Science 20 June 2008: Vol. 320. no. 5883, pp. 1638 - 1643
Tuned Responses of Astrocytes and Their Influence on Hemodynamic Signals in the Visual Cortex
Astrocytes have long been thought to act as a support network for neurons, with little role in information representation or processing. We used two- photon imaging of calcium signals in the ferret visual cortex in vivo to discover that astrocytes, like neurons, respond to visual stimuli, with distinct spatial receptive fields and sharp tuning to visual stimulus features including orientation and spatial frequency. The stimulus-feature
preferences of astrocytes were exquisitely mapped across the cortical surface, in close register with neuronal maps. The spatially restricted stimulus-specific component of the intrinsic hemodynamic mapping signal was highly sensitive toì+ astrocyte activation, indicating that astrocytes have a key role in coupling neuronal organization to mapping signals critical for noninvasive brain imaging. Furthermore, blocking astrocyte glutamate transporters influenced the magnitude and duration of adjacent visually driven neuronal responses.

Nature 453, 994-995 (19 June 2008)
Paralysed patients would benefit if their thoughts could become everyday actions. The demonstration that monkeys can use brain activity for precise control of an arm-like robot is a step towards that end. Strokes, spinal-cord injuries and degenerative neuromuscular disease all
cause damage that can severely compromise the ability of patients to use their muscles. The loss of mobility and independence that results from such motor deficits takes a devastating toll on their quality oflife.

Nature 453, 1098-1101 (19 June 2008) Cortical control of a prosthetic arm for self-feeding Arm movement is well represented in populations of neurons recorded from the motor cortex. Cortical activity patterns have been used in the new field of brain–machine interfaces to show how cursors on computer displays can be move in two- and three-dimensional space. Although the ability to move a cursor can be useful in its own right, this technology could be applied to restore arm and hand function for amputees and paralysed persons. However, the use of cortical signals to control a multi-jointed prosthetic device for direct real-time interaction with the physical environment ('embodiment') has not been demonstrated. Here we describe a system that permits embodied prosthetic control; we show how monkeys (Macaca mulatta) use their motor cortical activity to control a mechanized arm replica in a self-feeding task. In addition to the three dimensions of movement, the subjects' cortical signals also proportionally controlled a gripper on the end of the arm. Owing to the physical interaction between the monkey, the robotic arm and objects in the workspace, this new task presented a higher level of difficulty than previous virtual (cursor-control) experiments. Apart from an example of simple one- dimensional contro, previous experiments have lacked physical interaction even in cases where a robotic arm or hand was included in the control loop, because the subjects did not use it to interact with physical objects—an interaction that cannot be fully simulated. This demonstration of multi-degree-of-freedom embodied prosthetic control paves the way towards the development of dexterous prosthetic devices that could ultimately achieve arm and hand function at a near-natural level.

Nature 453, 1102-1106 (19 June 2008) Neural substrates of vocalization feedback monitoring in primate auditory cortex Vocal communication involves both speaking and hearing, often taking place concurrently. Vocal production, including human speech and animal vocalization, poses a number of unique challenges for the auditory system. It is important for the auditory system to monitor external sounds continuously from the acoustic environment during speaking despite the potential for sensory masking by self-generated sounds. It is also essential for the auditory system to monitor feedback of one's own voice. This self-monitoring may play a part in distinguishing between self-generated or externally generated auditory inputs and in detecting errors in our vocal production. Previous work in humans and other animals hasdemonstrated that the auditory cortex is largely suppressed during speaking or vocalizing. Despite the importance of self-monitoring, the underlying neural mechanisms in the mammalian brain, in particular the role of vocalization-induced suppression, remain virtually unknown. Here we show that neurons in the auditory cortex of marmoset monkeys (Callithrix jacchus) are sensitive to auditory feedback during vocal production, and that changes in the feedback alter the coding properties of these neurons. Furthermore, we found that the previously described cortical suppression during vocalizationactuall increased the sensitivity of these neurons to vocal feedback. This heightenedsensitivity to vocal feedback suggests that these neurons may have animportant role in auditoryself-monitoring. The Lancet Vol: 371 Issue: 9630, June 21 - 27 2008 pp: 2059-2060 Laquinimod, a new oral drug for multiple sclerosis Relapsing-remitting multiple sclerosis is an inflammatory demyelinating disease of the CNS that is presumed to have an autoimmune cause. In most patients, the disease is chronic and progresses over decades. Early stages are heralded by relapses of neurological dysfunction within the CNS associated with transient gadolinium-enhancing lesions on T1-weighted MRI that usually leave chronic non-enhancing T1 and T2 lesions in their wake. MRI measures of disease activity have been widely adopted to screen for effectiveness of new therapies in phase I and II clinical trials, although they do not serve as the sole determinant of efficacy in phase III trials. Approved immunomodulatory drugs for relapsing-remitting multiple sclerosis are< all injectable and include interferon β-1a (which is given either subcutaneously or intramuscularly), interferon β-1b and glatiramer acetate (subcutaneous), and mitoxantrone and natalizumab (intravenous). The drugs reduce the numbers of clinical relapses and new inflammatory lesions (on
MRI), and decrease short-term disability to varying degrees. Many patients would prefer oral drugs, and drug companies are seeking to provide oral treatments for multiple sclerosis with safety and efficacy that are similar to those of available treatments.

