The human motor cortex contributes to gravity compensation to maintain posture and during reaching.

The neural control of posture and movement is interdependent. During voluntary movement, the neural motor command is executed by the motor cortex through the corticospinal tract and its collaterals and subcortical targets. Here we address the question of whether the control mechanism for the postural adjustments at nonmoving joints is also involved in overcoming gravity at the moving joints. We used single-pulse transcranial magnetic stimulation to measure the corticospinal excitability in humans during postural and reaching tasks. We hypothesized that the corticospinal excitability is proportional to background muscle activity and the gravity-related joint moments during both static postures and reaching movements. To test this hypothesis, we used visual targets in virtual reality to instruct five postures and three movements with or against gravity. We then measured the amplitude and gain of motor evoked potentials in multiple arm and hand muscles at several phases of the reaching motion and during static postures. The stimulation caused motor evoked potentials in all muscles that were proportional to the muscle activity. During both static postures and reaching movements, the muscle activity and the corticospinal contribution to these muscles changed in proportion with the postural moments needed to support the arm against gravity, supporting the hypothesis. Notably, these changes happened not only in antigravity muscles. Altogether, these results provide evidence that the changes in corticospinal excitability cause muscle cocontraction that modulates limb stiffness. This suggests that the motor cortex is involved in producing postural adjustments that support the arm against gravity during posture maintenance and reaching.NEW & NOTEWORTHY Animal studies suggest that the corticospinal tract and its collaterals are crucial for producing postural adjustments that accompany movement in limbs other than the moving limb. Here we provide evidence for a similar control schema for both arm posture maintenance and gravity compensation during movement of the same limb. The observed interplay between the postural and movement control signals within the corticospinal tract may help explain the underlying neural motor deficits after stroke.

HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial.

INTRODUCTION: A potential concern with the use of dapivirine (DPV) for HIV prevention is the selection of a drug-resistant virus that could spread and reduce the effectiveness of non-nucleoside reverse transcriptase (NNRTI)-based first-line antiretroviral therapy. We evaluated HIV-1 seroconversions in MTN-020/ASPIRE for selection of drug resistance and evaluated the genetic basis for observed reductions in susceptibility to DPV. METHODS: MTN-020/ASPIRE was a placebo-controlled, Phase III safety and effectiveness study of DPV ring for HIV-1 prevention conducted at 15 sites in South Africa, Zimbabwe, Malawi and Uganda between 2012 and 2015. Plasma from individuals who seroconverted in ASPIRE was analysed for HIV-1 drug resistance using both population Sanger sequencing and next-generation sequencing (NGS) with unique molecular identifiers to report mutations at ≥1% frequency. DPV susceptibility of plasma-derived recombinant HIV-1 containing bulk-cloned full-length reverse transcriptase sequences from MTN-020/ASPIRE seroconversions was determined in TZM-bl cells. Statistical significance was calculated using the Fisher's exact test. RESULTS: Plasma from all 168 HIV seroconversions were successfully tested by Sanger sequencing; 57 of 71 DPV arm and 82 of 97 placebo (PLB) arm participants had NGS results at 1% sensitivity. Overall, 18/168 (11%) had NNRTI mutations including K101E, K103N/S, V106M, V108I, E138A/G, V179D/I/T and H221Y. Five samples from both arms had low-frequency NNRTI mutations that were not detected by Sanger sequencing. The frequency of NNRTI mutations from the DPV arm (11%) was not different from the PLB arm (10%; p = 0.80). The E138A mutation was detected in both the DPV (3 of 71 [4.2%]) and PLB arm (5 of 97 [5.2%]) and conferred modest reductions in DPV susceptibility in some reverse transcriptase backgrounds but not others. CONCLUSIONS: HIV-1 drug resistance including NNRTI resistance did not differ between the DPV and placebo arms of the MTN-020/ASPIRE study, indicating that drug resistance was not preferentially acquired or selected by the DPV ring and that the preventive benefit of DPV ring outweighs resistance risk.

A segmented forearm model of hand pronation-supination approximates joint moments for real time applications.

