SummaryInternal 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.
Organization of receptive surfaces reflects primary axes of perception. In vision, retinal coordinates reflect spatial coordinates. In audition, cochlear coordinates reflect tonal coordinates. However, the rules underlying the organization of the olfactory receptive surface are unknown. To test the hypothesis that organization of the olfactory epithelium reflects olfactory perception, we inserted an electrode into the human olfactory epithelium to directly measure odorant-induced evoked responses. We found that pairwise differences in odorant pleasantness predicted pairwise differences in response magnitude; that is, a location that responded maximally to a pleasant odorant was likely to respond strongly to other pleasant odorants, and a location that responded maximally to an unpleasant odorant was likely to respond strongly to other unpleasant odorants. Moreover, the extent of an individual's perceptual span predicted their span in evoked response. This suggests that, similarly to receptor surfaces for vision and audition, organization of the olfactory receptor surface reflects key axes of perception.
Paradoxically, improvements in emergency medicine have increased survival albeit with severe disability ranging from quadriplegia to "locked-in syndrome." Locked-in syndrome is characterized by intact cognition yet complete paralysis, and hence these individuals are "locked-in" their own body, at best able to communicate using eye blinks alone. Sniffing is a precise sensory-motor acquisition entailing changes in nasal pressure. The fine control of sniffing depends on positioning the soft palate, which is innervated by multiple cranial nerves. This innervation pattern led us to hypothesize that sniffing may remain conserved following severe injury. To test this, we developed a device that measures nasal pressure and converts it into electrical signals. The device enabled sniffs to control an actuator with speed similar to that of a hand using a mouse or joystick. Functional magnetic resonance imaging of device usage revealed a widely distributed neural network, allowing for increased conservation following injury. Also, device usage shared neural substrates with language production, rendering sniffs a promising bypass mode of communication. Indeed, sniffing allowed completely paralyzed locked-in participants to write text and quadriplegic participants to write text and drive an electric wheelchair. We conclude that redirection of sniff motor programs toward alternative functions allows sniffing to provide a control interface that is fast, accurate, robust, and highly conserved following severe injury.locked-in | quadriplegic | soft palate
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