Sex Effects on Mirror Overflow during Finger Tapping in Children with ADHD.

OBJECTIVES: The presence of excessive mirror overflow in children with Attention Deficit/Hyperactivity Disorder (ADHD) is discussed in numerous published reports. These reports, however, include a limited age range in their samples. The objective of this study is to examine the effects of diagnosis and sex on mirror overflow and standard deviation (SD) of tap time in children with and without ADHD across a larger age range (5-12 years) of children. METHODS: One-hundred and forty-eight children with ADHD and 112 age- and sex-matched typically developing (TD) children completed a finger sequencing task. Mirror overflow, SD of tap time, and mean tap time were measured using finger twitch transducers. RESULTS: Results reveal a significant diagnostic effect on mirror overflow such that boys and girls with ADHD demonstrate increased overflow compared to same-sex TD children. Boys with ADHD demonstrated more variable tap times compared to TD boys; no diagnostic effect was observed in the girls. CONCLUSIONS: Boys with ADHD exhibit anomalous motor variability; girls with ADHD show similar levels of variability as TD girls. Boys and girls with ADHD exhibit similar levels of excessive mirror overflow. This lack of sex differences on mirror overflow is distinct from reports finding sex effects on overflow and could result from an examination of a broader age range than is included in prior reports. Adolescent data would provide a greater understanding of the trajectory of anomalous mirror overflow across development. Examination of functional and structural connectivity would expand the current understanding of the neurobiological foundation of motor overflow.

Deep sr-DDL: Deep structurally regularized dynamic dictionary learning to integrate multimodal and dynamic functional connectomics data for multidimensional clinical characterizations.

We propose a novel integrated framework that jointly models complementary information from resting-state functional MRI (rs-fMRI) connectivity and diffusion tensor imaging (DTI) tractography to extract biomarkers of brain connectivity predictive of behavior. Our framework couples a generative model of the connectomics data with a deep network that predicts behavioral scores. The generative component is a structurally-regularized Dynamic Dictionary Learning (sr-DDL) model that decomposes the dynamic rs-fMRI correlation matrices into a collection of shared basis networks and time varying subject-specific loadings. We use the DTI tractography to regularize this matrix factorization and learn anatomically informed functional connectivity profiles. The deep component of our framework is an LSTM-ANN block, which uses the temporal evolution of the subject-specific sr-DDL loadings to predict multidimensional clinical characterizations. Our joint optimization strategy collectively estimates the basis networks, the subject-specific time-varying loadings, and the neural network weights. We validate our framework on a dataset of neurotypical individuals from the Human Connectome Project (HCP) database to map to cognition and on a separate multi-score prediction task on individuals diagnosed with Autism Spectrum Disorder (ASD) in a five-fold cross validation setting. Our hybrid model outperforms several state-of-the-art approaches at clinical outcome prediction and learns interpretable multimodal neural signatures of brain organization.

Increased interhemispheric somatomotor functional connectivity and mirror overflow in ADHD.

Mirror overflow is a developmental phenomenon defined as unintentional movements that mimic the execution of intentional movements in homologous muscles on the opposite side of the body. In children with attention-deficit/hyperactivity disorder (ADHD), mirror overflow is commonly excessive, abnormally persistent, and correlated with ADHD symptom severity. As such, it represents a promising clinical biomarker for disinhibited behavior associated with ADHD. Yet, the neural underpinnings of mirror overflow in ADHD remain unclear. Our objective was to test whether intrinsic interhemispheric functional connectivity between homologous regions of the somatomotor network (SMN) is associated with mirror overflow in school age children with and without ADHD using resting state functional magnetic resonance imaging. To this end, we quantified mirror overflow in 119 children (8-12 years old, 62 ADHD) during a finger sequencing task using finger twitch transducers affixed to the index and ring fingers. Group ICA was used to identify right- and left-lateralized SMNs and subject-specific back reconstructed timecourses were correlated to obtain a measure of SMN interhemispheric connectivity. We found that children with ADHD showed increased mirror overflow (p < 0.001; d = 0.671) and interhemispheric SMN functional connectivity (p = 0.023; d = 0.521) as compared to typically developing children. In children with ADHD, but not the typically developing children, there was a significant relationship between interhemispheric SMN functional connectivity and mirror overflow (t = 2.116; p = 0.039). Our findings of stronger interhemispheric functional connectivity between homologous somatomotor regions in children with ADHD is consistent with previous transcranial magnetic stimulation and diffusion-tractography imaging studies suggesting that interhemispheric cortical inhibitory mechanisms may be compromised in children with ADHD. The observed brain-behavior correlation further suggests that abnormally strong interhemispheric SMN connectivity in children with ADHD may diminish their ability to suppress overflow movements.