The Lancet Vol: 371 Issue: 9630, June 21 - 27 2008
Effect of laquinimod on MRI-monitored disease activity in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double- blind, placebo-controlled phaseIIb study Summary Background
A 24-week phase II trial has shown that 0·3 mg of laquinimod given daily to patients with relapsing-remitting multiple sclerosis was well tolerated and reduced the formation of active lesions. We assessed the effect of oral daily 0·3 and 0·6 mg laquinimod on MRI-monitored disease activity in a 36-week double- blind, placebo-controlled phase IIb study.
Methods The study was done in 51 centres in nine countries. Inclusion criteria were one or more relapses in the year before entry and at least one gadolinium enhancing (GdE) lesion on screening MRI. Of 720 patients screened, 306 eligible patients were enrolled. Patients, aged 18–50 years, were randomly assigned
to placebo (n=102), laquinimod 0·3 mg a day (n=98), or 0·6 mg a day (n=106).
Brain MRI scans and clinical assessments were done at week −4, baseline, and monhly from week 12 to week 36. The primary outcome was the cumulative number of GdE lesions at weeks 24, 28, 32, and 36. The principal analysis of the primary endpoint was done on the intention-to-treat cohort. This study is registered
with ClinicalTrials.gov , number NCT00349193 .
Findings Compared with placebo, treatment with laquinimod 0·6 mg per day showed a 40·4% reduction of the baseline adjusted mean cumulative number of GdE lesions per scan on the last four scans (simple means 4·2 [SD 9·2] vs 2·6 [5·3], p=0·0048); treatment with 0·3 mg per day showed no significant effects (3·9 [5·5] vs placebo, p=0·6740). Both doses of laquinimod were well tolerated, with some transient and dose-dependent increases in liver enzymes. A case of Budd-Chiari syndrome—ie, a thrombotic venous outflow obstruction of the liver—occurred after 1 month of exposure in a patient with underlying hypercoagulability who received 0·6 mg laquinimod. Anticoagulant treatment resulted in a decline of liver enzymes to normal without any clinical signs of hepatic decompensation.Interpretation In patients with relapsing-remitting multiple sclerosis, 0·6 mg per day laquinimod significantly reduced MRI-measured disease activity and was well tolerated.

NEJM Volume 358:2688-2697  June 19, 2008  Number 25
Electrocardiographic Abnormalities and Sudden Death in Myotonic Dystrophy Type 1
ABSTRACT
Background Sudden death can occur as a consequence of cardiac-conduction abnormalities in the neuromuscular disease myotonic dystrophy type 1. The determinants of the risk of sudden death remain imprecie.Methods We assessed whether the electrocardiogram (ECG) was useful in predicting sudden death in 406 adult patients with genetically confirmed myotonic dystrophy type 1. A patient was characterized as having a severe abnormality if the ECG had at least one of the following features: rhythm other than sinus, PR interval of 240 msec or more, QRS duration of 120 msec or more, or second-degree or third-degree atrioventricular block. Results Patients with severe abnormalities according to the entry ECG were older than patients without severe abnormalities, had more severe skeletal- muscle impairment, and were more likely to have heart failure, left ventricular systolic dysfunction, or atrial tachyarrhythmia. Such patients were more likely to receive a pacemaker or an implantable cardioverter–defibrillator during
the follow-up period. During a mean follow-up period of 5.7 years, 81 patients died; there were 27 sudden deaths, 32 deaths from progressive neuromuscular respiratory failure, 5 nonsudden deaths from cardiac causes, and 17 deaths from other causes. Among the 17 patients who died suddenly in whom postcollapse rhythm was evaluated, a ventricular tachyarrhythmia was observed in 9. A severe ECG abnormality (relative risk, 3.30; 95% confidence interval [CI], 1.24 to 8.78) and a clinical diagnosis of atrial tachyarrhythmia (relative risk, 5.18; 95% CI, 2.28 to 11.77) were independent risk factors for sudden death. Conclusions Patients with adult myotonic dystrophy type 1 are at high risk for arrhythmias and sudden death. A severe abnormality on the ECG and a diagnosis of an atrial tachyarrhythmia predict sudden death.
(ClinicalTrials.gov number, NCT00622453 [ClinicalTrials.gov] .)