Rapid adaptation of brain-computer interfaces to new neuronal ensembles or participants via generative modelling.

For brain-computer interfaces (BCIs), obtaining sufficient training data for algorithms that map neural signals onto actions can be difficult, expensive or even impossible. Here we report the development and use of a generative model-a model that synthesizes a virtually unlimited number of new data distributions from a learned data distribution-that learns mappings between hand kinematics and the associated neural spike trains. The generative spike-train synthesizer is trained on data from one recording session with a monkey performing a reaching task and can be rapidly adapted to new sessions or monkeys by using limited additional neural data. We show that the model can be adapted to synthesize new spike trains, accelerating the training and improving the generalization of BCI decoders. The approach is fully data-driven, and hence, applicable to applications of BCIs beyond motor control.

Evaluation of high-density, multi-contact nerve cuffs for activation of grasp muscles in monkeys.

OBJECTIVE: The objective of this work was to evaluate whether nerve cuffs can selectively activate hand muscles for functional electrical stimulation (FES). FES typically involves identifying and implanting electrodes in many individual muscles, but nerve cuffs only require implantation at a single site around the nerve. This method is surgically more attractive. Nerve cuffs may also more effectively stimulate intrinsic hand muscles, which are difficult to implant and stimulate without spillover to adjacent muscles. APPROACH: To evaluate its ability to selectively activate muscles, we implanted and tested the flat interface nerve electrode (FINE), which is designed to selectively stimulate peripheral nerves that innervate multiple muscles (Tyler and Durand 2002 IEEE Trans. Neural Syst. Rehabil. Eng. 10 294-303). We implanted FINEs on the nerves and bipolar intramuscular wires for recording compound muscle action potentials (CMAPs) from up to 20 muscles in each arm of six monkeys. We then collected recruitment curves while the animals were anesthetized. MAIN RESULT: A single FINE implanted on an upper extremity nerve in the monkey can selectively activate muscles or small groups of muscles to produce multiple, independent hand functions. SIGNIFICANCE: FINE cuffs can serve as a viable supplement to intramuscular electrodes in FES systems, where they can better activate intrinsic and extrinsic muscles with lower currents and less extensive surgery.

A Pilot Study of Femoropopliteal Artery Revascularisation with a Low Dose Paclitaxel Coated Balloon: Is Predilatation Necessary?

OBJECTIVE/BACKGROUND: The objective was to compare 2 year outcomes in patients treated with or without predilatation prior to drug coated balloon (DCB) angioplasty for symptomatic femoropopliteal lesions. METHODS: This prospective multicentre pilot study was conducted at three sites in Germany. It compared claudicants undergoing predilatation with a bare percutaneous transluminal angioplasty (PTA) balloon before DCB (predilatation group) with patients undergoing direct DCB (direct DCB group). Patients were followed for 2 years. Outcomes included late lumen loss at 6 months, and ankle brachial index (ABI), major adverse events, and primary patency at 2 years. A Clinical Events Committee and core laboratories analysed adverse events and angiographic/duplex images, respectively. RESULTS: Between December 2011 and November 2012, 50 patients were enrolled to the predilatation group (12% total occlusions) and 28 to the direct DCB group (5% total occlusions). Follow-up compliance at the 2 year visit was 88% (n = 44) and 86% (n = 24), respectively. Late lumen loss at 6 months was lower in the direct DCB group (0.03 ± 0.68 mm vs. 0.54 ± 0.97 mm; p = .01). Major adverse events over 2 years occurred in seven (15%) patients who underwent predilatation and in five (19%) after direct DCB. Mean ABI at 2 years was 0.94 ± 0.15 after predilatation and 1.0 ± 0.12 after direct DCB. Over 2 years, primary patency (80.3% vs. 78.2%; p = .55) was not statistically different between the groups. After propensity score adjustments, 2 year findings remained unchanged. CONCLUSION: Paclitaxel coated PTA, with or without bare predilatation, is effective over 2 years in symptomatic patients with femoropopliteal stenotic lesions. Adequately powered randomised controlled comparisons are required to confirm these preliminary results.

Brain-controlled neuromuscular stimulation to drive neural plasticity and functional recovery.

