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1.  Incremental Validity of Neuropsychological Assessment in the Identification and Treatment of Youth with ADHD 
The Clinical neuropsychologist  2013;28(1):26-48.
Comprehensive neuropsychological assessments for youth with ADHD allow for thorough consideration of co-occurring disorders and provide targeted recommendations for treating ADHD and comorbid conditions. This study offers a preliminary evaluation of the added value (compared to routine care) associated with neuropsychological assessment in the identification and treatment of ADHD in youth ages 3-17 years. First, we describe a novel measure developed to evaluate broad-based outcomes for youth with ADHD following neuropsychological assessment. Next, we compare parent ratings of child symptoms and quality of life between two groups of youth with ADHD: those who have recently received neuropsychological assessments (NP+), and those who have not (NP−). Participants were surveyed again 5 months after baseline to assess changes in symptoms, quality of life, and service utilization. While both groups experienced significant improvements in behavioral/emotional symptoms, the NP+ group had greater initiation of parent behavior management training and special education services and greater initiation of medication management over the follow-up period, compared with the NP− group. Satisfaction with neuropsychological assessment was high overall but slightly decreased over the course of the follow-up period. The findings offer preliminary support for the incremental efficacy of neuropsychological evaluation in the diagnosis and management of ADHD.
PMCID: PMC3943538  PMID: 24345262
ADHD; neuropsychological; testing; quality of life; utility; efficacy; outcome
2.  Neuropsychological function in children with primary complex motor stereotypies 
Complex motor stereotypies (CMS) are patterned, repetitive, rhythmic, and involuntary movements that persist over time. They are divided into two subgroups dependent on the presence of other developmental problems: ‘primary’ (development is otherwise typical) or ‘secondary’ (associated with autism, intellectual disability, or sensory deficits). There are no currently published studies that examine neuropsychological function in children with primary CMS. This case–control study examines whether children with primary CMS manifest neurobehavioral deficits.
Fifty-seven children with primary CMS (32 males, 25 females; mean age 6y 8mo, SD 2y 4mo, range 4–12y) with negative screens for autism and 57 comparison participants (32 males, 25 females; mean age 6y 6mo, SD 2y 1mo) completed neuropsychological assessments of IQ, reading ability, attention, language, and motor and executive functions. Parents completed ratings of their child’s repetitive movement severity.
The CMS group performed significantly less well than comparison participants on motor skills and IQ tests (both p<0.01), although IQ was consistently in the average range. One-third of the CMS group showed signs of developmental motor coordination difficulties. Parent report of stereotypy severity was significantly associated with parent report of inattention and executive dysfunction.
Children with primary CMS were found to have largely intact neuropsychological profiles. Stereotypy severity appears to be associated with executive dysfunction. Although motor difficulties were observed in children with CMS, these were not correlated with parent report of symptom severity.
PMCID: PMC4162830  PMID: 24814517
3.  Distinct frontal lobe morphology in girls and boys with ADHD 
NeuroImage : Clinical  2014;7:222-229.
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.
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.
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.
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.
•Children with ADHD showed reductions in cortical surface area.•Boys with ADHD showed overall reductions in total premotor cortex surface area.•Girls with ADHD showed overall reductions in total prefrontal cortex surface area.•Surface area in the ADHD group was associated with symptom severity.
PMCID: PMC4300006  PMID: 25610784
ADHD sex-differences; Cortical morphology; Development; Frontal lobe
4.  Clinical Utility of the Colorado Learning Difficulties Questionnaire 
Pediatrics  2013;132(5):e1257-e1264.
Behavioral disorders are highly comorbid with childhood learning disabilities (LDs), and accurate identification of LDs is vital for guiding appropriate interventions. However, it is difficult to conduct comprehensive assessment of academic skills within the context of primary care visits, lending utility to screening of academic skills via informant reports. The current study evaluated the clinical utility of a parent-reported screening measure in identifying children with learning difficulties.
