Science 18 July 2008:
Vol. 321. no. 5887, pp. 347 - 348 NEUROSCIENCE: Vertebrate Vocalizations
Did the mechanisms underlying vertebrate vocal abilities evolve from a single common ancestor?

Science 18 July 2008:
Vol. 321. no. 5887, pp. 350 - 352 DEVELOPMENTAL BIOLOGY: Grasping Limb Patterning
Recent studies offer insights into how a molecular signal controls the growth and patterning of the digits on vertebrate limbs during development.

Science 18 July 2008:
Vol. 321. no. 5887, pp. 372 - 376
Identification of SLEEPLESS, a Sleep-Promoting Factor
Sleep is an essential process conserved from flies to humans. The importance of sleep is underscored by its tight homeostatic control. Through a forward genetic screen, we identified a gene, sleepless, required for sleep in Drosophila. The sleepless gene encodes a brain-enriched, glycosylphosphatidylinositol-anchored protein. Loss of SLEEPLESS protein caused an extreme (>80%) reduction in sleep; a moderate reduction in SLEEPLESS had minimal effects on baseline sleep but markedly reduced the amount of recovery sleep after sleep deprivation. Genetic and molecular analyses revealed that quiver, a mutation that impairs Shaker-dependent potassium current, is an allele of sleepless. Consistent with this finding, Shaker protein levels were reduced in sleepless mutants. We propose that SLEEPLESS is a signaling molecule that connects sleep drive to lowered membrane excitability.

Science 18 July 2008:
Vol. 321. no. 5887, pp. 414 - 417
Bottom-Up Dependent Gating of Frontal Signals in Early Visual Cortex
The frontal eye field (FEF) is one of several cortical regions thought to modulate sensory inputs. Moreover, several hypotheses suggest that the FEF can only modulate early visual areas in the presence of a visual stimulus. To test for bottom-up gating of frontal signals, we microstimulated subregions in the FEF of two monkeys and measured the effects throughout the brain with functional magnetic resonance imaging. The activity of higher-order visual areas was strongly modulated by FEF stimulation, independent of visual stimulation. In contrast, FEF stimulation induced a topographically specific pattern of enhancement and suppression in early visual areas, but only in the presence of a visual stimulus. Modulation strength depended on stimulus contrast and on the presence of distractors. We conclude that bottom-up activation is needed to enable top-down modulation of early visual cortex and that stimulus saliency determines the strength of this modulation.

Science 18 July 2008:
Vol. 321. no. 5887, pp. 417 - 421
Evolutionary Origins for Social Vocalization in a Vertebrate Hindbrain–Spinal Compartment
The macroevolutionary events leading to neural innovations for social communication, such as vocalization, are essentially unexplored. Many fish vocalize during female courtship and territorial defense, as do amphibians, birds, and mammals. Here, we map the neural circuitry for vocalization in larval fish and show that the vocal network develops in a segment-like region across the most caudal hindbrain and rostral spinal cord. Taxonomic analysis demonstrates a highly conserved pattern between fish and all major lineages of vocal tetrapods. We propose that the vocal basis for acoustic communication among vertebrates evolved from an ancestrally shared developmental compartment already present in the early fishes.

Science 18 July 2008:
Vol. 321. no. 5887, pp. 421 - 422
Orbitofrontal Dysfunction in Patients with Obsessive-Compulsive Disorder and Their Unaffected Relatives
Obsessive-compulsive disorder (OCD) is characterized by repetitive thoughts and behaviors associated with underlying dysregulation of frontostriatal circuitry. Central to neurobiological models of OCD is the orbitofrontal cortex, a neural region that facilitates behavioral flexibility after negative feedback (reversal learning). We identified abnormally reduced activation of several cortical regions, including the lateral orbitofrontal cortex, during reversal learning in OCD patients and their clinically unaffected close relatives, supporting the existence of an underlying previously undiscovered endophenotype for this disorder.

