A cortico-cerebellar loop for motor planning
Open accessAbstract
Persistent and ramping neural activity in the frontal cortex anticipates specific movements 1-6. Preparatory activity is distributed across several brain regions 7,8, but it is unclear which brain areas are involved and how this activity is mediated by multi-regional interactions. The cerebellum is thought to be primarily involved in the short-timescale control of movement 9-12; however, roles for this structure in cognitive processes have also been proposed 13-16. In humans, cerebellar damage can cause defects in planning and working memory 13. Here we show that persistent representation of information in the frontal cortex during motor planning is dependent on the cerebellum. Mice performed a sensory discrimination task in which they used short-term memory to plan a future directional movement. A transient perturbation in the medial deep cerebellar nucleus (fastigial nucleus) disrupted subsequent correct responses without hampering movement execution. Preparatory activity was observed in both the frontal cortex and the cerebellar nuclei, seconds before the onset of movement. The silencing of frontal cortex activity abolished preparatory activity in the cerebellar nuclei, and fastigial activity was necessary to maintain cortical preparatory activity. Fastigial output selectively targeted the behaviourally relevant part of the frontal cortex through the thalamus, thus closing a cortico-cerebellar loop. Our results support the view that persistent neural dynamics during motor planning is maintained by neural circuits that span multiple brain regions 17, and that cerebellar computations extend beyond online motor control 13-15,18.
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Recent evidence in rodents shows that persistence of neuronal firing rates for working memory storage is not purely cortical but relies on interactions with subcortical structures including thalamus and cerebellar nuclei.
“Recent evidence in rodents demonstrated that the persistence of neuronal firing rates for working memory storage is not a purely cortical phenomenon but instead relies on the interactions with subcortical structures, including the thalamus (Guo et al., 2017) and cerebellar nuclei (Gao et al., 2018).”
From Conscious Processing and the Global Neuronal Workspace Hypothesis (2020) · cites this paper as Gao et al., 2018
Experimental — accuracy not yet measuredPersistent-activity reverberatory loops involve not only corticocortical connections but also subcortical regions, especially the thalamus and cerebellar nuclei.
“recent experimental evidence indicates that the reverberatory loops for persistent neuronal activity not only involve corticocortical interactions but also loop through subcortical regions with an important role for the thalamus and cerebellar nuclei (Gao et al., 2018; Guo et al., 2017).”
From Conscious Processing and the Global Neuronal Workspace Hypothesis (2020) · cites this paper as Gao et al., 2018
Experimental — accuracy not yet measuredThe cerebellum provides output to the cortex and tunes sensory input to facilitate behavioral adjustment in response to feedback.
“The cerebellum provides output to the cortex, and “tunes” sensory input to facilitate behavioral (particularly motor) adjustment in response to feedback(25–27).”
