Reliability in evaluator-based tests: using simulation-constructed models to determine contextually relevant agreement thresholds.

BACKGROUND: Indices of inter-evaluator reliability are used in many fields such as computational linguistics, psychology, and medical science; however, the interpretation of resulting values and determination of appropriate thresholds lack context and are often guided only by arbitrary "rules of thumb" or simply not addressed at all. Our goal for this work was to develop a method for determining the relationship between inter-evaluator agreement and error to facilitate meaningful interpretation of values, thresholds, and reliability. METHODS: Three expert human evaluators completed a video analysis task, and averaged their results together to create a reference dataset of 300 time measurements. We simulated unique combinations of systematic error and random error onto the reference dataset to generate 4900 new hypothetical evaluators (each with 300 time measurements). The systematic errors and random errors made by the hypothetical evaluator population were approximated as the mean and variance of a normally-distributed error signal. Calculating the error (using percent error) and inter-evaluator agreement (using Krippendorff's alpha) between each hypothetical evaluator and the reference dataset allowed us to establish a mathematical model and value envelope of the worst possible percent error for any given amount of agreement. RESULTS: We used the relationship between inter-evaluator agreement and error to make an informed judgment of an acceptable threshold for Krippendorff's alpha within the context of our specific test. To demonstrate the utility of our modeling approach, we calculated the percent error and Krippendorff's alpha between the reference dataset and a new cohort of trained human evaluators and used our contextually-derived Krippendorff's alpha threshold as a gauge of evaluator quality. Although all evaluators had relatively high agreement (> 0.9) compared to the rule of thumb (0.8), our agreement threshold permitted evaluators with low error, while rejecting one evaluator with relatively high error. CONCLUSIONS: We found that our approach established threshold values of reliability, within the context of our evaluation criteria, that were far less permissive than the typically accepted "rule of thumb" cutoff for Krippendorff's alpha. This procedure provides a less arbitrary method for determining a reliability threshold and can be tailored to work within the context of any reliability index.

Mechanics of mouse ocular motor plant quantified by optogenetic techniques.

Rigorous descriptions of ocular motor mechanics are often needed for models of ocular motor circuits. The mouse has become an important tool for ocular motor studies, yet most mechanical data come from larger species. Recordings of mouse abducens neurons indicate the mouse mechanics share basic viscoelastic properties with larger species but have considerably longer time constants. Time constants can also be extracted from the rate at which the eye re-centers when released from an eccentric position. The displacement can be accomplished by electrically stimulating ocular motor nuclei, but electrical stimulation may also activate nearby ocular motor circuitry. We achieved specific activation of abducens motoneurons through photostimulation in transgenic mice expressing channelrhodopsin in cholinergic neurons. Histology confirmed strong channelrhodopsin expression in the abducens nucleus with relatively little expression in nearby ocular motor structures. Stimulation was delivered as 20- to 1,000-ms pulses and 40-Hz trains. Relaxations were modeled best by a two-element viscoelastic system. Time constants were sensitive to stimulus duration. Analysis of isometric relaxation of isolated mouse extraocular muscles suggest the dependence is attributable to noninstantaneous decay of active forces in non-twitch fibers following stimulus offset. Time constants were several times longer than those obtained in primates, confirming that the mouse ocular motor mechanics are relatively sluggish. Finally, we explored the effects of 0.1- to 20-Hz sinusoidal photostimuli and demonstrated their potential usefulness in characterizing ocular motor mechanics, although this application will require further data on the temporal relationship between photostimulation and neuronal firing in extraocular motoneurons.

Flocculus Purkinje cell signals in mouse Cacna1a calcium channel mutants of escalating severity: an investigation of the role of firing irregularity in ataxia.

