Associations between event-related potentials and measures of attention and inhibition in the Continuous Performance Task in children with ADHD and normal controls

OBJECTIVES: First, to differentiate between inattention and impulsivity based on type of errors made in the AX version of the Continuous Performance Task (CPT), and second, to investigate whether differences in performance between children with attention-deficit hyperactivity disorder (ADHD) and normal controls also occur in specific forms of brain activity, namely event-related potentials (ERPs), presumably related to inattention and impulsivity or inhibition. METHOD: Sixteen ADHD and 16 normal control children performed the CPT-AX. ERPs were recorded at occipital (Oz), parietal (Pz), central (Cz), and frontal (Fz) leads. RESULTS: The ADHD children had a higher CPT-Inattention score and showed smaller parietal positive waves at a latency of approximately 300 msec in reaction to target stimuli, target P3s, likewise indicating less attention. In contrast, they showed neither higher CPT-Impulsivity nor a smaller frontocentral negative wave at about 200 msec (N2); the N2 is generally seen as reflecting inhibition. A subgroup of children with ADHD and oppositional defiant disorder (n = 6) had smaller N2 waves than controls, however. CONCLUSIONS: The ADHD group studied showed deficits in attention but not in impulsivity (or inhibition).     

A neuropsychological examination of the underlying deficit in attention deficit hyperactivity disorder: Frontal lobe versus right parietal lobe theories.

A neuropsychological approach was used to examine the frontal lobe and right parietal lobe theories of attention deficit hyperactivity disorder (ADHD). Considerable attempts were made to select as pure a group of ADHD boys as possible. The performance of 10-14-year-old ADHD boys (n?=?22), both on and off stimulant medication, was compared with the performance of non-ADHD control boys (n?=?22) on tasks purported to assess frontal lobe functioning (Stopping Task, Antisaccade Task, Tower of Hanoi) and right parietal lobe functioning (Visual-Spatial Cuing Task, Turning Task, Spatial Relations). Three important findings emerged: (a) unmedicated ADHD boys exhibited performance deficits on tasks in both frontal and parietal domains compared with control boys, (b) unmedicated ADHD boys appeared to be more severely impaired on the frontal tasks than on the parietal tasks, and (c) medicated ADHD boys performed better in both task domains compared with unmedicated ADHD boys. Several alternative interpretations of the results are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Quantitative brain magnetic resonance imaging in attention-deficit hyperactivity disorder

BACKGROUND: Anatomic magnetic resonance imaging (MRI) studies of attention-deficit hyperactivity disorder (ADHD) have been limited by small samples or measurement of single brain regions. Since the neuropsychological deficits in ADHD implicate a network linking basal ganglia and frontal regions, 12 subcortical and cortical regions and their symmetries were measured to determine if these structures best distinguished ADHD. METHODS: Anatomic brain MRIs for 57 boys with ADHD and 55 healthy matched controls, aged 5 to 18 years, were obtained using a 1.5-T scanner with contiguous 2-mm sections. Volumetric measures of the cerebrum, caudate nucleus, putamen, globus pallidus, amygdala, hippocampus, temporal lobe, cerebellum; a measure of prefrontal cortex; and related right-left asymmetries were examined along with midsagittal area measures of the cerebellum and corpus callosum. Interrater reliabilities were .82 or greater for all MRI measures. RESULTS: Subjects with ADHD had a 4.7% smaller total cerebral volume (P = .02). Analysis of covariance for total cerebral volume demonstrated a significant loss of normal right > left asymmetry in the caudate (P = .006), smaller right globus pallidus (P = .005), smaller right anterior frontal region (P = .02), smaller cerebellum (P = .05), and reversal of normal lateral ventricular asymmetry (P = .03) in the ADHD group. The normal age-related decrease in caudate volume was not seen, and increases in lateral ventricular volumes were significantly diminished in ADHD. CONCLUSION: This first comprehensive morphometric analysis is consistent with hypothesized dysfunction of right-sided prefrontal-striatal systems in ADHD.     

