Electrophysiological and Behavioral Outcomes of Berard Auditory Integration Training (AIT) in Children with Autism Spectrum Disorder

Autism is a pervasive developmental disorder of childhood characterized by deficits in social interaction, language, and stereotyped behaviors along with a restricted range of interests. It is further marked by an inability to perceive and respond to social and emotional signals in a typical manner. This might due to the functional disconnectivity of networks important for specific aspects of social cognition and behavioral control resulting in deficits of sensory information integration. According to several recent theories sensory processing and integration abnormalities may play an important role in impairments of perception, cognition, and behavior in individuals with autism. Among these sensory abnormalities, auditory perception distortion may contribute to many typical symptoms of autism. The present study used Berard’s technique of auditory integration training (AIT) to improve sound integration in children with autism. It also aimed to understand the abnormal neural and functional mechanisms underlying sound processing distortion in autism by incorporating behavioral, psychophysiological and neurophysiological outcomes. It was proposed that exposure to twenty 30-min AIT sessions (total 10 h of training) would result in improved behavioral evaluation scores, improve profile of cardiorespiratory activity, and positively affect both early [N1, mismatch negativity (MMN)] and late (P3) components of evoked potentials in auditory oddball task. Eighteen children with autism spectrum disorder (ASD) participated in the study. A group of 16 typically developing children served as a contrast group in the auditory oddball task. Autonomic outcomes of the study reflected a linear increase of heart rate variability measures and respiration rate. Comparison of evoked potential characteristics of children with ASD versus typically developing children revealed several group difference findings, more specifically, a delayed latency of N1 to rare and frequent stimuli, larger MMN; higher P3a to frequent stimuli, and at the same time delayed latency of P3b to rare stimuli in the autism group. Post-AIT changes in evoked potentials could be summarized as a decreased magnitude of N1 to rare stimuli, marginally lower negativity of MMN, and decrease of the P3a to frequent stimuli along with delayed latency and higher amplitude of the P3b to the rare stimuli. These evoked potential changes following completion of Berard AIT course are in a positive direction, making them less distinct from those recorded in age-matched group of typical children, thus could be considered as changes towards normalization. Parental questionnaires clearly demonstrated improvements in behavioral symptoms such as irritability, hyperactivity, repetitive behaviors and other important behavioral domains. The results of the study propose that more controlled research is necessary to document behavioral and psychophysiological changes resulting from Berard AIT and to provide explanation of the neural mechanisms of how auditory integration training may affect behavior and psychophysiological responses of children with ASD.     

Aberrant Interference of Auditory Negative Words on Attention in Patients with Schizophrenia

Previous research suggests that deficits in attention-emotion interaction are implicated in schizophrenia symptoms. Although disruption in auditory processing is crucial in the pathophysiology of schizophrenia, deficits in interaction between emotional processing of auditorily presented language stimuli and auditory attention have not yet been clarified. To address this issue, the current study used a dichotic listening task to examine 22 patients with schizophrenia and 24 age-, sex-, parental socioeconomic background-, handedness-, dexterous ear-, and intelligence quotient-matched healthy controls. The participants completed a word recognition task on the attended side in which a word with emotionally valenced content (negative/positive/neutral) was presented to one ear and a different neutral word was presented to the other ear. Participants selectively attended to either ear. In the control subjects, presentation of negative but not positive word stimuli provoked a significantly prolonged reaction time compared with presentation of neutral word stimuli. This interference effect for negative words existed whether or not subjects directed attention to the negative words. This interference effect was significantly smaller in the patients with schizophrenia than in the healthy controls. Furthermore, the smaller interference effect was significantly correlated with severe positive symptoms and delusional behavior in the patients with schizophrenia. The present findings suggest that aberrant interaction between semantic processing of negative emotional content and auditory attention plays a role in production of positive symptoms in schizophrenia. (224 words)     

Omega-3 fatty acids are related to abnormal emotion processing in adolescent boys with attention deficit hyperactivity disorder

BackgroundIn addition to the core symptoms, attention deficit hyperactivity disorder (ADHD) is associated with poor emotion regulation. There is some evidence that children and young adults with ADHD have lower omega-3 levels and that supplementation with omega-3 can improve both ADHD and affective symptoms. We therefore investigated differences between ADHD and non-ADHD children in omega-3/6 fatty acid plasma levels and the relationship between those indices and emotion-elicited event-related potentials (ERPs).MethodsChildren/adolescents with (n=31) and without ADHD (n=32) were compared in their plasma omega-3/6 indices and corresponding ERPs during an emotion processing task.ResultsChildren with ADHD had lower mean omega-3/6 and ERP abnormalities in emotion processing, independent of emotional valence relative to control children. ERP abnormalities were significantly associated with lower omega-3 levels in the ADHD group.ConclusionsThe findings reveal for the first time that lower omega-3 fatty acids are associated with impaired emotion processing in ADHD children.     

