A Mechanistic Link between Olfaction and Autism Spectrum Disorder

Liron Rozenkrantz, Ditza Zachor, Iris Heller, Anton Plotkin, Aharon Weissbrod, Kobi Snitz, Lavi Secundo, Noam Sobel

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


Internal action models (IAMs) are brain templates for sensory-motor coordination underlying diverse behaviors [1]. An emerging theory suggests that impaired IAMs are a common theme in autism spectrum disorder (ASD) [2-4]. However, whether impaired IAMs occur across sensory systems and how they relate to the major phenotype of ASD, namely impaired social communication [5], remains unclear. Olfaction relies on an IAM known as the sniff response, where sniff magnitude is automatically modulated to account for odor valence [6-12]. 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.

Original languageEnglish
Pages (from-to)1904-1910
Number of pages7
JournalCurrent Biology
Issue number14
StatePublished - 20 Jul 2015
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by pilot grants from the Benoziyo Center for Neurological Diseases and the Adelis Foundation, and major support came from ERC Adg # 670798. The results of this manuscript are under consideration of patent at the Weizmann Institute Office of Technology Transfer.

Publisher Copyright:
© 2015 The Authors.


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