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Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a behavioral phenotype characterized by impaired development of social-communicative skills and excessive repetitive and stereotyped behaviors. Despite high phenotypic heterogeneity in ASD, a meaningful subpopulation of children with ASD (∼90%) show significant general motor impairment. More focused studies on the nature of motor impairment in ASD reveal that children with ASD are particularly impaired on tasks such as ball catching and motor imitation that require efficient visual-motor integration (VMI). Motor computational approaches also provide evidence for VMI impairment showing that children with ASD form internal sensorimotor representations that bias proprioceptive over visual feedback. Impaired integration of visual information to form internal representations of others' and the external world may explain observed impairments on VMI tasks and motor imitation of others. Motor imitation is crucial for acquiring both social and motor skills, and impaired imitation skill may contribute to the observed core behavioral phenotype of ASD. The current review examines evidence supporting VMI impairment as a core feature of ASD that may contribute to both impaired motor imitation and social-communicative skill development. We propose that understanding the neurobiological mechanisms underlying VMI impairment in ASD may be key to discovery of therapeutics to address disability in children and adults with ASD. [ABSTRACT FROM AUTHOR]

Difficulties with praxis, the ability to perform learned skilled movements, have been robustly demonstrated in autism spectrum disorder (autism). However, praxis assessment is not routinely included in autism characterization batteries, in part because it is traditionally time consuming to administer and score. We test whether dyspraxia in autism can be captured with a brief measure. Youth with autism (n = 41) and matched typically developing controls (n = 32), aged 8–16 years, completed a 5-min praxis battery. The 19-item battery included four subtests: gesture to command, tool use, familiar imitation, and meaningless imitation. Video recordings were coded for error types and compared to participant characterization variables. Consistent with research using a lengthy battery, autistic youth made more errors overall, with a large effect size. Groups demonstrated similar distributions of error types, suggesting that dyspraxia in autism is not limited to a particular error form. In the autism group, praxis was associated with adaptive functioning, but not autism traits. A shortened battery is sufficiently sensitive to praxis differences between autistic and typically developing youth, increasing the feasibility of including praxis within clinical assessments or larger research batteries aimed at testing relationships with downstream skills. • A brief (5-min) battery is sufficiently sensitive to praxis differences between autistic and typically developing youth. • Weaknesses in praxis are associated with adaptive behavior skills in autistic youth. • Praxis assessment should be included in clinical assessments and larger research batteries. [ABSTRACT FROM AUTHOR]

Copying other people's mannerisms (i.e., mimicry) occurs spontaneously during social interactions, and is thought to contribute to sharing emotions, affiliation with partners and interaction quality. While previous research shows decreased mimicry of emotional facial expressions in autism spectrum disorders (ASD), we know relatively little about how non-emotional, non-facial behavioural mimicry manifests and, more importantly, what it means for autistic individuals' social interactions. In a controlled, semi-naturalistic interaction setting, this study examined how often autistic and neurotypical (NT) children mimicked a virtual partner's non-facial mannerisms as they engaged in an interactive story-telling activity. Subsequently, children reported how affiliated they felt towards their interaction partner using an established implicit measure of closeness and a set of questions. Results revealed reduced mimicry (p =.001, φ = 0.38) and less affiliation (p =.01, φ = 0.33) in ASD relative to NT children. Mimicry was associated with affiliation for NT (r (23) = 0.64, p =.0009), but not ASD, children (r (31) = 0.07, p =.72). These results suggest an autism-associated reduction in mimicry and that mimicry during social interactions may not substantially contribute to affiliation in autism. • Many people unconsciously copy (i.e., mimic) others' facial expressions or postures during a social interaction. • This study examined autistic and non-autistic children's mimicry of a virtual partner while playing a story-telling game. • The results showed that autistic children mimic their partner less than neurotypical children do. • Mimicry was related to increased affiliation with the partner for neurotypical children, but not for autistic children. [ABSTRACT FROM AUTHOR]

Autism is characterized by language and communication deficits. We investigated grammatical and lexical processes in high-functioning autism by contrasting the production of regular and irregular past-tense forms. Boys with autism and typically developing control boys did not differ in accuracy or error rates. However, boys with autism were significantly faster than controls at producing rule-governed past-tenses ( slip-slipped , plim-plimmed , bring-bringed ), though not lexically dependent past-tenses ( bring-brought , squeeze-squeezed , splim-splam ). This pattern mirrors previous findings from Tourette syndrome attributed to abnormalities of frontal/basal-ganglia circuits that underlie grammar. We suggest a similar abnormality underlying language in autism. Importantly, even when children with autism show apparently normal language (e.g., in accuracy or with diagnostic instruments), processes and/or brain structures subserving language may be atypical in the disorder. [ABSTRACT FROM AUTHOR]

Frontal corticostriatal circuits (FCSC) are involved in self-regulation of cognition, emotion, and motor function. While these circuits are implicated in attention-deficit/hyperactivity disorder (ADHD), the literature establishing FCSC associations with ADHD is inconsistent. This may be due to study variability in considerations of how fMRI motion regression was handled between groups, or study specific differences in age, sex, or the striatal subregions under investigation. Given the importance of these domains in ADHD it is crucial to consider the complex interactions of age, sex, striatal subregions and FCSC in ADHD presentation and diagnosis. In this large-scale study of 362 8–12 year-old children with ADHD (n = 165) and typically developing (TD; n = 197) children, we investigate associations between FCSC with ADHD diagnosis and symptoms, sex, and go/no-go (GNG) task performance. Results include: (1) increased striatal connectivity with age across striatal subregions with most of the frontal cortex, (2) increased frontal-limbic striatum connectivity among boys with ADHD only, mostly in default mode network (DMN) regions not associated with age, and (3) increased frontal-motor striatum connectivity to regions of the DMN were associated with greater parent-rated inattention problems, particularly among the ADHD group. Although diagnostic group differences were no longer significant when strictly controlling for head motion, with motion possibly reflecting the phenotypic variance of ADHD itself, the spatial distribution of all symptom, age, sex, and other ADHD group effects were nearly identical to the initial results. These results demonstrate differential associations of FCSC between striatal subregions with the DMN and FPN in relation to age, ADHD, sex, and inhibitory control. [ABSTRACT FROM AUTHOR]

