Inter-rater Reliability of the Revised Physical and Neurological Examination of Subtle Signs (PANESS) scored using video review.

The Physical and Neurological Examination of Subtle Signs (PANESS) is a brief neuromotor exam designed for use in children. This study examined the inter-rater reliability of PANESS scoring using video review in 23 typically developing youth, aged 10-18 years, who were either never-concussed or evaluated following clinical recovery from concussion. Moderate to excellent inter-rater reliability was identified across PANESS subscores and total score. The strongest inter-rater reliability was observed for the Timed Motor portion of the PANESS (ICCs >.90) suggesting that this section in particular may be a strong candidate for video-based scoring or telehealth administration.

Preliminary Use of the Physical and Neurological Examination of Subtle Signs for Detecting Subtle Motor Signs in Adolescents With Sport-Related Concussion.

Sensitive examination tools are needed to optimize evaluation after sports-related concussion. The Physical and Neurological Examination of Subtle Signs was preliminarily examined for sensitivity to motor changes in a pilot cohort of adolescents aged 13-17 yrs with sports-related concussion. A total of 15 adolescents (5 female adolescents) with sports-related concussion were evaluated up to three times: within 2 wks of injury, approximately 1 mo later (mean, 35 days between visits), and for those not recovered at the second visit, again after clinical recovery (mean, 70 days between the first and last visits for all participants). Comparison data were acquired from 20 age- and sex-matched healthy control athletes with no history of concussion who were evaluated twice (mean, 32 days apart). Main effects of group, time, and interaction effects were evaluated with an analysis of covariance, which controlled for socioeconomic status, times tested, and days between testing sessions. Adolescents with concussion had poorer Physical and Neurological Examination of Subtle Signs performance than controls did at all time points. Performance improved between visits within the concussion group, with no change within the control group. These findings suggest that the Physical and Neurological Examination of Subtle Signs merits additional study in larger cohorts and in combination with other markers of injury to facilitate an enhanced understanding of sports-related concussion and recovery.

Reduced subcortical volumes among preschool-age girls and boys with ADHD.

Anomalous brain structure and function are implicated in children with attention-deficit/hyperactivity disorder (ADHD). Most neuroimaging research, however, has examined school-aged children, despite the typical onset of symptoms in early childhood. This study compared the volumes of subcortical structures (caudate nucleus, putamen, globus pallidus, and thalamus) among preschoolers with ADHD and typically developing (TD) children. High resolution T1-weighted 3D MPRAGE images covering the whole brain were acquired on a 3T scanner and subcortical volumes were automatically extracted. Analyses were conducted in a total of 87 medication-naïve preschoolers, ages 4-5 years (47 with ADHD, 40 controls; 63% boys). ADHD was diagnosed using modified DSM-IV criteria based on review of developmental history, structured psychiatric interview and caregiver ratings. Compared to typically developing children, subcortical volumes were reduced among preschoolers with ADHD, with largest reductions in the caudate, globus pallidus, and thalamus. Among girls (but not boys) with ADHD, putamen and thalamus volumes were associated with ADHD symptom severity. The observed patterns of subcortical differences in preschoolers with ADHD (larger reductions in girls), contrasted with differences observed among school-aged children, (larger reductions in boys) suggests that children with ADHD show sexual dimorphism in neuroanatomical development that parallels early trajectory of symptom onset and attenuation.

Attention-Deficit/Hyperactivity Disorder: A Historical Neuropsychological Perspective.