Mutation of the Cacna1a gene for the P/Q (CaV2.1) calcium channel invariably leads to cerebellar dysfunction. The dysfunction has been attributed to disrupted rhythmicity of cerebellar Purkinje cells, but the hypothesis remains unproven. If irregular firing rates cause cerebellar dysfunction, then the irregularity and behavioral deficits should covary in a series of mutant strains of escalating severity. We compared firing irregularity in floccular and anterior vermis Purkinje cells in the mildly affected rocker and moderately affected tottering Cacna1a mutants and normal C57BL/6 mice. We also measured the amplitude and timing of modulations of floccular Purkinje cell firing rate during the horizontal vestibuloocular reflex (VOR, 0.25-1 Hz) and the horizontal and vertical optokinetic reflex (OKR, 0.125-1 Hz). We recorded Purkinje cells selective for rotational stimulation about the vertical axis (VAPCs) and a horizontal axis (HAPCs). Irregularity scaled with behavioral deficit severity in the flocculus but failed to do so in the vermis, challenging the irregularity hypothesis. Mutant VAPCs exhibited unusually strong modulation during VOR and OKR, the response augmentation scaling with phenotypic severity. HAPCs exhibited increased OKR modulation but in tottering only. The data contradict prior claims that modulation amplitude is unaffected in tottering but support the idea that attenuated compensatory eye movements in Cacna1a mutants arise from defective transfer of Purkinje cell signals to downstream circuitry, rather than attenuated synaptic transmission within the cerebellar cortex. Shifts in the relative sizes of the VAPC and HAPC populations raise the possibility that Cacna1a mutations influence the development of floccular zone architecture.

Dynamics of abducens nucleus neurons in the awake mouse.

The mechanics of the eyeball and orbital tissues (the "ocular motor plant") are a fundamental determinant of ocular motor signal processing. The mouse is used increasingly in ocular motor physiology, but little is known about its plant mechanics. One way to characterize the mechanics is to determine relationships between extraocular motoneuron firing and eye movement. We recorded abducens nucleus neurons in mice executing compensatory eye movements during 0.1- to 1.6-Hz oscillation in the light. We analyzed firing rates to extract eye position and eye velocity sensitivities, from which we determined time constants of a viscoelastic model of the plant. The majority of abducens neurons were already active with the eye in its central rest position, with only 6% recruited at more abducted positions. Firing rates exhibited largely linear relationships to eye movement, although there was a nonlinearity consisting of increasing modulation in proportion to eye movement as eye amplitudes became small (due to reduced stimulus amplitude or reduced alertness). Eye position and velocity sensitivities changed with stimulus frequency as expected for an ocular motor plant dominated by cascaded viscoelasticities. Transfer function poles lay at approximately 0.1 and 0.9 s. Compared with previously studied animal species, the mouse plant is stiffer than the rabbit but laxer than cat and rhesus. Differences between mouse and rabbit can be explained by scaling for eye size (allometry). Differences between the mouse and cat or rhesus can be explained by differing ocular motor repertoires of animals with and without a fovea or area centralis.

Proprioceptive Augmentation With Illusory Kinaesthetic Sensation in Stroke Patients Improves Movement Quality in an Active Upper Limb Reach-and-Point Task.

Stroke patients often have difficulty completing motor tasks even after substantive rehabilitation. Poor recovery of motor function can often be linked to stroke-induced damage to motor pathways. However, stroke damage in pathways that impact effective integration of sensory feedback with motor control may represent an unappreciated obstacle to smooth motor coordination. In this study we investigated the effects of augmenting movement proprioception during a reaching task in six stroke patients as a proof of concept. We used a wearable neurorobotic proprioceptive feedback system to induce illusory kinaesthetic sensation by vibrating participants' upper arm muscles over active limb movements. Participants were instructed to extend their elbow to reach-and-point to targets of differing sizes at various distances, while illusion-inducing vibration (90 Hz), sham vibration (25 Hz), or no vibration was applied to the distal tendons of either their biceps brachii or their triceps brachii. To assess the impact of augmented kinaesthetic feedback on motor function we compared the results of vibrating the biceps or triceps during arm extension in the affected arm of stroke patients and able-bodied participants. We quantified performance across conditions and participants by tracking limb/hand kinematics with motion capture, and through Fitts' law analysis of reaching target acquisition. Kinematic analyses revealed that injecting 90 Hz illusory kinaesthetic sensation into the actively contracting (agonist) triceps muscle during reaching increased movement smoothness, movement directness, and elbow extension. Conversely, injecting 90 Hz illusory kinaesthetic sensation into the antagonistic biceps during reaching negatively impacted those same parameters. The Fitts' law analyses reflected similar effects with a trend toward increased throughput with triceps vibration during reaching. Across all analyses, able-bodied participants were largely unresponsive to illusory vibrational augmentation. These findings provide evidence that vibration-induced movement illusions delivered to the primary agonist muscle involved in active movement may be integrated into rehabilitative approaches to help promote functional motor recovery in stroke patients.

Neurorobotic fusion of prosthetic touch, kinesthesia, and movement in bionic upper limbs promotes intrinsic brain behaviors.

