Cerebellar iTBS Modulates Cortical Network Properties: An fNIRS Study
Chuan Guo , Ayan Geng , Qinglei Wang , Junfan Shen , Chaojie Kan , Ying Shen , Tong Wang , Shizhe Zhu
Journal of Integrative Neuroscience ›› 2026, Vol. 25 ›› Issue (3) : 47653
The cortex and cerebellum have a closely connected closed-loop circuit. Intermittent theta burst stimulation (iTBS) targeting the cerebellum has shown promise in improving balance function and inducing neuroplasticity. This study investigates whether cerebellar iTBS can elicit cortical responses.
One hundred healthy volunteers were randomly assigned to a real or sham iTBS stimulation group. Functional near-infrared spectroscopy (fNIRS) measured cortical activation during resting, walking, and unilateral support tasks.
During the unilateral support task, graph theory analysis revealed significant changes in brain network properties, suggesting a deviation from optimal small-world organization and reduced global integration. No significant changes were observed during the walking and resting-state tasks.
These findings suggest that cerebellar iTBS can modulate cortical activity, though further studies are needed to confirm its clinical effects.
ChiCTR2300077916, https://www.chictr.org.cn/showproj.html?proj=207394.
cerebellum / cerebral cortex / intermittent theta burst stimulation / functional near-infrared spectroscopy
| [1] |
Schmahmann JD. The Cerebrocerebellar System. In Gruol DL, Koibuchi N, Manto M, Molinari M, Schmahmann JD, Shen Y (eds.) Essentials of Cerebellum and Cerebellar Disorders: A Primer For Graduate Students (pp. 77–86). Springer International Publishing: Cham. 2023. |
| [2] |
Koziol LF, Budding D, Andreasen N, D’Arrigo S, Bulgheroni S, Imamizu H, et al. Consensus paper: the cerebellum’s role in movement and cognition. Cerebellum (London, England). 2014; 13: 151–177. https://doi.org/10.1007/s12311-013-0511-x. |
| [3] |
Sokolov AA, Miall RC, Ivry RB. The Cerebellum: Adaptive Prediction for Movement and Cognition. Trends in Cognitive Sciences. 2017; 21: 313–332. https://doi.org/10.1016/j.tics.2017.02.005. |
| [4] |
Warthen KG, Walker NC, Wicklund BD, Gonzalez MM, Ramirez N, Gee SC, et al. Neuromodulation of the Cerebellum for Motor Applications: A Systematic Review. Journal of Integrative Neuroscience. 2024; 23: 195. https://doi.org/10.31083/j.jin2310195. |
| [5] |
Kelly RM, Strick PL. Cerebellar loops with motor cortex and prefrontal cortex of a nonhuman primate. The Journal of Neuroscience: the Official Journal of the Society for Neuroscience. 2003; 23: 8432–8444. https://doi.org/10.1523/JNEUROSCI.23-23-08432.2003. |
| [6] |
Krienen FM, Buckner RL. Segregated fronto-cerebellar circuits revealed by intrinsic functional connectivity. Cerebral Cortex (New York, N.Y.: 1991). 2009; 19: 2485–2497. https://doi.org/10.1093/cercor/bhp135. |
| [7] |
Fisher KM, Lai HM, Baker MR, Baker SN. Corticospinal activation confounds cerebellar effects of posterior fossa stimuli. Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology. 2009; 120: 2109–2113. https://doi.org/10.1016/j.clinph.2009.08.021. |
| [8] |
Hardwick RM, Lesage E, Miall RC. Cerebellar transcranial magnetic stimulation: the role of coil geometry and tissue depth. Brain Stimulation. 2014; 7: 643–649. https://doi.org/10.1016/j.brs.2014.04.009. |
| [9] |
Koch G, Bonnì S, Casula EP, Iosa M, Paolucci S, Pellicciari MC, et al. Effect of Cerebellar Stimulation on Gait and Balance Recovery in Patients With Hemiparetic Stroke: A Randomized Clinical Trial. JAMA Neurology. 2019; 76: 170–178. https://doi.org/10.1001/jamaneurol.2018.3639. |
| [10] |
Casula EP, Pellicciari MC, Ponzo V, Stampanoni Bassi M, Veniero D, Caltagirone C, et al. Cerebellar theta burst stimulation modulates the neural activity of interconnected parietal and motor areas. Scientific Reports. 2016; 6: 36191. https://doi.org/10.1038/srep36191. |
| [11] |
Wang B, Sun H, Pan X, Ma W, Dong L, Wang Q, et al. The effects of intermittent theta burst stimulation of the unilateral cerebellar hemisphere on swallowing-related brain regions in healthy subjects. Frontiers in Human Neuroscience. 2023; 17: 1100320. https://doi.org/10.3389/fnhum.2023.1100320. |