Abstract: While studies among adults implicate the amygdala and interconnecting brain regions in encoding emotional stimuli, few studies have examined whether developmental changes occur within this emotional-memory network during adolescence. The present study examined whether adolescents and adults differentially engaged the amygdala and hippocampus during successful encoding of emotional pictures, with either positive or negative valence. Eighteen adults and twelve adolescents underwent event-related fMRI while encoding emotional pictures. Approximately 30min later, outside the scanner, subjects were asked to recall the pictures seen during the scan. Age group differences in brain activity in the amygdala and hippocampus during encoding of the pictures that were later successfully and unsuccessfully recalled were separately compared for the positive and negative pictures. Adolescents, relative to adults, demonstrated enhanced activity in the right amygdala during encoding of positive pictures that were later recalled compared to not recalled. There were no age group differences in amygdala or hippocampal activity during successful encoding of negative pictures. The findings of preferential activity within the adolescent right amygdala during successful encoding of positive pictures may have implications for the increased reward and novelty seeking behavior, as well as elevated rates of psychopathology, observed during this distinct developmental period. [Copyright &y& Elsevier]

Abstract: Evidence exists for deficits in error monitoring in autism. These deficits may be particularly important because they may contribute to excessive perseveration and repetitive behavior in autism. We examined the neural correlates of error monitoring using functional magnetic resonance imaging (fMRI) in 8–12-year-old children with high functioning autism (HFA, n =11) and typically developing children (TD, n =15) during performance of a Go/No-Go task by comparing the neural correlates of commission errors versus correct response inhibition trials. Compared to TD children, children with HFA showed increased BOLD fMRI signal in the anterior medial prefrontal cortex (amPFC) and the left superior temporal gyrus (STempG) during commission error (versus correct inhibition) trials. A follow-up region-of-interest analysis also showed increased BOLD signal in the right insula in HFA compared to TD controls. Our findings of increased amPFC and STempG activity in HFA, together with the increased activity in the insula, suggest a greater attention towards the internally driven emotional state associated with making an error in children with HFA. Since error monitoring occurs across different cognitive tasks throughout daily life, an increased emotional reaction to errors may have important consequences for early learning processes. [Copyright &y& Elsevier]

The article offers a study which examines patterns of executive and oculomotor control in a group of boys and girls with attention-deficit/hyperactivity disorder (ADHD). It shows that sex differences in children with ADHD expand beyond symptom presentation to the development of oculomotor control. It depicts that saccade latency may express a specific deficit among girls having ADHD.

Abstract: Tourette''s syndrome (TS) is a developmental disorder characterized by motor and verbal tics. The tics, which are fast and involuntary, result from frontal/basal-ganglia abnormalities that lead to unsuppressed behaviors. Language has not been carefully examined in TS. We tested the processing of two basic aspects of language: idiosyncratic and rule-governed linguistic knowledge. Evidence suggests that idiosyncratic knowledge (e.g., in irregular past tense formation; bring–brought) is stored in a mental lexicon that depends on the temporal-lobe-based declarative memory system that also underlies conceptual knowledge. In contrast, evidence suggests that rule-governed combination (e.g., in regular past tenses; walk +-ed) takes place in a mental grammar that relies on the frontal/basal-ganglia-based procedural memory system, which also underlies motor skills such as how to use a hammer. We found that TS children were significantly faster than typically developing control children in producing rule-governed past tenses (slip–slipped, plim–plimmed, bring–bringed) but not irregular and other unpredictable past tenses (bring–brought, splim–splam). They were also faster than controls in naming pictures of manipulated (hammer) but not non-manipulated (elephant) items. These data were not explained by a wide range of potentially confounding subject- and item-level factors. The results suggest that the processing of procedurally based knowledge, both of grammar and of manipulated objects, is particularly speeded in TS. The frontal/basal-ganglia abnormalities may thus lead not only to tics, but also to a wider range of rapid behaviors, including the cognitive processing of rule-governed forms in language and other types of procedural knowledge. [Copyright &y& Elsevier]

Background: Attention-deficit/hyperactivity disorder (ADHD) has been shown to be associated with anomalous motor development, including excessive overflow movements. The neurological basis of these deficits has not been established. Functional magnetic resonance imaging (fMRI) was used to determine whether differences in brain activation during sequential finger tapping are present in children with ADHD compared with typically developing control subjects. Methods: Twenty-two right-handed children between 8 and 12 years old, 11 with ADHD and 11 typically developing control subjects closely matched for age and gender, performed self-paced sequential finger tapping during fMRI acquisition. Results: There were no significant between-group differences in speed of sequential finger tapping. The between-group whole-brain comparison showed greater magnitude of activation for control subjects than children with ADHD in the right superior parietal lobe during both right-handed and left-handed finger tapping. The region-of-interest analysis within Brodmann Area 4 revealed that children with ADHD showed a significantly smaller extent of fMRI activation in the primary motor cortex contralateral to the finger-sequencing hand. Conclusions: Despite similar speed of sequential finger tapping, children with ADHD showed decreased contralateral motor cortex and right parietal cortex activation during both right-handed finger sequencing (RHFS) and left-handed finger sequencing (LHFS). The fMRI findings suggest that children with ADHD have anomalous development of cortical systems necessary for execution of patterned movements. [Copyright &y& Elsevier]

