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J Physiol Volume 554, Number 2, 483-495, January 15, 2004 DOI: 10.1113/jphysiol.2003.048777
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Shaping the excitability of human motor cortex with premotor rTMS

Vincenzo Rizzo1,2, Hartwig R. Siebner1,5, Nicola Modugno1,3, Alessandra Pesenti1,4, Alexander Münchau6, Willibald Gerschlager7, Ruth M. Webb1 and John C. Rothwell1

1 Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College of London, London, UK2 Department of Neuroscience, Psychiatric and Anaethesiological Sciences, University of Messina, Italy3 Istituto Neurologico Mediterraneo Neuromed, Pozzilli, Italy,4 Dipartimento di Scienze Neurologiche e di Organi di Senso, IRCCS Ospedale Maggiore di Milano, Italy5 Department of Neurology, Christian-Albrechts-University, Kiel, Germany6 Neurology Department, Hamburg University, Germany7 Department of Neurology, University of Vienna, Austria

Recent studies have shown that low-frequency repetitive transcranial magnetic stimulation (rTMS) to the left dorsal premotor cortex has a lasting influence on the excitability of specific neuronal subpopulations in the ipsilateral primary motor hand area (M1HAND). Here we asked how these premotor to motor interactions are shaped by the intensity and frequency of rTMS and the orientation of the stimulating coil. We confirmed that premotor rTMS at 1 Hz and an intensity of 90% active motor threshold (AMT) produced a lasting decrease in corticospinal excitability probed with single-pulse TMS over the left M1HAND. Reducing the intensity to 80% AMT increased paired-pulse excitability at an interstimulus interval (ISI) of 7 ms. Opposite effects occurred if rTMS was given at 5 Hz: at 90% AMT, corticospinal excitability increased; at 80% AMT, paired-pulse excitability at ISI = 7 ms decreased. No effects were seen if rTMS was applied at the same intensities to prefrontal or primary motor cortices. These findings indicate that the intensity of premotor rTMS determines the net effect of conditioning on distinct populations of neurones in the ipsilateral M1HAND, but it is the frequency of rTMS that determines the direction of the induced change. By selecting the appropriate intensity and frequency, premotor rTMS allows to induce a predictable up- or down-regulation of the excitability in distinct neuronal circuits of human M1HAND.

(Received 6 June 2003; accepted after revision 10 October 2003; first published online 10 October 2003)
Corresponding author V. Rizzo: Clinica Neurologica II, Dipartimento di Scienze Neurologiche, Psichiatriche ed Anestesiologiche, Policlinico Universitario, Via Consolare Valeria, Gazzi, Messina, Italy.  Email: vince.riz{at}tiscalinet.it




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