Aaron L. Wong

Sensorimotor adaptation error signals are derived from realistic predictions of movement outcomes.

Neural systems that control movement maintain accuracy by adaptively altering motor commands in response to errors. It is often assumed that the error signal that drives adaptation is equivalent to the sensory error observed at the conclusion of a movement; for saccades, this is typically the visual (retinal) error. However, we instead propose that the adaptation error signal is derived as the difference between the observed visual error and a realistic prediction of movement outcome. Using a modified saccade-adaptation task in human subjects, we precisely controlled the amount of error experienced at the conclusion of a movement by back-stepping the target so that the saccade is hypometric (positive retinal error), but less hypometric than if the target had not moved (smaller retinal error than expected). This separates prediction error from both visual errors and motor corrections. Despite positive visual errors and forward-directed motor corrections, we found an adaptive decrease in saccade amplitudes, a finding that is well-explained by the employment of a prediction-based error signal. Furthermore, adaptive changes in movement size were linearly correlated to the disparity between the predicted and observed movement outcomes, in agreement with the forward-model hypothesis of motor learning, which states that adaptation error signals incorporate predictions of motor outcomes computed using a copy of the motor command (efference copy).

RalA and RalB function as the critical GTP sensors for GTP-dependent exocytosis

Although it has been established that the activation of GTPases by non-hydrolyzable GTP stimulates neurotransmitter release from many different secretory cell types, the underlying mechanisms remain unclear. In the present study we aimed to elucidate the functional role(s) for endogenous Ras-like protein A (RalA) and RalB GTPases in GTP-dependent exocytosis. For this purpose stable neuroendocrine pheochromocytoma 12 (PC12) cell lines were generated in which the expressions of both RalA and RalB were strongly downregulated. In these double knock-down cells GTP-dependent exocytosis was reduced severely and was restored after the expression of RalA or RalB was reintroduced by transfection. In contrast, Ca2+-dependent exocytosis and the docking of dense core vesicles analyzed by electron microscopy remained unchanged in the double knock-down cells. Furthermore, the transfected RalA and RalB appeared to be localized primarily on the dense core vesicles in undifferentiated and nerve growth factor-differentiated PC12 cells. Our results indicate that endogenous RalA and RalB function specifically as GTP sensors for the GTP-dependent exocytosis of dense core vesicles, but they are not required for the general secretory pathways, including tethering of vesicles to the plasma membrane and Ca2+-dependent exocytosis.

Early adaptation and compensation of clinical vestibular responses after unilateral vestibular deafferentation surgery.

Objective To describe vestibulo-ocular function in the immediate postoperative period after unilateral vestibular deafferentation from vestibular schwannoma resection. Study Design Prospective longitudinal study. Setting Tertiary medical center. Patients Five patients who underwent vestibular schwannoma resection via retrosigmoid approach. Interventions Bedside video-oculography and video head impulse testing (HIT). Main Outcome Measures Static and dynamic measures of vestibulo-ocular reflex (VOR) function including spontaneous nystagmus, skew deviation, VOR gain during HIT, and presence of saccades related to HIT. Results Mean ipsilesional horizontal VOR gain decreased from 0.88 ± 0.09 preoperatively to 0.27 ± 0.20 on POD 2 (p = 0.004). Mean contralesional VOR gain declined from 0.95 ± 0.1 preoperatively to 0.79 ± 0.17 on POD 2 (p = 0.032). By POD 4, ipsilesional VOR gain remained low, whereas contralesional VOR gain returned to baseline. Initially on POD 1 to 3, compensatory saccades occurred exclusively after the head stopped moving (overt) with latency of 192.8 ± 36.1 ms; by POD 5, saccade latency decreased to 134.5 ± 23.5 ms (p = 0.026), and saccades were occurring during the head rotation. Skew deviation was present and remained abnormal through POD 5 in 3 of the 5 patients. Conclusion In the postoperative period, gaze stability seems to improve from contralesional VOR gain restoration and reduced latency of compensatory saccades.

Keeping your head on target

The mechanisms by which the human brain controls eye movements are reasonably well understood, but those for the head less so. Here, we show that the mechanisms for keeping the head aimed at a stationary target follow strategies similar to those for holding the eyes steady on stationary targets. Specifically, we applied the neural integrator hypothesis that originally was developed for holding the eyes still in eccentric gaze positions to describe how the head is held still when turned toward an eccentric target. We found that normal humans make head movements consistent with the neural integrator hypothesis, except that additional sensory feedback is needed, from proprioceptors in the neck, to keep the head on target. We also show that the complicated patterns of head movements in patients with cervical dystonia can be predicted by deficits in a neural integrator for head motor control. These results support ideas originally developed from animal studies that suggest fundamental similarities between oculomotor and cephalomotor control, as well as a conceptual framework for cervical dystonia that departs considerably from current clinical views.

Saccade adaptation improves in response to a gradually introduced stimulus perturbation.

A major goal in the study of motor learning is to improve the extent to which subjects adapt their movements in response to errors. Recent attention has focused on the gradual-adaptation paradigm, in which an adaptive stimulus is introduced incrementally, rather than all at once as in conventional adaptation paradigms. However, there is disagreement - even among studies involving the same sensorimotor-learning task - as to the robustness of this approach. In particular, although all studies confirm that retention of learning is improved, not all agree that exposure to a gradual-adaptation paradigm can improve the extent of adaptation that takes place. Also, the paradigm has not previously been studied with saccadic eye movements, which are unique in that they typically lack online error feedback during each movement. To determine the effectiveness of gradual adaptation in this system, we compared saccadic adaptation performed with gradual and conventional adaptation paradigms. We find evidence consistent with more robust adaptation - in the sense of greater extent of adaptation as well as greater retention of learning (larger aftereffects) - in response to a gradual adaptation stimulus. The results suggest the need to develop alternative models of motor learning, as current error-based modeling efforts are unable to account for the increased extent of adaptation when subjects are only exposed to the full adaptive stimulus for a brief time.