Bionic prostheses have restorative potential. However, the complex interplay between intuitive motor control, proprioception, and touch that represents the hallmark of human upper limb function has not been revealed. Here, we show that the neurorobotic fusion of touch, grip kinesthesia, and intuitive motor control promotes levels of behavioral performance that are stratified toward able-bodied function and away from standard-of-care prosthetic users. This was achieved through targeted motor and sensory reinnervation, a closed-loop neural-machine interface, coupled to a noninvasive robotic architecture. Adding touch to motor control improves the ability to reach intended target grasp forces, find target durometers among distractors, and promote prosthetic ownership. Touch, kinesthesia, and motor control restore balanced decision strategies when identifying target durometers and intrinsic visuomotor behaviors that reduce the need to watch the prosthetic hand during object interactions, which frees the eyes to look ahead to the next planned action. The combination of these three modalities also enhances error correction performance. We applied our unified theoretical, functional, and clinical analyses, enabling us to define the relative contributions of the sensory and motor modalities operating simultaneously in this neural-machine interface. This multiperspective framework provides the necessary evidence to show that bionic prostheses attain more human-like function with effective sensory-motor restoration.

Probing the mechanism of saccade-associated head movements through observations of head movement propensity and cognition in the elderly.

Humans may accomplish gaze shifts by eye-only saccades or combined eye-head saccades. The mechanisms that determine whether the head moves remain poorly understood. Many observations can be explained if phylogenetically ancient circuits generate eye-head saccades by default and frontal cerebral structures interrupt this synergy when eye-only saccades are preferable. Saccade-associated head movements have been reported to increase in the elderly. To test the hypothesis of frontal inhibition of head movements, we investigated whether the increase is associated with a decline in frontal cognitive function. We measured head movement tendencies and cognition in volunteers aged 61-80. Measures of head movement tendency included the customary range of eye eccentricity, customary range of head eccentricity, range of target eccentricities evoking predominantly eye-only saccades, and two measures of head amplitude variation as a function of target eccentricity. Cognitive measures encompassed verbal fluency, verbal memory, non-verbal memory, and executive function. There was no correlation between cognition and any measure of head movement tendency. We combined these elderly data with measurements of head movements in a group aged 21-67 and found mildly reduced, not increased, head movement tendencies with age. However, when confronted with a task that could be accomplished without moving the head, young subjects were more likely to cease all head movements. While inconclusive regarding the hypothesis of inhibition of saccade-associated head movements by cerebral structures, the results indicate the need to distinguish between mechanisms that define head movement tendencies and mechanisms that adapt head motion to the geometry of a specific task.

Long-Term Home-Use of Sensory-Motor-Integrated Bidirectional Bionic Prosthetic Arms Promotes Functional, Perceptual, and Cognitive Changes.

Cutaneous sensation is vital to controlling our hands and upper limbs. It helps close the motor control loop by informing adjustments of grasping forces during object manipulations and provides much of the information the brain requires to perceive our limbs as a part of our bodies. This sensory information is absent to upper-limb prosthesis users. Although robotic prostheses are becoming increasingly sophisticated, the absence of feedback imposes a reliance on open-loop control and limits the functional potential as an integrated part of the body. Experimental systems to restore physiologically relevant sensory information to prosthesis users are beginning to emerge. However, the impact of their long-term use on functional abilities, body image, and neural adaptation processes remains unclear. Understanding these effects is essential to transition sensate prostheses from sophisticated assistive tools to integrated replacement limbs. We recruited three participants with high-level upper-limb amputation who previously received targeted reinnervation surgery. Each participant was fit with a neural-machine-interface prosthesis that allowed participants to operate their device by thinking about moving their missing limb. Additionally, we fit a sensory feedback system that allowed participants to experience touch to the prosthesis as touch on their missing limb. All three participants performed a long-term take-home trial. Two participants used their neural-machine-interface systems with touch feedback and one control participant used his prescribed, insensate prosthesis. A series of functional outcome metrics and psychophysical evaluations were performed using sensate neural-machine-interface prostheses before and after the take-home period to capture changes in functional abilities, limb embodiment, and neural adaptation. Our results demonstrated that the relationship between users and sensate neural-machine-interface prostheses is dynamic and changes with long-term use. The presence of touch sensation had a near-immediate impact on how the users operated their prostheses. In the multiple independent measures of users' functional abilities employed, we observed a spectrum of performance changes following long-term use. Furthermore, after the take-home period, participants more appropriately integrated their prostheses into their body images and psychophysical tests provided strong evidence that neural and cortical adaptation occurred.

Eye-head coupling tendencies in stationary and moving subjects.

