Reaching the limit of the oculomotor plant: 3D kinematics after abducens nerve stimulation during the torsional vestibulo-ocular reflex.

Accumulating evidence shows that the oculomotor plant is capable of implementing aspects of three-dimensional kinematics such as Listing's law and the half-angle rule. But these studies have only examined the eye under static conditions or with movements that normally obey these rules (e.g., saccades and pursuit). Here we test the capability of the oculomotor plant to rearrange itself as necessary for non-half-angle behavior. Three monkeys (Macaca mulatta) fixated five vertically displaced targets along the midsagittal plane while sitting on a motion platform that rotated sinusoidally about the naso-occipital axis. This activated the torsional, rotational vestibulo-ocular reflex, which exhibits a zero-angle or negative-angle rule (depending on the visual stimulus). On random sinusoidal cycles, we stimulated the abducens nerve and observed the resultant eye movements. If the plant has rearranged itself to implement this non-half-angle behavior, then stimulation should reveal this behavior. On the other hand, if the plant is only capable of half-angle behavior, then stimulation should reveal a half-angle rule. We find the latter to be true and therefore additional neural signals are likely necessary to implement non-half-angle behavior.

Revealing the kinematics of the oculomotor plant with tertiary eye positions and ocular counterroll.

Retinal information is two-dimensional, whereas eye movements are three-dimensional. The oculomotor system solves this degrees-of-freedom problem by constraining eye positions to zero torsion (Listing's law) and determining how eye velocities change with eye position (half-angle rule). Here we test whether the oculomotor plant, in the absence of well-defined neural commands, can implement these constrains mechanically, not just in a primary position but for all eye and head orientations. We stimulated the abducens nerve at tertiary eye positions and when ocular counterroll was induced at tilted head orientations. Stimulation-induced eye velocities follow the half-angle rule, even for tertiary eye positions, and microstimulation at tilted head orientations elicits eye positions that adhere to torsionally shifted planes, similar to naturally occurring eye movements. These results support the notion that oculomotor plant can continuously apply these three-dimensional rules correctly and appropriately for all eye and head orientations that obey Listing's law, demonstrating a major role of peripheral biomechanics in motor control.

Three-dimensional kinematics at the level of the oculomotor plant.

Motor systems often require that superfluous degrees of freedom be constrained. For the oculomotor system, a redundancy in the degrees of freedom occurs during visually guided eye movements and is solved by implementing Listing's law and the half-angle rule, kinematic constraints that limit the range of eye positions and angular velocities used by the eyes. These constraints have been attributed either to neurally generated commands or to the physical mechanics of the eye and its surrounding muscles and tissues (i.e., the ocular plant). To directly test whether the ocular plant implements the half-angle rule, critical to the maintenance of Listing's law, we microstimulated the abducens nerve with the eye at different initial vertical eye positions. We report that the electrically evoked eye velocity exhibits the same eye position dependence as seen in visually guided smooth-pursuit eye movements. These results support an important role for the ocular plant in providing a solution to the degrees-of-freedom problem during eye movements.

Sensorimotor and executive function slowing in anesthesiology residents after overnight shifts.

STUDY OBJECTIVE: Medical residents working overnight call shifts experience sleep deprivation and circadian clock disruption. This leads to deficits in sensorimotor function and increases in workplace accidents. Using quick tablet-based tasks, we investigate whether measureable executive function differences exist following a single overnight call versus routine shift, and whether factors like stress, rest and caffeine affect these measures. DESIGN: A prospective, observational, longitudinal, comparison study was conducted. SETTING: An academic tertiary hospital's main operating room suite staffed by attending anesthesiologists, anesthesiology residents, anesthesiologist assistants and nurse anesthetists. PATIENTS: Subjects were 30 anesthesiology residents working daytime shifts and 30 peers working overnight call shifts from the University of Texas Health Science Center at Houston. INTERVENTIONS: Before and after their respective work shifts, residents completed the Stanford Sleepiness Scale (SSS) and the ProPoint and AntiPoint tablet-based tasks. These latter tasks are designed to measure sensorimotor and executive functions, respectively. MEASUREMENTS: The SSS is a self-reported measure of sleepiness. Response times (RTs) are measured in the pointing tasks. MAIN RESULTS: Call residents exhibited increased RTs across their shifts (post-pre) on both ProPoint (p=0.002) and AntiPoint (p<0.002) tasks, when compared to Routine residents. Increased stress was associated with decreases in AntiPoint RT for Routine (p=0.007), but with greater increases in sleepiness for Call residents (p<0.001). Further, whether or not a Call resident consumed caffeine habitually was associated with ProPoint RT changes; with Call residents who habitually drink caffeine having a greater Pre-Post difference (i.e., more slowing, p<0.001) in ProPoint RT. CONCLUSIONS: These results indicate that (1) overnight Call residents demonstrate both sensorimotor and cognitive slowing compared to routine daytime shift residents, (2) sensorimotor slowing is greater in overnight Call residents who drink caffeine habitually, and (3) increased stress during a shift reduces (improves) cognitive RTs during routine daytime but not overnight call shifts.

