Julie B. Schweitzer

Effect of methylphenidate on executive functioning in adults with attention-deficit/hyperactivity disorder: normalization of behavior but not related brain activity.

BACKGROUND We examined the effect of prolonged methylphenidate (MPH) treatment on the functional neuroanatomy of executive functioning in adult men with attention-deficit/hyperactivity disorder (ADHD). METHODS Positron emission tomography with [(15)O] water measured alterations of regional cerebral blood flow (rCBF) during the Paced Auditory Serial Addition Task and a control task in 10 ADHD and 11 normal control men. Attention-deficit/hyperactivity disorder men were imaged unmedicated and after a clinically optimal dose of MPH for 3 weeks. RESULTS Methylphenidate improved ADHD task performance, reduced rCBF in the prefrontal cortex (PFC), and increased rCBF in the right thalamus and precentral gyrus. Comparisons between the ADHD and normal control groups showed that normal control participants exhibited greater anterior cingulate cortex and temporal gyrus rCBF than ADHD participants under both conditions. Executive functioning was associated with greater subcortical (basal ganglia and cerebellar vermis) activation in the ADHD than normal control group under both conditions. CONCLUSIONS Methylphenidate does not normalize task-related activity in ADHD. Task-related rCBF decreases in the PFC may be due to improved filtering out of task-irrelevant stimuli by way of MPH-mediated dopamine release in the PFC.

A Positron Emission Tomography Study Of Methylphenidate in Adults with ADHD: Alterations in Resting Blood Flow and Predicting Treatment Response

A hallmark symptom of attention-deficit hyperactivity disorder (ADHD) is an excess of motoric behavior or hyperactivity. Methylphenidate (MPH) is known to reduce hyperactivity in individuals with ADHD. Yet little is known about how it alters neural activity and how this relates to its clinical effects. The goal of this study is to examine MPH-induced changes during resting brain metabolism, and to examine how these changes correlate with measures of behavioral response to the drug. Measures of regional cerebral blood flow (rCBF) using positron emission tomography (PET) were acquired at rest for ten adult subjects with ADHD during both an unmedicated state and after a 3-week period of chronic dosing with a clinically optimal dose of MPH. Compared with the on-MPH condition, the off-MPH condition was associated with relative increases in rCBF bilaterally in the precentral gyri, left caudate nucleus, and right claustrum. The on-MPH condition was associated with relative increases in rCBF in the cerebellar vermis. A correlational analysis measured the relation between rCBF in the off-medication condition to change in ADHD ratings between the off- and on-MPH condition to identify brain regions associated with treatment response. The degree of change in the ratings was negatively correlated with rCBF increases in the midbrain, cerebellar vermis, and the precentral and middle frontal gyri in the off-MPH condition. The majority of these brain regions are involved in the planning and execution of motor behavior. These data suggest that MPH modulates brain regions associated with motor function to achieve a reduction in ADHD symptoms.

Working memory deficits in adults with ADHD: is there evidence for subtype differences?

BackgroundWorking memory performance is important for maintaining functioning in cognitive, academic and social activities. Previous research suggests there are prevalent working memory deficits in children with attention deficit hyperactivity disorder (ADHD). There is now a growing body of literature characterizing working memory functioning according to ADHD subtypes in children. The expression of working memory deficits in adults with ADHD and how they vary according to subtype, however, remains to be more fully documented.MethodsThis study assessed differences in working memory functioning between Normal Control (NC) adults (N = 18); patients with ADHD, Combined (ADHD-CT) Type ADHD (N = 17); and ADHD, Inattentive (ADHD-IA) Type (N = 16) using subtests from the Wechsler Adult Intelligence Scale-III and Wechsler Memory Scale-III and the Paced Auditory Serial Addition Task (PASAT).ResultsThe ADHD groups displayed significant weaknesses in contrast to the NC group on working memory tests requiring rapid processing and active stimulus manipulation. This included the Letter-Number-Sequencing test of the Wechsler scales, PASAT omission errors and the longest sequence of consecutive correct answers on the PASAT. No overall ADHD group subtype differences emerged; however differences between the ADHD groups and the NC group varied depending on the measure and the gender of the participants. Gender differences in performance were evident on some measures of working memory, regardless of group, with males performing better than females.ConclusionIn general, the data support a dimensional interpretation of working memory deficits experienced by the ADHD-CT and ADHD-IA subtypes, rather than an absolute difference between subtypes. Future studies should test the effects of processing speed and load on subtype performance and how those variables interact with gender in adults with ADHD.

Pharmacological management of attention-deficit hyperactivity disorder

Pharmacotherapy is the most common intervention for attention-deficit hyperactivity disorder (ADHD). Stimulant medications are highly efficacious and are the gold-standard for treating the inattention, impulsivity and excessive motoric activity associated with ADHD. Methylphenidate and amphetamine-based stimulants are now available in longer-acting, once-daily and shorter-acting divided dosing schedules. Several nonstimulant, second-line treatments are now available or under development for the treatment of ADHD in children and adults. This article reviews the support for a variety of pharmacological agents and the issues to be considered when selecting an agent. The authors conclude that there is a need for additional direct comparisons between the longer-acting agents to effectively guide the practicing clinician.

Effects of familiarity and methylphenidate on the neural correlates of working memory in attention deficit/hyperactivity disorder: A PET study

Introduction Attention deficit/hyperactivity disorder (ADHD) is a disorder commonly characterized by persistent inattention and/or excessive motor restlessness and impulsive behavior. It is now recognized that children and adults with ADHD exhibit deficits in working memory (1,2), and that such impairments are ameliorated by treatment with methylphenidate (3). Familiarity with tasks and situations has also been shown to increase ADHD symptomatology, rather than improve performance (4). The aim of the present study was to determine 1) the effect of familiarity on rCBF patterns in subjects with ADHD and 2) the effect of methylphenidate on those patterns.