Differential Prefrontal Cortex Activation During Inhibitory Control in Adolescents With and Without Childhood Attention-Deficit/Hyperactivity Disorder.

The authors examined inhibitory control processes in 8 adolescents diagnosed with attention-deficit/ hyperactivity disorder (ADHD) during childhood and in 8 adolescent control participants using functional MRI with the Stimulus and Response Conflict Tasks (K. W. Nassauer & J. M. Halperin, 2003). No group differences in performance were evident on measures of interference control and/or response competition created by location and direction stimuli. However, the ADHD group demonstrated significantly greater activation of the left ventrolateral prefrontal cortex during interference control as well as greater activation of the left anterior cingulate cortex, right ventrolateral prefrontal cortex, and left basal ganglia during the dual task of interference control and response competition. The magnitude of the prefrontal and basal ganglia activation was positively correlated with severity of ADHD. Response competition alone did not yield group differences in activation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Inhibition in verbal working memory revealed by brain activation

There are many occasions in which humans and other animals must inhibit the production of some behavior or inhibit the processing of some internal representation. Success in inhibitory processing under normal circumstances can be revealed by the fact that certain brain pathologies render inhibitory processing ineffective. These pathologies often have been associated with damage to frontal cortex, including lateral and inferior aspects. We provide behavioral evidence of a verbal working memory task that, by hypothesis, engaged inhibitory processing, and we show (by using positron emission tomograpny) that the inhibitory processing is associated with a lateral portion of the left prefrontal cortex. The task in which subjects engaged was item-recognition: Four target letters were presented for storage followed, after a brief interval, by a probe letter that could match a target letter or not. On some trials, when the probe did not match a target letter and therefore required a "no" response, the probe had matched a target letter of the previous trial, so on these trials a "yes" response was prepotent and had to be inhibited, by hypothesis. Compared with a condition in which no prepotent response was created, this condition yielded brain activation in left inferior frontal gyrus, in the region of Brodmann's area 45.     

Academic task persistence of normally achieving ADHD and control boys: Self-evaluations, and attributions.

The authors examined academic task persistence, pretask expectancies, self-evaluations, and attributions of boys with attention-dcficit/hyperactivity disorder (ADHD) as compared with control boys. Participants were 83 ADHD boys and 66 control boys, all normally achieving. Prior to the task, performance expectancies were assessed. After a success-failure manipulation with find-a-word puzzles, performance on subsequent trials, self-evaluations, and attributions were evaluated. Compared with controls, ADHD boys solved fewer test puzzles, quit working more often, and found fewer words on a generalization task. Consistent with these behavioral findings, research assistants rated ADHD boys as less effortful and less cooperative than control boys. Although ADHD boys did not differ significantly from controls in their posttask self-evaluations, they did differ significantly from controls in some aspects of their attributions. Attributional data indicated that ADHD boys endorsed luck as a reason for success more strongly and lack of effort as a reason for failure less strongly than controls. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Correction to Schulz et al. (2005).

Reports an error in the original article by Kurt P. Schulz, Cheuk Y. Tang, Jin Fan, David J. Marks, Angeles M. Cheung, Jeffrey H. Newcorn, and Jeffrey M. Halperin ((Neuropsychology, 2005, Vol. 19, No. 3, pp. 390-402). Some side headings in Tables 2 and 3 were incorrect, and the corrected tables appear here. (The following abstract of this article originally appeared in record 2005-05103-013). "The authors examined inhibitory control processes in 8 adolescents diagnosed with attention-deficit/ hyperactivity disorder (ADHD) during childhood and in 8 adolescent control participants using functional MRI with the Stimulus and Response Conflict Tasks (K. W. Nassauer & J. M. Halperin, 2003). No group differences in performance were evident on measures of interference control and/or response competition created by location and direction stimuli. However, the ADHD group demonstrated significantly greater activation of the left ventrolateral prefrontal cortex during interference control as well as greater activation of the left anterior cingulate cortex, right ventrolateral prefrontal cortex, and left basal ganglia during the dual task of interference control and response competition. The magnitude of the prefrontal and basal ganglia activation was positively correlated with severity of ADHD. Response competition alone did not yield group differences in activation." (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Magnetic resonance imaging correlates of attention-deficit/hyperactivity disorder in children.