Slowed Prosaccades and Increased Antisaccade Errors As a Potential Behavioral Biomarker of Multiple System Atrophy.

Current clinical diagnostic tools are limited in their ability to accurately differentiate idiopathic Parkinson's disease (PD) from multiple system atrophy (MSA) and other parkinsonian disorders early in the disease course, but eye movements may stand as objective and sensitive markers of disease differentiation and progression. To assess the use of eye movement performance for uniquely characterizing PD and MSA, subjects diagnosed with PD (N = 21), MSA (N = 11), and age-matched controls (C, N = 20) were tested on the prosaccade and antisaccade tasks using an infrared eye tracker. Twenty of these subjects were retested ~7 months later. Saccade latencies, error rates, and longitudinal changes in saccade latencies were measured. Both PD and MSA patients had greater antisaccade error rates than C subjects, but MSA patients exhibited longer prosaccade latencies than both PD and C patients. With repeated testing, antisaccade latencies improved over time, with benefits in C and PD but not MSA patients. In the prosaccade task, the normal latencies of the PD group show that basic sensorimotor oculomotor function remain intact in mid-stage PD, whereas the impaired latencies of the MSA group suggest additional degeneration earlier in the disease course. Changes in antisaccade latency appeared most sensitive to differences between MSA and PD across short time intervals. Therefore, in these mid-stage patients, increased antisaccade errors combined with slowed prosaccade latencies might serve as a useful marker for early differentiation between PD and MSA, and, antisaccade performance, a measure of MSA progression. Together, our findings suggest that eye movements are promising biomarkers for early differentiation and progression of parkinsonian disorders.

Impaired Cognitive Performance in Youth Athletes Exposed to Repetitive Head Impacts.

Worldwide, more than 22 million children and adolescents are exposed to repetitive head impacts (RHI) in soccer. Evidence indicates cumulative effects on brain structure, but it is not known whether exposure to RHI affects cognitive improvement in adolescents. The aim of the study was to determine whether exposure to RHI while heading the ball in soccer affects improvement in cognitive performance in adolescents over time. The study group consisted of a convenience sample of 16 male soccer players (mean age 15.7 ± 0.7 years). A comparison cohort of 14 male non-contact sports athletes (mean age 14.9 ± 1.1 years) was recruited from competitive athletic clubs and group-matched in age. Using the ProPoint and AntiPoint tasks, sensorimotor and cognitive functions were measured over both immediate (pre- vs. post-training) as well as across multiple time points within a play season. The number and type of head impacts that occurred during the training were counted. The main outcome measure was the change in response time (RT) in the ProPoint and AntiPoint tasks. The immediate (pre- vs. post-training) and longer-term (across a play season) change in RT was analyzed, and the effect of the number and type of head impacts was tested. Thirty athletes with and without exposure to RHI demonstrated a decrease in RT in both tasks immediately after training. Over the play season, both groups showed improvement in sensorimotor function. While the control group also improved in cognitive performance, the soccer players did not, however. Further, the more long headers performed, the slower the improvement in RT over the season. Youth athletes experience an immediate cognitive improvement after training most likely because of physical exercise. Results of this study also suggest an association between exposure to specific RHI (long headers) and lack of improvement in cognitive performance in youth athletes over time.

Neural control of 3-D gaze shifts in the primate.

The neural mechanisms that specify target locations for gaze shifts and then convert these into desired patterns of coordinated eye and head movements are complex. Much of this complexity is only revealed when one takes a realistic three-dimensional (3-D) view of these processes, where fundamental computational problems such as kinematic redundancy, reference-frame transformations, and non-commutativity emerge. Here we review the underlying mechanisms and solutions for these problems, starting with a consideration of the kinematics of 3-D gaze shifts in human and non-human primates. We then consider the neural mechanisms, including cortical representation of gaze targets, the nature of the gaze motor command used by the superior colliculus, and how these gaze commands are decomposed into brainstem motor commands for the eyes and head. A general conclusion is that fairly simple coding mechanisms may be used to represent gaze at the cortical and collicular level, but this then necessitates complexity for the spatial updating of these representations and in the brainstem sensorimotor transformations that convert these signals into eye and head movements.

