Temporal resolution relates to sensory hyperreactivity independently of stimulus detection sensitivity in individuals with autism spectrum disorder.

Researchers have been focusing on perceptual characteristics of autism spectrum disorder (ASD) in terms of sensory hyperreactivity. Previously, we demonstrated that temporal resolution, which is the accuracy to differentiate the order of two successive vibrotactile stimuli, is associated with the severity of sensory hyperreactivity. We currently examined whether an increase in the perceptual intensity of a tactile stimulus, despite its short duration, is derived from high temporal resolution and high frequency of sensory temporal summation. Twenty ASD and 22 typically developing (TD) participants conducted two psychophysical experimental tasks to evaluate detectable duration of vibrotactile stimulus with same amplitude and to evaluate temporal resolution. The sensory hyperreactivity was estimated using self-reported questionnaire. There was no relationship between the temporal resolution and the duration of detectable stimuli in both groups. However, the ASD group showed severe sensory hyperreactivity in daily life than TD group, and the ASD participants with severe sensory hyperreactivity tended to have high temporal resolution, not high sensitivity of detectable duration. Contrary to the hypothesis, there might be different processing between temporal resolution and sensitivity for stimulus detection. We suggested that the atypical temporal processing would affect to sensory reactivity in ASD.

Sensory and Social Subtypes of Japanese Individuals with Autism Spectrum Disorders.

Studies have proposed that individuals with autism spectrum disorder (ASD) can be divided into several subtypes depending on their sensory features. However, consideration of social communication features is also crucial for configuring ASD subtypes, because social and sensory features are tightly interrelated. In this study, we asked Japanese individuals with ASD to answer the Short Sensory Profile (SSP) and the Social Responsiveness Scale, Second Edition (SRS-2), which measure sensory and social aspects, respectively. Consequent latent profile analysis demonstrated that the participants could be divided into five subgroups: two groups exhibited opposite or inconsistent patterns between the SSP and SRS-2 scores, while the other groups exhibited consistent patterns. Our findings indicate the existence of diverse phenotypes in individuals with ASD.

Hand-foot coordination is significantly influenced by motion direction in individuals with autism spectrum disorder.

Generally, when individuals attempt to move two limbs rhythmically in the opposite direction (e.g., flex the left hand and extend the left foot along the sagittal plane), the movements tend to be instead performed in the same direction. This phenomenon, known as directional constraint, can be harnessed to examine the difficulties in movement coordination exhibited by most individuals with autism spectrum disorder (ASD). While such difficulties have already been investigated through standardized clinical assessments, they have not been examined through kinematic methods. Thus, we employed a clinical assessment scale in an experimentally controlled environment to investigate whether stronger directional constraint during the rhythmic movement of two limbs is more pronounced and associated with decreased movement coordination in individuals with ASD. ASD and typically developing (TD) participants were asked to rhythmically move two limbs either in the same or opposite directions. In addition, the coordination skills of participants were assessed using the Bruininks-Oseretsky Test of Motor Proficiency Second Edition (BOT-2). Subjects with ASD showed significantly stronger directional constraint than TD participants during the contralateral and ipsilateral movement of the hand and foot. According to the pooled data from both groups, participants who showed stronger directional constraint during these two movement conditions also exhibited poorer coordinated movement skills in the BOT-2. These results suggest that people with ASD may have difficulties in inhibiting the neural signals that synchronize the direction of inter-limb movements, thus resulting in coordination disabilities. LAY SUMMARY: Individuals with autism spectrum disorder (ASD) often exhibit difficulties in coordinated movements. We asked those with ASD and typically developing (TD) participants to move two limbs (e.g., left hand and left foot) either in the same or the opposite direction. Results demonstrated that participants with ASD had more difficulties in counteracting the tendency of their hand and foot to synchronously move in the same direction. Our findings suggested that difficulties to suppress synchronized movements of the hand and foot result in coordination disabilities.

Validation of the Japanese version of the Interoception Sensory Questionnaire for individuals with autism spectrum disorder.

