Anita D. Barber

Disruption of functional organization within the primary motor cortex in children with autism

Accumulating evidence suggests that motor impairments are prevalent in autism spectrum disorder (ASD), relate to the social and communicative deficits at the core of the diagnosis and may reflect abnormal connectivity within brain networks underlying motor control and learning. Parcellation of resting‐state functional connectivity data using spectral clustering approaches has been shown to be an effective means of visualizing functional organization within the brain but has most commonly been applied to explorations of normal brain function. This article presents a parcellation of a key area of the motor network, the primary motor cortex (M1), a key area of the motor control network, in adults, typically developing (TD) children and children with ASD and introduces methods for selecting the number of parcels, matching parcels across groups and testing group differences. The parcellation is based solely on patterns of connectivity between individual M1 voxels and all voxels outside of M1, and within all groups, a gross dorsomedial to ventrolateral organization emerged within M1 which was left–right symmetric. Although this gross organizational scheme was present in both groups of children, statistically significant group differences in the size and segregation of M1 parcels within regions of the motor homunculus corresponding to the upper and lower limbs were observed. Qualitative comparison of the M1 parcellation for children with ASD with that of younger and older TD children suggests that these organizational differences, with a lack of differentiation between lower limb/trunk regions and upper limb/hand regions, may be due, at least in part, to a delay in functional specialization within the motor cortex. Hum Brain Mapp 35:567–580, 2014.

Automated diagnoses of attention deficit hyperactive disorder using magnetic resonance imaging

Successful automated diagnoses of attention deficit hyperactive disorder (ADHD) using imaging and functional biomarkers would have fundamental consequences on the public health impact of the disease. In this work, we show results on the predictability of ADHD using imaging biomarkers and discuss the scientific and diagnostic impacts of the research. We created a prediction model using the landmark ADHD 200 data set focusing on resting state functional connectivity (rs-fc) and structural brain imaging. We predicted ADHD status and subtype, obtained by behavioral examination, using imaging data, intelligence quotients and other covariates. The novel contributions of this manuscript include a thorough exploration of prediction and image feature extraction methodology on this form of data, including the use of singular value decompositions (SVDs), CUR decompositions, random forest, gradient boosting, bagging, voxel-based morphometry, and support vector machines as well as important insights into the value, and potentially lack thereof, of imaging biomarkers of disease. The key results include the CUR-based decomposition of the rs-fc-fMRI along with gradient boosting and the prediction algorithm based on a motor network parcellation and random forest algorithm. We conjecture that the CUR decomposition is largely diagnosing common population directions of head motion. Of note, a byproduct of this research is a potential automated method for detecting subtle in-scanner motion. The final prediction algorithm, a weighted combination of several algorithms, had an external test set specificity of 94% with sensitivity of 21%. The most promising imaging biomarker was a correlation graph from a motor network parcellation. In summary, we have undertaken a large-scale statistical exploratory prediction exercise on the unique ADHD 200 data set. The exercise produced several potential leads for future scientific exploration of the neurological basis of ADHD.

Developmental Changes In Within- and Between-Network Connectivity Between Late Childhood and Adulthood

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.

Motor “Dexterity”?: Evidence that Left Hemisphere Lateralization of Motor Circuit Connectivity Is Associated with Better Motor Performance in Children

Motor control relies on well-established motor circuits, which are critical for typical child development. Although many imaging studies have examined task activation during motor performance, none have examined the relationship between functional intrinsic connectivity and motor ability. The current study investigated the relationship between resting state functional connectivity within the motor network and motor performance assessment outside of the scanner in 40 typically developing right-handed children. Better motor performance correlated with greater left-lateralized (mean left hemisphere-mean right hemisphere) motor circuit connectivity. Speed, rhythmicity, and control of movements were associated with connectivity within different individual region pairs: faster speed was associated with more left-lateralized putamen-thalamus connectivity, less overflow with more left-lateralized supplementary motor-primary motor connectivity, and less dysrhythmia with more left-lateralized supplementary motor-anterior cerebellar connectivity. These findings suggest that for right-handed children, superior motor development depends on the establishment of left-hemisphere dominance in intrinsic motor network connectivity.

Effects of working memory demand on neural mechanisms of motor response selection and control

Inhibitory control commonly recruits a number of frontal regions: pre-supplementary motor area (pre-SMA), frontal eye fields (FEFs), and right-lateralized posterior inferior frontal gyrus (IFG), dorsal anterior insula (DAI), dorsolateral prefrontal cortex (DLPFC), and inferior frontal junction (IFJ). These regions may directly implement inhibitory motor control or may be more generally involved in executive control functions. Two go/no-go tasks were used to distinguish regions specifically recruited for inhibition from those that additionally show increased activity with working memory demand. The pre-SMA and IFG were recruited for inhibition in both tasks and did not have greater activation for working memory demand on no-go trials, consistent with a role in inhibitory control. Activation in pre-SMA also responded to response selection demand and was increased with working memory on go trials specifically. The bilateral FEF and right DAI were commonly active for no-go trials. The FEF was also recruited to a greater degree with working memory demand on go trials and may bias top–down information when stimulus–response mappings change. The DAI, additionally responded to increased working memory demand on both go and no-go trials and may be involved in accessing sustained task information, alerting, or autonomic changes when cognitive demands increase. DLPFC activation was consistent with a role in working memory retrieval on both go and no-go trials. The inferior frontal junction, on the other hand, had greater activation with working memory specifically for no-go trials and may detect salient stimuli when the task requires frequent updating of working memory representations.

