Neuroanatomical Predictors of Transcranial Direct Current Stimulation (tDCS)-Induced Modifications in Neurocognitive Task Performance in Typically Developing Individuals.

Transcranial direct current stimulation (tDCS) is a noninvasive neuromodulation technique gaining more attention in neurodevelopmental disorders (NDDs). Due to the phenotypic heterogeneity of NDDs, tDCS is unlikely to be equally effective in all individuals. The present study aimed to establish neuroanatomical markers in typically developing (TD) individuals that may be used for the prediction of individual responses to tDCS. Fifty-seven male and female children received 2 mA anodal and sham tDCS, targeting the left dorsolateral prefrontal cortex (DLPFCleft), right inferior frontal gyrus, and bilateral temporoparietal junction. Response to tDCS was assessed based on task performance differences between anodal and sham tDCS in different neurocognitive tasks (N-back, flanker, Mooney faces detection, attentional emotional recognition task). Measures of cortical thickness (CT) and surface area (SA) were derived from 3 Tesla structural MRI scans. Associations between neuroanatomy and task performance were assessed using general linear models (GLM). Machine learning (ML) algorithms were employed to predict responses to tDCS. Vertex-wise estimates of SA were more closely linked to differences in task performance than measures of CT. Across ML algorithms, highest accuracies were observed for the prediction of N-back task performance differences following stimulation of the DLPFCleft, where 65% of behavioral variance was explained by variability in SA. Lower accuracies were observed for all other tasks and stimulated regions. This suggests that it may be possible to predict individual responses to tDCS for some behavioral measures and target regions. In the future, these models might be extended to predict treatment outcome in individuals with NDDs.

Intention Attribution in Children and Adolescents with Autism Spectrum Disorder: An EEG Study.

The ability to infer intentions from observed behavior and predict actions based on this inference, known as intention attribution (IA), has been hypothesized to be impaired in individuals with autism spectrum disorder (ASD). The underlying neural processes, however, have not been conclusively determined. The aim of this study was to examine the neural signature of IA in children and adolescents with ASD, and to elucidate potential links to contextual updating processes using electroencephalography. Results did not indicate that IA or early contextual updating was impaired in ASD. However, there was evidence of aberrant processing of expectation violations in ASD, particularly if the expectation was based on IA. Results are discussed within the context of impaired predictive coding in ASD.

Reward processing in adolescents with social phobia and depression.

OBJECTIVE: Impaired reward processing has been found in individuals with anxiety, but also major depressive disorder (MDD). Here, we studied neural correlates of reward anticipation and processing in a sample of youth with severe social phobia and comorbid depression (SP/MDD) and investigated the specific contribution of SP and MDD symptoms. METHODS: 15 affected, unmedicated and 25 typically developing (TD) youth completed a monetary gambling task, which included a positive, negative and ambiguous reward condition. Event-related potentials representing cue processing (cue P300), reward anticipation (stimulus preceding negativity, SPN), reward sensitivity (feedback related negativity, FRN) and reward processing (reward P300) were analysed. RESULTS: Reduced amplitudes of the right hemispheric (r)SPN and reward P300 were observed in SP/MDD compared to TD. Within the SP/MDD group SP symptoms correlated with larger rSPN, and FRN amplitudes. MDD symptoms correlated with smaller rSPN and smaller FRN positive-negative difference wave. CONCLUSIONS: Reward anticipation and feedback processing are reduced in SP/MDD. Higher SP symptoms are associated with stronger neural activation during reward anticipation and reward sensitivity. Depressive symptoms are associated with decreased reward anticipation and sensitivity. Findings are in line with the theory of heightened vigilance in anxiety and blunted reward processing due to anhedonia in MDD. SIGNIFICANCE: The study results can inform behavioural interventions for SP and MDD.

The effect of perceptual expectation on processing gain, attention and the perceptual decision bias in children and adolescents with Autism Spectrum Disorder (ASD).

Perceptual expectations influence perception, attention and the perceptual decision bias during visuospatial orienting, which is impaired in individuals with Autism Spectrum Disorder (ASD). In this study, we investigated whether during visuospatial orienting, perceptual expectations in ASD differentially influence perception, attention and the perceptual decision bias relative to neurotypical controls (NT). Twenty-three children and adolescents with ASD and 23 NT completed a visuospatial orienting task, which compared the effect of a valid relative to an invalid perceptual expectation on target detection (cue validity effect). Group differences were calculated regarding the cue validity effect on neural correlates of processing gain (N1a amplitude) and attention (N1pc amplitude), the perceptual decision bias and mean reaction time (RT). In ASD relative to NT, findings showed a reduced processing gain for validly relative to invalidly cued targets and increased attentional response following invalidly relative to validly cued targets. Increased attention correlated with faster performance across groups. Increased processing correlated with a higher perceptual decision bias and faster mean RT in NT, but not in ASD. Results suggest that during visuospatial orienting, perceptual expectations in ASD may drive changes in sensory processing and stimulus-driven attention, which may differentially guide behavioural responses.

Brain stimulation by tDCS as treatment option in Autism Spectrum Disorder-A systematic literature review.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and interaction as well as stereotypical and repetitive behavior. Transcranial direct current stimulation (tDCS) has been proposed as a new intervention method in ASD with the potential to improve cognitive, motor and social communication abilities by targeting specific underlying neuronal alterations. Here, we report results of a systematic literature review on tDCS effects on EEG and behavioral outcomes, and discuss tDCS as treatment option for ASD. PsychInfo, PubMed, ScienceDirect, Web of Science, https://clinicaltrials.gov and the German Clinical Trials Register (Deutsches Register Klinischer Studien) were searched systematically for randomized, sham-controlled clinical trials of tDCS in individuals with ASD, and information regarding study designs and relevant results was extracted. Six eligible studies were identified. The dorsolateral prefrontal cortex (DLPFC) was targeted in four trials, with core ASD symptoms and working memory as outcome measures. One study targeted the primary motor cortex (M1) with motor skills as outcome, and one study targeted the temporoparietal junction (TPJ) with social communication skills as outcome measure. Comparison of the implemented study designs showed high methodological variability between studies regarding stimulation parameters, trial design and outcome measures. Study results indicate initial support for improved cognitive and social communication skills in ASD following tDCS stimulation. However, systematic and comparison studies on the best combination of stimulation intensity, duration, location as well as task related stimulation are necessary, before results can be translated into routine clinical application.