Nature 453, 259 (2008)
Autism study panned by critics.Plan to use chelating agents on children comes under fire.
The leading US government funder of autism research is drawing fire over its proposal to run a randomized clinical trial of a treatment widely viewed by experts to be useless and potentially harmful, but that is broadly used for autism.
Chelation therapy, in which agents such as dimercaptosuccinic acid (DMSA) are used to bind metal ions in the blood so that they can be excreted easily, is an approved treatment for heavy-metal poisoning.

Nature 454, 284-285 (17 July 2008)
Motor neuron disease: The curious ways of ALS
That mutations in the SOD1 enzyme underlie inherited forms of a motor neuron disease known as ALS is clear. But the question of what the consequences of such mutations are seems to have more than one answer.
Amyotrophic lateral sclerosis (ALS) is a neurological disorder characterized by the selective premature degeneration and death of motor neurons, which control voluntary actions such as breathing and walking. The disease starts in adult life, and the ensuing progressive paralysis is typically fatal within a few years, usually owing to failure of the respiratory system.

Nature 454, 340-344 (17 July 2008)                         
The role of the orbitofrontal cortex in the pursuit of happiness and more specific rewards
Cues that reliably predict rewards trigger the thoughts and emotions normally evoked by those rewards. Humans and other animals will work, often quite hard, for these cues. This is termed conditioned reinforcement. The ability to use conditioned reinforcers to guide our behaviour is normally beneficial; however, it can go awry. For example, corporate icons, such as McDonald's Golden Arches, influence consumer behaviour in powerful and sometimes surprising ways, and drug-associated cues trigger relapse to drug seeking in addicts and animals exposed to addictive drugs, even after abstinence or extinction. Yet, despite their prevalence, it is not known how conditioned reinforcers control human or other animal behaviour. One possibility is that they act through the use of the specific rewards they predict; alternatively, they could control behaviour directly by activating emotions that are independent of any specific reward. In other words, the Golden Arches may drive business because they evoke thoughts of hamburgers and fries, or instead, may be effective because they also evoke feelings of hunger or happiness. Moreover, different brain circuits could support conditioned reinforcement mediated by thoughts of specific outcomes versus more general affective information. Here we have attempted to address these questions in rats. Rats were trained to learn that different cues predicted different rewards using specialized conditioning procedures that controlled whether the cues evoked thoughts of specific outcomes or general affective representations common to different outcomes. Subsequently, these rats were given the opportunity to press levers to obtain short and otherwise unrewarded presentations of these cues. We found that rats were willing to work for cues that evoked either outcome-specific or general affective representations. Furthermore the orbitofrontal cortex, a prefrontal region important for adaptive decision-making4, was critical for the former but not for the latter form of conditioned reinforcement.

JAMA. 2008;300(3):287-294.
Effect of Simvastatin on Cognitive Functioning in Children With Neurofibromatosis Type 1
A Randomized Controlled Trial
Context  Neurofibromatosis type 1 (NF1) is among the most common genetic disorders that cause learning disabilities. Recently, it was shown that statin-mediated inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase restores the cognitive deficits in an NF1 mouse model.
Objective  To determine the effect of simvastatin on neuropsychological, neurophysiological, and neuroradiological outcome measures in children with NF1.
Design, Setting, and Participants  Sixty-two of 114 eligible children (54%) with NF1 participated in a randomized, double-blind, placebo-controlled trial conducted between January 20, 2006, and February 8, 2007, at an NF1 referral center at a Dutch university hospital.
Intervention  Simvastatin or placebo treatment once daily for 12 weeks.
Main Outcome Measures  Primary outcomes were scores on a Rey complex figure test (delayed recall), cancellation test (speed), prism adaptation, and the mean brain apparent diffusion coefficient based on magnetic resonance imaging. Secondary outcome measures were scores on the cancellation test (standard deviation), Stroop color word test, block design, object assembly, Rey complex figure test (copy), Beery developmental test of visual-motor integration, and judgment of line orientation. Scores were corrected for baseline performance, age, and sex.
Results  No significant differences were observed between the simvastatin and placebo groups on any primary outcome measure: Rey complex figure test (β = 0.10; 95% confidence interval [CI], –0.36 to 0.56); cancellation test (β = –0.19; 95% CI, –0.67 to 0.29); prism adaptation (odds ratio = 2.0; 95% CI, 0.55 to 7.37); and mean brain apparent diffusion coefficient (β = 0.06; 95% CI, –0.07 to 0.20). In the secondary outcome measures, we found a significant improvement in the simvastatin group in object assembly scores (β = 0.54; 95% CI, 0.08 to 1.01), which was specifically observed in children with poor baseline performance (β = 0.80; 95% CI, 0.29 to 1.30). Other secondary outcome measures revealed no significant effect of simvastatin treatment.
Conclusion  In this 12-week trial, simvastatin did not improve cognitive function in children with NF1.

