Voluntary and involuntary contributions to perceptually guided saccadic choices resolved with millisecond precision.

In the antisaccade task, which is considered a sensitive assay of cognitive function, a salient visual cue appears and the participant must look away from it. This requires sensory, motor-planning, and cognitive neural mechanisms, but what are their unique contributions to performance, and when exactly are they engaged? Here, by manipulating task urgency, we generate a psychophysical curve that tracks the evolution of the saccadic choice process with millisecond precision, and resolve the distinct contributions of reflexive (exogenous) and voluntary (endogenous) perceptual mechanisms to antisaccade performance over time. Both progress extremely rapidly, the former driving the eyes toward the cue early on (∼100 ms after cue onset) and the latter directing them away from the cue ∼40 ms later. The behavioral and modeling results provide a detailed, dynamical characterization of attentional and oculomotor capture that is not only qualitatively consistent across participants, but also indicative of their individual perceptual capacities.

Motor selection dynamics in FEF explain the reaction time variance of saccades to single targets.

In studies of voluntary movement, a most elemental quantity is the reaction time (RT) between the onset of a visual stimulus and a saccade toward it. However, this RT demonstrates extremely high variability which, in spite of extensive research, remains unexplained. It is well established that, when a visual target appears, oculomotor activity gradually builds up until a critical level is reached, at which point a saccade is triggered. Here, based on computational work and single-neuron recordings from monkey frontal eye field (FEF), we show that this rise-to-threshold process starts from a dynamic initial state that already contains other incipient, internally driven motor plans, which compete with the target-driven activity to varying degrees. The ensuing conflict resolution process, which manifests in subtle covariations between baseline activity, build-up rate, and threshold, consists of fundamentally deterministic interactions, and explains the observed RT distributions while invoking only a small amount of intrinsic randomness.

Noninvasive brain-computer interface enables communication after brainstem stroke.

Brain-computer interfaces (BCIs) provide communication that is independent of muscle control, and can be especially important for individuals with severe neuromuscular disease who cannot use standard communication pathways or other assistive technology. It has previously been shown that people with amyotrophic lateral sclerosis (ALS) can successfully use BCI after all other means of independent communication have failed. The BCI literature has asserted that brainstem stroke survivors can also benefit from BCI use. This study used a P300-based event-related potential spelling system. This case study demonstrates that an individual locked-in owing to brainstem stroke was able to use a noninvasive BCI to communicate volitional messages. Over a period of 13 months, the participant was able to successfully operate the system during 40 of 62 recording sessions. He was able to accurately spell words provided by the experimenter and to initiate dialogues with his family. The results broadly suggest that, regardless of the precipitating event, BCI use may be of benefit to those with locked-in syndrome.

Decoupling speed and accuracy in an urgent decision-making task reveals multiple contributions to their trade-off.

A key goal in the study of decision making is determining how neural networks involved in perception and motor planning interact to generate a given choice, but this is complicated due to the internal trade-off between speed and accuracy, which confounds their individual contributions. Urgent decisions, however, are special: they may range between random and fully informed, depending on the amount of processing time (or stimulus viewing time) available in each trial, but regardless, movement preparation always starts early on. As a consequence, under time pressure it is possible to produce a psychophysical curve that characterizes perceptual performance independently of reaction time, and this, in turn, makes it possible to pinpoint how perceptual information (which requires sensory input) modulates motor planning (which does not) to guide a choice. Here we review experiments in which, on the basis of this approach, the origin of the speed-accuracy trade-off becomes particularly transparent. Psychophysical, neurophysiological, and modeling results in the "compelled-saccade" task indicate that, during urgent decision making, perceptual information-if and whenever it becomes available-accelerates or decelerates competing motor plans that are already ongoing. This interaction affects both the reaction time and the probability of success in any given trial. In two experiments with reward asymmetries, we find that speed and accuracy can be traded in different amounts and for different reasons, depending on how the particular task contingencies affect specific neural mechanisms related to perception and motor planning. Therefore, from the vantage point of urgent decisions, the speed-accuracy trade-off is not a unique phenomenon tied to a single underlying mechanism, but rather a typical outcome of many possible combinations of internal adjustments within sensory-motor neural circuits.

Octopamine and serotonin have opposite effects on antipredator behavior in the orb-weaving spider, Larinioides cornutus.