A joint network optimization framework to predict clinical severity from resting state functional MRI data.

We propose a novel optimization framework to predict clinical severity from resting state fMRI (rs-fMRI) data. Our model consists of two coupled terms. The first term decomposes the correlation matrices into a sparse set of representative subnetworks that define a network manifold. These subnetworks are modeled as rank-one outer-products which correspond to the elemental patterns of co-activation across the brain; the subnetworks are combined via patient-specific non-negative coefficients. The second term is a linear regression model that uses the patient-specific coefficients to predict a measure of clinical severity. We validate our framework on two separate datasets in a ten fold cross validation setting. The first is a cohort of fifty-eight patients diagnosed with Autism Spectrum Disorder (ASD). The second dataset consists of sixty three patients from a publicly available ASD database. Our method outperforms standard semi-supervised frameworks, which employ conventional graph theoretic and statistical representation learning techniques to relate the rs-fMRI correlations to behavior. In contrast, our joint network optimization framework exploits the structure of the rs-fMRI correlation matrices to simultaneously capture group level effects and patient heterogeneity. Finally, we demonstrate that our proposed framework robustly identifies clinically relevant networks characteristic of ASD.

Subtle Motor Findings During Recovery from Pediatric Traumatic Brain Injury: A Preliminary Report.

Pediatric traumatic brain injury (TBI) is a heterogeneous condition, varying in both severity and sequelae. The long-term motor deficits following severe TBI requiring inpatient rehabilitation are better established than those following milder forms of TBI. The authors examined motor performance 2 and 12 months postinjury in children without overt motor impairment using standard measures of upper limb function and the Physical and Neurological Examination for Subtle Signs (PANESS). The PANESS was sensitive to differences between children with TBI and uninjured children as well as to changes in children with TBI over time. These data suggest that subtle motor deficits are present after milder forms of TBI and, particularly those related to balance and gait, may persist even 12 months postinjury.

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.

The autism brain imaging data exchange: towards a large-scale evaluation of the intrinsic brain architecture in autism.

Autism spectrum disorders (ASDs) represent a formidable challenge for psychiatry and neuroscience because of their high prevalence, lifelong nature, complexity and substantial heterogeneity. Facing these obstacles requires large-scale multidisciplinary efforts. Although the field of genetics has pioneered data sharing for these reasons, neuroimaging had not kept pace. In response, we introduce the Autism Brain Imaging Data Exchange (ABIDE)-a grassroots consortium aggregating and openly sharing 1112 existing resting-state functional magnetic resonance imaging (R-fMRI) data sets with corresponding structural MRI and phenotypic information from 539 individuals with ASDs and 573 age-matched typical controls (TCs; 7-64 years) (http://fcon_1000.projects.nitrc.org/indi/abide/). Here, we present this resource and demonstrate its suitability for advancing knowledge of ASD neurobiology based on analyses of 360 male subjects with ASDs and 403 male age-matched TCs. We focused on whole-brain intrinsic functional connectivity and also survey a range of voxel-wise measures of intrinsic functional brain architecture. Whole-brain analyses reconciled seemingly disparate themes of both hypo- and hyperconnectivity in the ASD literature; both were detected, although hypoconnectivity dominated, particularly for corticocortical and interhemispheric functional connectivity. Exploratory analyses using an array of regional metrics of intrinsic brain function converged on common loci of dysfunction in ASDs (mid- and posterior insula and posterior cingulate cortex), and highlighted less commonly explored regions such as the thalamus. The survey of the ABIDE R-fMRI data sets provides unprecedented demonstrations of both replication and novel discovery. By pooling multiple international data sets, ABIDE is expected to accelerate the pace of discovery setting the stage for the next generation of ASD studies.

Genome-wide association study of shared components of reading disability and language impairment.

