Gianfranco Bosco

Sophisticated spinal contributions to motor control

The neural circuitry of the spinal cord is capable of solving some of the most complex problems in motor control. Therefore, spinal mechanisms are much more sophisticated than many neuroscientists give them credit for. A key issue in motor control is how sensory inputs direct and inform motor output,--that is, the sensorimotor process. Other major issues involve the actual control of the motor apparatus. In general, there are at least three basic requirements for motor control: the transformations that map information from sensory to motor coordinates, the specification of individual muscle activations to achieve a kinematic goal, and the control of multiple degrees of freedom. Here, we make the case that the vertebrate spinal cord has the capacity to solve each of these problems to a degree that is relevant for normal behavior.

Contributions of the Human Temporoparietal Junction and MT/V5+ to the Timing of Interception Revealed by Transcranial Magnetic Stimulation

To intercept a fast target at destination, hand movements must be centrally triggered ahead of target arrival to compensate for neuromechanical delays. The role of visual-motion cortical areas is unclear. They likely feed downstream parietofrontal networks with signals reflecting target motion, but do they also contribute internal timing signals to trigger the motor response? We disrupted the activity of human temporoparietal junction (TPJ) and middle temporal area (hMT/V5+) by means of transcranial magnetic stimulation (TMS) while subjects pressed a button to intercept targets accelerated or decelerated in the vertical or horizontal direction. Target speed was randomized, making arrival time unpredictable across trials. We used either repetitive TMS (rTMS) before task execution or double-pulse TMS (dpTMS) during target motion. We found that after rTMS and dpTMS at 100–200 ms from motion onset, but not after dpTMS at 300–400 ms, the button-press responses occurred earlier than in the control, with time shifts independent of target speed. This suggests that activity in TPJ and hMT/V5+ can feed downstream regions not only with visual-motion information, but also with internal timing signals used for interception at destination. Moreover, we found that TMS of hMT/V5+ affected interception of all tested motion types, whereas TMS of TPJ significantly affected only interception of motion coherent with natural gravity. TPJ might specifically gate visual-motion information according to an internal model of the effects of gravity.

Phase-specific sensory representations in spinocerebellar activity during stepping: evidence for a hybrid kinematic/kinetic framework

The dorsal spinocerebellar tract (DSCT) provides a major mossy fiber input to the spinocerebellum, which plays a significant role in the control of posture and locomotion. Recent work from our laboratory has provided evidence that DSCT neurons encode a global representation of hindlimb mechanics during passive limb movements. The framework that most successfully accounts for passive DSCT behavior is kinematics-based having the coordinates of the limb axis, limb-axis length and orientation. Here we examined the responses of DSCT neurons in decerebrate cats as they walked on a moving treadmill and compared them with the responses passive step-like movements of the hindlimb produced manually. We found that DSCT responses to active locomotion were quantitatively different from the responses to kinematically similar passive limb movements on the treadmill. The differences could not be simply accounted for by the difference in limb-axis kinematics in the two conditions, nor could they be accounted for by new or different response components. Instead, differences could be attributed to an increased relative prominence of specific response components occurring during the stance phase of active stepping, which may reflect a difference in the behavior of the sensory receptors and/or of the DSCT circuitry during active stepping. We propose from these results that DSCT neurons encode two global aspects of limb mechanics that are also important in controlling locomotion at the spinal level, namely the orientation angle of the limb axis and limb loading. Although limb-axis length seemed to be an independent predictor of DSCT activity during passive limb movements, we argue that it is not independent of limb loading, which is likely to be proportional to limb length under passive conditions.

Visual gravitational motion and the vestibular system in humans

The visual system is poorly sensitive to arbitrary accelerations, but accurately detects the effects of gravity on a target motion. Here we review behavioral and neuroimaging data about the neural mechanisms for dealing with object motion and egomotion under gravity. The results from several experiments show that the visual estimates of a target motion under gravity depend on the combination of a prior of gravity effects with on-line visual signals on target position and velocity. These estimates are affected by vestibular inputs, and are encoded in a visual-vestibular network whose core regions lie within or around the Sylvian fissure, and are represented by the posterior insula/retroinsula/temporo-parietal junction. This network responds both to target motions coherent with gravity and to vestibular caloric stimulation in human fMRI studies. Transient inactivation of the temporo-parietal junction selectively disrupts the interception of targets accelerated by gravity.

Catching what we can't see: manual interception of occluded fly-ball trajectories.

Control of interceptive actions may involve fine interplay between feedback-based and predictive mechanisms. These processes rely heavily on target motion information available when the target is visible. However, short-term visual memory signals as well as implicit knowledge about the environment may also contribute to elaborate a predictive representation of the target trajectory, especially when visual feedback is partially unavailable because other objects occlude the visual target. To determine how different processes and information sources are integrated in the control of the interceptive action, we manipulated a computer-generated visual environment representing a baseball game. Twenty-four subjects intercepted fly-ball trajectories by moving a mouse cursor and by indicating the interception with a button press. In two separate sessions, fly-ball trajectories were either fully visible or occluded for 750, 1000 or 1250 ms before ball landing. Natural ball motion was perturbed during the descending trajectory with effects of either weightlessness (0 g) or increased gravity (2 g) at times such that, for occluded trajectories, 500 ms of perturbed motion were visible before ball disappearance. To examine the contribution of previous visual experience with the perturbed trajectories to the interception of invisible targets, the order of visible and occluded sessions was permuted among subjects. Under these experimental conditions, we showed that, with fully visible targets, subjects combined servo-control and predictive strategies. Instead, when intercepting occluded targets, subjects relied mostly on predictive mechanisms based, however, on different type of information depending on previous visual experience. In fact, subjects without prior experience of the perturbed trajectories showed interceptive errors consistent with predictive estimates of the ball trajectory based on a-priori knowledge of gravity. Conversely, the interceptive responses of subjects previously exposed to fully visible trajectories were compatible with the fact that implicit knowledge of the perturbed motion was also taken into account for the extrapolation of occluded trajectories.

