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 non-invasive 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 typical developing (TD) individuals that may be used for the prediction of individual responses to tDCS. 57 TD male and female children received 2mA anodal and sham tDCS, targeting the left dorsolateral prefrontal cortex (DLPFCleft), right inferior frontal gyrus, and bilateral temporo-parietal 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 a general linear model. Machine learning (ML) algorithms were employed to predict responses to tDCS. Overall, 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 behavioural 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 behavioural measures and target regions. In the future, these models might be extended to predict treatment outcome in individuals with NDDs.Significance statement Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique that has recently gained more attention in neurodevelopmental disorders (NDDs), such as autism and attention-deficit/hyperactivity disorder. However, due to the phenotypic heterogeneity of NDDs, tDCS is unlikely to be equally effective in all individuals. The present study aimed to establish neuroanatomical biomarkers in typical developing individuals that may be used for the prediction of individual responses to tDCS. Our findings suggest that it may be possible to accurately predict individual responses to tDCS for some behavioural measures using measures of neuroanatomy. In the future, our models might be extended to predict treatment outcome in individuals with clinical diagnoses, and may allow for more individualized, person-centred interventions.

Segregated Dynamical Networks for Biological Motion Perception in the Mu and Beta Range Underlie Social Deficits in Autism.

OBJECTIVE: Biological motion perception (BMP) correlating with a mirror neuron system (MNS) is attenuated in underage individuals with autism spectrum disorder (ASD). While BMP in typically-developing controls (TDCs) encompasses interconnected MNS structures, ASD data hint at segregated form and motion processing. This coincides with less fewer long-range connections in ASD than TDC. Using BMP and electroencephalography (EEG) in ASD, we characterized directionality and coherence (mu and beta frequencies). Deficient BMP may stem from desynchronization thereof in MNS and may predict social-communicative deficits in ASD. Clinical considerations thus profit from brain-behavior associations. METHODS: Point-like walkers elicited BMP using 15 white dots (walker vs. scramble in 21 ASD (mean: 11.3 ± 2.3 years) vs. 23 TDC (mean: 11.9 ± 2.5 years). Dynamic Imaging of Coherent Sources (DICS) characterized the underlying EEG time-frequency causality through time-resolved Partial Directed Coherence (tPDC). Support Vector Machine (SVM) classification validated the group effects (ASD vs. TDC). RESULTS: TDC showed MNS sources and long-distance paths (both feedback and bidirectional); ASD demonstrated distinct from and motion sources, predominantly local feedforward connectivity, and weaker coherence. Brain-behavior correlations point towards dysfunctional networks. SVM successfully classified ASD regarding EEG and performance. CONCLUSION: ASD participants showed segregated local networks for BMP potentially underlying thwarted complex social interactions. Alternative explanations include selective attention and global-local processing deficits. SIGNIFICANCE: This is the first study applying source-based connectivity to reveal segregated BMP networks in ASD regarding structure, cognition, frequencies, and temporal dynamics that may explain socio-communicative aberrancies.

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.

Significance of Beta-Band Oscillations in Autism Spectrum Disorders During Motor Response Inhibition Tasks: A MEG Study.

In Autism Spectrum Disorders (ASD), impaired response inhibition and lack of adaptation are hypothesized to underlie core ASD symptoms, such as social communication and repetitive, stereotyped behavior. Thus, the aim of the present study was to compare neural correlates of inhibition, post-error adaptation, and reaction time variability in ASD and neuro-typical control (NTC) participants by investigating possible differences in error-related changes of oscillatory MEG activity. Twelve male NTC (mean age 20.3 ± 3.7) and fourteen male patients with ASD (mean age 17.8 ± 2.9) were included in the analysis. Subjects with ASD showed increased error-related reaction time variability. MEG analysis revealed decreased beta power in the ASD group in comparison to the NTC group over the centro-parietal channels in both, the pre-stimulus and post-response interval. In the ASD group, mean centro-parietal beta power negatively correlated with dimensional autism symptoms. In both groups, false alarms were followed by an early increase in temporo-frontal theta to alpha power; and by a later decrease in alpha to beta power at central and posterior sensors. Single trial correlations were additionally studied in the ASD group, who showed a positive correlation of pre-stimulus beta power with post-response theta, alpha, and beta power, particularly after hit trials. On a broader scale, the results deliver important insights into top-down control deficits that may relate to core symptoms observed in ASD.