This study compared magnetic resonance imaging size differences in several brain regions and neurocognitive function in a group of male and female children with attention-deficit/hyperactivity disorder (ADHD) with no comorbid learning disorders with a normal control group of children. The ADHD group demonstrated smaller total brain, superior prefrontal, and right superior prefrontal volumes, as well as significantly smaller areas for cerebellar lobules I-V and VIII-X, total corpus callosum area, and splenium. No group differences were observed for the inferior prefrontal, caudate, or cerebellar volumes, or for the area of cerebellar lobules VI-VII. In the ADHD group but not in the control group, greater right superior prefrontal volume predicted poorer performance on a test of sustained attention. Patterns of brain abnormality did not differ in male and female children with ADHD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

COMT val158Met and executive control: A test of the benefit of specific deficits to translational research.

The role of catechol-O-methyltransferase (COMT) val158met in prefrontal cortical deficits associated with the liability to schizophrenia remains controversial. This study evaluated 464 healthy adult participants using three measures of executive functions in working memory: a 3-back version of the N-back continuous performance task (CPT) and two variants of the AX-CPT. The interpretability of N-back performance was confounded by possible generalized deficits, whereas the AX variants included internal controls for uncovering specific deficits. There was no relationship between the COMT genotype and N-back performance, whereas val/val individuals had a specific deficit on a dot-pattern version of the AX-CPT. In this case, a specific executive function known as context processing appeared to be compromised. These data suggest that the interpretability gained by including task manipulations to uncover specific deficits can enhance associations between cognitive and genetic levels of analysis. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Components of attention in children with complex partial seizures with and without ADHD

PURPOSE: To evaluate attentional difficulties in children with complex partial seizures, we reviewed the records of 12 children with complex partial seizures with attention deficient hyperactivity disorder (CPS/ADHD); 21 children with CPS without ADHD (CPS); 22 children with ADHD; and 15 control children. METHODS: Each child completed a computerized performance test (CPT), which evaluated sustained attention, inhibition of response, response time, and consistency of response. The ADHD groups also completed the CPT after a dose of methylphenidate. RESULTS: The results found poorest performance on the CPT by the CPS/ADHD group. Particular difficulty in attention was found for children with epilepsy regardless of the ADHD diagnosis. When methylphenidate was administered to the ADHD groups, both groups improved in performance on the CPT. CONCLUSIONS: Epilepsy may predispose children to attention problems that can significantly interfere with learning. Similar improvement for children with CPS/ADHD was found with methylphenidate compared with baseline as for children with ADHD but without CPS.     

Inhibition in boys with attention deficit hyperactivity disorder as indexed by heart rate change.

A stop signal paradigm in combination with heart rate measures were used to test the hypothesis of deficient inhibitory processing in boys with attention deficit hyperactivity disorder (ADHD). The authors measured the inhibitory process initiated by a stop signal by observing its success, its latency using a horse race model, and its impact on the timing of the heartbeat. Boys with ADHD performed well and showed appropriate psychophysiological changes. Inhibition latencies were longer in the boys with ADHD, particularly those with concurrent oppositional defiant disorder, than in the controls. Cardiac evidence suggested that greater preparation was associated with inhibition failures in controls, but not in the boys with ADHD. Boys with ADHD seem capable of attending carefully to control responses, but this control appears less effective and arguably is more effortful than in other boys. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Concept activation and coordination of activation procedure require two different networks

In the present study, we used EEG-coherence analysis to assess general regional changes in neuronal activity related to semantic retrieval, testing the hypothesis that concept activation and coordination procedures are neurobiologically distinguishable. Four subjects had to decide whether or not a capital letter and a lower case letter have the identical name (e.g. Aa). This task requires two mental procedures: (i) the activation of concepts and (ii) their coordination, particularly when the interstimulus interval is shorter than the duration of concept activation. This memory retrieval of a concept appears to be subserved by two distinct networks: the left parietotemporal region for concept activation and the prefrontal region for coordination.     