The behavior patterns of hyperactivity, impulsivity and inattention that would ultimately become recognized as Attention-Deficit Hyperactivity Disorder (ADHD) have been described for centuries. Nevertheless, in the past 35 years, advances in diagnostic methods, identification of biomarkers, and treatments have advanced at an exponential rate. ADHD is now recognized as the most common behavioral disorder of childhood, with risks extending well into adulthood for both males and females, leading to its identification as a significant public health issue. This historical neuropsychological review of ADHD emphasizes scientific highlights in the past 35 years related to ADHD, including the evolution of the diagnosis (from Hyperkinetic Reaction of Childhood to ADHD), influential theories (executive functions, cognitive-energetic, delay aversion), landmark treatment studies (Multimodal Treatment of ADHD [MTA] and Preschool ADHD Treatment Study [PATS]), and advances in brain mapping techniques (anatomic, functional, and resting state magnetic resonance imaging, diffusion tensor imaging). The review concludes by highlighting the challenges of studying and treating a heterogeneous neurodevelopmental disorder like ADHD, with emphasis on associated disorders and conditions (learning disabilities, sluggish cognitive tempo), special populations (girls, preschoolers, adults), and recommendations for scientific inquiry in the next 35 years. Neuropsychologists are well positioned to address the clinical and research challenges of the next generation of studies, especially involving advances in understanding the sexual dimor.phism, full developmental course, and dynamic risks associated with ADHD. (JINS, 2017, 23, 916-929).

Rapid automatized naming (RAN) in children with ADHD: An ex-Gaussian analysis.

Children with ADHD demonstrate increased frequent "lapses" in performance on tasks in which the stimulus presentation rate is externally controlled, leading to increased variability in response times. It is less clear whether these lapses are also evident during performance on self-paced tasks, e.g., rapid automatized naming (RAN), or whether RAN inter-item pause time variability uniquely predicts reading performance. A total of 80 children aged 9 to 14 years-45 children with attention-deficit/hyperactivity disorder (ADHD) and 35 typically developing (TD) children-completed RAN and reading fluency measures. RAN responses were digitally recorded for analyses. Inter-stimulus pause time distributions (excluding between-row pauses) were analyzed using traditional (mean, standard deviation [SD], coefficient of variation [CV]) and ex-Gaussian (mu, sigma, tau) methods. Children with ADHD were found to be significantly slower than TD children (p < .05) on RAN letter naming mean response time as well as on oral and silent reading fluency. RAN response time distributions were also significantly more variable (SD, tau) in children with ADHD. Hierarchical regression revealed that the exponential component (tau) of the letter-naming response time distribution uniquely predicted reading fluency in children with ADHD (p < .001, ΔR2 = .16), even after controlling for IQ, basic reading, ADHD symptom severity and age. The findings suggest that children with ADHD (without word-level reading difficulties) manifest slowed performance on tasks of reading fluency; however, this "slowing" may be due in part to lapses from ongoing performance that can be assessed directly using ex-Gaussian methods that capture excessively long response times.

Examining the reinforcing value of stimuli within social and non-social contexts in children with and without high-functioning autism.

One of the key diagnostic criteria for autism spectrum disorder includes impairments in social interactions. This study compared the extent to which boys with high-functioning autism and typically developing boys "value" engaging in activities with a parent or alone. Two different assessments that can empirically determine the relative reinforcing value of social and non-social stimuli were employed: paired-choice preference assessments and progressive-ratio schedules. There were no significant differences between boys with high-functioning autism and typically developing boys on either measure. Moreover, there was a strong correspondence in performance across these two measures for participants in each group. These results suggest that the relative reinforcing value of engaging in activities with a primary caregiver is not diminished for children with autism spectrum disorder.

Distinct frontal lobe morphology in girls and boys with ADHD.

