[Show abstract][Hide abstract] ABSTRACT: Autism spectrum traits are postulated to lie on a continuum that extends between individuals with autism and individuals with typical development (TD). Social cognition properties that are deeply associated with autism spectrum traits have been linked to functional connectivity between regions within the brain's default mode network (DMN). Previous studies have shown that the resting-state functional connectivities (rs-FCs) of DMN are low and show negative correlation with the level of autism spectrum traits in individuals with autism spectrum disorder (ASD). However, it is unclear whether individual differences of autism spectrum traits are associated with the strength of rs-FCs of DMN in participants including the general population.
[Show abstract][Hide abstract] ABSTRACT: Individuals with Autism Spectrum Disorder (ASD) are thought to lack self-awareness and to experience difficulty empathising with others. Although these deficits have been demonstrated in previous studies, most of the target stimuli were constructed for typically developing (TD) individuals. We employed judgment tasks capable of indexing self-relevant processing in individuals with and without ASD. Fourteen Japanese males and one Japanese female with high-functioning ASD (17-41 years of age) and 13 Japanese males and two TD Japanese females ( 22-40 years of age), all of whom were matched for age and full and verbal intelligence quotient scores with the ASD participants, were enrolled in this study. The results demonstrated that the ventromedial prefrontal cortex was significantly activated in individuals with ASD in response to autistic characters and in TD individuals in response to non-autistic characters. Whereas the frontal-posterior network between the ventromedial prefrontal cortex and superior temporal gyrus participated in the processing of non-autistic characters in TD individuals, an alternative network was involved when individuals with ASD processed autistic characters. This suggests an atypical form of empathy in individuals with ASD toward others with ASD.
Social Cognitive and Affective Neuroscience 10/2014; 10(2). · 5.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Detection of the contingency between one's own behavior and consequent social events is important for normal social development, and impaired contingency detection may be a cause of Autism Spectrum Disorder (ASD). To depict the neural underpinnings of this contingency effect, 19 adults with ASD and 22 control participants underwent functional MRI while imitating another's actions and their actions being imitated by the other. As the extrastriate body area (EBA) receives efference copies of one's own movements, we predicted that the EBA would show an atypical response during contingency detection in ASD. We manipulated two factors: the congruency of the executed and observed actions, and the order of action execution and observation. Both groups showed the congruency effect in the bilateral EBA during imitation. When action preceded observation, the left EBA of the control group showed the congruency effect, representing the response to being imitated, indicating contingency detection. The ASD group showed a reduced contingency effect in the left EBA. These results indicate that the function of the EBA in the contingency detection is altered in ASD.
Neuroscience Research 10/2014; · 2.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study was designed to ascertain the relationship between visual attention for social information and oxytocin (OT) levels in Japanese preschool children with autism spectrum disorder (ASD). We hypothesized that poor visual attention for social information and low OT levels are crucially important risk factors associated with ASD. We measured the pattern of gaze fixation for social information using an eye-tracking system, and salivary OT levels by the Enzyme-Linked Immunosorbent Assay (ELISA). There was a positive association between salivary OT levels and fixation duration for an indicated object area in a finger-pointing movie in typically developing (TD) children. However, no association was found between these variables in children with ASD. Moreover, age decreased an individual's attention to people moving and pointed-at objects, but increased attention for mouth-in-the-face recognition, geometric patterns, and biological motions. Thus, OT levels likely vary during visual attention for social information between TD children and those with ASD. Further, aging in preschool children has considerable effect on visual attention for social information.
[Show abstract][Hide abstract] ABSTRACT: Children with attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) share many common symptoms, including attention deficit, behavioral problems, and difficulties with social skills. The aim of this study is to distinguish between ASD and ADHD by identifying the characteristic features of both the disorders, by using multidimensional assessments, including screening behavioral checklists, cognitive assessments, and comprehensive neurological battery. After screening for comorbid disorders, we carefully selected age-, sex-, IQ-, and socio-economic status-matched children with typical development (TD). In the Wechsler Intelligence Scale for children, a lower score was observed for the ASD group than for the TD group in Picture Concept, which is a subscale of Perceptual Reasoning. A lower score was shown by the ADHD group than by the TD group in the spatial working memory test in the Cambridge Neuropsychological Test Automated Battery (CANTAB®). Although ASD and ADHD have many similar symptoms, they can be differentiated by focusing on the behavioral and cognitive characteristics of executive function.