JAMA. 2008;300(3):274-276.
Awareness of Stroke Warning Symptoms—13 States and the District of Columbia, 2005
Although the number of deaths from stroke has declined substantially since the 1960s, in 2004, stroke remained the third leading cause of death in the United States, after heart disease and cancer. Approximately 54% of U.S. stroke deaths in 2004 occurred outside of a hospital. Intravenous administration of tissue plasminogen activator has clinical benefits for patients with acute ischemic stroke; however, treatment should begin within 3 hours of symptom onset for these benefits to be realized. For hemorrhagic stroke, immediate surgery (e.g., aneurysm repair) is crucial to prevent rebleeding that results in serious impairment or death in 40% to 60% of cases. A revised objective of Healthy People 2010 is to increase to 83% the proportion of persons who are aware of the warning symptoms of stroke and the need to telephone 9-1-1 immediately if someone appears to be having a stroke (objective no. 12-8).  To assess public awareness of stroke warning symptoms and the importance of seeking emergency care, CDC analyzed data from an optional module of the 2005 Behavioral Risk Factor Surveillance System (BRFSS) survey that was used in 13 states and the District of Columbia (DC). The results indicated that the percentages of respondents who recognized all five correct symptoms, identified an incorrect symptom, and recognized the need to telephone 9-1-1 was low; the percentage who met all three measures was 16.4%. In addition, disparities were observed by race/ethnicity, sex, and education level. Public health agencies, clinicians, and educators should continue to stress the importance of learning to recognize stroke symptoms and the need to telephone 9-1-1 when someone appears to be having a stroke.

JAMA  Vol. 300 No. 3, July 16, 2008    
Neurofibromatosis
Neurofibromatosis (NF) is a genetic disorder causing skin abnormalities and tumors that form on nerve tissues. These tumors can be small or large and can occur anywhere in the body, including the brain, spinal cord, large nerves, or smaller nerves. NF affects persons of both sexes and all racial groups. There are 2 types of neurofibromatosis, called NF1 and NF2. These are 2 distinct disorders that are caused by mutations (changes) in different genes. NF1 is also referred to as Von Recklinghausen disease and is a rather common genetic disease, affecting approximately 1 in 4000 individuals. Some patients who have NF1 only display characteristic skin abnormalities such as café-au-lait spots, which are flat, hyperpigmented (darker than surrounding skin) areas. Other patients can have severe physical complications such as malignant (cancerous) tumors or have mental retardation. The July 16, 2008, issue of JAMA includes an article about the learning deficits associated with NF. Learning disability is the most frequent complication in children with NF1.

BMJ 2008;337:a602
Editorials Antipsychotics for people with dementia Should be reserved for severe and persistent symptoms after assessment of risk and benefit
More than 25 million people worldwide have dementia, with a new case developing every seven seconds.1 While putative disease modifying agents are being developed, we are limited to symptomatic treatments for cognitive and non-cognitive features. Non-cognitive symptoms—referred to as behavioural and psychological symptoms of dementia—including agitation, psychosis, depression, and aggression, occur in up to half of those with dementia in the community and an even higher proportion in residential care. Antipsychotics have been widely prescribed off licence for these symptoms, and 20-50% of people with dementia in institutional care receive them.2 What is the evidence for their efficacy?