OBJECTIVE: This study investigated whether frontal lobe cortical morphology differs for boys and girls with ADHD (ages 8-12 years) in comparison to typically developing (TD) peers. METHOD: Participants included 226 children between the ages of 8-12 including 93 children with ADHD (29 girls) and 133 TD children (42 girls) for which 3T MPRAGE MRI scans were obtained. A fully automated frontal lobe atlas was used to generate functionally distinct frontal subdivisions, with surface area (SA) and cortical thickness (CT) assessed in each region. Analyses focused on overall diagnostic differences as well as examinations of the effect of diagnosis within boys and girls. RESULTS: Girls, but not boys, with ADHD showed overall reductions in total prefrontal cortex (PFC) SA. Localization revealed that girls showed widely distributed reductions in the bilateral dorsolateral PFC, left inferior lateral PFC, right medial PFC, right orbitofrontal cortex, and left anterior cingulate; and boys showed reduced SA only in the right anterior cingulate and left medial PFC. In contrast, boys, but not girls, with ADHD showed overall reductions in total premotor cortex (PMC) SA. Further localization revealed that in boys, premotor reductions were observed in bilateral lateral PMC regions; and in girls reductions were observed in bilateral supplementary motor complex. In line with diagnostic group differences, PMC and PFC SAs were inversely correlated with symptom severity in both girls and boys with ADHD. CONCLUSIONS: These results elucidate sex-based differences in cortical morphology of functional subdivisions of the frontal lobe and provide additional evidence of associations among SA and symptom severity in children with ADHD.

Jitter Reduces Response-Time Variability in ADHD: An Ex-Gaussian Analysis.

OBJECTIVE: "Jitter" involves randomization of intervals between stimulus events. Compared with controls, individuals with ADHD demonstrate greater intrasubject variability (ISV) performing tasks with fixed interstimulus intervals (ISIs). Because Gaussian curves mask the effect of extremely slow or fast response times (RTs), ex-Gaussian approaches have been applied to study ISV. METHOD: This study applied ex-Gaussian analysis to examine the effects of jitter on RT variability in children with and without ADHD. A total of 75 children, aged 9 to 14 years (44 ADHD, 31 controls), completed a go/no-go test with two conditions: fixed ISI and jittered ISI. RESULTS: ADHD children showed greater variability, driven by elevations in exponential (tau), but not normal (sigma) components of the RT distribution. Jitter decreased tau in ADHD to levels not statistically different than controls, reducing lapses in performance characteristic of impaired response control. CONCLUSION: Jitter may provide a nonpharmacologic mechanism to facilitate readiness to respond and reduce lapses from sustained (controlled) performance.

Performance lapses in children with attention-deficit/hyperactivity disorder contribute to poor reading fluency.

Children with Attention-Deficit/Hyperactivity Disorder (ADHD) demonstrate increased response variability compared with controls, which is thought to be associated with deficits in attention regulation and response control that subsequently affect performance of more cognitively demanding tasks, such as reading. The present study examined response variability during a computerized simple reaction time (RT) task in 67 children. Ex-Gaussian analyses separated the response time distribution into normal (mu and sigma) and exponential (tau) components; the association of each with reading fluency was examined. Children with ADHD had significantly slower, more variable, and more skewed RTs compared with controls. After controlling for ADHD symptom severity, tau (but not mu or mean RT) was significantly associated with reduced reading fluency, but not with single word reading accuracy. These data support the growing evidence that RT variability, but not simply slower mean response speed, is the characteristic of youth with ADHD and that longer response time latencies (tau) may be implicated in the poorer academic performance associated with ADHD.

Multiple task interference is greater in children with ADHD.

There is considerable lay discussion that children with attention deficit hyperactivity disorder (ADHD) have increased difficulty with multitasking, but there are few experimental data. In the current study, we examine the simultaneous processing of two stimulus-response tasks using the Psychological Refractory Period (PRP) effect. We hypothesized that children with ADHD would show a greater PRP effect, suggesting a prolonged "bottleneck" in stimulus-response processing. A total of 19 school-aged children with ADHD showed a prolonged PRP effect compared with 25 control children, suggesting a higher cognitive cost in ADHD for multitasking.

Comprehensive examination of frontal regions in boys and girls with attention-deficit/hyperactivity disorder.