Neural control of three-dimensional eye and head posture.

The neural commands for gaze control include not only signals that drive the eyes and head from one point to the next, but also those that hold the eyes and head steady at the end of each movement. Studies using microstimulation and chemical inactivation techniques, in head-fixed and head-free macaques, were used to investigate the role of the interstitial nucleus of Cajal (INC) in the production of the latter, tonic signals. The right INC was found to control clockwise-up and clockwise-down components of both eye and head orientation, whereas the left INC was found to control the counterclockwise-up and counterclockwise-down components. Temporary inactivation of the INC left the eyes and head unable to hold their final torsional and vertical positions after each gaze shift. Thus, the INC is strongly implicated in the production of the tonic, step-like commands that maintain eye and head orientations between gaze shifts. In addition, these studies also found that the INC represents the torsional and vertical commands for eye and head orientation using different coordinate coding strategies, optimally matched to the different three-dimensional postural constraints observed in the eye and head.

Optimal multisensory decision-making in a reaction-time task.

Humans and animals can integrate sensory evidence from various sources to make decisions in a statistically near-optimal manner, provided that the stimulus presentation time is fixed across trials. Little is known about whether optimality is preserved when subjects can choose when to make a decision (reaction-time task), nor when sensory inputs have time-varying reliability. Using a reaction-time version of a visual/vestibular heading discrimination task, we show that behavior is clearly sub-optimal when quantified with traditional optimality metrics that ignore reaction times. We created a computational model that accumulates evidence optimally across both cues and time, and trades off accuracy with decision speed. This model quantitatively explains subjects's choices and reaction times, supporting the hypothesis that subjects do, in fact, accumulate evidence optimally over time and across sensory modalities, even when the reaction time is under the subject's control.

A vestibular sensation: probabilistic approaches to spatial perception.

The vestibular system helps maintain equilibrium and clear vision through reflexes, but it also contributes to spatial perception. In recent years, research in the vestibular field has expanded to higher-level processing involving the cortex. Vestibular contributions to spatial cognition have been difficult to study because the circuits involved are inherently multisensory. Computational methods and the application of Bayes theorem are used to form hypotheses about how information from different sensory modalities is combined together with expectations based on past experience in order to obtain optimal estimates of cognitive variables like current spatial orientation. To test these hypotheses, neuronal populations are being recorded during active tasks in which subjects make decisions based on vestibular and visual or somatosensory information. This review highlights what is currently known about the role of vestibular information in these processes, the computations necessary to obtain the appropriate signals, and the benefits that have emerged thus far.

Human visuospatial updating after passive translations in three-dimensional space.

To maintain a stable representation of the visual environment as we move, the brain must update the locations of targets in space using extra-retinal signals. Humans can accurately update after intervening active whole-body translations. But can they also update for passive translations (i.e., without efference copy signals of an outgoing motor command)? We asked six head-fixed subjects to remember the location of a briefly flashed target (five possible targets were located at depths of 23, 33, 43, 63, and 150 cm in front of the cyclopean eye) as they moved 10 cm left, right, up, down, forward, or backward while fixating a head-fixed target at 53 cm. After the movement, the subjects made a saccade to the remembered location of the flash with a combination of version and vergence eye movements. We computed an updating ratio where 0 indicates no updating and 1 indicates perfect updating. For lateral and vertical whole-body motion, where updating performance is judged by the size of the version movement, the updating ratios were similar for leftward and rightward translations, averaging 0.84 +/- 0.28 (mean +/- SD) as compared with 0.51 +/- 0.33 for downward and 1.05 +/- 0.50 for upward translations. For forward/backward movements, where updating performance is judged by the size of the vergence movement, the average updating ratio was 1.12 +/- 0.45. Updating ratios tended to be larger for far targets than near targets, although both intra- and intersubject variabilities were smallest for near targets. Thus in addition to self-generated movements, extra-retinal signals involving otolith and proprioceptive cues can also be used for spatial constancy.

Human visuospatial updating after noncommutative rotations.

