Good Holders, Bad Shufflers: An Examination of Working Memory Processes and Modalities in Children with and without Attention-Deficit/Hyperactivity Disorder.

The aim of this study was to examine working memory (WM) modalities (visual-spatial and auditory-verbal) and processes (maintenance and manipulation) in children with and without attention-deficit/hyperactivity disorder (ADHD). The sample consisted of 63 8-year-old children with ADHD and an age- and sex-matched non-ADHD comparison group (N=51). Auditory-verbal and visual-spatial WM were assessed using the Digit Span and Spatial Span subtests from the Wechsler Intelligence Scale for Children Integrated - Fourth Edition. WM maintenance and manipulation were assessed via forward and backward span indices, respectively. Data were analyzed using a 3-way Group (ADHD vs. non-ADHD)×Modality (Auditory-Verbal vs. Visual-Spatial)×Condition (Forward vs. Backward) Analysis of Variance (ANOVA). Secondary analyses examined differences between Combined and Predominantly Inattentive ADHD presentations. Significant Group×Condition (p=.02) and Group×Modality (p=.03) interactions indicated differentially poorer performance by those with ADHD on backward relative to forward and visual-spatial relative to auditory-verbal tasks, respectively. The 3-way interaction was not significant. Analyses targeting ADHD presentations yielded a significant Group×Condition interaction (p=.009) such that children with ADHD-Predominantly Inattentive Presentation performed differentially poorer on backward relative to forward tasks compared to the children with ADHD-Combined Presentation. Findings indicate a specific pattern of WM weaknesses (i.e., WM manipulation and visual-spatial tasks) for children with ADHD. Furthermore, differential patterns of WM performance were found for children with ADHD-Predominantly Inattentive versus Combined Presentations. (JINS, 2016, 22, 1-11).

Differential impact of methylphenidate and atomoxetine on sustained attention in youth with attention-deficit/hyperactivity disorder.

BACKGROUND: This study examined the effects of atomoxetine (ATX) and OROS methylphenidate (MPH) on laboratory measures of inhibitory control and attention in youth with attention-deficit/hyperactivity disorder (ADHD). It was hypothesized that performance would be improved by both treatments, but response profiles would differ because the medications work via different mechanisms. METHODS: One hundred and two youth (77 male; mean age = 10.5 ± 2.7 years) with ADHD received ATX (1.4 ± 0.5 mg/kg) and MPH (52.4 ± 16.6 mg) in a randomized, double-blind, crossover design. Medication was titrated in 4-6-week blocks separated by a 2-week placebo washout. Inhibitory control and attention measures were obtained at baseline, following washout, and at the end of each treatment using Conners' Continuous Performance Test II (CPT-II), which provided age-adjusted T-scores for reaction time (RT), reaction time variability (RT variability), and errors. Repeated-measures analyses of variance were performed, with Time (premedication, postmedication) and Treatment type (ATX, MPH) entered as within-subject factors. Data from the two treatment blocks were checked for order effects and combined if order effects were not present. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov: NCT00183391. RESULTS: Main effects for Time on RT (p = .03), RTSD (p = .001), and omission errors (p = .01) were significant. A significant Drug × Time interaction indicated that MPH improved RT, RTSD, and omission errors more than ATX (p < .05). Changes in performance with treatment did not correlate with changes in ADHD symptoms. CONCLUSIONS: MPH has greater effects than ATX on CPT measures of sustained attention in youth with ADHD. However, the dissociation of cognitive and behavioral change with treatment indicates that CPT measures cannot be considered proxies for symptomatic improvement. Further research on the dissociation of cognitive and behavioral endpoints for ADHD is indicated.

Neurobiological basis of reinforcement-based decision making in adults with ADHD treated with lisdexamfetamine dimesylate: Preliminary findings and implications for mechanisms influencing clinical improvement.