Written and verbal languages are neurobehavioral traits vital to the development of communication skills. Unfortunately, disorders involving these traits-specifically reading disability (RD) and language impairment (LI)-are common and prevent affected individuals from developing adequate communication skills, leaving them at risk for adverse academic, socioeconomic and psychiatric outcomes. Both RD and LI are complex traits that frequently co-occur, leading us to hypothesize that these disorders share genetic etiologies. To test this, we performed a genome-wide association study on individuals affected with both RD and LI in the Avon Longitudinal Study of Parents and Children. The strongest associations were seen with markers in ZNF385D (OR = 1.81, P = 5.45 × 10(-7) ) and COL4A2 (OR = 1.71, P = 7.59 × 10(-7) ). Markers within NDST4 showed the strongest associations with LI individually (OR = 1.827, P = 1.40 × 10(-7) ). We replicated association of ZNF385D using receptive vocabulary measures in the Pediatric Imaging Neurocognitive Genetics study (P = 0.00245). We then used diffusion tensor imaging fiber tract volume data on 16 fiber tracts to examine the implications of replicated markers. ZNF385D was a predictor of overall fiber tract volumes in both hemispheres, as well as global brain volume. Here, we present evidence for ZNF385D as a candidate gene for RD and LI. The implication of transcription factor ZNF385D in RD and LI underscores the importance of transcriptional regulation in the development of higher order neurocognitive traits. Further study is necessary to discern target genes of ZNF385D and how it functions within neural development of fluent language.

A preliminary neuroimaging study of preschool children with ADHD.

Attention-deficit/hyperactivity disorder (ADHD) is a developmental disorder that, by current definition, has onset prior to age 7 years. MRI studies have provided some insight into brain differences associated with ADHD, but thus far have almost exclusively focused on children ages 7 years and older. To better understand the neurobiological development of ADHD, cortical and subcortical brain development should be systematically examined in younger children presenting with symptoms of the disorder. High-resolution anatomical (MPRAGE) images, acquired on a 3.0T scanner, were analyzed in a total of 26 preschoolers, ages 4-5 years (13 with ADHD, 13 controls, matched on age and sex). The ADHD sample was diagnosed using DSM-IV criteria, and screened for language disorders. Cortical regions were delineated and measured using automated methods in Freesurfer; basal ganglia structures were manually delineated. Children with ADHD showed significantly reduced caudate volumes bilaterally; in contrast there were no significant group differences in cortical volume or thickness in this age range. After controlling for age and total cerebral volume, left caudate volume was a significant predictor of hyperactive/impulsive, but not inattentive symptom severity. Anomalous basal ganglia, particularly caudate, development appears to play an important role among children presenting with early onset symptoms of ADHD.

Motor cortex inhibition: a marker of ADHD behavior and motor development in children.

OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is a childhood-onset behavioral diagnosis in which children often fail to meet age norms in development of motor control, particularly timed repetitive and sequential movements, motor overflow, and balance. The neural substrate of this motor delay may include mechanisms of synaptic inhibition in or adjacent to the motor cortex. The primary objective of this study was to determine whether transcranial magnetic stimulation (TMS)-evoked measures, particularly short interval cortical inhibition (SICI), in motor cortex correlate with the presence and severity of ADHD in childhood as well as with commonly observed delays in motor control. METHODS: In this case-control study, behavioral ratings, motor skills, and motor cortex physiology were evaluated in 49 children with ADHD (mean age 10.6 years, 30 boys) and 49 typically developing children (mean age 10.5 years, 30 boys), all right-handed, aged 8-12 years. Motor skills were evaluated with the Physical and Neurological Examination for Subtle Signs (PANESS) and the Motor Assessment Battery for Children version 2. SICI and other physiologic measures were obtained using TMS in the left motor cortex. RESULTS: In children with ADHD, mean SICI was reduced by 40% (p < 0.0001) and less SICI correlated with higher ADHD severity (r = -0.52; p = 0.002). Mean PANESS motor development scores were 59% worse in children with ADHD (p < 0.0001). Worse PANESS scores correlated modestly with less SICI (r = -.30; p = 0.01). CONCLUSION: Reduced TMS-evoked SICI correlates with ADHD diagnosis and symptom severity and also reflects motor skill development in children.

Quantifying excessive mirror overflow in children with attention-deficit/hyperactivity disorder.

