Atypical procedural learning in children with developmental coordination disorder: A combined behavioral and neuroimaging study.

While procedural learning (PL) has been implicated in delayed motor skill observed in developmental coordination disorder (DCD), few studies have considered the impact of co-occurring attentional problems. Furthermore, the neurostructural basis of PL in children remains unclear. We investigated PL in children with DCD while controlling for inattention symptoms, and examined the role of fronto-basal ganglia-cerebellar morphology in PL. Fifty-nine children (6-14 years; nDCD = 19, ncontrol = 40) completed the serial reaction time (SRT) task to measure PL. The Attention-Deficit Hyperactivity Disorder Rating Scale-IV was administered to measure inattention symptoms. Structural T1 images were acquired for a subset of participants (nDCD = 10, ncontrol = 28), and processed using FreeSurfer. Volume was extracted for the cerebellum, basal ganglia, and frontal regions. After controlling for inattention symptoms, the reaction time profile of controls was consistent with learning on the SRT task. This was not the case for those with DCD. SRT task performance was positively correlated with cerebellar cortical volume, and children with DCD trended towards lower cerebellar volume compared to controls. Children with DCD may not engage in PL during the SRT task in the same manner as controls, with this differential performance being associated with atypical cerebellar morphology.

Atypical alpha band microstates produced during eyes-closed resting state EEG in autism.

Electroencephalogram (EEG) microstates, which represent quasi-stable patterns of scalp topography, are a promising tool that has the temporal resolution to study atypical spatial and temporal networks in autism spectrum disorder (ASD). While current literature suggests microstates are atypical in ASD, their clinical utility, i.e., relationship with the core behavioural characteristics of ASD, is not fully understood. The aim of this study was to examine microstate parameters in ASD, and examine the relationship between these parameters and core behavioural characteristics in ASD. We compared duration, occurrence, coverage, global explained variance percentage, global field power and spatial correlation of EEG microstates between autistic and neurotypical (NT) adults. Modified k-means cluster analysis was used on eyes-closed, resting state EEG from 30 ASD (10 females, 28.97 ± 9.34 years) and 30 age-equated NT (13 females, 29.33 ± 8.88 years) adults. Five optimal microstates, A to E, were selected to best represent the data. Five microstate maps explaining 80.44% of the NT and 78.44% of the ASD data were found. The ASD group was found to have atypical parameters of microstate A, C, D, and E. Of note, all parameters of microstate C in the ASD group were found to be significantly less than NT. While parameters of microstate D, and E were also found to significantly correlate with subscales of the Ritvo Autism Asperger Diagnostic Scale - Revised (RAADS-R), these findings did not survive a Bonferroni Correction. These findings, in combination with previous findings, highlight the potential clinical utility of EEG microstates and indicate their potential value as a neurophysiologic marker that can be further studied.

Inhibitory dysfunction and social processing difficulties in autism: A comprehensive narrative review.

The primary inhibitory neurotransmitter γ-aminobutyric acid (GABA) has a prominent role in regulating neural development and function, with disruption to GABAergic signalling linked to behavioural phenotypes associated with neurodevelopmental disorders, particularly autism. Such neurochemical disruption, likely resulting from diverse genetic and molecular mechanisms, particularly during early development, can subsequently affect the cellular balance of excitation and inhibition in neuronal circuits, which may account for the social processing difficulties observed in autism and related conditions. This comprehensive narrative review integrates diverse streams of research from several disciplines, including molecular neurobiology, genetics, epigenetics, and systems neuroscience. In so doing it aims to elucidate the relevance of inhibitory dysfunction to autism, with specific focus on social processing difficulties that represent a core feature of this disorder. Many of the social processing difficulties experienced in autism have been linked to higher levels of the excitatory neurotransmitter glutamate and/or lower levels of inhibitory GABA. While current therapeutic options for social difficulties in autism are largely limited to behavioural interventions, this review highlights the psychopharmacological studies that explore the utility of GABA modulation in alleviating such difficulties.

EEG microstates in early-to-middle childhood show associations with age, biological sex, and alpha power.

