Effect of vestibular loss on head-on-trunk stability in individuals with vestibular schwannoma.

The vestibulo-collic reflex generates neck motor commands to produce head-on-trunk movements that are essential for stabilizing the head relative to space. Here we examined the effects of vestibular loss on head-on-trunk kinematics during voluntary behavior. Head and trunk movements were measured in individuals with vestibular schwannoma before and then 6 weeks after unilateral vestibular deafferentation via surgical resection of the tumor. Movements were recorded in 6 dimensions (i.e., 3 axes of rotation and 3 axes of translation) using small light-weight inertial measurement units while participants performed balance and gait tasks. Kinematic measures differed between individuals with vestibular schwannoma (at both time points) and healthy controls for the more challenging exercises, namely those performed in tandem position or on an unstable surface without visual input. Quantitative assessment of the vestibulo-ocular reflex (VOR) revealed a reduction in VOR gain for individuals with vestibular schwannoma compared to control subjects, that was further reduced following surgery. These findings indicated that the impairment caused by either the tumor or subsequent surgical tumor resection altered head-on-trunk kinematics in a manner that is not normalized by central compensation. In contrast, we further found that head-on-trunk kinematics in individuals with vestibular schwannoma were actually comparable before and after surgery. Thus, taken together, our results indicate that vestibular loss impacts head-on-trunk kinematics during voluntary balance and gait behaviors, and suggest that the neural mechanisms mediating adaptation alter the motion strategies even before surgery in a manner that may be maladaptive for long-term compensation.

Electrical stimulation of the peripheral and central vestibular system.

PURPOSE OF REVIEW: Electrical stimulation of the peripheral and central vestibular system using noninvasive (galvanic vestibular stimulation, GVS) or invasive (intracranial electrical brain stimulation, iEBS) approaches have a long history of use in studying self-motion perception and balance control. The aim of this review is to summarize recent electrophysiological studies of the effects of GVS, and functional mapping of the central vestibular system using iEBS in awake patients. RECENT FINDINGS: The use of GVS has become increasingly common in the assessment and treatment of a wide range of clinical disorders including vestibulopathy and Parkinson's disease. The results of recent single unit recording studies have provided new insight into the neural mechanisms underlying GVS-evoked improvements in perceptual and motor responses. Furthermore, the application of iEBS in patients with epilepsy or during awake brain surgery has provided causal evidence of vestibular information processing in mostly the middle cingulate cortex, posterior insula, inferior parietal lobule, amygdala, precuneus, and superior temporal gyrus. SUMMARY: Recent studies have established that GVS evokes robust and parallel activation of both canal and otolith afferents that is significantly different from that evoked by natural head motion stimulation. Furthermore, there is evidence that GVS can induce beneficial neural plasticity in the central pathways of patients with vestibular loss. In addition, iEBS studies highlighted an underestimated contribution of areas in the medial part of the cerebral hemispheres to the cortical vestibular network.

Internal states as a source of subject-dependent movement variability are represented by large-scale brain networks.

Humans' ability to adapt and learn relies on reflecting on past performance. These experiences form latent representations called internal states that induce movement variability that improves how we interact with our environment. Our study uncovered temporal dynamics and neural substrates of two states from ten subjects implanted with intracranial depth electrodes while they performed a goal-directed motor task with physical perturbations. We identified two internal states using state-space models: one tracking past errors and the other past perturbations. These states influenced reaction times and speed errors, revealing how subjects strategize from trial history. Using local field potentials from over 100 brain regions, we found large-scale brain networks such as the dorsal attention and default mode network modulate visuospatial attention based on recent performance and environmental feedback. Notably, these networks were more prominent in higher-performing subjects, emphasizing their role in improving motor performance by regulating movement variability through internal states.

Head movement kinematics are differentially altered for extended versus short duration gait exercises in individuals with vestibular loss.