The current study examined regional frontal lobe volumes based on functionally relevant subdivisions in contemporaneously recruited samples of boys and girls with and without attention-deficit/hyperactivity disorder (ADHD). Forty-four boys (21 ADHD, 23 control) and 42 girls (21 ADHD, 21 control), ages 8-13 years, participated. Sulcal-gyral landmarks were used to manually delimit functionally relevant regions within the frontal lobe: primary motor cortex, anterior cingulate, deep white matter, premotor regions [supplementary motor complex (SMC), frontal eye field, lateral premotor cortex (LPM)], and prefrontal cortex (PFC) regions [medial PFC, dorsolateral PFC (DLPFC), inferior PFC, lateral orbitofrontal cortex (OFC), and medial OFC]. Compared to sex-matched controls, boys and girls with ADHD showed reduced volumes (gray and white matter) in the left SMC. Conversely, girls (but not boys) with ADHD showed reduced gray matter volume in left LPM; while boys (but not girls) with ADHD showed reduced white matter volume in left medial PFC. Reduced left SMC gray matter volumes predicted increased go/no-go commission rate in children with ADHD. Reduced left LPM gray matter volumes predicted increased go/no-go variability, but only among girls with ADHD. Results highlight different patterns of anomalous frontal lobe development among boys and girls with ADHD beyond that detected by measuring whole lobar volumes.

Increased regional fractional anisotropy in highly screened attention-deficit hyperactivity disorder (ADHD).

Diffusion tensor imaging data were collected at 3.0 Tesla from 16 children with attention-deficit hyperactivity disorder (ADHD) and 16 typically developing controls, ages 9 to 14 years. Fractional anisotropy images were calculated and normalized by linear transformation. Voxel-wise and atlas-based region-of-interest analyses were performed. Using voxel-wise analysis, fractional anisotropy was found to be significantly increased in the attention-deficit hyperactivity disorder group in the right superior frontal gyrus and posterior thalamic radiation, and left dorsal posterior cingulate gyrus, lingual gyrus, and parahippocampal gyrus. No regions showed significantly decreased fractional anisotropy in attention-deficit hyperactivity disorder. Region-of-interest analysis revealed increased fractional anisotropy in the left sagittal stratum, that is, white matter that connects the temporal lobe to distant cortical regions. Only fractional anisotropy in the left sagittal stratum was significantly associated with attention-deficit hyperactivity disorder symptom severity. Several recent studies have reported pathological increases in fractional anisotropy in other conditions, highlighting the relevance of diffusion tensor imaging in identifying atypical white matter structure associated with neurodevelopmental processes.

Working memory influences processing speed and reading fluency in ADHD.

Processing-speed deficits affect reading efficiency, even among individuals who recognize and decode words accurately. Children with ADHD who decode words accurately can still have inefficient reading fluency, leading to a bottleneck in other cognitive processes. This "slowing" in ADHD is associated with deficits in fundamental components of executive function underlying processing speed, including response selection. The purpose of the present study was to deconstruct processing speed in order to determine which components of executive control best explain the "processing" speed deficits related to reading fluency in ADHD. Participants (41 ADHD, 21 controls), ages 9-14 years, screened for language disorders, word reading deficits, and psychiatric disorders, were administered measures of copying speed, processing speed, reading fluency, working memory, reaction time, inhibition, and auditory attention span. Compared to controls, children with ADHD showed reduced oral and silent reading fluency and reduced processing speed-driven primarily by deficits on WISC-IV Coding. In contrast, groups did not differ on copying speed. After controlling for copying speed, sex, severity of ADHD-related symptomatology, and GAI, slowed "processing" speed (i.e., Coding) was significantly associated with verbal span and measures of working memory but not with measures of response control/inhibition, lexical retrieval speed, reaction time, or intrasubject variability. Further, "processing" speed (i.e., Coding, residualized for copying speed) and working memory were significant predictors of oral reading fluency. Abnormalities in working memory and response selection (which are frontally mediated and enter into the output side of processing speed) may play an important role in deficits in reading fluency in ADHD, potentially more than posteriorally mediated problems with orienting of attention or perceiving the stimulus.

