Detection and discrimination of electrical stimuli from an upper limb cuff electrode inM. Mulatta.

Objective.Peripheral nerve interfaces seek to restore nervous system function through electrical stimulation of peripheral nerves. In clinical use, these devices should function reliably for years or decades. In this study, we assessed evoked sensations from multi-channel cuff electrode stimulation in macaque monkeys up to 711 d post-implantation.Approach.Three trained macaque monkeys received multi-channel cuff electrode implants at the median or ulnar nerves in the upper arm. Electrical stimuli from the cuff interfaces evoked sensations, which we measured via standard psychophysical tasks. We adjusted pulse amplitude or pulse width for each block with various electrode channel configurations to examine the effects of stimulus parameterization on sensation. We measured detection thresholds and just-noticeable differences (JNDs) at irregular, near-daily intervals for several months using Bayesian inferencing from trial data. We examined data trends using classical models such as Weber's Law and the strength-duration relationship using linear regression.Main results.Detection thresholds were similar between blocks with pulse width modulation and blocks with pulse amplitude modulation when represented as charge per pulse, the product of the amplitude and the pulse width. Conversely, Weber fractions-calculated as the slope of the regression between JND charge values and reference stimulus charge-were significantly different between pulse width and pulse amplitude modulation blocks for the discrimination task.Significance.Weber fractions were lower in blocks with amplitude modulation than in blocks with pulse width modulation, suggesting that pulse amplitude modulation allows finer resolution of sensory encoding above threshold. Consequently, amplitude modulation may enable a greater dynamic range for sensory perception with neuroprosthetic devices.

Spatial co-adaptation of cortical control columns in a micro-ECoG brain-computer interface.

OBJECTIVE: Electrocorticography (ECoG) has been used for a range of applications including electrophysiological mapping, epilepsy monitoring, and more recently as a recording modality for brain-computer interfaces (BCIs). Studies that examine ECoG electrodes designed and implanted chronically solely for BCI applications remain limited. The present study explored how two key factors influence chronic, closed-loop ECoG BCI: (i) the effect of inter-electrode distance on BCI performance and (ii) the differences in neural adaptation and performance when fixed versus adaptive BCI decoding weights are used. APPROACH: The amplitudes of epidural micro-ECoG signals between 75 and 105 Hz with 300 µm diameter electrodes were used for one-dimensional and two-dimensional BCI tasks. The effect of inter-electrode distance on BCI control was tested between 3 and 15 mm. Additionally, the performance and cortical modulation differences between constant, fixed decoding using a small subset of channels versus adaptive decoding weights using the entire array were explored. MAIN RESULTS: Successful BCI control was possible with two electrodes separated by 9 and 15 mm. Performance decreased and the signals became more correlated when the electrodes were only 3 mm apart. BCI performance in a 2D BCI task improved significantly when using adaptive decoding weights (80%-90%) compared to using constant, fixed weights (50%-60%). Additionally, modulation increased for channels previously unavailable for BCI control under the fixed decoding scheme upon switching to the adaptive, all-channel scheme. SIGNIFICANCE: Our results clearly show that neural activity under a BCI recording electrode (which we define as a 'cortical control column') readily adapts to generate an appropriate control signal. These results show that the practical minimal spatial resolution of these control columns with micro-ECoG BCI is likely on the order of 3 mm. Additionally, they show that the combination and interaction between neural adaptation and machine learning are critical to optimizing ECoG BCI performance.

High-frequency spectral changes in Dorsolateral Prefrontal Cortex for potential neuoroprosthetics.

Dorsolateral Prefrontal Cortex (DLPFC) has been associated with goal encoding in primates. Thus far, the majority of research involving DLPFC, including all electrophysiology studies, has been performed in non-human primates. In this paper, we explore the possibility of utilizing the cortical activity in DLPFC in humans for use in Brain-Computer Interfaces (BCIs). Electrocorticographic signals were recorded from seven patients with intractable epilepsy who had electrode coverage over DLPFC. These subjects performed a visuomotor target-based task to assess DLPFC's involvement in planning, execution, and accomplishment of the simple motor task. These findings demonstrate that there is a distinct high-frequency spectral component in DLPFC associated with accomplishment of the task. It is envisioned that these signals could potentially provide a novel verification of task accomplishment for a BCI.

