Human muscle spindles act as forward sensory models.

Modern theories of motor control incorporate forward models that combine sensory information and motor commands to predict future sensory states. Such models circumvent unavoidable neural delays associated with on-line feedback control. Here we show that signals in human muscle spindle afferents during unconstrained wrist and finger movements predict future kinematic states of their parent muscle. Specifically, we show that the discharges of type Ia afferents are best correlated with the velocity of length changes in their parent muscles approximately 100-160 ms in the future and that their discharges vary depending on motor sequences in a way that cannot be explained by the state of their parent muscle alone. We therefore conclude that muscle spindles can act as "forward sensory models": they are affected both by the current state of their parent muscle and by efferent (fusimotor) control, and their discharges represent future kinematic states. If this conjecture is correct, then sensorimotor learning implies learning how to control not only the skeletal muscles but also the fusimotor system.

Impedance control balances stability with metabolically costly muscle activation.

Humans are able to stabilize their movements in environments with unstable dynamics by selectively modifying arm impedance independently of force and torque. We further investigated adaptation to unstable dynamics to determine whether the CNS maintains a constant overall level of stability as the instability of the environmental dynamics is varied. Subjects performed reaching movements in unstable force fields of varying strength, generated by a robotic manipulator. Although the force fields disrupted the initial movements, subjects were able to adapt to the novel dynamics and learned to produce straight trajectories. After adaptation, the endpoint stiffness of the arm was measured at the midpoint of the movement. The stiffness had been selectively modified in the direction of the instability. The stiffness in the stable direction was relatively unchanged from that measured during movements in a null force field prior to exposure to the unstable force field. This impedance modification was achieved without changes in force and torque. The overall stiffness of the arm and environment in the direction of instability was adapted to the force field strength such that it remained equivalent to that of the null force field. This suggests that the CNS attempts both to maintain a minimum level of stability and minimize energy expenditure.

Central representation of dynamics when manipulating handheld objects.

To explore the neural mechanisms related to representation of the manipulation dynamics of objects, we performed whole-brain fMRI while subjects balanced an object in stable and highly unstable states and while they balanced a rigid object and a flexible object in the same unstable state, in all cases without vision. In this way, we varied the extent to which an internal model of the manipulation dynamics was required in the moment-to-moment control of the object's orientation. We hypothesized that activity in primary motor cortex would reflect the amount of muscle activation under each condition. In contrast, we hypothesized that cerebellar activity would be more strongly related to the stability and complexity of the manipulation dynamics because the cerebellum has been implicated in internal model-based control. As hypothesized, the dynamics-related activation of the cerebellum was quite different from that of the primary motor cortex. Changes in cerebellar activity were much greater than would have been predicted from differences in muscle activation when the stability and complexity of the manipulation dynamics were contrasted. On the other hand, the activity of the primary motor cortex more closely resembled the mean motor output necessary to execute the task. We also discovered a small region near the anterior edge of the ipsilateral (right) inferior parietal lobule where activity was modulated with the complexity of the manipulation dynamics. We suggest that this is related to imagining the location and motion of an object with complex manipulation dynamics.

Blocking central opiate function modulates hedonic impact and anterior cingulate response to rewards and losses.

Reward processing is linked to specific neuromodulatory systems with a dopaminergic contribution to reward learning and motivational drive being well established. Neuromodulatory influences on hedonic responses to actual receipt of reward, or punishment, referred to as experienced utility are less well characterized, although a link to the endogenous opioid system is suggested. Here, in a combined functional magnetic resonance imaging-psychopharmacological investigation, we used naloxone to block central opioid function while subjects performed a gambling task associated with rewards and losses of different magnitudes, in which the mean expected value was always zero. A graded influence of naloxone on reward outcome was evident in an attenuation of pleasure ratings for larger reward outcomes, an effect mirrored in attenuation of brain activity to increasing reward magnitude in rostral anterior cingulate cortex. A more striking effect was seen for losses such that under naloxone all levels of negative outcome were rated as more unpleasant. This hedonic effect was associated with enhanced activity in anterior insula and caudal anterior cingulate cortex, areas implicated in aversive processing. Our data indicate that a central opioid system contributes to both reward and loss processing in humans and directly modulates the hedonic experience of outcomes.