Head kinematics are altered in individuals with vestibular schwannoma (VS) during short duration gait tasks [i.e., Functional Gait Assessment (FGA)], both before and after surgery, yet whether these differences extend to longer duration gait exercises is currently unknown. Here we examined the effects of vestibular loss and subsequent compensation on head kinematics in individuals with VS during gait exercises of relatively extended versus short duration (< 10 versus 30 s), compared to age-matched controls. Six-dimensional head movements were recorded during extended and short duration gait exercises before and then 6 weeks after sectioning of the involved vestibular nerve (vestibular neurectomy). Standard functional, physiological, and subjective clinical assessments were also performed at each time point. Kinematics were differentially altered in individuals with vestibular loss at both time points during extended versus short duration exercises. Range of motion was significantly reduced in extended tasks. In contrast, movement variability predominately differed for the short duration exercises. Overall, our results indicate that quantifying head kinematics during longer duration gait tasks can provide novel information about how VS individuals compensate for vestibular loss, and suggest that measurements of range of motion versus variability can provide information regarding the different strategies deployed to maintain functional locomotion.

Internal models of self-motion: neural computations by the vestibular cerebellum.

The vestibular cerebellum plays an essential role in maintaining our balance and ensuring perceptual stability during activities of daily living. Here I examine three key regions of the vestibular cerebellum: the floccular lobe, anterior vermis (lobules I-V), and nodulus and ventral uvula (lobules X-IX of the posterior vermis). These cerebellar regions encode vestibular information and combine it with extravestibular signals to create internal models of eye, head, and body movements, as well as their spatial orientation with respect to gravity. To account for changes in the external environment and/or biomechanics during self-motion, the neural mechanisms underlying these computations are continually updated to ensure accurate motor behavior. To date, studies on the vestibular cerebellum have predominately focused on passive vestibular stimulation, whereas in actuality most stimulation is the result of voluntary movement. Accordingly, I also consider recent research exploring these computations during active self-motion and emerging evidence establishing the cerebellum's role in building predictive models of self-generated movement.

Prosthetic Stimulation of the Vestibular Nerve Can Evoke Robust Eye and Head Movements Despite Prior Labyrinthectomy.

HYPOTHESIS: Prosthetic electrical stimulation can evoke compensatory eye and head movement despite vestibular implant electrode insertion occurring years after prior labyrinthectomy. BACKGROUND: Vestibular implants sense head rotation and directly stimulate the vestibular nerve, bypassing damaged end organs. Animal research and current clinical trials have demonstrated the efficacy of this approach. However, candidacy criteria for vestibular implants currently require presence of a patent labyrinth in the candidate ear and at least aidable hearing in the opposite ear, thus excluding patients who have undergone prior labyrinthectomy for unilateral Menière's disease that later progressed to bilateral vestibular hypofunction. METHODS: Eight years after right unilateral labyrinthectomy, we implanted stimulating electrodes in the previously exenterated right ear ampullae of a rhesus macaque monkey. The left labyrinth had long-standing hypofunction due to intratympanic gentamicin injection and surgical disruption. We used three-dimensional video-oculography to measure eye movement responses to prosthetic electrical stimulation. We also measured head-movement responses to prosthetic stimulation with the head unrestrained. RESULTS: Bilateral vestibular hypofunction was confirmed by absence of vestibuloocular reflex responses to whole-body rotation without prosthetic stimulation. For a subset of the implanted electrodes, prosthetic vestibular stimulation evoked robust compensatory eye and head movements. One electrode reliably elicited responses aligned with the implanted ear's anterior canal nerve regardless of the return electrode used. Similarly, a second electrode also elicited responses consistent with excitation of the horizontal canal nerve. Responses grew quasilinearly with stimulation rate and current amplitude. CONCLUSION: Prosthetic electrical stimulation targeting the vestibular nerve can be effective years after labyrinthectomy, if at least some parts of the vestibular nerve's ampullary branches remain despite destruction or removal of the membranous labyrinth.