| [12] |
Rahman MA, Siddik AB, Ghosh TK, Khanam F, Ahmad M. A Narrative Review on Clinical Applications of fNIRS. Journal of Digital Imaging. 2020; 33: 1167–1184. https://doi.org/10.1007/s10278-020-00387-1. |
| [13] |
Vitorio R, Stuart S, Rochester L, Alcock L, Pantall A. fNIRS response during walking - Artefact or cortical activity? A systematic review. Neuroscience and Biobehavioral Reviews. 2017; 83: 160–172. https://doi.org/10.1016/j.neubiorev.2017.10.002. |
| [14] |
Zeng Y, Ye Z, Zheng W, Wang J. Efficacy of Cerebellar Transcranial Magnetic Stimulation for Post-stroke Balance and Limb Motor Function Impairments: Meta-analyses of Random Controlled Trials and Resting-State fMRI Studies. Cerebellum (London, England). 2024; 23: 1678–1696. https://doi.org/10.1007/s12311-024-01660-7. |
| [15] |
Jacobs JV, Lou JS, Kraakevik JA, Horak FB. The supplementary motor area contributes to the timing of the anticipatory postural adjustment during step initiation in participants with and without Parkinson’s disease. Neuroscience. 2009; 164: 877–885. https://doi.org/10.1016/j.neuroscience.2009.08.002. |
| [16] |
Tan HX, Wei QC, Chen Y, Xie YJ, Guo QF, He L, et al. The Immediate Effects of Intermittent Theta Burst Stimulation of the Cerebellar Vermis on Cerebral Cortical Excitability During a Balance Task in Healthy Individuals: A Pilot Study. Frontiers in Human Neuroscience. 2021; 15: 748241. https://doi.org/10.3389/fnhum.2021.748241. |
| [17] |
Zanto TP, Gazzaley A. Aging of the frontal lobe. Handbook of Clinical Neurology. 2019; 163: 369–389. https://doi.org/10.1016/B978-0-12-804281-6.00020-3. |
| [18] |
Deng ZD, Lisanby SH, Peterchev AV. Electric field depth-focality tradeoff in transcranial magnetic stimulation: simulation comparison of 50 coil designs. Brain Stimulation. 2013; 6: 1–13. https://doi.org/10.1016/j.brs.2012.02.005. |
| [19] |
Sauvé WM, Crowther LJ. The science of transcranial magnetic stimulation. Psychiatric Annals. 2014; 44: 279–283. |
| [20] |
Rothwell JC. Techniques and mechanisms of action of transcranial stimulation of the human motor cortex. Journal of Neuroscience Methods. 1997; 74: 113–122. https://doi.org/10.1016/s0165-0270(97)02242-5. |
| [21] |
Liao LY, Xie YJ, Chen Y, Gao Q. Cerebellar Theta-Burst Stimulation Combined With Physiotherapy in Subacute and Chronic Stroke Patients: A Pilot Randomized Controlled Trial. Neurorehabilitation and Neural Repair. 2021; 35: 23–32. https://doi.org/10.1177/1545968320971735. |
| [22] |
Zhuang R, Zhu S, Sui Y, Zhou M, Yang T, Wang C, et al. Age-Related Differences in Stepping Reactions to a Balance Perturbation: A Functional Near-Infrared Spectroscopy and Surface Electromyography Study. Brain Sciences. 2022; 12: 1479. https://doi.org/10.3390/brainsci12111479. |
| [23] |
Yücel MA, Lühmann AV, Scholkmann F, Gervain J, Dan I, Ayaz H, et al. Best practices for fNIRS publications. Neurophotonics. 2021; 8: 012101. https://doi.org/10.1117/1.NPh.8.1.012101. |
| [24] |
Kaplan L, Chow BW, Gu C. Neuronal regulation of the blood-brain barrier and neurovascular coupling. Nature Reviews. Neuroscience. 2020; 21: 416–432. https://doi.org/10.1038/s41583-020-0322-2. |
| [25] |
Friston KJ. Functional and effective connectivity: a review. Brain Connectivity. 2011; 1: 13–36. https://doi.org/10.1089/brain.2011.0008. |
| [26] |
Rubinov M, Sporns O. Complex network measures of brain connectivity: uses and interpretations. NeuroImage. 2010; 52: 1059–1069. https://doi.org/10.1016/j.neuroimage.2009.10.003. |
| [27] |
Yu Y, Zhou X, Wang H, Hu X, Zhu X, Xu L, et al. Small-World Brain Network and Dynamic Functional Distribution in Patients with Subcortical Vascular Cognitive Impairment. PloS One. 2015; 10: e0131893. https://doi.org/10.1371/journal.pone.0131893. |
| [28] |
Coffman KA, Dum RP, Strick PL. Cerebellar vermis is a target of projections from the motor areas in the cerebral cortex. Proceedings of the National Academy of Sciences of the United States of America. 2011; 108: 16068–16073. https://doi.org/10.1073/pnas.1107904108. |