Explicit knowledge enhances motor vigor and performance: motivation versus practice in sequence tasks

Motor skill learning involves a practice-induced improvement in the speed and/or accuracy of a discrete movement. It is often thought that paradigms involving repetitive practice of discrete movements performed in a fixed sequence result in a further enhancement of skill beyond practice of the individual movements in a random order. Sequence-specific performance improvements could, however, arise without practice as a result of knowledge of the sequence order; knowledge could operate by either enabling advanced motor planning of the known sequence elements or by increasing overall motivation. Here, we examined how knowledge and practice contribute to performance of a sequence of movements. We found that explicit knowledge provided through instruction produced practice-independent improvements in reaction time and execution quality. These performance improvements occurred even for random elements within a partially known sequence, indicative of a general motivational effect rather than a sequence-specific effect of advanced planning. This motivational effect suggests that knowledge influences performance in a manner analogous to reward. Additionally, practice led to similar improvements in execution quality for both known and random sequences. The lack of interaction between knowledge and practice suggests that any skill acquisition occurring during discrete sequence tasks arises solely from practice of the individual movement elements, independent of their order. We conclude that performance improvements in discrete sequence tasks arise from the combination of knowledge-based motivation and sequence-independent practice; investigating this interplay between cognition and movement may facilitate a greater understanding of the acquisition of skilled behavior.

Exploring the Fundamental Dynamics of Error-Based Motor Learning Using a Stationary Predictive-Saccade Task

The maintenance of movement accuracy uses prior performance errors to correct future motor plans; this motor-learning process ensures that movements remain quick and accurate. The control of predictive saccades, in which anticipatory movements are made to future targets before visual stimulus information becomes available, serves as an ideal paradigm to analyze how the motor system utilizes prior errors to drive movements to a desired goal. Predictive saccades constitute a stationary process (the mean and to a rough approximation the variability of the data do not vary over time, unlike a typical motor adaptation paradigm). This enables us to study inter-trial correlations, both on a trial-by-trial basis and across long blocks of trials. Saccade errors are found to be corrected on a trial-by-trial basis in a direction-specific manner (the next saccade made in the same direction will reflect a correction for errors made on the current saccade). Additionally, there is evidence for a second, modulating process that exhibits long memory. That is, performance information, as measured via inter-trial correlations, is strongly retained across a large number of saccades (about 100 trials). Together, this evidence indicates that the dynamics of motor learning exhibit complexities that must be carefully considered, as they cannot be fully described with current state-space (ARMA) modeling efforts.

A new "wireless" search-coil system

The scleral search-coil system is the accepted standard for precise and accurate recording of eye movements in the lab and clinic. One of the drawbacks of this system is the connecting wire that leads from the eye coil to the associated electronics; this wire causes irritation to the subject and has a tendency to break during experiments. We have developed a modified version of this technique, which uses a resonant scleral coil and no connecting wire. A transmitter sends a stream of pulses to the eye coil, and a receiver then detects the resonant oscillations re-radiated from the eye coil. The relative intensity of the signal as received by sets of orthogonal receiver coils determines the orientation of the eye coil. The new approach retains the advantages of accuracy, precision, and high sample rate, while making the system portable and more comfortable.

Similarities in error processing establish a link between saccade prediction at baseline and adaptation performance

Adaptive processes are crucial in maintaining the accuracy of body movements and rely on error storage and processing mechanisms. Although classically studied with adaptation paradigms, evidence of these ongoing error-correction mechanisms should also be detectable in other movements. Despite this connection, current adaptation models are challenged when forecasting adaptation ability with measures of baseline behavior. On the other hand, we have previously identified an error-correction process present in a particular form of baseline behavior, the generation of predictive saccades. This process exhibits long-term intertrial correlations that decay gradually (as a power law) and are best characterized with the tools of fractal time series analysis. Since this baseline task and adaptation both involve error storage and processing, we sought to find a link between the intertrial correlations of the error-correction process in predictive saccades and the ability of subjects to alter their saccade amplitudes during an adaptation task. Here we find just such a relationship: the stronger the intertrial correlations during prediction, the more rapid the acquisition of adaptation. This reinforces the links found previously between prediction and adaptation in motor control and suggests that current adaptation models are inadequate to capture the complete dynamics of these error-correction processes. A better understanding of the similarities in error processing between prediction and adaptation might provide the means to forecast adaptation ability with a baseline task. This would have many potential uses in physical therapy and the general design of paradigms of motor adaptation.

Using prediction errors to drive saccade adaptation: the implicit double-step task

A prediction-based error signal, neurally computed as the difference between predicted and observed movement outcomes, has been proposed as the driving force for motor learning. This suggests that the generation of predictive saccades to periodically paced targets—whose performance accuracy is actively maintained using this same error signal—invokes the motor-learning network. We examined whether a simple predictive-saccade task (implicit double-step adaptation, in which targets are gradually displaced outward to exaggerate normal hypometric movement errors) can stand in place of a traditional double-step saccade-adaptation task to induce an increase in saccade gain. We find that the implicit double-step adaptation task can induce significant gain-increase adaptation (of comparable magnitude to that of the standard double-step task) in normal control subjects. Unlike control subjects, patients with impaired cerebella are unable to adapt their saccades in response to this paradigm; this implies that the cerebellum is crucial for processing prediction-based error signals for motor learning.