Event-related fMRI was used to investigate the hypothesis that neural activity involved in response inhibition depends upon the nature of the response being inhibited. Two different Go/No-go tasks were compared—one with a high working memory load and one with low. The ‘simple’ Go/No-go task with low working memory load required subjects to push a button in response to green spaceships but not red spaceships. A ‘counting’ Go/No-go task (high working memory load) required subjects to respond to green spaceships as well as to those red spaceships preceded by an even number of green spaceships. In both tasks, stimuli were presented every 1.5 s with a 5:1 ratio of green-to-red spaceships. fMRI group data for each task were analyzed using random effects models to determine signal change patterns associated with Go events and No-go events (corrected P≤0.05). For both tasks, Go responses were associated with signal change in the left primary sensorimotor cortex, supplementary motor area (SMA) proper, and anterior cerebellum (right>left). For the simple task, No-go events were associated with activation in the pre-SMA; the working memory-loaded ‘counting’ task elicited additional No-go activation in the right dorsolateral prefrontal cortex. The findings suggest that neural contributions to response inhibition may be task dependent; the pre-SMA appears necessary for inhibition of unwanted movements, while the dorsolateral prefrontal cortex is recruited for tasks involving increased working memory load. [Copyright &y& Elsevier]

: BackgroundAnatomic magnetic resonance imaging (MRI) studies of attention-deficit/hyperactivity disorder (ADHD) have been limited by use of callosal rather than sulcal/gyral landmarks in defining cerebral lobes and functionally relevant sublobar regions (e.g., prefrontal cortex). We present an investigation of cerebral volumes in ADHD using a Talairach-based approach that uses cortical landmarks to define functionally relevant regions.: MethodsVolumes were compared between groups of 12 boys with ADHD and 12 age- and gender-matched control subjects, using a series of multiple analyses of variance.: ResultsBoys with ADHD had (on average) 8.3% smaller total cerebral volumes. Significant reductions in lobar volumes were seen only for the frontal lobes. Within the frontal lobes, a reduction was seen in both gray and white matter volumes, with some evidence suggesting lateralization of these findings: reduction in frontal white matter volume was specific to the left hemisphere; there was a bilateral reduction in frontal gray matter volume but more so in the right hemisphere. Subparcellation of the frontal lobe revealed smaller prefrontal, premotor, and deep white matter volumes.: ConclusionsFindings suggest that ADHD is associated with decreased frontal lobe gray and white matter volumes. More than one subdivision of the frontal lobes appears to be reduced in volume, suggesting that the clinical picture of ADHD encompasses dysfunctions attributable to anomalous development of both premotor and prefrontal cortices. [ABSTRACT FROM AUTHOR]

Assesses saccadic eye movements in boys with Tourette syndrome with or without attention-deficit hyperactivity disorder. Comparison of the eye movements in boys with Tourette and with that of an age-matched group of male controls; Examination of the motor response preparation, response inhibition and working memory of the subjects; Results and discussion.

• Motor imitation can be computed from a single 2D camera using automated methods. • 2D imitation scores better discriminate ASD from TD controls vs. a hand-coding method. • 2D imitation scores are significantly associated with the severity of ASD symptoms. Motor imitation difficulties are pervasive in children with Autism Spectrum Disorder (ASD). Previous research demonstrated the validity and reliability of an algorithm called Computerized Assessment of Motor Imitation (CAMI) using 3D depth cameras. However, incorporating CAMI into serious games and making it accessible in clinic and home settings requires a more scalable approach that uses "off-the-shelf" 2D cameras. In a brief (one-minute) task, children (23 ASD, 17 typically developing [TD]) imitated a model's dance movements while simultaneously being recorded using Kinect Xbox motion tracking technology (Kinect 3D) and a single 2D camera. Pose-estimation software (OpenPose 2D) was used on the 2D camera video to fit a skeleton to the imitating child. Motor imitation scores computed from the fully automated OpenPose 2D CAMI method were compared to scores computed from the Kinect 3D CAMI and Human Observation Coding (HOC) methods. Motor imitation scores obtained from the OpenPose 2D CAMI method were significantly correlated with scores obtained from the Kinect 3D CAMI method (r 40 = 0.82, p < 0.001) and the HOC method (r 40 = 0.80, p < 0.001). Both 2D and 3D CAMI methods showed better discriminative ability than the HOC, with the Kinect 3D CAMI method outperforming the OpenPose 2D CAMI method (area under ROC curve (AUC): AUC HOC = 0.799, AUC 2D-CAMI = 0.876, AUC 3D-CAMI = 0.94). Finally, all motor imitation scores were significantly associated with the social-communication impairment (all p ≤ 0.003). This pilot-study demonstrated that motor imitation can be automatically quantified using a single 2D camera. [ABSTRACT FROM AUTHOR]

Default mode network (DMN) dysfunction is theorized to play a role in attention lapses and task errors in children with attention-deficit/hyperactivity disorder (ADHD). In ADHD, the DMN is hyperconnected to task-relevant networks, and both increased functional connectivity and reduced activation are related to poor task performance. The current study extends existing literature by considering interactions between the DMN and task-relevant networks from a brain network perspective and by assessing how these interactions relate to response control. We characterized both static and time-varying functional brain network organization during the resting state in 43 children with ADHD and 43 age-matched typically developing (TD) children. We then related aspects of network integration to go/no-go performance. We calculated participation coefficient (PC), a measure of a region's inter-network connections, for regions of the DMN, canonical cognitive control networks (fronto-parietal, salience/cingulo-opercular), and motor-related networks (somatomotor, subcortical). Mean PC was higher in children with ADHD as compared to TD children, indicating greater integration across networks. Further, higher and less variable PC was related to greater commission error rate in children with ADHD. Together, these results inform our understanding of the role of the DMN and its interactions with task-relevant networks in response control deficits in ADHD. • The DMN is more integrated with task-relevant networks in children with ADHD. • Higher and less variable DMN integration relates to poorer response control in ADHD. • DMN dysfunction may play a key role in response control deficits in ADHD. [ABSTRACT FROM AUTHOR]