[Show abstract][Hide abstract] ABSTRACT: Background: Bipolar disorder (BD) has been linked with the manifestation of catatonia in subjects with autism spectrum disorders (ASD). Idiopathic basal ganglia calcification (IBGC) is characterized by movement disorders and various neuropsychiatric disturbances including mood disorder. Case: We present a patient with ASD and IBGC who developed catatonia presenting with prominent dystonic feature caused by comorbid BD, which was treated effectively with quetiapine. Conclusion: In addition to considering the possibility of neurodegenerative disease, careful psychiatric interventions are important to avoid overlooking treatable catatonia associated with BD in cases of ASD presenting with both prominent dystonic features and apparent fluctuation of the mood state.
[Show abstract][Hide abstract] ABSTRACT: A wide range of evidence supports the methylphenidate (MPH)-induced enhancement of prefrontal cortex (PFC) functioning and improvements in behavioral symptoms in patients with attention deficit hyperactivity disorder (ADHD). Although working memory (WM) has been hypothesized to be impaired in patients with ADHD, no pharmacological studies have examined visuospatial WM (VSWM) with near-infrared spectroscopy (NIRS).
The present study was designed to investigate the acute effects of MPH on neuropsychological performance and hemodynamic activation in children with ADHD during VSWM tasks.
The subject group included 10 boys and 1 girl previously diagnosed with ADHD. Two VSWM tasks of differing degrees of difficulty were conducted. This is the first study on the pharmacological effects of MPH in children with ADHD to evaluate hemodynamic responses in the PFC with simultaneous NIRS.
No significant differences were found in the scores for both spatial working memory (SWM) and score of spatial span (SSP) tasks between the MPH-off and MPH-on conditions. However, a significant MPH-effect on changes in oxy-hemoglobin levels in the PFC was found only in the SWM task.
These findings suggest that PFC activation might be affected by MPH, depending on the degree of difficulty of the particular task. Although the MPH-induced change on behavior may or may not be obvious, NIRS measurements might be useful for assessing the psychological effects of MPH even when performance changes were not observed in the cognitive tasks.
Child and Adolescent Psychiatry and Mental Health 01/2014; 8(1):273.
[Show abstract][Hide abstract] ABSTRACT: While patients with major depressive disorder typically have a reduced hippocampal volume, particularly in the cornu ammonis 1 (CA1), animal studies suggest that depressive mood is related to the dentate gyrus (DG). In this study, our objective was to clarify which hippocampal subregions are functionally associated with depressive mood in humans. We conducted a functional MRI (fMRI) study on 27 cognitively intact volunteers. Subjects performed a modified version of a delayed matching-to-sample task in an MRI scanner to investigate pattern separation-related activity during each phase of encoding, delay, and retrieval. In each trial, subjects learned a pair of sample cues. Functional MR images were acquired at a high spatial resolution, focusing on the hippocampus. Subjects also completed the Beck Depression Inventory (BDI), a questionnaire about depressive mood. Depending on the similarity between sample cues, activity in the DG/CA3 and medial CA1 in the anterior hippocampus changed only during encoding. Furthermore, the DG/CA3 region was more active during successful encoding trials compared to false trials. Activity in the DG/CA3 and lateral CA1 was negatively correlated with BDI scores. These results suggest that the DG/CA3 is the core region for pattern separation during the encoding phase and interacts with the medial CA1, depending on the similarity of the stimuli, in order to achieve effective encoding. Impaired activity in the DG/CA3, as well as in the lateral CA1, was found to be associated with depressive symptoms, even at a subclinical level. (238 words).
[Show abstract][Hide abstract] ABSTRACT: The objective of this study was to examine differences in episodic memory retrieval between individuals with autism spectrum disorder (ASD) and typically developing (TD) individuals. Previous studies have shown that personality similarities between readers and characters facilitated reading comprehension. Highly extraverted participants read stories featuring extraverted protagonists more easily and judged the outcomes of such stories more rapidly than did less extraverted participants. Similarly, highly neurotic participants judged the outcomes of stories with neurotic protagonists more rapidly than did participants with low levels of neuroticism. However, the impact of the similarity effect on memory retrieval remains unclear. This study tested our 'similarity hypothesis', namely that memory retrieval is enhanced when readers with ASD and TD readers read stories featuring protagonists with ASD and with characteristics associated with TD individuals, respectively.