Participants included 440 children (66.7% male), ages 5.25 to 17.83 years (mean = 10.32 years, SD = 3.06 years), referred for neuropsychological assessment. Academic difficulties were screened by parent report using the Colorado Learning Difficulties Questionnaire (CLDQ). Reading and math skills were assessed via individually administered academic achievement measures. Sensitivity, specificity, classification accuracy, and conditional probabilities were calculated to evaluate the efficacy of the CLDQ in predicting academic impairment.
Correlations between the CLDQ reading scale and reading achievement measures ranged from −0.35 to −0.65 and from −0.24 to −0.46 between the CLDQ math scale and math achievement measures (all P < .01). Sensitivity was good for both reading and math scales, whereas specificity was low. Taking into account the high base rate of reading and math LDs within our sample, the conditional probability of true negatives (96.2% reading, 85.1% math) was higher than for true positives (40.5% reading, 37.9% math).
Overall, the CLDQ may more accurately predict children without LDs than children with LDs. As such, the absence of parent-reported difficulties may be adequate to rule out an overt LD, whereas elevated scores likely indicate the need for more comprehensive assessment.
PMCID: PMC4074675  PMID: 24101755
learning disorders; rating scales; ADHD; achievement testing; sensitivity; specificity
5.  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.
PMCID: PMC3807832  PMID: 23838684
Attention; Dyslexia; Variability; Processing speed; Executive function; Ex-Gaussian analyses
6.  Letter to the Editor 
Neuro-Oncology  2013;15(11):1455.
PMCID: PMC3813425  PMID: 24174569
7.  Jitter Reduces Response-Time Variability in ADHD: An Ex-Gaussian Analysis 
Journal of attention disorders  2012;10.1177/1087054712464269.
“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.
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.
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.
Jitter may provide a nonpharmacologic mechanism to facilitate readiness to respond and reduce lapses from sustained (controlled) performance.
PMCID: PMC3600392  PMID: 23190614
ADHD; executive function; attention; variability; response time; statistics; ex-Gaussian; jitter
8.  The Kennedy Krieger Independence Scales–Spina Bifida Version: A Measure of Executive Components of Self-Management 
Rehabilitation psychology  2013;58(1):98-105.
Successful implementation of functional self-care skills depends upon adequate executive functioning; however, many scales assessing adaptive skills do not address the inherent executive burden of these tasks. This omission is especially relevant for individuals with spina bifida, for whom medical self-care tasks impose a significant burden requiring initiation and prospective memory. The Kennedy Krieger Independence Scales–Spina Bifida Version (KKIS–SB) is a caregiver-reported measure designed to address this gap; it assesses skills for managing both typical and spina bifida-related daily self-care demands, with a focus on the timely and independent initiation of adaptive skills.
Research Method/Design
Parents of 100 youth and young adults with spina bifida completed the KKIS–SB. Exploratory factor analysis and Pearson's correlations were used to assess the factor structure, reliability, and construct validity of the KKIS–SB.
The scale demonstrates excellent internal consistency (Cronbach's alpha = .891). Exploratory factor analysis yielded four factors, explaining 65.1% of the total variance. Two primary subscales were created, initiation of routines and prospective memory, which provide meaningful clinical information regarding management of a variety of typical (e.g., get up on time, complete daily hygiene routines on time) and spina bifida-specific self-care tasks (e.g., begin self-catheterization on time, perform self-examination for pressure sores).
Based upon internal consistency estimates and correlations with measures of similar constructs, initial data suggest good preliminary reliability and validity of the KKIS–SB.
PMCID: PMC4154366  PMID: 23438006
transition; adaptive functioning; validity; factor structure; executive function
9.  Classification of intellectual disability using the Wechsler Intelligence Scale for Children: Full Scale IQ or General Abilities Index? 
We examined the implications of using the Full Scale Intelligence Quotient (FSIQ) versus the General Abilities Index (GAI) for determination of intellectual disability using the Wechsler Intelligence Scales for Children, fourth edition (WISC-IV).
Children referred for neuropsychological assessment (543 males, 290 females; mean age 10y 5mo, SD 2y 9mo, range 6–16y) were administered the WISC-IV and the Adaptive Behavior Assessment System, Second Edition (ABAS-II).