A chronic generalized bi-directional brain-machine interface.

A bi-directional neural interface (NI) system was designed and prototyped by incorporating a novel neural recording and processing subsystem into a commercial neural stimulator architecture. The NI system prototype leverages the system infrastructure from an existing neurostimulator to ensure reliable operation in a chronic implantation environment. In addition to providing predicate therapy capabilities, the device adds key elements to facilitate chronic research, such as four channels of electrocortigram/local field potential amplification and spectral analysis, a three-axis accelerometer, algorithm processing, event-based data logging, and wireless telemetry for data uploads and algorithm/configuration updates. The custom-integrated micropower sensor and interface circuits facilitate extended operation in a power-limited device. The prototype underwent significant verification testing to ensure reliability, and meets the requirements for a class CF instrument per IEC-60601 protocols. The ability of the device system to process and aid in classifying brain states was preclinically validated using an in vivo non-human primate model for brain control of a computer cursor (i.e. brain-machine interface or BMI). The primate BMI model was chosen for its ability to quantitatively measure signal decoding performance from brain activity that is similar in both amplitude and spectral content to other biomarkers used to detect disease states (e.g. Parkinson's disease). A key goal of this research prototype is to help broaden the clinical scope and acceptance of NI techniques, particularly real-time brain state detection. These techniques have the potential to be generalized beyond motor prosthesis, and are being explored for unmet needs in other neurological conditions such as movement disorders, stroke and epilepsy.

Human motor cortical activity recorded with Micro-ECoG electrodes, during individual finger movements.

In this study human motor cortical activity was recorded with a customized micro-ECoG grid during individual finger movements. The quality of the recorded neural signals was characterized in the frequency domain from three different perspectives: (1) coherence between neural signals recorded from different electrodes, (2) modulation of neural signals by finger movement, and (3) accuracy of finger movement decoding. It was found that, for the high frequency band (60-120 Hz), coherence between neighboring micro-ECoG electrodes was 0.3. In addition, the high frequency band showed significant modulation by finger movement both temporally and spatially, and a classification accuracy of 73% (chance level: 20%) was achieved for individual finger movement using neural signals recorded from the micro-ECoG grid. These results suggest that the micro-ECoG grid presented here offers sufficient spatial and temporal resolution for the development of minimally-invasive brain-computer interface applications.

Two-dimensional movement control using electrocorticographic signals in humans.

We show here that a brain-computer interface (BCI) using electrocorticographic activity (ECoG) and imagined or overt motor tasks enables humans to control a computer cursor in two dimensions. Over a brief training period of 12-36 min, each of five human subjects acquired substantial control of particular ECoG features recorded from several locations over the same hemisphere, and achieved average success rates of 53-73% in a two-dimensional four-target center-out task in which chance accuracy was 25%. Our results support the expectation that ECoG-based BCIs can combine high performance with technical and clinical practicality, and also indicate promising directions for further research.

On the relationship between joint angular velocity and motor cortical discharge during reaching.

Single-unit activity in area M1 was recorded in awake, behaving monkeys during a three-dimensional (3D) reaching task performed in a virtual reality environment. This study compares motor cortical discharge rate to both the hand's velocity and the arm's joint angular velocities. Hand velocity is considered a parameter of extrinsic space because it is measured in the Cartesian coordinate system of the monkey's workspace. Joint angular velocity is considered a parameter of intrinsic space because it is measured relative to adjacent arm/body segments. In the initial analysis, velocity was measured as the difference in hand position or joint posture between the beginning and ending of the reach. Cortical discharge rate was taken as the mean activity between these two times. This discharge rate was compared through a regression analysis to either an extrinsic-coordinate model based on the three components of hand velocity or to an intrinsic-coordinate model based on seven joint angular velocities. The model showed that velocities about four degrees-of-freedom (elbow flexion/extension, shoulder flexion/extension, shoulder internal/external rotation, and shoulder adduction/abduction) were those best represented in the sampled population of recorded activity. Patterns of activity recorded across the cortical population at each point in time throughout the task were used in a second analysis to predict the temporal profiles of joint angular velocity and hand velocity. The population of cortical units from area M1 matched the hand velocity and three of the four major joint angular velocities. However, shoulder adduction/abduction could not be predicted even though individual cells showed good correlation to movement on this axis. This was also the only major degree-of-freedom not well correlated to hand velocity, suggesting that the other apparent relations between joint angular velocity and neuronal activity may be due to intrinsic-extrinsic correlations inherent in reaching movements.