As we move our bodies in space, we often undergo head and body rotations about different axes-yaw, pitch, and roll. The order in which we rotate about these axes is an important factor in determining the final position of our bodies in space because rotations, unlike translations, do not commute. Does our brain keep track of the noncommutativity of rotations when computing changes in head and body orientation and then use this information when planning subsequent motor commands? We used a visuospatial updating task to investigate whether saccades to remembered visual targets are accurate after intervening, whole-body rotational sequences. The sequences were reversed, either yaw then roll or roll then yaw, such that the final required eye movements to reach the same space-fixed target were different in each case. While each subject performed consistently irrespective of target location and rotational combination, we found great intersubject variability in their capacity to update. The distance between the noncommutative endpoints was, on average, half of that predicted by perfect noncommutativity. Nevertheless, most subjects did make eye movements to distinct final endpoint locations and not to one unique location in space as predicted by a commutative model. In addition, their noncommutative performance significantly improved when their less than ideal updating performance was taken into account. Thus the brain can produce movements that are consistent with the processing of noncommutative rotations, although it is often poor in using internal estimates of rotation for updating.

Interstitial nucleus of cajal encodes three-dimensional head orientations in Fick-like coordinates.

Two central, related questions in motor control are 1) how the brain represents movement directions of various effectors like the eyes and head and 2) how it constrains their redundant degrees of freedom. The interstitial nucleus of Cajal (INC) integrates velocity commands from the gaze control system into position signals for three-dimensional eye and head posture. It has been shown that the right INC encodes clockwise (CW)-up and CW-down eye and head components, whereas the left INC encodes counterclockwise (CCW)-up and CCW-down components, similar to the sensitivity directions of the vertical semicircular canals. For the eyes, these canal-like coordinates align with Listing's plane (a behavioral strategy limiting torsion about the gaze axis). By analogy, we predicted that the INC also encodes head orientation in canal-like coordinates, but instead, aligned with the coordinate axes for the Fick strategy (which constrains head torsion). Unilateral stimulation (50 microA, 300 Hz, 200 ms) evoked CW head rotations from the right INC and CCW rotations from the left INC, with variable vertical components. The observed axes of head rotation were consistent with a canal-like coordinate system. Moreover, as predicted, these axes remained fixed in the head, rotating with initial head orientation like the horizontal and torsional axes of a Fick coordinate system. This suggests that the head is ordinarily constrained to zero torsion in Fick coordinates by equally activating CW/CCW populations of neurons in the right/left INC. These data support a simple mechanism for controlling head orientation through the alignment of brain stem neural coordinates with natural behavioral constraints.

Three-dimensional eye-head coordination after injection of muscimol into the interstitial nucleus of Cajal (INC).

The interstitial nucleus of Cajal (INC) is thought to be the "neural integrator" for torsional/vertical eye position and head posture. Here, we investigated the coordination of eye and head movements after reversible INC inactivation. Three-dimensional (3-D) eye-head movements were recorded in three head-unrestrained monkeys using search coils. INC sites were identified by unit recording/electrical stimulation and then reversibly inactivated by 0.3 mul of 0.05% muscimol injection into 26 INC sites. After muscimol injection, the eye and head 1) began to drift (an inability to maintain stable fixation) torsionally: clockwise (CW)/counterclockwise (CCW) after left/right INC inactivation respectively. 2) The eye and head tilted torsionally CW/CCW after left/right INC inactivation, respectively. Horizontal gaze/head drifts were inconsistently present and did not result in considerable position offsets. Vertical eye drift was dependent on both vertical eye position and the magnitude of the previous vertical saccade, as in head-fixed condition. This correlation was smaller for gaze and head drift, suggesting that the gaze and head deficits could not be explained by a first-order integrator model. Ocular counterroll (OC) was completely disrupted. The gain of torsional vestibuloocular reflex (VOR) during spontaneous eye and head movements was reduced by 22% in both CW/CCW directions after either left or right INC inactivation. Our results suggest a complex interdependence of eye and head deficits after INC inactivation during fixation, gaze shifts, and VOR. Some of our results resemble the symptoms of spasmodic torticollis (ST).

Differences in the accuracy of human visuospatial memory after yaw and roll rotations.

Our ability to keep track of objects in the environment, even as we move, has been attributed to various cues including efference copies, vestibular signals, proprioception, and gravitational cues. However, the presence of some cues, such as gravity, may not be used to the same extent by different axes of motion (e.g., yaw vs. roll). We tested whether changes in gravitational cues can be used to improve visuospatial updating performance for yaw rotations as previously shown for roll. We found differences in updating for yaw and roll rotations in that yaw updating is not only associated with larger systematic errors but is also not facilitated by gravity in the same way as roll updating.

Roles of gravitational cues and efference copy signals in the rotational updating of memory saccades.