Evoked potentials in the brain of adolescents in norm and those with attention deficit during recognition of short-term acoustic stimuli

The effect of stimulus duration on auditory event-related potentials and performance of oddball task was studied in normal children and those with attention-deficit symptoms. Mismatch negativity was absent on presentation of short-term (11 ms) stimuli and present with longer stimuli (50 ms). The adolescents with deficit of attention performed much worse (errors of omission) with the short stimuli. The RT was significantly larger in subjects with attention-deficit with all types of tested stimulus duration. They also manifested a smaller P3b amplitude in response to task-relevant deviant stimuli and larger N2b peaks in response to the standard stimuli. It was possible to differentiate between the MMN and the N2b components owing to the fact that the MMN was absent with shorter stimuli. The findings suggest that there is a deficit in processing of sensory information at the cortical level in subjects with the attention-deficit symptoms.     

Reward Anticipation in Ventral Striatum and Individual Sensitivity to Reward: A Pilot Study of a Child-Friendly fMRI Task

Reward processing has been implicated in developmental disorders. However, the classic task to probe reward anticipation, the monetary incentive delay task, has an abstract coding of reward and no storyline and may therefore be less appropriate for use with developmental populations. We modified the task to create a version appropriate for use with children. We investigated whether this child-friendly version could elicit ventral striatal activation during reward anticipation in typically developing children and young adolescents (aged 9.5–14.5). In addition, we tested whether our performance-based measure of reward sensitivity was associated with anticipatory activity in ventral striatum. Reward anticipation was related to activity in bilateral ventral striatum. Moreover, we found an association between individual reward sensitivity and activity in ventral striatum. We conclude that this task assesses ventral striatal activity in a child-friendly paradigm. The combination with a performance-based measure of reward sensitivity potentially makes the task a powerful tool for developmental imaging studies of reward processing.     

Contextual Social Cognition Impairments in Schizophrenia and Bipolar Disorder

Background

The ability to integrate contextual information with social cues to generate social meaning is a key aspect of social cognition. It is widely accepted that patients with schizophrenia and bipolar disorders have deficits in social cognition; however, previous studies on these disorders did not use tasks that replicate everyday situations.

Methodology/Principal Findings

This study evaluates the performance of patients with schizophrenia and bipolar disorders on social cognition tasks (emotional processing, empathy, and social norms knowledge) that incorporate different levels of contextual dependence and involvement of real-life scenarios. Furthermore, we explored the association between social cognition measures, clinical symptoms and executive functions. Using a logistic regression analysis, we explored whether the involvement of more basic skills in emotional processing predicted performance on empathy tasks. The results showed that both patient groups exhibited deficits in social cognition tasks with greater context sensitivity and involvement of real-life scenarios. These deficits were more severe in schizophrenic than in bipolar patients. Patients did not differ from controls in tasks involving explicit knowledge. Moreover, schizophrenic patients’ depression levels were negatively correlated with performance on empathy tasks.

Conclusions/Significance

Overall performance on emotion recognition predicted performance on intentionality attribution during the more ambiguous situations of the empathy task. These results suggest that social cognition deficits could be related to a general impairment in the capacity to implicitly integrate contextual cues. Important implications for the assessment and treatment of individuals with schizophrenia and bipolar disorders, as well as for neurocognitive models of these pathologies are discussed.     

Facial and Prosodic Emotion Recognition Deficits Associate with Specific Clusters of Psychotic Symptoms in Schizophrenia

Background

Patients with schizophrenia perform significantly worse on emotion recognition tasks than healthy participants across several sensory modalities. Emotion recognition abilities are correlated with the severity of clinical symptoms, particularly negative symptoms. However, the relationships between specific deficits of emotion recognition across sensory modalities and the presentation of psychotic symptoms remain unclear. The current study aims to explore how emotion recognition ability across modalities and neurocognitive function correlate with clusters of psychotic symptoms in patients with schizophrenia.