Precentral gyrus functional connectivity signatures of autism

Motor impairments are prevalent in children with autism spectrum disorders (ASD) and are perhaps the earliest symptoms to develop. In addition, motor skills relate to the communicative/social deficits at the core of ASD diagnosis, and these behavioral deficits may reflect abnormal connectivity within brain networks underlying motor control and learning. Despite the fact that motor abnormalities in ASD are well-characterized, there remains a fundamental disconnect between the complexity of the clinical presentation of ASD and the underlying neurobiological mechanisms. In this study, we examined connectivity within and between functional subregions of a key component of the motor control network, the precentral gyrus, using resting state functional Magnetic Resonance Imaging data collected from a large, heterogeneous sample of individuals with ASD as well as neurotypical controls. We found that the strength of connectivity within and between distinct functional subregions of the precentral gyrus was related to ASD diagnosis and to the severity of ASD traits. In particular, connectivity involving the dorsomedial (lower limb/trunk) subregion was abnormal in ASD individuals as predicted by models using a dichotomous variable coding for the presence of ASD, as well as models using symptom severity ratings. These findings provide further support for a link between motor and social/communicative abilities in ASD.

Atypical lateralization of motor circuit functional connectivity in children with autism is associated with motor deficits

BackgroundAtypical lateralization of language-related functions has been repeatedly found in individuals with autism spectrum conditions (ASC). Few studies have, however, investigated deviations from typically occurring asymmetry of other lateralized cognitive and behavioural domains. Motor deficits are among the earliest and most prominent symptoms in individuals with ASC and precede core social and communicative symptoms.MethodsHere, we investigate whether motor circuit connectivity is (1) atypically lateralized in children with ASC and (2) whether this relates to core autistic symptoms and motor performance. Participants comprised 44 right-handed high-functioning children with autism (36 males, 8 females) and 80 typically developing control children (58 males, 22 females) matched on age, sex and performance IQ. We examined lateralization of functional motor circuit connectivity based on homotopic seeds derived from peak activations during a finger tapping paradigm. Motor performance was assessed using the Physical and Neurological Examination for Subtle Signs (PANESS).ResultsChildren with ASC showed rightward lateralization in mean motor circuit connectivity compared to typically developing children, and this was associated with poorer performance on all three PANESS measures.ConclusionsOur findings reveal that atypical lateralization in ASC is not restricted to language functions but is also present in circuits subserving motor functions and may underlie motor deficits in children with ASC. Future studies should investigate whether this is an age-invariant finding extending to adolescents and adults and whether these asymmetries relate to atypical lateralization in the language domain.

Motor overflow in children with attention-deficit/hyperactivity disorder is associated with decreased extent of neural activation in the motor cortex

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.

Neural Correlates of Visuomotor Learning in Autism.

Motor impairments are prevalent in children with autism spectrum disorder. The Serial Reaction Time Task, a well-established visuomotor sequence learning probe, has produced inconsistent behavioral findings in individuals with autism. Moreover, it remains unclear how underlying neural processes for visuomotor learning in children with autism compare to processes for typically developing children. Neural activity differences were assessed using functional magnetic resonance imaging during a modified version of the Serial Reaction Time Task in children with and without autism. Though there was no group difference in visuomotor sequence learning, underlying patterns of neural activation significantly differed when comparing sequence (ie, learning) to random (ie, nonlearning) blocks. Children with autism demonstrated decreased activity in brain regions implicated in visuomotor sequence learning: superior temporal sulcus and posterior cingulate cortex. The findings implicate differences in brain mechanisms that support initial sequence learning in autism and can help explain behavioral observations of autism-associated impairments in skill development (motor, social, communicative) reliant on visuomotor integration.

Altered functional connectivity in children with mild to moderate TBI relates to motor control

PURPOSE Functionally relevant alterations in resting state fMRI (rs-fMRI) connectivity have been identified in adults with traumatic brain injury (TBI). We evaluated rs-fMRI connectivity in children with TBI and explored the relationship between altered connectivity and measures of neurological function. METHODS Rs-fMRI was obtained in 14 children after TBI and 14 controls matched for age, sex, and handedness. Whole-brain connectivity was evaluated separately for the default mode network (DMN) and dorsal attention network (DAN); Between-group contrasts identified regions with altered connectivity between TBI and control cohorts. In children with TBI, the relationships between regions of altered connectivity and performance on relevant functional measures were examined. RESULTS Compared to controls, children with TBI showed significantly greater connectivity between DMN and right dorsal premotor cortex (RdPM) and between DAN and bilateral sensorimotor cortex (SM1). In children with TBI, greater DMN-RdPM connectivity was associated with worse motor performance whereas greater DAN-LSM1 connectivity was associated with better motor performance; furthermore, DMN-RdPM and DAN-LSM1 connectivity were negatively correlated. CONCLUSION Rs-fMRI reveals significant altered connectivity in children with TBI compared to controls. After TBI in children, patterns of altered connectivity appear divergent, with increased DMN-motor network connectivity associated with worse motor control whereas increased DAN-motor network connectivity appears compensatory.