Primates are able to localize a briefly flashed target despite intervening movements of the eyes, head, or body. This ability, often referred to as updating, requires extraretinal signals related to the intervening movement. With active roll rotations of the head from an upright position it has been shown that the updating mechanism is 3-dimensional, robust, and geometrically sophisticated. Here we examine whether such a rotational updating mechanism operates during passive motion both with and without inertial cues about head/body position in space. Subjects were rotated from either an upright or supine position, about a nasal-occipital axis, briefly shown a world-fixed target, rotated back to their original position, and then asked to saccade to the remembered target location. Using this paradigm, we tested subjects' abilities to update from various tilt angles (0, +/-30, +/-45, +/-90 degrees), to 8 target directions and 2 target eccentricities. In the upright condition, subjects accurately updated the remembered locations from all tilt angles independent of target direction or eccentricity. Slopes of directional errors versus tilt angle ranged from -0.011 to 0.15, and were significantly different from a slope of 1 (no compensation for head-in-space roll) and a slope of 0.9 (no compensation for eye-in-space roll). Because the eyes, head, and body were fixed throughout these passive movements, subjects could not use efference copies or neck proprioceptive cues to assess the amount of tilt, suggesting that vestibular signals and/or body proprioceptive cues suffice for updating. In the supine condition, where gravitational signals could not contribute, slopes ranged from 0.60 to 0.82, indicating poor updating performance. Thus information specifying the body's orientation relative to gravity is critical for maintaining spatial constancy and for distinguishing body-fixed versus world-fixed reference frames.

Three-dimensional eye-head coordination is implemented downstream from the superior colliculus.

How the brain transforms two-dimensional visual signals into multi-dimensional motor commands, and subsequently how it constrains the redundant degrees of freedom, are fundamental problems in sensorimotor control. During fixations between gaze shifts, the redundant torsional degree of freedom is determined by various neural constraints. For example, the eye- and head-in-space are constrained by Donders' law, whereas the eye-in-head obeys Listing's law. However, where and how the brain implements these laws is not yet known. In this study, we show that eye and head movements, elicited by unilateral microstimulations of the superior colliculus (SC) in head-free monkeys, obey the same Donders' strategies observed in normal behavior (i.e., Listing's law for final eye positions and the Fick strategy for the head). Moreover, these evoked movements showed a pattern of three-dimensional eye-head coordination, consistent with normal behavior, where the eye is driven purposely out of Listing's plane during the saccade portion of the gaze shift in opposition to a subsequent torsional vestibuloocular reflex slow phase, such that the final net torsion at the end of each head-free gaze shift is zero. The required amount of saccade-related torsion was highly variable, depending on the initial position of the eye and head prior to a gaze shift and the size of the gaze shift, pointing to a neural basis of torsional control. Because these variable, context-appropriate torsional saccades were correctly elicited by fixed SC commands during head-free stimulations, this shows that the SC only encodes the horizontal and vertical components of gaze, leaving the complexity of torsional organization to downstream control systems. Thus we conclude that Listing's and Donders' laws of the eyes and head, and their three-dimensional coordination mechanisms, must be implemented after the SC.

Midbrain control of three-dimensional head orientation.

Little is known about the neural mechanisms controlling head posture and why they fail in clinical syndromes like torticollis. It is well established, however, that the brain controls eye position by integrating eye velocity commands. By electrically stimulating and reversibly inactivating midbrain sites in the head-free (nonimmobilized) monkey, we found that the interstitial nucleus of Cajal functions as a neural integrator for head posture. We suggest that a bilateral imbalance in this structure, through either direct damage or inappropriate input, could be one of the mechanisms underlying torticollis.

Contribution of head movement to gaze command coding in monkey frontal cortex and superior colliculus.

Most of what we know about the neural control of gaze comes from experiments in head-fixed animals, but several "head-free" studies have suggested that fixing the head dramatically alters the apparent gaze command. We directly investigated this issue by quantitatively comparing head-fixed and head-free gaze trajectories evoked by electrically stimulating 52 sites in the superior colliculus (SC) of two monkeys and 23 sites in the supplementary eye fields (SEF) of two other monkeys. We found that head movements made a significant contribution to gaze shifts evoked from both neural structures. In the majority of the stimulated sites, average gaze amplitude was significantly larger and individual gaze trajectories were significantly less convergent in space with the head free to move. Our results are consistent with the hypothesis that head-fixed stimulation only reveals the oculomotor component of the gaze shift, not the true, planned goal of the movement. One implication of this finding is that when comparing stimulation data against popular gaze control models, freeing the head shifts the apparent coding of gaze away from a "spatial code" toward a simpler visual model in the SC and toward an eye-centered or fixed-vector model representation in the SEF.