Methods

111 participants who met the DSM-IV diagnostic criteria for schizophrenia and 70 healthy participants performed on a dual-modality emotion recognition task, the Diagnostic Analysis of Nonverbal Accuracy 2-Taiwan version (DANVA-2-TW), and selected subscales of WAIS-III. Of all, 92 patients received neurocognitive evaluations, including CPT and WCST. These patients also received the PANSS for clinical evaluation of symptomatology.

Results

The emotion recognition ability of patients with schizophrenia was significantly worse than healthy participants in both facial and vocal modalities, particularly fearful emotion. An inverse correlation was noted between PANSS total score and recognition accuracy for happy emotion. The difficulty of happy emotion recognition and earlier age of onset, together with the perseveration error in WCST predicted total PANSS score. Furthermore, accuracy of happy emotion and the age of onset were the only two significant predictors of delusion/hallucination. All the associations with happy emotion recognition primarily concerned happy prosody.

Discussion

Deficits in emotional processing in specific categories, i.e. in happy emotion, together with deficit in executive function, may reflect dysfunction of brain systems underlying severity of psychotic symptoms, in particular the positive dimension.     

Gender difference in N170 elicited under oddball task

Background

Some studies have reported gender differences in N170, a face-selective event-related potential (ERP) component. This study investigated gender differences in N170 elicited under oddball paradigm in order to clarify the effect of task demand on gender differences in early facial processing.

Findings

Twelve males and 10 females discriminated targets (emotional faces) from non-targets (emotionally neutral faces) under an oddball paradigm, pressing a button as quickly as possible in response to the target. Clear N170 was elicited in response to target and non-target stimuli in both males and females. However, females showed more negative amplitude of N170 in response to target compared with non-target, while males did not show different N170 responses between target and non-target.

Conclusions

The present results suggest that females have a characteristic of allocating attention at an early stage when responding to faces actively (target) compared to viewing faces passively (non-target). This supports previous findings suggesting that task demand is an important factor in gender differences in N170.     

Psychopathology in 7‐year‐old children with familial high risk of developing schizophrenia spectrum psychosis or bipolar disorder – The Danish High Risk and Resilience Study ‐ VIA 7, a population‐based cohort study

This study aimed to compare the psychopathological profiles of children at familial high risk of schizophrenia spectrum psychosis (FHR‐SZ) or bipolar disorder (FHR‐BP) with population‐based controls. We used Danish nationwide registers to retrieve a cohort of 522 seven‐year‐old children of parents with schizophrenia spectrum psychosis (N=202), bipolar disorder (N=120) or none of these disorders (N=200). Psychopathology was assessed by reports from multiple informants, including children, parents and teachers. Lifetime DSM‐IV diagnoses were ascertained by blinded raters through the Schedule for Affective Disorders and Schizophrenia for School‐Age Children. The dimensional assessment of psychopathology was performed by the Child Behavior Checklist, the Teacher's Report Form, a modified version of the ADHD‐Rating Scale, the Test Observation Form, and the State‐Trait Anxiety Inventory for Children. Current level of functioning was evaluated using the Children's Global Assessment Scale (CGAS). The prevalence of lifetime psychiatric diagnoses was significantly higher in both FHR‐SZ children (38.7%, odds ratio, OR=3.5, 95% confidence interval, CI: 2.2‐5.7, p < 0.001) and FHR‐BP children (35.6%, OR=3.1, 95% CI: 1.8‐5.3, p < 0.001) compared with controls (15.2%). FHR‐SZ children displayed significantly more dimensional psychopathology on all scales and subscales compared with controls except for the Anxious subscale of the Test Observation Form. FHR‐BP children showed higher levels of dimensional psychopathology on several scales and subscales compared with controls, but lower levels compared with FHR‐SZ children. Level of functioning was lower in both FHR‐SZ children (CGAS mean score = 68.2; 95% CI: 66.3‐70.2, p < 0.0001) and FHR‐BP children (73.7; 95% CI: 71.2‐76.3, p < 0.05) compared with controls (77.9; 95% CI: 75.9‐79.9). In conclusion, already at the age of seven, FHR‐SZ and FHR‐BP children show a higher prevalence of a broad spectrum of categorical and dimensional psychopathology compared with controls. These results emphasize the need for developing early intervention strategies towards this vulnerable group of children.     

