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.

Heart Rate Variability and Skin Conductance During Repetitive TMS Course in Children with Autism.

Autism spectrum disorder (ASD) is a developmental disorder marked by difficulty in social interactions and communication. ASD also often present symptoms of autonomic nervous system (ANS) functioning abnormalities. In individuals with autism the sympathetic branch of the ANS presents an over-activation on a background of the parasympathetic activity deficits, creating an autonomic imbalance, evidenced by a faster heart rate with little variation and increased tonic electrodermal activity. The objective of this study was to explore the effect of 12 sessions of 0.5 Hz repetitive transcranial magnetic stimulation (rTMS) over dorsolateral prefrontal cortex (DLPFC) on autonomic activity in children with ASD. Electrocardiogram and skin conductance level (SCL) were recorded and analyzed during each session of rTMS. The measures of interest were time domain (i.e., R-R intervals, standard deviation of cardiac intervals, NN50-cardio-intervals >50 ms different from preceding interval) and frequency domain heart rate variability (HRV) indices [i.e., power of high frequency (HF) and low frequency (LF) components of HRV spectrum, LF/HF ratio]. Based on our prior pilot studies it was proposed that the course of 12 weekly inhibitory low-frequency rTMS bilaterally applied to the DLPFC will improve autonomic balance probably through improved frontal inhibition of the ANS activity, and will be manifested in an increased length of cardiointervals and their variability, and in higher frequency-domain HRV in a form of increased HF power, decreased LF power, resulting in decreased LF/HF ratio, and in decreased SCL. Our post-12 TMS results showed significant increases in cardiac intervals variability measures and decrease of tonic SCL indicative of increased cardiac vagal control and reduced sympathetic arousal. Behavioral evaluations showed decreased irritability, hyperactivity, stereotype behavior and compulsive behavior ratings that correlated with several autonomic variables.

Behavioral, Cognitive, and Motor Preparation Deficits in a Visual Cued Spatial Attention Task in Autism Spectrum Disorder.

Abnormalities in motor skills have been regarded as part of the symptomatology characterizing autism spectrum disorder (ASD). It has been estimated that 80 % of subjects with autism display "motor dyspraxia" or clumsiness that are not readily identified in a routine neurological examination. In this study we used behavioral measures, event-related potentials (ERP), and lateralized readiness potential (LRP) to study cognitive and motor preparation deficits contributing to the dyspraxia of autism. A modified Posner cueing task was used to analyze motor preparation abnormalities in children with autism and in typically developing children (N = 30/per group). In this task, subjects engage in preparing motor response based on a visual cue, and then execute a motor movement based on the subsequent imperative stimulus. The experimental conditions, such as the validity of the cue and the spatial location of the target stimuli were manipulated to influence motor response selection, preparation, and execution. Reaction time and accuracy benefited from validly cued targets in both groups, while main effects of target spatial position were more obvious in the autism group. The main ERP findings were prolonged and more negative early frontal potentials in the ASD in incongruent trials in both types of spatial location. The LRP amplitude was larger in incongruent trials and had stronger effect in the children with ASD. These effects were better expressed at the earlier stages of LRP, specifically those related to response selection, and showed difficulties at the cognitive phase of stimulus processing rather that at the motor execution stage. The LRP measures at different stages reflect the chronology of cognitive aspects of movement preparation and are sensitive to manipulations of cue correctness, thus representing very useful biomarker in autism dyspraxia research. Future studies may use more advance and diverse manipulations of movement preparation demands in testing more refined specifics of dyspraxia symptoms to investigate functional connectivity abnormalities underlying motor skills deficits in autism.

Stigmatization of psychiatrists and general practitioners: results of an international survey.

The stigma of mental illness affects psychiatry as a medical profession and psychiatrists. The present study aimed to compare the extent and correlation patterns of perceived stigma in psychiatrists and general practitioners. An international multicenter survey was conducted in psychiatrists and general practitioners from twelve countries. Responses were received from N = 1,893 psychiatrists and N = 1,238 general practitioners. Aspects of stigma assessed in the questionnaire included perceived stigma, self-stigma (stereotype agreement), attitudes toward the other profession, and experiences of discrimination. Psychiatrists reported significantly higher perceived stigma and discrimination experiences than general practitioners. Separate multiple regression analyses showed different predictor patterns of perceived stigma in the two groups. Hence, in the psychiatrists group, perceived stigma correlated best with discrimination experiences and self-stigma, while in the general practitioners group it correlated best with self-stigma. About 17% of the psychiatrists perceive stigma as a serious problem, with a higher rate in younger respondents. Against this background, psychiatry as a medical profession should set a high priority on improving the training of young graduates. Despite the number of existing antistigma interventions targeting mental health professionals and medical students, further measures to improve the image of psychiatry and psychiatrists are warranted, in particular improving the training of young graduates with respect to raising awareness of own stigmatizing attitudes and to develop a better profession-related self-assertiveness.

