Tiopronin monolayer-protected silver nanoparticles with different core sizes (average diameter = 2, 5, 20 nm) were prepared by using different mole ratios of silver nitrate/tiopronin. Ligands on the silver particles were partially displaced by fluorescein-labeled thiolate single-stranded oligonucleotides or their complementary unlabeled oligonucleotides through ligand exchange. The fluorophores on silver particles showed a surface-enhanced fluorescence (SEF) dependent on the size of metallic cores. The particles could be coupled through hybridizations of oligonucleotides bound on the particles. The coupled particles were aggregated due to multiple displacements of oligonucleotides on each particle, resulting in stronger SEF. The dye-labeled oligonucleotides were assembled on the silver islands on the solid substrate, and the complementary oligonucleotide-displaced particles were coupled via oligonucleotide hybridization. The couplings between particles and islands resulted in an obvious fluorescence enhancement.

We assessed the preferred directions (PDs) of supplementary eye field (SEF) neurons during conditional visuomotor learning. Monkeys learned to select one of four saccadic eye movements in response to a foveal instruction stimulus (IS). ISs were either familiar or novel. Each familiar IS reliably evoked one saccade: 7 degrees left, right, up, or down form the central fixation point. Novel ISs initially triggered virtually random responses among those four possibilities, but the monkeys ultimately learned to select the instructed saccade. As reported previously, activity rates on novel IS trials significantly changed during learning. Some of these cells (learning-dependent) also have significant modulation on familiar IS trials, but others (learning-selective) lack such activity. Of the former, the familiar IS activity can be either directionally selective or omnidirectional. For most neurons, PDs were apparent during all phases of learning, but they were rarely constant. Only infrequently did a neuron's PD for novel ISs closely match that for familiar ISs throughout the learning process. In directional learning-dependent cells, the PD usually reoriented near the end of learning to resemble that for familiar IS trials. In omnidirectional cells, initially evident PDs dissipated with learning, even as the cell became more strongly modulated. Learning-selective cells typically began with significant PDs, but became unmodulated as learning progressed. Our findings show a pervasive lability in SEF PDs that may reflect a flexible and rapid remapping between inputs and responses within the premotor cortical network.

A gain-of-function Arabidopsis mutant was identified via activation tagging genetic screening. The mutant exhibited clustered ectopic floral buds on the surface of inflorescence stems. The mutant was designated as sef for stem ectopic flowers. Our detailed studies indicate that the ectopic flower meristems are initiated from the differentiated cortex cells. Inverse PCR and sequence analysis indicated that the enhancer-containing T-DNA from the activation tagging construct, SKI015, was inserted upstream of the previously cloned WUS gene encoding a homeodomain protein. Studies from RT-PCR, RNA in situ hybridization and transgenic plant analysis further confirmed that the phenotypes of sef are caused by the overexpression of WUS. Our results suggest that overexpression of WUS could trigger the cell pluripotence and reestablish a new meristem in cortex. The type of new meristems caused by WUS overexpression was dependent upon the developmental and physiological stages of a plant. With the help of some undefined factors in the reproductive organs the new meristems differentiated into floral buds. In a vegetative growth plant, however, only the new vegetative buds can be initiated upon the overexpression of WUS. These studies provide new insights of WUS on flower development.

BACKGROUND

Schizophrenia is characterized by executive functioning deficits, presumably mediated by prefrontal cortex dysfunction. For example, schizophrenia participants show performance deficits on ocular motor delayed response (ODR) tasks, which require both inhibition and spatial working memory for correct performance.

METHODS

The present functional magnetic resonance imaging (fMRI) study compared neural activity of 14 schizophrenia and 14 normal participants while they performed ODR tasks.

RESULTS

Schizophrenia participants generated: 1) more trials with anticipatory saccades (saccades made during the delay period), 2) memory saccades with longer latencies, and 3) memory saccades of decreased accuracy. Increased blood oxygenation level-dependent (BOLD) signal changes were observed in both groups in ocular motor circuitry (e.g., supplementary eye fields [SEF], lateral frontal eye fields [FEF], inferior parietal lobule [IPL], cuneus, and precuneus). The normal, but not the schizophrenia, group demonstrated BOLD signal changes in dorsolateral prefrontal regions (right Brodmann area [BA] 9 and bilateral BA 10), medial FEF, insula, thalamus, and basal ganglia. Correlations between percentage of anticipatory saccade trials and BOLD signal changes were more similar between groups for subcortical regions and less similar for cortical regions.