GAI and FSIQ were highly correlated; however, fewer children were identified as having intellectual disability using GAI (n=159) than when using FSIQ (n=196). Although the 44 children classified as having intellectual disability based upon FSIQ (but not GAI) had significantly higher adaptive functioning scores than those meeting intellectual disability criteria based upon both FSIQ and GAI, mean adaptive scores still fell within the impaired range. FSIQ and GAI were comparable in predicting impairments in adaptive functioning.
Using GAI rather than FSIQ in intellectual disability diagnostic decision making resulted in fewer individuals being diagnosed with intellectual disability; however, the mean GAI of the disqualified individuals was at the upper end of criteria for intellectual impairment (standard score 75), and these individuals remained adaptively impaired. As GAI and FSIQ were similarly predictive of overall adaptive functioning, the use of GAI for intellectual disability diagnostic decision making may be of limited value.
PMCID: PMC3748610  PMID: 23859669
10.  Association between radiation dose to neuronal progenitor cell niches and temporal lobes and performance on neuropsychological testing in children: a prospective study 
Neuro-Oncology  2013;15(3):360-369.
Neurocognitive toxicity from radiation therapy (RT) for brain tumors may be related to damage to neural progenitor cells that reside in the subventricular zone and hippocampus. This prospective study examines the relationship between RT dose to neural progenitor cell niches, temporal lobes, and cerebrum and neurocognitive dysfunction following cranial irradiation.
Standardized assessments of motor speed/dexterity, verbal memory, visual perception, vocabulary, and visuospatial working memory were conducted in 19 pediatric patients receiving cranial RT and 55 controls at baseline and 6, 15, and 27 months following completion of RT. Prescription doses ranged from 12 Gy to 59.4 Gy. Linear mixed effects regression model analyses were used to examine the relationships among neuropsychological performance, age, and radiation dose to the subventricular zone, hippocampus, temporal lobes, and cerebrum.
Performance on all neuropsychological tests, except vocabulary, was significantly reduced in patients relative to controls, particularly among younger children. Performance on motor speed/dexterity decreased with increasing dose to hippocampus (P < .05) and temporal lobes (P < .035). There was also a significant relationship between (i) reduced performance on verbal learning and increasing dose to the cerebrum (P = .022) and (ii) reduced performance on visual perception and increasing dose to the left temporal lobe (P = .038). There was no association between radiation dose to evaluated structures and performance on vocabulary or visuospatial working memory.
These prospective data demonstrate a significant association between increasing RT dose to hippocampus and temporal lobes and decline in neurocognitive skills following cranial irradiation. These findings have important implications for trials, including RTOG 0933 (hippocampal-sparing whole brain radiation therapy for brain metastases).
PMCID: PMC3578483  PMID: 23322748
brain irradiation; brain tumor; neural progenitor cell niches; neuropsychological performance
11.  Factor structure of paediatric timed motor examination and its relationship with IQ 
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.
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, 38male) 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, 38male). 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.
Among comparison individuals, factor analysis yielded two factors – repetitive and sequenced movements – with the sequenced factor significantly predictive of Verbal IQ (VIQ) (ΔR2=0.018, p=0.019), but not the repetitive factor (ΔR2=0.004, p=0.39). Factor analysis within the clinical group yielded two similar factors (repetitive and sequenced), both significantly predictive of VIQ, (ΔR2=0.028, p=0.015; ΔR2=0.046, p=0.002 respectively).
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.
