NEJM. Volume 358:6-7  January 3, 2008  Number 1
Seeking God in the Brain — Efforts to Localize Higher Brain Functions
Neuroscientists have long eschewed global questions about brain function, and books reviewing the current state of neuroscience usually allocate only a small section to "higher functions." But with the advent of novel imaging techniques such as positron-emission tomographic scanning and functional magnetic resonance imaging, attitudes have begun to change. It is now feasible to visualize functions of discrete brain regions while subjects are engaged in diverse activities — doing arithmetic, composing songs, writing poetry, or watching pornographic movies. Information about which parts of the brain are activated during various mental activities has supplemented and, in general, confirmed previous insights derived from observations of alterations of thinking and feeling associated with brain lesions, epilepsy, and the use of diverse drugs.

NEJM. Volume 358:18-27  January 3, 2008  Number 1
Functional Outcome after Language Mapping for Glioma Resection
Background Language sites in the cortex of the brain vary among patients. Language mapping while the patient is awake is an intraoperative technique designed to minimize language deficits associated with brain-tumor resection.
Methods To study language function after brain-tumor resection with language mapping, we examined 250 consecutive patients with gliomas. Positive language sites (i.e., language regions in the cortex of the brain, 1 cm by 1 cm, which were temporarily inactivated by means of a bipolar electrode) were identified and categorized into cortical language maps. The tumors were resected up to 1 cm from the cortical areas where intraoperative stimulation produced a disturbance in language. Our resection strategy did not require identification of the stimulation-induced language sites within the field of exposure.
Results A total of 145 of the 250 patients (58.0%) had at least one site with an intraoperative stimulation-induced speech arrest, 82 patients had anomia, and 23 patients had alexia. Overall, 3094 of 3281 cortical sites (94.3%) were not associated with stimulation-induced language deficits. A total of 159 patients (63.6%) had intact speech preoperatively. One week after surgery, baseline language function remained in 194 patients (77.6%), it worsened in 21 patients (8.4%), and 35 patients (14.0%) had new speech deficits. However, 6 months after surgery, only 4 of 243 surviving patients (1.6%) had a persistent language deficit. Cortical maps generated with intraoperative language data also showed surprising variability in language localization within the dominant hemisphere.
Conclusions Craniotomies tailored to limit cortical exposure, even without localization of positive language sites, permit most gliomas to be aggressively resected without language deficits. The composite language maps generated in our study suggest that our current models of human language organization insufficiently account for observed language function.

JAMA. 2008;299(1):39-52.
Effect of Testosterone Supplementation on Functional Mobility, Cognition, and Other Parameters
in Older Men
A Randomized Controlled Trial
Context  Serum testosterone levels decline significantly with aging. Testosterone supplementation to older men might beneficially affect the aging processes.
Objective  To investigate the effect of testosterone supplementation on functional mobility, cognitive function, bone mineral density, body composition, plasma lipids, quality of life, and safety parameters in older men with low normal testosterone levels.
Design, Setting, and Participants  Double-blind, randomized, placebo-controlled trial of 237 healthy men between the ages of 60 and 80 years with a testosterone level lower than 13.7 nmol/L conducted from January 2004 to April 2005 at a university medical center in the Netherlands.
Intervention  Participants were randomly assigned to receive 80 mg of testosterone undecenoate or a matching placebo twice daily for 6 months.
Main Outcome Measures  Functional mobility (Stanford Health Assessment Questionnaire, timed get up and go test, isometric handgrip strength, isometric leg extensor strength), cognitive function (8 different cognitive instruments), bone mineral density of the hip and lumbar spine (dual-energy x-ray absorptiometry scanning), body composition (total body dual-energy x-ray absorptiometry and abdominal ultrasound of fat mass), metabolic risk factors (fasting plasma lipids, glucose, and insulin), quality of life (Short-Form Health 36 Survey and the Questions on Life Satisfaction Modules), and safety parameters (serum prostate-specific antigen level, ultrasonographic prostate volume, International Prostate Symptom score, serum levels of creatinine, aspartate aminotransferase, alanine aminotransferase, -glutamyltransferase, hemoglobin, and hematocrit).
Results  A total of 207 men completed the study. During the study, lean body mass increased and fat mass decreased in the testosterone group compared with the placebo group but these factors were not accompanied by an increase of functional mobility or muscle strength. Cognitive function and bone mineral density did not change. Insulin sensitivity improved but high-density lipoprotein cholesterol decreased; by the end of the study, 47.8% in the testosterone group vs 35.5% in the placebo group had the metabolic syndrome (P = .07). Quality-of-life measures were no different except for one hormone-related quality-of-life measure that improved. No negative effects on prostate safety were detected.
Conclusion  Testosterone supplementation during 6 months to older men with a low normal testosterone concentration did not affect functional status or cognition but increased lean body mass and had mixed metabolic effects.

Science 4 January 2008: Vol. 319. no. 5859, p. 20 DOI: 10.1126/science.319.5859.20
GENETICS: The Elusive ALS Genes
Gene scans for amyotrophic lateral sclerosis, or Lou Gehrig's disease, have one big problem: Each one identifies a different gene.

