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

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 drug, 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.