Effects of Transcranial Direct Current Stimulation on Social Attention Patterns and Emotion Recognition Ability in Male Adolescents with Autism Spectrum Disorder.

Autism Spectrum Disorder (ASD) is characterized by impairments in social cognition including emotion recognition (ER) abilities. Common symptoms include unusual patterns of visual social attention, which are investigated as early developmental biomarkers for ASD. Transcranial Direct Current Stimulation (tDCS) has shown promising results in influencing social functioning in individuals with ASD. However, the effects of tDCS on social attention patterns and ER ability in adolescents with ASD remain unclear. This double-blind, sham-controlled, randomized clinical trial examined the effects of repeated sessions of tDCS on gaze behavior and ER ability in 22 male adolescents diagnosed with ASD. Participants received either 20 min of 2 mA active tDCS or sham stimulation for 10 days and an intra-stimulation training. Social allocation patterns were assessed using eye-tracking paradigms, including ER tasks. Our results indicated no tDCS-specific effects. Both groups showed improvements in ER and more frequent, faster, and longer fixations on the eyes than the mouth, and on social than nonsocial areas. In tasks with low social content, fixating the mouth seemed to increase ER accuracy. Understanding the effects of tDCS on social functioning in adolescents with ASD holds promise for the development of targeted interventions to improve their social cognition abilities.

Individual brain regulation as learned via neurofeedback is related to affective changes in adolescents with autism spectrum disorder.

BACKGROUND: Emotions often play a role in neurofeedback (NF) regulation strategies. However, investigations of the relationship between the induced neuronal changes and improvements in affective domains are scarce in electroencephalography-based studies. Thus, we extended the findings of the first study on slow cortical potential (SCP) NF in autism spectrum disorder (ASD) by linking affective changes to whole-brain activity during rest and regulation. METHODS: Forty-one male adolescents with ASD were scanned twice at rest using functional magnetic resonance imaging. Between scans, half underwent NF training, whereas the other half received treatment as usual. Furthermore, parents reported on their child's affective characteristics at each measurement. The NF group had to alternatingly produce negative and positive SCP shifts during training and was additionally scanned using functional magnetic resonance imaging while applying their developed regulation strategies. RESULTS: No significant treatment group-by-time interactions in affective or resting-state measures were found. However, we found increases of resting activity in the anterior cingulate cortex and right inferior temporal gyrus as well as improvements in affective characteristics over both groups. Activation corresponding to SCP differentiation in these regions correlated with the affective improvements. A further correlation was found for Rolandic operculum activation corresponding to positive SCP shifts. There were no significant correlations with the respective achieved SCP regulation during NF training. CONCLUSION: SCP NF in ASD did not lead to superior improvements in neuronal or affective functioning compared to treatment as usual. However, the affective changes might be related to the individual strategies and their corresponding activation patterns as indicated by significant correlations on the whole-brain level. Trial registration This clinical trial was registered at drks.de (DRKS00012339) on 20th April, 2017.

Evaluation of Neurofeedback Learning in Patients with ADHD: A Systematic Review.

NFB has a clear potential as a recognised treatment option for ADHD, but suffers from a lack of clarity about its efficacy, still unresolved after multiple controlled trials. Comparing learners and non-learners based on the evolution of patient-level indicators during the trial serves as a 'natural' control, and can help elucidate the mechanisms of NFB. We present a systematic review motivated by the need to establish the state of the art of patient learning during NFB treatment in current clinical literature. One particularly striking question we would like to answer here is whether existing NFB papers study learning variability, since only individual performance differences can give us information about mechanisms of learning. The results show that very few clinical trial reports have dealt with the heterogeneity of NFB learning, nor analysed whether NFB efficacy is dependent on NFB learning, even though NFB is believed to be a treatment based on learning to perform. In this systematic review we examine not only what has been reported, but also provide a critical analysis of possible flaws or gaps in existing studies, and discuss why no generalized conclusions about NFB efficacy have yet been made. Future research should focus on finding reliable ways of identifying the performers and studying participants' individual learning trajectories as it might enhance prognosis and the allocation of clinical resources.

Brain Stimulation for Emotion Regulation in Adolescents With Psychiatric Disorders: Study Protocol for a Clinical-Transdiagnostical, Randomized, Triple-Blinded and Sham-Controlled Neurotherapeutic Trial.