Arm trajectory and representation of movement processing in motor cortical activity.

We review experiments in which single-cell primary motor cortical activity was recorded from Rhesus monkeys (Macaca mulatta) while they performed reaching and drawing tasks. The directional tuning curves generated during reaching were modulated by the speed of movement and this was reflected in the magnitude of population vectors calculated from firing rates of a large population of cells. Directional and speed representation in the firing rates of these cells is robust across both reaching and drawing. Several behavioural invariants related to the speed of drawing were represented in the time-series of population vectors. This high fidelity neural representation of velocity found in motor cortex can be used to visualize the dynamics of motor cortical activity during drawing and suggests that the cost function governing the rate of drawing is bound by neural processing.

Prescription drugs and managed care: can 'free-market détente' hold?

The rapid rise in pharmaceutical benefits costs, often cited as a major contributor to the resurgence in health care cost growth, is beginning to strain the relationship between the pharmaceutical and the managed care industries in the United States. In interviews conducted in 1999, executives from both industries maintained a continued preference for a market-based resolution of these tensions. There is evidence, however, that this private-sector détente may give way in the face of the rising business and political pressures that both industries face. Active leadership will be required to prevent deterioration of the prevailing political climate toward economic controls.

Motor cortical representation of speed and direction during reaching.

The motor cortical substrate associated with reaching was studied as monkeys moved their hands from a central position to one of eight targets spaced around a circle. Single-cell activity patterns were recorded in the proximal arm area of motor cortex during the task. In addition to the well-studied average directional selectivity ("preferred direction") of single-cell activity, we also found the time-varying speed of movement to be represented in the cortical activity. A single equation relating motor cortical discharge rate to these two parameters was developed. This equation, which has both independent (speed only) and interactive (speed and direction) components, described a large portion of the time-varying motor cortical activity during the task. Electromyographic activity from a number of upper arm muscles was recorded during this task. Muscle activity was also found to be directionally tuned; however, the distributions of preferred directions were found to be significantly different from cortical activity. In addition, the effect of speed on cortical and muscle activity was also found to be significantly different.

Motor cortical activity during drawing movements: population representation during spiral tracing.

Monkeys traced spirals on a planar surface as unitary activity was recorded from either premotor or primary motor cortex. Using the population vector algorithm, the hand's trajectory could be accurately visualized with the cortical activity throughout the task. The time interval between this prediction and the corresponding movement varied linearly with the instantaneous radius of curvature; the prediction interval was longer when the path of the finger was more curved (smaller radius). The intervals in the premotor cortex fell into two groups, whereas those in the primary motor cortex formed a single group. This suggests that the change in prediction interval is a property of a single population in primary motor cortex, with the possibility that this outcome is due to the different properties generated by the simultaneous action of separate subpopulations in premotor cortex. Electromyographic (EMG) activity and joint kinematics were also measured in this task. These parameters varied harmonically throughout the task with many of the same characteristics as those of single cortical cells. Neither the lags between joint-angular velocities and hand velocity nor the lags between EMG and hand velocity could explain the changes in prediction interval between cortical activity and hand velocity. The simple spatial and temporal relationship between cortical activity and finger trajectory suggests that the figural aspects of this task are major components of cortical activity.

Motor cortical activity during drawing movements: population representation during lemniscate tracing.

