Biomechanical costs influence decisions made during ongoing actions.

Accurate interaction with the environment relies on the integration of external information about the spatial layout of potential actions and knowledge of their costs and benefits. Previous studies have shown that when given a choice between voluntary reaching movements, humans tend to prefer actions with lower biomechanical costs. However, these studies primarily focused on decisions made before the onset of movement ("decide-then-act" scenarios), and it is not known to what extent their conclusions generalize to many real-life situations, in which decisions occur during ongoing actions ("decide-while-acting").

Toward a neuroscience of natural behavior.

One of the most exciting new developments in systems neuroscience is the progress being made toward neurophysiological experiments that move beyond simplified laboratory settings and address the richness of natural behavior. This is enabled by technological advances such as wireless recording in freely moving animals, automated quantification of behavior, and new methods for analyzing large data sets. Beyond new empirical methods and data, however, there is also a need for new theories and concepts to interpret that data.

Vestibular contributions to online reach execution are processed via mechanisms with knowledge about limb biomechanics.

Studies of reach control with the body stationary have shown that proprioceptive and visual feedback signals contributing to rapid corrections during reaching are processed by neural circuits that incorporate knowledge about the physical properties of the limb (an internal model). However, among the most common spatial and mechanical perturbations to the limb are those caused by our body's own motion, suggesting that processing of vestibular signals for online reach control may reflect a similar level of sophistication. We investigated this hypothesis using galvanic vestibular stimulation (GVS) to selectively activate the vestibular sensors, simulating body rotation, as human subjects reached to remembered targets in different directions (forward, leftward, rightward).

Reaching decisions during ongoing movements.

Neurophysiological studies suggest that when decisions are made between concrete actions, the selection process involves a competition between potential action representations in the same sensorimotor structures involved in executing those actions. However, it is unclear how such models can explain situations, often encountered during natural behavior, in which we make decisions while were are already engaged in performing an action. Does the process of deliberation characterized in classical studies of decision-making proceed the same way when subjects are deciding while already acting? In the present study, human subjects continuously tracked a target moving in the horizontal plane and were occasionally presented with a new target to which they could freely choose to switch at any time, whereupon it became the new tracked target.

Role of Rostral Fastigial Neurons in Encoding a Body-Centered Representation of Translation in Three Dimensions.

Many daily behaviors rely critically on estimates of our body motion. Such estimates must be computed by combining neck proprioceptive signals with vestibular signals that have been transformed from a head- to a body-centered reference frame. Recent studies showed that deep cerebellar neurons in the rostral fastigial nucleus (rFN) reflect these computations, but whether they explicitly encode estimates of body motion remains unclear.

The influence of proprioceptive state on learning control of reach dynamics.

The motor system shows a remarkable capacity to generalize learned behavior to new contexts while simultaneously permitting learning of multiple and sometimes conflicting skills. To examine the influence of proprioceptive state on this capacity, we compared the effectiveness of changes in workspace location and limb orientation (horizontal vs. parasagittal plane posture) in facilitating learning of opposing dynamic force-field perturbations.

Evidence for a reference frame transformation of vestibular signal contributions to voluntary reaching.

To contribute appropriately to voluntary reaching during body motion, vestibular signals must be transformed from a head-centered to a body-centered reference frame. We quantitatively investigated the evidence for this transformation during online reach execution by using galvanic vestibular stimulation (GVS) to simulate rotation about a head-fixed, roughly naso-occipital axis as human subjects made planar reaching movements to a remembered location with their head in different orientations. If vestibular signals that contribute to reach execution have been transformed from a head-centered to a body-centered reference frame, the same stimulation should be interpreted as body tilt with the head upright but as vertical-axis rotation with the head inclined forward.

Learning to move machines with the mind.

Brain-computer interfaces (BCIs) extract signals from neural activity to control remote devices ranging from computer cursors to limb-like robots. They show great potential to help patients with severe motor deficits perform everyday tasks without the constant assistance of caregivers. Understanding the neural mechanisms by which subjects use BCI systems could lead to improved designs and provide unique insights into normal motor control and skill acquisition.

Multisensory integration: resolving sensory ambiguities to build novel representations.

Multisensory integration plays several important roles in the nervous system. One is to combine information from multiple complementary cues to improve stimulus detection and discrimination. Another is to resolve peripheral sensory ambiguities and create novel internal representations that do not exist at the level of individual sensors.

Computation of egomotion in the macaque cerebellar vermis.

The nodulus and uvula (lobules X and IX of the vermis) receive mossy fibers from both vestibular afferents and vestibular nuclei neurons and are thought to play a role in spatial orientation. Their properties relate to a sensory ambiguity of the vestibular periphery: otolith afferents respond identically to translational (inertial) accelerations and changes in orientation relative to gravity. Based on theoretical and behavioral evidence, this sensory ambiguity is resolved using rotational cues from the semicircular canals.

Internal models and neural computation in the vestibular system.

The vestibular system is vital for motor control and spatial self-motion perception. Afferents from the otolith organs and the semicircular canals converge with optokinetic, somatosensory and motor-related signals in the vestibular nuclei, which are reciprocally interconnected with the vestibulocerebellar cortex and deep cerebellar nuclei. Here, we review the properties of the many cell types in the vestibular nuclei, as well as some fundamental computations implemented within this brainstem-cerebellar circuitry.