Electroencephalographic (EEG) microstates can provide a unique window into the temporal dynamics of large-scale brain networks across brief (millisecond) timescales. Here, we analysed fundamental temporal features of microstates extracted from the broadband EEG signal in a large (N = 139) cohort of children spanning early-to-middle childhood (4-12 years of age). Linear regression models were used to examine if participants' age and biological sex could predict the temporal parameters GEV, duration, coverage, and occurrence, for five microstate classes (A-E) across both eyes-closed and eyes-open resting-state recordings. We further explored associations between these microstate parameters and posterior alpha power after removal of the 1/f-like aperiodic signal. The microstates obtained from our neurodevelopmental EEG recordings broadly replicated the four canonical microstate classes (A to D) frequently reported in adults, with the addition of the more recently established microstate class E. Biological sex served as a significant predictor in the regression models for four of the five microstate classes (A, C, D, and E). In addition, duration and occurrence for microstate E were both found to be positively associated with age for the eyes-open recordings, while the temporal parameters of microstates C and E both exhibited associations with alpha band spectral power. Together, these findings highlight the influence of age and sex on large-scale functional brain networks during early-to-middle childhood, extending understanding of neural dynamics across this important period for brain development.

Exploring the role of autistic traits and eating disorder psychopathology on mentalising ability in the general population.

BACKGROUND: This study evaluated the role of overlapping traits and characteristics related to autism spectrum disorder (autism) and anorexia nervosa (AN) in the general population, and the impact of these traits on mentalising ability. METHODS: A sample of young adults (N = 306), aged 18-25 years, was recruited to complete an online study that consisted of 4 measures: the Autism-Spectrum Quotient, Eating Disorder Examination Questionnaire, the Mentalization Scale, and the Reading the Mind in the Eyes task. RESULTS: Higher levels of autistic traits, particularly difficulty with attention switching, were associated with increased eating disorder psychopathology. Overall, autistic traits and eating disorder psychopathology were related among females, but not males. Difficulty with attention switching, however, was related to eating disorder psychopathology among both females and males. Autistic traits also appear to have a greater role in mentalising ability than does eating disorder psychopathology. CONCLUSION: The role of attention switching in overlapping traits of autism and eating disorder psychopathology needs to be more comprehensively evaluated by future research, as does the role of biological sex. Expanded knowledge in this field will help to better understand and evaluate symptoms at presentation, leading to clearer diagnoses and potentially better treatment outcomes.

A systematic review of cannabidiol trials in neurodevelopmental disorders.

Cannabis-derived compounds, such as cannabidiol (CBD) and delta-9-trans-tetrahydrocannabinol (THC), are increasingly prescribed for a range of clinical indications. These phyto-cannabinoids have multiple biological targets, including the body's endocannabinoid system. There is growing scientific interest in the use of CBD, a non-intoxicating compound, to ameliorate symptoms associated with neurodevelopmental disorders. However, its suitability as a pharmaceutical intervention has not been reliably established in these clinical populations. This systematic review examines the nine published randomised controlled trials (RCTs) that have probed the safety and efficacy of CBD in individuals diagnosed with attention deficit hyperactivity disorder, autism spectrum disorder, intellectual disability, Tourette Syndrome, and complex motor disorders. Studies were identified systematically through searching four databases: Medline, CINAHL complete, PsycINFO, and EMBASE. Inclusion criteria were randomised controlled trials involving CBD and participants with neurodevelopmental disorders. No publication year or language restrictions were applied. Relevant data were extracted from the identified list of eligible articles. After extraction, data were cross-checked between the authors to ensure consistency. Several trials indicate potential efficacy, although this possibility is currently too inconsistent across RCTs to confidently guide clinical usage. Study characteristics, treatment properties, and outcomes varied greatly across the included trials. The material lack of comparable RCTs leaves CBD's suitability as a pharmacological treatment for neurodevelopmental disorders largely undetermined. A stronger evidence base is urgently required to establish safety and efficacy profiles and guide the ever-expanding clinical uptake of cannabis-derived compounds in neurodevelopmental disorders. Prospero registration number: CRD42021267839.

Father trait anger and associations with father-infant bonding and caregiving: The mediating role of mentalizing.