The Interoception Sensory Questionnaire (ISQ) is a self-report instrument used to assess the characteristics of interoceptive processing in individuals with autism spectrum disorder (ASD). Previous studies have shown that scores of the ISQ are more appropriate than other subjective measures for evaluating difficulties in interoceptive processing in individuals with ASD. Yet, no prior research has demonstrated the validation of the ISQ in Japanese samples. This study attempted to validate the Japanese version of the ISQ (ISQ-J) by examining its psychometric properties. We confirmed the score distribution, internal consistency, and factor structure in Japanese samples. We also examined the relationships with other interoceptive questionnaires. In addition, we compared the scores of the ISQ-J between adolescents and adults with ASD participants and control participants. Results of confirmatory factor analyses showed that the reliability of the ISQ-J in adults with ASD reached an acceptable level of a one-factor structure with excellent internal consistency (α = 0.963). The result of the ISQ-J showed a significant positive correlation with the measure of awareness of interoceptive sensitivity for localized bodily states; on the other hand, a significant negative correlation was found with those integrated bodily states. In addition, the ISQ-J scores were significantly higher in the ASD group than in the control group. The current findings depend on self-report data (including a diagnosis of ASD) to measure validity constructs. Additionally, since the ISQ-J was surveyed in adults with ASD, it is unclear whether similar the results would be obtained if the ISQ-J were conducted with children. These results indicate the validity and reliability of the ISQ-J and provide a tool for assessing confusion of interoceptive information in Japanese adults with ASD.

The relationship between the effect of hand visibility on visuotactile temporal resolution and autistic traits.

Individuals with autism spectrum disorder (ASD) have atypical sensory processing, particularly when sensory stimuli are delivered from different modalities with a temporal lag of subseconds. Previous studies have suggested that individuals with ASD require a longer temporal lag to judge temporal orders of successive audiovisual stimuli than neurotypical individuals; however, it remains unclear whether a lower temporal resolution in the visuotactile domain is associated with an individual's autistic traits. In addition, a previous study demonstrated that visuotactile temporal resolution degraded when the participants saw a hand image on a display. In this study, we investigated whether the temporal resolution of the visuotactile stimuli degrades when the participant's own hand or rubber hands are visible, and whether the effect of the hand's visibility on the temporal resolution decreases according to an individual's autistic traits. We used the temporal order judgment (TOJ) of the vibrotactile stimulus delivered to the participant's index finger and an LED attached above their own hand or rubber hand. Our findings suggest that when participants could not see their hand, temporal order judgment tended to be coarser in participants with higher autistic traits. However, this tendency was not observed when they could see both their own or the rubber hands. Moreover, temporal resolution degraded when the participants could see their own hands. These results indicate that autistic traits influence the temporal resolution of visuotactile stimuli if they are delivered as external signals in TOJ.

Task-Related c-Fos Expression in the Posterior Parietal Cortex During the "Rubber Tail Task" Is Diminished in Ca2+-Dependent Activator Protein for Secretion 2 (Caps2)-Knockout Mice.

Rubber hand illusion (RHI), a kind of body ownership illusion, is sometimes atypical in individuals with autism spectrum disorder; however, the brain regions associated with the illusion are still unclear. We previously reported that mice responded as if their own tails were being touched when rubber tails were grasped following synchronous stroking to rubber tails and their tails (a "rubber tail illusion", RTI), which is a task based on the human RHI; furthermore, we reported that the RTI response was diminished in Ca2+-dependent activator protein for secretion 2-knockout (Caps2-KO) mice that exhibit autistic-like phenotypes. Importance of the posterior parietal cortex in the formation of illusory perception has previously been reported in human imaging studies. However, the local neural circuits and cell properties associated with this process are not clear. Therefore, we aimed to elucidate the neural basis of the RTI response and its impairment by investigating the c-Fos expression in both wild-type (WT) and Caps2-KO mice during the task since the c-Fos expression occurred soon after the neural activation. Immediately following the delivery of the synchronous stroking to both rubber tails and actual tails, the mice were perfused. Subsequently, whole brains were cryo-sectioned, and each section was immunostained with anti-c-Fos antibody; finally, c-Fos positive cell densities among the groups were compared. The c-Fos expression in the posterior parietal cortex was significantly lower in the Caps2-KO mice than in the WT mice. Additionally, we compared the c-Fos expression in the WT mice between synchronous and asynchronous conditions and found that the c-Fos-positive cell densities were significantly higher in the claustrum and primary somatosensory cortex of the WT mice exposed to the synchronous condition than those exposed to the asynchronous condition. Hence, the results suggest that decreased c-Fos expression in the posterior parietal cortex may be related to impaired multisensory integrations in Caps2-KO mice.