There is mounting evidence that appropriately timed neuromuscular stimulation can induce neural plasticity and generate functional recovery from motor disorders. This review addresses the idea that coordinating stimulation with a patient's voluntary effort might further enhance neurorehabilitation. Studies in cell cultures and behaving animals have delineated the rules underlying neural plasticity when single neurons are used as triggers. However, the rules governing more complex stimuli and larger networks are less well understood. We argue that functional recovery might be optimized if stimulation were modulated by a brain machine interface, to match the details of the patient's voluntary intent. The potential of this novel approach highlights the need for a better understanding of the complex rules underlying this form of plasticity.

History of frequent gum chewing is associated with higher unstimulated salivary flow rate and lower caries severity in healthy Chinese adults.

This was a single-center, prospective, cross-sectional study stratified by age and gender with the objective of determining the relationship between gum chewing history, salivary flow, and dental caries severity in adults. We enrolled 191 subjects aged 18-65 years who underwent assessments for gum chewing history, unstimulated salivary flow rate, salivary pH, and caries severity. Unstimulated salivary flow rate tended to decline with increasing age (p = 0.04), and significant differences in unstimulated salivary flow rate were also found for males (0.58 ± 0.32 ml/min) versus females (0.48 ± 0.30 ml/min) (p = 0.02). Weekly gum chewing frequency was greater in younger subjects (p = 0.001) while no age group differences were noted in pieces per day or chewing duration. Gum chewing habits were similar in males and females. A multivariate model demonstrated that only days per week chewing gum (p < 0.001) and gender (p = 0.007) were predictive of unstimulated salivary flow rate (R(2) = 0.40). Mean caries severity scores, assessed via ICDAS II and DMFT, increased with age. In multivariate analysis, age was positively associated with ICDAS (p = 0.001) and days per week chewing gum was negatively associated with ICDAS (p = 0.004), indicating that caries severity increased with age, and that days of chewing provided an inverse effect, with increased days of chewing being associated with decreased severity of caries. Overall, a history of frequent gum chewing is associated with higher unstimulated salivary flow rate and lower caries severity.

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.

Impact of a resistant dextrin on intestinal ecology: how altering the digestive ecosystem with NUTRIOSE®, a soluble fibre with prebiotic properties, may be beneficial for health.

OBJECTIVES: The prebiotic potential of NUTRIOSE®--a sugar-free, digestion-resistant dextrin--was evaluated in two randomized, placebo-controlled trials that included 48 and 40 healthy volunteers, respectively. METHODS: In study 1, the effect on colonic bacteria of NUTRIOSE® 10, 15 or 20 g/day administered for 14 days was examined; in study 2, gut microbial changes in response to NUTRIOSE® 8 g/day for 14 days were monitored using real-time polymerase chain reaction analysis. RESULTS: NUTRIOSE® increased proliferation of Bacteroides and inhibited Clostridum perfringens in both studies, increased ß-glucosidase activity (at 10 and 15 g/day) and decreased colonic pH (at 20 g/day). The increase in short-chain fatty acid production with NUTRIOSE® consumption was not statistically significant. There were no indications of gastrointestinal intolerance at any dose. CONCLUSIONS: According to commonly accepted definitions, NUTRIOSE® is a prebiotic soluble fibre that provides a beneficial effect on colonic ecology while preserving digestive comfort.

Small cell carcinoma of the cervix in liquid-based Pap test: utilization of split-sample immunocytochemical and molecular analysis.

