[The Relationship between the Autistic Traits and Everyday Memory Processing in Adults with Autism Spectrum Disorder and Healthy Adults].

We investigated the association between everyday memory and autistic traits in adults with autism spectrum disorder (ASD, n=22) and healthy adults (n=20) by using the Rivermead Behavioral Memory Test (RBMT). A generalized linear model (GLM) was used to explore the relationships between the subjects' performance on the RBMT as the objective variable and the composite score of the Autism Spectrum Quotient (AQ) as the explanatory variable. Multiple models were created with the AQ subscales ('Social skills,' 'Attention-shifting,' 'Attention to details,' 'Communication,' 'Imagination'), age, gender, the full-scale intelligence quotient (FSIQ), the Patient Health Questionnaire-9 (PHQ-9), and the General Anxiety Disorder-7 (GAD-7) scale added as the moderator variables. The GLM revealed that the AQ subscale 'Social skills' significantly predicted the RBMT-total scores with age, gender, and psychological measures scores as the moderator variables (Model 4: B=0.752, 95%CI: 0.191 to 1.313, p<0.01). Also, The GLM revealed that the AQ subscale 'Communication', in addition to 'Social skills', significantly predicted the RBMT- 'Prospective memory' (Model 4: B=0.298, 95%CI: 0.19 to 0.578, p<0.05). These results indicate an influence of social skills on everyday memory functioning, highlighting the weakness of memory processing in everyday life situations among individuals with ASD.

Individual cognitive therapy reduces frontal-thalamic resting-state functional connectivity in social anxiety disorder.

Introduction: Previous neuroimaging studies in social anxiety disorders (SAD) have reported potential neural predictors of cognitive behavioral therapy (CBT)-related brain changes. However, several meta-analyses have demonstrated that cognitive therapy (CT) was superior to traditional exposure-based CBT for SAD. Objective: To explore resting-state functional connectivity (rsFC) to evaluate the response to individual CT for SAD patients. Methods: Twenty SAD patients who attended 16-week individual CT were scanned pre- and post-therapy along with twenty healthy controls (HCs). The severity of social anxiety was assessed with the Liebowitz Social Anxiety Scale (LSAS). Multi-voxel pattern analysis (MVPA) was performed on the pre-CT data to extract regions associated with a change in LSAS (∆LSAS). Group comparisons of the seed-based rsFC analysis were performed between the HCs and pre-CT patients and between the pre-and post-CT patients. Results: MVPA-based regression analysis revealed that rsFC between the left thalamus and the frontal pole/inferior frontal gyrus was significantly correlated with ∆LSAS (adjusted R2 = 0.65; p = 0.00002). Compared with HCs, the pre-CT patients had higher rsFCs between the thalamus and temporal pole and between the thalamus and superior/middle temporal gyrus/planum temporale (p < 0.05). The rsFC between the thalamus and the frontal pole decreased post-CT (p < 0.05). Conclusion: SAD patients had significant rsFC between the thalamus and temporal pole, superior/middle temporal gyrus, and planum temporale, which may be indicators of extreme anxiety in social situations. In addition, rsFC between the thalamus and the frontal pole may be a neuromarker for the effectiveness of individual CT.

Associations between prenatal exposure to volatile organic compounds and neurodevelopment in 12-month-old children: The Japan Environment and Children's Study (JECS).

In recent years, there has been an increase in the number of problems associated with neurodevelopmental disorders in children, and there has been a growing interest in the relationship between environmental chemicals and children's health. The objective of this study was to examine whether an association exists between occupational or environmental prenatal maternal exposure to volatile organic compounds and the risk of neurodevelopmental disorders in children using Japanese translations of the Ages & Stages Questionnaires, Third Edition (J-ASQ-3). An increase in the risk of neurodevelopmental delay in 12-month-old children associated with maternal exposure to formalin or formaldehyde was identified in terms of problem-solving (odds ratio (OR): 1.76, 95% confidence interval (CI): 0.99-3.12) and personal-social skills (OR: 3.32, 95% CI: 1.46-7.55). It is not clear whether or not this tendency is reversible, and whether it is observed past 12 months of age. Further research and a preventive approach are needed.