CONCLUSIONS

These results suggest that executive functioning deficits in schizophrenia may be associated with dysfunction of the basal ganglia-thalamocortical circuitry, evidenced by decreased prefrontal cortex, basal ganglia, and thalamus activity in the schizophrenia group during ODR task performance.

Growth factor signaling by receptor tyrosine kinases regulates several cell fates, such as proliferation and differentiation. Sef was genetically identified as a negative regulator of fibroblast growth factor (FGF) signaling. Using bioinformatic methods and rapid amplification of cDNA ends-PCR, we isolated both the mouse and the human Sef genes, which encoded the Sef protein and Sef-S isoform that was generated through alternative splicing. We provide evidence that the Sef gene products were located mainly on the cell membrane. Co-immunoprecipitation and immunostaining experiments indicate that hSef interacts with FGFR1 and FGFR2 but not FGFR3. Our results demonstrated that stably expressed hSef strongly inhibits FGF2- or nerve growth factor-induced PC-12 cell differentiation. The intracellular domain of hSef is necessary for the inhibitory effect on FGF2-induced PC-12 cell differentiation. Furthermore, our data suggested Sef exerted the negative effect on FGF2-induced PC-12 cell differentiation through the prevention of Ras-mitogen-activated protein kinase signaling, possibly functioning upstream of the Ras molecule. These findings suggest that Sef may play an important role in the regulation of PC-12 cell differentiation.

Native grasses of semi-arid rangelands of the southwestern USA are more extensively colonized by dark septate endophytes (DSE) than by traditional mycorrhizal fungi. Roots of dominant grasses ( Bouteloua sp.) native to arid southwestern USA rangelands were prepared and stained using stains specific for fungi (trypan blue) and for lipids (sudan IV). This revealed extensive internal colonization of physiologically active roots by atypical fungal structures that appear to function as protoplasts, without a distinguishable wall or with very thin hyaline walls that escape detection by methods staining specifically for fungal chitin. These structures were presumed to be active fungal stages that progressed to form stained or melanized septate hyphae and microsclerotia characteristic of DSE fungi within dormant roots. The most conspicuous characteristic of these fungi were the unique associations that formed within sieve elements and the accumulation of massive quantities of lipids. This interface suggests a biologically significant location for carbon transfer between the plant and fungus. The continuous intimate association with all sieve elements, cortical and epidermal cells as well as external extension on the root surface and into the soil indicates that they are systemic and considerably more prevalent than previously thought. A fungal network associated with a mucilaginous complex observed on the root surface and its potential role in root function in dry soil is discussed. It is suggested that those fungi that non-pathogenically and totally colonize plant cells be classed as systemic endophytic fungi (SEF). This would refine the broad designation of DSE fungi. The potential mutualistic benefit of SEF for native plants in arid ecosystems based on the extent of lipid accumulation and its apparent distribution is discussed.

Four strains of diarrheagenic Escherichia coli originally isolated from distinct geographic regions were found to produce unusual thin aggregative fimbriae requiring depolymerization in formic acid prior to analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Immunoelectron microscopy of native fimbriae and Western blot (immunoblot) analysis of the corresponding 18-kDa fimbrins showed that these E. coli fimbriae were serologically cross-reactive with SEF 17 (Salmonella enteritidis fimbriae with a fimbrin molecular mass of 17 kDa). The E. coli and S. enteritidis fimbrins had similar total amino acid compositions and highly conserved N-terminal amino acid sequences. These results indicate that E. coli and S. enteritidis produce biochemically related, aggregative fimbriae which constitute a new type of intergenerically distributed fimbriae for which we propose the descriptive name GVVPQ fimbriae on the basis of the conserved N-terminal amino acid sequence.