PMCID: PMC3534928  PMID: 20412260
12.  The Neurobiological Profile of Girls with ADHD 
Since boys are more commonly diagnosed with Attention Deficit Hyperactivity Disorder (ADHD) than girls, the majority of theories and published research studies of ADHD have been based on samples comprised primarily (or exclusively) of boys. While psychosocial impairment in girls with ADHD is well established, the neuropsychological and neurobiological basis of these deficits is less consistently observed. There is growing evidence that boys’ and girls’ brains develop and mature at different rates, suggesting that the trajectory of early anomalous brain development in ADHD may also be sex-specific. It remains unclear, however, whether earlier brain maturation observed in girls with ADHD is protective. In this review, we outline the current theory and research findings that seek to establish a unique neurobiological profile of girls with ADHD, highlighting sex differences in typical brain development and among children with ADHD. The review highlights findings from neurological, neurocognitive, and behavioral studies. Future research directions are suggested, including the need for longitudinal neuroimaging and neurobehavioral investigation beginning as early as the preschool years, and continuing through adolescence and adulthood, with consideration of identified sex differences in the development of ADHD.
PMCID: PMC3534724  PMID: 19072756
childhood; development; executive functions; neuroimaging; ADHD; gender
13.  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.
PMCID: PMC3534734  PMID: 21923979
Segmentation; Premotor; Prefrontal; Supplementary Motor Complex (SMC); Pre-SMA; Gender; Sex; Childhood
14.  Increased Regional Fractional Anisotropy in Highly Screened Attention-Deficit Hyperactivity Disorder (ADHD) 
Journal of child neurology  2011;26(10):1296-1302.
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.
PMCID: PMC3526818  PMID: 21628699
attention-deficit hyperactivity disorder (ADHD); development; cognitive; diffusion tensor imaging; magnetic resonance imaging (MRI)
15.  The Effects of Napping on Cognitive Function in Preschoolers 
To determine the relationship between napping and cognitive function in preschool-aged children.
Daytime napping, nighttime sleep and cognitive function were assessed in fifty-nine typically developing children ages 3-5 years, who were enrolled in full-time childcare. Participants wore an actigraphy watch for 7 days to measure sleep and napping patterns, and completed neuropsychological testing emphasizing attention, response control, and vocabulary. Parents of participants completed behavior ratings and sleep logs during the study. Sleep/wake cycles were scored with the Sadeh algorithm.
Children who napped more on weekdays were also more likely to nap during weekends. Weekday napping and nighttime sleep were inversely correlated, such that those who napped more slept less at night, while total weekday sleep remained relatively constant. Weekday napping was significantly (negatively) correlated with vocabulary and auditory attention span, and weekday nighttime sleep was positively correlated with vocabulary. Nighttime sleep was also significantly negatively correlated with performance, such that those who slept less at night made more impulsive errors on a computerized go/no-go test.
Daytime napping is actually negatively correlated with neurocognitive function in preschoolers. Nighttime sleep appears to be more critical for development of cognitive performance. Cessation of napping may serve as a developmental milestone of brain maturation. Children who nap less do not appear to be sleep deprived, especially if they compensate with increased nighttime sleep. An alternative explanation is that children who sleep less at night are sleep deprived and require a nap. A randomized trial of nap restriction would be the next step in understanding the relationship between napping and neurocognitive performance.
PMCID: PMC3095909  PMID: 21217402
childhood; attention; sleep; cognition; actigraphy; preschool
16.  Defining the Roles of Actigraphy and Parent Logs for Assessing Sleep Variables in Preschool Children 
Behavioral sleep medicine  2011;9(3):184-193.
Actigraphy provides a non-invasive objective means to assess sleep–wake cycles. In young children, parent logs can also be useful for obtaining sleep–wake information. The authors hypothesized that actigraphy and parent logs were both equally valid instruments in healthy preschool-aged children. The authors studied 59 children aged 3 to 5 years in full-time day care. Each child was screened for medical problems and developmental delays before being fitted with an actigraphy watch, which was worn for 1 week. Parents maintained logs of sleep and wakefulness during the same period, with input from day care workers. In general, parents overestimated the amount of nighttime sleep measured by actigraphy by 13% to 22% (all significant). Although there was no difference in sleep onset times, parents reported later rise times on the weekend and fewer nighttime awakenings. There was no significant difference between parent logs and actigraphy with regard to daytime napping. The authors conclude that parent logs are best utilized in assessing daytime sleep and sleep onset, whereas actigraphy should be used to assess nighttime sleep and sleep offset time.