State anxiety modulates the effect of emotion cues on visual temporal sensitivity in autism spectrum disorder.

Atypical processing of stimulus inputs across a range of sensory modalities in autism spectrum disorder (ASD) is widely reported. Sensory processing is known to be influenced by bodily internal states such as physiological arousal and anxiety. As a sizeable proportion of ASD reportedly have co-morbid anxiety disorders that are linked with dysregulated arousal, we investigated if face emotion arousal cues influenced visual sensory sensitivity (indexed by temporal resolution) in ASD (n = 20) compared to a matched group of typically developed individuals (TD, n = 21). We asked further if emotion-cued changes in visual sensitivity were associated with individual differences in state and trait anxiety. Participants reported the laterality of the second of two consecutive Gaussian-blob flashes in a visual temporal order judgment task (v-TOJ), demanding higher-level visual processing. The key manipulation was presenting a task-irrelevant face emotion cue briefly at unexpected time points preceding the task-relevant flashes. Disgust vs. Neutral emotion signals significantly enhanced the visual temporal resolution in ASD. Individual state-anxiety scores showed a fair correlative trend with the emotion-cued changes in temporal resolution (Disgust versus Neutral) in ASD but missed statistical significance. Both these effects were absent in TD. The results show that individual state-anxiety levels likely modulate the effect of emotions on visual temporal sensitivity in ASD. The findings support a nuanced approach to understand the disparate sensory features in ASD, by factoring in the interplay of the individual reactivity to environmental affective information and the severity of anxiety.

Decreased utilization of allocentric coordinates during reaching movement in individuals with autism spectrum disorder.

Despite numerous reports of abnormalities in limb motor controls in spatial orientation in individuals with autism spectrum disorder (ASD), the underlying mechanisms have not been elucidated. We studied the influence of allocentric coordinates on ongoing reaching movements, which has been reported to strongly affect the reaching movements of typically developing (TD) individuals. ASD and TD participants observed a target presented randomly on one of the four corners of a frame on a screen. After it disappeared, another frame was presented slightly shifted leftward/rightward. The participants touched the memorized position of the target relatively congruent with a reference frame (allocentric condition) or ignoring it (egocentric condition). Results suggested that TD individuals were apt to touch the positions in allocentric manner rather than egocentric manner, while ASDs did not show this prioritization. Our findings demonstrate that decreased utilization of visual landmarks in ongoing movement may underlie motor disabilities in autism.

GABA Concentration in the Left Ventral Premotor Cortex Associates With Sensory Hyper-Responsiveness in Autism Spectrum Disorders Without Intellectual Disability.

Individuals with autism spectrum disorder (ASD) often exhibit abnormal processing of sensory inputs from multiple modalities and higher-order cognitive/behavioral response to those inputs. Several lines of evidence suggest that altered γ-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the brain, is a central characteristic of the neurophysiology of ASD. The relationship between GABA in particular brain regions and atypical sensory processing in ASD is poorly understood. We therefore employed 1H magnetic resonance spectroscopy (1H-MRS) to examine whether GABA levels in brain regions critical to higher-order motor and/or multiple sensory functions were associated with abnormal sensory responses in ASD. We evaluated atypical sensory processing with a clinically-validated assessment tool. Furthermore, we measured GABA levels in four regions: one each in the primary visual cortex, the left sensorimotor cortex, the left supplementary motor area (SMA), and the left ventral premotor cortex (vPMC). The latter two regions are thought to be involved in executing and coordinating cognitive and behavioral functions in response to multisensory inputs. We found severer sensory hyper-responsiveness in ASD relative to control participants. We also found reduced GABA concentrations in the left SMA but no differences in other regions of interest between ASD and control participants. A correlation analysis revealed a negative association between left vPMC GABA and the severity of sensory hyper-responsiveness across all participants, and the independent ASD group. These findings suggest that reduced inhibitory neurotransmission (reduced GABA) in a higher-order motor area, which modulates motor commands and integrates multiple sensory modalities, may underlie sensory hyper-responsiveness in ASD.

