Cerebellar Transcranial AC Stimulation Produces a Frequency-Dependent Bimodal Cerebellar Output Pattern.

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    • Source:
      Publisher: Springer Country of Publication: United States NLM ID: 101089443 Publication Model: Electronic Cited Medium: Internet ISSN: 1473-4230 (Electronic) Linking ISSN: 14734222 NLM ISO Abbreviation: Cerebellum Subsets: MEDLINE
    • Publication Information:
      Publication: <2006->: New York : Springer
      Original Publication: London : Martin Dunitz, c2002-
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    • Abstract:
      Cerebellar transcranial alternating current stimulation (ctACS) has the potential to be an appealing, non-invasive treatment option for psychiatric and neurological disorders. However, realization of this potential has been limited by gaps in our knowledge of how ctACS affects cerebellar output on single cell and population levels. Previously, we showed that AC stimulation applied to the cerebellar surface produced a strong, frequency-dependent modulation of Purkinje cell (PC) and cerebellar nuclear (CN) cell activity. Here, to approximate more closely the ctACS conditions, we investigated how AC stimulation applied to the external skull surface overlying crus 1 altered PC and CN activity in anesthetized adult female Sprague-Dawley rats. PC and CN activity showed a frequency-dependent modulation in response to ctACS at frequencies ranging from 0.5 to 80 Hz. A unimodal response was seen for most PCs across all frequencies, whereas most CN cells transitioned to bimodal patterns as stimulus frequency increased. The frequency-dependence of the phases of the local minima of the CN cell modulation were consistent with CN cells being driven synaptically by PC activity. Furthermore, comparison of responses with ipsilateral and contralateral placement of the stimulus electrode with respect to the recording site showed that the strength and pattern of the entrainment depended on the stimulus electrode location, suggesting that ctACS electrode placement could be used to target specific cerebellar output channels. In sum, the results show that transcranial stimulation of the cerebellar cortex can modulate cerebellar output, which has potential implications for its use in treating neurological and psychiatric disorders.
      Competing Interests: Declarations. Competing Interests: The authors declare no competing interests.
      (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
    • References:
      Grimaldi G, Argyropoulos GP, Boehringer A, Celnik P, Edwards MJ, Ferrucci R, Galea JM, Groiss SJ, Hiraoka K, Kassavetis P, Lesage E, Manto M, Miall RC, Priori A, Sadnicka A, Ugawa Y, Ziemann U. Non-invasive cerebellar stimulation—a consensus paper. Cerebellum. 2014;13:121–38. https://doi.org/10.1007/s12311-013-0514-7 . (PMID: 10.1007/s12311-013-0514-723943521)
      Fertonani A, Ferrari C, Miniussi C. What do you feel if I apply transcranial electric stimulation? Safety, sensations and secondary induced effects. Clin Neurophysiol. 2015;126:2181–8. https://doi.org/10.1016/j.clinph.2015.03.015 . (PMID: 10.1016/j.clinph.2015.03.01525922128)
      Grimaldi G, Argyropoulos GP, Bastian A, Cortes M, Davis NJ, Edwards DJ, Ferrucci R, Fregni F, Galea JM, Hamada M, Manto M, Miall RC, Morales-Quezada L, Pope PA, Priori A, Rothwell J, Tomlinson SP, Celnik P. Cerebellar transcranial direct current stimulation (ctDCS): A novel approach to understanding cerebellar function in health and disease. Neuroscientist. 2016;22:83–97. https://doi.org/10.1177/1073858414559409 . (PMID: 10.1177/1073858414559409254062244712385)
      Priori A, Ciocca M, Parazzini M, Vergari M, Ferrucci R. Transcranial cerebellar direct current stimulation and transcutaneous spinal cord direct current stimulation as innovative tools for neuroscientists: Cerebellar and Spinal tDCS. J Physiol (Lond). 2014;592:3345–69. https://doi.org/10.1113/jphysiol.2013.270280 . (PMID: 10.1113/jphysiol.2013.27028024907311)
      Ferrucci R, Marceglia S, Vergari M, Cogiamanian F, Mrakic-Sposta S, Mameli F, Zago S, Barbieri S, Priori A. Cerebellar Transcranial Direct Current Stimulation Impairs the Practice-dependent Proficiency Increase in Working Memory. J Cogn Neurosci. 2008;20:1687–97. https://doi.org/10.1162/jocn.2008.20112 . (PMID: 10.1162/jocn.2008.2011218345990)
      Galea JM, Vazquez A, Pasricha N, Orban de Xivry JJ and Celnik P. Dissociating the roles of the cerebellum and motor cortex during adaptive learning: the motor cortex retains what the cerebellum learns. Cereb Cortex 2011: 21:1761–70. https://doi.org/10.1093/cercor/bhq246.