Small cell (neuroendocrine) carcinoma of the uterine cervix (SMCC) is a rare, highly aggressive malignant neoplasm. Both conventional and liquid-based cytology (LBC) cervical smears have low sensitivity in diagnosing SMCC, requiring immunocytochemical (ICH) confirmation. We present the first series of SMCC primarily diagnosed in cytology specimens, and ICH studies performed on the residual LBC specimens with subsequent confirmation of the diagnosis on surgical pathology specimens. Immunocytochemical stains for keratin, p16INK4, and neuroendocrine markers (synaptophysin, chromogranin, CD56) were performed on additional ThinPrep slides. HPV test used chromogenic in situ hybridization high risk HPV DNA probe. The Pap smears in all three specimens were highly cellular with a mixture of squamous cells and numerous well-preserved single or small cohesive clusters of malignant epithelial cells. Tumor cells were small, monomorphic with minimal cytoplasm and high nuclear/cytoplasmic ratio. There was significant nuclear overlap, but no nuclear molding, or smudging of nuclear chromatin. The chromatin pattern was stippled. A background tumor diathesis was prominent. Atypical squamous cells of undetermined significance (ASCUS) were noted in one case, and markedly abnormal squamous cells were seen in another case. The main cytology differential diagnoses included high-grade squamous intraepithelial lesion and an endometrial adenocarcinoma. Immunocytochemical positivity for the neuroendocrine markers supported the diagnoses of SMCC in all three cases. The morphologic features of the concurrent surgical pathology specimens were typical of SMCC. The tissue diagnoses were also confirmed by immunohistochemistry. Our study allows us to conclude that SMCC can be primarily diagnosed in LBC specimens using a panel of immunocytochemical stains.

Motor cortical prediction of EMG: evidence that a kinetic brain-machine interface may be robust across altered movement dynamics.

During typical movements, signals related to both the kinematics and kinetics of movement are mutually correlated, and each is correlated to some extent with the discharge of neurons in the primary motor cortex (M1). However, it is well known, if not always appreciated, that causality cannot be inferred from correlations. Although these mutual correlations persist, their nature changes with changing postural or dynamical conditions. Under changing conditions, only signals directly controlled by M1 can be expected to maintain a stable relationship with its discharge. If one were to rely on noncausal correlations for a brain-machine interface, its generalization across conditions would likely suffer. We examined this effect, using multielectrode recordings in M1 as input to linear decoders of both end point kinematics (position and velocity) and proximal limb myoelectric signals (EMG) during reaching. We tested these decoders across tasks that altered either the posture of the limb or the end point forces encountered during movement. Within any given task, the accuracy of the kinematic predictions tended to be somewhat better than the EMG predictions. However, when we used the decoders developed under one task condition to predict the signals recorded under different postural or dynamical conditions, only the EMG decoders consistently generalized well. Our results support the view that M1 discharge is more closely related to kinetic variables like EMG than it is to limb kinematics. These results suggest that brain-machine interface applications using M1 to control kinetic variables may prove to be more successful than the more standard kinematic approach.

The KineSpring load absorber implant: rationale, design and biomechanical characterization.

Osteoarthritis (OA) of the knee is the leading cause of disability in the adult population. Although a number of treatments for knee OA are available, none effectively prevent OA progression. Currently, a wide therapeutic gap exists for patients who have unsuccessfully exhausted conservative OA treatments but who are hesitant or ineligible to undergo invasive surgery. The KineSpring device is a novel, joint preserving, minimally invasive implant that reduces medial compartment loading without significantly impacting the loading of the lateral compartment. This article describes the rationale for and the design of the KineSpring device and summarizes results of initial biomechanical testing in an OA cadaver model.

Concentric and eccentric isokinetic resistance training similarly increases muscular strength, fat-free soft tissue mass, and specific bone mineral measurements in young women.

UNLABELLED: Women participated in 5 months of unilateral concentric (n = 37) or eccentric (n = 33) isokinetic resistance training of the legs and arms. Limb muscular strength increased as did total body, leg, and arm fat-free soft tissue mass, total body BMC, hip BMD, and forearm BMC and BMD. Isokinetic training benefits bone mineral acquisition. INTRODUCTION AND HYPOTHESIS: Isokinetic resistance training (IRT) is osteogenic; however, it is not known if concentric or eccentric modalities of IRT produce differential effects on bone. We tested our hypothesis that high-load eccentric versus concentric mode of IRT would produce greater increases in muscular strength, fat-free soft tissue mass (FFSTM), bone mineral density (BMD) and content (BMC) in trained legs and arms. METHODS: Participants were randomized to 5 months of concentric (n = 37) or eccentric (n = 33) training. The non-dominant leg and arm were used during training; dominant limbs served as controls. Muscular strength was measured with an isokinetic dynamometer; body composition was measured by dual-energy X-ray absorptiometry. RESULTS: Muscular strength of the concentrically and eccentrically trained leg (18.6%; 28.9%) and arm (12.5%; 24.6%) significantly increased with training. Gains in total body (TB) BMC (p < 0.05) and, in the trained limbs, total proximal femur BMD (p < 0.05) and total forearm BMD (p < 0.05) and BMC (p < 0.05) occurred in both groups. FFSTM increased for the TB and trained leg and arm (all p < 0.001) in both modes. CONCLUSION: Regardless of the mode, high-intensity, slow-velocity IRT increases muscular strength and FFSTM of trained limbs and imparts benefits to TB BMC and site-specific BMD and BMC in young women.