Trait anger reflects a tendency to feel irritation, annoyance, and rage, and involves a narrowing of cognition and attention. This narrowed scope may impact the capacity to understand the mental states of oneself and others (mentalizing), which for fathers of infants may compromise bonding and caregiving involvement. Here, we investigated the extent to which mentalizing mediated the relationship between father trait anger and both father-infant bonding and father involvement in infant caregiving. Data were from 168 fathers (M = 30.04 years of age, SD = 1.36) of 190 infants (M = 7.58 months of age, SD = 5.06) in the longitudinal Men and Parenting Pathways (MAPP) study. We assessed fathers' preconception trait anger at Wave 1 and their mentalizing 2 years later at Wave 3. At Waves 3, 4, and/or 5, we assessed father-infant bonding and father involvement in infant caregiving when men had an infant younger than 18 months of age. Associations were examined using path analysis. Poorer mentalizing fully mediated the relationship between preconception trait anger and father-infant bonding (total score), but not involvement in infant caregiving. Further, poorer mentalizing fully mediated the relationships between trait anger and each component of the father-infant bond (i.e., patience and tolerance, affection and pride, and pleasure in interactions). Findings suggest that for men high on trait anger, targeted interventions that facilitate mentalizing capacities may help to develop a foundation for a strong father-infant bond. Interventions may be offered on becoming a father (perinatal), or prior to becoming a father (preconception) to prevent future bonding problems.

Resting state electroencephalography power correlates with individual differences in implicit sequence learning.

Neuroimaging resting state paradigms have revealed synchronised oscillatory activity is present even in the absence of completing a task or mental operation. One function of this neural activity is likely to optimise the brain's sensitivity to forthcoming information that, in turn, likely promotes subsequent learning and memory outcomes. The current study investigated whether this extends to implicit forms of learning. A total of 85 healthy adults participated in the study. Resting state electroencephalography was first acquired from participants before they completed a serial reaction time task. On this task, participants implicitly learnt a visuospatial-motor sequence. Permutation testing revealed a negative correlation between implicit sequence learning and resting state power in the upper theta band (6-7 Hz). That is, lower levels of resting state power in this frequency range were associated with superior levels of implicit sequence learning. This association was observed at midline-frontal, right-frontal and left-posterior electrodes. Oscillatory activity in the upper theta band supports a range of top-down processes including attention, inhibitory control and working memory, perhaps just for visuospatial information. Our results may be indicating that disengaging theta-supported top-down attentional processes improves implicit learning of visuospatial-motor information that is embedded in sensory input. This may occur because the brain's sensitivity to this type of information is optimally achieved when learning is driven by bottom-up processes. Moreover, the results of this study further demonstrate that resting state synchronised brain activity influences subsequent learning and memory.

An Investigation of Age-related Neuropathophysiology in Autism Spectrum Disorder Using Fixel-based Analysis of Corpus Callosum White Matter Micro- and Macrostructure.

Fixel-based analysis was used to probe age-related changes in white matter micro- and macrostructure of the corpus callosum between participants with (N = 54) and without (N = 50) autism spectrum disorder (ASD). Data were obtained from the Autism Brain Imaging Data Exchange-II (ABIDE-II). Compared to age-matched controls, young adolescents with ASD (11.19 ± 7.54 years) showed reduced macroscopic fiber cross-section (logFC) and combined fiber-density and cross-section (FDC). Reduced fiber-density (FD) and FDC was noted in a marginally older (13.87 ± 3.15 years) ASD cohort. Among the oldest ASD cohort (17.07 ± 3.56 years), a non-significant trend indicative of reduced FD was noted. White matter aberration appears greatest and most widespread among younger ASD cohorts. This supports the suggestion that some early neuropathophysiological indicators in ASD may dissipate with age.

A systematic review of the neurobiological effects of theta-burst stimulation (TBS) as measured using functional magnetic resonance imaging (fMRI).