In order to see clearly when a target is moving slowly, primates with high acuity foveae use smooth-pursuit and vergence eye movements. The former rotates both eyes in the same direction to track target motion in frontal planes, while the latter rotates left and right eyes in opposite directions to track target motion in depth. Together, these two systems pursue targets precisely and maintain their images on the foveae of both eyes. During head movements, both systems must interact with the vestibular system to minimize slip of the retinal images. The primate frontal cortex contains two pursuit-related areas; the caudal part of the frontal eye fields (FEF) and supplementary eye fields (SEF). Evoked potential studies have demonstrated vestibular projections to both areas and pursuit neurons in both areas respond to vestibular stimulation. The majority of FEF pursuit neurons code parameters of pursuit such as pursuit and vergence eye velocity, gaze velocity, and retinal image motion for target velocity in frontal and depth planes. Moreover, vestibular inputs contribute to the predictive pursuit responses of FEF neurons. In contrast, the majority of SEF pursuit neurons do not code pursuit metrics and many SEF neurons are reported to be active in more complex tasks. These results suggest that FEF- and SEF-pursuit neurons are involved in different aspects of vestibular-pursuit interactions and that eye velocity coding of SEF pursuit neurons is specialized for the task condition.

A pseudo-strain energy function (pseudo-SEF) describing the biomechanical properties of large conduit arteries under the influence of vascular smooth muscle (VSM) tone is proposed. In contrast to previous models that include the effects of smooth muscle contraction through generation of an active stress, in this study we consider the vascular muscle as a structural element whose contribution to load bearing is modulated by the contraction. This novel pseudo-SEF models not only arterial mechanics at maximal VSM contraction but also the myogenic contraction of the VSM in response to local increases in stretch. The proposed pseudo-SEF was verified with experimentally obtained pressure-radius curves and zero-stress state configurations from rat carotid arteries displaying distinct differences in VSM tone: arteries from normotensive rats displaying minimal VSM tone and arteries from hypertensive rats exhibiting significant VSM tone. The pressure-radius curves were measured in three different VSM states: fully relaxed, maximally contracted, and normal VSM tone. The model fitted the experimental data very well (r2>> 0.99) in both the normo- and hypertensive groups for all three states of VSM activation. The pseudo-SEF was used to illustrate the localized reduction of circumferential stress in the arterial wall due to normal VSM tone, suggesting that the proposed pseudo-SEF can be of general utility for describing stress distribution not only under passive VSM conditions, as most SEFs proposed so far, but also under physiological and pathological conditions with varying levels of VSM tone.

Multiple fibroblast growth factor (FGF) axis alterations are known to occur in prostate cancer. Here we simultaneously profiled key components of this axis to determine their relevance in disease progression. An optimized immunohistochemistry protocol was used in expression analysis of FGF2, FGF8, FGFR1, FGFR4, and Sef (similar expression to FGF) in a single TMA of prostate cancer. FGF ligands and receptors were overexpressed in cancers compared to benign samples (p < 0.0001), while Sef expression was reduced (p < 0.0001). There was a positive association between higher grades and increased FGFR4 (p = 0.02), FGF2, and FGF8 (p = 0.002 and p < 0.0001). Sef expression was progressively lower with increasing grade (p = 0.005). Clinical stage was positively associated with FGF2, FGF8, and FGFR4 expression (p = 0.005, 0.03, and 0.012) but not with FGFR1 or Sef expression. Only reduced Sef was associated with bone metastasis (p = 0.02) and was also predictive of subsequent metastasis in initially localized tumours (p = 0.004). Down-regulation of Sef and increased FGFR4 were also the only independent variables associated with disease-specific survival (HR 1.73, p = 0.04 and HR 0.56, p = 0.01). In in vitro studies, silencing Sef enhanced the cell response to FGFs (p < 0.001) and substantially mitigated the effectiveness of an FGFR1 inhibitor. Conversely, increased Sef blocked the response to FGFs and had a comparable suppressive effect to the inhibitor. This study demonstrates that increased FGFR4 and reduced Sef may be critical FGF alterations associated with prostate cancer progression. Sef may also have a role in the tumour response to FGFR inhibition and warrants further investigation in this context.

