Neural control of finger movement via intracortical brain-machine interface.

OBJECTIVE: Intracortical brain-machine interfaces (BMIs) are a promising source of prosthesis control signals for individuals with severe motor disabilities. Previous BMI studies have primarily focused on predicting and controlling whole-arm movements; precise control of hand kinematics, however, has not been fully demonstrated. Here, we investigate the continuous decoding of precise finger movements in rhesus macaques. APPROACH: In order to elicit precise and repeatable finger movements, we have developed a novel behavioral task paradigm which requires the subject to acquire virtual fingertip position targets. In the physical control condition, four rhesus macaques performed this task by moving all four fingers together in order to acquire a single target. This movement was equivalent to controlling the aperture of a power grasp. During this task performance, we recorded neural spikes from intracortical electrode arrays in primary motor cortex. MAIN RESULTS: Using a standard Kalman filter, we could reconstruct continuous finger movement offline with an average correlation of ρ = 0.78 between actual and predicted position across four rhesus macaques. For two of the monkeys, this movement prediction was performed in real-time to enable direct brain control of the virtual hand. Compared to physical control, neural control performance was slightly degraded; however, the monkeys were still able to successfully perform the task with an average target acquisition rate of 83.1%. The monkeys' ability to arbitrarily specify fingertip position was also quantified using an information throughput metric. During brain control task performance, the monkeys achieved an average 1.01 bits s-1 throughput, similar to that achieved in previous studies which decoded upper-arm movements to control computer cursors using a standard Kalman filter. SIGNIFICANCE: This is, to our knowledge, the first demonstration of brain control of finger-level fine motor skills. We believe that these results represent an important step towards full and dexterous control of neural prosthetic devices.

Chronic recording of hand prosthesis control signals via a regenerative peripheral nerve interface in a rhesus macaque.

OBJECTIVE: Loss of even part of the upper limb is a devastating injury. In order to fully restore natural function when lacking sufficient residual musculature, it is necessary to record directly from peripheral nerves. However, current approaches must make trade-offs between signal quality and longevity which limit their clinical potential. To address this issue, we have developed the regenerative peripheral nerve interface (RPNI) and tested its use in non-human primates. APPROACH: The RPNI consists of a small, autologous partial muscle graft reinnervated by a transected peripheral nerve branch. After reinnervation, the graft acts as a bioamplifier for descending motor commands in the nerve, enabling long-term recording of high signal-to-noise ratio (SNR), functionally-specific electromyographic (EMG) signals. We implanted nine RPNIs on separate branches of the median and radial nerves in two rhesus macaques who were trained to perform cued finger movements. MAIN RESULTS: No adverse events were noted in either monkey, and we recorded normal EMG with high SNR (>8) from the RPNIs for up to 20 months post-implantation. Using RPNI signals recorded during the behavioral task, we were able to classify each monkey's finger movements as flexion, extension, or rest with >96% accuracy. RPNI signals also enabled functional prosthetic control, allowing the monkeys to perform the same behavioral task equally well with either physical finger movements or RPNI-based movement classifications. SIGNIFICANCE: The RPNI signal strength, stability, and longevity demonstrated here represents a promising method for controlling advanced prosthetic limbs and fully restoring natural movement.

Personality type and neural circulatory control.

Psychosocial factors, including type A personality, anger, hostility, and anxiety, have been implicated in the pathogenesis of cardiovascular disease. Abnormal sympathetic responses to stress may help explain the link between certain behavior patterns and cardiovascular disease. We tested the hypothesis that in normal humans, type A personality characteristics are associated with exaggerated heart rate, pressor, and sympathetic nerve responses to mental and physical stress. We measured heart rate, blood pressure, and muscle sympathetic nerve activity (obtained with direct intraneural recordings) at rest and during stress in 45 healthy subjects (19 men and 26 women, age 29.2+/-8.7 years) who had no chronic diseases and were taking no medications. Subjects were divided into tertiles based on type A scores. There were no significant differences in sympathetic or hemodynamic reactivity among the 3 different intensity levels of type A characteristics. Baseline measures and responses to stress tests were similar across the 3 groups. Sympathetic and hemodynamic changes during stress tests were also similar in subject groups stratified according to anger scale and cynicism scale. Sympathetic nerve and hemodynamic measurements at rest and during stress were not different in normal subjects with type A characteristics. Abnormalities in sympathetic or cardiovascular reactivity are unlikely to be implicated in any excess of cardiovascular disease in people with type A personality characteristics.