Humans exhibit considerable individuality in their propensity to make head movements during horizontal saccades. These variations originate in multiple quantifiable characteristics, including individuals' preferred ranges of gaze, eye-in-head, and head-on-neck eccentricity. Such "eye-head tendencies" have been uniformly assessed in seated subjects. It is unknown whether they continue to influence behavior when subjects are in motion. Previous studies of eye-head coordination in subjects ambulating in laboratories would predict that wholly different eye-head tendencies become ascendant when subjects ambulate. We tested this prediction by recording eye and head positions in normal subjects in an outdoor environment as they spontaneously regarded their surroundings while seated, passively riding in a wheelchair, and ambulating. Individuals exhibited the usual subject-to-subject variations in the preferred ranges of eye, head, and gaze position, but their own behavior was similar across the different conditions. While ambulation did affect some of the measured eye-head tendencies, passively riding had similar effects, indicating that these effects relate more to motion through the environment than to the act of walking. In a surprising departure from studies of eye-head coordination in subjects ambulating in laboratory environments, neither head nor gaze was particularly strongly aligned with the direction of travel. Thus, the neural mechanisms of walking do not demand that specific gaze or head orientations be maintained continuously, at least not in the common situation of a non-challenging path that can be negotiated without much attention. In such situations eye and head control is flexible, and the eye-head tendencies manifesting when stationary can emerge.

Using sensory discrimination in a foraging-style task to evaluate human upper-limb sensorimotor performance.

Object stiffness discrimination is fundamental to shaping the way we interact with our environment. Investigating the sensorimotor mechanisms underpinning stiffness discrimination may help further our understanding of healthy and sensory-impaired upper limb function. We developed a metric that leverages sensory discrimination techniques and a foraging-based analysis to characterize participant accuracy and discrimination processes of sensorimotor control. Our metric required searching and discriminating two variants of test-object: rubber blocks and spring cells, which emphasized cutaneous-force and proprioceptive feedback, respectively. We measured the number of test-objects handled, selection accuracy, and foraging duration. These values were used to derive six indicators of performance. We observed higher discrimination accuracies, with quicker search and handling durations, for blocks compared to spring cells. Correlative analyses of accuracy, error rates, and foraging times suggested that the block and spring variants were, in fact, unique sensory tasks. These results provide evidence that our metric is sensitive to the contributions of sensory feedback, motor control, and task performance strategy, and will likely be effective in further characterizing the impact of sensory feedback on motor control in healthy and sensory-impaired populations.

Characterization of the Sense of Agency over the Actions of Neural-machine Interface-operated Prostheses.

This work describes a methodological framework that can be used to explicitly and implicitly characterize the sense of agency developed over the neural-machine interface (NMI) control of sensate virtual or robotic prosthetic hands. The formation of agency is fundamental in distinguishing the actions that we perform with our limbs as being our own. By striving to incorporate advanced upper-limb prostheses into these same perceptual mechanisms, we can begin to integrate an artificial limb more closely into the user's existing cognitive framework for limb control. This has important implications in promoting user acceptance, use, and effective control of advanced upper-limb prostheses. In this protocol, participants control a virtual prosthetic hand and receive kinesthetic sensory feedback through their preexisting NMIs. A series of virtual grasping tasks are performed and perturbations are systematically introduced to the kinesthetic feedback and virtual hand movements. Two separate measures of agency are employed: established psychophysical questionnaires (to capture the explicit experience of agency) and a time interval estimate task to capture the implicit sense of agency (intentional binding). Results of this protocol (questionnaire scores and time interval estimates) can be analyzed to quantify the extent of agency formation.

Idiosyncratic variations in eye-head coupling observed in the laboratory also manifest during spontaneous behavior in a natural setting.

The tendency to generate head movements during saccades varies from person to person. Head movement tendencies can be measured as subjects fixate sequences of illuminated targets, but the extent to which such measures reflect eye-head coupling during more natural behaviors is unknown. We quantified head movement tendencies in 20 normal subjects in a conventional laboratory experiment and in an outdoor setting in which the subjects directed their gaze spontaneously. In the laboratory, head movement tendencies during centrifugal saccades could be described by the eye-only range (EOR), customary ocular motor range (COMR), and the customary head orientation range (CHOR). An analogous EOR, COMR, and CHOR could be extracted from the centrifugal saccades executed in the outdoor setting. An additional six measures were introduced to describe the preferred ranges of eyes-in-head and head-on-torso manifest throughout the outdoor recording, i.e., not limited to the orientations following centrifugal saccades. These 12 measured variables could be distilled by factor analysis to one indoor and six outdoor factors. The factors reflect separable tendencies related to preferred ranges of visual search, head eccentricity, and eye eccentricity. Multiple correlations were found between the indoor and outdoor factors. The results demonstrate that there are multiple types of head movement tendencies, but some of these influence behavior across rather different experimental settings and tasks. Thus behavior in the two settings likely relies on common neural mechanisms, and the laboratory assays of head movement tendencies succeed in probing the mechanisms underlying eye-head coupling during more natural behaviors.