Salmonella enteritidis 27655-3b and a few diarrheagenic Escherichia coli strains produce morphologically and antigenically related, thin, aggregative fimbriae, collectively named GVVPQ fimbriae (S. K. Collinson, L. Emödy, T. J. Trust, and W. W. Kay, J. Bacteriol. 174:4490-4495, 1992). To determine whether GVVPQ fimbriae are common to Salmonella spp. and other enteropathogenic members of the family Enterobacteriaceae, 113 isolates were phenotypically screened for Congo red binding and aggregative colony morphology. Presumptive positive and representative negative strains were examined by Western blotting (immunoblotting) by using antiserum to SEF 17, the native GVVPQ fimbria of S. enteritidis. Only four S. enteritidis strains and six E. coli isolates possessed substantial amounts of GVVPQ fimbriae after 24 h of incubation on T medium. Following 5 days of incubation, 56 of 93 Salmonella isolates (60%) and 1 of 7 additional E. coli clinical isolates possessed detectable levels of GVVPQ fimbriae. Since variable expression of GVVPQ fimbriae was observed among Salmonella isolates and some E. coli strains produced scant amounts, as revealed by immunoelectron microscopy, the ability to produce these fimbriae was evaluated by genotypic screening. The structural gene for the SEF 17 fimbrin, agfA, was amplified by the polymerase chain reaction, cloned, and sequenced to provide a characterized DNA probe. An agfA DNA fragment hybridized strongly to 603 of 604 (99.8%) Salmonella isolates but very weakly to 31 of 266 other members of the family Enterobacteriaceae including 26 of 137 E. coli strains, 3 of 14 Citrobacter spp., and single isolates of Shigella sonnei and Enterobacter cloacae. The agfA DNA probe proved to be a valuable diagnostic tool for Salmonella isolates arrayed on hydrophobic grid membrane filters. Unique agfA sequences were targeted in the development of a polymerase chain reaction assay specific for Salmonella spp.

The precise function of the supplementary eye field (SEF) is poorly understood. Although electrophysiological and functional imaging studies are important for demonstrating when SEF neurones are active, lesion studies are critical to establish the functions for which the SEF is essential. Here we report a series of investigations performed on an extremely rare individual with a highly focal lesion of the medial frontal cortex. High-resolution structural imaging demonstrated that his lesion was confined to the region of the left paracentral sulcus, the anatomical locus of the SEF. Behavioural testing revealed that the patient was significantly impaired when required to switch between anti- and pro-saccades, when there were conflicting rules governing stimulus-response mappings for saccades. Similarly, the results of an arbitrary stimulus-response associative learning task demonstrated that he was impaired when required to select the appropriate saccade from conflicting eye movement responses, but not for limb movements on an analogous manual task. When making memory-guided saccadic sequences, the patient demonstrated hypometria, like patients with Parkinson's disease, but had no significant difficulties in reproducing the order of saccades correctly on a task that emphasized accuracy with a wide temporal segregation between responses. These findings are consistent with the hypothesis that the SEF plays a key role in implementing control when there is conflict between several, ongoing competing saccadic responses, but not when eye movements need to be made accurately in sequence.

Cerebral deficit has been implicated in the genesis of strabismus and in the mechanisms adopted to compensate for the visual disorder. Voxel-based morphometry (VBM) was applied to magnetic resonance images of strabismic adults to detect any abnormal brain anatomy, which could not be easily identified by simple inspection. The gray matter volume in strabismic adults was smaller than that in normal subjects at the areas consistent with the occipital eye field (OEF) and parietal eye field (PEF). However, greater gray matter volume was found in strabismic adults relative to normal controls at the areas consistent with the frontal eye field (FEF), the supplementary eye field (SEF), the prefrontal cortex (PFC), and subcortical regions such as the thalamus and the basal ganglia. These opposite gray matter changes in the visual and the oculomotor processing areas are compatible with a hypothesis of plasticity in the oculomotor regions to compensate for the cortical deficits in the visual processing areas.

1. We quantitatively compared the effects of eye position within the orbit on saccadic eye movements electrically elicited from two oculomotor areas of the macaque monkey's frontal lobe cortex: the frontal eye field (FEF) and the supplementary eye field (SEF). 2. The effect of eye position on electrically elicited saccades was studied by delivering 70-ms trains of intracortical microstimulation while the monkeys fixated a spot of light. Tests of different fixation points located across a rectangular array were randomly intermixed. Complete experiments were carried out on 38 sites in three FEFs of two monkeys and 59 sites from three SEFs of the same two monkeys. Stimulation currents for the array experiments were usually 10-20 microA above the site threshold; the average current used was 36 microA for FEF and 49 microA for SEF. 3. The magnitude of effect of the initial eye position on the elicited saccade's dimensions was quantified at each site by computing the linear regression of saccadic eye movement displacement on the eye position within the orbit when stimulation was applied. This computation was done separately for the horizontal and vertical axes. We call the resulting pair of regression coefficients "orbital perturbation indexes." Indexes of 0.0 represent elicited saccades that do not change their trajectory with different initial eye positions (constant-vector saccades), whereas indexes of -1.0 represent elicited saccades that end at the same orbital position regardless of initial eye position (goal-directed saccades). 4. The effect of eye position varied across sites. In both FEF and SEF, the orbital perturbation indexes were distributed between approximately 0.0 and -0.5, with the horizontal and vertical indexes highly correlated across sites. 5. The average orbital perturbation indexes were small for both eye fields and were not significantly different. The mean horizontal indexes were -0.13 and -0.16 for SEF and FEF, respectively. The mean vertical indexes were -0.16 and -0.13. Neither SEF versus FEF difference was statistically significant. 6. In both SEF and FEF, sites yielding larger-amplitude saccades generally had larger orbital effects than sites yielding smaller saccades. This relationship accounted for the majority of the variability of the orbital perturbation indexes across sites in both SEF and FEF. 7. These results indicate that SEF and FEF are not distinguished from each other by the orbital dependence of their electrically elicited saccades. Thus they do not confirm the previously hypothesized dichotomy that FEF codes constant-vector saccades and SEF codes goal-directed saccades.(ABSTRACT TRUNCATED AT 400 WORDS)

