Callosal abnormalities disrupt interhemispheric communications that impair the recovery of a series of neurological and psychiatric disorders. Understanding interhemispheric communication could help identify treatments for disorders with dysfunctional callosal transmission. This study aimed to validate the sensitivity of a TMS-EEG-based measure of interhemispheric signal propagation (ISP) to GABA B receptor modulation, while independently replicating the pharmacological mechanisms of interhemispheric inhibition. A group of 29 participants received an oral dose of either baclofen, a GABA B receptor agonist, or a placebo. Before and after drug intake, single-pulse TMS-EEG was applied to assess ISP in both the motor and prefrontal regions. Our findings indicated that baclofen increased interhemispheric inhibition over the motor region, indexed by significantly decreased ISP ( p = 0.037). No significant effect was observed in the dorsolateral prefrontal region ( p = 0.186), suggesting regional specificity in GABA B receptor modulation of ISP. These findings uncovered the pharmacological mechanisms of interhemispheric inhibition as indexed by ISP. They also highlight the potential of ISP for characterising interhemispheric communication, which could inform the treatment for a series of disorders with dysfunctional callosal transmission.
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