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.

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.

Neural architecture of human language: Hierarchical structure building is independent from working memory.

Using functional magnetic resonance imaging (fMRI), we show that the neural substrate of language does not overlap with that for verbal working memory when we carefully define verbal working memory in sentence processing. Object-Subject-Verb (OSV) sentences in Japanese were contrasted with canonical Subject-Object-Verb (SOV) sentences, which had less hierarchy in linguistic structure. This contrast revealed the posterior part of Broca's area and the left posterior middle temporal gyrus (pMTG) as the neural bases for hierarchical structure building. Furthermore, we changed verbal working memory load in OSV sentences by adding modifiers to the subject or object noun phrases; this resulted in the activation in the op9, which is situated in the frontal operculum and is adjacent to, but not situated in, Broca's area. The neuroanatomical segregation of language processing from verbal working memory suggests independence of the faculty of language from the verbal working memory system, providing evidence for the domain-specificity of language in human cognition.

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.

Neural capacity limits during unconscious semantic processing.

A growing body of neuroimaging data suggests that direct measurements of brain activity can reveal subliminal effects that remain invisible with behavior measures alone. We examined whether sentence comprehension processes could be triggered by a sequence of masked words. On each trial, participants viewed a rapid sequence of masked or unmasked words, including a subject noun, three adverbs and followed by a visible target verb. To probe the capacity limits of unconscious processing, we measured event-related potentials associated with the semantic congruency between the noun and the verb, while varying the subject position in each sentence. Unmasked sentences produced significant behavioral effects of congruency, paralleled by robust N400 effects, independently of subject-verb distance. By contrast, masked sentences produced no behavioral effect and elicited N400 effects only when subjects and verbs were separated by 0 or 1 word. The present results suggest that semantic integration of multiple words can occur unconsciously only if the distance between the words to be integrated does not exceed two words. Although the possibility remains that even longer sequence of invisible words may produce similar neural effects in different experimental settings, our ERP data show that only conscious perception gives access to a buffer that enables robust sentence-level processing independently of temporal distance.

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.

Mirror-image discrimination in the literate brain: a causal role for the left occpitotemporal cortex.

Previous studies show that the primate and human visual system automatically generates a common and invariant representation from a visual object image and its mirror reflection. For humans, however, this mirror-image generalization seems to be partially suppressed through literacy acquisition, since literate adults have greater difficulty in recognizing mirror images of letters than those of other visual objects. At the neural level, such category-specific effect on mirror-image processing has been associated with the left occpitotemporal cortex (L-OTC), but it remains unclear whether the apparent "inhibition" on mirror letters is mediated by suppressing mirror-image representations covertly generated from normal letter stimuli. Using transcranial magnetic stimulation (TMS), we examined how transient disruption of the L-OTC affects mirror-image recognition during a same-different judgment task, while varying the semantic category (letters and non-letter objects), identity (same or different), and orientation (same or mirror-reversed) of the first and second stimuli. We found that magnetic stimulation of the L-OTC produced a significant delay in mirror-image recognition for letter-strings but not for other objects. By contrast, this category specific impact was not observed when TMS was applied to other control sites, including the right homologous area and vertex. These results thus demonstrate a causal link between the L-OTC and mirror-image discrimination in literate people. We further suggest that left-right sensitivity for letters is not achieved by a local inhibitory mechanism in the L-OTC but probably relies on the inter-regional coupling with other orientation-sensitive occipito-parietal regions.

Eating tools in hand activate the brain systems for eating action: a transcranial magnetic stimulation study.

There is increasing neuroimaging evidence suggesting that visually presented tools automatically activate the human sensorimotor system coding learned motor actions relevant to the visual stimuli. Such crossmodal activation may reflect a general functional property of the human motor memory and thus can be operating in other, non-limb effector organs, such as the orofacial system involved in eating. In the present study, we predicted that somatosensory signals produced by eating tools in hand covertly activate the neuromuscular systems involved in eating action. In Experiments 1 and 2, we measured motor evoked response (MEP) of the masseter muscle in normal humans to examine the possible impact of tools in hand (chopsticks and scissors) on the neuromuscular systems during the observation of food stimuli. We found that eating tools (chopsticks) enhanced the masseter MEPs more greatly than other tools (scissors) during the visual recognition of food, although this covert change in motor excitability was not detectable at the behavioral level. In Experiment 3, we further observed that chopsticks overall increased MEPs more greatly than scissors and this tool-driven increase of MEPs was greater when participants viewed food stimuli than when they viewed non-food stimuli. A joint analysis of the three experiments confirmed a significant impact of eating tools on the masseter MEPs during food recognition. Taken together, these results suggest that eating tools in hand exert a category-specific impact on the neuromuscular system for eating.