Abnormal neural responses to social exclusion in schizophrenia

Social exclusion is an influential concept in politics, mental health and social psychology. Studies on healthy subjects have implicated the medial prefrontal cortex (mPFC), a region involved in emotional and social information processing, in neural responses to social exclusion. Impairments in social interactions are common in schizophrenia and are associated with reduced quality of life. Core symptoms such as delusions usually have a social content. However little is known about the neural underpinnings of social abnormalities. The aim of this study was to investigate the neural substrates of social exclusion in schizophrenia. Patients with schizophrenia and healthy controls underwent fMRI while participating in a popular social exclusion paradigm. This task involves passing a 'ball' between the participant and two cartoon representations of other subjects. The extent of social exclusion (ball not being passed to the participant) was parametrically varied throughout the task. Replicating previous findings, increasing social exclusion activated the mPFC in controls. In contrast, patients with schizophrenia failed to modulate mPFC responses with increasing exclusion. Furthermore, the blunted response to exclusion correlated with increased severity of positive symptoms. These data support the hypothesis that the neural response to social exclusion differs in schizophrenia, highlighting the mPFC as a potential substrate of impaired social interactions.     

Waist to hip ratio and breast size modulate the processing of female body silhouettes: An EEG study

Waist-to-hip ratio (WHR) and breast size are considered important biological features defining female body attractiveness; but their neurophysiological correlates remain largely unknown. To shed light on this issue, behavioral and electroencephalographic responses were recorded while healthy heterosexual men and women completed an oddball task, which was then followed by an attractiveness judgement task. In both cases participants were presented with female body forms that combined 0.6, 0.7 or 0.8 WHRs with small or large breast sizes. Brain activity dynamics were explored using temporal principal component analysis of the event-related potentials data. Variance in the data was explained mostly by eight temporal factors for the oddball task and six for the attractiveness judgement task. Lower WHRs seemed to gather larger processing resources than higher WHRs at early perceptual-related processes during the oddball task. The less attractive WHRs and breast sizes, in contrast, seemed to boost allocation of resources later in the processing stream, which may be due to a negativity bias enhancing evaluation and decision-making processes. This inference is supported by results from the attractiveness judgement task, although the observer's gender may also play a role. Finally, LORETA analysis of the temporal factors indicate that variations in WHR may modulate activation of frontal regions, such as the anterior cingulate and orbitofrontal cortex, that are related with reward processing and decision-making; while variations in breast size may influence activity in posterior parietal regions involved in human body perception. This paper highlights the biological importance of female body physical features in defining attractiveness, and the neurophysiological correlates that are implicated.     

Event-related potentials in schizotypal personality disorder and schizophrenia

The article analyzes event-related potentials in the Go/NoGo test of patients with schizophrenia and schizotypal personality disorder in relation to healthy subjects. Differences identified in the group of patients with schizophrenia are consistent with previous studies and indicate disruption in processes associated with different stages of visual information processing and executive functions. Specific features of brain activity in patients with schizotypal personality disorder were significantly less pronounced and presumably pointed to changes in the processes of attention redistribution and action monitoring. The results agree well with the clinical symptoms of schizophrenia and schizotypal personality disorder, so that this technique can be considered a possible additional diagnostic criterion for these disorders.     

The Development of Associate Learning in School Age Children

Associate learning is fundamental to the acquisition of knowledge and plays a critical role in the everyday functioning of the developing child, though the developmental course is still unclear. This study investigated the development of visual associate learning in 125 school age children using the Continuous Paired Associate Learning task. As hypothesized, younger children made more errors than older children across all memory loads and evidenced decreased learning efficiency as memory load increased. Results suggest that age-related differences in performance largely reflect continued development of executive function in the context of relatively developed memory processes.     