Conversion of a highly selective sigma-1 receptor-ligand to sigma-2 receptor preferring ligands with anticocaine activity.

Cocaine's toxicity can be mitigated by blocking its interaction with sigma-1 receptors. The involvement of sigma-2 receptors remains unclear. To investigate their potential role, we have designed compounds through a convergent synthesis utilizing a highly selective sigma-1 ligand and elements of a selective sigma-2 ligand.

Coordinate transformations and sensory integration in the detection of spatial orientation and self-motion: from models to experiments.

An accurate internal representation of our current motion and orientation in space is critical to navigate in the world and execute appropriate action. The force of gravity provides an allocentric frame of reference that defines one's motion relative to inertial (i.e.

Purkinje cells in posterior cerebellar vermis encode motion in an inertial reference frame.

The ability to orient and navigate through the terrestrial environment represents a computational challenge common to all vertebrates. It arises because motion sensors in the inner ear, the otolith organs, and the semicircular canals transduce self-motion in an egocentric reference frame. As a result, vestibular afferent information reaching the brain is inappropriate for coding our own motion and orientation relative to the outside world.

A reevaluation of the inverse dynamic model for eye movements.

To construct an appropriate motor command from signals that provide a representation of desired action, the nervous system must take into account the dynamic characteristics of the motor plant to be controlled. In the oculomotor system, signals specifying desired eye velocity are thought to be transformed into motor commands by an inverse dynamic model of the eye plant that is shared for all types of eye movements and implemented by a weighted combination of eye velocity and position signals. Neurons in the prepositus hypoglossi and adjacent medial vestibular nuclei (PH-BT neurons) were traditionally thought to encode the "eye position" component of this inverse model.

Sensory convergence solves a motion ambiguity problem.

Our inner ear is equipped with a set of linear accelerometers, the otolith organs, that sense the inertial accelerations experienced during self-motion. However, as Einstein pointed out nearly a century ago, this signal would by itself be insufficient to detect our real movement, because gravity, another form of linear acceleration, and self-motion are sensed identically by otolith afferents. To deal with this ambiguity, it was proposed that neural populations in the pons and midline cerebellum compute an independent, internal estimate of gravity using signals arising from the vestibular rotation sensors, the semicircular canals.

Sensory vestibular contributions to constructing internal models of self-motion.

The ability to navigate in the world and execute appropriate behavioral and motor responses depends critically on our capacity to construct an accurate internal representation of our current motion and orientation in space. Vestibular sensory signals are among those that may make an essential contribution to the construction of such 'internal models'. Movement in a gravitational environment represents a situation where the construction of internal models becomes particularly important because the otolith organs, like any linear accelerometer, sense inertial and gravitational accelerations equivalently.

Pursuit--vestibular interactions in brain stem neurons during rotation and translation.

Under natural conditions, the vestibular and pursuit systems work synergistically to stabilize the visual scene during movement. How translational vestibular signals [translational vestibuloocular reflex (TVOR)] are processed in the premotor pathways for slow eye movements continues to remain a challenging question. To further our understanding of how premotor neurons contribute to this processing, we recorded neural activities from the prepositus and rostral medial vestibular nuclei in macaque monkeys.

Neurons compute internal models of the physical laws of motion.

A critical step in self-motion perception and spatial awareness is the integration of motion cues from multiple sensory organs that individually do not provide an accurate representation of the physical world. One of the best-studied sensory ambiguities is found in visual processing, and arises because of the inherent uncertainty in detecting the motion direction of an untextured contour moving within a small aperture. A similar sensory ambiguity arises in identifying the actual motion associated with linear accelerations sensed by the otolith organs in the inner ear.

An integrative neural network for detecting inertial motion and head orientation.

The ability to navigate in the world and execute appropriate behavioral responses depends critically on the contribution of the vestibular system to the detection of motion and spatial orientation. A complicating factor is that otolith afferents equivalently encode inertial and gravitational accelerations. Recent studies have demonstrated that the brain can resolve this sensory ambiguity by combining signals from both the otoliths and semicircular canal sensors, although it remains unknown how the brain integrates these sensory contributions to perform the nonlinear vector computations required to accurately detect head movement in space.

Cerebellar signatures of vestibulo-ocular reflex motor learning.

The vestibulo-ocular reflex (VOR) comprises an outstanding system to perform studies that probe possible cerebellar roles in motor learning. Novel VOR gains can be induced (learned) by the wearing of minifying or magnifying lenses, and learning requires the presence of the cerebellum. Previously, it was shown that Purkinje cells change their head velocity sensitivities with learning and that this change was thought to be inappropriate to be causal for the changed behavior.

Resolution of sensory ambiguities for gaze stabilization requires a second neural integrator.

The ability to simultaneously move in the world and maintain stable visual perception depends critically on the contribution of vestibulo-ocular reflexes (VORs) to gaze stabilization. It is traditionally believed that semicircular canal signals drive compensatory responses to rotational head disturbances (rotational VOR), whereas otolith signals compensate for translational movements [translational VOR (TVOR)]. However, a sensory ambiguity exists because otolith afferents are activated similarly during head translations and reorientations relative to gravity (i.