Phase-IIa randomized, double-blind, sham-controlled, parallel group trial on anodal transcranial direct current stimulation (tDCS) over the left and right tempo-parietal junction in autism spectrum disorder-StimAT: study protocol for a clinical trial.

BACKGROUND: Autism spectrum disorder (ASD) is characterized by impaired social communication and interaction, and stereotyped, repetitive behaviour and sensory interests. To date, there is no effective medication that can improve social communication and interaction in ASD, and effect sizes of behaviour-based psychotherapy remain in the low to medium range. Consequently, there is a clear need for new treatment options. ASD is associated with altered activation and connectivity patterns in brain areas which process social information. Transcranial direct current stimulation (tDCS) is a technique that applies a weak electrical current to the brain in order to modulate neural excitability and alter connectivity. Combined with specific cognitive tasks, it allows to facilitate and consolidate the respective training effects. Therefore, application of tDCS in brain areas relevant to social cognition in combination with a specific cognitive training is a promising treatment approach for ASD. METHODS: A phase-IIa pilot randomized, double-blind, sham-controlled, parallel-group clinical study is presented, which aims at investigating if 10 days of 20-min multi-channel tDCS stimulation of the bilateral tempo-parietal junction (TPJ) at 2.0 mA in combination with a computer-based cognitive training on perspective taking, intention and emotion understanding, can improve social cognitive abilities in children and adolescents with ASD. The main objectives are to describe the change in parent-rated social responsiveness from baseline (within 1 week before first stimulation) to post-intervention (within 7 days after last stimulation) and to monitor safety and tolerability of the intervention. Secondary objectives include the evaluation of change in parent-rated social responsiveness at follow-up (4 weeks after end of intervention), change in other ASD core symptoms and psychopathology, social cognitive abilities and neural functioning post-intervention and at follow-up in order to explore underlying neural and cognitive mechanisms. DISCUSSION: If shown, positive results regarding change in parent-rated social cognition and favourable safety and tolerability of the intervention will confirm tDCS as a promising treatment for ASD core-symptoms. This may be a first step in establishing a new and cost-efficient intervention for individuals with ASD. TRIAL REGISTRATION: The trial is registered with the German Clinical Trials Register (DRKS), DRKS00014732 . Registered on 15 August 2018. PROTOCOL VERSION: This study protocol refers to protocol version 1.2 from 24 May 2019.

Facilitation of biological motion processing by group-based autism specific social skills training.

Abnormalities in neurophysiological correlates of social perception are a well-known feature of autism spectrum disorder (ASD). However, little is known if and how ASD specific behavioral interventions may affect neural processing in ASD. The aim of the current study was to investigate for the first time, whether the group-based social skills training SOSTA-FRA would elicit changes in neurophysiological correlates of social perception in high-functioning ASD individuals aged 8-17 years. Event-related potentials (ERPs) of a facial emotion recognition (FER) and a biological motion perception task were examined. ERPs were compared between a randomized intervention and a treatment as usual group at three time points (baseline, post-intervention, and at 3 months follow-up). A reduction of P100 amplitude in the right hemisphere and a trend toward reduced N200 latency in the biological motion task were found after the training only in the intervention group, whereas behavioral performance remained stable. Change in N200 latencies and parent-rated social responsiveness showed small but statistically nonsignificant correlations. No changes were observed regarding FER. Results indicate that the intervention changed neural correlates of social perception in ASD. Especially neural correlates of biological motion perception, which is an important prerequisite for successful social interaction, were sensitive to change. ERPs of social perception tasks that are impaired in ASD can well be used to objectively measure neural processing improvement by behavioral intervention. Autism Res 2018, 11: 1376-1387. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: It is well known that people with autism spectrum disorder (ASD) process social information differently than other people and that these differences can also be seen in their brain activity. We also know that behavioral therapies, such as group-based social skills trainings can help people with ASD improve their behavior. But it is unclear how therapy changes social processing in the brain. The aim of our study was therefore to examine how neural processing of social stimuli changed after behavioral intervention. Comparing a group of children and adolescents that received the group-based social skills training SOSTA-FRA to a control group we found that the neural processing of human motion became faster and involved less brain resources after the intervention, while behavioral performance remained stable. No changes were seen for the processing of emotional facial expressions. We recommend that future studies should also analyze changes in brain function as well as behavioral changes as a secondary therapy outcome parameter.

Neural Correlates of Explicit Versus Implicit Facial Emotion Processing in ASD.

The underlying neural mechanisms of implicit and explicit facial emotion recognition (FER) were studied in children and adolescents with autism spectrum disorder (ASD) compared to matched typically developing controls (TDC). EEG was obtained from N = 21 ASD and N = 16 TDC. Task performance, visual (P100, N170) and cognitive (late positive potential) event-related-potentials, as well as coherence were compared across groups. TDC showed a task-dependent increase and a stronger lateralization of P100 amplitude during the explicit task and task-dependent modulation of intra-hemispheric coherence in the beta band. In contrast, the ASD group showed no task dependent modulation. Results indicate disruptions in early visual processing and top-down attentional processes as contributing factors to FER deficits in ASD.