Confidence in beliefs about pain predicts expectancy effects on pain perception and anticipatory processing in right anterior insula.

Psychological factors play a major role in exacerbating chronic pain. Effective self-management of pain is often hindered by inaccurate beliefs about the nature of pain which lead to a high degree of emotional reactivity. Probabilistic models of perception state that greater confidence (certainty) in beliefs increases their influence on perception and behavior. In this study, we treat confidence as a metacognitive process dissociable from the content of belief. We hypothesized that confidence is associated with anticipatory activation of areas of the pain matrix involved with top-down modulation of pain. Healthy volunteers rated their beliefs about the emotional distress that experimental pain would cause, and separately rated their level of confidence in this belief. Confidence predicted the influence of anticipation cues on experienced pain. We measured brain activity during anticipation of pain using high-density EEG and used electromagnetic tomography to determine neural substrates of this effect. Confidence correlated with activity in right anterior insula, posterior midcingulate and inferior parietal cortices during the anticipation of pain. Activity in the right anterior insula predicted a greater influence of anticipation cues on pain perception, whereas activity in right inferior parietal cortex predicted a decreased influence of anticipatory cues. The results support probabilistic models of pain perception and suggest that confidence in beliefs is an important determinant of expectancy effects on pain perception.

Transducer and base compliance alter the in situ 6 dof force measured from muscle during an isometric contraction in a multi-joint limb.

Although musculoskeletal models are commonly used, validating the muscle actions predicted by such models is often difficult. In situ isometric measurements are a possible solution. The base of the skeleton is immobilized and the endpoint of the limb is rigidly attached to a 6-axis force transducer. Individual muscles are stimulated and the resulting forces and moments recorded. Such analyses generally assume idealized conditions. In this study we have developed an analysis taking into account the compliances due to imperfect fixation of the skeleton, imperfect attachment of the force transducer, and extra degrees of freedom (dof) in the joints that sometimes become necessary in fixed end contractions. We use simulations of the rat hindlimb to illustrate the consequences of such compliances. We show that when the limb is overconstrained, i.e., when there are fewer dof within the limb than are restrained by the skeletal fixation, the compliances of the skeletal fixation and of the transducer attachment can significantly affect measured forces and moments. When the limb dofs and restrained dofs are matched, however, the measured forces and moments are independent of these compliances. We also show that this framework can be used to model limb dofs, so that rather than simply omitting dofs in which a limb does not move (e.g., abduction at the knee), the limited motion of the limb in these dofs can be more realistically modeled as a very low compliance. Finally, we discuss the practical implications of these results to experimental measurements of muscle actions.

Is titin a 'winding filament'? A new twist on muscle contraction.

Recent studies have demonstrated a role for the elastic protein titin in active muscle, but the mechanisms by which titin plays this role remain to be elucidated. In active muscle, Ca(2+)-binding has been shown to increase titin stiffness, but the observed increase is too small to explain the increased stiffness of parallel elastic elements upon muscle activation. We propose a 'winding filament' mechanism for titin's role in active muscle. First, we hypothesize that Ca(2+)-dependent binding of titin's N2A region to thin filaments increases titin stiffness by preventing low-force straightening of proximal immunoglobulin domains that occurs during passive stretch. This mechanism explains the difference in length dependence of force between skeletal myofibrils and cardiac myocytes. Second, we hypothesize that cross-bridges serve not only as motors that pull thin filaments towards the M-line, but also as rotors that wind titin on the thin filaments, storing elastic potential energy in PEVK during force development and active stretch. Energy stored during force development can be recovered during active shortening. The winding filament hypothesis accounts for force enhancement during stretch and force depression during shortening, and provides testable predictions that will encourage new directions for research on mechanisms of muscle contraction.