Responses of Chemosensory Perception to Stimulation of the Human Brain

Objective Significant advances have been made in our understanding of the neural substrates of human chemosensory processing, involving the piriform cortex, insula, and orbitofrontal cortex. However, the important and challenging issues are to localize the brain regions with high anatomic precision that can causally produce chemosensory perception and further delineate the topography of different classifications of chemosensory perception. Methods We quantitatively measured subjective responses of chemosensory perception to intracranial electrical stimulation over the brain in neurosurgical patients (n = 302) with medically refractory epilepsy. Results The chemosensory perceptions including olfaction, gustation, and chemesthesis were elicited in 21 of 302 patients (7%). Chemosensory responses were evoked in 53 (0.2%) of 21,661 stimulated sites. The highest response rate (1.8%) was in the insula (37/2,051 stimulated sites from 15/163 patients). The chemosensory perception emerged predominantly during stimulation of the insula along the central sulcus axis. Notably, there existed a distinct pattern that the anteroventral insula predominately represented orthonasal olfaction, whereas different chemosensory modalities converged in the mid‐dorsal insula. Interpretation This study provided a detailed characterization of chemosensory perception across the brain, especially in the insula. These results suggest that the cortex along the banks of the central sulcus of the insula may play a role in producing the supramodal sensation of flavor. It also indicates that dysfunction of the central insula should be considered during the evaluation of chemosensory‐related epileptic seizures. ANN NEUROL 2023;93:175–183