The complementary dominance hypothesis: a model for remediating the 'good' hand in stroke survivors.

The complementary dominance hypothesis is a novel model of motor lateralization substantiated by decades of research examining interlimb differences in the control of upper extremity movements in neurotypical adults and hemisphere-specific motor deficits in stroke survivors. In contrast to earlier ideas that attribute handedness to the specialization of one hemisphere, our model proposes complementary motor control specializations in each hemisphere. The dominant hemisphere mediates optimal control of limb dynamics as required for smooth and efficient movements, whereas the non-dominant hemisphere mediates impedance control, important for countering unexpected mechanical conditions and achieving steady-state limb positions. Importantly, this model proposes that each hemisphere contributes its specialization to both arms (though with greater influence from either arm's contralateral hemisphere) and thus predicts that lesions to one hemisphere should produce hemisphere-specific motor deficits in not only the contralesional arm, but also the ipsilesional arm of stroke survivors - a powerful prediction now supported by a growing body of evidence. Such ipsilesional arm motor deficits vary with contralesional arm impairment, and thus individuals with little to no functional use of the contralesional arm experience both the greatest impairments in the ipsilesional arm, as well as the greatest reliance on it to serve as the main or sole manipulator for activities of daily living. Accordingly, we have proposed and tested a novel intervention that reduces hemisphere-specific ipsilesional arm deficits and thereby improves functional independence in stroke survivors with severe contralesional impairment.

Symmetry and synchrony of bimanual movements are not predicated on interlimb control coupling.

Previous studies suggest that bimanual coordination recruits neural mechanisms that explicitly couple control of the arms, resulting in symmetric kinematics. However, the higher symmetry for actions that require congruous joint motions compared with noncongruous joint motions calls into question the concept of control coupling as a general policy. An alternative view proposes that codependence might emerge from an optimal feedback controller that minimizes control effort and costs in task performance. Support for this view comes from studies comparing conditions in which both hands move a shared or independent virtual objects. Because these studies have mainly focused on congruous bimanual movements, it remains unclear if kinematic symmetry emerges from such control policies. We now examine movements with congruous or noncongruous joint motions (inertially symmetric or asymmetric, respectively) under shared or independent cursors conditions. We reasoned that if a control policy minimizes kinematic differences between limbs, spatiotemporal symmetry should remain relatively unaffected by inertial asymmetries. As shared tasks reportedly elicit greater interlimb codependence, these conditions should elicit higher bilateral covariance regardless of inertial asymmetries. Our results indicate a robust spatiotemporal symmetry only under inertially symmetric conditions, regardless of cursor condition. We simulated bimanual reaching using an optimal feedback controller with and without explicit costs of kinematic asymmetry, finding that only the latter mirrored our empirical data. Our findings support the hypothesis that bimanual control policies do not include kinematic asymmetry as a cost when it is not demanded by task constraints suggesting that kinematic symmetry depends critically on mechanical movement conditions.NEW & NOTEWORTHY Previously, the control coupling hypothesis and task-dependent control hypothesis have been shown to be robust in the bimanually symmetrical movement, but whether the same policy remains robust in the bimanually asymmetrical movement remains unclear. Here, with evidence from empirical and simulation data, we show that a spatiotemporal symmetry between the arms is not predicated on control coupling, but instead it is predicated on the symmetry of mechanical conditions (e.g. limb inertia) between the arms.

Bilateral arm movements are coordinated via task-dependent negotiations between independent and codependent control, but not by a "coupling" control policy.

Prior research has shown that coordination of bilateral arm movements might be attributed to either control policies that minimize performance and control costs regardless of bilateral symmetry or by control coupling, which activates bilaterally homologous muscles as a single unit to achieve symmetric performance. We hypothesize that independent bimanual control (movements of one arm are performed without influence on the other) and codependent bimanual control (two arms are constrained to move together with high spatiotemporal symmetry) are two extremes on a coordination spectrum that can be negotiated to meet infinite variations in task demands. To better understand and distinguish between these views, we designed a task where minimization of either control costs or asymmetry would yield different patterns of coordination. Participants made bilateral reaches with a shared visual cursor to a midline target. We then covertly varied the gain contribution of either hand to the shared cursor's horizontal position. Across two experiments, we show that bilateral coordination retains high task-dependent sensitivity to subtle visual feedback gain asymmetries applied to the shared cursor. Specifically, we found a change from strong spatial covariation between hands during equal gains to more independent control during asymmetric gains, which occurred rapidly and with high specificity to the dimension of gain manipulation. Furthermore, the extent of spatial covariation was graded to the magnitude of perpendicular gain asymmetry between hands. These findings suggest coordination of bilateral arm movements flexibly maneuvers along a continuous coordination spectrum in a task-dependent manner that cannot be explained by bilateral control coupling.NEW & NOTEWORTHY Minimization of performance and control costs and efferent coupling between bilaterally homologous muscle groups have been separately hypothesized to describe patterns of bimanual coordination. Here, we address whether the mechanisms mediating independent and codependent control between limbs can be weighted for successful task performance. Using bilaterally asymmetric visuomotor gain perturbations, we show bimanual coordination can be characterized as a negotiation along a spectrum between extremes of independent and codependent control, but not efferent control coupling.

Chronic intermittent hypoxia enhances disease progression in myeloma-resistant mice.

Obesity is the only known modifiable risk factor for multiple myeloma (MM), an incurable cancer of bone marrow plasma cells. The mechanism linking the two is unknown. Obesity is associated with an increased risk of sleep apnea, which results in chronic intermittent hypoxia (CIH), and drives solid tumor aggressiveness. Given the link between CIH and solid tumor progression, we tested the hypothesis that CIH drives the proliferation of MM cells in culture and their engraftment and progression in vivo. Malignant mouse 5TGM1 cells were cultured in CIH, static hypoxia, or normoxia as a control in custom, gas-permeable plates. Typically MM-resistant C57BL/6J mice were exposed to 10 h/day CIH (AHI = 12/h), static hypoxia, or normoxia for 7 days, followed by injection with 5TGM1 cells and an additional 28 days of exposure. CIH and static hypoxia slowed the growth of 5TGM1 cells in culture. CIH-exposed mice developed significantly more MM than controls (67 vs. 12%, P = 0.005), evidenced by hindlimb paralysis, gammopathy, bone lesions, and bone tumor formation. Static hypoxia was not a significant driver of MM progression and did not reduce survival (P = 0.117). Interestingly, 5TGM1 cells preferentially engrafted in the bone marrow and promoted terminal disease in CIH mice, despite a lower tumor burden, compared with the positive controls. These first experiments in the context of hematological cancer demonstrate that CIH promotes MM through mechanisms distinct from solid tumors and that sleep apnea may be a targetable risk factor in patients with or at risk for blood cancer.