      Brunoni AR, Ferrucci R, Bortolomasi M, Vergari M, Tadini L, Boggio PS, Giacopuzzi M, Barbieri S and Priori A. Transcranial direct current stimulation (tDCS) in unipolar vs. bipolar depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry 2011: 35:96–101. https://doi.org/10.1016/j.pnpbp.2010.09.010.
      Ferrucci R, Giannicola G, Rosa M, Fumagalli M, Boggio PS, Hallett M, Zago S, Priori A. Cerebellum and processing of negative facial emotions: Cerebellar transcranial DC stimulation specifically enhances the emotional recognition of facial anger and sadness. Cogn Emot. 2012;26:786–99. https://doi.org/10.1080/02699931.2011.619520 . (PMID: 10.1080/02699931.2011.61952022077643)
      Herzfeld DJ, Pastor D, Haith AM, Rossetti Y, Shadmehr R, O’Shea J. Contributions of the cerebellum and the motor cortex to acquisition and retention of motor memories. Neuroimage. 2014;98:147–58. https://doi.org/10.1016/j.neuroimage.2014.04.076 . (PMID: 10.1016/j.neuroimage.2014.04.07624816533)
      Bocci T, De Carolis G, Ferrucci R, Paroli M, Mansani F, Priori A, Valeriani M, Sartucci F. Cerebellar transcranial direct current stimulation (ctDCS) ameliorates phantom limb pain and non-painful phantom limb sensations. Cerebellum. 2019;18:527–35. https://doi.org/10.1007/s12311-019-01020-w . (PMID: 10.1007/s12311-019-01020-w30830672)
      Naro A, Bramanti A, Leo A, Manuli A, Sciarrone F, Russo M, Bramanti P, Calabrò RS. Effects of cerebellar transcranial alternating current stimulation on motor cortex excitability and motor function. Brain Struct Funct. 2017;222:2891–906. https://doi.org/10.1007/s00429-016-1355-1 . (PMID: 10.1007/s00429-016-1355-128064346)
      Miyaguchi S, Otsuru N, Kojima S, Saito K, Inukai Y, Masaki M and Onishi H. Transcranial alternating current stimulation with gamma oscillations over the primary motor cortex and cerebellar hemisphere improved visuomotor performance. Front Behav Neurosci 2018: 12. https://doi.org/10.3389/fnbeh.2018.00132.
      Feng T, Zhang L, Wu Y, Tang L, Chen X, Li Y, Shan C. Exploring the therapeutic effects and mechanisms of transcranial alternating current stimulation on improving walking ability in stroke patients via modulating cerebellar gamma frequency band—a narrative review. Cerebellum. 2024;23:1593–603. https://doi.org/10.1007/s12311-023-01632-3 . (PMID: 10.1007/s12311-023-01632-337962773)
      Ward LM. Synchronous neural oscillations and cognitive processes. Trends Cogn Sci. 2003;7:553–9. https://doi.org/10.1016/j.tics.2003.10.012 . (PMID: 10.1016/j.tics.2003.10.01214643372)
      Koepsell K, Wang X, Hirsch J and Sommer FT. Exploring the function of neural oscillations in early sensory systems. Front Neurosci 2010: 3. https://doi.org/10.3389/neuro.01.010.2010.
