The web of laughter: frontal and limbic projections of the anterior cingulate cortex revealed by cortico-cortical evoked potential from sites eliciting laughter.

According to an evolutionist approach, laughter is a multifaceted behaviour affecting social, emotional, motor and speech functions. Albeit previous studies have suggested that high-frequency electrical stimulation (HF-ES) of the pregenual anterior cingulate cortex (pACC) may induce bursts of laughter-suggesting a crucial contribution of this region to the cortical control of this behaviour-the complex nature of laughter implies that outward connections from the pACC may reach and affect a complex network of frontal and limbic regions. Here, we studied the effective connectivity of the pACC by analysing the cortico-cortical evoked potentials elicited by single-pulse electrical stimulation of pACC sites whose HF-ES elicited laughter in 12 patients. Once these regions were identified, we studied their clinical response to HF-ES, to reveal the specific functional target of pACC representation of laughter. Results reveal that the neural representation of laughter in the pACC interacts with several frontal and limbic regions, including cingulate, orbitofrontal, medial prefrontal and anterior insular regions-involved in interoception, emotion, social reward and motor behaviour. These results offer neuroscientific support to the evolutionist approach to laughter, providing a possible mechanistic explanation of the interplay between this behaviour and emotion regulation, speech production and social interactions. This article is part of the theme issue 'Cracking the laugh code: laughter through the lens of biology, psychology and neuroscience'.