Background: Anxiety, conduct and depressive disorders represent three highly prevalent psychiatric conditions in adolescents. A shared underpinning of these disorders is a shortcoming in emotion regulation, connected to the functioning of the ventromedial prefrontal cortex. Thus, an intervention able to target the suggested neural correlate seems to be highly desirable, aiming to hinder a maladaptive development of emotion regulation abilities and chronification of associated psychiatric disorders. As transcranial direct current stimulation (tDCS) was repeatedly demonstrated as a safe and non-invasive method to modulate specific brain activity, research is in demand to evaluate neurotherapeutic applications in adolescents with psychiatric disorders. Method: This transdiagnostic, randomized, triple-blind and sham-controlled clinical neurostimulation trial primary aims to investigate if emotion regulation abilities are increased after tDCS in adolescents with psychiatric disorders. Secondly, disorder-specific changes in the anxiety, depression or conduct disorder will be investigated, as well as changes in quality of life, and cognitive and emotional functioning after tDCS intervention. We will include 108 adolescents with psychiatric disorders, displaying a substantial deficit in emotion regulation. Of these, one third each has to be primarily diagnosed with a depressive, anxiety or conduct disorder, respectively. Participants will be randomized to the experimental group (n = 54) receiving real anodal tDCS, or to the control group (n = 54) receiving sham tDCS. Brain stimulation will be applied for 20 min on five consecutive days twice targeting the ventromedial prefrontal cortex (vmPFC). Changes in emotion regulation, together with changes in disorder-specific clinical symptoms will be recorded by multi-informant psychological ratings. To inspect changes in behavior and gaze, computerized tasks and an eye tracker system will be used. Changes in brain responses to emotional and cognitive stimuli will be examined with three functional magnetic resonance imaging (fMRI) paradigms. In addition, a resting state MRI will be acquired to investigate possible changes in brain connectivity. Discussion: By investigating "emotion regulation" as transdiagnostic treatment target, this project is oriented toward the Research Domain Criteria framework with a dimensional view on mental illness. The study aims at investigating the potential of tDCS as non-invasive intervention for depressive, anxiety and conduct disorders in adolescents and broadening the scientific foundation for its clinical application. Clinical Trial Registration: The study is ongoing and has been registered in the German Registry of Clinical Trials (DRKS-ID: DRKS00025601X) on the 28.06.2021.

Impulsivity Moderates the Effect of Neurofeedback Training on the Contingent Negative Variation in Autism Spectrum Disorder.

Background: The contingent negative variation (CNV) is a well-studied indicator of attention- and expectancy-related processes in the human brain. An abnormal CNV amplitude has been found in diverse neurodevelopmental psychiatric disorders. However, its role as a potential biomarker of successful clinical interventions in autism spectrum disorder (ASD) remains unclear. Methods: In this randomized controlled trial, we investigated how the CNV changes following an intensive neurofeedback training. Therefore, twenty-one adolescents with ASD underwent 24 sessions of slow cortical potential (SCP) neurofeedback training. Twenty additional adolescents with ASD formed a control group and received treatment as usual. CNV waveforms were obtained from a continuous performance test (CPT), which all adolescents performed before and after the corresponding 3-month long training period. In order to utilize all available neural time series, trial-based area under the curve values for all four electroencephalogram (EEG) channels were analyzed with a hierarchical Bayesian model. In addition, the model included impulsivity, inattention, and hyperactivity as potential moderators of change in CNV. Results: Our model implies that impulsivity moderates the effects of neurofeedback training on CNV depending on group. In the control group, the average CNV amplitude decreased or did not change after treatment as usual. In the experimental group, the CNV changed depending on the severity of comorbid impulsivity symptoms. The average CNV amplitude of participants with low impulsivity scores decreased markedly, whereas the average CNV amplitude of participants with high impulsivity increased. Conclusion: The degree of impulsivity seems to play a crucial role in the changeability of the CNV following an intensive neurofeedback training. Therefore, comorbid symptomatology should be recorded and analyzed in future EEG-based brain training interventions. Clinical Trial Registration: https://www.drks.de, identifier DRKS00012339.

Effects of an intensive slow cortical potentials neurofeedback training in female and male adolescents with autism spectrum disorder : Are there sex differences?

BACKGROUND: This study aims to compare the effects of neurofeedback training on male and female adolescents with autism spectrum disorder (ASD). Furthermore, it examines sex differences regarding improvements in co-occurring psychopathological symptoms, cognitive flexibility and emotion recognition abilities. The study might provide first hints whether there is an influence of sex on treatment outcomes. METHODS: Six female and six male adolescents with ASD were matched according to age, IQ and symptom severity. All participants received 24 sessions of electroencephalography-based neurofeedback training. Before and after the intervention, psychological data for measuring co-occurring psychopathological symptoms as well as behavioral data for measuring cognitive flexibility and emotion recognition abilities were recorded. RESULTS: Caregivers rated statistically significant higher psychopathological problems in female than in male adolescents with ASD at baseline. Apart from that, no statistically significant sex-related differences were revealed in this sample; however, male adolescents tended to report greater improvements of externalizing, internalizing and total symptoms, whereas females experienced smaller improvements of externalizing and total problems, but no improvements of internalizing problems. Regarding caregivers' assessments, more improvement of total problems was reported for females. For males, only improvements of internalizing and total problems were described. CONCLUSION: This study reveals preliminary results that sex-related differences might play a role when evaluating treatment outcomes after neurofeedback training regarding comorbid psychopathological symptoms. Adolescents' self-report and parental assessments, especially concerning psychopathological symptoms, should be combined and considered in future studies to help prevent sex bias in adolescents with ASD.

