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Cerebral Cortex Advance Access published online on September 12, 2008
Cerebral Cortex, doi:10.1093/cercor/bhn144
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© The Author 2008. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Paired Associative Stimulation of Left and Right Human Motor Cortex Shapes Interhemispheric Motor Inhibition based on a Hebbian Mechanism

V. Rizzo1, H. S. Siebner2,3, F. Morgante1, C. Mastroeni1, P. Girlanda1 and A. Quartarone1

1 Department of Neurosciences, Psychiatry and Anaesthesiology, University of Messina, Sicily 98100, Italy, 2 Department of Neurology, Christian-Albrecht-University, Schittenhelmstrasse 10, 24105 Kiel, Germany, 3 Danish Research Centre for Magnetic Resonance, Hvidovre University Hospital, DK 2650 Copenhagen, Denmark

Address correspondence to Dr. Angelo Quartarone, Clinica Neurologica 2, Policlinico Universitario, 98125 Messina, Italy. Email: angelo.quartarone{at}unime.it.

This study was designed to examine whether corticocortical paired associative stimulation (cc-PAS) can modulate interhemispheric inhibition (IHI) in the human brain. Twelve healthy right-handed volunteers received 90 paired transcranial stimuli to the right and left primary motor hand area (M1HAND) at an interstimulus interval (ISI) of 8 ms. Left-to-right cc-PAS (first pulse given to left M1HAND) attenuated left-to-right IHI for one hour after cc-PAS. Left-to-right cc-PAS also increased corticospinal excitability in the conditioned right M1HAND. These effects were not seen in an asymptomatic individual with callosal agenesis. Additional experiments showed no changes in left-to-right IHI or corticospinal excitability when left-to-right cc-PAS was given at an ISI of 1 ms or at multiple ISIs in random order. At the behavioral level, left-to-right cc-PAS speeded responses with the left but not right index finger during a simple reaction time task. Right-to-left cc-PAS (first pulse given to right M1HAND) reduced right-to-left IHI without increasing corticospinal excitability in left M1HAND. These results provide a proof of principle that cc-PAS can induce associative plasticity in connections between the targeted cortical areas. The efficacy of cc-PAS to induce lasting changes in excitability depends on the exact timing of the stimulus pairs suggesting an underlying Hebbian mechanism.

Key Words: associative plasticity • corticocortical connectivity • Hebbian plasticity • interhemispheric inhibition • motor cortex • paired associative stimulation • transcranial magnetic stimulation


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