Emily R. Oby

Restoration of grasp following paralysis through brain-controlled stimulation of muscles

Patients with spinal cord injury lack the connections between brain and spinal cord circuits that are essential for voluntary movement. Clinical systems that achieve muscle contraction through functional electrical stimulation (FES) have proven to be effective in allowing patients with tetraplegia to regain control of hand movements and to achieve a greater measure of independence in daily activities. In existing clinical systems, the patient uses residual proximal limb movements to trigger pre-programmed stimulation that causes the paralysed muscles to contract, allowing use of one or two basic grasps. Instead, we have developed an FES system in primates that is controlled by recordings made from microelectrodes permanently implanted in the brain. We simulated some of the effects of the paralysis caused by C5 or C6 spinal cord injury by injecting rhesus monkeys with a local anaesthetic to block the median and ulnar nerves at the elbow. Then, using recordings from approximately 100 neurons in the motor cortex, we predicted the intended activity of several of the paralysed muscles, and used these predictions to control the intensity of stimulation of the same muscles. This process essentially bypassed the spinal cord, restoring to the monkeys voluntary control of their paralysed muscles. This achievement is a major advance towards similar restoration of hand function in human patients through brain-controlled FES. We anticipate that in human patients, this neuroprosthesis would allow much more flexible and dexterous use of the hand than is possible with existing FES systems.

Toward the Restoration of Hand Use to a Paralyzed Monkey: Brain-Controlled Functional Electrical Stimulation of Forearm Muscles

Loss of hand use is considered by many spinal cord injury survivors to be the most devastating consequence of their injury. Functional electrical stimulation (FES) of forearm and hand muscles has been used to provide basic, voluntary hand grasp to hundreds of human patients. Current approaches typically grade pre-programmed patterns of muscle activation using simple control signals, such as those derived from residual movement or muscle activity. However, the use of such fixed stimulation patterns limits hand function to the few tasks programmed into the controller. In contrast, we are developing a system that uses neural signals recorded from a multi-electrode array implanted in the motor cortex; this system has the potential to provide independent control of multiple muscles over a broad range of functional tasks. Two monkeys were able to use this cortically controlled FES system to control the contraction of four forearm muscles despite temporary limb paralysis. The amount of wrist force the monkeys were able to produce in a one-dimensional force tracking task was significantly increased. Furthermore, the monkeys were able to control the magnitude and time course of the force with sufficient accuracy to track visually displayed force targets at speeds reduced by only one-third to one-half of normal. Although these results were achieved by controlling only four muscles, there is no fundamental reason why the same methods could not be scaled up to control a larger number of muscles. We believe these results provide an important proof of concept that brain-controlled FES prostheses could ultimately be of great benefit to paralyzed patients with injuries in the mid-cervical spinal cord.

Neural representations of social status hierarchy in human inferior parietal cortex.

Mental representations of social status hierarchy share properties with that of numbers. Previous neuroimaging studies have shown that the neural representation of numerical magnitude lies within a network of regions within inferior parietal cortex. However the neural basis of social status hierarchy remains unknown. Using fMRI, we studied subjects while they compared social status magnitude of people, objects and symbols, as well as numerical magnitude. Both social status and number comparisons recruited bilateral intraparietal sulci. We also observed a semantic distance effect whereby neural activity within bilateral intraparietal sulci increased for semantically close relative to far numerical and social status comparisons. These results demonstrate that social status and number comparisons recruit distinct and overlapping neuronal representations within human inferior parietal cortex.

Local field potentials allow accurate decoding of muscle activity

Local field potentials (LFPs) in primary motor cortex include significant information about reach target location and upper limb movement kinematics. Some evidence suggests that they may be a more robust, longer-lasting signal than action potentials (spikes). Here we assess whether LFPs can also be used to decode upper limb muscle activity, a complex movement-related signal. We record electromyograms from both proximal and distal upper limb muscles from monkeys performing a variety of reach-to-grasp and isometric wrist force tasks. We show that LFPs can be used to decode activity from both proximal and distal muscles with performance rivaling that of spikes. Thus, motor cortical LFPs include information about more aspects of movement than has been previously demonstrated. This provides further evidence suggesting that LFPs could provide a highly informative, long-lasting signal source for neural prostheses.

Functional Connectivity and Tuning Curves in Populations of Simultaneously Recorded Neurons

How interactions between neurons relate to tuned neural responses is a longstanding question in systems neuroscience. Here we use statistical modeling and simultaneous multi-electrode recordings to explore the relationship between these interactions and tuning curves in six different brain areas. We find that, in most cases, functional interactions between neurons provide an explanation of spiking that complements and, in some cases, surpasses the influence of canonical tuning curves. Modeling functional interactions improves both encoding and decoding accuracy by accounting for noise correlations and features of the external world that tuning curves fail to capture. In cortex, modeling coupling alone allows spikes to be predicted more accurately than tuning curve models based on external variables. These results suggest that statistical models of functional interactions between even relatively small numbers of neurons may provide a useful framework for examining neural coding.