Vestibular motor control.

The vestibular system is an essential sensory system that generates motor reflexes that are crucial for our daily activities, including stabilizing the visual axis of gaze and maintaining head and body posture. In addition, the vestibular system provides us with our sense of movement and orientation relative to space and serves a vital role in ensuring accurate voluntary behaviors. Neurophysiological studies have provided fundamental insights into the functional circuitry of vestibular motor pathways. A unique feature of the vestibular system compared to other sensory systems is that the same central neurons that receive direct input from the afferents of the vestibular component of the 8th nerve can also directly project to motor centers that control vital vestibular motor reflexes. In turn, these reflexes ensure stabilize gaze and the maintenance of posture during everyday activities. For instance, a direct three-neuron pathway mediates the vestibulo-ocular reflex (VOR) pathway to provide stable gaze. Furthermore, recent studies have advanced our understanding of the computations performed by the cerebellum and cortex required for motor learning, compensation, and voluntary movement and navigation. Together, these findings have provided new insights into how the brain ensures accurate self-movement during our everyday activities and have also advanced our knowledge of the neurobiological mechanisms underlying disorders of vestibular processing.

Complexes of vertebrate TMC1/2 and CIB2/3 proteins form hair-cell mechanotransduction cation channels.

Calcium and integrin-binding protein 2 (CIB2) and CIB3 bind to transmembrane channel-like 1 (TMC1) and TMC2, the pore-forming subunits of the inner-ear mechanoelectrical transduction (MET) apparatus. Whether these interactions are functionally relevant across mechanosensory organs and vertebrate species is unclear. Here we show that both CIB2 and CIB3 can form heteromeric complexes with TMC1 and TMC2 and are integral for MET function in mouse cochlea and vestibular end organs as well as in zebrafish inner ear and lateral line. Our AlphaFold 2 models suggest that vertebrate CIB proteins can simultaneously interact with at least two cytoplasmic domains of TMC1 and TMC2 as validated using nuclear magnetic resonance spectroscopy of TMC1 fragments interacting with CIB2 and CIB3. Molecular dynamics simulations of TMC1/2 complexes with CIB2/3 predict that TMCs are structurally stabilized by CIB proteins to form cation channels. Overall, our work demonstrates that intact CIB2/3 and TMC1/2 complexes are integral to hair-cell MET function in vertebrate mechanosensory epithelia.

Neural substrates of perception in the vestibular thalamus during natural self-motion: A review.

Accumulating evidence across multiple sensory modalities suggests that the thalamus does not simply relay information from the periphery to the cortex. Here we review recent findings showing that vestibular neurons within the ventral posteriolateral area of the thalamus perform nonlinear transformations on their afferent input that determine our subjective awareness of motion. Specifically, these neurons provide a substrate for previous psychophysical observations that perceptual discrimination thresholds are much better than predictions from Weber's law. This is because neural discrimination thresholds, which are determined from both variability and sensitivity, initially increase but then saturate with increasing stimulus amplitude, thereby matching the previously observed dependency of perceptual self-motion discrimination thresholds. Moreover, neural response dynamics give rise to unambiguous and optimized encoding of natural but not artificial stimuli. Finally, vestibular thalamic neurons selectively encode passively applied motion when occurring concurrently with voluntary (i.e., active) movements. Taken together, these results show that the vestibular thalamus plays an essential role towards generating motion perception as well as shaping our vestibular sense of agency that is not simply inherited from afferent input.

The Neural Basis for Biased Behavioral Responses Evoked by Galvanic Vestibular Stimulation in Primates.