Direct comparison of the task-dependent discharge of M1 in hand space and muscle space.

Since its introduction in the early 1980s, the concept of a "preferred direction" for neuronal discharge has proven to be a powerful means of studying motor areas of the brain. In the current paper, we introduce the concept of a "muscle-space"-preferred direction (PD(M)) that is analogous to the familiar hand-space-preferred direction (PD(H)). PD(M) reflects the similarity between the discharge of a given neuron and the activity of each muscle in much the way that PD(H) reflects the similarity of discharge with motion along each of the three Cartesian coordinate axes. We used PD(M) to analyze the data recorded from neurons in the primary motor cortex (M1) of three different monkeys. The monkeys performed center-out movements within two different cubical workspaces centered either to the left or right of the monkey's shoulder while we simultaneously recorded neuronal discharge, muscle activity, and limb orientation. We calculated preferred directions in both hand space and muscle space, and computed the angles between these vectors under a variety of conditions. PDs for different neurons were broadly distributed throughout both hand space and muscle space, but the muscle-space vectors appeared to form clusters of functionally similar neurons. In general, repeated estimates of PD(M) were more stable over time than were similar estimates of PD(H). Likewise, there was less change in PD(M) than in PD(H) for data recorded from the two different workspaces. However, although a majority of neurons had this muscle-like property, a significant minority was more stable in Cartesian hand space, reflecting a heterogeneity of function within M1.

Movement-related discharge in the cerebellar nuclei persists after local injections of GABA(A) antagonists.

Limb movement-related neurons in the cerebellar nuclei (CN) typically produce bursts of discharge in association with movement. Consequently, given the inhibitory nature of the Purkinje cell (PC) projection to CN, it is puzzling that only a minority of movement-related PCs pause; the majority burst. Some of the movement-related CN activity may be the result of excitation from collaterals of mossy and climbing fiber projections to the cerebellar cortex. The only other input to CN is diffuse and neuromodulatory, from locus ceruleus and raphe nuclei. To investigate the role of the excitatory mossy fiber input, single units in CN were recorded in macaque monkeys during the performance of reaching and manipulation tasks, before and after blocking the PC input with local microinjections of GABA(A) antagonists (bicuculline or SR95531). After these injections, the movement-related modulation of CN discharge was greater and began earlier, compared with the modulation in the preinjection group of neurons. These observations indicate that an important excitatory drive is provided by extracerebellar inputs to CN, most likely from collaterals of mossy fibers. PCs may serve primarily to regulate this activity, by either pausing or bursting as necessary.

Low density of CD1+ cells in the synovial tissue of patients with rheumatoid arthritis.

OBJECTIVE: CD1 molecules present microbial and self glycolipid antigens to a defined T cell subset with features of natural killer cells. CD1 molecules are up-regulated by inflammatory stimuli such as GM-CSF, and we would expect to find increased CD1 expression in the synovium of patients with rheumatoid arthritis (RA) as compared to osteoarthritis (OA). This study was initiated to compare the density of CD1a+, CD1b+, and CD1c+ synovial cells in RA and OA patients. METHODS: Expression of CD1a+, CD1b+, and CD1c+ molecules in synovial tissue was assessed by semiquantitative immunohistochemistry. For comparison, serological, functional, and typical immunohistochemical markers of inflammation were detected. RESULTS: Although patients with RA as compared to OA had highly significantly increased signs of inflammation, the density of CD1a+, CD1b+, and CD1c+ synovial cells was similar This was also true for the density of CD1+ cells in relation to that of activated CD163+ macrophages. There was a high correlation between the densities of CD1a,b,c positive cells, which suggests the existence of similar regulatory pathways. In a combined analysis of RA and OA patients, there existed a negative association between prior NSAID therapy and the density of CD1a+, CD1b+, and CD1c+ synoviocytes in relation to CD163+ macrophages. This is interesting because a similar immunosuppressive aspect of NSAID has never been shown before and this might represent a hitherto unrecognized immunosuppressive aspect of NSAID. CONCLUSION: Considering the high synovial inflammation in patients with RA, the densities of CD1a+, CD1b+, and CD1c+ synovial cells were low compared to patients with OA. Further studies in RA patients are needed to clarify whether a defect in CD1 regulation may exist. Such a defect may lead to an insufficient immune response against microbial glycolipids, which would support smoldering or repeated inadequately responded infection.