Eighteen Japanese individuals (one female) with high-functioning ASD (aged 17 to 40 years) and 17 age- and intelligence quotient (IQ)-matched Japanese (one female) TD participants (aged 22 to 40 years) read 24 stories; 12 stories featured protagonists with ASD characteristics, and the other 12 featured TD protagonists. Participants read a single sentence at a time and pressed a spacebar to advance to the next sentence. After reading all 24 stories, they were asked to complete a recognition task about the target sentence in each story.
To investigate episodic memory in ASD, we analyzed encoding based on the reading times for and readability of the stories and retrieval processes based on the accuracy of and response times for sentence recognition. Although the results showed no differences between ASD and TD groups in encoding processes, they did reveal inter-group differences in memory retrieval. Although individuals with ASD demonstrated the same level of accuracy as did TD individuals, their patterns of memory retrieval differed with respect to response times.
Individuals with ASD more effectively retrieved ASD-congruent than ASD-incongruent sentences, and TD individuals retrieved stories with TD more effectively than stories with ASD protagonists. Thus, similarity between reader and story character had different effects on memory retrieval in the ASD and TD groups.
[Show abstract][Hide abstract] ABSTRACT: Subjects with autism spectrum disorders (ASDs) often exhibit behavioral symptoms such as aggressiveness and irritability. The purpose of this study was to examine the efficacy and the tolerability of aripiprazole switched from risperidone in children and adolescents with ASD.
This prospective, 12-week, open-label study included 9 male subjects with ASD (age range, 9-22 years; mean ± SD age, 14.8 ± 4.0 years) followed up for 12 weeks after switching to aripiprazole from risperidone. The primary outcome measures were the Clinical Global Impression-Improvement scales and the irritability subscale of the Aberrant Behavior Checklist.
The mean ± SD maintenance dosages of risperidone and aripiprazole were 0.6 ± 0.4 mg/d and 4.8 ± 4.0 mg/d, respectively. The mean ± SD scores of the irritability subscale of the Aberrant Behavior Checklist before switching to aripiprazole (baseline) and 12 weeks after switching to aripiprazole (end point) were 14.8 ± 7.6 and 13.1 ± 8.0, respectively. The mean ± SD Clinical Global Impression-Improvement score, a comparison from baseline to end point, was 2.4 ± 0.7. Mild somnolence was observed only in 1 subject. No significant changes in vital signs, weight, electrocardiogram, or laboratory measures occurred during switching to aripiprazole. Serum prolactin levels decreased significantly from 17.3 ± 9.4 ng/mL (baseline) to 2.3 ± 1.7 ng/mL (end point).
The results show that aripiprazole might be generally well tolerated and might constitute an alternative treatment of subjects with ASD who experience poor efficacy or tolerability issues with risperidone treatment. Additional long-term controlled studies are needed to evaluate the efficacy and the safety of switching to aripiprazole from other antipsychotics in subjects with ASD.
[Show abstract][Hide abstract] ABSTRACT: Patients with autism spectrum disorders (ASDs) exhibit core autistic symptoms including social impairments from early childhood and mostly show secondary disabilities such as irritability and aggressive behavior based on core symptoms. However, there are still no radical treatments of social impairments in these patients. Oxytocin has been reported to play important roles in multiple social behaviors dependent on social recognition, and has been expected as one of the effective treatments of social impairments of patients with ASDs.
We present a case of a 16-year-old girl with autistic disorder who treated by long-term administration of oxytocin nasal spray. Her autistic symptoms were successfully treated by two month administration; the girl's social interactions and social communication began to improve without adverse effects. Her irritability and aggressive behavior also improved dramatically with marked decreases in aberrant behavior checklist scores from 69 to 7.
This case is the first to illustrate long-term administration of oxytocin nasal spray in the targeted treatment of social impairments in a female with autistic disorder. This case suggests that long-term nasal oxytocin spray is promising and well-tolerated for treatment of social impairments of patients with ASDs.