In this study, we experimentally elevated levels of octopamine and serotonin in an orb-weaving spider, and observed the effects on the antipredator behavior thanatosis (death feigning), activity level, and running speed. We found that octopamine significantly shortened the duration of thanatosis, and its effect wore off over 24 h. We also found that serotonin significantly lengthened thanatosis, but in this case, the effect persisted for over 24 h. Neither octopamine nor serotonin affected the general activity or running speed of the spiders. To our knowledge, this is the first study to directly explore the role of biogenic amines on a specific antipredator behavior in spiders. Given that spiders must be both aggressive toward prey, yet wary of predators, we believe that this system will be an outstanding model to explore connections between behavioral ecology and neurochemistry.

Measurement of S-100B for risk classification of victims sustaining minor head injury--first pilot study in Brazil.

BACKGROUND: Release of the neuronal protein S-100B into the circulation has been suggested as a specific indication of neuronal damage. The hypothesis that S-100B is a useful and cost-effective screening tool for the management of minor head injuries was tested. METHODS: Fifty consecutive patients sustaining isolated minor head injury were prospectively evaluated in the emergency room of a Brazilian hospital by routine cranial computed tomography scan. Venous blood samples (processed to serum) were assayed for S-100B using a newly developed immunoassay test kit. Twenty-one normal healthy individuals served as negative controls. Data are presented as median and 25 to 75 percentiles. RESULTS: Patients reached the emergency room an average of 45 minutes (range: 30-62 minutes) after minor head injury. Six of 50 patients (12%) showed relevant posttraumatic lesions in the initial cranial computed tomography scan and were counted as positive. The median systemic concentration of S-100B in those patients was 0.75 microg/L (range: 0.66-6.5 microg/L), which was significantly different (U-test, P < .05) from the median concentration of 0.26 microg/L (range: 0.12-0.65 microg/L), of patients without posttraumatic lesions as counted by the cranial computed tomography. A sensitivity of 100%, a specificity of 20%, a positive predictive value of 15%, and a negative predictive value of 100% was calculated for the detection of patients suffering from intracranial lesions. CONCLUSIONS: Protein S-100B had a very high sensitivity and negative predictive value and could have an important role in ruling out the need for cranial computed tomography scan after minor head injury. This appears to be of substantial clinical relevance, particularly in countries where trauma incidence is high and medical resources are limited, such as in Brazil.

Serum S-100B protein levels during and after successful carotid artery stenting or carotid endarterectomy.

PURPOSE: To characterize the course of S-100B serum levels, a reliable marker for cellular brain damage, in patients undergoing carotid artery stenting (CAS) or endarterectomy (CEA) for carotid artery stenosis compared to control groups undergoing hemithyroidectomy (HT) or coronary angiography (CA). METHODS: Forty-six consecutive patients scheduled for revascularization of internal carotid artery (ICA) stenosis were included in the study. Fourteen patients (11 men; median age 70 years, interquartile range [IQR] 63-74) were selected for treatment with CAS, while CEA was performed in 31 patients (24 men; median age 68 years, IQR 54-78) during the same time period. Fourteen consecutive patients (8 men; median age 60 years, IQR 48-70) undergoing CA for suspected coronary heart disease and 14 patients (10 women; median age 36 years, IQR 26-54) undergoing HT for a single thyroid nodule served as controls. RESULTS: All procedures were completed successfully. During ICA clamping in CEA patients without postoperative neurological deficits, median S-100B serum levels transiently increased from 0.04 to 0.26 ng/mL (p<0.01) and returned to baseline levels after declamping. Median S-100B serum levels of CAS patients without neurological impairment remained at baseline values. No increase in S-100B levels occurred in either control group. Three CEA patients who suffered from neurological deficits (1 transient ischemic attack and 1 major stroke) showed sustained elevation of S-100B serum levels 6 hours after extubation. CONCLUSION: In patients without neurological complications, CEA but not CAS was associated with a transient increase in the S-100B serum levels. Results indicate that the increase in S-100B does not originate from extracerebral sources, but rather appears to represent an impairment of the blood-brain barrier integrity or subtle brain cell damage probably due to hypoperfusion during clamping. Sustained elevation of S-100B serum levels corresponded to the development of postoperative neurological deficits.

