during decerebrate walking. Thus, the array is capable of recording more effectively from more DRGs neurons than has been achieved by conventional recording techniques. The recording selectivity and stability of the array, coupled with the large number of neurons that can be recorded simultaneously, provide attractive features for better understanding sensorimotor control principles.

A practical interface to the peripheral nervous system (or to the spinal cord) that could be used in a neuroprosthetic application must have two features: it should be able to selectively stimulate a large number of individual muscle groups in a highly specific fashion; and it should also be able to stimulate these muscles in a broadly graded fashion in a manner similar to the way they are stimulated naturally. We have developed a new type of silicon based microelectrode array which consists of 100 penetrating needles that project out from a thin silicon substrate. We have developed such an electrode array and have evaluated it in a series of acute implantations in cat sciatic nerve. Using a high velocity insertion technique, the array can be inserted through the epineurium and perineurium with little damage to the propagation of neural activity through the implantation site. The array records single- and multi-unit sensory information. It is capable of generating muscle twitches with single, biphasic 200 usec current pulses in the 1-10 microampere range.

Visual stimuli are represented in neuronal firing of a 2D highly interconnected network of ganglion cells driven by the stimuli. As a result, the network is able to encode more features of the visual stimuli than can the single neurons that make up the network. We have recorded the simultaneous responses of 15 ganglion cells in the isolated, perfused turtle retina to simple visual stimuli circles of various diameters, intensities and colors. We trained a three-layer neural network to classify the responses in terms of stimulus color, size and intensity. The network performed poorly in the classification of the test stimuli. Further, concurrently recorded responses did not do significantly better at specifying the stimulus than did sequentially recorded responses. The approach provides a formalism that allows one to assess the effects of response variability on the ability of the network to classify responses.

Restoration of motor function to individuals who have had spinal cord injuries or stroke has been hampered by the lack of an interface to the peripheral nervous system. A suitable interface should provide selective stimulation of a large number of individual muscle groups with graded recruitment of force. We have developed a new neural interface, the Utah Slanted Electrode Array (USEA), that was designed to be implanted into peripheral nerves. Its goal is to provide such an interface that could be useful in rehabilitation as well as neuroscience applications. In this study, the stimulation capabilities of the USEA were evaluated in acute experiments in cat sciatic nerve. The recruitment properties and the selectivity of stimulation were examined by determining the target muscles excited by stimulation via each of the 100 electrodes in the array and using force transducers to record the force produced in these muscles. It is shown in the results that groups of up to 15 electrodes were inserted into individual fascicles. Stimulation slightly above threshold was selective to one muscle group for most individual electrodes. At higher currents, co-activation of agonist but not antagonist muscles was observed in some instances. Recruitment curves for the electrode array were broader with twitch thresholds starting at much lower currents than for cuff electrodes. In these experiments, it is also shown that certain combinations of electrode pairs, inserted into an individual fascicle, excite fiber populations with substantial overlap, whereas other pairs appear to address independent populations. We conclude that the USEA permits more selective stimulation at much lower current intensities with more graded recruitment of individual muscles than is achieved by conventional cuff electrodes.

We are investigating the representation of simple visual objects by groups of retinal ganglion cells and are simultaneously recording the responses of ganglion cells in the isolated turtle retina with 15 out of an array of 100 penetrating microelectrodes. Stimulation is with circular spots of light of various intensities, diameters and colors. We have trained a three layer artificial neural network to estimate the stimulus parameters and have challenged it to classify the color, size and intensity of test stimuli. Individual ganglion cells are poor encoders of stimulus features, but the 15 cells in our sample allow one to classify intensity, color and spot diameter to within 0.6 log units, 61 nm, and 0.68 mm, respectively.