Associations between autism spectrum disorder and eating disorders with and without self-induced vomiting: an empirical study.

BACKGROUND: Although approximately 23% of anorexia nervosa (AN) patients have concomitant autism spectrum disorder (ASD), it is clinically difficult to determine ASD coexistence in patients with eating disorders. Restrictive AN is more common in younger patients and self-induced vomiting usually appears during adolescence/young adulthood, in order to prevent gaining weight caused by overeating. However, some patients are tolerant of weight gain even if they start overeating. It is important to understand the essential difference between those who vomit and those who do not vomit. In this study, we hypothesised that the absence of self-induced vomiting may be associated with the presence of ASD and aimed to assess the presence of ASD traits in each eating disorder (EDs). Clarifying this association helps to consider the coexistence of ASD in the clinical setting and can lead to the next detailed ASD evaluation, and as a result, helps to determine the appropriate treatment and support individually. METHODS: We retrospectively evaluated 43 females aged 15-45 years who attended Chiba University Hospital between 2012 and 2016 using the Eating Disorder Examination Questionnaire (EDE-Q) and Autism-Spectrum Quotient (AQ) to quantify the severity of the EDs and to identify whether ASD traits were present. RESULTS: There was no difference in the AQ score between bingeing-purging type AN and restricting type AN. However, there was significant difference in the AQ score between bulimia nervosa and binge EDs (BED). Of the 4 ED subtypes, BED had the highest ASD traits. The non-vomiting group with illness duration < 4 years had a significantly higher AQ communication score than the vomiting group with illness duration ≥4 years. CONCLUSIONS: There was a difference in the AQ score by the presence or absence of self-induced vomiting. The results of this study suggest an association between high scores on AQ and non-vomiting. Thus, evaluation of patients for the absence of self-induced vomiting while assessing them for EDs may help us to understand the association with ASD traits.

Cognitive-behavioral family therapy as psychoeducation for adolescents with high-functioning autism spectrum disorders: Aware and Care for my Autistic Traits (ACAT) program study protocol for a pragmatic multisite randomized controlled trial.

BACKGROUND: One aim of an autism spectrum disorder (ASD) diagnosis is to obtain special support for the disorder, though this does not guarantee practical support. We developed a psychoeducational program using cognitive-behavioral therapy (CBT) and Aware and Care for my Autistic Traits (ACAT) for Japanese adolescents with high-functioning ASD and their parents. METHODS: This multisite study is a randomized controlled trial. In total, 24 participants will be assigned to the ACAT group and 24 to the treatment-as-usual (TAU) group. The ACAT group will receive a weekly 100-min session for 6 weeks, regular medical care, and one follow-up session. In this ongoing clinical trial, we will compare the scores of the measures recorded in the pre- and post-intervention stages between the ACAT and TAU groups. A total of 41 patients out of a target of 48 have participated in the trial to date. The primary outcome measure is the Autism Knowledge Questionnaire. Secondary outcome measures include Barriers to Access to Care Evaluation 3rd Edition, the Strengths and Difficulties Questionnaire, the Vineland Adaptive Behavior Scales second edition, the Parenting Resilience Elements Questionnaire, the General Health Questionnaire 12, and the Depression Self-Rating Scale for Children assessments, as well as an electroencephalographic recording. DISCUSSION: It is expected that participants in the ACAT group will significantly increase their self-understanding and awareness of ASD symptoms compared to those in the TAU group. Additionally, the ACAT group is expected to exhibit improved social adaptation and mental health if children and parents are able to better understand the ASD characteristics through sessions. This intervention will contribute to the establishment of an effective evidence-based treatment strategy for adolescents with ASD. TRIAL REGISTRATION: UMIN Register 000029851 . Registered on January 06, 2018.

Hemodynamic responses in prefrontal cortex and personality characteristics in patients with bulimic disorders: a near-infrared spectroscopy study.