OBJECTIVES: Qualitative observations have revealed that children with attention-deficit/hyperactivity disorder (ADHD) show increased overflow movements, a motor sign thought to reflect impaired inhibitory control. The goal of this study was to develop and implement methods for quantifying excessive mirror overflow movements in children with ADHD. METHODS: Fifty right-handed children aged 8.2-13.3 years, 25 with ADHD (12 girls) and 25 typically developing (TD) control children (10 girls), performed a sequential finger-tapping task, completing both left-handed (LHFS) and right-handed finger sequencing (RHFS). Phasic overflow of the index and ring fingers was assessed in 34 children with video recording, and total overflow in 48 children was measured by calculating the total angular displacement of the index and ring fingers with electrogoniometer recordings. RESULTS: Phasic overflow and total overflow across both hands were greater in children with ADHD than in TD children, particularly during LHFS. Separate gender analyses revealed that boys, but not girls, with ADHD showed significantly more total phasic overflow and total overflow than did their gender-matched control children. CONCLUSIONS: The quantitative overflow measures used in this study support past qualitative findings that motor overflow persists to a greater degree in children with ADHD than in age-matched TD peers. The quantitative findings further suggest that persistence of mirror overflow is more prominent during task execution of the nondominant hand and reveal gender-based differences in developmental neural systems critical to motor control. These quantitative measures will assist future physiologic investigation of the brain basis of motor control in ADHD.

Age-related changes in motor subtle signs among girls and boys with ADHD.

OBJECTIVE: To examine differences in age-related improvement in motor speed and neurologic subtle signs (overflow and dysrhythmia) among boys and girls with and without attention-deficit hyperactivity disorder (ADHD). METHOD: Diagnosis of ADHD was determined by structured parent interview and administration of ADHD-specific and broad behavior rating scales. Motor function was assessed using the revised Physical and Neurological Assessment of Subtle Signs. Three primary outcome variables were obtained: 1) total time, 2) total overflow, and 3) total dysrhythmia. Effects of age, group, and sex were assessed. RESULTS: Both control and ADHD groups showed improvement on timed tasks with age; however, controls were consistently faster across the age span. Controls and girls with ADHD showed steady age-related reduction of overflow and dysrhythmia, whereas boys with ADHD had little improvement in these signs through age 14 years. CONCLUSION: Results indicated that girls with attention-deficit hyperactivity disorder (ADHD) performed similarly to age-matched controls on a quantified motor examination. These results parallel patterns of findings from neuroimaging studies, in which neurologic anomalies in areas related to motor control are present in boys with ADHD, but more equivocal in girls with ADHD. Sex-related differences observed in children with ADHD likely extend beyond symptom presentation to development of motor control, and are likely related to earlier brain maturation in girls.

Left-right differences on timed motor examination in children.

Age-related change in the difference between left- and right-side speed on motor examination may be an important indicator of maturation. Cortical maturation and myelination of the corpus callosum are considered to be related to increased bilateral skill and speed on timed motor tasks. We compared left minus right foot, hand, and finger speed differences using the Revised Physical and Neurological Assessment for Subtle Signs (PANESS; Denckla, 1985); examining 130 typically developing right-handed children (65 boys, 65 girls) ages 7-14. Timed tasks included right and left sets of 20 toe taps, 10 toe-heel alternation sequences, 20 hand pats, 10 hand pronate-supinate sets, 20 finger taps, and 5 sequences of each finger-to-thumb apposition. For each individual, six difference scores between left- and right-sided speeded performances of timed motor tasks were analyzed. Left-right differences decreased significantly with age on toe tapping, heel-toe alternations, hand pronation-supination, finger repetition, and finger sequencing. There were significant gender effects for heel-toe sequences (boys showing a greater left-right difference than girls), and a significant interaction between age and gender for hand pronation-supination, such that the magnitude of the left-right difference was similar for younger, compared with older girls, while the difference was significantly larger for younger, compared to older boys. Speed of performing right and left timed motor tasks equalizes with development; for some tasks, the equalization occurs earlier in girls than in boys.

Dyspraxia in autism: association with motor, social, and communicative deficits.