PMCID: PMC3206727  PMID: 21722013
17.  Multiple Task Interference is Greater in Children with ADHD 
Developmental Neuropsychology  2012;37(2):119-133.
There is considerable lay discussion that children with Attention-Deficit/Hyperactivity Disorder (ADHD) have increased difficult 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 multi-tasking.
PMCID: PMC3313619  PMID: 22339226
Multi-tasking; Executive Function; ADHD; Processing Speed; Psychological Refractory Period
18.  Neuroimaging and neuropsychological follow-up study in a pediatric brain tumor patient treated with surgery and radiation 
Neurocase  2010;16(1):74-90.
Intracranial tumors are the most common neoplasms of childhood, accounting for approximately 20% of all pediatric malignancies. Radiation therapy has led directly to significant increases in survival of children with certain types of intracranial tumors; however, given the aggressive nature of this therapy, children are at risk for exhibiting changes in brain structure, neuronal biochemistry, and neurocognitive functioning. In this case report, we present neuropsychological, magnetic resonance imaging, proton magnetic resonance spectroscopic imaging, and diffusion tensor imaging data for two adolescents (one patient with ependymal spinal cord tumor with intracranial metastases, and one healthy, typically developing control) from three time points as defined by the patient's radiation schedule (baseline before the patient's radiation therapy, 6 months following completion of the patient's radiation, and 27 months following the patient's radiation). In the patient, there were progressive decreases in gray and white matter volumes as well as early decreases in mean N-acetyl aspartate/choline (NAA/Cho) ratios and fractional anisotropy (FA) in regions with normal appearance on conventional MRI. At the last follow-up, NAA/Cho and FA tended to change in the direction to normal values in selected regions. At the same time, the patient had initial reduction in language and motor skills, followed by return to baseline, but later onset delay in visuospatial and visual perceptual skills. Results are discussed in terms of sensitivity of the four techniques to early and late effects of treatment, and avenues for future investigations.
PMCID: PMC2911148  PMID: 20391187
Neuroimaging; Neuropsychological; Neoplasm; Radiation; Diffusion; Magnetic resonance spectroscopy
19.  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.
PMCID: PMC2827644  PMID: 20003583
Executive function; Childhood; Variability; Attention; Continuous performance test; Noradrenergic; Locus ceruleus
20.  Response variability in rapid automatized naming predicts reading comprehension 
A total of 37 children ages 8 to 14 years, screened for word-reading difficulties (23 with attention-deficit/hyperactivity disorder, ADHD; 14 controls) completed oral reading and rapid automatized naming (RAN) tests. RAN trials were segmented into pause and articulation time and intraindividual variability. There were no group differences on reading or RAN variables. Color- and letter-naming pause times and number-naming articulation time were significant predictors of reading fluency. In contrast, number and letter pause variability were predictors of comprehension. Results support analysis of subcomponents of RAN and add to literature emphasizing intraindividual variability as a marker for response preparation, which has relevance to reading comprehension.
PMCID: PMC2829106  PMID: 19221923
Reading; Attention-deficit/hyperactivity disorder; Dyslexia; Comprehension; Executive function; Variability
21.  Relationship of Temporal Lobe Volumes to Neuropsychological Test Performance in Healthy Children 
Brain and cognition  2008;68(2):171-179.
Ecological validity of neuropsychological assessment includes the ability of tests to predict real-world functioning and/or covary with brain structures. Studies have examined the relationship between adaptive skills and test performance, with less focus on the association between regional brain volumes and neurobehavioral function in healthy children. The present study examined the relationship between temporal lobe gray matter volumes and performance on two neuropsychological tests hypothesized to measure temporal lobe functioning (Visual Perception-VP; Peabody Picture Vocabulary Test, Third Edition-PPVT-III) in 48 healthy children ages 5-18 years. After controlling for age and gender, left and right temporal and left occipital volumes were significant predictors of VP. Left and right frontal and temporal volumes were significant predictors of PPVT-III. Temporal volume emerged as the strongest lobar correlate with both tests. These results provide convergent and discriminant validity supporting VP as a measure of the “what” system; but suggest the PPVT-III as a complex measure of receptive vocabulary, potentially involving executive function demands.