Noninvasive electrical stimulation of the vestibular system in humans has become an increasingly popular tool with a broad range of research and clinical applications. However, common assumptions regarding the neural mechanisms that underlie the activation of central vestibular pathways through such stimulation, known as galvanic vestibular stimulation (GVS), have not been directly tested. Here, we show that GVS is encoded by VIIIth nerve vestibular afferents with nonlinear dynamics that differ markedly from those predicted by current models. GVS produced asymmetric activation of both semicircular canal and otolith afferents to the onset versus offset and cathode versus anode of applied current, that in turn produced asymmetric eye movement responses in three awake-behaving male monkeys. Additionally, using computational methods, we demonstrate that the experimentally observed nonlinear neural response dynamics lead to an unexpected directional bias in the net population response when the information from both vestibular nerves is centrally integrated. Together our findings reveal the neural basis by which GVS activates the vestibular system, establish that neural response dynamics differ markedly from current predictions, and advance our mechanistic understanding of how asymmetric activation of the peripheral vestibular system alters vestibular function. We suggest that such nonlinear encoding is a general feature of neural processing that will be common across different noninvasive electrical stimulation approaches.SIGNIFICANCE STATEMENT Here, we show that the application of noninvasive electrical currents to the vestibular system (GVS) induces more complex responses than commonly assumed. We recorded vestibular afferent activity in macaque monkeys exposed to GVS using a setup analogous to human studies. GVS evoked notable asymmetries in irregular afferent responses to cathodal versus anodal currents. We developed a nonlinear model explaining these GVS-evoked afferent responses. Our model predicts that GVS induces directional biases in centrally integrated head motion signals and establishes electrical stimuli that recreate physiologically plausible sensations of motion. Altogether, our findings provide new insights into how GVS activates the vestibular system, which will be vital to advancing new clinical and biomedical applications.

Vestibular Contributions to Primate Neck Postural Muscle Activity during Natural Motion.

To maintain stable posture of the head and body during our everyday activities, the brain integrates information across multiple sensory systems. Here, we examined how the primate vestibular system, independently and in combination with visual sensory input, contributes to the sensorimotor control of head posture across the range of dynamic motion experienced during daily life. We recorded activity of single motor units in the splenius capitis and sternocleidomastoid muscles in rhesus monkeys during yaw rotations spanning the physiological range of self-motion (up to 20 Hz) in darkness. Splenius capitis motor unit responses continued to increase with frequency up to 16 Hz in normal animals, and were strikingly absent following bilateral peripheral vestibular loss. To determine whether visual information modulated these vestibular-driven neck muscle responses, we experimentally controlled the correspondence between visual and vestibular cues of self-motion. Surprisingly, visual information did not influence motor unit responses in normal animals, nor did it substitute for absent vestibular feedback following bilateral peripheral vestibular loss. A comparison of muscle activity evoked by broadband versus sinusoidal head motion further revealed that low-frequency responses were attenuated when low- and high-frequency self-motion were experienced concurrently. Finally, we found that vestibular-evoked responses were enhanced by increased autonomic arousal, quantified via pupil size. Together, our findings directly establish the vestibular system's contribution to the sensorimotor control of head posture across the dynamic motion range experienced during everyday activities, as well as how vestibular, visual, and autonomic inputs are integrated for postural control.SIGNIFICANCE STATEMENT Our sensory systems enable us to maintain control of our posture and balance as we move through the world. Notably, the vestibular system senses motion of the head and sends motor commands, via vestibulospinal pathways, to axial and limb muscles to stabilize posture. By recording the activity of single motor units, here we show, for the first time, that the vestibular system contributes to the sensorimotor control of head posture across the dynamic motion range experienced during everyday activities. Our results further establish how vestibular, autonomic, and visual inputs are integrated for postural control. This information is essential for understanding both the mechanisms underlying the control of posture and balance, and the impact of the loss of sensory function.

Head movement kinematics are altered during balance stability exercises in individuals with vestibular schwannoma.

