Abstract
Accurate internal estimates of self-motion and orientation relative to gravity are fundamental for stabilizing gaze, controlling posture, and navigating through dynamic environments. Prevailing theories propose that the cerebellar nodulus and uvula (NU) employ internal models to suppress sensory input arising from predictable, self-generated motion. However, this assumption has never been directly tested. Here, we recorded NU Purkinje cell activity in rhesus monkeys during active and passive head movements. We found neurons responsive to passive translations remained equally sensitive to self-generated movements, encoding net head motion in space irrespective of its source. Furthermore, external perturbation did not influence these ground-truth encoding. When active head motion was blocked, Purkinje cell activity remained unchanged – demonstrating a lack of efference copy integration. During active tilts, NU neurons encoded both dynamic motion and static orientation relative to gravity. These findings challenge the internal model hypothesis and establish the NU as a ground-truth, context-invariant estimator of self-motion, supporting stable behavior in dynamic environments.
Data availability
The processed data that support the findings of this study are available in figshare with the identifier https://doi.org/10.6084/m9.figshare.30811046.
Code availability
The custom written codes for this manuscript have been deposited on GitHub (https://github.com/CullenLab/Nodulus-uvula-encoding-of-motion).
References
Horlings, C. G. et al. Vestibular and proprioceptive influences on trunk movements during quiet standing. Neuroscience 161, 904–914 (2009).
Kuo, A. D., Speers, R. A., Peterka, R. J. & Horak, F. B. Effect of altered sensory conditions on multivariate descriptors of human postural sway. Exp. Brain Res. 122, 185–195 (1998).
Peterka, R. J. Sensory integration for human balance control. Handb. Clin. Neurol. 159, 27–42 (2018).
Mildren, R. L. & Cullen, K. E. Vestibular contributions to primate neck postural muscle activity during natural motion. J. Neurosci. 43, 2326–2337 (2023).
Brooks, J. X. & Cullen, K. E. Predictive sensing: the role of motor signals in sensory processing. Biol. Psychiatry Cogn. Neurosci. Neuroimaging 4, 842–850 (2019).
Zobeiri, O. A. & Cullen, K. E. Cerebellar Purkinje cells in male macaques combine sensory and motor information to predict the sensory consequences of active self-motion. Nat. Commun. 15, 4003 (2024).
Roy, J. E. & Cullen, K. E. Selective processing of vestibular reafference during self-generated head motion. J. Neurosci. 21, 2131–2142 (2001).
Carriot, J., Brooks, J. X. & Cullen, K. E. Multimodal integration of self-motion cues in the vestibular system: active versus passive translations. J. Neurosci. 33, 19555–19566 (2013).
Brooks, J. X., Carriot, J. & Cullen, K. E. Learning to expect the unexpected: rapid updating in primate cerebellum during voluntary self-motion. Nat. Neurosci. 18, 1310–1317 (2015).
Cullen, K. E. Vestibular processing during natural self-motion: implications for perception and action. Nat. Rev. Neurosci. 20, 346–363 (2019).
Cullen, K. E. Internal models of self-motion: neural computations by the vestibular cerebellum. Trends Neurosci 46, 986–1002 (2023).
Laurens, J. The otolith vermis: a systems neuroscience theory of the Nodulus and Uvula. Front. Syst. Neurosci. 16, 886284 (2022).
Cullen, K. E. & Minor, L. B. Semicircular canal afferents similarly encode active and passive head-on-body rotations: implications for the role of vestibular efference. J. Neurosci. 22, RC226 (2002).
Sadeghi, S. G., Minor, L. B. & Cullen, K. E. Response of vestibular-nerve afferents to active and passive rotations under normal conditions and after unilateral labyrinthectomy. J. Neurophysiol. 97, 1503–1514 (2007).
Jamali, M., Sadeghi, S. G. & Cullen, K. E. Response of vestibular nerve afferents innervating utricle and saccule during passive and active translations. J. Neurophysiol. 101, 141–149 (2009).
Mackrous, I., Carriot, J. & Cullen, K. E. Context-independent encoding of passive and active self-motion in vestibular afferent fibers during locomotion in primates. Nat. Commun. 13, 120 (2022).
Fujita, H., Kodama, T. & du Lac, S. Modular output circuits of the fastigial nucleus for diverse motor and nonmotor functions of the cerebellar vermis. Elife 9, e58613 (2020).
Starr, M. S. & Summerhayes, M. Role of the ventromedial nucleus of the thalamus in motor behaviour—I. Effects of focal injections of drugs. Neuroscience 10, 1157–1169 (1983).
Goto, M., Swanson, L. W. & Canteras, N. S. Connections of the nucleus incertus. J. Comp. Neurol. 438, 86–122 (2001).
Cornwall, J., Cooper, J. D. & Phillipson, O. T. Afferent and efferent connections of the laterodorsal tegmental nucleus in the rat. Brain Res. Bull. 25, 271–284 (1990).
Mildren, R. L. & Cullen, K. E. Sensorimotor transformations for postural control in the vermis of the cerebellum. J. Neurosci. 45, e0249252025 (2025).
