Interleaved transcranial magnetic stimulation and fMRI suggests that lamotrigine and valproic acid have different effects on corticolimbic activity

Xingbao Li, Raffaella Ricci, Charles H. Large, Berry Anderson, Ziad Nahas, Daryl E. Bohning, Mark S. George

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Rationale Combined transcranial magnetic stimulation (TMS) and functional, magnetic resonance imaging (fMRI) can be used to study anticonvulsant drugs. A previous study showed that lamotrigine (LTG) inhibited brain, activation induced when. TMS was applied over motor cortex, whereas it increased activation, induced by TMS applied over prefrontal cortex. Objectives The present double-blind, placebo-controlled, crossover study in 30 healthy subjects again combined TMS and fMRI to test whether the effects seen previously with LTG would be confirmed and to compare these with a second anticonvulsant drag, valproic acid (VPA). Results Statistical parametric mapping analysis showed that both LTG and VPA, compared to placebo, inhibited TMSinduced activation of the motor cortex. In contrast, when TMS was applied over prefrontal cortex, LTG increased the activation of limbic regions, confirming previous results; VPA had no effect. Conclusion We conclude that LTG and VPA have similar inhibitory effects on motor circuits, but differing effects on the prefrontal corticolimbic system. The study demonstrates that a combination of TMS and fMRI techniques may be useful in the study of the effects of neuroactive drugs on specific brain circuits.

Original languageEnglish (US)
Pages (from-to)233-244
Number of pages12
Issue number3
StatePublished - Apr 2010

Bibliographical note

Funding Information:
Acknowledgments This study was funded primarily by an unrestricted research grant from GlaxoSmithKline to Dr. George, as well as from Center for Advanced Imaging Research and Brain Stimulation Laboratory infrastructure and resources. CHL is a full-time employee of GlaxoSmithKline S.p.A. None of the other authors has equity or financial conflicts. Drs. Li and George had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.


  • Anticonvulsant
  • Corticolimbic system
  • FMRI
  • Lamotrigine
  • Motor cortex
  • Neuroimaging
  • Transcranial magnetic stimulation
  • Valproic acid


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