Impaired performance of skilled gestures, referred to as dyspraxia, is consistently reported in children with autism; however, its neurological basis is not well understood. Basic motor skill deficits are also observed in children with autism and it is unclear whether dyspraxia observed in children with autism can be accounted for by problems with motor skills. Forty-seven high-functioning children with an autism spectrum disorder (ASD), autism, or Asperger syndrome (43 males, four females; mean age 10y 7m [SD 1y 10m], mean Full-scale IQ (FSIQ) 99.4 [SD 15.9]), and 47 typically developing (TD) controls (41 males, six females; mean age 10y 6m [SD 1y 5m], mean FSIQ 113.8 [SD 12.3], age range 8-4y) completed: (1) the Physical and Neurological Assessment of Subtle Signs, an examination of basic motor skills standardized for children, and (2) a praxis examination that included gestures to command, to imitation, and with tool-use. Hierarchical regression was used to examine the association between basic motor skill performance (i.e. times to complete repetitive limb movements) and praxis performance (total praxis errors). After controlling for age and IQ, basic motor skill was a significant predictor of performance on praxis examination. Nevertheless, the ASD group continued to show significantly poorer praxis than controls after accounting for basic motor skill. Furthermore, praxis performance was a strong predictor of the defining features of autism, measured using the Autism Diagnostic Observation Schedule, and this correlation remained significant after accounting for basic motor skill. Results indicate that dyspraxia in autism cannot be entirely accounted for by impairments in basic motor skills, suggesting the presence of additional contributory factors. Furthermore, praxis in children with autism is strongly correlated with the social, communicative, and behavioral impairments that define the disorder, suggesting that dyspraxia may be a core feature of autism or a marker of the neurological abnormalities underlying the disorder.

Sex differences in cerebral laterality of language and visuospatial processing.

Sex differences on language and visuospatial tasks are of great interest, with differences in hemispheric laterality hypothesized to exist between males and females. Some functional imaging studies examining sex differences have shown that males are more left lateralized on language tasks and females are more right lateralized on visuospatial tasks; however, findings are inconsistent. Here we used functional magnetic resonance imaging to study thirty participants, matched on task performance, during phonological and visuospatial tasks. For each task, region-of-interest analyses were used to test differences in cerebral laterality. Results indicate that lateralization differences exist, with males more left lateralized during the phonological task and showing greater bilateral activity during the visuospatial task, whereas females showed greater bilateral activity during the phonological task and were more right lateralized during the visuospatial task. Our data provide clear evidence for differences in laterality between males and females when processing language versus visuospatial information.

Normal physiological emotions but differences in expression of conscious feelings in children with high-functioning autism.

To provide insight into what aspects of the emotional circuit might be affected in high-functioning autism, we measured indices of physiological emotions and of the expression of conscious feelings in 10 children with high-functioning autism or Asperger syndrome and 10 comparison participants. Pleasant, unpleasant, and neutral pictures were presented while skin conductance responses were measured. Self-report ratings of pleasantness and interestingness were taken between pictures. Skin conductance responses did not differ between the groups. Self report ratings were different, with the children with autism giving more similar answers to the two questions than the comparison children. Impairments in socio-emotional expression in autism may be related to deficits in perception and/or expression of conscious feelings; physiological emotions may be relatively preserved.

Subtle executive impairment in children with autism and children with ADHD.

BACKGROUND: The executive functions of inhibition, planning, flexible shifting of actions, and working memory are commonly reported to be impaired in neurodevelopmental disorders. METHOD: We compared these abilities in children (8-12 years) with high functioning autism (HFA, n = 17), attention deficit-hyperactivity disorder (ADHD, n = 21) and healthy controls (n = 32). Response inhibition was assessed using the Stroop Color and Word Test (Golden, 1978). Problem solving, set-shifting, and nonverbal memory were assessed using three tasks, respectively, from the CANTAB (Cambridge Cognition, 1996): the Stockings of Cambridge task; the Intra-Dimensional/Extra-Dimensional set-shifting task; and the Spatial Working Memory task (SWM) with tokens hidden behind 3, 4, 6, and 8 boxes. RESULTS: There were no group differences on the response inhibition, planning, or set-shifting tasks. On the SWM task, children with HFA made significantly more between-search errors compared with controls on both the most difficult problems (8-box) and on the mid-difficulty problems (6-box); however, children with ADHD made significantly more errors compared to controls on the most difficult (8-box) problems only. CONCLUSION: Our findings suggest that spatial working memory is impaired in both ADHD and HFA, and more severely in the latter. More detailed investigation is needed to examine the mechanisms that differentially impair spatial working memory, but on this set of tasks there appears to be sparing of other executive functions in these neuropsychiatric developmental disorders.

Megalencephaly in NF1: predominantly white matter contribution and mitigation by ADHD.