Extended maintenance delays decrease the accuracy of information stored in spatial working memory. In order to elucidate the network underlying sustained spatial working memory, 16 subjects were scanned using fast event-related fMRI as they performed an oculomotor delayed response task containing trials with "short" (2.5 s) or "long" (10 s) delay periods. Multiple cortical and subcortical regions were common to both delay trial types indicating core task regions. Three patterns of activity were found in a subset of core regions that reflect underlying processes: maintenance-related (e.g., left FEF, right supramarginal gyrus (SMG)), response planning-related (e.g., right FEF, SEF), and motor response-related (e.g., lateral cerebellum (declive)) activation. Several regions were more active during long than short delay trials, including multiple sites in DLPFC (BA 9, 46), indicating a circuitry dynamically recruited to support sustained working memory. Our results suggest that specialized brain processes support extended periods of working memory.

Salmonella enterica serotype Enteritidis (S. enteritidis) is a major food-borne pathogen, and its incidence among all Salmonella serotypes has increased dramatically in the last two decades. To study the virulence characteristics of clinical isolates of S. enteritidis, we determined the 50% lethal doses (LD(50)) in mice of isolates of two major phage types (4 and 8). Isolates of both phage types showed a wide range of LD(50) after oral inoculation, varying from under 10(2) organisms to over 10(8) organisms. No significant difference in LD(50) was observed between the phage types. These observations indicated that clinical isolates of S. enteritidis are highly heterogeneous in their ability to cause death in mice. We compared the LD(50)s of these isolates to the results observed from in vitro pathogenicity assays. We also analyzed these isolates for recognized Salmonella virulence loci (spv, sodCI, sopE, and sef). The in vitro phenotypes of the isolates showed no obvious correlation with their LD(50) in any given assay, and the virulence genes tested were present in all isolates. However, the isolate with the lowest LD(50) (isolate 97A 2472) was resistant to acidified sodium nitrite (ASN). Moreover, the most acid-susceptible, macrophage-susceptible, and ASN-susceptible isolates were attenuated for virulence in mice. These results, based on extensive analysis of clinical isolates of S. enteritidis, demonstrate the complex nature of Salmonella pathogenesis in mice. Our results also indicate the limitation of in vitro assays in predicting in vivo virulence.

The outcomes of many decisions are uncertain and therefore need to be evaluated. We studied this evaluation process by recording neuronal activity in the supplementary eye field (SEF) during an oculomotor gambling task. While the monkeys awaited the outcome, SEF neurons represented attributes of the chosen option, namely, its expected value and the uncertainty of this value signal. After the gamble result was revealed, a number of neurons reflected the actual reward outcome. Other neurons evaluated the outcome by encoding the difference between the reward expectation represented during the delay period and the actual reward amount (i.e., the reward prediction error). Thus, SEF encodes not only reward prediction error but also all the components necessary for its computation: the expected and the actual outcome. This suggests that SEF might actively evaluate value-based decisions in the oculomotor domain, independent of other brain regions.

To investigate how single neurons in the supplementary eye field (SEF) participate in sequential performance of multiple saccades, we analyzed presaccadic activity while monkeys were performing three saccades in six different orders from memory. The saccades in each sequence were separated by a fixation period and initiated from the same fixation point with intervening return saccades. We found that the majority of the presaccadic activity of the SEF neurons differed significantly depending on the numerical position of saccades in each sequence (rank order). This rank-order selectivity was found in parallel with the selectivity for the sequence of three saccades. Our data suggest a role for SEF neurons in the coding of temporally ordered saccadic eye movements.

