The Sense of Effort and two Models of Single-Joint Motor Control

Two sets of experiments were carried out. In the first set, human subjects were asked to make the same effort with the elbow flexors at different joint angles under isometric conditions. In some experiments, the subjects were standing with the arm in a vertical (parasagittal) plane; in others, they were seated with the arm in a horizontal (transverse) plane. When muscular torque at a given effort level (ordinate) was plotted as a function of elbow joint angle (abscissa), the resulting isoeffort torque-angle profiles tended to be flat or negatively sloping over a range from 45° to 135°, and they were often nonmonotonic. Increases in effort up to near-maximal levels caused the isoeffort torque-angle profiles to shift upward with little alteration in shape. In the second set of experiments, seated subjects with the arm horizontal resisted baseline torques produced by a motor that acted to extend the elbow joint. Unexpected increases and decreases in torque were superimposed on the baseline torque. The subjects either were instructed to intervene and return the elbow to the initial (90°) position, or were told, “Do not intervene voluntarily; let the motor move your arm.” Effort was reported both under baseline conditions and after the changes in torque. It was found that changes in effort were a function of the changes in torque opposed by the elbow flexors, and were similar whether the subject had repositioned the arm or allowed it to be moved by the motor. In the latter case, the arm came to rest after displacements that were a function of the size and direction of the torque change. For individual subjects, the largest angular displacements ranged from ° 10° to °20° for changes in torque of ° 10 N.m. There was no evidence for any angular dependence of the effort judgments at a given torque over this angular range. Depending on whether effort is primarily an efferent perception proportional to voluntary motor activity or also has a significant afferent (involuntary) component, different models of motor control are supported by these data.     

The effect of an mGluR5 inhibitor on procedural memory and avoidance discrimination impairments in Fmr1 KO mice

Fragile X syndrome (FXS) is the most common inherited form of intellectual disability. Patients with FXS do not only suffer from cognitive problems, but also from abnormalities/deficits in procedural memory formation. It has been proposed that a lack of fragile X mental retardation protein (FMRP) leads to altered long-term plasticity by deregulation of various translational processes at the synapses, and that part of these impairments might be rescued by the inhibition of type I metabotropic glutamate receptors (mGluRs). We recently developed the Erasmus Ladder, which allows us to test, without any invasive approaches, simultaneously, both procedural memory formation and avoidance behavior during unperturbed and perturbed locomotion in mice. Here, we investigated the impact of a potent and selective mGluR5 inhibitor (Fenobam) on the behavior of Fmr1 KO mice during the Erasmus Ladder task. Fmr1 KO mice showed deficits in associative motor learning as well as avoidance behavior, both of which were rescued by intraperitoneal administration of Fenobam. While the Fmr1 KO mice did benefit from the treatment, control littermates suffered from a significant negative side effect in that their motor learning skills, but not their avoidance behavior, were significantly affected. On the basis of these studies in the FXS animal model, it may be worthwhile to investigate the effects of mGluR inhibitors on both the cognitive functions and procedural skills in FXS patients. However, the use of mGluR inhibitors appears to be strongly contraindicated in healthy controls or non-FXS patients with intellectual disability.