Science 4 January 2008: Vol. 319. no. 5859, pp. 39 - 40 DOI: 10.1126/science.1153231
NEUROSCIENCE:Rules of Plasticit
Ongoing sensory experience may improve performance through a signaling mechanism that strengthens synapses beyond their initial potential.

Science 4 January 2008: Vol. 319. no. 5859, pp. 101 - 104
DOI: 10.1126/science.1143808
Ongoing in Vivo Experience Triggers Synaptic Metaplasticity in the Neocortex
In vivo experience can occlude subsequent induction of long-term potentiation and enhance long-term depression of synaptic responses. Although a reduced capacity for synaptic strengthening may function to prevent excessive excitation, such an effect paradoxically implies that continued experience or training should not improve and may even degrade neural representations. In mice, we examined the effect of ongoing whisker stimulation on synaptic strengthening at layer 4-2/3 synapses in the barrel cortex. Although N-methyl-D-aspartate receptors were required to initiate strengthening, they subsequently suppressed further potentiation at these synapses in vitro and in vivo. Despite this transition, synaptic strengthening continued with additional sensory activity but instead required the activation of metabotropic glutamate receptors, suggesting a mechanism by which continued experience can result in increasing synaptic strength over time.

Science 4 January 2008: Vol. 319. no. 5859, pp. 104 - 106 DOI: 10.1126/science.114926
Small Circuits for Large Tasks: High-Speed Decision-Making in Archerfish
The enormous progress made in functional magnetic resonance imaging technology allows us to watch our brains engage in complex cognitive and social tasks. However, our understanding of what actually is computed in the underlying cellular networks is hindered by the vast numbers of neurons involved. Here, we describe a vertebrate system, shaped for top speed, in which a complex and plastic decision is performed by surprisingly small circuitry that can be studied at cellular resolution.

Nature 451, 24-25 (3 January 2008) | doi:10.1038/451024a; Published online 2 January 2008
Neuroscience: Love hangover
In many species, males have developed strategies to safeguard their genetic material from dilution by that of competing males. Fruitflies achieve this by altering the behaviour of their partners.
Sex can be transformative. Humans often romanticize the after-effects of copulation, but for most organisms there are real biological consequences to mating that go beyond the transfer of sperm.

Nature 451, 61-64 (3 January 2008) | doi:10.1038/nature06445; Received 19 August 2007; Accepted 2 November 2007; Published online 19 December 2007
Sparse optical microstimulation in barrel cortex drives learned behaviour in freely moving mice
Electrical microstimulation can establish causal links between the activity of groups of neurons and perceptual and cognitive functions. However, the number and identities of neurons microstimulated, as well as the number of action potentials evoked, are difficult to ascertain. To address these issues we introduced the light-gated algal channel channelrhodopsin-2 (ChR2)9 specifically into a small fraction of layer 2/3 neurons of the mouse primary somatosensory cortex. ChR2 photostimulation in vivo reliably generated stimulus-locked action potentials at frequencies up to 50 Hz. Here we show that naive mice readily learned to detect brief trains of action potentials (five light pulses, 1 ms, 20 Hz). After training, mice could detect a photostimulus firing a single action potential in approximately 300 neurons. Even fewer neurons (approximately 60) were required for longer stimuli (five action potentials, 250 ms). Our results show that perceptual decisions and learning can be driven by extremely brief epochs of cortical activity in a sparse subset of supragranular cortical pyramidal neurons.

Nature 451, 65-68 (3 January 2008) | doi:10.1038/nature06447; Received 7 July 2007; Accepted 1 November 2007; Published online 19 December 2007
Behavioural report of single neuron stimulation in somatosensory cortex
Understanding how neural activity in sensory cortices relates to perception is a central theme of neuroscience. Action potentials of sensory cortical neurons can be strongly correlated to properties of sensory stimuli1 and reflect the subjective judgements of an individual about stimuli. Microstimulation experiments have established a direct link from sensory activity to behaviour, suggesting that small neuronal populations can influence sensory decisions. However, microstimulation does not allow identification and quantification
of the stimulated cellular elements. The sensory impact of individual cortical neurons therefore remains unknown. Here we show that stimulation of single neurons in somatosensory cortex affects behavioural responses in a detection task. We trained rats to respond to microstimulation of barrel cortex at low current intensities. We then initiated short trains of action potentials in single neurons by juxtacellular stimulation. Animals responded significantly more often in single-cell stimulation trials than in catch trials without stimulation. Stimulation effects varied greatly between cells, and on average in 5% of trials a response was induced. Whereas stimulation of putative excitatory neurons led to weak biases towards responding, stimulation of putative inhibitory neurons led to more variable and stronger sensory effects. Reaction times for single-cell stimulation were long and variable. Our results demonstrate that single neuron activity can cause
a change in the animal's detection behaviour, suggesting a much sparser cortical code for sensations than previously anticipated.