      Maris E, Fries P and Ede Fv. Diverse phase relations among neuronal rhythms and their potential function. Trends Neurosci 2016: 39:86–99. https://doi.org/10.1016/j.tins.2015.12.004.
      Middleton FA, Strick PL. Cerebellar projections to the prefrontal cortex of the primate. J Neurosci. 2001;21:700–12. https://doi.org/10.1523/JNEUROSCI.21-02-00700.2001 . (PMID: 10.1523/JNEUROSCI.21-02-00700.2001111604496763818)
      Asan AS, Lang EJ, Sahin M. Entrainment of cerebellar purkinje cells with directional AC electric fields in anesthetized rats. Brain Stimul. 2020;13:1548–58. https://doi.org/10.1016/j.brs.2020.08.017 . (PMID: 10.1016/j.brs.2020.08.017329190907722055)
      Avlar B, Rahman R, Vendidandi S, Cetinkaya E, Asan AS, Sahin M and Lang EJ. Modulation of cerebellar cortical, cerebellar nuclear and vestibular nuclear activity using alternating electric currents. Front Syst Neurosci 2023: 17.
      Kang Q, Lang EJ and Sahin M. Transsynaptic entrainment of cerebellar nuclear cells by alternating currents in a frequency dependent manner. Front Neurosci 2023: 17.
      Asan AS, Gok S, Sahin M. Electrical fields induced inside the rat brain with skin, skull, and dural placements of the current injection electrode. PLoS ONE. 2019;14:e0203727. https://doi.org/10.1371/journal.pone.0203727 . (PMID: 10.1371/journal.pone.0203727306295786328113)
      Hornik K, Grün B. movMF: an R package for fitting mixtures of von Mises-Fisher distributions. J Stat Softw. 2014;58:1–31. https://doi.org/10.18637/jss.v058.i10 . (PMID: 10.18637/jss.v058.i10)
      Lorah J, Womack A. Value of sample size for computation of the Bayesian information criterion (BIC) in multilevel modeling. Behav Res. 2019;51:440–50. https://doi.org/10.3758/s13428-018-1188-3 . (PMID: 10.3758/s13428-018-1188-3)
      Hankin RKS. Circular statistics in R. J Stat Softw. 2015;66:1–3. https://doi.org/10.18637/jss.v066.b05 . (PMID: 10.18637/jss.v066.b05)
      Bates D, Mächler M, Bolker B, Walker S. Fitting linear mixed-effects models using lme4. J Stat Softw. 2015;67:1–48. https://doi.org/10.18637/jss.v067.i01 . (PMID: 10.18637/jss.v067.i01)
      Kuznetsova A, Brockhoff PB, Christensen RHB. lmerTest package: tests in linear mixed effects models. J Stat Softw. 2017;82:1–26. https://doi.org/10.18637/jss.v082.i13 . (PMID: 10.18637/jss.v082.i13)
      Mardia KV. Statistics of directional data. J R Stat Soc Series B Stat Methodol. 1975;37:349–71. https://doi.org/10.1111/j.2517-6161.1975.tb01550.x . (PMID: 10.1111/j.2517-6161.1975.tb01550.x)
      Kang Q, Talesh AR, Lang EJ and Sahin M. Transynaptic modulation of cerebellar nuclear cells with theta-burst stimulation. submitted.
      Blenkinsop TA, Lang EJ. Synaptic action of the olivocerebellar system on cerebellar nuclear spike activity. J Neurosci. 2011;31:14708–20. https://doi.org/10.1523/JNEUROSCI.3323-11.2011 . (PMID: 10.1523/JNEUROSCI.3323-11.2011219943873711508)
      Chan CY, Nicholson C. Modulation by applied electric fields of Purkinje and stellate cell activity in the isolated turtle cerebellum. J Physiol (Lond). 1986;371:89–114. https://doi.org/10.1113/jphysiol.1986.sp015963 . (PMID: 10.1113/jphysiol.1986.sp0159633701658)
      Sánchez-León CA, Campos GS-G, Fernández M, Sánchez-López A, Medina JF and Márquez-Ruiz J. Somatodendritic orientation determines tDCS-induced neuromodulation of Purkinje cell activity in awake mice. eLife 2024: 13. https://doi.org/10.7554/eLife.100941.1.