Effectiveness of domain-based intervention for language development in Japanese hearing-impaired children: a multicenter study.

OBJECTIVE: Decreasing language delay in hearing-impaired children is a key issue in the maintenance of their quality of life. Language training has been presented mainly by experience-based training; effective intervention programs are crucially important for their future. The aim of this study was to confirm the efficacy of 6-month domain-based language training of school-age, severe-to-profound hearing-impaired children. METHODS: We conducted a controlled before-after study involving 728 severe-to-profound prelingual hearing-impaired children, including an intervention group (n = 60), control group (n = 30), and baseline study group (n = 638). Language scores of the participants and questionnaires to the caregivers/therapists were compared before and after the intervention. Average monthly increase in each language score of the control group and baseline study group were compared with those of the intervention group. RESULTS: Language scores and the results of the questionnaire of the intervention group showed a significant improvement (P < .05). The average monthly language growth of the intervention group was twice that of the control group and 3 to 4 times that of the baseline study group (P < .05). The effect size was largest in communication (1.914), followed by syntax (0.931). CONCLUSION: Domain-based language training improved the language development and daily communication of hearing-impaired children without any adverse effects.

TMS-induced artifacts on EEG can be reduced by rearrangement of the electrode's lead wire before recording.

OBJECTIVE: Our purpose was to establish a technique to reduce residual artifacts after transcranial magnetic stimulation (TMS) from electroencephalographic (EEG) signals. METHODS: We investigated the effects of coil direction and stimulus intensity on residual artifacts in an artificial circuit, and tested whether or not the size of the circuit area affects the residual artifact (the model study). Based on the results, the optimization by rearranging the electrode's lead wire was tested on the human scalp (the human study). RESULTS: The residual artifact after TMS was dependent on the direction of the figure-of-eight coil, and on the artificial circuit area size. CONCLUSIONS: In accordance with the model study, the scalp EEG shows that TMS-induced artifacts can be reduced dramatically before the amplifier input stages in TMS-EEG experiments by a step-wise procedure rearranging the lead wires relative to the fixed coil orientation. SIGNIFICANCE: Our technique makes it possible to significantly reduce the residual artifacts from recordings of short-latency TMS-evoked potentials.

The role of the dorsolateral prefrontal cortex in the inhibition of stereotyped responses.

Stereotyped behaviors should be inhibited under some circumstances in order to encourage appropriate behavior. Psychiatrists have used the modified rock-paper-scissors (RPS) task to examine the inhibition of stereotyped behavior. When subjects are required to lose in response to a gesture, it is difficult for them to lose, and they have a tendency to win involuntarily. It is thought that the win response is the stereotyped response in the RPS task, and the difficulty in making positive attempts to lose is due to the requirement for inhibition of the stereotyped response. In this study, we investigated the brain regions related to inhibition of the stereotyped response using functional magnetic resonance imaging (fMRI). Subjects were assigned to one of two groups: the "win group" or the "lose group." The lose group showed higher activation of the left dorsolateral prefrontal cortex (DLFPC) when compared to the win group. We also delivered transcranial magnetic stimulation (TMS) while the subjects performed the modified RPS task to investigate whether the left DLPFC (middle frontal gyrus, Brodmann area, BA 9) was directly involved in the inhibition of the stereotyped response. When TMS was delivered before onset of the visual stimulus, the subjects displayed increased response errors. In particular, the subjects had a tendency to win erroneously in a lose condition even though they were required to lose. These results indicate involvement of the left DLPFC in inhibition of the stereotyped responses, which suggests that this region is associated with inhibition of the preparatory setting for stereotyped responses rather than inhibition of ongoing processing to produce a stereotyped response.

An fMRI study of musicians with focal dystonia during tapping tasks.