PURPOSE: This study sought to identify the prefrontal cortex hemodynamic response that is dependent on cognitive performance in patients with bulimic disorders (BD), and investigate its association with personality characteristics. METHODS: Nineteen female patients with BD and 23 healthy women were recruited. Their personality characteristics related to eating disorders were examined using a self-reporting questionnaire, namely the eating disorder inventory-2 (EDI-2). Cerebral blood flow response in the prefrontal cortex during the digit span backward task (DSBT) was measured using near-infrared spectroscopy (NIRS). Change in oxygenated hemoglobin concentration (ΔoxyHb), obtained using NIRS, were used as an index of brain activity. Further, the relationship between prefrontal cortical activity and personality characteristics was investigated in patients with BD. RESULTS: The cognitive performance of patients with BD was significantly lower in the DSBT compared with healthy subjects. There was no difference between the groups in ΔoxyHb during the task. Task scores of patients with BD correlated with asceticism and perfectionism. Moreover, the asceticism score was negatively correlated with ΔoxyHb of the bilateral prefrontal cortex in patients with BD. CONCLUSION: The results suggest that cognitive performance and brain activity induced during DSBT might be affected by asceticism in BD patients. LEVEL OF EVIDENCE: III, case-control study.

Alterations of mental defeat and cognitive flexibility during cognitive behavioral therapy in patients with major depressive disorder: a single-arm pilot study.

OBJECTIVE: Mental defeat affects the occurrence and chronicity of depression and cognitive flexibility. This study aimed to examine changes in mental defeat and cognitive flexibility scores after cognitive behavioral therapy including IR. In the intervention group, patients with depression (n = 18, mean age = 37.89 years) received 15 cognitive behavioral therapy sessions. Patients completed the Beck Depression Inventory-II; Mental Defeat Scale; Cognitive Flexibility Scale; EuroQol five dimensions questionnaire; Patient Health Questionnaire-9 and seven-item Generalized Anxiety Disorder Scale before the intervention, after six sessions, and post-intervention. The healthy control group (n = 33, mean age = 37.91) completed all scales once and did not receive treatment. RESULTS: Post-cognitive behavioral therapy, a significant decrease was observed in Beck Depression Inventory-II, Mental Defeat Scale, Cognitive Flexibility Scale, and Patient Health Questionnaire-9 scores. Although mental defeat and cognitive flexibility did not reach the level of the healthy control group, they demonstrated improvement. Therefore, when treating depression, mental defeat and cognitive flexibility should be measured in addition to depressive symptoms. Trial registration This study was registered retrospectively in the national UMIN Clinical Trials Registry on July 25, 2016 (registration ID: UMIN000023320).

Insensitivity of auditory mismatch negativity to classical fear conditioning and extinction in healthy humans.

The relationship between auditory mismatch negativity (MMN) and the neural cognitive processes of fear has been suggested in both healthy participants and patients with fear-related mental disorders such as post-traumatic stress disorder and panic disorder. The present study sought to confirm whether the MMN is affected by classical fear conditioning in healthy participants. MMN amplitude, N1 amplitude, and skin conductance level (SCL) in 20 healthy volunteers during a fear-conditioning paradigm consisting of three phases (habituation, fear acquisition, and fear extinction) were recorded. Red and blue light signals were presented as the conditioned stimuli CS+ (threat cue) and CS- (safety cue), respectively. In addition, an aversive electrical stimulus was delivered as the unconditioned stimulus with CS+ in the fear-acquisition phase. No MMN amplitude changes were observed between the CS types during the three phases. In the acquisition phase, the mean SCL during CS+ was significantly higher than that during CS-. The MMN amplitude and deviant N1 amplitude in the extinction phase were significantly lower than those in the other phases regardless of the CS type. Despite the clear alteration of SCL between CS types in the acquisition phase, no significant differences in MMN were observed. Decreased MMN and deviant N1 in the fear-extinction phase were considered to be mainly due to decreased arousal or attention level. Results indicate that the auditory MMN amplitude was not affected by the cognitive process of fear recognized by other sense modalities.