BACKGROUND: ADHD is often described as a disorder of altered reward sensitivity, yet few studies have examined the extent to which: (i) treatments for ADHD impact reward-related mechanisms; and (ii) changes in the reward system are associated with clinical improvement. This study addresses these issues - examining the extent to which clinical improvement following lisdexamfetamine (LDX) treatment is associated with changes in brain reward system activation. METHODS: Twenty adults (M = 11, 55%, F = 9, 45%), ages 19-52 (M = 33.9, SD = 10.0) with ADHD participated in a randomized cross-over study with lisdexamfetamine (LDX) and placebo (PB). Changes in brain activation were assessed during functional magnetic resonance (fMRI) scans: after receiving 3-5 weeks of treatment with LDX and 3-5 weeks of no drug/PB. fMRI contrasts were derived from the passive-avoidance (PA) learning task, which assessed reward-related learning using computational variables. We analyzed the following conditions: the Choice-Phase, modulated by the expected value (EV; i.e., object-choose and object-reject), and the Feedback-Phase, modulated by the prediction error (PE; i.e., reward and punish). Clinical symptom severity was assessed via interview with the ADHD-Rating Scale (ADHD-RS-IV). To address the primary objective, we performed group-level mass-univariate regression analyses between LDX and PB of percent change of the ADHD-RS total scores and the four contrast images under the Choice- and Feedback-conditions. Significance was set at a whole-brain voxel-wise threshold of p < 0.05 with family-wise error (FWE) correction and an extent (cluster) threshold of 50 contiguous voxels. RESULTS: Improvement in ADHD symptoms with LDX was accompanied by significantly increased activation in a series of brain regions previously implicated in reinforcement processing in the choice and feedback conditions (e.g., left caudate and putamen, right orbitofrontal cortex, left middle frontal, superior frontal, and precentral gyri). CONCLUSIONS: These findings, while preliminary, are the first to show that ADHD symptom improvement with stimulant treatment is associated with increased responsiveness of brain systems engaged in reward processing. Results support the hypothesis that LDX treatment may restore balance to dysfunction (e.g., hypoactivation) within the brain reward circuitry in adults with ADHD. Trial RegistrationClinicaltrials.gov Identifier: NCT01924429.

Cogmed Working Memory Training for youth with ADHD: a closer examination of efficacy utilizing evidence-based criteria.

The current review applied the evidence-based treatment criteria espoused by the Society for Clinical Child and Adolescent Psychology (Silverman & Hinshaw, 2008 ) to specifically evaluate the short-term and longer term efficacy of Cogmed Working Memory Training (CWMT) as a treatment for youth with Attention-Deficit/Hyperactivity Disorder (ADHD). Utilizing a systematic literature search, 7 studies that employed the school-age version of CWMT were identified for this review. The data reviewed herein suggest mixed findings regarding the benefit of CWMT for youth with ADHD. Two randomized controlled studies have demonstrated that CWMT led to improvements in neuropsychological outcomes and parent-rated ADHD symptoms relative to wait-list control and placebo treatment conditions. Another study demonstrated effects of CWMT relative to a placebo condition on an analog observation of behavior during an academic task, although this study did not find an effect of CWMT on parent-rated ADHD. Finally, an additional study utilizing an active comparison control condition did not find incremental benefits of CWMT on parent- or teacher-rated ADHD. Critical issues in interpreting existing studies include lack of alignment between demonstrated outcomes and the hypothesized model of therapeutic benefit of CWMT, issues with equivalence of control conditions, and individual differences that may moderate treatment response. Collectively, the strengths and limitations of the studies reviewed suggest that CWMT is best defined as a Possibly Efficacious Treatment for youth with ADHD. We suggest future directions for research and conclude with clinical implications of our findings for the treatment of youth with ADHD.

Preparatory activity and connectivity in dorsal anterior cingulate cortex for cognitive control.