Repeated Sessions of Transcranial Direct Current Stimulation on Adolescents With Autism Spectrum Disorder: Study Protocol for a Randomized, Double-Blind, and Sham-Controlled Clinical Trial.

Background: Social-emotional difficulties are a core symptom of autism spectrum disorder (ASD). Accordingly, individuals with ASD have problems with social cognition such as recognizing emotions from other peoples' faces. Various results from functional magnetic resonance imaging and electroencephalography studies as well as eye-tracking data reveal a neurophysiological basis of these deficits by linking them to abnormal brain activity. Thus, an intervention targeting the neural origin of ASD impairments seems warranted. A safe method able to influence neural activity is transcranial direct current stimulation (tDCS). This non-invasive brain stimulation method has already demonstrated promising results in several neuropsychiatric disorders in adults and children. The aim of this project is to investigate the effects of tDCS on ASD symptoms and their neural correlates in children and adolescents with ASD. Method: This study is designed as a double-blind, randomized, and sham-controlled trial with a target sample size of 20 male participants (aged 12-17 years) diagnosed with ASD. Before randomization, the participants will be stratified into comorbid depression, comorbid ADHS/conduct disorder, or no-comorbidity groups. The intervention phase comprises 10 sessions of anodal or sham tDCS applied over the left prefrontal cortex within 2 consecutive weeks. To engage the targeted brain regions, participants will perform a social cognition training during the stimulation. TDCS-induced effects on ASD symptoms and involved neural circuits will be investigated through psychological, neurophysiological, imaging, and behavioral data at pre- and post-measurements. Tolerability will be evaluated using a standardized questionnaire. Follow-up assessments 1 and 6 months after the intervention will examine long-lasting effects. Discussion: The results of this study will provide insights into the changeability of social impairments in ASD by investigating social and emotional abilities on different modalities following repeated sessions of anodal tDCS with an intra-simulation training. Furthermore, this trial will elucidate the tolerability and the potential of tDCS as a new treatment approach for ASD in adolescents. Clinical Trial Registration: The study is ongoing and has been registered in the German Registry of Clinical Trials (DRKS00017505) on 02/07/2019.

Balancing the brain of offenders with psychopathy? Resting state EEG and electrodermal activity after a pilot study of brain self-regulation training.

Although investigation of the brains of criminals began quite early in the history of psychophysiological research, little is known about brain plasticity of offenders with psychopathy. Building on our preliminary study reporting successful brain self-regulation using slow cortical potential (SCP) neurofeedback in offenders with psychopathy, we investigated the central nervous and autonomic peripheral changes occurring after brain self-regulation in a group of severe male offenders with psychopathy. Regarding the central nervous system, an overall suppression of the psychopathic overrepresentation of slow frequency bands was found, such as delta and theta band activity, after EEG neurofeedback. In addition, an increase in alpha band activity could be observed after the SCP self-regulation training. Electrodermal activity adaptively changed according to the regulation task, and this flexibility improved over training time. The results of this study point towards a constructive learning process and plasticity in neural and peripheral measures of offenders with psychopathy.

Consensus on the reporting and experimental design of clinical and cognitive-behavioural neurofeedback studies (CRED-nf checklist).

Neurofeedback has begun to attract the attention and scrutiny of the scientific and medical mainstream. Here, neurofeedback researchers present a consensus-derived checklist that aims to improve the reporting and experimental design standards in the field.

Brain self-regulation in criminal psychopaths.

Psychopathic individuals are characterized by impaired affective processing, impulsivity, sensation-seeking, poor planning skills and heightened aggressiveness with poor self-regulation. Based on brain self-regulation studies using neurofeedback of Slow Cortical Potentials (SCPs) in disorders associated with a dysregulation of cortical activity thresholds and evidence of deficient cortical functioning in psychopathy, a neurobiological approach seems to be promising in the treatment of psychopathy. The results of our intensive brain regulation intervention demonstrate, that psychopathic offenders are able to gain control of their brain excitability over fronto-central brain areas. After SCP self-regulation training, we observed reduced aggression, impulsivity and behavioral approach tendencies, as well as improvements in behavioral-inhibition and increased cortical sensitivity for error-processing. This study demonstrates improvements on the neurophysiological, behavioral and subjective level in severe psychopathic offenders after SCP-neurofeedback training and could constitute a novel neurobiologically-based treatment for a seemingly change-resistant group of criminal psychopaths.