Multimodal alterations of directed connectivity profiles in patients with attention-deficit/hyperactivity disorders.

Functional and effective connectivity measures for tracking brain region interactions that have been investigated using both electroencephalography (EEG) and magnetoencephalography (MEG) bringing up new insights into clinical research. However, the differences between these connectivity methods, especially at the source level, have not yet been systematically studied. The dynamic characterization of coherent sources and temporal partial directed coherence, as measures of functional and effective connectivity, were applied to multimodal resting EEG and MEG data obtained from 11 young patients (mean age 13.2 ± 1.5 years) with attention-deficit/hyperactivity disorder (ADHD) and age-matched healthy subjects. Additionally, machine-learning algorithms were applied to the extracted connectivity features to identify biomarkers differentiating the two groups. An altered thalamo-cortical connectivity profile was attested in patients with ADHD who showed solely information outflow from cortical regions in comparison to healthy controls who exhibited bidirectional interregional connectivity in alpha, beta, and gamma frequency bands. We achieved an accuracy of 98% by combining features from all five studied frequency bands. Our findings suggest that both types of connectivity as extracted from EEG or MEG are sensitive methods to investigate neuronal network features in neuropsychiatric disorders. The connectivity features investigated here can be further tested as biomarkers of ADHD.

Innate or Acquired? - Disentangling Number Sense and Early Number Competencies.

The clinical profile termed developmental dyscalculia (DD) is a fundamental disability affecting children already prior to arithmetic schooling, but the formal diagnosis is often only made during school years. The manifold associated deficits depend on age, education, developmental stage, and task requirements. Despite a large body of studies, the underlying mechanisms remain dubious. Conflicting findings have stimulated opposing theories, each presenting enough empirical support to remain a possible alternative. A so far unresolved question concerns the debate whether a putative innate number sense is required for successful arithmetic achievement as opposed to a pure reliance on domain-general cognitive factors. Here, we outline that the controversy arises due to ambiguous conceptualizations of the number sense. It is common practice to use early number competence as a proxy for innate magnitude processing, even though it requires knowledge of the number system. Therefore, such findings reflect the degree to which quantity is successfully transferred into symbols rather than informing about quantity representation per se. To solve this issue, we propose a three-factor account and incorporate it into the partly overlapping suggestions in the literature regarding the etiology of different DD profiles. The proposed view on DD is especially beneficial because it is applicable to more complex theories identifying a conglomerate of deficits as underlying cause of DD.

The effect of feature-based attention on flanker interference processing: An fMRI-constrained source analysis.

The present study examined whether feature-based cueing affects early or late stages of flanker conflict processing using EEG and fMRI. Feature cues either directed participants' attention to the upcoming colour of the target or were neutral. Validity-specific modulations during interference processing were investigated using the N200 event-related potential (ERP) component and BOLD signal differences. Additionally, both data sets were integrated using an fMRI-constrained source analysis. Finally, the results were compared with a previous study in which spatial instead of feature-based cueing was applied to an otherwise identical flanker task. Feature-based and spatial attention recruited a common fronto-parietal network during conflict processing. Irrespective of attention type (feature-based; spatial), this network responded to focussed attention (valid cueing) as well as context updating (invalid cueing), hinting at domain-general mechanisms. However, spatially and non-spatially directed attention also demonstrated domain-specific activation patterns for conflict processing that were observable in distinct EEG and fMRI data patterns as well as in the respective source analyses. Conflict-specific activity in visual brain regions was comparable between both attention types. We assume that the distinction between spatially and non-spatially directed attention types primarily applies to temporal differences (domain-specific dynamics) between signals originating in the same brain regions (domain-general localization).