Relationships among bone mineral density, body composition, and isokinetic strength in young women.

The purpose of this study was to examine the relationships among bone mineral density (BMD), body composition, and isokinetic strength in young women. Subjects were 76 women (age: 20 +/- 2 yr, height: 164 +/- 6 cm, weight: 57 +/- 6 kg, body fat: 27 +/- 4%) with a normal body mass index (18-25 kg/m(2)). Total body, nondominant proximal femur, and nondominant distal forearm BMD were measured with dual-energy x-ray absorptiometry. Isokinetic concentric (CON) and eccentric (ECC) strength of the nondominant thigh and upper arm were measured at 60 deg/sec. Fat-free mass (FFM) correlated (P < 0.001) with BMD of the total body (r = 0.56) and femoral neck (r = 0.52), whereas fat mass (FM) did not relate to BMD at any site. Leg FFM, but not FM, correlated with BMD in all regions of interest at the proximal femur. Weak associations were observed between arm FFM and forearm BMD. Isokinetic strength did not relate to BMD at any site after correcting for regional FFM. In conclusion, strong, independent associations exist between BMD and FFM, but not FM or isokinetic strength, in young women.

The effect of urethral instrumentation on uroflowmetry.

OBJECTIVE: To evaluate in a prospective study the effect of urethral instrumentation (flexible cystoscopy) on uroflowmetry, and in particular the peak urinary flow rate (Qmax). PATIENTS AND METHODS: Thirty-two consecutive patients (median age 61.8 years, range 24-80) undergoing flexible cystoscopy were included in the analysis. Patients with active urethral stricture disease or urinary infection were excluded. The indications for cystoscopy included haematuria (44%), voiding symptoms (66%), history of bladder cancer (19%), and history of perineal trauma (3%). Patients underwent uroflowmetry immediately before instrumentation. The postvoid residual volume (PVR) was measured by bladder catheterization. After cystoscopy the bladder was completely emptied and then filled with the same volume of sterile normal saline (bladder volume = voided volume + PVR), and the patient underwent a second uroflowmetry. RESULTS: Patients with voiding symptoms (21, 66%) had a median (range) American Urological Association symptom score of 17 (4-34), a Bother score of 16 (1-23), and Quality of Life score of 3 (1-6). The mean Qmax was 16.9 (4.5-36.9) and 13.3 (4.5-39.4) mL/s before and after cystoscopy, respectively (P = 0.029). The mean percentage difference in Qmax was + 27 (- 23 to 139)% higher before than after cystoscopy. After cystoscopy, up to 25% (eight) and 21% (seven) patients had a lower Qmax, from > 15 to < 15 mL/s and from > 12 to < 12 mL/s, respectively. There were no significant differences in the bladder volume and PVR (P = 0.914 and 0.984, respectively). CONCLUSIONS: Urethral instrumentation by flexible cystoscopy significantly alters Qmax. A 'false' mean change in Qmax (favouring improvement) of +27% would result if uroflowmetry data after instrumentation were used at baseline. Therefore, study protocols for benign prostatic obstruction should exclude uroflowmetry data obtained after urethral instrumentation; failure to exclude such data will lead to disproportionately greater improvements in Qmax that are independent of the therapy delivered.

Prediction of muscle activity by populations of sequentially recorded primary motor cortex neurons.