Discrimination of attention deficit hyperactivity disorder by the continuous performance test

OBJECTIVE: To investigate the Continuous Performance Test in discriminating a group of 56 attention deficit hyperactivity disorder (ADHD) children from 56 school children individually matched for age, sex and social class. METHODOLOGY: The children all completed the Continuous Performance Task (CPT). The mothers and teachers completed a Conners Parent-Teacher Rating Scale for the clinic children. RESULTS: The ADHD sample was selected so that the average IQ was 99.8 to match the school sample. A non-parametric discriminant function showed that the subtests of the CPT that best discriminated ADHD were age-normalized errors of commission (NCPTC) and age-normalized mean reaction time (NMNRT). CONCLUSION: Optimal use of the CPT for discrimination of ADHD should include age normalization and mean reaction time to targets. Further evoked potential studies may show brief cortical events involved in reaction time over the course of the CPT, and the processes involved in behavioural control.     

Adolescent outcome of boys with attention-deficit/hyperactivity disorder and social disability: Results from a 4-year longitudinal follow-up study.

IQ-achievement discrepancy methodology similar to that used in defining learning disabilities has recently been used to identify a subset of boys with attention-deficit/hyperactivity disorder (ADHD) evidencing marked impairment in social functioning. In this study, 2 issues were examined: (a) What is the longitudinal outcome of boys with ADHD identified at baseline as "socially disabled?" (b) Is social disability at baseline a significant predictor of severe long-term outcomes (such as substance use disorders) in boys with ADHD? If so, are its predictive relationships accounted for by conditions that are comorbid with ADHD? Results showed that, at follow-up, ADHD boys with ADHD who also had social disability evidenced significantly higher rates of mood, anxiety, disruptive, and substance use disorders, compared with nonsocially disabled boys with ADHD and comparison boys without ADHD. Findings also showed that social disability at baseline in boys with ADHD was a significant predictor of later conduct disorder and most substance use disorders after baseline mood and conduct disorders and behavior checklist ratings of aggressive behavior and attention problems were controlled. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Masculinized finger-length ratios of boys, but not girls, are associated with attention-deficit/hyperactivity disorder.

Gonadal hormones may exert permanent organizational effects on sexually dimorphic finger-length ratios and sexually dimorphic behavior expressed in childhood attention deficit- hyperactivity disorder (ADHD). This study extended recent work examining associations between finger-length ratios (specifically, 2D:4D) and ADHD in a well-characterized, clinically diagnosed, community-recruited sample of boys and girls. A multistage, diagnostic procedure was utilized to identify 113 children with ADHD and 137 non-ADHD comparison children. Right-hand digit ratios showed significant mean differences by gender, as well as associations with ADHD diagnosis. Boys with ADHD had more masculinized digit ratios than control-group boys. More masculine right 2D:4D and 3D:4D ratios were correlated with parent- and teacher-rated inattentive and hyperactive-impulsive symptoms in boys but not in girls. Masculinized finger-length ratios were associated with hyperactive-impulsive and oppositional- defiant symptoms, but associations were largest with symptoms of inattention. It is concluded that prenatal, organizational effects of gonadal hormones may play a role in the development of ADHD and contribute to explaining sex differences in the prevalence rates of this childhood disorder. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hemispheric processing of categorical and coordinate spatial relations in vision and visual imagery

Right-handed subjects participated in a visual half-field experiment using "clock" stimuli. For the Categorical task, subjects indicated whether the long and short hands of a clock were above or below the horizontal midline of the dial. For the Coordinate task, they indicated whether the long and short hands of a clock formed an angle that is more or less than 60 degrees. For both tasks, clock stimuli were either analog clocks (Visual version) or digital clocks from which subjects generated images of analog clocks (Imagery version). The results indicated that for both the Visual and Imagery versions, there was a nonsignificant trend toward a left hemisphere advantage in the Categorical task, whereas there was a significant right hemisphere advantage in the Coordinate task. Implications of the results were discussed from the viewpoints of task factors in hemispheric processing of visual imagery, Kosslyn's (1987, 1994) computational model of vision and visual imagery, and vision/imagery isomorphism.     