Fitts' Law in the Control of Isometric Grip Force With Naturalistic Targets.

Fitts' law models the relationship between amplitude, precision, and speed of rapid movements. It is widely used to quantify performance in pointing tasks, study human-computer interaction, and generally to understand perceptual-motor information processes, including research to model performance in isometric force production tasks. Applying Fitts' law to an isometric grip force task would allow for quantifying grasp performance in rehabilitative medicine and may aid research on prosthetic control and design. We examined whether Fitts' law would hold when participants attempted to accurately produce their intended force output while grasping a manipulandum when presented with images of various everyday objects (we termed this the implicit task). Although our main interest was the implicit task, to benchmark it and establish validity, we examined performance against a more standard visual feedback condition via a digital force-feedback meter on a video monitor (explicit task). Next, we progressed from visual force feedback with force meter targets to the same targets without visual force feedback (operating largely on feedforward control with tactile feedback). This provided an opportunity to see if Fitts' law would hold without vision, and allowed us to progress toward the more naturalistic implicit task (which does not include visual feedback). Finally, we changed the nature of the targets from requiring explicit force values presented as arrows on a force-feedback meter (explicit targets) to the more naturalistic and intuitive target forces implied by images of objects (implicit targets). With visual force feedback the relation between task difficulty and the time to produce the target grip force was predicted by Fitts' law (average r2 = 0.82). Without vision, average grip force scaled accurately although force variability was insensitive to the target presented. In contrast, images of everyday objects generated more reliable grip forces without the visualized force meter. In sum, population means were well-described by Fitts' law for explicit targets with vision (r2 = 0.96) and implicit targets (r2 = 0.89), but not as well-described for explicit targets without vision (r2 = 0.54). Implicit targets should provide a realistic see-object-squeeze-object test using Fitts' law to quantify the relative speed-accuracy relationship of any given grasper.

Implicit Grasp Force Representation in Human Motor Cortical Recordings.

In order for brain-computer interface (BCI) systems to maximize functionality, users will need to be able to accurately modulate grasp force to avoid dropping heavy objects while also being able to handle fragile items. We present a case-study consisting of two experiments designed to identify whether intracortical recordings from the motor cortex of a person with tetraplegia could predict intended grasp force. In the first task, we were able classify neural responses to attempted grasps of four objects, each of which required similar grasp kinematics but different implicit grasp force targets, with 69% accuracy. In the second task, the subject attempted to move a virtual robotic arm in space to grasp a simple virtual object. For each trial, the subject was asked to grasp the virtual object with the force appropriate for one of the four objects from the first experiment, with the goal of measuring an implicit representation of grasp force. While the subject knew the grasp force during all phases of the trial, accurate classification was only achieved during active grasping, not while the hand moved to, transported, or released the object. In both tasks, misclassifications were most often to the object with an adjacent force requirement. In addition to the implications for understanding the representation of grasp force in motor cortex, these results are a first step toward creating intelligent algorithms to help BCI users grasp and manipulate a variety of objects that will be encountered in daily life. Clinical Trial Identifier: NCT01894802 https://clinicaltrials.gov/ct2/show/NCT01894802.

Illusory movement perception improves motor control for prosthetic hands.

To effortlessly complete an intentional movement, the brain needs feedback from the body regarding the movement's progress. This largely nonconscious kinesthetic sense helps the brain to learn relationships between motor commands and outcomes to correct movement errors. Prosthetic systems for restoring function have predominantly focused on controlling motorized joint movement. Without the kinesthetic sense, however, these devices do not become intuitively controllable. We report a method for endowing human amputees with a kinesthetic perception of dexterous robotic hands. Vibrating the muscles used for prosthetic control via a neural-machine interface produced the illusory perception of complex grip movements. Within minutes, three amputees integrated this kinesthetic feedback and improved movement control. Combining intent, kinesthesia, and vision instilled participants with a sense of agency over the robotic movements. This feedback approach for closed-loop control opens a pathway to seamless integration of minds and machines.