BACKGROUND: Megalencephaly is a frequent CNS manifestation in neurofibromatosis type 1 (NF1); however, its tissue composition, modification by attention deficit hyperactivity disorder (ADHD), and relationship with unidentified bright objects (UBO) remain controversial. METHODS: Eighteen male patients with NF1, seven of whom had ADHD (NF1+ADHD), were compared with 18 age- and sex-matched controls in terms of MRI-, Talairach-based brain, cerebral, lobar, and sublobar gray and white matter volumes. Twelve subjects with NF1 had UBO in the centrencephalic region, whereas six had no UBO or exclusively infratentorial lesions. RESULTS: Patients with NF1 without ADHD (NF1-pure) had the largest total cerebral, gray, and white matter volumes with larger parietal/somatosensory white matter volumes than controls, particularly if UBO were present in the basal ganglia. All subjects with NF1 (including NF1+ADHD) had larger total and frontal white matter volumes than controls. Smaller frontal/right prefrontal gray matter volumes were found in NF1+ADHD when compared with NF1-pure patients. CONCLUSIONS: The increase in frontal and parietal white matter volumes in male patients with NF1, including the preferential centrencephalic distribution, supports the hypothesis that NF1's white matter pathology encompasses but is not limited to visible UBO. Male patients with NF1+ADHD, as compared with NF1-pure patients, showed frontal reductions that are largely consistent with those found in idiopathic ADHD.

Disproportionate increases of white matter in right frontal lobe in Tourette syndrome.

OBJECTIVE: Based on previous findings implicating abnormalities of cortico-striatal-thalamo-cortical circuitry in Tourette syndrome (TS), the authors performed a volumetric analysis of frontal and nonfrontal tissue (gray + white matter) in boys with TS, with and without attention deficit hyperactivity disorder (ADHD). METHODS: Frontal and nonfrontal gray and white matter compartment volumes, obtained by a MRI protocol, were analyzed with a 2 x 2 factorial multivariate analysis of variance approach for associations with a TS or ADHD factor in 11 boys with TS only, 14 with TS + ADHD, 12 with ADHD only, and 26 healthy boys. RESULTS: In subjects with TS, the right frontal lobe showed a larger proportion of white matter. In addition, results were consistent with previous reports of reduced frontal lobe volumes associated with ADHD. Our analyses suggested these reductions to be mainly the consequence of smaller gray matter volumes, particularly on the left. CONCLUSIONS: These findings, suggesting the volumetric composition of frontal lobe tissue to be different in TS, support the hypothesis proposing frontostriatal pathway involvement in the pathophysiology of the disorder. Differences in composition of right frontal lobe attributable to white matter do not definitively implicate the hypothesized fiber pathways; however, considered in the context of the unilateral directionality of frontal-striatal circuitry, these results suggest the white matter connections as one explanation for basal ganglia anomalies (loss of normal left > right asymmetry) in TS.

Oculomotor abnormalities in attention deficit hyperactivity disorder: a preliminary study.

BACKGROUND: Prevailing hypotheses suggest that attention deficit hyperactivity disorder (ADHD) is secondary to dysfunction of motor intentional systems mediated by prefrontal circuitry. Oculomotor paradigms provide a mechanism for examining and localizing dysfunction at the interface between movement and cognition. OBJECTIVE: Three different saccade tasks (reflexive or prosaccades, antisaccades, and memory-guided saccades) were used to examine functions necessary for the planning and the execution of eye movements, including motor response preparation, response inhibition, and working memory. METHODS: The study included 19 children with ADHD, divided into two groups: a group of 8 children on methylphenidate at the time of testing and a group of 11 children not taking any psychoactive medication. Results from the two groups were compared with those from 25 age- and gender-matched normal control children. RESULTS: Both groups of children with ADHD made significantly more directional errors than did controls on the antisaccade task and significantly more anticipatory errors than did controls on the memory-guided saccade task, findings that are consistent with deficits in response inhibition. There were no significant differences in prosaccade latency, although unmedicated children with ADHD showed significantly greater variability in latency on the prosaccade task than did controls. On the memory-guided saccade task there were no significant differences in saccade accuracy; however, unmedicated children with ADHD showed longer saccade latency than did either controls or medicated children with ADHD. CONCLUSIONS: Oculomotor findings suggest that deficits in prefrontal functions, in particular response inhibition, contribute to behavioral abnormalities observed in ADHD. Findings also suggest that the administration of methylphenidate is associated with improvements in the consistency of motor response. Although there were no observed improvements in response inhibition with methylphenidate, conclusions await a design in which subjects complete testing both on and off medication.