Neuromodulation integrating rTMS and neurofeedback for the treatment of autism spectrum disorder: an exploratory study.

Autism spectrum disorder (ASD) is a pervasive developmental disorder characterized by deficits in social interaction, language, stereotyped behaviors, and restricted range of interests. In previous studies low frequency repetitive transcranial magnetic stimulation (rTMS) has been used, with positive behavioral and electrophysiological results, for the experimental treatment in ASD. In this study we combined prefrontal rTMS sessions with electroencephalographic (EEG) neurofeedback (NFB) to prolong and reinforce TMS-induced EEG changes. The pilot trial recruited 42 children with ASD (~14.5 years). Outcome measures included behavioral evaluations and reaction time test with event-related potential (ERP) recording. For the main goal of this exploratory study we used rTMS-neurofeedback combination (TMS-NFB, N = 20) and waitlist (WTL, N = 22) groups to examine effects of 18 sessions of integrated rTMS-NFB treatment or wait period) on behavioral responses, stimulus and response-locked ERPs, and other functional and clinical outcomes. The underlying hypothesis was that combined TMS-NFB will improve executive functions in autistic patients as compared to the WTL group. Behavioral and ERP outcomes were collected in pre- and post-treatment tests in both groups. Results of the study supported our hypothesis by demonstration of positive effects of combined TMS-NFB neurotherapy in active treatment group as compared to control WTL group, as the TMS-NFB group showed significant improvements in behavioral and functional outcomes as compared to the WTL group.

Measuring the stigma of psychiatry and psychiatrists: development of a questionnaire.

The stigma of mental illness is a severe burden for people suffering from mental illness both in private and public life, also affecting their relatives, their close social network, and the mental health care system in terms of disciplines, providers, and institutions. Interventions against the stigma of mental illness employ complementary strategies (e.g., protest, education, and contact) and address different target groups (e.g., school children and teachers, journalists, stakeholders). Within this framework, the World Psychiatric Association has adopted an Action Plan with the goal to improve the image of psychiatry and to reduce potential stigmatizing attitudes toward psychiatry and psychiatrists. To evaluate such interventions, a questionnaire has been developed that assesses opinions and attitudes toward psychiatrists and psychiatry in different samples of medical specialists (psychiatrists and general practitioners). The questionnaire comprises scales about perceived stigma in terms of the perception of societal stereotypes, self-stigma in terms of stereotype agreement, perceived stigma in terms of structural discriminations, discrimination experiences, stigma outcomes, and attitudes toward a second medical discipline. It is available in several languages (Arab, English, German, Japanese, Polish, and Spanish) and can easily be adapted for utilization in other medical specialties.

Event-related potential study of the effects of emotional facial expressions on task performance in euthymic bipolar patients.

There appears to be a significant disconnect between symptomatic and functional recovery in bipolar disorder (BD). Some evidence points to interepisode cognitive dysfunction. We tested the hypothesis that some of this dysfunction was related to emotional reactivity in euthymic bipolar subjects may effect cognitive processing. A modification of emotional gender categorization oddball task was used. The target was gender (probability 25%) of faces with negative, positive, and neutral emotional expression. The experiment had 720 trials (3 blocks × 240 trials each). Each stimulus was presented for 150 ms, and the EEG/ERP responses were recorded for 1,000 ms. The inter-trial interval was varied in 1,100-1,500 ms range to avoid expectancy effects. Task took about 35 min to complete. There were 9 BD and 9 control subjects matched for age and gender. Reaction time (RT) was globally slower in BD subjects. The centro-parietal amplitudes at N170 and N200, and P200 and P300 were generally smaller in the BD group compared to controls. Latency was shorter to neutral and negative targets in BD. Frontal P200 amplitude was higher to emotional negative facial non-targets in BD subjects. The frontal N200 in response to positive facial emotion was less negative in BD subjects. The frontal P300 of BD subjects was lower to emotionally neutral targets. ERP responses to facial emotion in BD subjects varied significantly from normal controls. These variations are consistent with the common depressive symptomology seen in long term studies of bipolar subjects.