BACKGROUND: Balance stabilization exercises are often prescribed to facilitate compensation in individuals with vestibular schwannoma (VS). However, both the assessment and prescription of these exercises are reliant on clinical observations and expert opinion rather than on quantitative evidence. The aim of this study was to quantify head motion kinematics in individuals with vestibular loss while they performed commonly prescribed balance stability exercises. METHODS: Using inertial measurement units, head movements of individuals with vestibular schwannoma were measured before and after surgical deafferentation and compared with age-matched controls. RESULTS: We found that individuals with vestibular schwannoma experienced more variable head motion compared to healthy controls both pre- and postoperatively, particularly in absence of visual input, but that there was little difference between preoperative and postoperative kinematic measurements for our vestibular schwannoma group. We further found correlations between head motion kinematic measures during balance exercises, performed in the absence of visual input, and multiple clinical measurements for preoperative VS subjects. Subjects with higher head motion variability also had worse DVA scores, moved more slowly during the Timed up and Go and gait speed tests, and had lower scores on the functional gait assessment. In contrast, we did not find strong correlations between clinical measures and postoperative head kinematics for the same VS subjects. CONCLUSIONS: Our data suggest that further development of such metrics based on the quantification of head motion has merit for the assessment and prescription of balance exercises, as demonstrated by the calculation of a "kinematic score" for identifying the most informative balance exercise (i.e., "Standing on foam eyes closed").

Optokinetic set-point adaptation functions as an internal dynamic calibration mechanism for oculomotor disequilibrium.

Experience-dependent brain circuit plasticity underlies various sensorimotor learning and memory processes. Recently, a novel set-point adaptation mechanism was identified that accounts for the pronounced negative optokinetic afternystagmus (OKAN) following a sustained period of unidirectional optokinetic nystagmus (OKN) in larval zebrafish. To investigate the physiological significance of optokinetic set-point adaptation, animals in the current study were exposed to a direction-alternating optokinetic stimulation paradigm that better resembles their visual experience in nature. Our results reveal that not only was asymmetric alternating stimulation sufficient to induce the set-point adaptation and the resulting negative OKAN, but most strikingly, under symmetric alternating stimulation some animals displayed an inherent bias of the OKN gain in one direction, and that was compensated by the similar set-point adaptation. This finding, supported by mathematical modeling, suggests that set-point adaptation allows animals to cope with asymmetric optokinetic behaviors evoked by either external stimuli or innate oculomotor biases.

The Bárány Society position on 'Cervical Dizziness'.

This paper describes the Bárány Society Classification OverSight Committee (COSC) position on Cervical Dizziness, sometimes referred to as Cervical Vertigo. This involved an initial review by a group of experts across a broad range of fields, and then subsequent review by the Bárány Society COSC. Based upon the so far published literature, the Bárány Society COSC takes the view that the evidence supporting a mechanistic link between an illusory sensation of self-motion (i.e. vertigo - spinning or otherwise) and neck pathology and/or symptoms of neck pain - either by affecting the cervical vertebrae, soft tissue structures or cervical nerve roots - is lacking. When a combined head and neck movement triggers an illusory sensation of spinning, there is either an underlying common vestibular condition such as migraine or BPPV or less commonly a central vestibular condition including, when acute in onset, dangerous conditions (e.g. a dissection of the vertebral artery with posterior circulation stroke and, exceedingly rarely, a vertebral artery compression syndrome). The Committee notes, that migraine, including vestibular migraine, is by far, the commonest cause for the combination of neck pain and vestibular symptoms. The committee also notes that since head movement aggravates symptoms in almost any vestibular condition, the common finding of increased neck muscle tension in vestibular patients, may be linked as both cause and effect, to reduced head movements. Additionally, there are theoretical mechanisms, which have not been explored, whereby cervical pain may promote vaso-vagal, cardio-inhibitory reflexes and hence by presyncopal mechanisms, elicit   transient   disorientation and/or imbalance. The committee accepts that further research is required to answer the question as to whether those rare cases in which neck muscle spasm is associated with a vague sense of spatial disorientation and/or imbalance, is indeed linked to impaired neck proprioception. Future studies should ideally be placebo controlled and double-blinded where possible, with strict inclusion and exclusion criteria that aim for high specificity at the cost of sensitivity. To facilitate further studies in "cervical dizziness/vertigo", we provide a narrative view of the important confounds investigators should consider when designing controlled mechanistic and therapeutic studies. Hence, currently, the Bárány COSC refrains from proposing any preliminary diagnostic criteria for clinical use outside a research study. This position may change as new research evidence is provided.