Theta burst stimulation (TBS) is associated with the modulation of a range of clinical, cognitive, and behavioural outcomes, but specific neurobiological effects remain somewhat unclear. This systematic literature review investigated resting-state and task-based functional magnetic resonance imaging (fMRI) outcomes post-TBS in healthy human adults. Fifty studies that applied either continuous-or intermittent-(c/i) TBS, and adopted a pretest-posttest or sham-controlled design, were included. For resting-state outcomes following stimulation applied to motor, temporal, parietal, occipital, or cerebellar regions, functional connectivity generally decreased in response to cTBS and increased in response to iTBS, though there were some exceptions to this pattern of response. These findings are mostly consistent with the assumed long-term depression (LTD)/long-term potentiation (LTP)-like plasticity effects of cTBS and iTBS, respectively. Task-related outcomes following TBS were more variable. TBS applied to the prefrontal cortex, irrespective of task or state, also produced more variable responses, with no consistent patterns emerging. Individual participant and methodological factors are likely to contribute to the variability in responses to TBS. Future studies assessing the effects of TBS via fMRI must account for factors known to affect the TBS outcomes, both at the level of individual participants and of research methodology.

Individual differences in procedural learning are associated with fiber specific white matter microstructure of the superior cerebellar peduncles in healthy adults.

Functional neuroimaging has consistently implicated the fronto-basal ganglia-cerebellar circuit in procedural learning-defined as the incidental acquisition of sequence information through repetition. Limited work has probed the role of white matter fiber pathways that connect the regions in this network, such as the superior cerebellar peduncles (SCP) and the striatal premotor tracts (STPMT), in explaining individual differences in procedural learning. High angular diffusion weighted imaging was acquired from 20 healthy adults aged 18-45 years. Fixel-based analysis was performed to extract specific measures of white matter microstructure (fiber density; FD) and macrostructure (fiber cross-section; FC), from the SCP and STPMT. These fixel metrics were correlated with performance on the serial reaction time (SRT) task, and sensitivity to the sequence was indexed by the difference in reaction time between the final block of sequence trials and the randomized block (namely, the 'rebound effect'). Analyses revealed a significant positive relationship between FD and the rebound effect in segments of both the left and right SCP (pFWE < .05). That is, increased FD in these tracts was associated with greater sensitivity to the sequence on the SRT task. No significant associations were detected between fixel metrics in the STPMT and the rebound effect. Our results support the likely role of white matter organization in the basal ganglia-cerebellar circuit in explaining individual differences in procedural learning.

Father trait anger: Associations with father-infant bonding and subsequent parenting stress.

Introduction: Parent anger presents a risk to family safety and child development. Father trait anger may also compromise the early relational context of fathers and offspring, yet evidence is lacking. The aim of this study is to examine effects of father trait anger on parenting stress in the toddler years, and the mediational role of father-infant bonding. Method: Data were from 177 Australian fathers of 205 children. Trait anger (total, angry temperament, and angry reaction), father-infant bonding subscales (patience and tolerance, affection and pride, and pleasure in interaction), and subsequent parenting stress (parental distress, difficult child, and parent-child dysfunctional interaction) were assessed. At each of the subscale levels, mediational path models examined whether father-infant bonding explained the relationship between trait anger and parenting stress. Models were presented where there was at least a small association between the mediator and both the predictor and outcome. Results: Patience and tolerance was the only domain of father-infant bonding correlated with both trait anger and all parenting stress outcomes. Patience and tolerance partially mediated the effect of total trait anger on parental distress and fully mediated effects on difficult child and parent-child dysfunctional interaction. Patience and tolerance fully mediated relationships between angry temperament and all domains of parenting stress. Angry reactions only had a direct effect on parental distress. Discussion: Father trait anger both directly and indirectly (through patience and tolerance in the father-infant bond) impacts their experiences of parenting stress in the toddler years. Early interventions to manage father trait anger and improve father-infant bonding may benefit fathers and children.

Greenness modifies the association between ambient air pollution and cognitive function in Australian adolescents, but not in mid-life adults.