From Functional disruption of cerebello-thalamo-cortical networks in obsessive-compulsive disorder (2020) · cites this paper as [27]
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Cites
Nonrigid registration using free-form deformations: application to breast mr images
Rueckert, D., Sonoda, L. I., Hayes, C., Hill, D. L. G., Leach, M. O., & Hawkes, D. J. (1999) · IEEE Transactions on Medical Imaging · doi:10.1109/42.796284 · Cited by 5,265 · see citing works
The cerebellar cognitive affective syndrome
Schmahmann, J. (1998) · Brain · doi:10.1093/brain/121.4.561 · Cited by 3,230 · see citing works
Mnemonic coding of visual space in the monkey's dorsolateral prefrontal cortex
Funahashi, S., Bruce, C. J., & Goldman-Rakic, P. S. (1989) · Journal of Neurophysiology · doi:10.1152/jn.1989.61.2.331 · Cited by 2,685 · see citing works
Cellular basis of working memory
Goldman-Rakic, P. S. (1995) · Neuron · doi:10.1016/0896-6273(95)90304-6 · Cited by 2,663 · see citing works
A mesoscale connectome of the mouse brain
Oh, S. W., Harris, J. A., Ng, L., Winslow, B., Cain, N., Mihalas, S., Wang, Q., Lau, C., Kuan, L., Henry, A. M., et al. (2014) · Nature · doi:10.1038/nature13186 · Cited by 2,612 · see citing works
Internal models in the cerebellum
Wolpert, D. M., Miall, R. C., & Kawato, M. (1998) · Trends in Cognitive Sciences · doi:10.1016/s1364-6613(98)01221-2 · Cited by 2,469 · see citing works
Cerebellum and nonmotor function
Strick, P. L., Dum, R. P., & Fiez, J. A. (2009) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.31.060407.125606 · Cited by 1,777 · see citing works
A toolbox of Cre-dependent optogenetic transgenic mice for light-induced activation and silencing
Madisen, L., Mao, T., Koch, H., Zhuo, J.-M., Berenyi, A., Fujisawa, S., Hsu, Y.-W. A., Garcia, A. J., Gu, X., Zanella, S., et al. (2012) · Nature Neuroscience · doi:10.1038/nn.3078 · Cited by 1,398 · see citing works
Self-citationControl of mental activities by internal models in the cerebellum
Ito, M. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2332 · Cited by 1,356 · see citing works
Synaptic reverberation underlying mnemonic persistent activity
Wang, X.-J. (2001) · Trends in Neurosciences · doi:10.1016/s0166-2236(00)01868-3 · Cited by 1,059 · see citing works
Autistic-like behaviour and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice
Tsai, P. T., Hull, C., Chu, Y., Greene-Colozzi, E., Sadowski, A. R., Leech, J. M., Steinberg, J., Crawley, J. N., Regehr, W. G., & Sahin, M. (2012) · Nature · doi:10.1038/nature11310 · Cited by 888 · see citing works
Cortical Control of Arm Movements: A Dynamical Systems Perspective
Shenoy, K. V., Sahani, M., & Churchland, M. M. (2013) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-062111-150509 · Cited by 835 · see citing works
Anticipatory activity of motor cortex neurons in relation to direction of an intended movement.
Tanji, J., & Evarts, E. (1976) · Journal of Neurophysiology · doi:10.1152/jn.1976.39.5.1062 · Cited by 740 · see citing works
Flow of cortical activity underlying a tactile decision in mice
Guo, Z. V., Li, N., Huber, D., Ophir, E., Gutnisky, D., Ting, J. T., Feng, G., & Svoboda, K. (2014) · Neuron · doi:10.1016/j.neuron.2013.10.020 · Cited by 715 · cited 9× · see citing works
“The light transmission through the intact skull was 50% 19 .”
InfluentialSelf-citationZhao, S., Ting, J. T., Atallah, H. E., Qiu, L., Tan, J., Gloss, B., Augustine, G. J., Deisseroth, K., Luo, M., Graybiel, A. M., et al. (2011) · Nature Methods · doi:10.1038/nmeth.1668 · Cited by 653 · see citing works
Riehle, A., & Requin, J. (1989) · Journal of Neurophysiology · doi:10.1152/jn.1989.61.3.534 · Cited by 597 · see citing works
A motor cortex circuit for motor planning and movement
Li, N., Chen, T.-W., Guo, Z. V., Gerfen, C., & Svoboda, K. (2015) · Nature · doi:10.1038/nature14178 · Cited by 578 · see citing works