Dorsal anterior cingulate cortex (dACC) is composed of functionally distinct subregions that may contribute to the top-down control of response selection and preparation. Multiple motor areas have been identified in dACC, including an anterior zone implicated in conflict monitoring and a caudal zone involved in movement execution. This study tested the involvement of a third cingulate area, the posterior zone of dACC, in the top-down control of response selection and preparation. Sixteen healthy young adults were scanned with event-related functional magnetic resonance imaging while performing a cued go/no-go task that was designed to minimize response conflicts. The activation and functional connectivity of dACC were tested with standard convolution models and psychophysiological interaction analyses, respectively. Ready cues that informed the direction of the impending response triggered preparatory neural activity in the posterior zone of dACC and strengthened functional connectivity with the anterior and caudal zones of dACC, as well as perigenual anterior cingulate cortex, frontal operculum, dorsolateral prefrontal cortex, sensory association cortices, and extra-pyramidal motor areas. The preparatory cues activated dACC above and beyond the general arousing effects common to cues despite negligible conflict in the go/no-go task. The integration of cognitive, sensorimotor, and incentive signals in dACC places the region in an ideal position to select and prepare appropriate behavioral responses to achieve higher-level goals.

Dopamine transporter gene variation modulates activation of striatum in youth with ADHD.

Polymorphisms in the 3'UTR variable number tandem repeat (VNTR) of exon 15 of the dopamine transporter gene (DAT1) have been linked to attention-deficit hyperactivity disorder (ADHD); moreover, variability in DAT1 3'UTR genotype may contribute to both heterogeneity of the ADHD phenotype and differences in response to stimulant medications. The impact of this VNTR on neuronal function in individuals with ADHD remains unclear despite evidence that the polymorphisms influence dopamine transporter expression. Thus, we used event-related functional magnetic resonance imaging to examine the impact of DAT1 3'UTR genotype on brain activation during response inhibition in unmedicated children and adolescents with ADHD. Twenty-one youth with ADHD who were homozygous for the 10-repeat (10R) allele of the DAT1 3'UTR and 12 youth who were carriers of the 9-repeat (9R) allele were scanned while they performed a Go/No-Go task. Response inhibition was modeled by contrasting activation during correct No-Go trials versus correct Go trials. Participants who were homozygous for the DAT1 3'UTR 10R allele and those who had a single 9R allele did not differ on percent of trials with successful inhibition, which was the primary measure of inhibitory control. Yet, youth with the DAT1 3'UTR 10R/10R genotype had significantly greater inhibitory control-related activation than those with one 9R allele in the left striatum, right dorsal premotor cortex, and bilaterally in the temporoparietal cortical junction. These findings provide preliminary evidence that neural activity related to inhibitory control may differ as a function of DAT1 3'UTR genotype in youth with ADHD.

Training Executive, Attention, and Motor Skills (TEAMS): a Preliminary Randomized Clinical Trial of Preschool Youth with ADHD.

This preliminary randomized controlled trial compared Training Executive, Attention and Motor Skills (TEAMS), a played-based intervention for preschool children with attention-deficit/hyperactivity disorder (ADHD), to an active comparison intervention consisting of parent education and support (ClinicalTrials.gov Identifier: NCT01462032). The primary aims were to gauge preliminary efficacy and assist in further development of TEAMS. Four- and 5-year-old children with ADHD were randomly assigned to receive TEAMS (N = 26) or the comparison intervention (N = 26) with blinded assessments by parents, teachers and clinicians ascertained pretreatment, post-treatment, and 1- and 3-months post-treatment. Changes in ADHD severity, impairment, parenting factors, and neuropsychological functioning over time as a function of treatment condition were assessed using the PROC MIXED procedure in SAS. Across most measures, significant main effects for Time emerged; both treatments were associated with reduced ADHD symptoms that persisted for three months post-treatment. There were no significant Treatment effects or Time x Treatment interactions on symptom and impairment measures, suggesting that the magnitude of improvement did not differ between the two interventions. However, significant correlations emerged between the magnitude of behavioral change, as assessed by parents and clinicians, and the amount of time families engaged in TEAMS-related activities during treatment. Across a wide array of parenting and neuropsychological measures, there were few significant group differences over time. TEAMS and other psychosocial interventions appear to provide similar levels of benefit. Play-based interventions like TEAMS represent a potentially viable alternative/addition to current ADHD treatments, particularly for young children, but more research and further development of techniques are necessary.

Anxiety, methylphenidate response, and working memory in children with ADHD.

