Science 30 May 2008: Vol. 320. no. 5880 1143.
PARKINSON'S DISEASE: Streamlined Clinical Trials, From a Home Computer
A Parkinson's research and treatment center and the genetic testing company 23andMe are experimenting with an unusual new approach to clinical trials: have participants assess themselves from their home computers potentially using everything from videos of tremors to a mouse that senses motor abilities.

Science 30 May 2008: Vol. 320. no. 5880 1172-1173.
MEDICINE: Activating a Repressor
A factor implicated in autism spectrum disorders can both suppress and activate the expression of genes involved in neurodevelopment.

Science 30 May 2008:
Vol. 320. no. 5880, pp. 1191 - 1195
Predicting Human Brain Activity Associated with the Meanings of Nouns
The question of how the human brain represents conceptual knowledge has been debated in many scientific fields. Brain imaging studies have shown that different spatial patterns of neural activation are associated with thinking about different semantic categories of pictures and words (for example, tools, buildings, and animals). We present a computational model that predicts the functional magnetic resonance imaging (fMRI) neural activation associated with words for which fMRI data are not yet available. This model is trained with a combination of data from a trillion-word text corpus and observed fMRI data associated with viewing several dozen concrete nouns. Once trained, the model predicts fMRI activation for thousands of other concrete nouns in the text corpus, with highly significant accuracies over the 60 nouns for which we currently have fMRI data.

Science 30 May 2008:
Vol. 320. no. 5880, pp. 1213 - 1216
Ancestral Monogamy Shows Kin Selection Is Key to the Evolution of Eusociality
Close relatedness has long been considered crucial to the evolution of eusociality. However, it has recently been suggested that close relatedness may be a consequence, rather than a cause, of eusociality. We tested this idea with a comparative analysis of female mating frequencies in 267 species of eusocial bees, wasps, and ants. We found that mating with a single male, which maximizes relatedness, is ancestral for all eight independent eusocial lineages that we investigated. Mating with multiple males is always derived. Furthermore, we found that high polyandry (>2 effective mates) occurs only in lineages whose workers have lost reproductive totipotency. These results provide the first evidence that monogamy was critical in the evolution of eusociality, strongly supporting the prediction of inclusive fitness theory.

Science 30 May 2008:
Vol. 320. no. 5880, pp. 1217 - 1220
Log or Linear? Distinct Intuitions of the Number Scale in Western and Amazonian Indigene Cultures
The mapping of numbers onto space is fundamental to measurement and to mathematics. Is this mapping a cultural invention or a universal intuition shared by all humans regardless of culture and education? We probed number-space mappings in the Mundurucu, an Amazonian indigene group with a reduced numerical lexicon and little or no formal education. At all ages, the Mundurucu mapped symbolic and nonsymbolic numbers onto a logarithmic scale, whereas Western adults used linear mapping with small or symbolic numbers and logarithmic mapping when numbers were presented nonsymbolically under conditions that discouraged counting. This indicates that the mapping of numbers onto space is a universal intuition and that this initial intuition of number is logarithmic. The concept of a linear number line appears to be a cultural invention that fails to develop in the absence of formal education.

Science 30 May 2008:
Vol. 320. no. 5880, pp. 1224 - 1229
MeCP2, a Key Contributor to Neurological Disease, Activates and Represses Transcription
Mutations in the gene encoding the transcriptional repressor methyl-CpG binding protein 2 (MeCP2) cause the neurodevelopmental disorder Rett syndrome. Loss of function as well as increased dosage of the MECP2 gene cause a host of neuropsychiatric disorders. To explore the molecular mechanism(s) underlying these disorders, we examined gene expression patterns in the hypothalamus of mice that either lack or overexpress MeCP2. In both models, MeCP2 dysfunction induced changes in the expression levels of thousands of genes, but unexpectedly the majority of genes (85%) appeared to be activated by MeCP2. We selected six genes and confirmed that MeCP2 binds to their promoters. Furthermore, we showed that MeCP2 associates with the transcriptional activator CREB1 at the promoter of an activated target but not a repressed target. These studies suggest that MeCP2 regulates the expression of a wide range of genes in the hypothalamus and that it can function as both an activator and a repressor of transcription.

Nature 453, 570-571 (2008)
Genetic testing for everyone
Private companies are starting to test customers' DNA for gene variants linked to an increased risk of conditions such as obesity or Alzheimer's disease. Helen Pearson looks at whether knowledge really is power when it comes to disease avoidance.

