Effect of treatment with stimulant medication on nonverbal executive function and visuomotor speed in children with attention deficit/hyperactivity disorder (ADHD).

This study used a novel hidden maze learning test to examine the nature and magnitude of impairment on separable aspects of executive function in 36 children with ADHD. A within-subject analysis of children with ADHD was also conducted to assess cognitive effects of open-label stimulant treatment. Compared to 31 age-matched controls, unmedicated children with ADHD were slower and made significantly more errors that were indicative of relative impairment in prepotent response inhibition and ability to "maintain set" while using simple rules to complete the task. Open-label administration of stimulant medication led to faster and more efficient performance, with children with ADHD making fewer perseverative and rule-break errors than when off medication. This instrument might be useful in monitoring treatment response in specific aspects of executive function and in assisting with dose-titration decisions.

Reversal of scopolamine-induced deficits with a single dose of donepezil, an acetylcholinesterase inhibitor.

BACKGROUND: To develop a more rapid screening paradigm for novel cognitive enhancers, the authors sought to determine the utility of a well-known pharmacologic model of induced dementia (scopolamine challenge), paired with a sensitive neuropsychological test, for assessing the ability of a single oral dose of a current treatment for Alzheimer's disease (donepezil) to improve cognitive performance in healthy elderly subjects. METHODS: Thirty-two (4 groups of 8) healthy elderly volunteers were put randomly into a double-blind, placebo-controlled, modified crossover design study. In Part 1, 16 subjects received donepezil (5 mg) or placebo separately in a crossover fashion. In Part 2, the remaining 2 groups of 8 subjects received scopolamine (0.3 mg subcutaneously) with each group then were assigned randomly to receive donepezil (5 mg) or placebo (in a crossover fashion) 3 hours postbaseline. A novel measure of visuospatial working memory and executive controls, the Groton Maze Learning Test (GMLT), was administered to each subject at baseline and at 2.5, 4, 5.5, 7, and 9 hours after dosing of donepezil. RESULTS: With scopolamine, subjects showed slower psychomotor speed, reduced accuracy and learning efficiency, and longer time required to navigate a hidden maze. Concurrent administration of donepezil significantly reversed these deficits and resulted in a faster recovery time. In addition, single doses of donepezil alone led to improved psychomotor speed, accuracy, and learning efficiency. CONCLUSIONS: Robust effects of single-dose donepezil on cognition can be readily observed, with the use of a complex hidden maze learning task, both with and without a scopolamine-induced deficit model in healthy elderly adults.

Mini-Mental State Exam performance of older African Americans: effect of age, gender, education, hypertension, diabetes, and the inclusion of serial 7s subtraction versus "world" backward on score.

The Mini-Mental State Exam (MMSE) is a clinically ubiquitous yet incompletely standardized instrument. Though the test offers considerable examiner leeway, little data exist on the normative consequences of common administration variations. We sought to: (a) determine the effects of education, age, gender, health status, and a common administration variation (serial 7s subtraction vs. "world" spelled backward) on MMSE score within a minority sample, (b) provide normative data stratified on the most empirically relevant bases, and (c) briefly address item failure rates. African American citizens (N = 298) aged 55-87 living independently in the community were recruited by advertisement, community recruitment, and word of mouth. Total score with "world" spelled backward exceeded total score with serial 7s subtraction across all levels of education, replicating findings in Caucasian samples. Education is the primary source of variance on MMSE score, followed by age. In this cohort, women out-performed men when "world" spelled backward was included, but there was no gender effect when serial 7s subtraction was included in MMSE total score. To ensure an appropriate interpretation of MMSE scores, reports, whether clinical or in publications of research findings, should be explicit regarding the administration method. Stratified normative data are provided.

Perception of alcohol intoxication shows acute tolerance while executive functions remain impaired.

Several psychological constructs (e.g., subjective perception of intoxication, visuomotor speed) display acute tolerance to alcohol, that is, show improvement at declining blood alcohol concentrations (BACs) relative to equivalent rising BACs. However, methodological challenges emerge when attempting to make such comparisons across limbs of the BAC curve, which have proven a barrier to advancing research on acute tolerance. To date, no studies have made multiple comparisons across the entire BAC trajectory. This study employs experimental procedures that overcome some of these difficulties, offering a clearer picture of recovery of impairment for subjective perception of intoxication and cognitive performance and the relationship between them. Twenty participants were assessed at multiple time points over 2 days. Continuous subjective perception of intoxication ratings and cognitive data derived from a computerized measure were paired with a novel analytic paradigm, which allowed comparisons at identified BACs. Results showed acute tolerance for individuals' subjective perception of intoxication and for performance on cognitive tasks measuring visuomotor speed and learning efficiency (recovery from impairment). In contrast, performance on measures of executive function and short-term memory showed no significant difference between limbs at exact concentrations (no recovery from impairment). Therefore, despite participants feeling less intoxicated over time, many cognitive functions remained impaired. The implication for these findings in terms of drunken driving behavior are substantial, suggesting that people may be likely to drive once they subjectively perceive that they have recovered from the acute intoxicating effects of alcohol, despite the persistence of "higher order" cognitive impairments.

Safety and proof of principle study of cerebellar vermal theta burst stimulation in refractory schizophrenia.

BACKGROUND: Early invasive electrical stimulation studies suggested that enhancement of cerebellar vermal activity might prove valuable in symptomatic treatment of refractory neuropsychiatric diseases via modulation of emotion and affect. This proof of principle study aimed to test this hypothesis using noninvasive brain stimulation, and to explore the safety of this protocol in schizophrenia. METHODS: Eight treatment-refractory patients with schizophrenia underwent ten sessions of intermittent theta burst stimulation (TBS) to the cerebellar vermis using MRI-guided transcranial magnetic stimulation (TMS). Assessments included side effect questionnaires, cardiovascular monitoring, psychiatric evaluations and comprehensive neuropsychological testing before and after TBS and at one-week follow-up. RESULTS: Overall, TBS was tolerated well with mild side effects primarily comprising neck pain and headache. No serious adverse events occurred. Diastolic blood pressure (BP) showed mild decreases for five minutes post-TBS; no significant changes were detected for systolic BP or pulse. PANSS negative subscale showed significant improvements following TBS and during the follow-up. Calgary Depression Scale and self-report visual analog scales for Happiness and Sadness pointed to significant mood elevation. Neuropsychological testing revealed significantly fewer omissions in working memory and interference conditions of a Continuous Performance Test, a longer spatial span and better delay organization on the Rey-Osterrieth Complex Figure during follow-up. No significant worsening in psychiatric or neuropsychological measures was detected. CONCLUSIONS: Theta burst stimulation of the cerebellar vermis is safe and well-tolerated, while offering the potential to modulate affect, emotion and cognition in schizophrenia. Future randomized, sham-stimulation controlled studies are warranted to support the clinical efficacy of this technique.