Paradigms and parallels: A commentary on the transformation of the self East and West.

Ways of gaining enhanced self understanding have developed in every culture. A modern way of referring to this understanding is insight, defined as the individual's understanding of associations between past and present, typical relationship patterns and their vicissitudes, emotional experiences, and psychological symptoms. This paper explores the similarities and differences among the approaches developed in Europe, the United States, and Asia. An example of evolving changes in psychoanalytic theory and practice in the United States, embodied in the body of work called "self psychology" is described as an illustration of how "western" approaches may be incorporating wisdom from "eastern" practice.

Training the trainers: Finding new educational opportunities in the virtual world.

The COVID-19 pandemic has disrupted scientific gatherings and conferences, opening up opportunities for virtual learning platforms. Realizing the potential of online academic exchanges, the World Psychiatric Association (WPA) also developed virtual avenues and information systems for capacity building of mental health professionals across the world. Among its first such initiatives, the WPA organized a virtual Train the Trainers workshop, where 123 psychiatrists, psychiatric trainees, and educators from 45 countries participated. The innovative and interactive workshop allowed participants to get to know each other, exchange educational and professional experiences, and ask questions or receive advice from experts. Keynote speakers, including WPA President Prof. Afzal Javed and Prof. Norman Sartorius, stressed upon the importance of finding innovative solutions in psychiatry training and the need to improve teaching and training in the field of psychiatry, especially in the provision of leadership and communication skills. Online training methods can provide easy access to academics and students while reducing the organizational and logistical costs. They have the potential to improve educational equality and allow the voice of the underprivileged scientists to be heard across the globe. The devastating impact on access to mental health services during COVID-19 underscores the urgent need for online training, particularly in countries where the ratio of psychiatrists to patients is inadequate and doctors concentrate more on treatment than on research and education. Virtual educational interventions could prove incredibly useful in the future just as they are being successfully utilized in local and regional contexts during the pandemic.

Low-frequency repetitive transcranial magnetic stimulation (rTMS) affects event-related potential measures of novelty processing in autism.

In our previous study on individuals with autism spectrum disorder (ASD) (Sokhadze et al., Appl Psychophysiol Biofeedback 34:37-51, 2009a) we reported abnormalities in the attention-orienting frontal event-related potentials (ERP) and the sustained-attention centro-parietal ERPs in a visual oddball experiment. These results suggest that individuals with autism over-process information needed for the successful differentiation of target and novel stimuli. In the present study we examine the effects of low-frequency, repetitive Transcranial Magnetic Stimulation (rTMS) on novelty processing as well as behavior and social functioning in 13 individuals with ASD. Our hypothesis was that low-frequency rTMS application to dorsolateral prefrontal cortex (DLFPC) would result in an alteration of the cortical excitatory/inhibitory balance through the activation of inhibitory GABAergic double bouquet interneurons. We expected to find post-TMS differences in amplitude and latency of early and late ERP components. The results of our current study validate the use of low-frequency rTMS as a modulatory tool that altered the disrupted ratio of cortical excitation to inhibition in autism. After rTMS the parieto-occipital P50 amplitude decreased to novel distracters but not to targets; also the amplitude and latency to targets increased for the frontal P50 while decreasing to non-target stimuli. Low-frequency rTMS minimized early cortical responses to irrelevant stimuli and increased responses to relevant stimuli. Improved selectivity in early cortical responses lead to better stimulus differentiation at later-stage responses as was made evident by our P3b and P3a component findings. These results indicate a significant change in early, middle-latency and late ERP components at the frontal, centro-parietal, and parieto-occipital regions of interest in response to target and distracter stimuli as a result of rTMS treatment. Overall, our preliminary results show that rTMS may prove to be an important research tool or treatment modality in addressing the stimulus hypersensitivity characteristic of autism spectrum disorders.

Event-related potential study of novelty processing abnormalities in autism.