OBJECTIVE: To investigate the effects of methylphenidate (MPH) on components of working memory (WM) in children with ADHD and determine whether MPH produces differential effects on WM in children with comorbid anxiety (ANX). METHOD: Participants were a clinical sample of 130 children with ADHD, aged 6 to 12 years old (32% comorbid ANX). Each child participated in an acute randomized, double-blind, placebo-controlled, crossover trial with single challenges of three MPH doses. Four WM measures were used that varied in processing demands (storage versus manipulation of information) and modality (auditory-verbal; visual-spatial). RESULTS: MPH improved auditory-verbal manipulation but only in the non-ANX children with ADHD. It had no effect on auditory-verbal storage of information. Also, MPH improved the ability to manipulate visual-spatial information in both ADHD groups, but beneficial effects on visual-spatial storage were evident only in children without comorbid ANX. CONCLUSIONS: Findings provide insight into potential mechanisms underlying individual differences in treatment response in ADHD, which may facilitate more targeted treatments.

Low Working Memory rather than ADHD Symptoms Predicts Poor Academic Achievement in School-Aged Children.

This study examined whether working memory (WM), inattentive symptoms, and/or hyperactive/impulsive symptoms significantly contributed to academic, behavioral, and global functioning in 8-year-old children. One-hundred-sixty 8-year-old children (75.6% male), who were originally recruited as preschoolers, completed subtests from the Wechsler Intelligence Scale for Children-Fourth Edition, Integrated and Wechsler Individual Achievement Test-Second Edition to assess WM and academic achievement, respectively. Teachers rated children's academic and behavioral functioning using the Vanderbilt Rating Scale. Global functioning, as rated by clinicians, was assessed by the Children's Global Assessment Scale. Multiple linear regressions were completed to determine the extent to which WM (auditory-verbal and visual-spatial) and/or inattentive and hyperactive/impulsive symptom severity significantly contributed to academic, behavioral, and/or global functioning. Both auditory-verbal and visual-spatial WM but not ADHD symptom severity, significantly and independently contributed to measures of academic achievement (all p < 0.01). In contrast, both WM and inattention symptoms (p < 0.01), but not hyperactivity-impulsivity (p > 0.05) significantly contributed to teacher-ratings of academic functioning. Further, inattention and hyperactivity/impulsivity (p < 0.04), but not WM (p > 0.10) were significantly associated with teacher-ratings of behavioral functioning and clinician-ratings of global functioning. Taken together, it appears that WM in children may be uniquely related to academic skills, but not necessarily to overall behavioral functioning.

Lisdexamfetamine Targets Amygdala Mechanisms That Bias Cognitive Control in Attention-Deficit/Hyperactivity Disorder.

BACKGROUND: Prefrontal-limbic circuits that form the neural architecture for emotion to influence behavior have been implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD) and represent a potentially important target of medication treatment that has not been substantively evaluated. This study tested the effect of the psychostimulant prodrug lisdexamfetamine dimesylate on amygdala activation and connectivity during the emotional bias of response execution and inhibition. METHODS: Twenty-five adults with ADHD were scanned twice with event-related functional magnetic resonance imaging while performing an emotional go/no-go task after 3 to 4 weeks of lisdexamfetamine treatment and 3 weeks off medication in a randomized, counterbalanced, hybrid crossover design. Drug, trial type, and face emotion (happy, sad, or neutral) were included as within-subjects factors in repeated measures analyses of activation and connectivity. RESULTS: Lisdexamfetamine was associated with increased right amygdala activation and reduced psychophysiological interactions with the orbital aspect of the left inferior frontal gyrus specifically for responses to sad faces compared with placebo, but there was no effect on the accuracy of response execution or inhibition. The relative gain in right amygdala activation in response to sad faces for lisdexamfetamine was correlated with a reduction in symptoms of ADHD. CONCLUSIONS: Treatment with lisdexamfetamine potentiates affective encoding in amygdala, purportedly via catecholaminergic mechanisms, but functionally disconnects the amygdala from inferior frontal regions that encode behavioral significance-resulting in reduced emotional bias of cognitive control. Pinpointing the neurophysiologic underpinnings of therapeutic improvement with lisdexamfetamine represents a first step in developing targeted approaches to treatment of ADHD.

