Approaches to Understanding Multisensory Dysfunction in Autism Spectrum Disorder

Abstract

Abnormal sensory responses are a DSM‐5 symptom of autism spectrum disorder (ASD), and research findings demonstrate altered sensory processing in ASD. Beyond difficulties with processing information within single sensory domains, including both hypersensitivity and hyposensitivity, difficulties in multisensory processing are becoming a core issue of focus in ASD. These difficulties may be targeted by treatment approaches such as “sensory integration,” which is frequently applied in autism treatment but not yet based on clear evidence. Recently, psychophysical data have emerged to demonstrate multisensory deficits in some children with ASD. Unlike deficits in social communication, which are best understood in humans, sensory and multisensory changes offer a tractable marker of circuit dysfunction that is more easily translated into animal model systems to probe the underlying neurobiological mechanisms. Paralleling experimental paradigms that were previously applied in humans and larger mammals, we and others have demonstrated that multisensory function can also be examined behaviorally in rodents. Here, we review the sensory and multisensory difficulties commonly found in ASD, examining laboratory findings that relate these findings across species. Next, we discuss the known neurobiology of multisensory integration, drawing largely on experimental work in larger mammals, and extensions of these paradigms into rodents. Finally, we describe emerging investigations into multisensory processing in genetic mouse models related to autism risk. By detailing findings from humans to mice, we highlight the advantage of multisensory paradigms that can be easily translated across species, as well as the potential for rodent experimental systems to reveal opportunities for novel treatments. Lay Summary Sensory and multisensory deficits are commonly found in ASD and may result in cascading effects that impact social communication. By using similar experiments to those in humans, we discuss how studies in animal models may allow an understanding of the brain mechanisms that underlie difficulties in multisensory integration, with the ultimate goal of developing new treatments. Autism Res 2020, 13: 1430–1449. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.

The Lost Neural Hierarchy of the Autistic Self—Locked-Out of the Mental Self and Its Default-Mode Network

“…This may account for the extreme degrees of ego-centeredness of ASD subjects: they can neither access their own self nor others’ selves on the mental level, which leaves them with no choice but to focus on the more physical layers of their own self, i.e., ego-centeredness. Whether such restriction to the intero- and exteroceptive layers of their self can also account for the often-observed abnormalities in sensory input processing with abnormally strong perceptual experiences [ 18 , 19 , 20 , 21 , 22 , 109 , 110 ] remains to be shown in the future.…”

“…Autism spectrum disorder (ASD) is a complex psychiatric condition that is characterized by multiple symptoms. Cognitive symptoms like changes in autobiographical/episodic memory [ 1 , 2 , 3 , 4 ] are coupled with deficits in social cognition as in theory of mind [ 5 , 6 , 7 ], affective changes including emotion, empathy, and facial expression [ 8 , 9 , 10 ], hypersystemizing [ 11 ], motor symptoms like difficulty of action imitation [ 12 , 13 , 14 ], stereotypies and repetitions [ 15 , 16 , 17 ], and multimodal sensory integration [ 18 , 19 , 20 , 21 , 22 ]. Yet, on a deeper level beneath the various functions, an altered sense of self, i.e., self-awareness, has been described and is a key disturbance of autism [ 23 ].…”

Rare Opportunities for Insights Into Serotonergic Contributions to Brain and Bowel Disorders: Studies of the SERT Ala56 Mouse

“…Finally, SERT Ala56 mice display abnormal repetitive behavior, indicated by repeated cycling to the top of their cage, registered in an automated system as increased “hanging bouts” (Veenstra-VanderWeele et al, 2012 ). In keeping with evidence of altered sensory integration in ASD (Siemann et al, 2017 , 2020 ), additional studies have revealed a reduced ability of SERT Ala56 mice to integrate multiple sensory cues to facilitate operant responding for reward (Siemann et al, 2017 ). In humans, SERT Ala56 is found in unaffected as well as ASD subjects, likely reflecting the nature of complex diseases, in which many genes each contribute small amounts of risk, and thus additional genetic background influences diagnosis or penetrance of the disease.…”

Closing the species gap: Translational approaches to studying sensory processing differences relevant for autism spectrum disorder

“…Auditory temporal processing can also be assessed by determining the extent that a subject can detect a brief silent gap in an otherwise continuous background noise. In humans, this gap detection ability has been assessed using a psychophysical task (Foss-Feig et al, 2017), whereas testing in rodents has used a modified acoustic startle paradigm (see Section 2), in which a silent gap (rather than a prepulse) was presented just prior to the BOX 1 Case example: Task coordination between species enables correct conclusions Audiovisual temporal binding has been extensively studied in autistic and non-autistic individuals using both complex speech stimuli (e.g., /ga/; both sensory and semantic processing required) and simple flash-beep stimuli (de Boer-Schellekens et al, 2013;Siemann et al, 2020;Stevenson & Wallace, 2013). Such studies reveal that the presence of behavioral differences in ASD may depend both on stimulus complexity and task design (de Boer-Schellekens et al, 2013;.…”