Epilepsy and the smell of fear

• Published in: Epilepsy & behavior Vol. 121; p. 108078
• Main Authors: Maa, E.H., Arnold, J., Bush, C.K.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.08.2021
• Subjects: Canine scent detection; Epilepsy biomarker; Fear signalling; Human alarm pheromone; Menthone; Fear signalling; Human alarm pheromone; Canine scent detection; Menthone; Epilepsy biomarker
• ISSN: 1525-5050; 1525-5069
• DOI: 10.1016/j.yebeh.2021.108078

•Menthone has been identified as the dominant constituent of seizure-scented sweat.•Canines were unable to distinguish between fear-scented and seizure-scented sweat.•Menthone may be an important pre-ictal biomarker of pending seizure.•We believe we are the first to identify menthone as a human alarm pheromone. In our canine scent detection research involving a specific volatile organic compound (VOC) associated with human epileptic seizure, we began to suspect involvement of the primitive neural networks associated with production of a previously undescribed human alarm pheromone as the origin of our seizure scent. We hypothesized that if we presented fear-scented sweat to our canine seizure scent detection team, and they identified the fear scent as their seizure scent, then that would suggest that they are identical compounds. Following consent and approval, sweat samples taken from volunteers associated with the Brooke Gordon Comprehensive Epilepsy Center at Denver Health were processed by the Canine Assistants (CA) service dog team that had been imprinted to recognize the unique seizure scent from our previous study. In part one, sweat samples were collected from subjects, who had no prior history of epilepsy or seizures, under two different testing environments: watching a scary movie (It) and a neutral/comedy movie (Airplane!). In part two, a larger follow-up study utilizing fear sweat, exercise sweat, epilepsy sweat, and other distractor scents were provided in a multiple choice paradigm to better understand the inter-rater reliability of the canine responses. In part one, our canine seizure scent detection team identified fear-scented sweat samples as their seizure scent in 4 of 5 study participants. There was almost perfect agreement of seizure scent detection during fear scent trials between the canine seizure scent detectors with a kappa value of 0.814 (95% CI: 0.668–0.960). In part two, (utilizing eleven different subjects) our canine scent detection team identified samples of either fear or seizure sweat with a sensitivity of 82% and a specificity of 100% (no false positives) from among the multiple choices offered. Additionally, there was 92% agreement between the members of the canine scent detection team. While this hypothesis testing study is small and deserves replication, it confirms that the Canine Assistants seizure scent detection team consistently and accurately identified fear-scented sweat as their seizure scent, implying that the VOC, menthone, is common to both conditions. This further implies that human seizure propagation and fear network circuitry may share a common anatomy, and that menthone may not only be an early seizure biomarker, but a newly described human alarm pheromone.