Reaction time (RT) is associated with increased amplitude of the Blood Oxygen-Level Dependent (BOLD) response in cognitive control regions. The current study examined whether the Primary Condition (PC) effect and RT-BOLD effect both reflect the same cognitive control processes. In addition, RT-BOLD effects were examined in two Go/No-go tasks with different demands to determine whether RT-related activity is task-dependent, reflecting the recruitment of task-specific cognitive processes. Data simulations showed that RT-related activity could be distinguished from that of the primary condition if it is mean-centered. In that case, RT-related activity reflects periodically-engaged processes rather than “time-on-task” (ToT). RT-related activity was mostly distinct from that of the primary Go contrast, particularly for the perceptual decision task. Therefore, RT effects can reflect additional cognitive processes that are not captured by the PC contrast consistent with a periodic-engagement account. RT-BOLD effects occurred in a separate set of regions for the two tasks. For the task requiring a perceptual decision, RT-related activity occurred within occipital and posterior parietal regions supporting visual attention. For the task requiring a working memory decision, RT-related activity occurred within fronto-parietal regions supporting the maintenance and retrieval of task representations. The findings suggest that RT-related activity reflects task-specific processes that are periodically-engaged, particularly during less demanding tasks. [ABSTRACT FROM AUTHOR]

Abstract: One of the most consistent findings in children with ADHD is increased moment-to-moment variability in reaction time (RT). The source of increased RT variability can be examined using ex-Gaussian analyses that divide variability into normal and exponential components and Fast Fourier transform (FFT) that allow for detailed examination of the frequency of responses in the exponential distribution. Prior studies of ADHD using these methods have produced variable results, potentially related to differences in task demand. The present study sought to examine the profile of RT variability in ADHD using two Go/No-go tasks with differing levels of cognitive demand. A total of 140 children (57 with ADHD and 83 typically developing controls), ages 8–13 years, completed both a “simple” Go/No-go task and a more “complex” Go/No-go task with increased working memory load. Repeated measures ANOVA of ex-Gaussian functions revealed for both tasks children with ADHD demonstrated increased variability in both the normal/Gaussian (significantly elevated sigma) and the exponential (significantly elevated tau) components. In contrast, FFT analysis of the exponential component revealed a significant task×diagnosis interaction, such that infrequent slow responses in ADHD differed depending on task demand (i.e., for the simple task, increased power in the 0.027–0.074Hz frequency band; for the complex task, decreased power in the 0.074–0.202Hz band). The ex-Gaussian findings revealing increased variability in both the normal (sigma) and exponential (tau) components for the ADHD group, suggest that both impaired response preparation and infrequent “lapses in attention” contribute to increased variability in ADHD. FFT analyses reveal that the periodicity of intermittent lapses of attention in ADHD varies with task demand. The findings provide further support for intra-individual variability as a candidate intermediate endophenotype of ADHD. [Copyright &y& Elsevier]

Abstract: FMRI studies of response inhibition consistently reveal frontal lobe activation. Localization within the frontal cortex, however, varies across studies and appears dependent on the nature of the task. Activation likelihood estimate (ALE) meta-analysis is a powerful quantitative method of establishing concurrence of activation across functional neuroimaging studies. For this study, ALE was used to investigate concurrent neural correlates of successfully inhibited No-go stimuli across studies of healthy adults performing a Go/No-go task, a paradigm frequently used to measure response inhibition. Due to the potential overlap of neural circuits for response selection and response inhibition, the analysis included only event-related studies contrasting No-go activation with baseline, which allowed for inclusion of all regions that may be critical to visually guided motor response inhibition, including those involved in response selection. These Go/No-go studies were then divided into two groups: “simple” Go/No-go tasks in which the No-go stimulus was always the same, and “complex” Go/No-go tasks, in which the No-go stimulus changed depending on context, requiring frequent updating of stimulus–response associations in working memory. The simple and complex tasks demonstrated distinct patterns of concurrence, with right dorsolateral prefrontal and inferior parietal circuits recruited under conditions of increased working memory demand. Common to both simple and complex Go/No-go tasks was concurrence in the pre-SMA and the left fusiform gyrus. As the pre-SMA has also been shown to be involved in response selection, the results support the notion that the pre-SMA is critical for selection of appropriate behavior, whether selecting to execute an appropriate response or selecting to inhibit an inappropriate response. [Copyright &y& Elsevier]

Dysfunction of frontal–striatal–thalamic–frontal circuitry has been hypothesized to underlie both attention deficit hyperactivity disorder (ADHD) and Tourette syndrome (TS). Several research groups have therefore used anatomic magnetic resonance imaging (aMRI) to obtain volumetric measurements of subregions of the frontal lobe in these disorders. Most previous studies have relied on subparcellation methods that utilize callosal landmarks to derive subregions of the frontal lobe. In contrast, we present here an investigation of frontal lobe morphometry in ADHD and TS based on a reliable frontal subparcellation protocol that combines contiguous sulcal/gyral boundaries to derive frontal lobe modules based on prior functional studies. This highly reliable procedure subdivides the frontal lobe into five major modules: prefrontal, premotor, motor (precentral gyrus), anterior cingulate, and deep white matter. The first four modules are also segmented into gray and gyral white matter compartments. The protocol was applied to T1-weighted, SPGR coronal MRI images of 13 school-aged boys with ADHD, 13 boys with TS, and 13 age- and gender-matched controls. In ADHD, we found volumetric reductions in both the gray and white matter of the prefrontal cortex. These findings, in conjunction with previous reports on basal ganglia abnormalities, suggest that prefrontal–striatal pathways may be anomalous in ADHD. In TS, we found volumetric decreases in the left deep frontal white matter. Decreases in deep white matter suggest the presence of abnormalities in long associational and projection fiber bundles in TS. The findings of this study both confirm and extend our knowledge of the neurobiology of ADHD and TS, indicating that the reliable parcellation method presented has the potential of increasing our understanding of the role of the frontal lobe in developmental and psychiatric disorders. [Copyright &y& Elsevier]