Preliminary evidence of beneficial effects of methylphenidate on listening comprehension in children with attention-deficit/hyperactivity disorder.

OBJECTIVE: The effect of methylphenidate (MPH) on listening comprehension for information passages, and on working memory, was examined in a clinical sample of 16 children with attention-deficit/hyperactivity disorder (ADHD). METHOD: Drug effects on comprehension of spoken language at the levels of single sentences and passages, and on verbal and visual-spatial working memory (WM) skills were assessed over a 4-day placebo-controlled, double-blind, crossover treatment trial of MPH at low, medium, and high doses. Concurrent behavior ratings were also completed. Data were analyzed at both group and individual levels; individual improvements using average change scores were analyzed to explore interrelationships among comprehension, WM, and behavioral responses to MPH. RESULTS: There was a significant effect of drug on comprehension of inferences from challenging listening passages (F = 3.1, p ,0.05), and on visual-spatial working memory performance (F = 3.3, p ,0.05), with significant linear dose-response relationships evident for both domains. Individual improvements in comprehension using averaged placebo-dose change scores were not related to improvements in behavior with MPH, or to improvements in WM in this sample. CONCLUSIONS: Findings provide preliminary evidence that MPH affects higher-level language comprehension skills, which require sustained attention and mental effort. If generalizable to classroom listening skills, these findings have implications for clinicians and teachers involved with children with ADHD.

Striatal Activation Predicts Differential Therapeutic Responses to Methylphenidate and Atomoxetine.

OBJECTIVE: Methylphenidate has prominent effects in the dopamine-rich striatum that are absent for the selective norepinephrine transporter inhibitor atomoxetine. This study tested whether baseline striatal activation would predict differential response to the two medications in youth with attention-deficit/hyperactivity disorder (ADHD). METHOD: A total of 36 youth with ADHD performed a Go/No-Go test during functional magnetic resonance imaging at baseline and were treated with methylphenidate and atomoxetine using a randomized cross-over design. Whole-brain task-related activation was regressed on clinical response. RESULTS: Task-related activation in right caudate nucleus was predicted by an interaction of clinical responses to methylphenidate and atomoxetine (F1,30 = 17.00; p < .001). Elevated caudate activation was associated with robust improvement for methylphenidate and little improvement for atomoxetine. The rate of robust response was higher for methylphenidate than for atomoxetine in youth with high (94.4% vs. 38.8%; p = .003; number needed to treat = 2, 95% CI = 1.31-3.73) but not low (33.3% vs. 50.0%; p = .375) caudate activation. Furthermore, response to atomoxetine predicted motor cortex activation (F1,30 = 14.99; p < .001). CONCLUSION: Enhanced caudate activation for response inhibition may be a candidate biomarker of superior response to methylphenidate over atomoxetine in youth with ADHD, purportedly reflecting the dopaminergic effects of methylphenidate but not atomoxetine in the striatum, whereas motor cortex activation may predict response to atomoxetine. These data do not yet translate directly to the clinical setting, but the approach is potentially important for informing future research and illustrates that it may be possible to predict differential treatment response using a biomarker-driven approach. CLINICAL TRIAL REGISTRATION INFORMATION: Stimulant Versus Nonstimulant Medication for Attention Deficit Hyperactivity Disorder in Children; https://clinicaltrials.gov/; NCT00183391.

Comparative Evaluation of Child Behavior Checklist-Derived Scales in Children Clinically Referred for Emotional and Behavioral Dysregulation.