| [29] |
Harrington A, Hammond-Tooke GD. Theta Burst Stimulation of the Cerebellum Modifies the TMS-Evoked N100 Potential, a Marker of GABA Inhibition. PloS One. 2015; 10: e0141284. https://doi.org/10.1371/journal.pone.0141284. |
| [30] |
Jörntell H, Hansel C. Synaptic memories upside down: bidirectional plasticity at cerebellar parallel fiber-Purkinje cell synapses. Neuron. 2006; 52: 227–238. https://doi.org/10.1016/j.neuron.2006.09.032. |
| [31] |
Fernandez L, Rogasch NC, Do M, Clark G, Major BP, Teo WP, et al. Cerebral Cortical Activity Following Non-invasive Cerebellar Stimulation-a Systematic Review of Combined TMS and EEG Studies. Cerebellum (London, England). 2020; 19: 309–335. https://doi.org/10.1007/s12311-019-01093-7. |
| [32] |
Caspers S, Geyer S, Schleicher A, Mohlberg H, Amunts K, Zilles K. The human inferior parietal cortex: cytoarchitectonic parcellation and interindividual variability. NeuroImage. 2006; 33: 430–448. https://doi.org/10.1016/j.neuroimage.2006.06.054. |
| [33] |
Sukal-Moulton T, de Campos AC, Alter KE, Huppert TJ, Damiano DL. Relationship between sensorimotor cortical activation as assessed by functional near infrared spectroscopy and lower extremity motor coordination in bilateral cerebral palsy. NeuroImage. Clinical. 2018; 20: 275–285. https://doi.org/10.1016/j.nicl.2018.07.023. |
| [34] |
Koenraadt KLM, Roelofsen EGJ, Duysens J, Keijsers NLW. Cortical control of normal gait and precision stepping: an fNIRS study. NeuroImage. 2014; 85 Pt 1: 415–422. https://doi.org/10.1016/j.neuroimage.2013.04.070. |
| [35] |
Lee JH, Kyeong S, Kang H, Kim DH. Structural and functional connectivity correlates with motor impairment in chronic supratentorial stroke: a multimodal magnetic resonance imaging study. Neuroreport. 2019; 30: 526–531. https://doi.org/10.1097/WNR.0000000000001247. |
| [36] |
Bassett DS, Bullmore ET. Small-World Brain Networks Revisited. The Neuroscientist: a Review Journal Bringing Neurobiology, Neurology and Psychiatry. 2017; 23: 499–516. https://doi.org/10.1177/1073858416667720. |
| [37] |
Mihaescu AS, Kim J, Masellis M, Graff-Guerrero A, Cho SS, Christopher L, et al. Graph theory analysis of the dopamine D2 receptor network in Parkinson’s disease patients with cognitive decline. Journal of Neuroscience Research. 2021; 99: 947–965. https://doi.org/10.1002/jnr.24760. |
| [38] |
Yuan Z, Xu W, Bao J, Gao H, Li W, Peng Y, et al. Task-State Cortical Motor Network Characteristics by Functional Near-Infrared Spectroscopy in Subacute Stroke Show Hemispheric Dominance. Frontiers in Aging Neuroscience. 2022; 14: 932318. https://doi.org/10.3389/fnagi.2022.932318. |
| [39] |
Siegel JS, Seitzman BA, Ramsey LE, Ortega M, Gordon EM, Dosenbach NUF, et al. Re-emergence of modular brain networks in stroke recovery. Cortex; a Journal Devoted to the Study of the Nervous System and Behavior. 2018; 101: 44–59. https://doi.org/10.1016/j.cortex.2017.12.019. |
| [40] |
Chen X, Liu M, Wu Z, Cheng H. Topological Abnormalities of Functional Brain Network in Early-Stage Parkinson’s Disease Patients With Mild Cognitive Impairment. Frontiers in Neuroscience. 2020; 14: 616872. https://doi.org/10.3389/fnins.2020.616872. |
| [41] |
Murase N, Duque J, Mazzocchio R, Cohen LG. Influence of interhemispheric interactions on motor function in chronic stroke. Annals of Neurology. 2004; 55: 400–409. https://doi.org/10.1002/ana.10848. |
| [42] |
Katagiri N, Kawakami S, Okuyama S, Koseki T, Kudo D, Namba S, et al. Single-Session Cerebellar Transcranial Direct Current Stimulation Affects Postural Control Learning and Cerebellar Brain Inhibition in Healthy Individuals. Cerebellum (London, England). 2021; 20: 203–211. https://doi.org/10.1007/s12311-020-01208-5. |
| [43] |
Thomson RH, Maller JJ, Daskalakis ZJ, Fitzgerald PB. Blood oxygenation changes resulting from suprathreshold transcranial magnetic stimulation. Brain Stimulation. 2011; 4: 165–168. https://doi.org/10.1016/j.brs.2010.10.003. |
National Natural Science Foundation of China (NSFC)(82302882)
Key Medical Discipline Project of Jiangsu Province(XK201110)
/
| 〈 |
|
〉 |