Irritability refers to a proneness for anger, and is a symptom of internalizing and externalizing psychopathology. Since irritability is associated with significant cross-sectional and longitudinal impairments, research on the behavioral and neural correlates of pediatric irritability in populations at risk for significant irritability is of paramount importance. Irritability can be assessed in the laboratory using behavioral paradigms that elicit frustration. Few behavioral frustration paradigms have been designed to measure the effects of frustration on cognitive control. Therefore, the goal of the present study was to validate a behavioral frustration paradigm for use in school-age children which addressed some of the limitations of prior research. Participants included children, ages 8-12 years, who were either typically developing (TD; n = 38) or diagnosed with attention-deficit/hyperactivity disorder (ADHD; n = 67), which provided a sample of children with a range of baseline irritability. All participants completed the Frustration Go/No-Go (GNG) task, and self-reported irritability was assessed using the Affective Reactivity Index. Results showed that across participants, self-reported frustration, commission error rate, and tau all increased with the addition of frustration, with similar effect sizes in ADHD and TD groups. Further, self-reported irritability, moreso than ADHD symptoms, predicted changes in self-reported frustration during the task. Together, these results support the construct validity of the Frustration GNG task as a means of assessing the effect of frustration on cognitive control. Clinical applications and future directions are discussed. [ABSTRACT FROM AUTHOR]

Highlights • Anomalous basal ganglia morphology was detected in ADHD boys but not ADHD girls. • Significant diagnosis by sex interactions were observed for basal ganglia volumes. • ADHD boys showed compression of subregions connecting to limbic, executive and motor cortices. • Reduced basal ganglia volumes correlated with weaker response control in boys. • Compression within executive and motor circuits correlated with response control in boys. Abstract Anomalous basal ganglia morphology may contribute to deficient motor response control in children with attention-deficit/hyperactivity disorder (ADHD). This study expands upon recent evidence of sex differences in subcortical morphology and motor response control deficits among children with ADHD to examine basal ganglia volume and shape in relation to motor response control. Participants included 8–12 year-old children with ADHD (n = 52, 21 girls) and typically developing (TD) controls (n = 45, 19 girls). High resolution T1-weighted 3D MPRAGE images covering the whole brain were acquired for all participants on a 3 T scanner. Participants performed two computer-based go/no-go tasks that differed in the extent to which working memory was necessary to guide response selection. Shape-based morphometric analyses were performed in addition to traditional volumetric comparisons and correlations with measures of motor response control were examined. Boys with ADHD consistently demonstrated increased commission error rate and response variability, regardless of task demands, suggesting broad response control deficits. In contrast, response control deficits among girls with ADHD varied depending on task demands and performance measures. Volumetric reductions and inward deformation (compression) on the dorsal surface of the globus pallidus and within subregions of the putamen receiving projections from limbic, executive and motor cortices were observed in boys, but not girls, with ADHD relative to TD children. Mediation analyses revealed that putamen and globus pallidus volumes mediated the relationship between diagnosis and commission error rate. Furthermore, reduced volumes of these structures and localized inward deformation within executive and motor circuits correlated with poorer response control, particularly under conditions of increased cognitive load. These findings suggest that anomalous basal ganglia morphology is related to impaired motor response control among boys with ADHD. [ABSTRACT FROM AUTHOR]

Altered striatal development contributes to core deficits in motor and inhibitory control, impulsivity, and inattention associated with attention-deficit/hyperactivity disorder and may likewise play a role in deficient reward processing and emotion regulation in psychosis and depression. The maturation of striatal connectivity has not been well characterized, particularly as it relates to clinical symptomatology. Resting-state functional connectivity with striatal subdivisions was examined for 926 participants (8–22 years of age, 44% male) from the general population who had participated in two large cross-sectional studies. Developing circuits were identified and growth charting of age-related connections was performed to obtain individual scores reflecting relative neurodevelopmental attainment. Associations of clinical symptom scales (attention-deficit/hyperactivity disorder, psychosis, depression, and general psychopathology) with the resulting striatal connectivity age-deviation scores were then tested using elastic net regression. Linear and nonlinear developmental patterns occurred across 231 striatal age-related connections. Both unique and overlapping striatal age-related connections were associated with the four symptom domains. Attention-deficit/hyperactivity disorder severity was related to age-advanced connectivity across several insula subregions, but to age-delayed connectivity with the nearby inferior frontal gyrus. Psychosis was associated with advanced connectivity with the medial prefrontal cortex and superior temporal gyrus, while aberrant limbic connectivity predicted depression. The dorsal posterior insula, a region involved in pain processing, emerged as a strong contributor to general psychopathology as well as to each individual symptom domain. Developmental striatal pathophysiology in the general population is consistent with dysfunctional circuitry commonly found in clinical populations. Atypical age-normative connectivity may thereby reflect aberrant neurodevelopmental processes that contribute to clinical risk. [ABSTRACT FROM AUTHOR]

Poor frustration tolerance is a significant impairment in children with ADHD. The current study examined the effect of frustration on response control using a novel frustration paradigm. In particular, girls with ADHD had the greatest difficulties when frustration was added to a response control task, which may have important implications for and associations with functional outcomes. [Extracted from the article]

Background: Complex motor stereotypies in children are repetitive rhythmic movements that have a predictable pattern and location, seem purposeful, but serve no obvious function, tend to be prolonged, and stop with distraction, e.g., arm or hand flapping, waving. They occur in both "primary" (otherwise typically developing) and secondary conditions. These movements are best defined as habitual behaviors and therefore pathophysiologically hypothesized to reside in premotor to posterior putamen circuits. This study sought to clarify the underlying neurobiologic abnormality in children with primary complex motor stereotypies using structural neuroimaging, emphasizing brain regions hypothesized to underlie these atypical behaviors.Methods: High-resolution anatomic magnetic resonance images, acquired at 3.0 T, were analyzed in children aged eight to twelve years (20 with primary complex motor stereotypies and 20 typically developing). Frontal lobe subregions and striatal structures were delineated for analysis.Results: Significant reductions (P = 0.045) in the stereotypies group were identified in total putamen volume but not in caudate, nucleus accumbens, or frontal subregions. There were no group differences in total cerebral volume.Conclusions: Findings of a smaller putamen provide preliminary evidence suggesting the potential involvement of the habitual pathway as the underlying anatomic site in primary complex motor stereotypies. [ABSTRACT FROM AUTHOR]