年龄相关的情绪偏向效应的时间进程

来自记忆、注意和决策等领域的大量研究发现,在加工情绪刺激时老年人具有正性情绪偏向或负性情绪规避的特点.本研究采用oddball变式,将情绪面孔图片作为分心刺激呈现.实验过程中记录被试脑电,考察不同情绪效价对脑电波的影响,同时考察老年人在非任务相关条件下情绪加工和情绪调节的时间进程.研究发现,在相对早期时间窗口(270~460 ms),年轻组脑电不受情绪效价影响,而老年组中悲伤情绪面孔较之快乐和中性情绪面孔引发了一个更大的正成分(P3a).在晚期时间窗口(500~850 ms),年轻组中悲伤情绪面孔吸引了被试更多注意并引发了一个更大的正性慢波.相反,老年组在晚期加工阶段,情绪效价效应消失.研究揭示了老年人和年轻人在加工非任务相关的情绪刺激时存在的时间进程差异,年龄相关的正性情绪效应发生在晚期时间窗口,表现为年轻组的负性情绪偏向和老年组的无情绪偏向.研究结果为社会情绪选择理论提供了来自脑电数据的支持.     

Testosterone Is Inversely Related to Brain Activity during Emotional Inhibition in Schizophrenia

Sex steroids affect cognitive function as well as emotion processing and regulation. They may also play a role in the pathophysiology of schizophrenia. However, the effects of sex steroids on cognition and emotion-related brain activation in schizophrenia are poorly understood. Our aim was to determine the extent to which circulating testosterone relates to brain activation in men with schizophrenia compared to healthy men during cognitive-emotional processing. We assessed brain activation in 18 men with schizophrenia and 22 age-matched healthy men during an emotional go/no-go task using fMRI and measured total serum testosterone levels on the same morning. We performed an ROI analysis to assess the relationship between serum testosterone and brain activation, focusing on cortical regions involved the emotional go/no-go task. Slower RT and reduced accuracy was observed when participants responded to neutral stimuli, while inhibiting responses to negative stimuli. Healthy men showed a robust increase in activation of the middle frontal gyrus when inhibiting responses to negative stimuli, but there was no significant association between activation and serum testosterone level in healthy men. Men with schizophrenia showed a less pronounced increase in activation when inhibiting responses to negative stimuli; however, they did show a strong inverse association between serum testosterone level and activation of the bilateral middle frontal gyrus and left insula. Additionally, increased accuracy during inhibition of response to negative words was associated with both higher serum testosterone levels and decreased activation of the middle frontal gyrus in men with schizophrenia only. We conclude that endogenous hormone levels, even within the normal range, may play an enhanced modulatory role in determining the neural and behavioural response during cognitive-emotional processing in schizophrenia.     

Features of the spectral power of the EEG rhythms in autistic children and their relation with the progress of different symptoms in schizophrenia

Right hemispheric dominance of the baseline alpha-band spectral power was revealed in 5-7 years boys with autism. This feature persisted during performance of a cognitive task (counting). Also, boys with autism showed lowered level of the alpha spectral power as compared with healthy children. In healthy children, the gamma spectral power increased during performance of the cognitive task as compared to baseline state. Autistic persons showed higher values of the gamma spectral power as compared with normal boys. Boys with autism showed less expressed changes in the gamma spectral power during the cognitive task than healthy children. The reduced spectral power of the alpha band in autistic boys may serve as a precursor of conversion from autism to schizophrenia. Higher level of the gamma spectral power in autistic boys is characteristic also of schizophrenic patients with positive symptoms. Lowered levels of fast rhythms reactivity revealed in autistic boys and the same effect earlier described in schizophrenic adults probably have the similar nature.     

Auditory Processing under Cross-Modal Visual Load Investigated with Simultaneous EEG-fMRI

Cognitive task demands in one sensory modality (T1) can have beneficial effects on a secondary task (T2) in a different modality, due to reduced top-down control needed to inhibit the secondary task, as well as crossmodal spread of attention. This contrasts findings of cognitive load compromising a secondary modality’s processing. We manipulated cognitive load within one modality (visual) and studied the consequences of cognitive demands on secondary (auditory) processing. 15 healthy participants underwent a simultaneous EEG-fMRI experiment. Data from 8 participants were obtained outside the scanner for validation purposes. The primary task (T1) was to respond to a visual working memory (WM) task with four conditions, while the secondary task (T2) consisted of an auditory oddball stream, which participants were asked to ignore. The fMRI results revealed fronto-parietal WM network activations in response to T1 task manipulation. This was accompanied by significantly higher reaction times and lower hit rates with increasing task difficulty which confirmed successful manipulation of WM load. Amplitudes of auditory evoked potentials, representing fundamental auditory processing showed a continuous augmentation which demonstrated a systematic relation to cross-modal cognitive load. With increasing WM load, primary auditory cortices were increasingly deactivated while psychophysiological interaction results suggested the emergence of auditory cortices connectivity with visual WM regions. These results suggest differential effects of crossmodal attention on fundamental auditory processing. We suggest a continuous allocation of resources to brain regions processing primary tasks when challenging the central executive under high cognitive load.     