Deficient fear conditioning in psychopathy as a function of interpersonal and affective disturbances.

The diminished fear reactivity is one of the most valid physiological findings in psychopathy research. In a fear conditioning paradigm, with faces as conditioned stimulus (CS) and electric shock as unconditioned stimulus (US), we investigated a sample of 14 high psychopathic violent offenders. Event related potentials, skin conductance responses (SCR) as well as subjective ratings of the CSs were collected. This study assessed to which extent the different facets of the psychopathy construct contribute to the fear conditioning deficits observed in psychopaths. Participants with high scores on the affective facet subscale of the Psychopathy Checklist-Revised (PCL-R) showed weaker conditioned fear responses and lower N100 amplitudes compared to low scorers. In contrast, high scorers on the affective facet rated the CS+ (paired) more negatively than low scorers regarding the CS- (unpaired). Regarding the P300, high scores on the interpersonal facet were associated with increased amplitudes to the CS+ compared to the CS-, while the opposed pattern was found for the antisocial facet. Both, the initial and terminal contingent negative variation indicated a divergent pattern: participants with pronounced interpersonal deficits, showed increased cortical negativity to the CS+ compared to the CS-, whereas a reversed CS+/CS- differentiation was found in offenders scoring high on the antisocial facet. The present study revealed that deficient fear conditioning in psychopathy was most pronounced in offenders with high scores on the affective facet. Event related potentials suggest that participants with distinct interpersonal deficits showed increased information processing, whereas the antisocial facet was linked to decreased attention and interest to the CS+. These data indicate that an approach to the facets of psychopathy can help to resolve ambiguous findings in psychopathy research and enables a more precise and useful description of this disorder.

Inter-individual differences in successful perspective taking during pain perception mediates emotional responsiveness in self and others: an fMRI study.

Human empathy is an important component of social cognition that involves complex processes of emotional perspective taking and the issue of self/other distinction. Empathic perception enables us to experience negative emotions when someone else undergoes painful events. We investigated the influence of an extended time interval (10s) and subjective performance evaluation (following each trial) of perspective taking on the cortical and subcortical correlates of pain empathy in eighteen healthy subjects using functional magnetic resonance imaging (fMRI). Subjects were presented pictures of hands and feet in painful and non-painful situations. They were instructed to simply view the picture (View) or adopt either their own perspective (Self) or the perspective of a third-person (Other). Prolonged time intervals of stimulus presentation enabled the analysis of different perspective taking processes (Self versus Other). Enhanced activation in the left supramarginal gyrus was detected for adopting the Self compared to the Other perspective. Time course analysis showed an early peak in the trials, suggesting that taking the first-person perspective is an intuitive more automatic process. The comparison between the Other and Self condition evoked stronger activity in dorso- and ventrolateral prefrontal areas and the superior temporal sulcus (STS). For these areas, a peak in the later phase of the trials was found, suggesting that taking the third-person perspective requires more effort and is an ongoing process. This was also supported by the fact that the participants were subjectively more successful in adopting the Self perspective compared to the Other. Our findings support that especially during the Other condition, prolonged time periods seem to facilitate empathic responses. Individual ratings of performance enabled the comparison between subjects that were successful and unsuccessful at taking the Self or Other perspective. For Self, differential activations were found in the left insula and postcentral gyrus. For Other, differential activations were mainly observed in the left pallidum, bilateral VLPFC, the right middle orbitofrontal cortex OFC and the middle cingulate cortex (MCC). These results suggest that trial-specific success ratings allow us to disentangle differences between effort-related and successful engagement in perspective taking. These two adjustments to the well-known paradigm showed new insight into the aspects of perspective taking during pain perception.

Prefrontal brain asymmetry and aggression in imprisoned violent offenders.

Anterior brain asymmetry, assessed through the alpha and beta band in resting-state electroencephalogram (EEG) is associated with approach-related behavioral dispositions, particularly with aggression in the general population. To date, the association between frontal asymmetry and aggression has not been examined in highly aggressive groups. We examined the topographic characteristics of alpha and beta activity, the relation of both asymmetry metrics to trait aggression, and whether alpha asymmetry was extreme in anterior regions according to clinical standards in a group of imprisoned violent offenders. As expected, these individuals were characterized by stronger right than left-hemispheric alpha activity, which was putatively extreme in anterior regions in one third of the cases. We also report that in line with observations made in the general population, aggression was associated with stronger right-frontal alpha activity in these violent individuals. This suggests that frontal alpha asymmetry, as a correlate of trait aggression, might be utilizable as an outcome measure in studies which assess the effects of anti-aggressiveness training in violent offenders.