[Show abstract][Hide abstract] ABSTRACT: Background: Autism spectrum disorder is a developmental disorder which is characterized by the lack of social interaction with others, including natural communication and eye contact (DSM-IV-TR, American Psychiatric Association, 2000). Individuals with autism lack self-awareness (Lombardo et al., 2009; Toichi et al., 2002) and have difficulty empathizing with others (Baron-Cohen, 1995; Lombardo et al., 2007). Although these deficits were observed by previous studies, most of the target stimuli were constructed for neurotypical individuals. It is still unclear how individuals with autism understand other people with autism.
Objectives: We investigated whether individuals with autism show self-awareness and empathize with protagonists of sentences who have autistic traits using fMRI. We hypothesized that ventromedial prefrontal cortex (vmPFC), known to be sensitive to self-relevant information processing (Lombardo et al., 2009), should be activated when judging someone similar to themselves.
Methods: 15 (2 females) high-functioning individuals with autism spectrum disorder and 15 (2 females) neurotypical control participants participated in the experiment. Age and IQs were matched between the groups. During the fMRI scan, participants read sentences and made judgments about them by using 2 buttons (Yes or No). Each sentence described the protagonist’s behavior as autistic or non-autistic. For Self judgments with an autistic protagonist, they read a sentence (e.g., I would rather be alone than with others) and made a judgment (Do you agree with the sentence?). For Other judgments with a non-autistic protagonist, they read a sentence (e.g., Yuya would rather be with others than alone) and made a judgment (Do you think you are similar to him?). Gender was matched between the participant and the protagonist.
Results: In the behavioral results, the interaction between group and protagonist was significant (F (1, 28) = 27.20, p < .05, MSe = 6.28, Prep = .99, ηp2= .49). Post hoc analysis showed that while the autism group rated Yes responses for autistic protagonists more than the control group (F (1, 28) = 16.26, p < .05, MSe = 4.55, Prep = .99, ηp2= .37), the control group rated Yes responses for non-autistic protagonists more than the autistic participants (F (1, 28) = 35.52, p < .05, MSe = 2.75, Prep = .99, ηp2= .56). Thus, both groups found matched protagonists similar to themselves. In the fMRI study, during Self and Other judgments, vmPFC was activated in both groups: when the autistic group judged protagonists with autistic behavior, and the control group judged protagonists without autistic behavior. Moreover, in the Other judgment, precuneus was activated when the autistic group judged protagonists with autistic behavior and the control group judged protagonists without autistic behavior.
Conclusions: These findings suggest that individuals with autism spectrum disorder show self-awareness toward other individuals similar to themselves as well as neurotypical individuals do. Individuals with autism are likely to empathize with other people with autism. As these findings explain the characteristics of individuals with autism, they may also contribute to improving special needs education, educational intervention, and developmental support for individuals with autism.
2012 International Meeting for Autism Research; 05/2012
[Show abstract][Hide abstract] ABSTRACT: Subjects with Pervasive Developmental Disorders (PDD) often exhibit behavioral symptoms such as aggressiveness and irritability, which are targets of psychopharmacologic intervention. This retrospective study was designed to examine children and adolescents with PDD experiencing tolerability issues with risperidone treatment, and thereby assess the efficacy and tolerability of switching to aripiprazole.
This naturalistic study included 23 subjects with PDD (16 males, 7 females, age range 9-24 years, mean age 15.1±3.9 years) diagnosed according to DSM-IV criteria and followed up for 14.9±8.4 weeks after switching to aripiprazole from risperidone. Outcome measures were the Clinical Global Impression-Severity (CGI-S) and CGI Improvement (CGI-I) scales.
The mean CGI-S scores of pre-aripiprazole treatment and post-aripiprazole treatment were, respectively 4.7±1.4 and 4.6±1.3. Mean maintenance dosages of risperidone and aripiprazole were, respectively, 0.7±0.5mg/day and 2.8±1.3mg/day. The mean CGI-I score, which shows the difference induced by switching from risperidone to aripiprazole, was 3.4±0.8 for the whole sample, suggesting that the efficacy of risperidone for treating behavioral problems of PDD was maintained by aripiprazole. Some improvement of safety/tolerability issues such as increased appetite, somnolence, hyperprolactinemia, and amenorrhea occurred after switching to aripiprazole.