PMCID: PMC2592537  PMID: 18513844
Neuropsychological Tests; Visual Perception; Receptive Language; MRI; Brain Volumes; Temporal Lobe; Normal Development; PPVT
22.  Neuroimaging correlates of parent ratings of working memory in typically developing children 
The purpose of the present study was to investigate construct validity of parent ratings of working memory in children, using a multi-trait/multi-method design including neuroimaging, rating scales, and performance-based measures. Thirty-five typically developing children completed performance-based tests of working memory and nonexecutive function (EF) skills, received volumetric MRI, and were rated by parents on both EF-specific and broad behavior rating scales. After controlling for total cerebral volume and age, parent ratings of working memory were significantly correlated with frontal gray, but not temporal, parietal, or occipital gray, or any lobar white matter volumes. Performance-based measures of working memory were also moderately correlated with frontal lobe gray matter volume; however, non-EF parent ratings and non-EF performance-based measures were not correlated with frontal lobe volumes. Results provide preliminary support for the convergent and discriminant validity of parent ratings of working memory, and emphasize their utility in exploring brain–behavior relationships in children. Rating scales that directly examine EF skills may potentially have ecological validity, not only for “everyday” function, but also as correlates of brain volume.
PMCID: PMC2742624  PMID: 19128526
Working memory; Executive function; Ecological validity; Rating scales; MRI; Brain volumes; Normal development
23.  Working Memory Influences Processing Speed and Reading Fluency in ADHD 
Child Neuropsychology  2011;17(3):209-224.
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, 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 intra-subject 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.
PMCID: PMC3309419  PMID: 21287422
Reading; Attention; Child; Dyslexia; Fluency; Working Memory; Executive Function
24.  Prediction of ADHD in Boys and Girls Using the D-KEFS 
To examine patterns of executive dysfunction associated with ADHD, 123 children (54 ADHD, 69 controls) ages 8–16 years were administered selected subtests from the Delis-Kaplan Executive Function System (D-KEFS). Children with ADHD performed significantly worse than controls on measures of both basic (less executive demand) skills and those with more executive demand from the Color-Word Interference and Tower subtests; however, no group differences were noted on any of the D-KEFS contrast scores. Most subtype comparisons yielded no differences; however, children with the Combined subtype outperformed children with the Inattentive subtype on measures of both basic and executive skills from the Trail Making Test. Children with ADHD demonstrate executive dysfunction that is identified by both D-KEFS summary, but not contrast scores. In this carefully screened sample of children with ADHD, few significant differences were found between groups suggesting limited sensitivity or specificity of the D-KEFS for classifying children with ADHD.
PMCID: PMC2427435  PMID: 18243646
ADHD; Subtype; Executive Function; Classification; Children; Pediatrics
The Clinical neuropsychologist  2008;22(5):826-841.
To examine effects of group (Attention-Deficit/Hyperactivity Disorder [ADHD] versus Typically Developing [TD]), sex, and ADHD subtype on “process/optional” measures of executive functioning, children (n = 123; 54 ADHD, 69 TD) aged 8−16 completed subtests from the D-KEFS. No group, sex, or ADHD subtype effects were found on optional measures from the Trail Making, Color–Word Interference, and Tower tests. A significant interaction was found for Verbal Fluency Total Repetition Errors; boys with Combined/Hyperactive-Impulsive (ADHD-C/HI) type ADHD performed better than ADHD-C/HI girls, whereas girls with Inattentive type ADHD (ADHD-I) performed better than ADHDI boys. Overall, children with ADHD did not differ from TD on most optional measures from the D-KEFS. When sex and ADHD subtype were considered, children with the subtype of ADHD less common for sex were at greater risk for poorer performance.
PMCID: PMC2575661  PMID: 18609314
Process approach; ADHD; Executive function; D-KEFS

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