Spontaneous recovery of fear differs among early - late adolescent and adult male mice.

Adolescence is a vulnerable period for developing anxiety-related mental disorders such as post-traumatic stress disorder (PTSD), which requires a long-term course of therapy when a traumatic event has been experienced during childhood. However, the biological mechanism underlying these age-dependent characteristics remains unclear. In the present study, we used early adolescent, late adolescent and adult (4-, 8-, and 15-week old) male mice to examine age differences in fear memory, fear extinction, and spontaneous recovery of fear. We also measured the activation of extracellular signal-regulated kinase (ERK) 2 in the dorsal hippocampus (dHip) and the basolateral amygdala (BLA) following a spontaneous recovery test. Our major findings were as follows: (1) early adolescent and adult mice did not recover the fear response; only late adolescent mice recovered the fear response. (2) The ERK2 in the dHip was more activated after the spontaneous recovery test in late adolescent mice than in adult mice, and the ERK2 in the BLA was more activated after the spontaneous recovery test in adult mice than in late adolescent mice. These results suggest that there exists a unique period in which spontaneous recovery occurs and that these late adolescent behavioral signatures may be related to alteration in the ERK2 phosphorylation in the dHip and BLA.

Paternal methyl donor deficient diets during development affect male offspring behavior and memory-related gene expression in mice.

It has become increasingly evident that the methylation of DNA, known as an epigenetic marker, affects behavior in animals. In our previous study, a methyl-donors (folate, methionine, and choline)-deficient (FMCD) diet during the juvenile period could be shown to affect anxiety-like behavior and fear memory, accompanied by alteration in some gene expression and their methylations in the hippocampus. One question is whether the fear memory of a parent affects the fear responses of offspring. To explore this question in the present study, C57BL/6 J male (F0) mice were given a FMCD diet from 3 to 12 weeks of age. After confirming the effect of the FMCD diet on the behavior and gene expression of F0 mice, their male offspring (F1-FMCD mice) were examined using the same behavioral batteries and genetic analysis. F0 diet-based differences in F1 behavior were observed, accompanied by the differences in the expression of memory-related genes (Camk2α and PP1) and promoter methylation of the PP1 gene in the hippocampus. Our results add evidence that behavior and gene expression of the F1 generation could be altered due to differences in the father's intake of methyl-donor nutrients.

Differential effects of high-definition transcranial direct current stimulation on verbal working memory performance according to sensory modality.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that modulates cortical excitability in a polarity-dependent manner. The diffuse nature of tDCS makes it difficult to investigate the optimal stimulation parameters for more effective and specific cognitive enhancement; to address this deficit, a more focalized stimulation technique, high-definition tDCS (HD-tDCS), has been developed. To date, only a few studies have examined the effects of HD-tDCS on cognitive functions; and none has investigated the effects of HD-tDCS on different sensory modalities of verbal working memory. Therefore, the present study compared the effects of prefrontal HD-tDCS on visual and auditory working memory tasks. Twenty healthy participants completed three sessions of each modality task, and additionally a sustained attention task. Anodal or sham HD-tDCS was administered to the dorsolateral prefrontal cortex (DLPFC) during the second session of the task in a parallel, single-blind design. Anodal stimulation to the DLPFC significantly enhanced the visual verbal working memory accuracy during and 20 min after the stimulation. In contrast, auditory verbal working memory performance was not modulated by anodal stimulation. Anodal stimulation to the DLPFC showed no effect on any other cognitive functions. The present study revealed the differential effects of HD-tDCS on two different modalities (visual vs. auditory) of working memory performance: important preliminary findings for the establishment of a more effective and specific use of tDCS.

Gender-specific associations of depression and anxiety symptoms with mental rotation.