Zobeiri, O. A. & Cullen, K. E. Distinct representations of body and head motion are dynamically encoded by Purkinje cell populations in the macaque cerebellum. Elife 11, e75018 (2022).
Sauerbrei, B. A., Lubenov, E. V. & Siapas, A. G. Structured variability in Purkinje cell activity during locomotion. Neuron 87, 840–852 (2015).
Laurens, J., Meng, H. & Angelaki, D. E. Computation of linear acceleration through an internal model in the macaque cerebellum. Nat. Neurosci. 16, 1701–1708 (2013).
Mackrous, I., Carriot, J., Jamali, M. & Cullen, K. E. Cerebellar prediction of the dynamic sensory consequences of gravity. Curr. Biol. 29, 2698–2710.e4 (2019).
Angelaki, D. E. & Hess, B. J. Inertial representation of angular motion in the vestibular system of rhesus monkeys. II. Otolith-controlled transformation that depends on an intact cerebellar nodulus. J. Neurophysiol. 73, 1729–1751 (1995).
Angelaki, D. E. & Hess, B. J. Lesion of the nodulus and ventral uvula abolish steady-state off-vertical axis otolith response. J. Neurophysiol. 73, 1716–1720 (1995).
Yakusheva, T. A. et al. Purkinje cells in posterior cerebellar vermis encode motion in an inertial reference frame. Neuron 54, 973–985 (2007).
Yakusheva, T., Blazquez, P. M. & Angelaki, D. E. Frequency-selective coding of translation and tilt in macaque cerebellar nodulus and uvula. J. Neurosci. 28, 9997–10009 (2008).
Yakusheva, T., Blazquez, P. M. & Angelaki, D. E. Relationship between complex and simple spike activity in macaque caudal vermis during three-dimensional vestibular stimulation. J. Neurosci. 30, 8111–8126 (2010).
Barmack, N. H. & Pettorossi, V. E. Adaptive balance in posterior cerebellum. Front. Neurol. 12, 635259 (2021).
Laurens, J. & Angelaki, D. E. A unified internal model theory to resolve the paradox of active versus passive self-motion sensation. Elife 6, e28074 (2017).
Dugué, G. P., Tihy, M., Gourévitch, B. & Léna, C. Cerebellar re-encoding of self-generated head movements. Elife 6, e26179 (2017).
Einstein, A. Ü ber das Relativitätsprinzip und die aus demselben gezogenen Folgerungen. Jahrbuch der Radioaktivität und Elektronik 4, 411–462 (1907).
Angelaki, D. E. & Cullen, K. E. Vestibular system: the many facets of a multimodal sense. Annu. Rev. Neurosci. 31, 125–150 (2008).
Brooks, J. X. & Cullen, K. E. Early vestibular processing does not discriminate active from passive self-motion if there is a discrepancy between predicted and actual proprioceptive feedback. J. Neurophysiol. 111, 2465–2478 (2014).
Carriot, J., Jamali, M., Brooks, J. X. & Cullen, K. E. Integration of canal and otolith inputs by central vestibular neurons is subadditive for both active and passive self-motion: implication for perception. J. Neurosci. 35, 3555–3565 (2015).
Brooks, J. X. & Cullen, K. E. The primate cerebellum selectively encodes unexpected self-motion. Curr. Biol. 23, 947–955 (2013).
Cullen, K. E. & Brooks, J. X. Neural correlates of sensory prediction errors in monkeys: evidence for internal models of voluntary self-motion in the cerebellum. Cerebellum 14, 31–34 (2015).
Yates, B. J. & Bronstein, A. M. The effects of vestibular system lesions on autonomic regulation: observations, mechanisms, and clinical implications. J. Vestib. Res. 15, 119–129 (2005).
Yates, B. J., Bolton, P. S. & Macefield, V. G. Vestibulo-sympathetic responses. Compr. Physiol. 4, 851–887 (2014).
Merfeld, D. M., Park, S., Gianna-Poulin, C., Black, F. O. & Wood, S. Vestibular perception and action employ qualitatively different mechanisms. II. VOR and perceptual responses during combined Tilt & Translation. J. Neurophysiol. 94, 199–205 (2005).
Green, A. M. & Angelaki, D. E. Coordinate transformations and sensory integration in the detection of spatial orientation and self-motion: from models to experiments. Prog. Brain Res. 165, 155–180 (2007).
Laurens, J. & Angelaki, D. E. The functional significance of velocity storage and its dependence on gravity. Exp. Brain Res. 210, 407–422 (2011).
Matsushita, M. & Tanami, T. Spinocerebellar projections from the central cervical nucleus in the cat, as studied by anterograde transport of wheat germ agglutinin-horseradish peroxidase. J. Comp. Neurol. 266, 376–397 (1987).
Matsushita, M. & Wang, C. L. Projection pattern of vestibulocerebellar fibers in the anterior vermis of the cat: an anterograde wheat germ agglutinin-horseradish peroxidase study. Neurosci. Lett. 74, 25–30 (1987).