BACKGROUND: We recently developed the Child Behavior Checklist-Mania Scale (CBCL-MS), a novel and short instrument for the assessment of mania-like symptoms in children and adolescents derived from the CBCL item pool and have demonstrated its construct validity and temporal stability in a longitudinal general population sample. OBJECTIVE: The aim of this study was to evaluate the construct validity of the 19-item CBCL-MS in a clinical sample and to compare its discriminatory ability to that of the 40-item CBCL-dysregulation profile (CBCL-DP) and the 34-item CBCL-Externalizing Scale. METHODS: The study sample comprised 202 children, aged 7-12 years, diagnosed with DSM-defined attention deficit hyperactivity disorder (ADHD), conduct disorder (CD), oppositional defiant disorder (ODD), and mood and anxiety disorders based on the Diagnostic Interview Schedule for Children. The construct validity of the CBCL-MS was tested by means of a confirmatory factor analysis. Receiver operating characteristics (ROC) curves and logistic regression analyses adjusted for sex and age were used to assess the discriminatory ability relative to that of the CBCL-DP and the CBCL-Externalizing Scale. RESULTS: The CBCL-MS had excellent construct validity (comparative fit index = 0.97; Tucker-Lewis index = 0.96; root mean square error of approximation = 0.04). Despite similar overall performance across scales, the clinical range scores of the CBCL-DP and the CBCL-Externalizing Scale were associated with higher odds for ODD and CD, while the clinical range scores of the CBCL-MS were associated with higher odds for mood disorders. The concordance rate among the children who scored within the clinical range of each scale was over 90%. CONCLUSION: CBCL-MS has good construct validity in general population and clinical samples and is therefore suitable for both clinical practice and research.

Impact of occupational, physical, and speech and language therapy in preschoolers with hyperactive/inattentive symptoms: A naturalistic 2-year follow-up study.

OBJECTIVE: Impact of speech and language therapy (ST) and occupational/physical therapy (OT/PT) on language and motor skills was examined in hyperactive/inattentive children. METHODS: Preschoolers were divided into those receiving and not receiving ST or OT/PT. RESULTS: Children receiving ST showed no gains in language functioning relative to those not receiving ST. OT/PT yielded similar results for motor functions. Hours of a service did not predict improvement. However, children who received ST showed improvement in social skills. DISCUSSION: The apparent lack of benefit suggests the need for further investigation into efficacy of these treatments in hyperactive/inattentive preschool children.

Neural mechanisms underlying the therapeutic actions of guanfacine treatment in youth with ADHD: a pilot fMRI study.

Twenty-five youth with attention-deficit/hyperactivity disorder (ADHD) were scanned with functional magnetic resonance imaging (fMRI) while performing a Go/No-go task before and after 6-8 weeks of randomized once-daily treatment with either the α2A-adrenergic receptor agonist guanfacine or placebo. Clinical improvement was greater for guanfacine than placebo and was differentially associated with reduced activation for guanfacine compared with placebo in the right midcingulate cortex/supplementary motor area and the left posterior cingulate cortex.

Methylphenidate improves visual-spatial memory in children with attention-deficit/hyperactivity disorder.

OBJECTIVE: To investigate the effect of methylphenidate (MPH) on visual-spatial memory, as measured by subtests of the Cambridge Neuropsychological Testing Automated Battery (CANTAB), in children with attention-deficit/hyperactivity disorder (ADHD). Visual-spatial memory is a core component of working memory that has been shown to be impaired in ADHD, irrespective of comorbid reading and/or language problems. METHOD: A clinic-referred sample of school-age children with a confirmed DSM-IV diagnosis of ADHD (n = 26) completed tests of visual-spatial memory, planning ability, and recognition memory in an acute, randomized, placebo-controlled, crossover trial with three single fixed doses of MPH. MPH effects on right-handed and left-handed motor control were also assessed. RESULTS: MPH significantly improved performance on a self-ordered, updating visual-spatial working memory task and on maintenance of visual-spatial information but had no effects on measures of visual-spatial planning ability or recognition memory. Also, MPH significantly improved left-handed motor control. CONCLUSIONS: Beneficial effects of MPH on visual-spatial processing in ADHD are selective and restricted to visual-spatial memory.

The development of selective inhibitory control across the life span.

A modification of the stop-signal task was used to investigate the development of selective inhibitory control. A group of 317 participants, age 6 to 82 years, performed a visual choice reaction time (go) task and attempted to selectively inhibit their response to the go task when hearing one of two randomly presented tones (1000 Hz, 250 Hz), each presented on 20% of trials. Measures of response execution and inhibition were assessed by using reaction times to the go signal (GoRT) and stop signal (SSRT), respectively. Results indicated that SSRT gets faster with increasing age throughout childhood, with pronounced slowing in older adulthood. In addition, strong evidence was obtained for age-related speeding in GoRT throughout childhood, with marked slowing throughout adulthood. Subsequent hierarchical regression analyses illustrated that the age-related changes in selective inhibitory control could not be explained simply by overall slowing or speeding of responses. Findings are discussed in regard to the decay and maturation of selective inhibitory control across the life span.