Background Imitation, which is impaired in children with autism spectrum disorder (ASD) and critically depends on the integration of visual input with motor output, likely impacts both motor and social skill acquisition in children with ASD; however, it is unclear what brain mechanisms contribute to this impairment. Children with ASD also exhibit what appears to be an ASD-specific bias against using visual feedback during motor learning. Does the temporal congruity of intrinsic activity, or functional connectivity, between motor and visual brain regions contribute to ASD-associated deficits in imitation, motor, and social skills? Methods We acquired resting-state functional magnetic resonance imaging scans from 100 8- to 12-year-old children (50 ASD). Group independent component analysis was used to estimate functional connectivity between visual and motor systems. Brain-behavior relationships were assessed by regressing functional connectivity measures with social deficit severity, imitation, and gesture performance scores. Results We observed increased intrinsic asynchrony between visual and motor systems in children with ASD and replicated this finding in an independent sample from the Autism Brain Imaging Data Exchange. Moreover, children with more out-of-sync intrinsic visual-motor activity displayed more severe autistic traits, while children with greater intrinsic visual-motor synchrony were better imitators. Conclusions Our twice replicated findings confirm that visual-motor functional connectivity is disrupted in ASD. Furthermore, the observed temporal incongruity between visual and motor systems, which may reflect diminished integration of visual consequences with motor output, was predictive of the severity of social deficits and may contribute to impaired social-communicative skill development in children with ASD. [ABSTRACT FROM AUTHOR]

Objective: Sexual dimorphism is evident in attention-deficit/hyperactivity disorder (ADHD), including subtype prevalence, adverse outcomes, and neural phenotype. Neurobiological studies of ADHD suggest that boys show more abnormalities in motor and premotor structure and function, whereas girls differ from typically developing (TD) peers in prefrontal circuitry. We applied diffusion tensor imaging (DTI) to identify ADHD-related sex-specific differences in motor/premotor and prefrontal white matter (WM) microstructure in children.Method: DTI estimated differences in WM microstructure among 120 children 8 to 12 years of age, 60 with ADHD (30 boys and 30 girls) and 60 controls (30 boys and 30 girls), matched on age, IQ, and handedness. Effects of diagnosis and sex on fractional anisotropy (FA) were assessed in motor/premotor and prefrontal regions. Group differences in FA and associations with response control (e.g., reaction time variability [CVRT] and commission error rate) were examined separately within sex.Results: Sex-by-diagnosis interactions were observed for FA in primary motor (M1) and medial orbitofrontal (MOFC) cortex. Post hoc tests revealed that boys with ADHD showed bilateral reductions in FA within M1, compared with TD peers; in contrast, girls with ADHD showed higher FA bilaterally within MOFC. Decreased M1 FA was associated with higher CVRT in boys and higher commission error rates in girls. For MOFC, lower FA was associated with greater CVRT and commission error rates across all participants with ADHD.Conclusion: ADHD affects the white matter of boys and girls differently; boys appear to be more affected in regions responsible for control of basic actions, whereas girls show more abnormalities in regions responsible for higher-level, top-down control. [ABSTRACT FROM AUTHOR]

Motor overflow is a developmental phenomenon that typically disappears by late childhood. Abnormal persistence of motor overflow is often present in children with attention-deficit/hyperactivity disorder (ADHD). This study employed functional magnetic resonance imaging (fMRI) during a finger-sequencing task to examine whether excessive motor overflow in children with ADHD is associated with decreased extent of motor circuit activation. Thirty-four right-handed children (18 typically developing controls, 16 ADHD) completed fMRI while performing a finger-sequencing task. Motor overflow was evaluated during a finger-sequencing task and a motor examination (the PANESS) performed outside the scanner. Diagnostic differences in behavioral measures of overflow and extent of activation in the contralateral and ipsilateral motor network ROIs were examined, along with correlations between overflow and extent of activation. Children with ADHD demonstrated greater overflow and lesser extent of activation in left primary motor cortex (BA4) and bilateral premotor cortex (BA6) and supplementary motor area (SMA) during right-hand finger-sequencing compared to controls. Decreased extent of primary motor and premotor activation correlated with increased hand-related overflow movements in children with ADHD but not controls. These findings suggest that overflow movements in children with ADHD may reflect decreased recruitment of neural circuitry involved in active inhibition of homologous motor circuitry unnecessary to task execution. [ABSTRACT FROM AUTHOR]

Abstract: The cortical dynamics of somatosensory processing can be investigated using vibrotactile psychophysics. It has been suggested that different vibrotactile paradigms target different cortical mechanisms, and a number of recent studies have established links between somatosensory cortical function and measurable aspects of behavior. The relationship between cortical mechanisms and sensory function is particularly relevant with respect to developmental disorders in which altered inhibitory processing has been postulated, such as in ASD and ADHD. In this study, a vibrotactile battery consisting of nine tasks (incorporating reaction time, detection threshold, and amplitude- and frequency discrimination) was applied to a cohort of healthy adults and a cohort of typically developing children to assess the feasibility of such a vibrotactile battery in both cohorts, and the performance between children and adults was compared. These results showed that children and adults were both able to perform these tasks with a similar performance, although the children were slightly less sensitive in frequency discrimination. Performance within different task-groups clustered together in adults, providing further evidence that these tasks tap into different cortical mechanisms, which is also discussed. This clustering was not observed in children, which may be potentially indicative of development and a greater variability. In conclusion, in this study, we showed that both children and adults were able to perform an extensive vibrotactile battery, and we showed the feasibility of applying this battery to other (e.g., neurodevelopmental) cohorts to probe different cortical mechanisms. [Copyright &y& Elsevier]