Self-citationMaintenance of persistent activity in a frontal thalamocortical loop
Guo, Z. V., Inagaki, H. K., Daie, K., Druckmann, S., Gerfen, C. R., & Svoboda, K. (2017) · Nature · doi:10.1038/nature22324 · Cited by 529 · see citing works
Self-citationRobust neuronal dynamics in premotor cortex during motor planning
Li, N., Daie, K., Svoboda, K., & Druckmann, S. (2016) · Nature · doi:10.1038/nature17643 · Cited by 492 · see citing works
Self-citationCerebellar granule cells encode the expectation of reward
Wagner, M. J., Kim, T. H., Savall, J., Schnitzer, M. J., & Luo, L. (2017) · Nature · doi:10.1038/nature21726 · Cited by 485 · see citing works
Fried, I., Mukamel, R., & Kreiman, G. (2011) · Neuron · doi:10.1016/j.neuron.2010.11.045 · Cited by 459 · see citing works
Procedures for Behavioral Experiments in Head-Fixed Mice
Guo, Z. V., Hires, S., Li, N., O'Connor, D. H., Komiyama, T., Ophir, E., Huber, D., Bonardi, C., Morandell, K., Gutnisky, D., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0088678 · Cited by 427 · see citing works
Self-citationDistinct descending motor cortex pathways and their roles in movement
Economo, M. N., Viswanathan, S., Tasic, B., Bas, E., Winnubst, J., Menon, V., Graybuck, L. T., Nguyen, T. N., Smith, K. A., Yao, Z., et al. (2018) · Nature · doi:10.1038/s41586-018-0642-9 · Cited by 415 · see citing works
Self-citationLewis, P. M., Gritli-Linde, A., Smeyne, R. J., Kottmann, A. H., & McMahon, A. P. (2004) · Developmental Biology · doi:10.1016/j.ydbio.2004.03.007 · Cited by 379 · see citing works
Neural mechanisms of movement planning: motor cortex and beyond
Svoboda, K., & Li, N. (2018) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2017.10.023 · Cited by 347 · see citing works
Self-citationComputer simulation of cerebellar information processing
Medina, J. F., & Mauk, M. D. (2000) · Nature Neuroscience · doi:10.1038/81486 · Cited by 335 · see citing works
Discrete attractor dynamics underlies persistent activity in the frontal cortex
Inagaki, H. K., Fontolan, L., Romani, S., & Svoboda, K. (2019) · Nature · doi:10.1038/s41586-019-0919-7 · Cited by 334 · see citing works
Self-citationShort latency cerebellar modulation of the basal ganglia
Chen, C. H., Fremont, R., Arteaga-Bracho, E. E., & Khodakhah, K. (2014) · Nature Neuroscience · doi:10.1038/nn.3868 · Cited by 286 · see citing works
Encoding of action by the Purkinje cells of the cerebellum
Herzfeld, D. J., Kojima, Y., Soetedjo, R., & Shadmehr, R. (2015) · Nature · doi:10.1038/nature15693 · Cited by 281 · see citing works
Neural antecedents of self-initiated actions in secondary motor cortex
Murakami, M., Vicente, M. I., Costa, G. M., & Mainen, Z. F. (2014) · Nature Neuroscience · doi:10.1038/nn.3826 · Cited by 272 · see citing works
Cerebellum involvement in cortical sensorimotor circuits for the control of voluntary movements
Proville, R. D., Spolidoro, M., Guyon, N., Dugué, G. P., Selimi, F., Isope, P., Popa, D., & Léna, C. (2014) · Nature Neuroscience · doi:10.1038/nn.3773 · Cited by 268 · see citing works
Precise Control of Movement Kinematics by Optogenetic Inhibition of Purkinje Cell Activity
Heiney, S. A., Kim, J., Augustine, G. J., & Medina, J. F. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.4547-13.2014 · Cited by 253 · see citing works
Ohyama, T., Nores, W. L., Murphy, M. B., & Mauk, M. D. (2003) · Trends in Neurosciences · doi:10.1016/s0166-2236(03)00054-7 · Cited by 244 · see citing works
Allen reference atlas : a digital color brain atlas of the C57Black/6J male mouse
Dong, H. (2008) · Wiley eBooks · Cited by 228 · see citing works
A Map of Anticipatory Activity in Mouse Motor Cortex
Chen, T., Li, N., Daie, K., & Svoboda, K. (2017) · Neuron · doi:10.1016/j.neuron.2017.05.005 · Cited by 218 · see citing works
