Anne-Claude V. Bédard

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.

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.

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.

Common and Unique Therapeutic Mechanisms of Stimulant and Nonstimulant Treatments for Attention-Deficit/Hyperactivity Disorder

CONTEXT Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent and impairing psychiatric disorder that affects both children and adults. There are Food and Drug Administration-approved stimulant and nonstimulant medications for treating ADHD; however, little is known about the mechanisms by which these different treatments exert their therapeutic effects. OBJECTIVE To contrast changes in brain activation related to symptomatic improvement with use of the stimulant methylphenidate hydrochloride vs the nonstimulant atomoxetine hydrochloride. DESIGN Functional magnetic resonance imaging before and after 6 to 8 weeks of treatment with methylphenidate (n = 18) or atomoxetine (n = 18) using a parallel-groups design. SETTING Specialized ADHD clinical research program at Mount Sinai School of Medicine, New York, New York. PARTICIPANTS Thirty-six youth with ADHD (mean [SD] age, 11.2 [2.7] years; 27 boys) recruited from randomized clinical trials. MAIN OUTCOME MEASURES Changes in brain activation during a go/no-go test of response inhibition and investigator-completed ratings on the ADHD Rating Scale-IV-Parent Version. RESULTS Treatment with methylphenidate vs atomoxetine was associated with comparable improvements in both response inhibition on the go/no-go test and mean (SD) improvements in ratings of ADHD symptoms (55% [30%] vs 57% [25%]). Improvement in ADHD symptoms was associated with common reductions in bilateral motor cortex activation for both treatments. Symptomatic improvement was also differentially related to gains in task-related activation for atomoxetine and reductions in activation for methylphenidate in the right inferior frontal gyrus, left anterior cingulate/supplementary motor area, and bilateral posterior cingulate cortex. These findings were not attributable to baseline differences in activation. CONCLUSIONS Treatment with methylphenidate and atomoxetine produces symptomatic improvement via both common and divergent neurophysiologic actions in frontoparietal regions that have been implicated in the pathophysiology of ADHD. These results represent a first step in delineating the neurobiological basis of differential response to stimulant and nonstimulant medications for ADHD.

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.

Preventive Interventions for ADHD: A Neurodevelopmental Perspective

It is proposed that the time is ripe for the development of secondary preventive interventions for attention-deficit/hyperactivity disorder (ADHD). By targeting preschool children, a developmental stage during which ADHD symptoms first become evident in most children with the disorder, many of the adverse long-term consequences that typify the trajectory of ADHD may be avoided. A dynamic/interactive model of the biological and environmental factors that contribute to the emergence and persistence of ADHD throughout the lifespan is proposed. Based on this model, it is argued that environmental influences and physical exercise can be used to enhance neural growth and development, which in turn should have an enduring and long-term impact on the trajectory of ADHD. Central to this notion are 2 hypotheses: 1) environmental influences can facilitate structural and functional brain development, and 2) changes in brain structure and function are directly related to ADHD severity over the course of development and the degree to which the disorder persists or remits with time. We present experimental and correlational data supporting the first hypothesis and longitudinal data in individuals with ADHD supporting the second. The case is made for initiating such an intervention during the preschool years, when the brain is likely to be more “plastic” and perhaps susceptible to lasting modifications, and before complicating factors, such as comorbid psychiatric disorders, academic failure, and poor social and family relationships emerge, making successful treatment more difficult. Finally, we review recent studies in young children with ADHD that might fall under the umbrella of secondary prevention.

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. (J. of Att. Dis. 2008; 11(5) 546-557)

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.

Training executive, attention, and motor skills: a proof-of-concept study in preschool children With ADHD.

Objective: To examine whether cognitive enhancement can be delivered through play to preschoolers with ADHD and whether it would affect severity of ADHD symptoms. Method: Twenty-nine 4- and 5-year-old children and their parents participated in separate group sessions (3-5 children/group). Child groups were introduced games designed to enhance inhibitory control, working memory, attention, visuospatial abilities, planning, and motor skills. Parent groups were encouraged playing these games with their children at least 30 to 45 min/day and taught strategies for scaffolding difficulty levels and dealing with obstacles to daily playing. Results: Parent ratings and session attendance indicated considerable satisfaction with the program. Parent (p < .001) and teacher (p = .003) ratings on the ADHD-Rating Scale–IV (ADHD-RS-IV) indicated significant improvement in ADHD severity from pre- to post-treatment, which persisted 3 months later. Conclusion: This play-based intervention for preschoolers with ADHD is readily implemented at home. Preliminary evidence suggests efficacy beyond the termination of active treatment.

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.