Activity was recorded extracellularly from single cells in motor and premotor cortex as monkeys traced figure-eights on a touch-sensitive computer monitor using the index finger. Each unit was recorded individually, and the responses collected from four hemispheres (3 primary motor and 1 dorsal premotor) were analyzed as a population. Population vectors constructed from this activity accurately and isomorphically represented the shape of the drawn figures showing that they represent the spatial aspect of the task well. These observations were extended by examining the temporal relation between this neural representation and finger displacement. Movements generated during this task were made in four kinematic segments. This segmentation was clearly evident in a time series of population vectors. In addition, the (2)/(3) power law described for human drawing was also evident in the neural correlate of the monkey hand trajectory. Movement direction and speed changed continuously during the task. Within each segment, speed and direction changed reciprocally. The prediction interval between the population vector and movement direction increased in the middle of the segments where curvature was high, but decreased in straight portions at the beginning and end of each segment. In contrast to direction, prediction intervals between the movement speed and population vector length were near-constant with only a modest modulation in each segment. Population vectors predicted direction (vector angle) and speed (vector length) throughout the drawing task. Joint angular velocity and arm muscle EMG were well correlated to hand direction, suggesting that kinematic and kinetic parameters are correlated in these tasks.

Health information policy: on preparing for the next war.

As policymakers demand more and better information about health care, the private health information technology industry is investing heavily to produce the "paperless clinical enterprise" of the future: the infrastructure that will be required to satisfy those demands. Developments on a number of policy fronts, however--from medical privacy legislation to clinical software regulation to "telehealth"--suggest the need for a conscious health information policy that will inform the debate in each niche area with a larger sense of whether public policy will promote or retard private innovation in this area. Given the stakes involved, and the immediacy of the issues, leadership in this direction is badly needed.

Federal regulation of managed care: an impulse in search of a theory?

Although there is growing demand for regulation of the managed care industry, regulatory proponents have yet to articulate a clear theory of regulation. Most observers acknowledge consumer information problems that regulation could address, but there is no consensus regarding regulation of the broader public concern about restrictive medical-necessity determinations by health plans. Concerns about these issues--which fall within the gray areas of divergent clinical opinion--may be difficult or impossible to address by explicit regulation. If policymakers forbear on regulation of medical-necessity determinations, private market innovation may ultimately remedy this problem.

A computationally efficient method for solving the redundant problem in biomechanics.

Determining the optimal set of musculotendon forces with which to produce a forward dynamic simulation of movement typically involves a huge investment of time and computational resources. A new, computationally efficient method is proposed that simultaneously achieves the desired trajectory and the dynamically optimized set of muscle stresses, and hence forces, according to the maximal endurance criterion function of Crowninshield and Brand (1981). Muscle-induced accelerations of the system resulting from unit stress contractions of individual muscles are superposed via the new pseudoinverse method to yield the desired motion trajectory. The method is tested on a control problem involving a five degree-of-freedom (DOF), 30 muscle, upper extremity model, which incorporates a dual rigid-body forearm to represent pronation and supination more adequately. The pseudoinverse method delivered the desired motion to within 0.25 degrees for each DOF during a three-second simulation. It is anticipated that the methodology can be easily and accurately applied to other highly redundant optimal control problems in biomechanics.

Global budgeting in the OECD countries.

Many of the Organization for Economic Cooperation and Development countries use global budgeting to control all or certain portions of their health care expenditures. Although the use of global budgets as a cost-containment tool has not been implemented in the United States in any comprehensive way, recent health care reform initiatives have increased the need for research into such tools. In general, the structure, process, and effectiveness of global budgets vary enormously from country to country, in part because the underlying social welfare system of each country is unique.

A sense of urgency: state governments and health care in the 1990s.

Unless President Clinton induces Congress to move exceedingly quickly to roll Medicaid into some larger reform scheme, his administration will be under heavy pressure to free states to pursue their own health care reform agendas. At that juncture, the most likely casualty would be the ERISA preemption.

Long-term care financing through Federal tax incentives.

Congress and the Administration are currently exploring various methods of promoting access to long-term care. In this article, an inventory of recent legislative proposals for using the Federal tax code to expand access to long-term care services is provided. Proposals are arrayed along a functional typology that includes tax mechanisms to encourage accumulation of funds, promote purchase of long-term care insurance, or induce the diversion of funds accumulated for another purpose (such as individual retirement accounts). The proposals are evaluated against the public policy objective of encouraging risk pooling to minimize social cost.