To better understand visual processing abnormalities in autism we studied the attention orienting related frontal event potentials (ERP) and the sustained attention related centro-parietal ERPs in a three stimulus oddball experiment. The three stimulus oddball paradigm was aimed to test the hypothesis that individuals with autism abnormally orient their attention to novel distracters as compared to controls. A dense-array 128 channel EGI electroencephalographic (EEG) system was used on 11 high-functioning children and young adults with autism spectrum disorder (ASD) and 11 age-matched, typically developing control subjects. Patients with ASD showed slower reaction times but did not differ in response accuracy. At the anterior (frontal) topography the ASD group showed significantly higher amplitudes and longer latencies of early ERP components (e.g., P100, N100) to novel distracter stimuli in both hemispheres. The ASD group also showed prolonged latencies of late ERP components (e.g., P2a, N200, P3a) to novel distracter stimuli in both hemispheres. However, differences were more profound in the right hemisphere for both early and late ERP components. Our results indicate augmented and prolonged early frontal potentials and a delayed P3a component to novel stimuli, which suggest low selectivity in pre-processing and later-stage under-activation of integrative regions in the prefrontal cortices. Also, at the posterior (centro-parietal) topography the ASD group showed significantly prolonged N100 latencies and reduced amplitudes of the N2b component to target stimuli. In addition, the latency of the P3b component was prolonged to novel distracters in the ASD group. In general, the autistic group showed prolonged latencies to novel stimuli especially in the right hemisphere. These results suggest that individuals with autism over-process information needed for the successful differentiation of target and novel stimuli. We propose the potential application of ERP evaluations in a novelty task as outcome measurements in the biobehavioral treatment (e.g., EEG biofeedback, TMS) of autism.

Partnerships for interdisciplinary collaborative global well-being.

Health is a state of complete physical, mental, and social well-being and not merely the absence of disease or infirmity. The multifaceted intertwined nature of optimal health, mental health, and well-being requires operational, sustainable interdisciplinary partnerships in order to improve personal and global well-being and happiness. The initial step must be the assessment of the nature and magnitude of local problems in the global context. The WHO annual reports may be an adequate departure point as they can demonstrate the global nature of stressful situations and their association with physical and mental stress-related disorders. Therein, mental health professionals should spearhead change and progress. Attitudes need to be pro-active and partnerships are essential. Pertinent data should be evaluated by local experts who will determine the needs and how best to face them and achieve solutions. Hopefully, common regional denominators will lead to the formation of Regional Interdisciplinary Collaborative Alliances (RICAs) who will share needed resources and focus particularly on vulnerable populations. The RICAs would be supported by experts and technological facilities located in developed economy centers. The long-term goal is to turn the concept of pursuit of happiness into a well-perceived reality.

Exploratory Study of rTMS Neuromodulation Effects on Electrocortical Functional Measures of Performance in an Oddball Test and Behavioral Symptoms in Autism.

There is no accepted pathology to autism spectrum disorders (ASD) but research suggests the presence of an altered excitatory/inhibitory (E/I) bias in the cerebral cortex. Repetitive transcranial magnetic stimulation (rTMS) offers a non-invasive means of modulating the E/I cortical bias with little in terms of side effects. In this study, 124 high functioning ASD children (IQ > 80, <18 years of age) were recruited and assigned using randomization to either a waitlist group or one of three different number of weekly rTMS sessions (i.e., 6, 12, and 18). TMS consisted of trains of 1.0 Hz frequency pulses applied over the dorsolateral prefrontal cortex (DLPFC). The experimental task was a visual oddball with illusory Kanizsa figures. Behavioral response variables included reaction time and error rate along with such neurophysiological indices such as stimulus and response-locked event-related potentials (ERP). One hundred and twelve patients completed the assigned number of TMS sessions. Results showed significant changes from baseline to posttest period in the following measures: motor responses accuracy [lower percentage of committed errors, slower latency of commission errors and restored normative post-error reaction time slowing in both early and later-stage ERP indices, enhanced magnitude of error-related negativity (ERN), improved error monitoring and post-error correction functions]. In addition, screening surveys showed significant reductions in aberrant behavior ratings and in both repetitive and stereotypic behaviors. These differences increased with the total number of treatment sessions. Our results suggest that rTMS, particularly after 18 sessions, facilitates cognitive control, attention and target stimuli recognition by improving discrimination between task-relevant and task-irrelevant illusory figures in an oddball test. The noted improvement in executive functions of behavioral performance monitoring further suggests that TMS has the potential to target core features of ASD.