Abstract: A number of behavioral changes occur between late childhood and adulthood, including maturation of social cognition, reward receptivity, impulsiveness, risk-taking and cognitive control. Although some of these abilities show linear improvements with age, some abilities may temporarily worsen, reflecting both the restructuring and/or strengthening of connections within some brain systems. The current study uses resting state functional connectivity to examine developmental differences between late childhood and adulthood in task positive (TP) regions, which play a role in cognitive control functions, and task negative (TN) regions, which play a role in social cognition, self-referential, and internally-directed thought. Within the TP network, developmental differences in connectivity were found with the left dorsolateral prefrontal cortex. Within the TN network, developmental differences in connectivity were found with a broad area of the medial prefrontal cortex and the right parahippocampal gyrus. Connections between the two networks also showed significant developmental differences. Stronger anticorrelations were found in the TN maps of the adult group for the right anterior insula/inferior frontal gyrus, bilateral anterior inferior parietal lobule, bilateral superior parietal lobule and an anterior portion of the right posterior cingulate cortex. There was a significant brain–behavior relationship between the strength of anticorrelation in these regions and inhibitory control performance on two Go/No-go tasks suggesting that the development of anticorrelations between late childhood and adulthood supports mature inhibitory control. Overall, maturation of these networks occurred in specific regions which are associated with cognitive control of goal-directed behavior, including those involved in working memory, social cognition, and inhibitory control. [Copyright &y& Elsevier]

Abstract: Children affected by attention-deficit/hyperactivity disorder demonstrate diminished intrahemispheric inhibition (short interval cortical inhibition), as measured by transcranial magnetic stimulation. This study determined whether interhemispheric inhibition (ipsilateral silent period latency) correlates with clinical behavioral rating and motor control deficits of affected children. In 114 right-handed children (aged 8-12 years; age/sex-matched; 50 affected, 64 controls), we performed comprehensive assessments of behavior, motor skills, and cognition. Transcranial magnetic stimulation reliably elicited ipsilateral silent periods in 54 children (23 affected); all were on average older than those with unobtainable measures. Mean ipsilateral silent period latency was 5 milliseconds longer in the affected group (P = 0.007). Longer latencies correlated with more severe behavioral symptom scores (r = 0.38, P = 0.007), particularly hyperactivity (r = 0.39, P = 0.006), and with worse motor ratings on the Physical and Neurological Examination for Soft Signs (r = 0.27, P = 0.05). Longer latency also correlated with short interval cortical inhibition (r = 0.36, P = 0.008). Longer ipsilateral silent period latencies suggest interhemispheric inhibitory signaling is slower in affected children. The deficit in this inhibitory measure may underlie developmental, behavioral, and motor impairments in children with attention-deficit/hyperactivity disorder. [Copyright &y& Elsevier]

The article presents research on neural patterns that are associated with trials preceding inhibitory errors in children with and without attention-deficit/hyperactivity disorder (ADHD). It reveals that typically developing (TD) children demonstrated activation in the precuneus/posterior cingulate cortex and parahippocampal and middle frontal gyri while comparing pre-error with pre-correct trials. The preliminary data also notes the difference between children with ADHD and TD children.

The article presents a study on the association of basal ganglia abnormalities with the behavioral features of autism spectrum disorder (ASD). It states that basal ganglia shape of 45 typically developing (TP) boys and 32 boys with ASD were examined using large deformation diffeomorphic metric mapping (LDDMM). The results show that changes were seen on the right basal ganglia shape of boys with ASD compared to TD boys.

Abstract: The ability to examine associations between neuropsychiatric conditions and functionally relevant frontal lobe sub-regions is a fundamental goal in neuropsychiatry, but methods for identifying frontal sub-regions in MR (magnetic resonance) images are not well established. Prior published techniques have principally defined gyral regions that do not necessarily correspond to known functional divisions. We present a method in which sulcal–gyral landmarks are used to manually delimit functionally relevant regions within the frontal lobe: primary motor cortex, anterior cingulate, deep white matter, premotor cortex regions (supplementary motor complex (SMC), frontal eye field and lateral premotor cortex) and prefrontal cortex (PFC) regions (medial PFC, dorsolateral PFC (DLPFC), inferior PFC, lateral orbitofrontal cortex (OFC) and medial OFC). Feasibility was tested by applying the protocol to brain MR data from 15 boys with attention-deficit/hyperactivity disorder (ADHD) and 15 typically developing controls, 8–12 years old. Intra- and inter-rater intraclass correlation coefficients were calculated using parcellation volumes from a subset of that group. Inter-rater results for the 22 hemisphere specific sub-regions ranged from 0.724 to 0.997, with all but seven values above 0.9. Boys with ADHD showed significantly smaller left hemisphere SMC and DLPFC volumes after normalization for total cerebral volume. These findings support the method as a reliable and valid technique for parcellating the frontal lobe into functionally relevant sub-regions. [Copyright &y& Elsevier]

Mirror overflow is involuntary movement that accompanies unilateral voluntary movement on the opposite side of the body, and is commonly seen in Attention-Deficit/Hyperactivity Disorder (ADHD). Children with ADHD show asymmetry in mirror overflow between dominant and non-dominant hand, yet there are competing mechanistic accounts of why this occurs. Using EEG during a sequential, unimanual finger-tapping task, we found that children with ADHD exhibited significantly more mirror overflow than typically developing (TD) controls, especially during the tapping of the non-dominant hand. Furthermore, source-level EEG oscillation analysis revealed that children with ADHD showed decreased alpha (8–12 Hz) event-related desynchronization (ERD) compared with controls in both hemispheres, but only during tapping of the non-dominant hand. Moreover, only the ERD ipsilateral to the mirror overflow during non-dominant hand movement correlated with both magnitude of overflow movements and higher ADHD symptom severity (Conners ADHD Hyperactivity/Impulsiveness scale) in children with ADHD. TD controls did not show these relationships. Our findings suggest that EEG differences in finger-tapping in ADHD are related primarily to voluntary movement in the non-dominant hand. Our results are also consistent with the Ipsilateral Corticospinal Tract (CST) Hypothesis, which posits that the atypical persistence of mirror overflow in ADHD may originate in the sensorimotor areas ipsilateral to mirror overflow and be transmitted via non-decussating CST fibers. • ADHD-related differences in brain activation related to mirror overflow are driven by the voluntary movement of the non-dominant hand. • Similarly, hyperactive/impulsive symptoms are associated with task-related activation only during movement of the non-dominant hand. • Our findings are consistent with the potential role of non-decussating cortical-spinal tracts in mirror overflow in ADHD. [ABSTRACT FROM AUTHOR]