      Kebschull JM, Casoni F, Consalez GG, Goldowitz D, Hawkes R, Ruigrok TJH, Schilling K, Wingate R, Wu J, Yeung J, Uusisaari MY. Cerebellum lecture: the cerebellar nuclei—core of the cerebellum. Cerebellum. 2023. https://doi.org/10.1007/s12311-022-01506-0 . (PMID: 10.1007/s12311-022-01506-03678168910951048)
      Zhang X, Hancock R, Santaniello S. Transcranial direct current stimulation of cerebellum alters spiking precision in cerebellar cortex: A modeling study of cellular responses. PLoS Comput Biol. 2021;17:e1009609. https://doi.org/10.1371/journal.pcbi.1009609 . (PMID: 10.1371/journal.pcbi.1009609348826808691604)
      Purpura DP, McMurtry JG. Intracellular activities and evoked potential changes during polarization of motor cortex. J Neurophysiol. 1965;28:166–85. https://doi.org/10.1152/jn.1965.28.1.166 . (PMID: 10.1152/jn.1965.28.1.16614244793)
      Bikson M, Inoue M, Akiyama H, Deans JK, Fox JE, Miyakawa H, Jefferys JGR. Effects of uniform extracellular DC electric fields on excitability in rat hippocampal slices in vitro: Modulation of neuronal function by electric fields. J Physiol (Lond). 2004;557:175–90. https://doi.org/10.1113/jphysiol.2003.055772 . (PMID: 10.1113/jphysiol.2003.05577214978199)
      Harvey RJ, Napper RMA. Quantitatives studies on the mammalian cerebellum. Prog Neurobiol. 1991;36:437–63. https://doi.org/10.1016/0301-0082(91)90012-P . (PMID: 10.1016/0301-0082(91)90012-P1947173)
      Pichitpornchai C, Rawson JA, Rees S. Morphology of parallel fibres in the cerebellar cortex of the rat: An experimental light and electron microscopic study with biocytin. J Comp Neurol. 1994;342:206–20. https://doi.org/10.1002/cne.903420205 . (PMID: 10.1002/cne.9034202058201032)
      Isope P, Barbour B. Properties of unitary granule cell→Purkinje cell synapses in adult rat cerebellar slices. J Neurosci. 2002;22:9668–78. https://doi.org/10.1523/JNEUROSCI.22-22-09668.2002 . (PMID: 10.1523/JNEUROSCI.22-22-09668.2002124278226757845)
      Radman T, Ramos RL, Brumberg JC, Bikson M. Role of cortical cell type and morphology in subthreshold and suprathreshold uniform electric field stimulation in vitro. Brain Stimul. 2009;2:215-28.e3. https://doi.org/10.1016/j.brs.2009.03.007 . (PMID: 10.1016/j.brs.2009.03.007201615072797131)
      Pollok B, Boysen A-C, Krause V. The effect of transcranial alternating current stimulation (tACS) at alpha and beta frequency on motor learning. Behav Brain Res. 2015;293:234–40. https://doi.org/10.1016/j.bbr.2015.07.049 . (PMID: 10.1016/j.bbr.2015.07.04926225845)
    • Grant Information:
      R01NS122741 United States NS NINDS NIH HHS; R01NS122741 United States NS NINDS NIH HHS; R01NS122741 United States NS NINDS NIH HHS
    • Contributed Indexing:
      Keywords: Alternating current stimulation; Cerebellar nuclei; Neuromodulation of cerebellum; Purkinje cell; Transcranial electrical stimulation
    • Publication Date:
      Date Created: 20250102 Date Completed: 20250102 Latest Revision: 20250102
    • Publication Date:
      20250102
    • Accession Number:
      10.1007/s12311-024-01756-0
    • Accession Number:
      39745631