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.

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.

Enhanced use of gaze cue in a face-following task after brief trial experience in individuals with autism spectrum disorder.

Eye movements toward sequentially presented face images with or without gaze cues were recorded to investigate whether those with ASD, in comparison to their typically developing (TD) peers, could prospectively perform the task according to gaze cues. Line-drawn face images were sequentially presented for one second each on a laptop PC display, and the face images shifted from side-to-side and up-and-down. In the gaze cue condition, the gaze of the face image was directed to the position where the next face would be presented. Although the participants with ASD looked less at the eye area of the face image than their TD peers, they could perform comparable smooth gaze shift to the gaze cue of the face image in the gaze cue condition. This appropriate gaze shift in the ASD group was more evident in the second half of trials in than in the first half, as revealed by the mean proportion of fixation time in the eye area to valid gaze data in the early phase (during face image presentation) and the time to first fixation on the eye area. These results suggest that individuals with ASD may benefit from the short-period trial experiment by enhancing the usage of gaze cue.

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.

Action performance in children with autism spectrum disorder at preschool age: a pilot study.

Objectives: Motor deficits related to imitation have been observed in autism spectrum disorder (ASD) patients. This pilot investigation focused on motor performances, including daily tool-use actions, performing an action in the absence of the tool, and imitating (copying tool-use action presented visually), in eight children with ASD and eight children with typical development (TD), with all of pre-school age (4-6 years). Methods: Motor performances were compared between the children with ASD and TD. Differences between an actual tool-use action and performing a tool-use action without the tool according to verbal instruction were also assessed between the groups. Results: Children with ASD showed impairments in imitating, but their actual tool-use actions and tool-use actions without tools following verbal instruction were not different from those of TD children. The spatial error rate in the tasks was higher in children with ASD. Conclusions: The present study indicates that disturbance in imitating actions appears by the age of 4-6 years in children with ASD, possibly as a characteristic symptom affecting motor performance at pre-school age. Generalized apraxia might follow by the age of 8 years or older.

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.

Older Adolescents and Young Adults With Autism Spectrum Disorder Have Difficulty Chaining Motor Acts When Performing Prehension Movements Compared to Typically Developing Peers.

It is known that motor actions performed by individuals with autism spectrum disorders (ASD) are clumsy and a previous study revealed that children with ASD of around 8 years old showed less smooth movement and dysfunction of appropriate usage of online vision for grip aperture control. The present study investigates whether and how the kinematic properties of reach-to-grasp movements in older adolescents and adults with ASD [mean (±SD) age: 18.3 ± 2.1] differ from those in typically developing (TD) peers [mean (±SD) age: 19.1 ± 2.2]. Revealing the kinematic properties of reach-to-grasp movements in older adolescents and adults with ASD is indispensable in determining the developmental trajectory of this motor behavior in individuals with ASD. While wearing liquid crystal shutter goggles, participants reached for and grasped a cylinder with a diameter of either 4 or 6 cm. Two visual conditions were tested: a full vision (FV) condition (the goggles remained transparent during the movement) and a no vision (NV) condition (the goggles were closed immediately after the movement was initiated). These two visual conditions were either alternated with each trial in a single experimental session (alternated condition) or blocked within the session (blocked condition). We found that the reaching movement smoothness calculated as a normalized jerk score (i.e., index of skilled, coordinated human movements) of ASD participants did not differ significantly from that of TD peers although ASD participants showed smoother reaching in the alternated condition than in the blocked condition. The influence of online vision and its visual condition schedule on grip aperture during the in-flight phase was remarkably similar between the ASD and TD groups. Furthermore, we found that ASD group experienced a significant longer transition period from grasping end (i.e., stable holding when touching the surface of the object) to uplift initiation than the TD group. The results suggest that (1) deficits in movement smoothness and the use of online vision for motor control are rectified by the time individuals with ASD reach late adolescence and (2) older adolescents and adults with ASD still have difficulties chaining motor acts.

Perceptions regarding a range of work-related issues and corresponding support needs of individuals with an intractable disease.

A number of persons with an intractable disease (ID) experience work-related problems that could lead to job loss. The aim of this study was to ascertain perceptions regarding a range of work-related issues and corresponding support needs of individuals with an ID. Potential participants were people ages 15 to 64 with one of the 130 intractable chronic diseases designated in the Act to Comprehensively Support the Daily and Social Activities of Persons with Disabilities (Comprehensive Support for the Disabled Act). Participants completed a self-administered questionnaire. With the assistance of patients' organizations, 3,000 questionnaires were mailed to potential participants. Questions included demographic characteristics, family concerns, employment/supported employment, work accommodations, and other aspects of life. Responses were received from 889 (29.6%) participants, and respondents had 57 IDs. Forty-six-point-seven percent of respondents reported being unemployed due to fatigue and/or long-term treatment. Nearly half of the unemployed respondents reported that they had been unable to work despite their willingness to do so. Common requests for accommodation included flexible work hours, working at home, and job/workplace modifications. Only 30% of respondents knew about job training programs and supported work available for persons with disabilities. The results of the study are relevant for employees, employers, and occupational health/human resource professionals. The issue of reasonable accommodations for persons with an ID needs to be addressed in future research in order to promote continued work by those persons.