BACKGROUND: Men score higher on mental rotation tasks compared to women and suffer from depression and anxiety at half the rate of women. The objective of this study was to confirm the gender-specific effects of depression and anxiety on mental rotation performance. METHODS: We collected data in non-experimental conditions from 325 university students at three universities. Participants completed rating scales of depressive and anxiety symptoms, and then simultaneously performed a mental rotation task using tablet devices. RESULTS: We observed no significant difference between men and women in the depressive and anxiety symptoms and task response time. Men had a significantly higher correct answer rate compared with women. The scores of depression and anxiety of all participants were positively correlated. Task response time correlated positively with intensity of depressive symptoms and anxiety in women, but not in men. Women with high depressive symptoms had significantly longer response times than did women with low depressive symptoms, while men had no differences due to depressive symptoms. LIMITATIONS: We did not directly examine brain functions; therefore, the underlying neurobiological results are only based on previous knowledge and action data. CONCLUSIONS: The pathology of depression and anxiety was reflected in the correct answer rate and response time in relation to the gender difference of brain function used in mental rotation.

Development of the fear regulation system from early adolescence to young adulthood in female mice.

Onset of fear-related disorders such as post-traumatic stress disorder is enhanced from adolescence until adulthood. However, the biological mechanisms underlying this vulnerability remain unclear. Therefore, we investigated contextual fear memory and extinction in 4-, 6-, 8-, 10-, and 15-week-old female mice. We also measured phosphorylation of ERK2 in the medial prefrontal cortex (mPFC) and the dorsal hippocampus following fear conditioning or extinction in 6- and 15-week-old mice. We found that 10- and 15-week-old mice showed stronger fear memory and more resistance to fear extinction than 6-week-old mice. Moreover, 15-week-old mice showed lower ERK2 phosphorylation levels following fear extinction in the mPFC than those 6 weeks old. Our results suggest that female mice acquire strong fear memory and resistance to fear extinction throughout adulthood, which may be related to alteration in ERK2 activation in the mPFC.

Does cognitive behavioral therapy alter mental defeat and cognitive flexibility in patients with panic disorder?

OBJECTIVE: Mental defeat and cognitive flexibility have been studied as explanatory factors for depression and posttraumatic stress disorder. This study examined mental defeat and cognitive flexibility scores in patients with panic disorder (PD) before and after cognitive behavioral therapy (CBT), and compared them to those of a gender- and age-matched healthy control group. RESULTS: Patients with PD (n = 15) received 16 weekly individual CBT sessions, and the control group (n = 35) received no treatment. Patients completed the Mental Defeat Scale and the Cognitive Flexibility Scale before the intervention, following eight CBT sessions, and following 16 CBT sessions, while the control group did so only prior to receiving CBT (baseline). The patients' pre-CBT Mental Defeat and Cognitive Flexibility Scale scores were significantly higher on the Mental Defeat Scale and lower on the Cognitive Flexibility Scale than those of the control group participants were. In addition, the average Mental Defeat Scale scores of the patients decreased significantly, from 22.2 to 12.4, while their average Cognitive Flexibility Scale scores increased significantly, from 42.8 to 49.5. These results suggest that CBT can reduce mental defeat and increase cognitive flexibility in patients with PD Trial registration The study was registered retrospectively in the national UMIN Clinical Trials Registry on June 10, 2016 (registration ID: UMIN000022693).

Comparison of brain activity between motor imagery and mental rotation of the hand tasks: a functional magnetic resonance imaging study.

Motor imagery (MI) has been considered effective in learning and practicing movements in many fields. However, when evaluating the effectiveness of this technique, the examiner has no way of assessing the participant's motor imagery process. As an alternative, we have been exploring a mental body-part rotation task, in which the examiner can estimate the participant's motivation and ability to sustain attention through the scored results. In this study, we aimed to investigate the possible application of a mental rotation (MRot) task and used fMRI to compare the brain activity during the MRot task with that during an MI task in healthy volunteers. Increased blood oxygenation level-dependent signals were observed bilaterally in the premotor areas and supplementary motor area during performance of both MI and MRot tasks. Our findings suggest that MRot could be an alternative to MI.