BMJ 2008;337:a734News
NICE recommendations have had little effect on multiple sclerosis services five years on
Nearly two thirds of patients with multiple sclerosis in England and Wales are unable to access neurological rehabilitation services, an audit shows.
The Royal College of Physicians of London and the MS Trust surveyed 1300 people with the condition, 127 acute NHS hospital trusts, 140 primary care trusts and local health boards, and seven strategic health authorities and regional offices during January and February 2008. Questions were based on guidelines for managing the illness from the National Institute for Health and Clinical Excellence (NICE).

The Lancet Vol: 372 Issue: 9633, July 12 - 18 2008   pp: 116
Neurodevelopmental consequences of very preterm births
Béatrice Larroque and colleagues (March 8, p 813) report different negative neurodevelopmental consequences of very preterm births in a 5-year follow-up cohort and the resulting use of rehabilitation care. This study reflects a dynamic of profound changes in obstetric and paediatric practices in France in the late 1990s, which included the creation of level III neonatal units and a neonatal care referral network between hospitals.
Despite the substantial advances in research on fetal growth and the neonatal adaptation to extrauterine life that drove this dynamic, the current state of scientific knowledge is insufficient for ruling out the risk of brain damage closely associated with the immaturity of the brain during its ex-utero development in very preterm children. Therefore, results from prospective investigations such as Larroque and colleagues' and others should be integrated in a teleological perspective beyond merely neonatal care, for these investigations provide essential arguments for preventing prematurity, which is feasible only with a two-pronged, biomedical and psychosocial approach.

The Lancet
Vol: 372 Issue: 9633, July 12 - 18 2008    pp: 176
A deviated tongue
In April, 2006, an 88-year-old man was admitted to our hospital with dehydration and severe weight loss; he was unable to swallow solids or liquids. His other medical problems included atrial fibrillation, hypertension, and benign prostatic hypertrophy: he was prescribed warfarin, bendroflumethiazide, and alfuzosin hydrochloride. He was an ex-smoker, and rarely drank alcohol. He had attended an otolaryngology clinic the month before, having had difficulty swallowing solids for 3 months, during which his weight had decreased by 12 kg. In the otolaryngology clinic, fibre-optic nasal endoscopy and a gastrograffin swallow test had shown a normal cervical and thoracic oesophagus. The doctor had found the patient to be dysarthric, but did not think that the dysphagia was caused by a problem with the tongue, mouth, or throat. The patient was then seen in a gastroenterology clinic, where an oesophageal cause of dysphagia was ruled out, and a neurological cause suspected. However, before the patient could have MRI of the brain as an outpatient, he was brought by ambulance to us.

NEJM Volume 359:294-303  July 17, 2008  Number 3
Case 22-2008 — A 52-Year-Old Woman with Fever and Confusion
Presentation of Case
Dr. Marylyn M. Addo (Infectious Disease): A 52-year-old woman was admitted to this hospital in late summer because of fever and confusion. The patient had been well until 9 days earlier, when she told family members that she felt unwell. During the next 4 days, fatigue, lethargy, tenderness over the mastoid, tingling of the tongue, myalgias of the legs, and headache developed. Five days before admission, she saw her primary care physician; results of routine laboratory tests were said to be normal. Computed tomography (CT) of the mastoid was scheduled.

NEJM Volume 359:311-313  July 17, 2008  Number 3
Carotid Stenting versus Endarterectomy
To the Editor: Gurm and colleagues (April 10 issue)1 conclude that carotid stenting is not inferior to carotid endarterectomy in high-risk patients. This conclusion may be misleading. First, patients were at high risk not for stroke but for surgery. Second, in the absence of controls, the best strategy could have been medical therapy alone. A pooled analysis of the Asymptomatic Carotid Atherosclerosis Study2 and the Asymptomatic Carotid Surgery Trial3 shows that in patients with asymptomatic carotid artery stenosis (71% of patients randomly assigned to a study group in the Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy [SAPPHIRE] study) who did not undergo immediate surgery, the risks after a mean follow-up of 3.16 years were 8.6% for any stroke and 14.3% for any cause of death, which are similar to the risks observed in the stenting group of the SAPPHIRE trial after 3 years of follow-up (9.0% and 18.6%, respectively). Finally, if the subjects were at high risk for surgery, which was therefore not an appropriate option for most patients, a noninferior technique cannot be recommended either.