The article presents a study that focuses on the attention-deficit/hyperactivity disorder (ADHD) in children. It examines the neural correlates of the increased intrasubject variability (ISV) in the task performance in children with the disorder compared to typically developing (TD) children. It indicates the use of a Go/No-go task with a motor response for the reduction of extraneous cognitive demands. It reveals that children with ADHD for whom increased pre-supplementary motor area activation had presented more ISV, compared to TD children.

Abstract: During tasks requiring response inhibition, intra-individual response time variability, a measure of motor response preparation, has been found to correlate with errors of commission, such that individuals with higher variability show increased commission errors. This study used fMRI to examine the neural correlates of response variability in 30 typically developing children, ages 8–12, using a simplified Go/No-go task with minimal cognitive demands. Lower variability was associated with Go activation in the anterior cerebellum (culmen) and with No-go activation in the rostral supplementary motor area (pre-SMA), the postcentral gyrus, the anterior cerebellum (culmen) and the inferior parietal lobule. For both Go and No-go events, higher variability was associated with activation in prefrontal cortex and the caudate. The findings have implications for neuropsychiatric disorders such as ADHD and suggest that during response inhibition, children with more consistent performance are able to rely on premotor circuits involving the pre-SMA, important for response selection; those with less consistent performance instead recruit prefrontal circuits involved in more complex aspects of behavioral control. [Copyright &y& Elsevier]

• Machine-learning classification challenge on functional MRI connectomes. • Transfer learning for co-morbid neuropsychiatric disorders diagnosis. • Challenge design and data collection focusing on ADHD, and ASD with ADHD comorbidity. • Containerized submission platform, which remains open for testing new approaches. • Extensive performance evaluation of different methods based on 16 metrics. [Display omitted] Large, open-source datasets, such as the Human Connectome Project and the Autism Brain Imaging Data Exchange, have spurred the development of new and increasingly powerful machine learning approaches for brain connectomics. However, one key question remains: are we capturing biologically relevant and generalizable information about the brain, or are we simply overfitting to the data? To answer this, we organized a scientific challenge, the Connectomics in NeuroImaging Transfer Learning Challenge (CNI-TLC), held in conjunction with MICCAI 2019. CNI-TLC included two classification tasks: (1) diagnosis of Attention-Deficit/Hyperactivity Disorder (ADHD) within a pre-adolescent cohort; and (2) transference of the ADHD model to a related cohort of Autism Spectrum Disorder (ASD) patients with an ADHD comorbidity. In total, 240 resting-state fMRI (rsfMRI) time series averaged according to three standard parcellation atlases, along with clinical diagnosis, were released for training and validation (120 neurotypical controls and 120 ADHD). We also provided Challenge participants with demographic information of age, sex, IQ, and handedness. The second set of 100 subjects (50 neurotypical controls, 25 ADHD, and 25 ASD with ADHD comorbidity) was used for testing. Classification methodologies were submitted in a standardized format as containerized Docker images through ChRIS, an open-source image analysis platform. Utilizing an inclusive approach, we ranked the methods based on 16 metrics: accuracy, area under the curve, F1-score, false discovery rate, false negative rate, false omission rate, false positive rate, geometric mean, informedness, markedness, Matthew's correlation coefficient, negative predictive value, optimized precision, precision, sensitivity, and specificity. The final rank was calculated using the rank product for each participant across all measures. Furthermore, we assessed the calibration curves of each methodology. Five participants submitted their method for evaluation, with one outperforming all other methods in both ADHD and ASD classification. However, further improvements are still needed to reach the clinical translation of functional connectomics. We have kept the CNI-TLC open as a publicly available resource for developing and validating new classification methodologies in the field of connectomics. [ABSTRACT FROM AUTHOR]

Child abuse and other forms of adversity are associated with alterations in threat processing and emotion regulation brain circuits. The goal of the current investigation is to determine if the availability of positive social support can ameliorate the negative impact of adversity on these brain systems. Subjects included 55 children ages 7–16 (X = 11.8, SD = 2.0). Approximately one-third of the cohort had no significant history of adversity, one-third had a history of moderate adversity, and one-third had a history of severe adversity. Brain imaging was conducted at the University of Vermont using a 3.0 T Philips scanner. The Emotional Go-NoGo task with fearful and calm facial stimuli was used to assess the neural correlates of threat processing and emotion regulation in children during functional magnetic resonance imaging (fMRI). Dimensional measures of anxiety, social supports, and children's adverse experiences were also obtained. A conjunction analysis was used to test if trauma-related brain activation in responding to fearful vs. calm targets was impacted by social support. This approach identified multiple activation foci, including a cluster extending from the left amygdala to several other key brain regions involved in emotion regulation, including the orbitofrontal cortex, anterior cingulate cortex (ACC), anterior insula, nucleus accumbens, and frontal pole (Family Wise Error (FWE) correction, p < 0.05). Greater social support may reduce the effect that adversity has on neural processing of threat stimuli, consistent with the protective role of positive supports in promoting resilience and recovery demonstrated in the literature. [ABSTRACT FROM AUTHOR]