Event Abstract

Back to Event

CEREBELLAR THETA BURST STIMULATION IMPAIRS MEMORY CONSOLIDATION IN EYE-BLINK CLASSICAL CONDITIONING

Jessica Monaco1, 2*, Lorenzo Rocchi3, Egidio D‘Angelo2 and John Rothwell3
  • 1 Brain Connectivity Center, C. Mondino National Neurological Institute, Italy
  • 2 Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy,, Italy
  • 3 TMS Research Unit, "Sobell" Department of Motor Neuroscience and Movement Disorders. UCL Institute of Neurology, United Kingdom

ABSTRACT Associative learning of sensorimotor contingences, as it occurs in eyeblink classical conditioning (EBCC), is known to involve the cerebellum but the mechanisms remain controversial. EBCC involves fast and slow learning processes in sequence, which correspond to memory acquisition and consolidation and are thought to reside in the cerebellar cortex and deep cerebellar nuclei, respectively. Recently, the fast learning process has been modulated by cerebellar continuous theta burst stimulation (cTBS). Here, we asked whether cerebellar cTBS can affect the slow learning process as well. The experiments were performed on 36 healthy volunteers by comparing the effect of cTBS on the cerebellar hemispheres to sham stimulation: in all cases, cTBS was delivered just after the first EBCC training session and was followed by a second EBCC session 10 minutes later. Both right and left cerebellar cTBS significantly decreased the number of conditioned responses all along the second EBCC session (p<0.001 compared to the SHAM cTBS). These data support a model, in which cTBS impaired memory consolidation by interfering with the transfer of memory, that was acquired during the fast learning process, from the cerebellar cortex to deep cerebellar nuclei. METHODS Experimental design: 36 naive healthy volunteers were randomly subdivided in three groups of 12 subjects. Each group underwent a different cTBS protocol (i.e. right cTBS, left cTBS and SHAM cTBS). EBCC paradigm was tested as previously in Monaco et al 2014, with two EBCC sessions: EBCCpre cTBS and EBCCpost cTBS 10’ after transcranial intervention. Data analysis: The number of CRs were counted manually and detected from eletromyographic recordings in each block, in a time window from 300 ms before US onset to the US onset itself. The difference in number of CRs (∆CRs = (number of CRs in EBCCpost-cTBS) – (number of CRs in EBCCpre-cTBS) was used for the non-parametric statistic analysis. RESULTS Cerebellar cTBS decreased the number of CRs in the early EBCC re-acquisition phase just few minutes after the first EBCC session. ∆CRs in each block separately: Kruskal-Wallis tests showed a significant difference in ∆CRs in the three groups across acquisition blocks 1 to 6 (all p < 0.05) while ∆CRs in extinction block 7 is similar (H2= 2.723, p = 0.256); Mann-Whitney tests showed that both right and left cerebellar cTBS caused a significant decrease of ∆CRs across acquisition blocks 1 to 6 when compared to SHAM cTBS group (all p < 0.05)(Figure 1). The curves of EBCC learning showed differences in the EBCCpost compared to EBCCpre sessions (Figure 2). We are developing a realistic Spiking cerebellar Neural Network (SNN) with plasticity at multiple sites (cortical and nuclear), embedded within a loop able to implement the experimental EBCC data in order to validate neurophysiological mechanisms shown in previous studies (Antonietti et al 2016). This could be useful to understand the cTBS effects both on fast and slow learning phases and investigate the cerebellar plasticity dynamics at different sites. CONCLUSIONS The cTBS protocol interferes with the early EBCC re-acquisition phase just a few minutes after the first EBCC session. This result suggests that cTBS is able to interfere with the memory consolidation process during the early memory transfer phase from cortical to nuclear sites (Medina et al 2001; Garrido et al 2013), possibly by acting on specific processes of cerebellar plasticity. The fast acquisition and extinction phases during EBCC training sessions occur as in previous studies (Monaco et al 2014; Hoffland et al 2012). The CRs occurrence following repeated pairing of CS and US in the second EBCC session reappears with a decreased number after 10 minutes from the first EBCC session demonstrating an interference with the early consolidation process.

Figure 1
Image
Figure 2
Image

Acknowledgements

This work was supported by grants of European Union to ED and AP (CEREBNET FP7-ITN238686, REALNET FP7-ICT270434, Human Brain Project (HBP-604102), by the Italian Ministry of Health to ED and GK (RF-2009-1475845; GR-2009-1591859) and the Human Brain Project (HBP).

References

Monaco, J., Casellato, C., Koch, G., and D'angelo, E. (2014). Cerebellar theta burst stimulation dissociates memory components in eyeblink classical conditioning. Eur J Neurosci 40, 3363-3370
Hoffland, B.S., Bologna, M., Kassavetis, P., Teo, J.T., Rothwell, J.C., Yeo, C.H., Van De Warrenburg, B.P., and Edwards, M.J. (2012). Cerebellar theta burst stimulation impairs eyeblink classical conditioning. J Physiol 590, 887-897.
Medina JF, Garcia KS, Mauk MD (2001) A mechanism for savings in the cerebellum. J Neurosci 21:4081-4089.
Garrido JA, Luque NR, D'Angelo E, Ros E (2013) Distributed cerebellar plasticity implements adaptable gain control in a manipulation task: a closed-loop robotic simulation. Front Neural Circuits 7:159.
Gerwig M, Guberina H, Esser AC, Siebler M, Schoch B, Frings M, Kolb FP, Aurich V, Beck A, Forsting M, Timmann D (2010) Evaluation of multiple-session delay eyeblink conditioning comparing patients with focal cerebellar lesions and cerebellar. Behav Brain Res. 15;212(2):143-51

Keywords: Cerebellum, EYE BLINK CLASSICAL CONDITIONING, Transcranial magnetic stimulation (TMS), memory and learning, consolidation

Conference: The Cerebellum inside out: cells, circuits and functions , ERICE (Trapani), Italy, 1 Dec - 5 Dec, 2016.

Presentation Type: poster

Topic: Cellular & Molecular Neuroscience

Citation: Monaco J, Rocchi L, D‘Angelo E and Rothwell J (2019). CEREBELLAR THETA BURST STIMULATION IMPAIRS MEMORY CONSOLIDATION IN EYE-BLINK CLASSICAL CONDITIONING. Conference Abstract: The Cerebellum inside out: cells, circuits and functions . doi: 10.3389/conf.fncel.2017.37.00002

Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters.

The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated.

Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed.

For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions.

Received: 29 Nov 2016; Published Online: 25 Jan 2019.

* Correspondence: PhD. Jessica Monaco, Brain Connectivity Center, C. Mondino National Neurological Institute, Pavia, Pavia, 27100, Italy, jessica.monaco01@universitadipavia.it