Brain development and ADHD

Krain, Amy L.; Castellanos, F. Xavier

doi:10.1016/j.cpr.2006.01.005

Cited by 421 publications

(338 citation statements)

References 68 publications

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“…Furthermore, it has been suggested that neuropsychologic deficits underlying ADHD, such as impairments in response inhibition, delay aversion or working memory, are associated with structural or functional brain abnormalities or both in the frontal-striatal-cerebellar circuits. 28 In the present study, we found that regional cerebral perfusion depended on the presence of the C allele of the ADRA2A MspI polymorphism in ADHD. Patients with ADHD who carried the C allele had lower perfusion in the bilateral orbitofrontal regions than ADHD patients without the C allele.…”

Section: Discussionmentioning

confidence: 60%

Regional differences in cerebral perfusion associated with the α-2A-adrenergic receptor genotypes in attention deficit hyperactivity disorder

Kim¹,

Kim²,

Kang

et al. 2010

jpn

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Background: Neurobiologic studies have suggested that dysregulation of central noradrenergic systems may be involved in the pathophysiology of attention deficit hyperactivity disorder (ADHD), and it has been hypothesized that genetic changes in the norepinephrine pathways might contribute to dysfunction of the prefrontal cortex circuits in ADHD. We previously reported decreased cerebral blood flow in the right lateral prefrontal cortex and both orbitofrontal cortices in children with ADHD. Genetic investigations have shown that the α-2A-adrenergic receptor gene (ADRA2A) is associated with ADHD. Our aim was to examine whether the presence of a risk allele of the ADRA2A MspI polymorphism is associated with differences in regional cerebral blood flow in boys with ADHD. Methods: We recruited 21 Korean boys with ADHD (mean age 9.9, standard deviation [SD] 2.7 yr) and 11 age-and sex-matched controls (mean age 10.6 [SD 2.1] yr). Each participant underwent technetium-99m-hexamethylpropylene amine oxime ( 99m Tc-HMPAO) single-photon emission computed tomography. We performed image analyses with voxel-wise t statistics using SPM2. Results: We found regional hypoperfusion in the prefrontal regions, including the right orbitofrontal and right medial gyri, and the bilateral putamen and cerebellum in boys with ADHD relative to controls (p < 0.0005, uncorrected for multiple comparisons). Boys with ADHD who carried the C allele (n = 13) at the ADRA2A MspI polymorphism had reduced perfusion in the bilateral orbitofrontal regions compared with those without the C allele (n = 8) (p < 0.0005, uncorrected for multiple comparisons). Limitations: This study was limited by the small sample size, and we did not obtain genetic data from the controls. Conclusion: Our findings suggest that regional differences in cerebral perfusion in the orbitofrontal cortex represent an intermediate neuroimaging phenotype associated with the ADRA2A MspI polymorphism; these data support the validity of the noradrenergic hypothesis regarding the pathophysiology of ADHD.

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Section: Discussionmentioning

confidence: 60%

Regional differences in cerebral perfusion associated with the α-2A-adrenergic receptor genotypes in attention deficit hyperactivity disorder

Kim¹,

Kim²,

Kang

et al. 2010

jpn

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“…In a voxel-based morphometric study, the temporal lobe and cerebellum were found to have a lower grey matter volume in ADHD children than in control participants [58] . Structural studies show a correlation between specific phenotypes and alterations in brain structure, especially in frontal-striatal-cere- bellar circuits [59] . In functional studies, under-activation in the temporal lobe was observed in adult ADHD patients in working memory and decision-making tasks.…”

Section: Superior and Middle Temporal Gyrimentioning

confidence: 99%

Effects of methylphenidate on resting-state brain activity in normal adults: an fMRI study

et al. 2013

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Methylphenidate (MPH) is one of the most commonly used stimulants for the treatment of attention deficit hyperactivity disorder (ADHD). Although several studies have evaluated the effects of MPH on human brain activation during specific cognitive tasks using functional magnetic resonance imaging (fMRI), few studies have focused on spontaneous brain activity. In the current study, we investigated the effect of MPH on the intra-regional synchronization of spontaneous brain activity during the resting state in 18 normal adult males. A handedness questionnaire and the Wechsler Adult Intelligence Scale were applied before medication, and a resting-state fMRI scan was obtained 1 h after medication (20 mg MPH or placebo, order counterbalanced between participants). We demonstrated that: (1) there were no significant differences in the performance of behavioral tasks between the MPH and placebo groups; (2) the left middle and superior temporal gyri had stronger MPHrelated regional homogeneity (ReHo); and (3) the left lingual gyrus had weaker MPH-related ReHo. Our findings showed that the ReHo in some brain areas changes with MPH compared to placebo in normal adults, even though there are no behavioral differences. This method can be applied to patients with mental illness who may be treated with MPH, and be used to compare the difference between patients taking MPH and normal participants, to help reveal the mechanism of how MPH works.