Intrafascicular stimulation of monkey arm nerves evokes coordinated grasp and sensory responses

High-count microelectrode arrays implanted in peripheral nerves could restore motor function after spinal cord injury or sensory function after limb loss. In this study, we implanted Utah Slanted Electrode Arrays (USEAs) intrafascicularly at the elbow or shoulder in arm nerves of rhesus monkeys (n = 4) under isoflurane anesthesia. Input-output curves indicated that pulse-width-modulated single-electrode stimulation in each arm nerve could recruit single muscles with little or no recruitment of other muscles. Stimulus trains evoked specific, natural, hand movements, which could be combined via multielectrode stimulation to elicit coordinated power or pinch grasp. Stimulation also elicited short-latency evoked potentials (EPs) in primary somatosensory cortex, which might be used to provide sensory feedback from a prosthetic limb. These results demonstrate a high-resolution, high-channel-count interface to the peripheral nervous system for restoring hand function after neural injury or disruption or for examining nerve structure.

Movement representation in the primary motor cortex and its contribution to generalizable EMG predictions

It is well known that discharge of neurons in the primary motor cortex (M1) depends on end-point force and limb posture. However, the details of these relations remain unresolved. With the development of brain-machine interfaces (BMIs), these issues have taken on practical as well as theoretical importance. We examined how the M1 encodes movement by comparing single-neuron and electromyographic (EMG) preferred directions (PDs) and by predicting force and EMGs from multiple neurons recorded during an isometric wrist task. Monkeys moved a cursor from a central target to one of eight peripheral targets by exerting force about the wrist while the forearm was held in one of two postures. We fit tuning curves to both EMG and M1 activity measured during the hold period, from which we computed both PDs and the change in PD between forearm postures (ΔPD). We found a unimodal distribution of these ΔPDs, the majority of which were intermediate between the typical muscle response and an unchanging, extrinsic coordinate system. We also discovered that while most neuron-to-EMG predictions generalized well across forearm postures, end-point force measured in extrinsic coordinates did not. The lack of force generalization was due to musculoskeletal changes with posture. Our results show that the dynamics of most of the recorded M1 signals are similar to those of muscle activity and imply that a BMI designed to drive an actuator with dynamics like those of muscles might be more robust and easier to learn than a BMI that commands forces or movements in external coordinates.

Electrical conduction block in large nerves: high-frequency current delivery in the nonhuman primate.

Recent studies have made significant progress toward the clinical implementation of high‐frequency conduction block (HFB) of peripheral nerves. However, these studies were performed in small nerves, and questions remain regarding the nature of HFB in large‐diameter nerves. This study in nonhuman primates shows reliable conduction block in large‐diameter nerves (up to 4.1 mm) with relatively low‐threshold current amplitude and only moderate nerve discharge prior to the onset of block. Muscle Nerve, 2011

Nerve cuff stimulation and the effect of fascicular organization for hand grasp in nonhuman primates

The overall goal of this work is to introduce nerve cuff electrodes into upper extremity hand grasp systems. The first challenge is to develop a nerve cuff electrode that can selectively activate multiple hand functions from common upper extremity peripheral nerves. The Flat Interface Nerve Electrode (FINE) has shown selective stimulation capability in animal trials. The FINE wraps around the nerve and gently reshapes the nerve and aligns the fascicles within the nerve. Our hypothesis is that the FINE can selectively stimulate multi-fascicular nerves in the human upper extremity resulting in selective hand function. To assess the ability of the FINE to produce control of a hand with many degrees of freedom, we have tested the FINE in nonhuman primates. Fascicular organization and fascicle count are important factors to consider when determining electrode placement. The proximal nerve is an attractive electrode location to access both extrinsic and intrinsic muscles in the upper extremity. A challenge with the nonhuman primate model is that the nonhuman primate median and ulnar nerves both have uni-fascicular regions proximally. The human proximal median and ulnar nerves have an encouraging anatomy of multi-fasciculated nerves with redundant fascicles that may result in more selective hand function than is capable in the nonhuman primate.

Prediction of Muscle Activity from Cortical Signals to Restore Hand Grasp in Subjects with Spinal Cord Injury.

Publisher Summary Spinal cord injury (SCI) leaves patients partially or entirely unable to activate muscles that are innervated by nerves below the level of injury. Roughly half of SCIs occur above the sixth cervical vertebra, thereby affecting all four limbs and leaving the individuals unable to grasp objects effectively with their hands. There are important changes to both the muscles and the brain that occur as a result of either the injury or subsequent disuse; the essential problem is that motor commands, still formulated in the brain, can no longer reach the muscles. Functional electrical stimulation (FES) has been used for nearly five decades in an attempt to restore some level of motor function to paralyzed individuals through electrical stimulation of muscles. FES has successfully been applied to provide appropriately timed dorsiflexion for patients suffering foot drop as a result of SCI or stroke, and other systems provide some support for stance or walking. Stimulation of the phrenic nerve has been used in the case of high-level injuries to replace or augment the use of an external ventilator, and systems have been devised to provide bowel and bladder control.