Exposure to ambient air pollution has been associated with reduced cognitive function in childhood and later life, with too few mid-life studies to draw conclusions. In contrast, residential greenness has been associated with enhanced cognitive function throughout the lifecourse. Here we examine the extent to which (1) ambient air pollution and residential greenness predict later cognitive function in adolescence and mid-life, and (2) greenness modifies air pollution-cognitive function associations. PARTICIPANTS: 6220 adolescents (51% male) and 2623 mid-life adults (96% mothers) from the Longitudinal Study of Australian Children. MEASURES: Exposures: Annual average particulate matter <2.5 µm (PM2.5), nitrogen dioxide (NO2) and greenness (Normalised Difference Vegetation Index) for residential addresses from validated land-use regression models over a 10-13-year period. OUTCOMES: Cognitive function from CogState tests of attention, working memory and executive function, dichotomised into poorer (worst quartile) versus not poor. ANALYSES: Adjusted mixed-effects generalised linear models with residential greenness assessed as an effect modifier (high vs. low divided at median). The annual mean for PM2.5 and NO2 across exposure windows was 6.3-6.8 µg/m3, and 5.5-7.1 ppb, respectively. For adolescents, an IQR increment of NO2 was associated with 19-24% increased odds of having poorer executive function across all time windows, while associations weren't observed between air pollution and other outcomes. For adults, high NO2 predicted poorer cognitive function across all outcomes, while high PM2.5 predicted poorer attention only. There was little evidence of associations between greenness and cognitive function in adjusted models for both generations. Interactions were found between residential greenness, air pollutants and cognitive function in adolescents, but not adults. The magnitude of effects was similar across generations and exposure windows. Findings highlight the potential benefits of cognitive health associated with the regulation of air pollution and urban planning strategies for increasing green spaces and vegetation.

Examination of Cerebellar Grey-Matter Volume in Children with Neurodevelopmental Disorders: a Coordinated Analysis Using the ACAPULCO Algorithm.

Alterations in cerebellar morphology relative to controls have been identified in children with autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and developmental coordination disorder (DCD). However, it is not clear if common cerebellar regions are affected in each neurodevelopmental disorder and whether cerebellar morphological changes reflect a generic developmental vulnerability, or disorder-specific characteristic. The present study concatenated anatomical MRI scans from five existing cohorts, resulting in data from 252 children between the age of 7 and 12 years (ASD = 58, ADHD = 86, DCD = 22, Controls = 86). The ACAPULCO processing pipeline for cerebellar segmentation was conducted on T1-weighted images. A voxel-wise approach with general linear model was used to compare grey-matter volume of the 27 cerebellar lobules between each clinical group and controls. Our findings revealed that the ADHD group showed lower grey-matter volume in the left Crus I - part of the executive/non-motor portion of the cerebellum, relative to controls (p = 0.02). This no longer remained significant after controlling for medication status. There were no regions of significant differences in volume of the cerebellar lobules in ASD or DCD compared to controls. Future work will conduct harmonisation of behavioural data (cognitive and motor outcomes) across cohorts, enabling more advanced analyses to identify symptom cluster across neurodevelopmental disorders.

Functional brain connectivity during exposure to the scale and color of interior built environments.

Understanding brain activity linked to built environment exposure is important, as it may affect underlying cognitive, perceptual, and emotional processes, which have a critical influence in our daily life. As our time spent inside buildings is rising, and mental health problems have become more prevalent, it is important we investigate how design characteristics of the built environment impact brain function. In this study, we utilized electroencephalography to understand whether the design elements of scale and color of interior built environments modulate functional brain connectivity (i.e., brain network communication). Using a Cave Automatic Virtual Environment, while controlling indoor environmental quality responsible for physiological comfort, healthy adult participants aged 18-55 years (66 for scale, subset of 18 for color), were exposed to context-neutral indoor room scenes presented for two-minutes each. Our results show that both enlarging and reducing scale enhanced theta connectivity across the left temporoparietal region and right frontal region. We also found when reducing the built environment scale, there was a network exhibiting greater high-gamma connectivity, over the right frontoparietal region. For color, the condition (blue) contrasted to our achromatic control (white) increased theta connectivity in the frontal hemispheres. These findings identify a link between theta and gamma oscillations during exposure to the scale and color of the built environment, showing that design characteristics of the built environment could affect our cognitive processes and mental health. This suggests that, through the design of buildings, we may be able to mediate performance and health outcomes, which could lead to major health and economic benefits for society.