Neural Basis of Extremely High Temporal Sensitivity: Insights From a Patient With Autism.

The human brain is sensitive to incoming sensory information across multiple time scales. Temporal scales of information represented in the brain generally constrain behavior. Despite reports of the neural correlates of millisecond timing, how the human brain processes sensory stimuli in the sub-second range (≤100 ms) and its behavioral implications are areas of active scientific inquiry. An autism spectrum disorder (ASD) patient showed a tactile discrimination threshold of 6.49 ms on a temporal order judgment (TOJ) task which was approximately 10-fold superior than other ASD and healthy controls (59 and 69 ms, respectively). To investigate the brain regions of this extremely high temporal resolution in the patient, we used functional magnetic resonance imaging (fMRI) during TOJ. We observed greater activity notably in the left superior temporal gyrus (STG) and precentral gyrus (PrG) compared to that of controls. Generally, the left superior frontal gyrus (SFG) correlated positively, while the opercular part of right inferior frontal gyrus (IFG) correlated negatively, with the correct TOJ rate across all subjects (the patient + 22 healthy controls). We found that the performance was negatively correlated with the strength of neural responses in the right IFG overall in 30 participants (the patient + 22 healthy and 7 ASD controls). Our data reveal superior ability of this particular case of ASD in the millisecond scale for sensory inputs. We highlight several neural correlates of TOJ underlying the facilitation and/or inhibition of temporal resolution in humans.

Cutaneous and stick rabbit illusions in individuals with autism spectrum disorder.

Prediction is the process by which future events are anticipated based on past events; in contrast, postdiction is the retrospective interpretation of past events based on latter, more recent events. The prediction and postdiction are suggested to be similar based on theoretical models. Previous studies suggest that prediction is impaired in individuals with autism spectrum disorder (ASD). However, it is unclear whether postdiction is also impaired in individuals with ASD. In this study, we evaluated postdiction in individuals with ASD using the cutaneous and stick rabbit illusion paradigms in which the perceived location of a touch shifts postdictively in response to a subsequent touch stimulus. We observed significant cutaneous and stick rabbit illusion in both typically developing (TD) and ASD groups; therefore, postdiction was functional in individuals with ASD. Our present results suggest that postdiction involves a different neuronal process than prediction. We also observed that the ASD group exhibited significantly larger individual difference compared with the TD group in the stick rabbit illusion, which is considered to reflect extension of body schema to external objects. We discuss implications of the individual difference among the ASD participants in the context of sports requiring interactions between the body and external objects.

Altered GABA Concentration in Brain Motor Area Is Associated with the Severity of Motor Disabilities in Individuals with Autism Spectrum Disorder.

Several motor disabilities accompanied with autism spectrum disorder (ASD) are widely known despite limited reports of underlying neural mechanisms. Gamma-aminobutyric acid (GABA) levels in the motor-related cortical areas modulate several motor performances in healthy participants. We hypothesized that abnormal GABA concentrations in the primary motor area (M1) and supplementary motor area (SMA) associate with different motor difficulties for ASD adolescents/adults. We found that increased GABA concentrations in M1 measured using 1H-magnetic resonance spectroscopy exhibited lower motor performance in tasks requiring increased muscle strength while lower GABA concentrations in SMA were associated with lower scores in tests measuring body coordination. The degrees of neural inhibition in the M1 and SMA regions would contribute to different dimensions of motor disabilities in autism.

Rubber tail illusion is weakened in Ca2+-dependent activator protein for secretion 2 (Caps2)-knockout mice.

Body ownership is a fundamental aspect of self-consciousness. Illusion of body ownership is caused by updating body representation through multisensory integration. Synchronous visuotactile stimulation of a hand and rubber hand leads to illusory changes in body ownership in humans, but this is impaired in individuals with autism spectrum disorder (ASD). We previously reported that mice also exhibit body ownership illusion. With synchronous stroking of a tail and rubber tail, mice responded as if their own tails were being touched when the rubber tails were grasped ('rubber tail illusion'). However, it remains unknown whether deficits in illusion of body ownership occur in mouse models of autism. Here, we examined whether the 'rubber tail illusion' occurred in Ca2+-dependent activator protein for secretion 2-knockout (Caps2-KO) mice, which exhibit autistic-like phenotypes. During the synchronous stroking, response rates were significantly lower in Caps2-KO mice than in wild-type mice. There were no significant differences between the response rates of wild-type and Caps2-KO mice during the asynchronous stroking. The 'rubber tail illusion' was weak in Caps2-KO mice, suggesting that Caps2-KO mice experienced weaker visuotactile integration during the task. The rubber tail task will be a useful tool in mouse models of autism to evaluate atypical sensory processing.