An autopsy case of frontotemporal lobar degeneration with the appearance of fused in sarcoma inclusions (basophilic inclusion body disease) clinically presenting corticobasal syndrome.

We describe an autopsy case of basophilic inclusion body disease (BIBD), a subtype of frontotemporal lobar degeneration (FTLD) with the appearance of fused in sarcoma (FUS) inclusions (FTLD-FUS), clinically presenting corticobasal syndrome (CBS). A 54-year-old man initially developed worsening of stuttering and right hand clumsiness. Neurological examinations revealed rigidity in the right upper and lower extremities, buccofacial apraxia, and right-side dominant limb-kinetic and ideomotor apraxia. Neuroimaging showed asymmetric left-dominant brain atrophy and a cerebral blood flow reduction in the ipsilateral frontal region. At 56 years, his apraxia had advanced, and ideational apraxia was observed. Furthermore, the asymmetry in the limb-kinetic and ideomotor apraxia had disappeared, and both conditions had become bilateral. He had a new onset of aphasia. His symptoms progressed and he died 9 years after the initial symptoms. The brain weighed 955 g. Diffuse brain atrophy was most obvious in the bilateral frontotemporal regions. The atrophy of the left superior frontal and precentral gyri and bilateral basal ganglia was remarkable. Histologically, there was a marked loss of neurons with gliosis in the affected areas, where basophilic neuronal cytoplasmic inclusions were observed. The inclusions were immunoreactive for FUS, p62, and TATA-binding protein-associated factor 15 (TAF15), but not for phosphorylated tau, transactive response DNA-binding protein of 43 kDa (TDP-43), neurofilament protein, or Ewing sarcoma (EWS). From these pathological findings, this case was diagnosed as having BIBD as an FTLD-FUS variant. Spinal cord lower motor neurons were spared in number, similar to primary lateral sclerosis. Mutations in FUS were undetectable. Common background pathologies for CBS include corticobasal degeneration, Alzheimer's disease, PSP, FTLD with phosphorylated TDP-43 inclusions (FTLD-TDP), Pick's disease, Lewy body disease and CJD. However, FTLD-FUS (BIBD) has been rarely reported. Our case suggested further pathological heterogeneity in CBS than had previously been reported. It is necessary to consider FTLD-FUS (BIBD) as a background pathology for CBS in the future.

Neural basis of the retrieval of people's names: evidence from brain-damaged patients and fMRI.

The aim of this study was to identify the neuroanatomical basis of the retrieval of people's names. Lesion data showed that patients with language-dominant temporal lobectomy had impairments in their ability to retrieve familiar and newly learned people's names, whereas patients with language-nondominant temporal lobectomy had difficulty retrieving newly learned people's names. Functional magnetic resonance imaging experiments revealed activations in the left temporal polar region during the retrieval of familiar and newly learned people's names, and in the right superior temporal and bilateral prefrontal cortices during the retrieval of newly learned information from face cues. These data provide new evidence that the left anterior temporal region is crucial for the retrieval of people's names irrespective of their familiarity and that the right superior temporal and bilateral prefrontal areas are crucial for the process of associating newly learned people's faces and names.

The role of the basal forebrain in episodic memory retrieval: a positron emission tomography study.

Human lesion data indicate that the basal forebrain or orbitofrontal cortex, or both, as well as medial temporal and diencephalic structures, is important for normal memory and that its disruption causes the pure amnesic syndrome, in which episodic memory is grossly impaired while other kinds of memory remain preserved. Among these critical areas, functional imaging studies have so far failed to detect activation of the basal forebrain, although activation in the nearby orbitofrontal cortex has been reported during episodic memory retrieval. We employed positron emission tomography to elucidate the neural basis of episodic memory recall utilizing two types of time cues and successfully detected activity in the basal forebrain for the first time. Specifically, recall of previously memorized words from temporal cues was associated with activity in the basal forebrain, right middle frontal gyrus, right superior temporal gyrus, and posterior cingulate gyrus, whereas their recall from person cues was associated with activity in the left insula, right middle frontal gyrus, and posterior cingulate gyrus. Furthermore, percentage increases of regional blood flow in the basal forebrain were correlated with behavioral data of successful recall. Our results provide clear evidence that the human basal forebrain has a specific role in episodic memory recall, especially that from time-contextual information.