Musician's dystonia is a type of task specific dystonia for which the pathophysiology is not clear. In this study, we performed functional magnetic resonance imaging to investigate the motor-related brain activity associated with musician's dystonia. We compared brain activities measured from subjects with focal hand dystonia and normal (control) musicians during right-hand, left-hand, and both-hands tapping tasks. We found activations in the thalamus and the basal ganglia during the tapping tasks in the control group but not in the dystonia group. For both groups, we detected significant activations in the contralateral sensorimotor areas, including the premotor area and cerebellum, during each tapping task. Moreover, direct comparison between the dystonia and control groups showed that the dystonia group had greater activity in the ipsilateral premotor area during the right-hand tapping task and less activity in the left cerebellum during the both-hands tapping task. Thus, the dystonic musicians showed irregular activation patterns in the motor-association system. We suggest that irregular neural activity patterns in dystonic subjects reflect dystonic neural malfunction and consequent compensatory activity to maintain appropriate voluntary movements.

Visual stimuli for the P300 brain-computer interface: a comparison of white/gray and green/blue flicker matrices.

OBJECTIVE: The white/gray flicker matrix has been used as a visual stimulus for the so-called P300 brain-computer interface (BCI), but the white/gray flash stimuli might induce discomfort. In this study, we investigated the effectiveness of green/blue flicker matrices as visual stimuli. METHODS: Ten able-bodied, non-trained subjects performed Alphabet Spelling (Japanese Alphabet: Hiragana) using an 8 x 10 matrix with three types of intensification/rest flicker combinations (L, luminance; C, chromatic; LC, luminance and chromatic); both online and offline performances were evaluated. RESULTS: The accuracy rate under the online LC condition was 80.6%. Offline analysis showed that the LC condition was associated with significantly higher accuracy than was the L or C condition (Tukey-Kramer, p < 0.05). No significant difference was observed between L and C conditions. CONCLUSIONS: The LC condition, which used the green/blue flicker matrix was associated with better performances in the P300 BCI. SIGNIFICANCE: The green/blue chromatic flicker matrix can be an efficient tool for practical BCI application.

Anterior prefrontal cortex activities during the inhibition of stereotyped responses in a neuropsychological rock-paper-scissors task.

Stereotyped responses must be suppressed at certain times during daily life, which can be difficult for patients with lesions in the frontal cortices. Neuropsychologists have used the rock-paper-scissors (RPS) task to evaluate patients' ability to suppress a stereotyped response. In this study, we measured functional magnetic resonance imaging signals to investigate how frontal cortex activities change corresponding to subjects' performance as they tried to lose (successfully inhibiting the typical response to win) when presented with a gesture signifying rock, paper, or scissors. Performance rates ranged from 50% to 100%, and results indicated that activation in the bilateral anterior part of the prefrontal cortex increased parametrically corresponding to subjects' successful performance. This result implies that the anterior prefrontal cortex plays a key role in the successful completion of a modified RPS task and may play a role in the suppression of stereotyped responses.

Modulation of corticospinal excitability during lengthening and shortening contractions in the first dorsal interosseus muscle of humans.

Lengthening and shortening contractions are the fundamental patterns of muscle activation underlying various movements. It is still unknown whether or not there is a muscle-specific difference in such a fundamental pattern of muscle activation. The purpose of this study was, therefore, to investigate whether or not the relationship between lengthening and shortening contractions in the modulation of corticospinal excitability in the first dorsal interosseus (FDI) muscle is the same as that of previously tested muscles because the hand muscles are anatomically and functionally different from the other muscles. To this end, we investigated the relationship between the input-output curves of the corticospinal pathway (i.e., the relationship between the stimulus intensities vs. the area of motor-evoked potentials) during lengthening and shortening contractions in 17 healthy subjects. The shape of this relationship was sigmoidal and characterized by a plateau value, maximum slope, and threshold. The plateau value was at the same level between lengthening and shortening contractions. However, the maximum slope (P < 0.01) and threshold (P < 0.01) were significantly higher during lengthening contractions than during shortening contractions. These findings were different from the results of other muscles tested in previous studies (i.e., the soleus muscle and the elbow flexors). That is to say, the plateau value and the maximum slope during lengthening contractions were significantly lower than those during shortening contractions in previous studies. This study provides tentative evidence that the relationship between lengthening and shortening contractions in the modulation of corticospinal excitability differs between muscles, indicating that the underlying neural control is not necessarily the same even though the fundamental patterns of muscle activation are carried out.

Testing Bayesian models of human coincidence timing.