Higher Tactile Temporal Resolution as a Basis of Hypersensitivity in Individuals with Autism Spectrum Disorder.

Many individuals with autism spectrum disorder (ASD) have symptoms of sensory hypersensitivity. Several studies have shown high individual variations in temporal processing of tactile stimuli. We hypothesized that these individual differences are linked to differences in hyper-reactivity among individuals with ASD. Participants performed two tasks as to vibrotactile stimuli: One is a temporal order judgement task, and another is a detection task. We found that individuals with ASD with higher temporal resolution tended to have more severe hypersensitivity symptoms. In contrast, the tactile detection threshold/sensitivity were related to the severities of stereotyped behaviour and restricted interests, rather than to hypersensitivity. Our findings demonstrate that higher temporal resolution to sensory stimuli may contribute to sensory hypersensitivity in individuals with ASD.

Spontaneous Discriminative Response to the Biological Motion Displays Involving a Walking Conspecific in Mice.

Recent translational studies using mice have contributed toward elucidating the neural, genetic, and molecular basis of social communication deficits. Nevertheless, many components of visual processes underlying mice sociality remain unresolved, including perception of bodily-movement. Here, we aimed to reveal the visual sensitivity of mice to information on bodily motion using biological motion displays depicted by simple geometric dots. We introduced biological motions extracted from walking mice vs. corresponding meaningless scrambled motions, in which the spatial configurations of each path of dots were shuffled. The apparatus was a three-chambered box with an opening between the chambers, and each side chamber had a monitor. We measured the exploration time of mice within the apparatus during the test, with two types of displays being presented. Mice spent more time in the chamber with the scrambled motion displays, indicating that animals spontaneously discriminated stimuli, with the scrambled motion being relatively novel. Furthermore, mice might have detected socially familiar cues from the biological motion displays. Subsequent testing revealed that additional mice showed no bias to the static versions of the stimuli used in the Movie test. Thus, we confirmed that mice modulated their behavior by focusing on the motion information of the stimuli, rather than the spatial configurations of each dot. Our findings provide a new perspective on how visual processing contributes to underlying social behavior in mice, potentially facilitating future translational studies of social deficits with respect to genetic and neural bases.

Effects of spatial consistency and individual difference on touch-induced visual suppression effect.

Crossmodal studies have reported not only facilitatory but also inhibitory perceptual interactions. For instance, tactile stimulation to the index finger of a hand leads to the degradation of visual discrimination performance (touch-induced visual suppression, TIVS). It has been suggested that the magnitude of TIVS depends on the spatial congruency of visuo-tactile stimuli and on individual differences in task performance. We performed a detailed investigation of the effects of spatial consistency and individual differences on the occurrence of TIVS. The visual target and tactile stimulus were presented at co-localized, ipsilateral but not co-localized, or contralateral positions. The degree of autistic traits has been reported to be well variable among the general population and to reflect differences in sensory processing. Therefore, we assessed the magnitude of autistic traits using the autism-spectrum quotient (AQ) as an index of individual differences. TIVS occurred particularly at the ipsilateral but not co-localized position. In contrast, the magnitude of the TIVS was positively correlated with the AQ score when the stimuli were presented at the co-localized position. These findings suggest that the occurrence of TIVS can be modulated both by the spatial relationship between the visual and tactile stimuli and by individual differences in autistic traits.

[Hypersensitivity as Extraordinary High Temporal Processing in Individuals with Autism-Spectrum Disorders].