Salmonella enteritidis was previously shown to produce fimbriae composed of 14,000-molecular-weight (Mr) fimbrin monomers (J. Feutrier, W. W. Kay, and T. J. Trust, J. Bacteriol. 168:221-227, 1986). Another distinct fimbrial structure, comprising 21,000-Mr fimbrin monomers, has now been identified. These fimbriae are simply designated as SEF 14 and SEF 21, respectively (for S. enteritidis fimbriae and the Mr [in thousands] of the fimbrin monomer). A simple method for the purification of both structures was developed by using the different biochemical properties of these fimbriae. SEF 21 remained intact after being boiled in sodium dodecyl sulfate but readily dissociated into subunits of 21,000 Mr at pH 2.2. The overall amino acid composition and the N-terminal amino acid sequence of the SEF 21 fimbrin were distinct from those of SEF 14 but were virtually identical to the predicted sequence for type 1 fimbrin of Salmonella typhimurium. Immunoelectron microscopy of S. enteritidis clearly revealed fimbrial structures that reacted with immune serum specific to the 21,000-Mr fimbrin. Immune sera raised against this subunit were cross-reactive with type 1 fimbrins found in whole-cell lysates of S. typhimurium, Salmonella illinois, and Salmonella cubana. However, there was no cross-reaction with Escherichia coli type 1 fimbriae or with other fimbrins produced by S. enteritidis. Under certain growth conditions, S. enteritidis produced both SEF 14 and SEF 21. However, when S. enteritidis was grown at 30 degrees C or lower, only the 21,000-Mr SEF 21 fimbrin could be detected. There was a direct correlation between mannose-sensitive hemagglutination and the presence of SEF 21.

1. Intracortical microstimulation was used to localize and define the smooth and saccadic eye movement subregions of the frontal eye field (FEF) and the supplementary eye field (SEF) in nine hemispheres of six Cebus apella monkeys and to map the hand/arm areas in the dorsal premotor area and other adjacent areas in five hemispheres of three C. apella monkeys. Monkeys were anesthetized during experiments with Telazol, a dissociative agent that has no significant effect on microstimulation-induced eye movement parameters (current threshold, velocity, and duration). The functional subregions were defined with the use of low threshold current (< or = 50 microA). Electrically elicited eye movements were videotaped and quantified. The two types of eye movements were clearly distinguished by their significantly different duration and velocity (P < 0.0001) and their different responses to long stimulus trains. 2. The saccadic subregion of the FEF in Cebus monkeys is in the same location as in macaque monkeys (Walker's areas 8a and 45). Most of the functional and anatomic characteristics of the saccadic subregion of Cebus are the same as those reported in the saccadic FEF subregion of macaque monkeys. 3. A subregion in which only smooth eye movements were evoked was found in the posterior shoulder of the superior arcuate sulcus near its medial tip. A band of inexcitable cortex separated the SEF and this smooth eye movement subregion of the FEF. This supports the proposal that the smooth eye movement subregion is independent of the SEF but is analogous to the saccadic subregion of the FEF. The existence of two subregions of the FEF was further confirmed by single-unit recording results. It is proposed that the smooth eye movement subregion in Cebus monkeys may be comparable with the one described in macaque monkeys. 4. Both saccadic and smooth eye movements were also reliably evoked in the SEF in each hemisphere studied. This result strongly indicates that the SEF is concerned with not only saccadic eye movements, as previously reported, but also with smooth (pursuit) eye movements.

Recently, we examined the neuronal substrate of predictive pursuit during memory-based smooth pursuit and found that supplementary eye fields (SEFs) contain signals coding assessment and memory of visual motion direction, decision not-to-pursue ("no-go"), and preparation for pursuit. To determine whether these signals were unique to the SEF, we examined the discharge of 185 task-related neurons in the caudal frontal eye fields (FEFs) in 2 macaques. Visual motion memory and no-go signals were also present in the caudal FEF but compared with those in the SEF, the percentage of neurons coding these signals was significantly lower. In particular, unlike SEF neurons, directional visual motion responses of caudal FEF neurons decayed exponentially. In contrast, the percentage of neurons coding directional pursuit eye movements was significantly higher in the caudal FEF than in the SEF. Unlike SEF inactivation, muscimol injection into the caudal FEF did not induce direction errors or no-go errors but decreased eye velocity during pursuit causing an inability to compensate for the response delays during sinusoidal pursuit. These results indicate significant differences between the 2 regions in the signals represented and in the effects of chemical inactivation suggesting that the caudal FEF is primarily involved in generating motor commands for smooth-pursuit eye movements.