Nature 453, 598-599 (29 May 2008)
Science & Music: The neural roots of music
Laurel Trainor explains how the emotional power of music depends on the structure of the ear, and on our basic encoding of information.
In search of an original voice, the dominant composers of the mid-twentieth century — Arnold Schoenberg, Pierre Boulez and their disciples — rejected the tonal and rhythmic forms of the past. They adhered to rigorous compositional techniques such as the serial tone-row method — in which all notes of the chromatic scale occur equally often in a repeating row — banishing tonality.

JAMA. 2008;299(20):2391-2400.
Escitalopram and Problem-Solving Therapy for Prevention of Poststroke Depression
A Randomized Controlled Trial
Context  Depression occurs in more than half of patients who have experienced a stroke. Poststroke depression has been shown in numerous studies to be associated with both impaired recovery in activities of daily living and increased mortality.
Prevention of depression thus represents a potentially important goal. Objective  To determine whether treatment with escitalopram or problem-solving therapy over the first year following acute stroke will decrease the number of depression cases that develop compared with placebo medication.

Design, Setting, and Participants  A multisite randomized controlled trial for prevention of depression among 176 nondepressed patients was conducted within 3 months following acute stroke from July 9, 2003, to October 1, 2007. The 12-month trial included 3 groups: a double-blind placebo-controlled comparison of escitalopram (n = 59) with placebo (n = 58), and a nonblinded problem-solving therapy group (n = 59).
Main Outcome Measures  The main outcome measure was the development of major or minor poststroke depression based on symptoms elicited by the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (DSM-IV) and the diagnostic criteria from DSM-IV for depression due to stroke with major depressive-like episode or minor depression (ie, research criteria).

Results  Patients who received placebo were significantly more likely to develop depression than individuals who received escitalopram (11 major and 2 minor cases of depression [22.4%] vs 3 major and 2 minor cases of depression [8.5%], adjusted hazard ratio [HR], 4.5; 95% confidence interval [CI], 2.4-8.2; P < .001) and also more likely than individuals who received problem-solving therapy (5 major and 2 minor cases of depression [11.9%], adjusted HR, 2.2; 95% CI, 1.4-3.5; P < .001). These results were adjusted for history of mood disorders and remained significant after considering possible confounders such as age, sex, treatment site, and severity of impairment in the model. Using an intention-to-treat conservative method of analyzing the data, which assumed that all 27 patients who did not start randomized treatment would have developed depression, and controlling for prior history of mood disorders, escitalopram was superior to placebo (23.1% vs 34.5%; adjusted HR, 2.2; 95% CI, 1.2-3.9; P = .007), while problem-solving therapy was not significantly better than placebo (30.5% vs 34.5%; adjusted HR, 1.1; 95% CI, 0.8-1.5; P = .51). Adverse events, including all-cause hospitalizations, nausea, and adverse effects associated with escitalopram were not significantly different between the 3 groups.

Conclusions  In this study of nondepressed patients with recent stroke, the use of escitalopram or problem-solving therapy resulted in a significantly lower incidence of depression over 12 months of treatment compared with placebo, but problem-solving therapy did not achieve significant results over placebo using the intention-to-treat conservative method of analysis.

JAMA. 2008;299(20):2375-2376.
Researchers Identify Neurological Risks
Chicago—A chemical, a common class of drugs, and lifestyle factors are all tied to increased risk of cognitive decline or neurological disease, according to findings presented at the Annual Meeting of the American Academy of Neurology in April.
Workplace formaldehyde exposure, such as that experienced by beauticians, may be a risk factor for amyotrophic lateral sclerosis. Studies highlighted at the meeting linked formaldehyde exposure to an increased risk of amyotrophic lateral sclerosis (ALS), the use of anticholinergic drugs to faster cognitive decline, and heavy drinking and smoking to an earlier onset of Alzheimer disease. Another study found that having a larger hippocampus may protect against the development of dementia.

JAMA. 2008;299(20):2379.
Methamphetamine Addiction
The mechanism behind the highly addictive nature of methamphetamine has been identified, according to a study funded in part by the National Institute of Neurological Disorders and Stroke, the National Institute of Child Health and Human Development, and the National Institute on Drug Abuse. Like many addictive drugs, methamphetamine stimulates the release of dopamine, which triggers pleasurable sensations. But the precise neurological changes caused by chronic use that underlie the intense craving and tendency to relapse were not well understood.