Evaluation of the Triple Code Model of numerical processing-Reviewing past neuroimaging and clinical findings.

This review reconciles past findings on numerical processing with key assumptions of the most predominant model of arithmetic in the literature, the Triple Code Model (TCM). This is implemented by reporting diverse findings in the literature ranging from behavioral studies on basic arithmetic operations over neuroimaging studies on numerical processing to developmental studies concerned with arithmetic acquisition, with a special focus on developmental dyscalculia (DD). We evaluate whether these studies corroborate the model and discuss possible reasons for contradictory findings. A separate section is dedicated to the transfer of TCM to arithmetic development and to alternative accounts focusing on developmental questions of numerical processing. We conclude with recommendations for future directions of arithmetic research, raising questions that require answers in models of healthy as well as abnormal mathematical development. WHAT THIS PAPER ADDS: This review assesses the leading model in the field of arithmetic processing (Triple Code Model) by presenting knowledge from interdisciplinary research. It assesses the observed contradictory findings and integrates the resulting opposing viewpoints. The focus is on the development of arithmetic expertise as well as abnormal mathematical development. The original aspect of this article is that it points to a gap in research on these topics and provides possible solutions for future models.

Differences and Similarities for Spatial and Feature-Based Selective Attentional Orienting.

Using selective attention, we prioritize behaviorally relevant information out of all surrounding stimulation. Attention can be oriented intentionally to spatial and/or non-spatial properties (feature-based attention). When comparing spatial and feature-based attention, previous studies identified a common fronto-parietal network, although some reported specific activation for spatial attention and few found higher activation for feature-based attention. Most studies examining differences between attention types investigated the cueing epoch. We examined reorienting processing (after invalid cueing) and correctly focused attention (after valid cueing) for spatial and feature-based orienting using fMRI in two human samples with 40 participants overall and identical stimuli, stimulus probabilities, and timing for all conditions. A fronto-parietal network including parts of the ventral orienting network was activated for reorienting and focused attention for both attention types. Common activity over validities and attention types was located in bilateral IPL/SMG, bilateral IFG/insula, and the cerebellum. A network of mainly posterior areas showed higher activity for spatial compared to feature-based orienting. Conversely, no specialized areas for spatial focused attention or for feature-based attention (reorienting/focusing) was observed. The posterior clusters specialized for spatial reorienting showed overlapping activity with clusters involved in common spatial and feature-based reorienting as well as focused attention over attention types. Therefore, the results hint at a superordinate fronto-parietal network for both attention types during reorienting and focusing, with a spatial specialization of posterior sub-regions.

fMRI-constrained source analysis reveals early top-down modulations of interference processing using a flanker task.

Usually, incongruent flanker stimuli provoke conflict processing whereas congruent flankers should facilitate task performance. Various behavioral studies reported improved or even absent conflict processing with correctly oriented selective attention. In the present study we attempted to reinvestigate these behavioral effects and to disentangle neuronal activity patterns underlying the attentional cueing effect taking advantage of a combination of the high temporal resolution of Electroencephalographic (EEG) and the spatial resolution of functional magnetic resonance imaging (fMRI). Data from 20 participants were acquired in different sessions per method. We expected the conflict-related N200 event-related potential (ERP) component and areas associated with flanker processing to show validity-specific modulations. Additionally, the spatio-temporal dynamics during cued flanker processing were examined using an fMRI-constrained source analysis approach. In the ERP data we found early differences in flanker processing between validity levels. An early centro-parietal relative positivity for incongruent stimuli occurred only with valid cueing during the N200 time window, while a subsequent fronto-central negativity was specific to invalidly cued interference processing. The source analysis additionally pointed to separate neural generators of these effects. Regional sources in visual areas were involved in conflict processing with valid cueing, while a regional source in the anterior cingulate cortex (ACC) seemed to contribute to the ERP differences with invalid cueing. Moreover, the ACC and precentral gyrus demonstrated an early and a late phase of congruency-related activity differences with invalid cueing. We discuss the first effect to reflect conflict detection and response activation while the latter more likely originated from conflict monitoring and control processes during response competition.