Children with high functioning autism show increased prefrontal and temporal cortex activity during error monitoring.

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 8­12-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.

Neuropsychological profile of executive function in girls with attention-deficit/hyperactivity disorder.

The majority of research on neurobehavioral functioning among children with Attention-Deficit/Hyperactivity Disorder (ADHD) is based on samples comprised primarily (or exclusively) of boys. Although functional impairment is well established, available research has yet to specify a neuropsychological profile distinct to girls with ADHD. The purpose of this study was to examine performance within four components of executive function (EF) in contemporaneously recruited samples of girls and boys with ADHD. Fifty-six children with ADHD (26 girls) and 90 controls (42 girls), ages 8-13, were administered neuropsychological tests emphasizing response inhibition, response preparation, working memory, and planning/shifting. There were no significant differences in age or SES between boys or girls with ADHD or their sex-matched controls; ADHD subtype distribution did not differ by sex. Compared with controls, children with ADHD showed significant deficits on all four EF components. Girls and boys with ADHD showed similar patterns of deficit on tasks involving response preparation and working memory; however, they manifested different patterns of executive dysfunction on tasks related to response inhibition and planning. Girls with ADHD showed elevated motor overflow, while boys with ADHD showed greater impairment during conscious, effortful response inhibition. Girls, but not boys with ADHD, showed impairment in planning. There were no differences between ADHD subtypes on any EF component. These findings highlight the importance of studying boys and girls separately (as well as together) when considering manifestations of executive dysfunction in ADHD.

Factor structure of paediatric timed motor examination and its relationship with IQ.

AIM: Brain systems supporting higher cognitive and motor control develop in a parallel manner, dependent on functional integrity and maturation of related regions, suggesting neighbouring neural circuitry. Concurrent examination of motor and cognitive control can provide a window into neurological development. However, identification of performance-based measures that do not correlate with IQ has been a challenge. Method Timed motor performance from the Physical and Neurological Examination of Subtle Signs and IQ were analysed in 136 children aged 6 to 16 (mean age 10y 2.6mo, SD 2y 6.4mo; 98 female, 38 male) attending an outpatient neuropsychology clinic and 136 right-handed comparison individuals aged 6 to 16 (mean age 10y 3.1mo, SD 2y 6.1mo; 98 female, 38 male). Timed activities--three repetitive movements (toe tapping, hand patting, finger tapping) and three sequenced movements (heel-toe tap, hand pronate/supinate, finger sequencing) each performed on the right and left--were included in exploratory factor analyses. Results Among comparison individuals, factor analysis yielded two factors--repetitive and sequenced movements--with the sequenced factor significantly predictive of Verbal IQ (VIQ) (DeltaR(2)=0.018, p=0.019), but not the repetitive factor (DeltaR(2)=0.004, p=0.39). Factor analysis within the clinical group yielded two similar factors (repetitive and sequenced), both significantly predictive of VIQ, (DeltaR(2)=0.028, p=0.015; DeltaR(2)=0.046, p=0.002 respectively). Interpretation Among typical children, repetitive timed tasks may be independent of IQ; however, sequenced tasks share more variance, implying shared neural substrates. Among neurologically vulnerable populations, however, both sequenced and repetitive movements covary with IQ, suggesting that repetitive speed is more indicative of underlying neurological integrity.

Corpus callosum segment circumference is associated with response control in children with attention-deficit hyperactivity disorder (ADHD).

