title: A Mechanistic Link between Olfaction and Autism Spectrum Disorder.
abstract: Internal action models (IAMs) are brain templates for sensory-motor coordination underlying diverse behaviors. An emerging theory suggests that impaired IAMs are a common theme in autism spectrum disorder (ASD). However, whether impaired IAMs occur across sensory systems and how they relate to the major phenotype of ASD, namely impaired social communication, remains unclear. Olfaction relies on an IAM known as the sniff response, where sniff magnitude is automatically modulated to account for odor valence. To test the failed IAM theory in olfaction, we precisely measured the non-verbal non-task-dependent sniff response concurrent with pleasant and unpleasant odors in 36 children--18 with ASD and 18 matched typically developing (TD) controls. We found that whereas TD children generated a typical adult-like sniff response within 305 ms of odor onset, ASD children had a profoundly altered sniff response, sniffing equally regardless of odor valance. This difference persisted despite equal reported odor perception and allowed for 81% correct ASD classification based on the sniff response alone (binomial, p < 0.001). Moreover, increasingly aberrant sniffing was associated with increasingly severe ASD (r = -0.75, p < 0.001), specifically with social (r = -0.72, p < 0.001), but not motor (r < -0.38, p > 0.18), impairment. These results uncover a novel ASD marker implying a mechanistic link between the underpinnings of olfaction and ASD and directly linking an impaired IAM with impaired social abilities.
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, 234 Herzel Street, Rehovot 76100, Israel. Electronic address: liron.rozenkrantz@gmail.com.
authors.forename: Liron
authors.initials: L
authors.lastname: Rozenkrantz
authors.affiliation: The Autism Center and Department of Pediatrics, Assaf Harofeh Medical Center, 1 Road 44, Zerifin 70300, Israel.
authors.forename: Ditza
authors.initials: D
authors.lastname: Zachor
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, 234 Herzel Street, Rehovot 76100, Israel.
authors.forename: Iris
authors.initials: I
authors.lastname: Heller
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, 234 Herzel Street, Rehovot 76100, Israel.
authors.forename: Anton
authors.initials: A
authors.lastname: Plotkin
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, 234 Herzel Street, Rehovot 76100, Israel.
authors.forename: Aharon
authors.initials: A
authors.lastname: Weissbrod
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, 234 Herzel Street, Rehovot 76100, Israel.
authors.forename: Kobi
authors.initials: K
authors.lastname: Snitz
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, 234 Herzel Street, Rehovot 76100, Israel.
authors.forename: Lavi
authors.initials: L
authors.lastname: Secundo
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, 234 Herzel Street, Rehovot 76100, Israel. Electronic address: noam.sobel@weizmann.ac.il.
authors.forename: Noam
authors.initials: N
authors.lastname: Sobel
mesh_terms: D000067877:Autism Spectrum Disorder / Q000209:etiology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007557:Israel; D008297:Male; D009812:Odorants / Q000032:analysis*; D012903:Smell