Musculoskeletal modeling is a new computational tool to reverse engineer human control systems, which require efficient algorithms running in real-time. Human hand pronation-supination movement is accomplished by movement of the radius and ulna bones relative to each other via the complex proximal and distal radioulnar joints, each with multiple degrees of freedom (DOFs). Here, we report two simplified models of this complex kinematic transformation implemented as a part of a 20 DOF model of the hand and forearm. The pronation/supination DOF was implemented as a single rotation joint either within the forearm segment or separating proximal and distal parts of the forearm segment. Torques produced by the inverse dynamic simulations with anatomical architecture of the forearm (OpenSim model) were used as the "gold standard" in the comparison of two simple models. Joint placement was iteratively optimized to achieve the closest representation of torques during realistic hand movements. The model with a split forearm segment performed better than the model with a solid forearm segment in simulating pronation/supination torques. We conclude that simplifying pronation/supination DOF as a single-axis rotation between arm segments is a viable strategy to reduce the complexity of multi-DOF dynamic simulations.

Computational evidence for nonlinear feedforward modulation of fusimotor drive to antagonistic co-contracting muscles.

The sensorimotor integration during unconstrained reaching movements in the presence of variable environmental forces remains poorly understood. The objective of this study was to quantify how much the primary afferent activity of muscle spindles can contribute to shaping muscle coactivation patterns during reaching movements with complex dynamics. To achieve this objective, we designed a virtual reality task that guided healthy human participants through a set of planar reaching movements with controlled kinematic and dynamic conditions that were accompanied by variable muscle co-contraction. Next, we approximated the Ia afferent activity using a phenomenological model of the muscle spindle and muscle lengths derived from a musculoskeletal model. The parameters of the spindle model were altered systematically to evaluate the effect of fusimotor drive on the shape of the temporal profile of afferent activity during movement. The experimental and simulated data were analyzed with hierarchical clustering. We found that the pattern of co-activation of agonistic and antagonistic muscles changed based on whether passive forces in each movement played assistive or resistive roles in limb dynamics. The reaching task with assistive limb dynamics was associated with the most muscle co-contraction. In contrast, the simulated Ia afferent profiles were not changing between tasks and they were largely reciprocal with homonymous muscle activity. Simulated physiological changes to the fusimotor drive were not sufficient to reproduce muscle co-contraction. These results largely rule out the static set and α-γ coactivation as the main types of fusimotor drive that transform the monosynaptic Ia afferent feedback into task-dependent co-contraction of antagonistic muscles. We speculate that another type of nonlinear transformation of Ia afferent signals that is independent of signals modulating the activity of α motoneurons is required for Ia afferent-based co-contraction. This transformation could either be applied through a complex nonlinear profile of fusimotor drive that is not yet experimentally observed or through presynaptic inhibition.

Correction: Biomechanical Constraints Underlying Motor Primitives Derived from the Musculoskeletal Anatomy of the Human Arm.

[This corrects the article DOI: 10.1371/journal.pone.0164050.].

Biomechanical Constraints Underlying Motor Primitives Derived from the Musculoskeletal Anatomy of the Human Arm.

Neural control of movement can only be realized though the interaction between the mechanical properties of the limb and the environment. Thus, a fundamental question is whether anatomy has evolved to simplify neural control by shaping these interactions in a beneficial way. This inductive data-driven study analyzed the patterns of muscle actions across multiple joints using the musculoskeletal model of the human upper limb. This model was used to calculate muscle lengths across the full range of motion of the arm and examined the correlations between these values between all pairs of muscles. Musculoskeletal coupling was quantified using hierarchical clustering analysis. Muscle lengths between multiple pairs of muscles across multiple postures were highly correlated. These correlations broadly formed two proximal and distal groups, where proximal muscles of the arm were correlated with each other and distal muscles of the arm and hand were correlated with each other, but not between groups. Using hierarchical clustering, between 11 and 14 reliable muscle groups were identified. This shows that musculoskeletal anatomy does indeed shape the mechanical interactions by grouping muscles into functional clusters that generally match the functional repertoire of the human arm. Together, these results support the idea that the structure of the musculoskeletal system is tuned to solve movement complexity problem by reducing the dimensionality of available solutions.