Modulation of Dorsal Spinocerebellar Responses to Limb Movement. I. Effect of Serotonin

Spinocerebellar neurons (DSCT) receive converging sensory information from various sensory receptors in the hindlimbs and lower trunk. Previous studies have shown that sensory processing by DSCT neurons results in a representation of global hindlimb kinematic parameters such as the length and the orientation of the limb axis. In addition to the sensory input, the DSCT circuitry also receives a descending input from the raphe nuclei in the brain stem. Recent studies have demonstrated that the raphe serotonergic terminals synapse directly on DSCT neurons and exert a differential modulatory influence on their sensory inputs. We examined the role of serotonergic modulation on the DSCT representation of hindlimb kinematic parameters by recording DSCT activity during passive hindlimb movements before and after perturbing serotonergic transmission. We used two types of perturbation: electrical stimulation of the raphe areas in the brain stem to release serotonin in the spinal cord (42 neurons) and intravenous administration of serotonergic agonists or antagonists, mostly the 5HTP2 antagonist ketanserin (30 neurons). We found that movement responses were altered in approximately 70% of the DSCT units studied with each protocol. Changes could include shifts in mean firing rate, increases or decreases in response amplitude, and changes in response waveform. We used a principal component analysis (PCA) to examine waveform components and to determine how they contributed to the response waveform changes caused by serotonin perturbation. Such changes could be explained by new or different response components that might indicate a modification in the data processing or by a different weighting of existing components that might indicate a modification of synaptic weighting. The results were consistent with the second alternative. We found that the same underlying response components could account for both control responses and those altered by serotonin perturbations. The observed changes in waveform could be entirely accounted for by a re-weighting of response components. In particular, the changes observed after raphe stimulation could be accounted for by selective changes in the weighting of the first principal component (PC) with only minor changes of the weighting of the second PC. Because these response components were shown previously to correlate with the limb axis orientation and length trajectories respectively, the finding is consistent with the idea that limb axis length and orientation information are processed separately within the spinal circuitry.

Cerebellar encoding of limb position

In this paper, we review single and multijoint studies that, over the years, have provided insight on the cerebellar encoding of limb spatial position. In particular, we present support to the idea that the cerebellum integrates signals from multiple sources to encode global limb parameters. Then, we highlight the result of recent studies that analyzed quantitatively the relationships between limb endpoint position and cerebellar activity. These findings suggest that the cerebellum may share with other central sensorymotor structures an anisotropic representation of limb position characterized by a strong bias along the anteroposterior axis. Finally, we speculate that this anisotropy may also subtend an internal representation of limb mechanics.

Information processing in the spinocerebellar system.

The purpose of this study was to determine whether sensory information about limb kinematics relayed to the cerebellum over spinocerebellar pathways may be modified at the cerebellar level. We tested this by recording from dorsal spinocerebellar tract (DSCT) and Purkinje cells under the same experimental conditions in which the hindlimbs of anesthetized cats were passively moved through a series of step-like movement cycles. A population analysis of the response behavior showed that DSCT neurons encode a combination of limb axis position and movement velocity, whereas the Purkinje cells located in the DSCT cerebellar target areas encode limb axis velocity and position independently. We conclude from this that the cerebellum may somehow extract a velocity component from the afferent input signal.

Processing of Limb Kinematics in the Interpositus Nucleus

Neural representations of limb movement kinematic parameters are common among central nervous system structures involved in motor control, such as the interpositus nucleus of the cerebellum. Much experimental evidence indicates that neurons in the interpositus may encode limb kinematic parameters both during active, voluntary actions and during limb motion imposed passively, which entrains only sensory afferents. With respect to the sensory processing of information related to movement kinematics, we show that interpositus neuronal activity can parse out the directional from the scalar component (i.e., the movement speed) of the velocity vector. Moreover, a differential role for the anterior and posterior portion of interpositus in encoding these parameters emerged from these data, since the activity of the posterior interpositus was specifically associated to changes of movement speed. Limb movement representations in the interpositus nucleus may be instrumental for the control of goal-directed movements such as shaping hand during grasping or precise foot placement during gait. Finally, we discuss the idea that sensory information about the movement kinematics contribute to both feedback and anticipatory processes for limb movement control.

Filling gaps in visual motion for target capture.

A remarkable challenge our brain must face constantly when interacting with the environment is represented by ambiguous and, at times, even missing sensory information. This is particularly compelling for visual information, being the main sensory system we rely upon to gather cues about the external world. It is not uncommon, for example, that objects catching our attention may disappear temporarily from view, occluded by visual obstacles in the foreground. Nevertheless, we are often able to keep our gaze on them throughout the occlusion or even catch them on the fly in the face of the transient lack of visual motion information. This implies that the brain can fill the gaps of missing sensory information by extrapolating the object motion through the occlusion. In recent years, much experimental evidence has been accumulated that both perceptual and motor processes exploit visual motion extrapolation mechanisms. Moreover, neurophysiological and neuroimaging studies have identified brain regions potentially involved in the predictive representation of the occluded target motion. Within this framework, ocular pursuit and manual interceptive behavior have proven to be useful experimental models for investigating visual extrapolation mechanisms. Studies in these fields have pointed out that visual motion extrapolation processes depend on manifold information related to short-term memory representations of the target motion before the occlusion, as well as to longer term representations derived from previous experience with the environment. We will review recent oculomotor and manual interception literature to provide up-to-date views on the neurophysiological underpinnings of visual motion extrapolation.