Spatially regulated translation in embryos: asymmetric expression of maternal Wnt-11 along the dorsal-ventral axis in Xenopus.

Transition from symmetry to asymmetry is a central theme in cell and developmental biology. In Xenopus embryos, dorsal-ventral asymmetry is initiated by a microtubule-dependent cytoplasmic rotation during the first cell cycle after fertilization. Here we show that the cytoplasmic rotation initiates differential cytoplasmic polyadenylation of maternal Xwnt-11 RNA, encoding a member of the Wnt family of cell-cell signaling factors. Translational regulation of Xwnt-11 mRNA along the dorsal-ventral axis results in asymmetric accumulation of Xwnt-11 protein. These results demonstrate spatially regulated translation of a maternal cell-signaling factor along the vertebrate dorsal-ventral axis and represent a novel mechanism for Wnt gene regulation. Spatial regulation of maternal RNA translation, which has been established in invertebrates, appears to be an evolutionarily conserved mechanism in the generation of intracellular asymmetry and the consequential formation of the multicellular body pattern.

Xenopus poly (A) binding protein maternal RNA is localized during oogenesis and associated with large complexes in blastula.

Maternal mRNAs are synthesized during oogenesis and often stored for use during early embryogenesis, before the onset of zygotic transcription. The temporal and spatial regulation of maternal RNAs is likely to be crucial mechanism for the establishment of the body pattern. In the course of a study that identified a Xenopus maternal mRNA that is translationally regulated along the dorsoventral axis, several RNAs were found to behave anomalously in polysomal analysis and are further characterized here. As controls for polysome analysis, elF4E RNA and D7.1 RNA were equally translated in both dorsal and ventral cells, whereas the cell-cell signaling factor noggin RNA was not translated in either cell type. Maternal RNAs encoding poly (A) binding protein (PABP), Vg1 and Xcat-2 were associated with large complexes that, in contrast to polysomes, were not dissociated in magnesium-free buffer. Vg1 and Xcat-2 maternal mRNAs have been shown to be localized during oogenesis to the vegetal hemisphere of the oocyte [Rebagliati et al., 1985; Mosquera et al., 1993]. In situ hybridization analysis indicated that PABP RNA was also localized during oogenesis, to the animal hemisphere in stage VI oocytes. This suggests that association of maternal mRNAs with large EDTA-insensitive mRNP complexes is correlated with intracellular localization, but the specific localization within the oocyte is dependent upon the RNA species.

The use of intravenous pentamidine as prophylaxis against Pneumocystis carinii pneumonia in patients with HIV infection.

The purpose of this study is to report on the use of monthly intravenous pentamidine as prophylaxis against Pneumocystis carinii pneumonia (PCP) within a central London HIV unit. A retrospective case note analysis of HIV-seropositive individuals using intravenous pentamidine as PCP prophylaxis was carried out. Aspects examined included reasons for using the regimen, compliance, adverse reactions and episodes of PCP. Eight patients were studied. There was no prophylaxis failure in 5 patients. Three patients developed PCP whilst on the regimen, although their compliance was poor. In patients who are intolerant of established prophylaxis regimens, intravenous pentamidine may be a useful alternative. It is well tolerated, although compliance is the main problem. Further prospective studies are indicated to assess its efficacy.

Premature closure of the triradiate cartilage. Report of a case.

A case of early closure of the triradiate cartilage, probably secondary to neonatal septic arthritis of the right hip, is reported. Tomograms of the hip showed the triradiate cartilage closed posteriorly, with the anterior portion still open. These findings were confirmed at operation. An arthrogram and a CT scan of the right hip showed subluxation of the femoral head. This unique complication, after an episode of septic arthritis of the hip, has not before been reported in the literature.

Bilateral sacroilac dislocations in an adolescent. A case report.

This is a case report of a 15-year-old female who sustained bilateral closed sacroiliac dislocations. She was successfully treated with bilateral skeletal traction and manual closed reduction. The sacroiliac joints redislocated partially despite further traction. Reduction by traction and pelvic sling was then recovered and further displacement was prevented. She regained full range of motion of her hips. This is an uncommon injury produced only by severe trauma.