Methylphenidate improves Stroop naming speed, but not response interference, in children with attention deficit hyperactivity disorder.

OBJECTIVE: The goal of this study was to investigate the effect of methylphenidate (MPH) on response interference, as measured by the Stoop Color and Word Test, in children with attention deficit hyperactivity disorder (ADHD). Response interference is a core component of response inhibition that has been shown to be impaired in children with ADHD. METHODS: A clinic-referred sample of school-aged children with a confirmed Diagnostic and Statistical Manual of Mental Disorders (4th ed.) diagnosis of ADHD and good reading skills (n = 31) completed the Stroop Color and Word Test in an acute, randomized, placebo-controlled, crossover trial with three single fixed doses of MPH. RESULTS: MPH did not improve response interference on the Stroop Color and Word Test but did significantly improve color naming and word naming abilities. CONCLUSION: Response interference, as measured by the Stroop Color and Word Test, is not improved by MPH in children with ADHD. In addition, findings demonstrate strongly positive MPH effects on the highly effortful process of color naming, which has previously been demonstrated as impaired in children with ADHD. MPH was also shown to have a positive but smaller effect on word naming speed.

Selective inhibition in children with attention-deficit hyperactivity disorder off and on stimulant medication.

Selective inhibition requires discrimination between auditory signals and is assessed using a modification of the stop-signal task. Selective inhibition was assessed in a group of 59 clinic-referred, DSM-IV-diagnosed children with attention-deficit hyperactivity disorder (ADHD) and compared to that of a community sample of 59 children. Methylphenidate (MPH) effects on selective inhibition were assessed in a subset of the ADHD sample that participated in an acute, randomized, placebo-controlled, crossover trial with 3 fixed doses of MPH. Children with ADHD performed more poorly than controls on the majority of selective stop-signal task parameters: they exhibited more anticipatory (invalid) responses, with less accurate and more variable responses on the response execution task, as well as a slower selective inhibition process. MPH improved speed of both inhibition and response execution processes; it also reduced variability of response execution and decreased nonselective inhibition. On the one hand, findings are consistent with purported inhibition deficit in ADHD, but on the other hand, suggest that neither the impairment itself, nor MPH effects, were restricted to inhibition.

Reduced prefrontal efficiency for visuospatial working memory in attention-deficit/hyperactivity disorder.

OBJECTIVE: Visuospatial working memory impairments have been implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). However, most ADHD research has focused on the neural correlates of nonspatial mnemonic processes. This study examined brain activation and functional connectivity for visuospatial working memory in youth with and without ADHD. METHOD: Twenty-four youth with ADHD and 21 age- and sex-matched healthy controls were scanned with functional magnetic resonance imaging while performing an N-back test of working memory for spatial position. Block-design analyses contrasted activation and functional connectivity separately for high (2-back) and low (1-back) working memory load conditions versus the control condition (0-back). The effect of working memory load was modeled with linear contrasts. RESULTS: The 2 groups performed comparably on the task and demonstrated similar patterns of frontoparietal activation, with no differences in linear gains in activation as working memory load increased. However, youth with ADHD showed greater activation in the left dorsolateral prefrontal cortex (DLPFC) and left posterior cingulate cortex (PCC), greater functional connectivity between the left DLPFC and left intraparietal sulcus, and reduced left DLPFC connectivity with left midcingulate cortex and PCC for the high load contrast compared to controls (p < .01; k > 100 voxels). Reanalysis using a more conservative statistical approach (p < .001; k > 100 voxels) yielded group differences in PCC activation and DLPFC-midcingulate connectivity. CONCLUSION: Youth with ADHD show decreased efficiency of DLPFC for high-load visuospatial working memory and greater reliance on posterior spatial attention circuits to store and update spatial position than healthy control youth. Findings should be replicated in larger samples.