J Physiol Volume 586, Number 16, 3871-3879, August 15, 2008 DOI: 10.1113/jphysiol.2008.152736
The physiological basis of the effects of intermittent theta burst stimulation of the human motor cortex
V. Di Lazzaro1,2,
F. Pilato1,
M. Dileone1,
P. Profice1,
A. Oliviero1,3,
P. Mazzone4,
A. Insola5,
F. Ranieri1,
M. Meglio6,
P. A. Tonali1,2 and
J. C. Rothwell7
1 Institute of Neurology, Università Cattolica, L. go A. Gemelli 8, 00168 Rome, Italy
2
Fondazione Don C. Gnocchi, Rome, Italy
3
FENNSI Group, Hospital Nacional de Paraplejicos, SESCAM, Finca la Peraleda, 45071 Toledo, Spain
4
Neurochirurgia CTO, Via S. Nemesio 21, 00145 Rome, Italy
5
Neurofisiologia CTO, Via S. Nemesio 21, 00145 Rome, Italy
6
Institute of Neurosurgery, Università Cattolica, L. go A. Gemelli 8, 00168 Rome, Italy
7
Sobell Department of Neurophysiology, Institute of Neurology and The National Hospital for Neurology & Neurosurgery, Queen Square, London WC1N 3BG, UK
Theta burst stimulation (TBS) is a form of repetitive transcranial magnetic stimulation (TMS). When applied to motor cortex it leads to after-effects on corticospinal and corticocortical excitability that may reflect LTP/LTD-like synaptic effects. An inhibitory form of TBS (continuous, cTBS) suppresses MEPs, and spinal epidural recordings show this is due to suppression of the I1 volley evoked by TMS. Here we investigate whether the excitatory form of TBS (intermittent, iTBS) affects the same I-wave circuitry. We recorded corticospinal volleys evoked by single pulse TMS of the motor cortex before and after iTBS in three conscious patients who had an electrode implanted in the cervical epidural space for the control of pain. As in healthy subjects, iTBS increased MEPs, and this was accompanied by a significant increase in the amplitude of later I-waves, but not the I1 wave. In two of the patients we tested the excitability of the contralateral cortex and found a significant suppression of the late I-waves. The extent of the changes varied between the three patients, as did their age. To investigate whether age might be a significant contributor to the variability we examined the effect of iTBS on MEPs in 18 healthy subjects. iTBS facilitated MEPs evoked by TMS of the conditioned hemisphere and suppressed MEPs evoked by stimulation of the contralateral hemisphere. There was a slight but non-significant decline in MEP facilitation with age, suggesting that interindividual variability was more important than age in explaining our data. In a subgroup of 10 subjects we found that iTBS had no effect on the duration of the ipsilateral silent period suggesting that the reduction in contralateral MEPs was not due to an increase in ongoing transcallosal inhibition. In conclusion, iTBS affects the excitability of excitatory synaptic inputs to pyramidal tract neurones that are recruited by a TMS pulse, both in the stimulated hemisphere and in the contralateral hemisphere. However the circuits affected differ from those influenced by the inhibitory, cTBS, protocol. The implication is that cTBS and iTBS may have different therapeutic targets.
(Received 18 February 2008;
accepted after revision 15 June 2008;
first published online 19 June 2008)
Corresponding author V. Di Lazzaro: Istituto di Neurologia, Università Cattolica, L. go A. Gemelli 8, 00168 Rome, Italy. Email: vdilazzaro{at}rm.unicatt.it
Copyright © 2008 The Physiological Society.