A sensorimotor control task often requires an accurate estimation of the timing of the arrival of an external target (e.g., when hitting a pitched ball). Conventional studies of human timing processes have ignored the stochastic features of target timing: e.g., the speed of the pitched ball is not generally constant, but is variable. Interestingly, based on Bayesian theory, it has been recently shown that the human sensorimotor system achieves the optimal estimation by integrating sensory information with prior knowledge of the probabilistic structure of the target variation. In this study, we tested whether Bayesian integration is also implemented while performing a coincidence-timing type of sensorimotor task by manipulating the trial-by-trial variability (i.e., the prior distribution) of the target timing. As a result, within several hundred trials of learning, subjects were able to generate systematic timing behavior according to the width of the prior distribution, as predicted by the optimal Bayesian model. Considering the previous studies showing that the human sensorimotor system uses Bayesian integration in spacing and force-grading tasks, our result indicates that Bayesian integration is fundamental to all aspects of human sensorimotor control. Moreover, it was noteworthy that the subjects could adjust their behavior both when the prior distribution was switched from wide to narrow and vice versa, although the adjustment was slower in the former case. Based on a comparison with observations in a previous study, we discuss the flexibility and adaptability of Bayesian sensorimotor learning.

Selective activation and deactivation of the human brain structures between speeded and precisely timed tapping responses to identical visual stimulus: an fMRI study.

We investigated the difference between brain activities in speeded and precisely timed responses to identical visual stimulus using fMRI. Stimulus used was a row of seven light-emitting diodes (LEDs) lightened up one after another with constant speed within a trial but with various speeds between trials. Subjects were asked to execute finger-thumb tapping with the right hand in response to the onset of the first LED light in the reaction time (RT) task and in anticipation of the onset of the last (i.e., seventh) LED light in the timing task. In control condition, they were asked to passively view the stimulus without motor response. Results showed that various movement-related areas including contralateral cingulate motor cortex were commonly activated for both tasks relative to the control condition, suggesting these structures are involved in general perception and response execution rather than specific function for speeded or precisely timed responses. In the RT task, the presupplementary motor area extending to the cingulate sulcus was activated more strongly than in the timing task probably to focus attention to the onset of the first LED light unpredictably presented after random foreperiods. The lateral occipital area extending to the temporo-parieto-occipital junction was activated more strongly in the timing task than in the RT task; the same area was deactivated in the RT task relative to the control condition. Auditory-related areas were also deactivated in the both tasks. This inter- and intramodal task-specific modification including deactivation underscores significance of the context for perception and action and can have an important role in dexterous or skilled performance.

1/f-type fluctuation in human visuomotor transformation.

In the absence of vision of the limb, movements toward a visual target exhibit substantial errors which are considered to originate mainly in the visuomotor transformation process. To determine the time-dependent property of human visuomotor transformation, we investigated the error sequences in movements toward visual target using scaling analyses. When subjects could see their controlling limb, the error sequences could not be distinguished from a random sequence. On the other hand, when the controlling limb was invisible, the error sequences were not random in order, but exhibited 1/f-type time correlation. This finding that the variation in human visuomotor transformation shows 1/f-type fluctuation provides a significant index for mathematical modeling and system identification in human visuomotor control.

Sustained muscle contractions maintained by autonomous neuronal activity within the human spinal cord.

It is well known that muscle contraction can be easily evoked in the human soleus muscle by applying single-pulse electrical stimulation to the tibial nerve at the popliteal fossa. We herein reveal the unexpected phenomenon of muscle contractions that can be observed when train stimulation is used instead. We found, in 11 human subjects, that transient electrical train stimulation (1-ms pulses, 50 Hz, 2 s) was able to induce sustained muscle contractions in the soleus muscle that outlasted the stimulation period for greater than 1 min. Subjects were unaware of their own muscle activity, suggesting that this is an involuntary muscle contraction. In fact, the excitability of the primary motor cortex (M1) with the sustained muscle contractions evaluated by transcranial magnetic stimulation was lower than the excitability with voluntary muscle contractions even when both muscle contraction levels were matched. This finding indicates that M1 was less involved in maintaining the muscle contractions. Furthermore, the muscle contractions did not come from spontaneous activity of muscle fibers or from reverberating activity within closed neuronal circuits involving motoneurons. These conclusions were made based on the respective evidence: 1) the electromyographic activity was inhibited by stimulation of the common peroneal nerve that has inhibitory connections to the soleus motoneuron pool and 2) it was not abolished after stopping the reverberation (if any) for approximately 100 ms by inducing the silent period that followed an H-reflex. These findings indicate that the sustained muscle contractions induced in this study are most likely to be maintained by autonomous activity of motoneurons and/or interneurons within the human spinal cord.