Value of Self-Disclosure to Parents and Peers During Adolescence.

Self-disclosure is a crucial part of developing close interpersonal relationships during adolescence. In particular, sharing information with a greater depth of intimacy is thought to strengthen social bonds and thus support mental health. The current study investigated the value for different depths of self-disclosures to close others (mothers and best friends) during adolescence and its association with mental health and well-being. Fifty-four girls (11.0-15.9 years) completed a forced-choice monetary paradigm to assess value for self-disclosures and questionnaires on mental health. Participants significantly valued (i.e., forfeited monetary reward) for disclosures to both mothers and best friends, although intimate disclosures were more "costly" than superficial disclosures. Greater value for intimate self-disclosures to mothers was also associated with better mental health and well-being.

Effects of non-invasive brain stimulation in dystonia: a systematic review and meta-analysis.

Background: Deep brain stimulation is a highly effective treatment of dystonia but is invasive and associated with risks, such as intraoperative bleeding and infections. Previous research has used non-invasive brain stimulation (NIBS) in an attempt to alleviate symptoms of dystonia. The results of these studies, however, have been variable, leaving efficacy unclear. Objectives: This study aimed to evaluate the effects of NIBS on symptoms of dystonia and determine whether methodological characteristics are associated with variability in effect size. Methods: Web of Science, Embase, and MEDLINE Complete databases were searched for articles using any type of NIBS as an intervention in dystonia patients, with changes in dystonia symptoms the primary outcome of interest. Results: Meta-analysis of 27 studies demonstrated a small effect size for NIBS in reducing symptoms of dystonia (random-effects Hedges' g = 0.21, p = .002). Differences in the type of NIBS, type of dystonia, and brain region stimulated had a significant effect on dystonia symptoms. Meta-regression revealed that 10 sessions of active stimulation and the application of concurrent motor training programs resulted in significantly larger mean effect sizes. Conclusion: NIBS has yielded small improvements to dystonic symptoms, but effect sizes depended on methodological characteristics, with more sessions of stimulation producing a larger response. Future research should further investigate the application of NIBS parallel to motor training, in addition to providing a greater quantity of sessions, to help define optimal parameters for NIBS protocols in dystonia. Registration: PROSPERO 2020, CRD42020175944.

Resting state electroencephalography microstates in autism spectrum disorder: A mini-review.

Atypical spatial organization and temporal characteristics, found via resting state electroencephalography (EEG) microstate analysis, have been associated with psychiatric disorders but these temporal and spatial parameters are less known in autism spectrum disorder (ASD). EEG microstates reflect a short time period of stable scalp potential topography. These canonical microstates (i.e., A, B, C, and D) and more are identified by their unique topographic map, mean duration, fraction of time covered, frequency of occurrence and global explained variance percentage; a measure of how well topographical maps represent EEG data. We reviewed the current literature for resting state microstate analysis in ASD and identified eight publications. This current review indicates there is significant alterations in microstate parameters in ASD populations as compared to typically developing (TD) populations. Microstate parameters were also found to change in relation to specific cognitive processes. However, as microstate parameters are found to be changed by cognitive states, the differently acquired data (e.g., eyes closed or open) resting state EEG are likely to produce disparate results. We also review the current understanding of EEG sources of microstates and the underlying brain networks.

Right anterior theta connectivity predicts autistic social traits in typically developing children.

Growing evidence supports functional network alterations in autism spectrum disorder, however much less is known about the neural mechanisms underlying autistic traits in typically developing children. Using resting-state electroencephalographic (EEG) recordings, we examined whether functional connectivity could predict autistic trait expression in 127 children aged between 4 and 12 years. Regression models showed that right anterior theta connectivity was a significant predictor of autistic traits (p = 0.013), with increased connectivity in this region associated with greater autistic trait expression. These results corroborate similar recent findings in adults, extending this observation to a cohort of children spanning early-to-middle childhood. These findings further highlight EEG-derived functional connectivity as a sensitive physiological correlate of autistic trait expression in typically developing children.