The antisaccade task is a classic task of oculomotor control that requires participants to inhibit a saccade to a target and instead make a voluntary saccade to the mirror opposite location. By comparison, the prosaccade task requires participants to make a visually-guided saccade to the target. These tasks have been studied extensively using behavioral oculomotor, electrophysiological, and neuroimaging in both non-human primates and humans. In humans, the antisaccade task is under active investigation as a potential endophenotype or biomarker for multiple psychiatric and neurological disorders. A large and growing body of literature has used functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) to study the neural correlates of the antisaccade and prosaccade tasks. We present a quantitative meta-analysis of all published voxel-wise fMRI and PET studies (18) of the antisaccade task and show that consistent activation for antisaccades and prosaccades is obtained in a fronto-subcortical-parietal network encompassing frontal and supplementary eye fields (SEFs), thalamus, striatum, and intraparietal cortex. This network is strongly linked to oculomotor control and was activated to a greater extent for antisaccade than prosaccade trials. Antisaccade but not prosaccade trials additionally activated dorsolateral and ventrolateral prefrontal cortices. We also found that a number of additional regions not classically linked to oculomotor control were activated to a greater extent for antisaccade vs. prosaccade trials; these regions are often reported in antisaccade studies but rarely commented upon. While the number of studies eligible to be included in this meta-analysis was small, the results of this systematic review reveal that antisaccade and prosaccade trials consistently activate a distributed network of regions both within and outside the classic definition of the oculomotor network.

OBJECTIVE

Endoscopic retrograde cholangiopancreatography (ERCP) is a complex procedure, which requires appropriate sedation. The aim of this prospective, randomized, double-blind study was to compare the quality and characteristics of sedation with midazolam or propofol in patients undergoing ERCP.

METHODS

A total of 32 patients undergoing ERCP were randomly allocated for sedation with propofol (n = 15) or midazolam (n = 17). Blood pressure, heart rate, and O2 saturation were monitored. Sedation was maintained at near constant levels by use of the spectral edge frequency (SEF) technique, an EEG-based method for measuring the depth of sedation. Clinical variables, patient cooperation, time to recovery, and amnesia served as outcome variables.

RESULTS

There was no significant difference between the two study groups in patient characteristics. The "target SEF" was 13.6 +/- 0.7 Hz for the propofol group and 14.8 +/- 1.1 Hz for the midazolam group (n.s.). The only clinical parameter with a significant difference between the groups was the percent of time in which the heart rate deviated more than 20% from baseline for at least 2 minutes, i.e. 14.6 +/- 2.0 % for propofol and 48.2 +/- 38.0% for midazolam (P<0.01). Patient cooperation was better in the propofol group than in the midazolam group (full cooperation, 13/15 vs. 1/17, respectively; P<0.001). Patient recovery was significantly quicker in the propofol group (P<0.001). The degree of amnesia was similar in both groups; no patient in either group remembered details of the procedure.

CONCLUSIONS

ERCP is better tolerated by patients sedated with propofol compared with midazolam, with a shorter recovery time and lesser hemodynamic side effects. Propofol should be considered to be the sedative drug of choice for ERCP.

Humans are metacognitive: they monitor and control their cognition. Our hypothesis was that neuronal correlates of metacognition reside in the same brain areas responsible for cognition, including frontal cortex. Recent work demonstrated that nonhuman primates are capable of metacognition, so we recorded from single neurons in the frontal eye field, dorsolateral prefrontal cortex, and supplementary eye field of monkeys (Macaca mulatta) that performed a metacognitive visual-oculomotor task. The animals made a decision and reported it with a saccade, but received no immediate reward or feedback. Instead, they had to monitor their decision and bet whether it was correct. Activity was correlated with decisions and bets in all three brain areas, but putative metacognitive activity that linked decisions to appropriate bets occurred exclusively in the SEF. Our results offer a survey of neuronal correlates of metacognition and implicate the SEF in linking cognitive functions over short periods of time.