Measurement of S-100B for risk classification of victims sustaining minor head injury: first pilot study in Brazil

INTRODUÇÃO: A liberação da proteína neuronal S-100B na circulação tem sido sugerida como indicadora de dano neuronal. Foi testada a hipótese de que a S-100B é um marcador útil e custo efetivo para a triagem de pacientes com trauma craniano leve. MÉTODO: Cinqüenta pacientes consecutivos com trauma craniano isolado foram prospectivamente avaliados na sala de emergência de um Centro de Trauma brasileiro pela tomografia computadorizada de crânio e por amostras de sangue venoso, para a medida no soro da proteína S-100B utilizando um teste recentemente desenvolvido; 21 pessoas normais foram utilizadas como controles negativos. Os resultados são apresentados como mediana e percentis 25-75. RESULTADOS: Os pacientes chegaram ao Centro de Trauma em média 45 min (30-62) após o trauma craniano leve. Seis dos 50 pacientes tiveram lesões pós-traumáticas relevantes segundo a tomografia computadorizada de crânio inicial (12%) e foram considerados como positivos. A concentração mediana de S-100B nestes pacientes foi de 0,75µg/L (0,66-6,5), significativamente maior (U-teste, p<0,05) do que a concentração mediana de 0,26µg/L (0.12-0.65) dos pacientes sem lesões pós-traumáticas, segundo a tomografia computadorizada de crânioCCT-. O cálculo para a detecção dos pacientes com lesões intra-cranianas revelou sensibilidade de 100%, especificidade de 20%, valor preditivo positivo de 15% and valor preditivo negativo de 100%. CONCLUSÃO: A proteína S-100B tem altas taxas de sensibilidade e valor preditivo negativo, podendo ter um importante papel para descartar a necessidade de tomografia de crânio após trauma craniano leve. Acreditamos que este achado é de relevância clínica, principalmente em países onde o trauma é muito frequente e os recursos médicos limitados.

Genome analysis of multiple pathogenic isolates of Streptococcus agalactiae: implications for the microbial "pan-genome".

The development of efficient and inexpensive genome sequencing methods has revolutionized the study of human bacterial pathogens and improved vaccine design. Unfortunately, the sequence of a single genome does not reflect how genetic variability drives pathogenesis within a bacterial species and also limits genome-wide screens for vaccine candidates or for antimicrobial targets. We have generated the genomic sequence of six strains representing the five major disease-causing serotypes of Streptococcus agalactiae, the main cause of neonatal infection in humans. Analysis of these genomes and those available in databases showed that the S. agalactiae species can be described by a pan-genome consisting of a core genome shared by all isolates, accounting for approximately 80% of any single genome, plus a dispensable genome consisting of partially shared and strain-specific genes. Mathematical extrapolation of the data suggests that the gene reservoir available for inclusion in the S. agalactiae pan-genome is vast and that unique genes will continue to be identified even after sequencing hundreds of genomes.

Comparative genomics of trypanosomatid parasitic protozoa.

A comparison of gene content and genome architecture of Trypanosoma brucei, Trypanosoma cruzi, and Leishmania major, three related pathogens with different life cycles and disease pathology, revealed a conserved core proteome of about 6200 genes in large syntenic polycistronic gene clusters. Many species-specific genes, especially large surface antigen families, occur at nonsyntenic chromosome-internal and subtelomeric regions. Retroelements, structural RNAs, and gene family expansion are often associated with syntenic discontinuities that-along with gene divergence, acquisition and loss, and rearrangement within the syntenic regions-have shaped the genomes of each parasite. Contrary to recent reports, our analyses reveal no evidence that these species are descended from an ancestor that contained a photosynthetic endosymbiont.

The role of interferon-alpha in a successful murine tumor therapy.

Combination therapy using reovirus type 3 and the chemo-therapeutic agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) is sufficient to cure approximately 80% of EL-4 lymphoma tumor-bearing BD2F1 male mice. Cured animals can be challenged with the EL-4 tumor, in the absence of the therapy, to yield 100% survival, whereas those challenged with heterologous tumor produce 0% survival. These results strongly suggest that a host-immune response is responsible for the observed therapeutic effect. Reovirus, a double-stranded RNA virus, is an efficient inducer of type I interferon. In an effort to determine the role of virus in this therapy, we substituted interferon-alpha (IFN-alpha) for reovirus in the therapy. Doses of IFN-alpha from 1000-10,000 U were capable of replacing reovirus to produce cure rates similar to reovirus. Spleen cells isolated from therapy-treated animals demonstrated high levels of cytotoxicity against the natural killer cell-sensitive cell line YAC-1, but not against EL-4 tumor. In vitro stimulation of isolated spleen cells by IFN-alpha resulted in a high level of natural killer cell activity, but no cytotoxicity against the EL-4 tumor. A significant antiproliferative effect against the EL-4 tumor in cell culture was demonstrated by IFN-alpha. Finally, therapy-treated, tumor-bearing mice that were injected with anti-IFN-alpha + -beta antibodies had similar survival levels as control mice, indicating that other cytokines might also play a role in promoting tumor killing. These investigations suggest that IFN-alpha may be a mediator of antitumor activity in the reovirus therapy system.