Response control is impaired in attention-deficit hyperactivity disorder (ADHD). Given the corpus callosum's role in response control, we compared callosal morphology in 64 children with ADHD and 64 typically developing children, aged 7 to 13 years, and investigated the relationships between callosal morphology and response control. Area and circumference of 5 callosal segments (genu, rostral body, midbody, isthmus, and splenium) were normalized for cerebral volume and examined for correlation with mean reaction time, intrasubject variability, and/or commission error rate from a go/no-go task. There were no between-group differences in segment areas or circumferences. Reaction time correlated with midbody circumference for boys with ADHD and isthmus circumference for girls with ADHD. For the entire cohort, rostral body circumference correlated with intrasubject variability. Impaired response control in ADHD is associated with anomalies in frontal interhemispheric connections. Future studies examining callosal shape will illuminate the anatomic basis of correlations between callosal segment circumference and response control.

Toward a narrower, more pragmatic view of developmental dyspraxia.

Apraxia traditionally refers to impaired ability to carry out skilled movements in the absence of fundamental sensorimotor, language, or general cognitive impairment sufficient to preclude them. The child neurology literature includes a much broader and varied usage of the term developmental dyspraxia. It has been used to describe a wide range of motor symptoms, including clumsiness and general coordination difficulties, in various developmental disorders (including autistic spectrum disorders, developmental language disorders, and perinatal stroke). We argue for the need to restrict use of the term developmental dyspraxia to describe impaired performance of skilled gestures, recognizing that, unlike acquired adult-onset apraxia, coexisting sensory and motor problems can also be present.

Interstimulus jitter facilitates response control in children with ADHD.

Interstimulus "jitter" involves randomization of intervals between successive stimulus events, and can facilitate performance on go/no-go tests among healthy adults, though its effect in clinical populations is unclear. Children with Attention-deficit/Hyperactivity Disorder (ADHD) commonly exhibit deficient response control, leading to increased intra-subject variability (ISV), which has been linked to anomalous functioning within frontal circuits, as well as their interaction with posterior "default mode" regions. We examined effects of interstimulus jitter on response variability in 39 children, ages 9-14 years (25 ADHD, 14 controls). Participants completed 2 computerized go/no-go tests: one with fixed interstimulus interval (ISI) and one with jittered ISI. Repeated measures analysis of variance (ANOVA) revealed a significant group-by test interaction, such that introduction of jitter produced a significant decrease in ISV among children with ADHD, but not among controls. Whereas children with ADHD were significantly more variable than controls on the go/no-go test with fixed ISI, their performance with jittered ISI was equivalent to that of controls. Jittering stimulus presentation provides a nonpharmacologic mechanism for improving response control in ADHD. This bottom-up approach may be mediated by increases in vigilance through noradrenergic circuits that facilitate maintenance of frontal circuits critical to response control.

White matter microstructural differences linked to left perisylvian language network in children with dyslexia.

Studies of dyslexia using diffusion tensor imaging (DTI) have reported fractional anisotropy (FA) differences in left inferior frontal gyrus (LIFG) and left temporo-parietal white matter, suggesting that impaired reading is associated with atypical white matter microstructure in these regions. These anomalies might reflect abnormalities in the left perisylvian language network, long implicated in dyslexia. While DTI investigations frequently report analyses on multiple tensor-derived measures (e.g., FA, orientation, tractography), it is uncommon to integrate analyses to examine the relationships between atypical findings. For the present study, semi-automated techniques were applied to DTI data in an integrated fashion to examine white matter microstructure in 14 children with dyslexia and 17 typically developing readers (ages 7-16 years). Correlations of DTI metrics (FA and fiber orientation) to reading skill (accuracy and speed) and to probabilistic tractography maps of the left perisylvian language tracts were examined. Consistent with previous reports, our findings suggest FA decreases in dyslexia in LIFG and left temporo-parietal white matter. The LIFG FA finding overlaps an area showing differences in fiber orientation in an anterior left perisylvian language pathway. Additionally, a positive correlation of FA to reading speed was found in a posterior circuit previously associated with activation on functional imaging during reading tasks. Overall, integrating results from several complementary semi-automated analyses reveals evidence linking atypical white matter microstructure in dyslexia to atypical fiber orientation in circuits implicated in reading including the left perisylvian language network.