4-aminopyridine does not enhance flocculus function in tottering, a mouse model of vestibulocerebellar dysfunction and ataxia.

The potassium channel antagonist 4-aminopyridine (4-AP) improves a variety of motor abnormalities associated with disorders of the cerebellum. The most rigorous quantitative data relate to 4-AP's ability to improve eye movement deficits in humans referable to dysfunction of the cerebellar flocculus. Largely based on work in the ataxic mouse mutant tottering (which carries a mutation of the Cacna1a gene of the P/Q voltage-activated calcium channel), 4-AP is hypothesized to function by enhancing excitability or rhythmicity of floccular Purkinje cells. We tested this hypothesis by determining whether systemic or intrafloccular administration of 4-AP would ameliorate the eye movement deficits in tottering that are attributable to flocculus dysfunction, including the reductions in amplitude of the yaw-axis vestibulo-ocular reflex (VOR) and vision-enhanced vestibulo-ocular reflex (VVOR), and the optokinetic reflex (OKR) about yaw and roll axes. Because tottering's deficits increase with age, both young and elderly mutants were tested to detect any age-dependent 4-AP effects. 4-AP failed to improve VOR, VVOR, and OKR gains during sinusoidal stimuli, although it may have reduced the tendency of the mutants' responses to VOR and VVOR to decline over the course of a one-hour recording session. For constant-velocity optokinetic stimuli, 4-AP generated some enhancement of yaw OKR and upward-directed roll OKR, but the effects were also seen in normal C57BL/6 controls, and thus do not represent a specific reversal of the electrophysiological consequences of the tottering mutation. Data support a possible extra-floccular locus for the effects of 4-AP on habituation and roll OKR. Unilateral intrafloccular 4-AP injections did not affect ocular motility, except to generate mild eye elevations, consistent with reduced floccular output. Because 4-AP did not produce the effects expected if it normalized outputs of floccular Purkinje cells, there is a need for further studies to elucidate the drug's mechanism of action on cerebellar motor dysfunction.

Handheld cellular phones restrict head movements and range of visual regard.

Numerous studies have reported the ability of mobile phones to distract users and thereby degrade performance of concurrent tasks. Less is known about whether the phone-holding posture can itself influence concurrent motor activities. Horizontal eye movements are often coordinated with head movements, particularly when the amplitude of the gaze shift is large. Holding a phone to one ear has been shown to restrict the range of spontaneously generated head movements. In order to determine whether the phone-holding posture also influences gaze, we recorded eye and head movements as volunteers looked about themselves spontaneously. Holding the phone to the ear narrowed the range of gaze, principally in subjects who exhibit a strong propensity to move the head with the eyes. We argue that visual exploration may be influenced by the balance between costs and benefits of turning the head, with the phone-holding posture increasing the costs. The effects on gaze would be seen most clearly in subjects who have a higher predilection for coupling eye and head movements. Conversely, this effect would be minimal if tested in tasks that rarely elicit head movements in the specific subjects being tested. The results emphasize the close coordination between eye and head movements, and have implications for the design of ergonomic studies comparing the effects of handheld vs. hands-free mobile phones on performance of specific tasks, such as driving.

The ataxic mouse as a model for studying downbeat nystagmus.

Downbeat nystagmus (DBN) is a common eye movement complication of cerebellar disease. Use of mice to study pathophysiology of vestibulocerebellar disease is increasing, but it is unclear if mice can be used to study DBN; it has not been reported in this species. We determined whether DBN occurs in the ataxic mutant tottering, which carries a mutation in the Cacna1a gene for P/Q calcium channels. Spontaneous DBN occurred only rarely, and its magnitude did not exhibit the relationship to head tilt seen in human patients. DBN during yaw rotation was more common and shares some properties with the tilt-independent, gaze-independent component of human DBN, but differs in its dependence on vision. Hyperactivity of otolith circuits responding to pitch tilts is hypothesized to contribute to the gaze-independent component of human DBN. Mutants exhibited hyperactivity of the tilt maculo-ocular reflex (tiltMOR) in pitch. The hyperactivity may serve as a surrogate for DBN in mouse studies. TiltMOR hyperactivity correlates with hyperdeviation of the eyes and upward deviation of the head during ambulation; these may be alternative surrogates. Muscimol inactivation of the cerebellar flocculus suggests a floccular role in the tiltMOR hyperactivity and provides insight into the rarity of frank DBN in ataxic mice.