Drug interactions in human neuropathic pain pharmacotherapy

The effects of 0.3 mg/kg methylphenidate (MPH) and expectancy regarding medication on the performance and task persistence of 60 boys with attention deficit hyperactivity disorder (ADHD) were investigated. In a balanced-placebo design, boys in 4 groups (received placebo/drug crossed with told placebo/drug) completed the task in success and failure conditions. Medication improved participants' task persistence following failure. Participants' task performance was not affected by whether they thought they had received medication or placebo. Children made internal attributions for success and made external attributions for failure, regardless of medication or expectancy. These findings confirm previous reports that it is the pharmacological activity of MPH that affects ADHD children's self-evaluations and persistence. The results contradict anecdotal reports that MPH causes dysfunctional attributions and confirm previous studies showing that medication does not produce adverse effects on the causal attributions of children with ADHD.     

Working memory for complex figures: An fMRI comparison of letter and fractal n-back tasks.

n-back letter and fractal tasks were administered to I I participants during functional magnetic resonance imaging to test process specificity theories of prefrontal cortex (PFC) function and assess task validity. Tasks were matched on accuracy, but fractal n-back responses were slower and more conservative. Maintenance (1-back minus O-back) activated inferior parietal and dorsolateral PFC, with additional activation in right ventrolateral PFC during letter n-back and left lingual gyrus during fractal n-back. Maintenance plus manipulation (2-back minus 0-back) activated inferior parietal, Broca's area, insula, and dorsolateral and ventral PFC, with greater right dorsolateral PFC activation for letter n-back. Manipulation only (2-back minus 1-back) produced additional and equivalent dorsolateral PFC and anterior cingulate activation in both tasks. Results support fractal n-back validity and indicate substantial overlap in working memory functions of dorsal and ventral PFC. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Secretory production of erythropoietin and the extracellular domain of the erythropoietin receptor by Bacillus brevis: affinity purification and characterization

OBJECTIVE: To study the safety and efficacy of methylphenidate in children with the dual diagnosis of epilepsy and attention deficit hyperactivity disorder (ADHD). STUDY DESIGN: Thirty children, aged 6.4 to 16.4 years, with epilepsy and ADHD were studied during a 4-month period. During the initial 2 months of the study, the children were treated with antiepileptic drugs (AEDs) only, and for the remaining 2 months, methylphenidate was added at a morning dose of 0.3 mg/kg. They underwent neurologic assessment, brain computed tomography, IQ testing, and assessment with the Childhood Behavior Checklist at baseline before methylphenidate therapy. Electroencephalography, AED determinations, and the continuous-performance task (CPT) test were done at baseline and after 2 months of methylphenidate therapy. A double-blind, crossover design was used to compare the effects of methylphenidate versus placebo on an electroencephalogram, AED levels, and the CPT. On the 2 days of testing, the child received AEDs and a capsule containing either placebo or methylphenidate. RESULTS: None of the 25 children of this sample who were seizure free had attacks while taking methylphenidate. Of the 5 children with seizures, 3 had an increase in attacks, whereas the other 2 showed no change or a reduction. There were no significant changes in AED levels or electroencephalographic findings. Methylphenidate benefited 70% of children according to parental report; methylphenidate also enhanced performance on the CPT. Side effects of methylphenidate were mild and transient. CONCLUSION: Methylphenidate is effective in treating children with epilepsy and ADHD and safe in children who are seizure free. Caution is warranted for those still having seizures while receiving AED therapy.