Prefrontal neurons predict choices during an auditory same-different task

The detection of stimuli is critical for an animal's survival [1]. However, it is not adaptive for an animal to respond automatically to every stimulus that is present in the environment [2-5]. Given that the prefrontal cortex (PFC) plays a key role in executive function [6-8], we hypothesized that PFC activity should be involved in context-dependent responses to uncommon stimuli. As a test of this hypothesis, monkeys participated in a same-different task, a variant of an oddball task [2]. During this task, a monkey heard multiple presentations of a "reference" stimulus that were followed by a "test" stimulus and reported whether these stimuli were the same or different. While they participated in this task, we recorded from neurons in the ventrolateral prefrontal cortex (vPFC; a cortical area involved in aspects of nonspatial auditory processing [9, 10]). We found that vPFC activity was correlated with the monkeys' choices. This finding demonstrates a direct link between single neurons and behavioral choices in the PFC on a nonspatial auditory task.     

Vasopressin and cognitive processes: Two event-related potential studies

Two experiments studied the influence of arginine-vasopressin (AVP) on cognitive processes by means of an electrophysiological measure, the late positive complex (LPC) of the event-related potential. The LPC varies systematically with cognitive processes. The classical oddball paradigm and an incidental memory task (structural encoding of emotional adjectives) were used. The two studies differed only in the dose of AVP (study 1: three time nasal application of 10 IU AVP; study 2: 20 IU). In study 1, AVP intake enhanced memory performance. The LPC elicited by oddball stimuli was not influenced by AVP, neither when compared before and after intake nor when compared to placebo treatment. However, specific influences of AVP on the LPC elicited during the structural encoding task were observed. In both studies, AVP intake resulted in a marked change of the scalp distribution of the P3 component, which is a prominent part of the LPC. Furthermore, subjects treated with the lower dose of AVP showed a more positive P3 component on emotional (negative and positive) adjectives, when compared to neutral ones. The results suggest that vasopressin influences the central nervous processing of the emotional content of stimuli.     

Impaired Prefrontal Hemodynamic Maturation in Autism and Unaffected Siblings

Background

Dysfunctions of the prefrontal cortex have been previously reported in individuals with autism spectrum disorders (ASD). Previous studies reported that first-degree relatives of individuals with ASD show atypical brain activity during tasks associated with social function. However, developmental changes in prefrontal dysfunction in ASD and genetic influences on the phenomena remain unclear. In the present study, we investigated the change in hemoglobin concentration in the prefrontal cortex as measured with near-infrared spectroscopy, in children and adults with ASD during the letter fluency test. Moreover, to clarify the genetic influences on developmental changes in the prefrontal dysfunction in ASD, unaffected siblings of the ASD participants were also assessed.

Methodology/Principal Findings

Study participants included 27 individuals with high-functioning ASD, age- and IQ-matched 24 healthy non-affected siblings, and 27 unrelated healthy controls aged 5 to 39 years. The relative concentration of hemoglobin ([Hb]) in the prefrontal cortex was measured during the letter fluency task. For children, neither the [oxy-Hb] change during the task nor task performances differed significantly among three groups. For adults, the [oxy-Hb] increases during the task were significantly smaller in the bilateral prefrontal cortex in ASD than those in control subjects, although task performances were similar. In the adult siblings the [oxy-Hb] change was intermediate between those in controls and ASDs.

Conclusion/Significance

Although indirectly due to a cross-sectional design, the results of this study indicate altered age-related change of prefrontal activity during executive processing in ASD. This is a first near-infrared spectroscopy study that implies alteration in the age-related changes of prefrontal activity in ASD and genetic influences on the phenomena.