Jasmin, L. & Courville, J. Distribution of external cuneate nucleus afferents to the cerebellum: I. Notes on the projections from the main cuneate and other adjacent nuclei. An experimental study with radioactive tracers in the cat. J. Comp. Neurol. 261, 481–496 (1987).
Sheliga, B. M., Yakushin, S. B., Silvers, A., Raphan, T. & Cohen, B. Control of spatial orientation of the angular vestibulo-ocular reflex by the nodulus and uvula of the vestibulocerebellum. Ann. N Y Acad. Sci. 871, 94–122 (1999).
Dietrichs, E. The cerebellar corticonuclear and nucleocortical projections in the cat as studied with anterograde and retrograde transport of horseradish peroxidase. V. The posterior lobe vermis and the flocculo-nodular lobe. Anat. Embryol. 167, 449–462 (1983).
Bernard, J. F. Topographical organization of olivocerebellar and corticonuclear connections in the rat—A WGA-HRP study: I. Lobules IX, X, and the flocculus. J. Comp. Neurol. 263, 241–258 (1987).
Ikeda, Y., Noda, H. & Sugita, S. Olivocerebellar and cerebelloolivary connections of the oculomotor region of the fastigial nucleus in the macaque monkey. J. Comp. Neurol. 284, 463–488 (1989).
Goldberg, J. M. et al. The Vestibular System: A Sixth Sense (Oxford University Press, 2012).
Manzoni, D., Andre, P. & Bruschini, L. Coupling sensory inputs to the appropriate motor responses: new aspects of cerebellar function. Arch. Ital. Biol. 142, 199–215 (2004).
Barmack, N. H. et al. Cerebellar nodulectomy impairs spatial memory of vestibular and optokinetic stimulation in rabbits. J. Neurophysiol. 87, 962–975 (2002).
Cohen, B., Wearne, S., Dai, M. & Raphan, T. Spatial orientation of the angular vestibulo-ocular reflex. J. Vestib. Res. 9, 163–172 (1999).
Wearne, S., Raphan, T. & Cohen, B. Control of spatial orientation of the angular vestibuloocular reflex by the nodulus and uvula. J. Neurophysiol. 79, 2690–2715 (1998).
Wiest, G., Deecke, L., Trattnig, S. & Mueller, C. Abolished tilt suppression of the vestibulo-ocular reflex caused by a selective uvulo-nodular lesion. Neurology 52, 417–419 (1999).
Mauritz, K. H., Dichgans, J. & Hufschmidt, A. Quantitative analysis of stance in late cortical cerebellar atrophy of the anterior lobe and other forms of cerebellar ataxia. Brain 102, 461–482 (1979).
Bailey, P. & Cushing, H. Medulloblastoma cerebelli: a common type of midcerebellar glioma of childhood. Arch. Neurol. Psychiatry. 14, 192–223 (1925).
Diener, H. C., Dichgans, J., Bacher, M. & Guschlbauer, B. Characteristic alterations of long-loop “reflexes” in patients with Friedreich’s disease and late atrophy of the cerebellar anterior lobe. J. Neurol. Neurosurg. Psychiatry 47, 679–685 (1984).
Ye, B. S. et al. Clinical manifestations of cerebellar infarction according to specific lobular involvement. Cerebellum 9, 571–579 (2010).
Dow, R. S. Effect of lesions in the vestibular part of the cerebellum in primates. Arch. Neurol. Psychiatry 40, 500–520 (1938).
Massot, C., Schneider, A. D., Chacron, M. J. & Cullen, K. E. The vestibular system implements a linear-nonlinear transformation in order to encode self-motion. PLoS Biol 10, e1001365 (2012).
Cherif, S., Cullen, K. E. & Galiana, H. L. An improved method for the estimation of firing rate dynamics using an optimal digital filter. J. Neurosci. Methods 173, 165–171 (2008).
Carpenter, J. & Bithell, J. Bootstrap confidence intervals: when, which, what? A practical guide for medical statisticians. Stat. Med. 19, 1141–1164 (2000).
Sylvestre, P. A. & Cullen, K. E. Quantitative analysis of abducens neuron discharge dynamics during saccadic and slow eye movements. J. Neurophysiol. 82, 2612–2632 (1999).
Acknowledgements
We thank Dale Roberts for providing technical assistance, Dr. Tim Harris for providing prototype high-density electrodes along with technical expertise, Lex Gomez for assistance with data processing, and all Cullen lab members for critical feedback on the manuscript and figures. This work was supported by funding from the National Institute on Deafness and Other Communication Disorders (R01-DC002390 and R01-DC018061) (K.E.C.), as well as a Natural Sciences and Engineering Postdoctoral Fellowship and Kavli Neuroscience Discovery Institute Distinguished Postdoctoral Fellowship (R.L.M).
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R.L.M. designed and conducted experiments, analyzed the data, and wrote the manuscript. K.E.C. designed the experiments, supervised the project, and wrote the manuscript.
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Mildren, R.L., Cullen, K.E. Ground-truth encoding of self-motion in the primate cerebellar nodulus and uvula. Nat Commun (2026). https://doi.org/10.1038/s41467-026-69909-9
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DOI: https://doi.org/10.1038/s41467-026-69909-9
