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.

Inducing Cortical Plasticity to Manipulate and Consolidate Subjective Time Interval Production.

OBJECTIVES: Time awareness may change depending on the mental state or disease conditions, although each individual perceives his/her own sense of time as stable and accurate. Nevertheless, the processes that consolidate altered duration production remain unclear. The present study aimed to manipulate the subjective duration production via memory consolidation through the modulation of neural plasticity. MATERIALS AND METHODS: We first performed false feedback training of duration or length production and examined the period required for natural recovery from the altered production. Next, persistent neural plasticity was promoted by quadripulse transcranial magnetic stimulation (QPS) over the right dorsolateral prefrontal cortex (DLPFC), temporoparietal junction (TPJ), and primary motor cortex (M1). We conducted the same feedback training in the individual and studied how the time course of false learning changed. RESULTS: We observed that altered duration production after false feedback returned to baseline within two hours. Next, immediate exposure to false feedback during neural plasticity enhancement revealed that in individuals who received QPS over the right DLPFC, but not over TPJ or M1, false duration production was maintained for four hours; furthermore, the efficacy persisted for at least one week. CONCLUSION: These findings suggest that, while learned altered duration production decays over several hours, QPS over the right DLPFC enables the consolidation of newly learned duration production.

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.

Perception of chasing in squirrel monkeys (Saimiri sciureus).

Understanding the intentions of others is crucial in developing positive social relationships. Comparative human and non-human animal studies have addressed the phylogenetic origin of this ability. However, few studies have explored the importance of motion information in distinguishing others' intentions and goals in non-human primates. This study addressed whether squirrel monkeys (Saimiri sciureus) are able to perceive a goal-directed motion pattern-specifically, chasing-represented by two geometric objects. In Experiment 1, we trained squirrel monkeys to discriminate a "Chasing" sequence from a "Random" sequence. We then confirmed that this discrimination transferred to new stimuli ("Chasing" and "Random") in a probe test. To determine whether the monkeys used similarities of trajectory to discriminate chasing from random motion, we also presented a non-chasing "Clone" sequence in which the trajectories of the two figures were identical. Three of six monkeys were able to discriminate "Chasing" from the other sequences. In Experiment 2, we confirmed humans' recognition of chasing with the stimuli from Experiment 1. In Experiment 3, the three monkeys for which discrimination did not transfer to the new stimuli in Experiment 1 were trained to discriminate between "Chasing" and "Clone" sequences. At testing, all three monkeys had learned to discriminate chasing, and two transferred their learning to new stimuli. Our results suggest that squirrel monkeys use goal-directed motion patterns, rather than simply similarity of trajectory, to discriminate chasing. Further investigation is necessary to identify the motion characteristics that contribute to this discrimination.

Role of the subthalamic nucleus in perceiving and estimating the passage of time.

Sense of time (temporal sense) is believed to be processed by various brain regions in a complex manner, among which the basal ganglia, including the striatum and subthalamic nucleus (STN), play central roles. However, the precise mechanism for processing sense of time has not been clarified. To examine the role of the STN in temporal processing of the sense of time by directly manipulating STN function by switching a deep brain stimulation (DBS) device On/Off in 28 patients with Parkinson's disease undergoing STN-DBS therapy. The test session was performed approximately 20 min after switching the DBS device from On to Off or from Off to On. Temporal sense processing was assessed in three different tasks (time reproduction, time production, and bisection). In the three temporal cognitive tasks, switching STN-DBS to Off caused shorter durations to be produced compared with the switching to the On condition in the time production task. In contrast, no effect of STN-DBS was observed in the time bisection or time reproduction tasks. These findings suggest that the STN is involved in the representation process of time duration and that the role of the STN in the sense of time may be limited to the exteriorization of memories formed by experience.

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.

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.

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.

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.

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.

Preferential attentional engagement drives attentional bias to snakes in Japanese macaques (Macaca fuscata) and humans (Homo sapiens).

In humans, attentional biases have been shown to negative (dangerous animals, physical threat) and positive (high caloric food, alcohol) stimuli. However, it is not clear whether these attentional biases reflect on stimulus driven, bottom up, or goal driven, top down, attentional processes. Here we show that, like humans, Japanese macaques show an attentional bias to snakes in a dot probe task (Experiment 1). Moreover, this attentional bias reflects on bottom up driven, preferential engagement of attention by snake images (Experiment 2a), a finding that was replicated in a study that used the same methodology in humans (Experiment 2b). These results are consistent with the notion that attentional bias to snakes reflects on an evolutionarily old, stimulus driven threat detection mechanism which is found in both species.

Goal attribution to inanimate moving objects by Japanese macaques (Macaca fuscata).

Humans interpret others' goals based on motion information, and this capacity contributes to our mental reasoning. The present study sought to determine whether Japanese macaques (Macaca fuscata) perceive goal-directedness in chasing events depicted by two geometric particles. In Experiment 1, two monkeys and adult humans were trained to discriminate between Chasing and Random sequences. We then introduced probe stimuli with various levels of correlation between the particle trajectories to examine whether participants performed the task using higher correlation. Participants chose stimuli with the highest correlations by chance, suggesting that correlations were not the discriminative cue. Experiment 2 examined whether participants focused on particle proximity. Participants differentiated between Chasing and Control sequences; the distance between two particles was identical in both. Results indicated that, like humans, the Japanese macaques did not use physical cues alone to perform the discrimination task and integrated the cues spontaneously. This suggests that goal attribution resulting from motion information is a widespread cognitive phenotype in primate species.

[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.

Dopamine-dependent visual attention preference to social stimuli in nonhuman primates.

RATIONALE: Dopamine (DA) plays a central role in reward processing. Accumulating evidence suggests that social interaction and social stimuli have rewarding properties that activate the DA reward circuits. However, few studies have attempted to investigate how DA is involved in the processing of social stimuli. OBJECTIVES: In this study, we investigated the effects of pharmacological manipulations of DA D1 and D2 receptors on social vs. nonsocial visual attention preference in macaques. METHODS: Japanese macaques were subjected to behavioral tests in which visual attention toward social (monkey faces with and without affective expressions) and nonsocial stimuli was examined, with D1 and D2 antagonist administration. RESULTS: The macaques exhibited significantly longer durations of gazing toward the images with social cues than did those with nonsocial cues. Both D1 and D2 antagonist administration decreased duration of gazing toward the social images with and without affective valences. In addition, although D1 antagonist administration increased the duration of gazing toward the nonsocial images, D2 antagonism had no effect. CONCLUSIONS: These results suggest that both D1 and D2 receptors may have roles in the processing of social signals but through separate mechanisms.