Self-citationInteractions between prefrontal cortex and cerebellum revealed by trace eyelid conditioningPreprint
Kalmbach, B. E., Ohyama, T., Kreider, J. C., Riusech, F., & Mauk, M. D. (2009) · Learning & Memory · doi:10.1101/lm.1178309 · Cited by 136 · see citing works
Low-dimensional and monotonic preparatory activity in mouse anterior lateral motor cortex
Inagaki, H. K., Inagaki, M., Romani, S., & Svoboda, K. (2018) · The Journal of Neuroscience · doi:10.1523/jneurosci.3152-17.2018 · Cited by 111 · see citing works
Self-citationA GABAergic nigrotectal pathway for coordination of drinking behavior
Rossi, M. A., Li, H. E., Lu, D., Kim, I. H., Bartholomew, R. A., Gaidis, E., Barter, J. W., Kim, N., Cai, M., Soderling, S. H., et al. (2016) · Nature Neuroscience · doi:10.1038/nn.4285 · Cited by 85 · see citing works
Circuits in the rodent brainstem that control whisking in concert with other orofacial motor actions
McElvain, L. E., Friedman, B., Karten, H. J., Svoboda, K., Wang, F., Deschênes, M., & Kleinfeld, D. (2018) · Neuroscience · doi:10.1016/j.neuroscience.2017.08.034 · Cited by 82 · see citing works
Self-citationDiscrete attractor dynamics underlying selective persistent activity in frontal cortexPreprint
Inagaki, H. K., Fontolan, L., Romani, S., & Svoboda, K. (2017) · bioRxiv · doi:10.1101/203448 · Cited by 17 · see citing works
Self-citationDistinct descending motor cortex pathways and their roles in movementPreprint
Economo, M. N., Viswanathan, S., Tasic, B., et al. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/229260 · Cited by 9 · see citing works
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Conscious Processing and the Global Neuronal Workspace Hypothesis
Mashour, G. A., Roelfsema, P., Changeux, J.-P., & Dehaene, S. (2020) · Neuron · doi:10.1016/j.neuron.2020.01.026 · Cited by 1,164 · see citing works
“Persistent neuronal activity allows the nervous system to bridge the time between sensory stimuli, task instructions, and actions that need to take place at a later point in time (Fuster, 1997).”
BackgroundDiscrete attractor dynamics underlies persistent activity in the frontal cortex
Inagaki, H. K., Fontolan, L., Romani, S., & Svoboda, K. (2019) · Nature · doi:10.1038/s41586-019-0919-7 · Cited by 334 · see citing works
Self-citationTasserie, J., Uhrig, L., Sitt, J. D., Manasova, D., Dupont, M., Dehaene, S., & Jarraya, B. (2022) · Science Advances · doi:10.1126/sciadv.abl5547 · Cited by 171 · see citing works
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Staiger, J. F., & Petersen, C. C. H. (2021) · Physiological Reviews · doi:10.1152/physrev.00019.2019 · Cited by 165 · see citing works
Cerebellar Neurodynamics Predict Decision Timing and Outcome on the Single-Trial Level
Lin, Q., Manley, J., Helmreich, M., Schlumm, F., Li, J. M., Robson, D. N., Engert, F., Schier, A., Nöbauer, T., & Vaziri, A. (2020) · Cell · doi:10.1016/j.cell.2019.12.018 · Cited by 122 · see citing works
A Genetically Defined Compartmentalized Striatal Direct Pathway for Negative Reinforcement
Xiao, X., Deng, H., Furlan, A., Yang, T., Zhang, X., Hwang, G.-R., Tucciarone, J., Wu, P., He, M., Palaniswamy, R., et al. (2020) · Cell · doi:10.1016/j.cell.2020.08.032 · Cited by 101 · see citing works
An integrative, multiscale view on neural theories of consciousness
Storm, J. F., Klink, P. C., Aru, J., Senn, W., Goebel, R., Pigorini, A., Avanzini, P., Vanduffel, W., Roelfsema, P. R., Massimini, M., et al. (2024) · Neuron · doi:10.1016/j.neuron.2024.02.004 · Cited by 114 · see citing works
“…sub-millimeter ultra-high field fMRI during ambiguous sensory stimulation fulfills the criteria for the search of content-specific NCC outlined by Chalmers 15 and Koch et al. 16 cerebellar nuclei, 85,86 which is in line with a broad network of long-range connections supporting a global workspace.”