Function of bidirectional sensitivity in the otolith organs established by transcription factor Emx2.

Otolith organs of the inner ear are innervated by two parallel afferent projections to the brainstem and cerebellum. These innervations were proposed to segregate across the line of polarity reversal (LPR) within each otolith organ, which divides the organ into two regions of hair cells (HC) with opposite stereociliary orientation. The relationship and functional significance of these anatomical features are not known. Here, we show regional expression of Emx2 in otolith organs, which establishes LPR, mediates the neuronal segregation across LPR and constitutes the bidirectional sensitivity function. Conditional knockout (cKO) of Emx2 in HCs lacks LPR. Tmie cKO, in which mechanotransduction was abolished selectively in HCs within the Emx2 expression domain also lacks bidirectional sensitivity. Analyses of both mutants indicate that LPR is specifically required for mice to swim comfortably and to traverse a balance beam efficiently, but LPR is not required for mice to stay on a rotating rod.

Loss of Flocculus Purkinje Cell Firing Precision Leads to Impaired Gaze Stabilization in a Mouse Model of Spinocerebellar Ataxia Type 6 (SCA6).

Spinocerebellar Ataxia Type 6 (SCA6) is a mid-life onset neurodegenerative disease characterized by progressive ataxia, dysarthria, and eye movement impairment. This autosomal dominant disease is caused by the expansion of a CAG repeat tract in the CACNA1A gene that encodes the α1A subunit of the P/Q type voltage-gated Ca2+ channel. Mouse models of SCA6 demonstrate impaired locomotive function and reduced firing precision of cerebellar Purkinje in the anterior vermis. Here, to further assess deficits in other cerebellar-dependent behaviors, we characterized the oculomotor phenotype of a knock-in mouse model with hyper-expanded polyQ repeats (SCA684Q). We found a reduction in the efficacy of the vestibulo-ocular reflex (VOR) and optokinetic reflex (OKR) in SCA6 mutant mice, without a change in phase, compared to their litter-matched controls. Additionally, VOR motor learning was significantly impaired in SCA684Q mice. Given that the floccular lobe of the cerebellum plays a vital role in the generation of OKR and VOR calibration and motor learning, we investigated the firing behavior and morphology of floccular cerebellar Purkinje cells. Overall, we found a reduction in the firing precision of floccular lobe Purkinje cells but no morphological difference between SCA684Q and wild-type mice. Taken together, our findings establish that gaze stabilization and motor learning are impaired in SCA684Q mice and suggest that altered cerebellar output contributes to these deficits.

A prosthesis utilizing natural vestibular encoding strategies improves sensorimotor performance in monkeys.

Sensory pathways provide complex and multifaceted information to the brain. Recent advances have created new opportunities for applying our understanding of the brain to sensory prothesis development. Yet complex sensor physiology, limited numbers of electrodes, and nonspecific stimulation have proven to be a challenge for many sensory systems. In contrast, the vestibular system is uniquely suited for prosthesis development. Its peripheral anatomy allows site-specific stimulation of 3 separate sensory organs that encode distinct directions of head motion. Accordingly, here, we investigated whether implementing natural encoding strategies improves vestibular prosthesis performance. The eye movements produced by the vestibulo-ocular reflex (VOR), which plays an essential role in maintaining visual stability, were measured to quantify performance. Overall, implementing the natural tuning dynamics of vestibular afferents produced more temporally accurate VOR eye movements. Exploration of the parameter space further revealed that more dynamic tunings were not beneficial due to saturation and unnatural phase advances. Trends were comparable for stimulation encoding virtual versus physical head rotations, with gains enhanced in the latter case. Finally, using computational methods, we found that the same simple model explained the eye movements evoked by sinusoidal and transient stimulation and that a stimulation efficacy substantially less than 100% could account for our results. Taken together, our results establish that prosthesis encodings that incorporate naturalistic afferent dynamics and account for activation efficacy are well suited for restoration of gaze stability. More generally, these results emphasize the benefits of leveraging the brain's endogenous coding strategies in prosthesis development to improve functional outcomes.