Most individuals with autism-spectrum disorders have hypersensitivity/hyposensitivity to various types of sensory stimuli. Although several hypotheses such as higher sensitivity to stimuli, alterations in brain structure and function, and dysfunction of inhibitory systems at the molecular level have been suggested, there is no convincing evidence. We found that individuals with high temporal resolution tended to have strong hypersensitivity to sensory stimuli and vice versa. In addition, we focused on a case with extraordinarily high temporal resolution across the tactile, auditory, and audio-tactile domains. We believe that studying such an extreme case of temporal processing could facilitate an understanding of the neural basis of time perception.

Salivary Oxytocin Concentration Associates with the Subjective Feeling of Body Ownership during the Rubber Hand Illusion.

Oxytocin is a hormone of the posterior pituitary that promotes lactation, maternal bonding, and birth. Recent studies have shown that oxytocin may modulate social recognition in both sexes, and thus it may be related to empathy. Brain regions that are associated with social recognition and empathy (e.g., the insular cortex) are activated in the rubber hand illusion (RHI), which involves illusory ownership of a rubber hand caused by brush strokes applied synchronously to both a rubber hand and one of the participant's hand, which is hidden from view. It is intriguing to examine whether oxytocin modulates plastic changes in body representation, such as the changes occurring in the RHI. In the present study, we investigated the relationship between salivary oxytocin concentration and the feeling of rubber hand ownership. Brush strokes were applied synchronously or asynchronously to the participant's hand and a rubber hand on different days. Salivary oxytocin was measured before and after the behavioral tasks. We found that participants who had high concentrations of salivary oxytocin tended to feel strong ownership of the rubber hand. We also found that the participants with a high autism spectrum quotient (AQ) score who particularly felt difficulties in social skills and communications tended to feel weak rubber hand ownership. We observed that illusory body ownership was closely linked to social communications and a related neuroendocrine basis. The results of the present study suggest that an individual's salivary oxytocin concentration can predict the extent to which the individual experiences the RHI; furthermore, oxytocin might modulate the sensation of body ownership.

Neural mechanisms underlying touch-induced visual perceptual suppression: An fMRI study.

Crossmodal studies have demonstrated inhibitory as well as facilitatory neural effects in higher sensory association and primary sensory cortices. A recent human behavioral study reported touch-induced visual perceptual suppression (TIVS). Here, we introduced an experimental setting in which TIVS could occur and investigated brain activities underlying visuo-tactile interactions using a functional magnetic resonance imaging technique. While the suppressive effect of touch on vision was only found for half of the participants who could maintain their baseline performance above chance level (i.e. TIVS was not well replicated here), we focused on individual differences in the effect of touch on vision. This effect could be suppressive or enhancement, and the neuronal basis of these differences was analyzed. We found larger inhibitory responses in the anterior part of the right visual cortex (V1, V2) with higher TIVS magnitude when visuo-tactile stimuli were presented as spatially congruent. Activations in the right anterior superior temporal region, including the secondary somatosensory cortical area, were more strongly related to those in the visual cortex (V1, V2) with higher TIVS magnitude. These results indicate that inhibitory neural modulations from somatosensory to visual cortices and the resulting inhibitory neural responses in the visual cortex could be involved in TIVS.

The Rubber Tail Illusion as Evidence of Body Ownership in Mice.

The ownership of one's body parts represents a fundamental aspect of self-consciousness. Accumulating empirical evidence supports the existence of this concept in humans and nonhuman primates, but it is unclear whether nonprimate mammals experience similar feelings. Therefore, the present study used rubber tails to investigate body ownership in rodents. When the real tails and rubber tails were synchronously stroked, the mice responded as if their own tails were touched when the rubber tails were grasped. In contrast, when the stimuli were delivered asynchronously, there was a significantly lower mean response rate when the rubber tail was grasped. These findings suggest that mice may experience body ownership of their tails, suggestive of the rubber hand illusion in humans. SIGNIFICANCE STATEMENT: To explore the manner in which the ownership of body parts is experienced, this study specifically used the rubber hand illusion (RHI), in which self-consciousness can be extended out of one's own body. Accumulating empirical evidence supports the existence of this concept in humans and nonhuman primates, but it remains unclear whether nonprimate mammals experience similar feelings. This study demonstrated for the first time that mice may experience body ownership of their tails, which is suggestive of the RHI in humans and provides evidence that may highlight how humans experience the ownership of body parts.