Cerebellar plasticity and associative memories are controlled by perineuronal nets
Carulli, D., Broersen, R., de Winter, F., Muir, E. M., Mešković, M., de Waal, M., de Vries, S., Boele, H.-J., Canto, C. B., De Zeeuw, C. I., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1916163117 · Cited by 110 · see citing works
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Kalidindi, H. T., Cross, K. P., Lillicrap, T. P., Omrani, M., Falotico, E., Sabes, P. N., & Scott, S. H. (2021) · eLife · doi:10.7554/elife.67256 · Cited by 83 · see citing works
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Deng, H., Xiao, X., Yang, T., Ritola, K., Hantman, A., Li, Y., Huang, Z. J., & Li, B. (2021) · Cell · doi:10.1016/j.cell.2021.11.019 · Cited by 75 · see citing works
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Bizzi, E., & Ajemian, R. (2020) · Journal of Neurophysiology · doi:10.1152/jn.00715.2019 · Cited by 49 · see citing works
Functional disruption of cerebello-thalamo-cortical networks in obsessive-compulsive disorder
Sha, Z., Edmiston, E. K., Versace, A., Fournier, J. C., Graur, S., Greenberg, T., Lima Santos, J. P., Chase, H. W., Stiffler, R. S., Bonar, L., et al. (2020) · Biological Psychiatry: Cognitive Neuroscience and Neuroimaging · doi:10.1016/j.bpsc.2019.12.002 · Cited by 48 · see citing works
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Ohtsuki, G., Shishikura, M., & Ozaki, A. (2020) · The FEBS Journal · doi:10.1111/febs.15355 · Cited by 27 · see citing works
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Chong, H. R., Ranjbar-Slamloo, Y., Ho, M. Z. H., Ouyang, X., & Kamigaki, T. (2023) · Nature Communications · doi:10.1038/s41467-023-43142-0 · Cited by 19 · see citing works
- Authors
- Gao, Z., Davis, C., Thomas, A. M., Economo, M. N., Abrego, A. M., Svoboda, K., De Zeeuw, C. I., & Li, N.
- Affiliations
- Erasmus MC (NL)
- Baylor College of Medicine (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Li, Nuo
- Venue
- Nature
- Published
- 2018-10-17
- Volume
- 563
- Issue
- 7729
- Pages
- 113-116
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC6212318
- OpenAlex
- W2898022217
- Cited by
- 417
- References
- 41
- Citations by year
- 2026: 38 · 2025: 44 · 2024: 60 · 2023: 64 · 2022: 58 · 2021: 61 · 2020: 53 · 2019: 35 · 2018: 2
- FWCI
- 22.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (publishedVersion)
- PubMed Central (acceptedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- OpenBU (Boston University) (submittedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R21NS104781)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Motor Control and Adaptation
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- motor planning, frontal cortex, cerebellum, fastigial nucleus, preparatory activity, persistent activity, short-term memory, thalamus, neural circuits
- MeSH terms
- Animals, Cerebellum, Cues, Female, Frontal Lobe, Male, Movement, Neural Pathways, Neurons, Psychomotor Performance, Thalamus, Mice
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