Sensory adaptation mediates efficient and unambiguous encoding of natural stimuli by vestibular thalamocortical pathways.

Sensory systems must continuously adapt to optimally encode stimuli encountered within the natural environment. The prevailing view is that such optimal coding comes at the cost of increased ambiguity, yet to date, prior studies have focused on artificial stimuli. Accordingly, here we investigated whether such a trade-off between optimality and ambiguity exists in the encoding of natural stimuli in the vestibular system. We recorded vestibular nuclei and their target vestibular thalamocortical neurons during naturalistic and artificial self-motion stimulation. Surprisingly, we found no trade-off between optimality and ambiguity. Using computational methods, we demonstrate that thalamocortical neural adaptation in the form of contrast gain control actually reduces coding ambiguity without compromising the optimality of coding under naturalistic but not artificial stimulation. Thus, taken together, our results challenge the common wisdom that adaptation leads to ambiguity and instead suggest an essential role in underlying unambiguous optimized encoding of natural stimuli.

Distinct representations of body and head motion are dynamically encoded by Purkinje cell populations in the macaque cerebellum.

The ability to accurately control our posture and perceive our spatial orientation during self-motion requires knowledge of the motion of both the head and body. However, while the vestibular sensors and nuclei directly encode head motion, no sensors directly encode body motion. Instead, the integration of vestibular and neck proprioceptive inputs is necessary to transform vestibular information into the body-centric reference frame required for postural control. The anterior vermis of the cerebellum is thought to play a key role in this transformation, yet how its Purkinje cells transform multiple streams of sensory information into an estimate of body motion remains unknown. Here, we recorded the activity of individual anterior vermis Purkinje cells in alert monkeys during passively applied whole-body, body-under-head, and head-on-body rotations. Most Purkinje cells dynamically encoded an intermediate representation of self-motion between head and body motion. Notably, Purkinje cells responded to both vestibular and neck proprioceptive stimulation with considerable heterogeneity in their response dynamics. Furthermore, their vestibular responses were tuned to head-on-body position. In contrast, targeted neurons in the deep cerebellar nuclei are known to unambiguously encode either head or body motion across conditions. Using a simple population model, we established that combining responses of~40-50 Purkinje cells could explain the responses of these deep cerebellar nuclei neurons across all self-motion conditions. We propose that the observed heterogeneity in Purkinje cell response dynamics underlies the cerebellum's capacity to compute the dynamic representation of body motion required to ensure accurate postural control and perceptual stability in our daily lives.

Context-independent encoding of passive and active self-motion in vestibular afferent fibers during locomotion in primates.

The vestibular system detects head motion to coordinate vital reflexes and provide our sense of balance and spatial orientation. A long-standing hypothesis has been that projections from the central vestibular system back to the vestibular sensory organs (i.e., the efferent vestibular system) mediate adaptive sensory coding during voluntary locomotion. However, direct proof for this idea has been lacking. Here we recorded from individual semicircular canal and otolith afferents during walking and running in monkeys. Using a combination of mathematical modeling and nonlinear analysis, we show that afferent encoding is actually identical across passive and active conditions, irrespective of context. Thus, taken together our results are instead consistent with the view that the vestibular periphery relays robust information to the brain during primate locomotion, suggesting that context-dependent modulation instead occurs centrally to ensure that coding is consistent with behavioral goals during locomotion.