Increased Subjective Distaste and Altered Insula Activity to Umami Tastant in Patients with Bulimia Nervosa.

The aim of this study was to examine differences in brain neural activation in response to monosodium glutamate (MSG), the representative component of umami, between patients with bulimia nervosa (BN) and healthy women (HW) controls. We analyzed brain activity after ingestion of an MSG solution using functional magnetic resonance imaging (fMRI) in a group of women with BN (n = 18) and a group of HW participants (n = 18). Both groups also provided a subjective assessment of the MSG solution via a numerical rating scale. The BN group subjectively rated the MSG solution lower in pleasantness and liking than the control group, although no difference in subjective intensity was noted. The fMRI results demonstrated greater activation of the right insula in the BN group versus the control group. Compared with the HW controls, the BN patients demonstrated both altered taste perception-related brain activity and more negative hedonic scores in response to MSG stimuli. Different hedonic evaluation, expressed as the relative low pleasing taste of umami tastant and associated with altered insula function, may explain disturbed eating behaviors, including the imbalance in food choices, in BN patients.

Feasibility of cognitive remediation therapy for adults with autism spectrum disorders: a single-group pilot study.

BACKGROUND: Set-shifting (SS) difficulties and weak central coherence (CC) are commonly associated with autism spectrum disorders (ASD). Cognitive remediation therapy (CRT) aims to improve such cognitive processing; however, there are no reports on CRT for patients with ASD. This pilot study aimed to provide preliminary evidence to support the use of CRT for individuals with ASD and provide data to inform future studies. PARTICIPANTS AND METHODS: Nineteen individuals with ASD were recruited and administered a series of neuropsychological and questionnaire measures to examine cognitive function and clinical outcomes such as anxiety and depression. Participants received CRT, and cognitive function and clinical variables were re-evaluated at postintervention and after 3 months. RESULTS: The participants demonstrated significant improvement in CC and anxiety at postintervention, which was maintained at 3-month follow-up. Although SS scores had improved with a large effect size, this was not statistically significant. CONCLUSION: CRT improved CC and anxiety scores for individuals with ASD, suggesting that CRT is an effective treatment for individuals with ASD.

Repetitive Transcranial Magnetic Stimulation Changes Cerebral Oxygenation on the Left Dorsolateral Prefrontal Cortex in Bulimia Nervosa: A Near-Infrared Spectroscopy Pilot Study.

Previous studies showed that food craving in eating disorders can be weakened with high-frequency repetitive transcranial magnetic stimulation (rTMS) on the left dorsolateral prefrontal cortex (DLPFC). The aims of this study were to assess cerebral oxygenation change induced with rTMS and to assess the short-term impact of rTMS on food craving and other bulimic symptoms in patients with bulimia nervosa (BN). Eight women diagnosed with BN according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria participated in this study. We measured haemoglobin concentration changes in the DLPFC with near-infrared spectroscopy during cognitive tasks measuring self-regulatory control in response to food photo stimuli, both at baseline and after a single session of rTMS. Subjective ratings for food cravings demonstrated significant reduction. A significant decrease in cerebral oxygenation of the left DLPFC was also observed after a single session of rTMS. Measurement with NIRS after rTMS intervention may be applicable for discussing the mechanisms underlying rTMS modulation in patients with BN.

Longitudinal Follow-Up of Mirror Movements after Stroke: A Case Study.

Mirror movement (MM), or visible involuntary movements of a relaxed hand during voluntary fine finger movements of an activated opposite hand, can be observed in the hand that is on the unaffected side of patients with stroke. In the present study, we longitudinally examined the relationship between voluntary movement of the affected hand and MM in the unaffected hand in a single case. We report a 73-year-old woman with a right pontine infarct and left moderate hemiparesis. MM was observed as an extension movement of the unaffected right index finger during extension movement of the affected left index finger. The affected right index movement was found to increase, while MM of the unaffected left index finger was observed to decrease with time. These results indicate that the assessment of MM might be useful for studying the process of motor recovery in patients with stroke.