We have adopted an analysis that produces a post hoc prediction of the time course of electromyogram (EMG) activity from the discharge of ensembles of neurons recorded sequentially from the primary motor cortex (M1) of a monkey. Over several recording sessions, we collected data from 50 M1 neurons and several distal forelimb muscles during a stereotyped precision grip task. Ensemble averages were constructed from 5 to 10 trials for each neuron and EMG signal. We used multiple linear regression on randomly chosen subsets of these neurons to find the best fit between the neuronal and EMG data. The fixed delay between neuronal and EMG signals that yielded the largest coefficient of determination (R(2)) between predicted and actual EMG was 50 ms. R(2) averaged 0.83 for ensembles composed of 15 neurons. If, instead, each neuronal signal was delayed by the time of its peak cross-correlation with the EMG signal, R(2) increased to 0.88. Using all 50 neurons, R(2) under these conditions averaged nearly 0.97. A similar analysis was conducted with signals recorded during both a power grip and a precision grip task. Quality of the fit dropped dramatically when parameters from the precision grip for a given set of neurons were used to fit data recorded during the power grip. However, when a single set of regression parameters was used to fit a combination of the two tasks, the quality of the fits decreased by <10% from that of a single task.

Features of motor performance that drive adaptation in rapid hand movements.

In order to explore how subjects correct for errors in movement and adapt their motor programs, we studied rapid hand movements. Subjects grasped a grooved knob and made brisk turning movements to various targets, similar to tuning a radio dial. A motor attached to the knob shaft was configured to apply a destabilizing negative viscous perturbation. Following a period of practice with no perturbations, the negative viscosity was engaged, which caused a large change in overall kinematics: the peak velocity increased, the movement amplitude was too large, and discrete corrective submovements were generated to bring the pointer back onto the target. After about an hour and nearly 1000 trials, subjects learned to move accurately in the new dynamic environment, returning their overall kinematics near to previous levels. Measures of performance included the endpoint error of the primary movement (the initial movement segment), the frequency and amplitude of corrective submovements, task success rate, mean squared jerk, and deviation from a "normal" angular velocity temporal profile. Both the amplitude and frequency of corrective submovements decreased progressively during adaptation as the subjects made fewer target overshoot errors. These results are consistent with motor learning schemes in which adaptation of the motor controller is driven by an attempt to reduce the endpoint error of the primary movement. While there have been many theories regarding what is being optimized in motor control, in general, biologically plausible mechanisms for implementing these schemes have not been described. A biologically plausible optimization criterion is the minimization of the occurrence and amplitude of corrective submovements, since the latter have been proposed as realistic climbing fiber training signals for adaptive changes in the cerebellum. We postulate that the other criteria that have been proposed are instead secondary to an increased accuracy of the primary movement and a corresponding decrease in the occurrence and amplitude of corrective submovements.

Primary motor cortical neurons encode functional muscle synergies.

Many different kinematic and kinetic signals have been proposed as possible variables under the control of the primary motor cortex. Despite the presence of direct projections to motor neurons, muscle activation has received less attention as a controlled variable. Furthermore, although it is well known that descending fibers project to multiple motor pools, an objective, quantitative study of the relation between neuronal modulation and the activity of groups of muscles has not previously been reported. We have recorded the discharge of 310 neurons located in the primary motor cortex of two monkeys, along with the activity of a variety of arm and hand muscles. Data were recorded while the monkey reached to and pressed a series of illuminated buttons. The similarity of a given neuron's discharge with respect to each muscle was determined by calculating the linear cross-correlation between its discharge rate and each rectified, filtered electromyogram. A "functional linkage vector" was then constructed, which expressed the similarity of that neuron's discharge to the entire set of muscles. We discovered discrete groups of functional linkage vectors within the high order muscle space for both monkeys which corresponded to functional properties of the neurons measured by other methods. Several of these groups appeared to represent a functional synergy of muscles, such as those required to extend the limb, press a button, or open the hand in preparation for the press. When the dimensionality of this space was reduced by a principal components analysis, the originally identified clusters of neurons remained well separated. These results are consistent with the hypothesis that the discharge of individual neurons in the primary motor cortex encodes the activity of a relatively small number of functionally relevant groups of muscles. It will be important to determine whether these results will also apply to more complex behavior, and to what extent these functional muscle synergy representations remain fixed across behaviors.