Results show that switching to aripiprazole might be generally well tolerated and might constitute an alternative treatment for subjects with PDD who experience tolerability issues with risperidone treatment. Additional long-term controlled studies of PDD subjects should be undertaken to evaluate the efficacy and safety of switching to aripiprazole from other antipsychotics.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 04/2012; 37(1):128-31. · 4.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Persons with autism spectrum disorders (ASD) are known to have difficulty in eye contact (EC). This may make it difficult for their partners during face to face communication with them. To elucidate the neural substrates of live inter-subject interaction of ASD patients and normal subjects, we conducted hyper-scanning functional MRI with 21 subjects with autistic spectrum disorder (ASD) paired with typically-developed (normal) subjects, and with 19 pairs of normal subjects as a control. Baseline EC was maintained while subjects performed real-time joint-attention task. The task-related effects were modeled out, and inter-individual correlation analysis was performed on the residual time-course data. ASD-Normal pairs were less accurate at detecting gaze direction than Normal-Normal pairs. Performance was impaired both in ASD subjects and in their normal partners. The left occipital pole (OP) activation by gaze processing was reduced in ASD subjects, suggesting that deterioration of eye-cue detection in ASD is related to impairment of early visual processing of gaze. On the other hand, their normal partners showed greater activity in the bilateral occipital cortex and the right prefrontal area, indicating a compensatory workload. Inter-brain coherence in the right IFG that was observed in the Normal-Normal pairs (Saito et al., 2010) during EC diminished in ASD-Normal pairs. Intra-brain functional connectivity between the right IFG and right superior temporal sulcus (STS) in normal subjects paired with ASD subjects was reduced compared with in Normal-Normal pairs. This functional connectivity was positively correlated with performance of the normal partners on the eye-cue detection. Considering the integrative role of the right STS in gaze processing, inter-subject synchronization during EC may be a prerequisite for eye cue detection by the normal partner.
Frontiers in Human Neuroscience 01/2012; 6:268. · 2.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recent human studies have indicated that adverse parenting experiences during childhood and adolescence are associated with adulthood hypothalamus-pituitary-adrenal (HPA) axis hypoactivity. Chronic HPA axis hypoactivity inhibits hippocampal gray matter (GM) development, as shown by animal studies. However, associations among adverse parenting experiences during childhood and adolescence, HPA axis activity, and brain development, particularly hippocampal development, are insufficiently investigated in humans. In this voxel-based structural magnetic resonance imaging study, using a cross-sectional design, we examined the associations among the scores of parental bonding instrument (PBI; a self-report scale to rate the attitudes of parents during the first 16 years), cortisol response determined by the dexamethasone/corticotropin-releasing hormone test, and regional or total hippocampal GM volume in forty healthy young adults with the following features: aged between 18 and 35 years, no cortisol hypersecretion in response to the dexamethasone test, no history of traumatic events, or no past or current conditions of significant medical illness or neuropsychiatric disorders. As a result, parental overprotection scores significantly negatively correlated with cortisol response. Additionally, a significant positive association was found between cortisol response and total or regional hippocampal GM volume. No significant association was observed between PBI scores and total or regional hippocampal GM volume. In conclusion, statistical associations were found between parental overprotection during childhood and adolescence and adulthood HPA axis hypoactivity, and between HPA axis hypoactivity and hippocampal GM volume reduction in healthy young adults, but no significant relationship was observed between any PBI scores and adulthood hippocampal GM volume.
Human Brain Mapping 12/2011; 33(9):2211-23. · 6.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Individuals with autism spectrum disorders (ASD) show impaired emotional responses to self-face processing, but the underlying neural bases are unclear. Using functional magnetic resonance imaging, we investigated brain activity when 15 individuals with high-functioning ASD and 15 controls rated the photogenicity of self-face images and photographs of others' faces. Controls showed a strong correlation between photogenicity ratings and extent of embarrassment evoked by self-face images; this correlation was weaker among ASD individuals, indicating a decoupling between the cognitive evaluation of self-face images and emotional responses. Individuals with ASD demonstrated relatively low self-related activity in the posterior cingulate cortex (PCC), which was related to specific autistic traits. There were significant group differences in the modulation of activity by embarrassment ratings in the right insular (IC) and lateral orbitofrontal cortices. Task-related activity in the right IC was lower in the ASD group. The reduced activity in the right IC for self-face images was associated with weak coupling between cognitive evaluation and emotional responses to self-face images. The PCC is responsible for self-referential processing, and the IC plays a role in emotional experience. Dysfunction in these areas could contribute to the lack of self-conscious behaviors in response to self-reflection in ASD individuals.