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“…Krain and Castellanos (2006) suggested that these brain deficits were non-progressive and associated with the disorder (presumably from the result of early genetic and/or environmental factors), rather than consequences of treatment of the disorder with stimulant drugs. Shaw et al (2006) and Shaw et al (2007) reported differences in brain development based on measures of cortical thickness, which was reduced in childhood in ADHD cases compared with controls.…”

Section: Long-term Cognitive Effects Of Stimulant Medicationmentioning

confidence: 99%

“…Here, we will focus on three of the most prominent that use reaction time (RT) as a measure of performance: (a) the Stop Signal Task (STOP) that requires the cued inhibition of response to stimulus after a signal; (b) the reverse continuous performance task (CPT) (GoNoGo) that requires response to most but not all stimuli in a series; and (c) the attentional network task (ANT) that requires response to central stimuli in the face of temporal, spatial, and conflicting surrounding cues. We will build on reviews that relate these tasks to the brain imaging literature of structure (Krain and Castellanos, 2006), function (Dickstein et al, 2006), and connectivity (Bush, 2010), and emphasize advances over the past decade in the conceptualization and evaluation of neural processes and networks that may be abnormal in ADHD, and thus may mediate the effects of stimulant medication on cognition in individuals with ADHD. …”

mentioning

confidence: 99%

Understanding the Effects of Stimulant Medications on Cognition in Individuals with Attention-Deficit Hyperactivity Disorder: A Decade of Progress

Swanson

Baler

Volkow

2010

Neuropsychopharmacol

216

165

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The use of stimulant drugs for the treatment of children with attention-deficit hyperactivity disorder (ADHD) is one of the most widespread pharmacological interventions in child psychiatry and behavioral pediatrics. This treatment is well grounded on controlled studies showing efficacy of low oral doses of methylphenidate and amphetamine in reducing the behavioral symptoms of the disorder as reported by parents and teachers, both for the cognitive (inattention and impulsivity) and noncognitive (hyperactivity) domains. Our main aim is to review the objectively measured cognitive effects that accompany the subjectively assessed clinical responses to stimulant medications. Recently, methods from the cognitive neurosciences have been used to provide information about brain processes that underlie the cognitive deficits of ADHD and the cognitive effects of stimulant medications. We will review some key findings from the recent literature, and then offer interpretations of the progress that has been made over the past decade in understanding the cognitive effects of stimulant medication on individuals with ADHD. Neuropsychopharmacology Reviews (2011) 36, 207-226; doi:10.1038/npp.2010; published online 29 September 2010Keywords: methylphenidate; amphetamine; dopamine; prefrontal cortex; executive function; cognitive enhancement INTRODUCTIONCognitive deficits and behavioral symptoms associated with attention-deficit/hyperactivity disorder (ADHD) have been studied intensively and are well documented in the literature. Stimulant drugs (methylphenidate (MP) and amphetamine (AMP)) are particularly effective for the clinical treatment of ADHD, and accordingly, pediatricians and psychiatrists have been prescribing them for over seven decades (Bradley, 1937). Clear reductions in symptoms justify treatment with stimulant medications (MTA, 1999b), but the cognitive effects are less clear. Here, we will review the current understanding of some underlying neural processes that may account for the ADHD symptoms of inattention and impulsivity, and we will review evidence from neuropsychological and neuroimaging studies about how stimulant medications may affect these processes. To focus our review, we will not revisit related topics that are addressed elsewhere: the medical use of non-stimulant drugs to treat ADHD (Dopheide and Pliszka, 2009;Waxmonsky, 2005), the non-medical use of stimulants and non-stimulants for cognitive enhancement (Sahakian and Morein-Zamir, 2007;Stix, 2009), and nonmedical alternative treatments based on neurofeedback (Gevensleben et al, 2009) and working memory training (Klingberg et al, 2005) that have recently been evaluated and have gained some support in randomized clinical trials.In the Diagnostic and Statistical Manual (DSM) of the American Psychiatric Association, Version IV (APA, 1994(APA, , 2000, the cognitive symptoms of ADHD are grouped into two domains: inattention and hyperactivity/impulsivity. Currently, nine are specified for inattention (poor attending to details, sustaining attention, lis...

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Brain development and ADHD

Cited by 421 publications

References 68 publications

Regional differences in cerebral perfusion associated with the α-2A-adrenergic receptor genotypes in attention deficit hyperactivity disorder

Regional differences in cerebral perfusion associated with the α-2A-adrenergic receptor genotypes in attention deficit hyperactivity disorder

Effects of methylphenidate on resting-state brain activity in normal adults: an fMRI study

Understanding the Effects of Stimulant Medications on Cognition in Individuals with Attention-Deficit Hyperactivity Disorder: A Decade of Progress

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