Distinct Stages of Moment-to-Moment Processing in the Cinguloopercular and Frontoparietal Networks.

Control of goal-directed tasks is putatively carried out via the cinguloopercular (CO) and frontoparietal (FP) systems. However, it remains unclear whether these systems show dissociable moment-to-moment processing during distinct stages of a trial. Here, we characterize dynamics in the CO and FP networks in a meta-analysis of 5 decision-making tasks using fMRI, with a specialized "slow reveal" paradigm which allows us to measure the temporal characteristics of trial responses. We find that activations in left FP, right FP, and CO systems form separate clusters, pointing to distinct roles in decision-making. Left FP shows early "accumulator-like" responses, suggesting a role in pre-decision processing. CO has a late onset and transient response linked to the decision event, suggesting a role in performance reporting. The majority of right FP regions show late onsets with prolonged responses, suggesting a role in post-recognition processing. These findings expand upon past models, arguing that the CO and FP systems relate to distinct stages of processing within a trial. Furthermore, the findings provide evidence for a heterogeneous profile in the FP network, with left and right FP taking on specialized roles. This evidence informs our understanding of how distinct control networks may coordinate moment-to-moment components of complex actions.

Encoding processes during retrieval tasks.

Episodic memory encoding is pervasive across many kinds of task and often arises as a secondary processing effect in tasks that do not require intentional memorization. To illustrate the pervasive nature of information processing that leads to episodic encoding, a form of incidental encoding was explored based on the "Testing" phenomenon: The incidental-encoding task was an episodic memory retrieval task. Behavioral data showed that performing a memory retrieval task was as effective as intentional instructions at promoting episodic encoding. During fMRI imaging, subjects viewed old and new words and indicated whether they remembered them. Relevant to encoding, the fate of the new words was examined using a second, surprise test of recognition after the imaging session. fMRI analysis of those new words that were later remembered revealed greater activity in left frontal regions than those that were later forgotten - the same pattern of results as previously observed for traditional incidental and intentional episodic encoding tasks. This finding may offer a partial explanation for why repeated testing improves memory performance. Furthermore, the observation of correlates of episodic memory encoding during retrieval tasks challenges some interpretations that arise from direct comparisons between "encoding tasks" and "retrieval tasks" in imaging data. Encoding processes and their neural correlates may arise in many tasks, even those nominally labeled as retrieval tasks by the experimenter.

Human fetal and neonatal movement patterns: Gender differences and fetal-to-neonatal continuity.

Longitudinal quantification of leg movements per minute for human subjects during both fetal and neonatal periods was accomplished from videotapings conducted antenatally (ultrasonography 30, 34, and 37 weeks gestational age) and postnatally (birth and 6 weeks of age). Fetal/neonatal subjects displayed decreasing numbers of leg movements per minute during antenatal development (30 to 37 weeks), followed by increasing numbers of leg movements per minute during postnatal development (birth to 6 weeks of age). Male subjects displayed greater numbers of leg movements per minute than female subjects during both antenatal and postnatal development. Fetal-to-neonatal continuity for numbers of leg movements per minute was found for comparisons between fetal (37 weeks gestational age) and neonatal (during sleep states at birth) measures, and females displayed a stronger and different movement continuity pattern than males. These results indicate a differential time course for neurobehavioral development of male and female fetuses/neonates, and the findings have implications for the clinical assessment of fetal neurobehavioral development and well-being.

Memory's echo: vivid remembering reactivates sensory-specific cortex.

A fundamental question in human memory is how the brain represents sensory-specific information during the process of retrieval. One hypothesis is that regions of sensory cortex are reactivated during retrieval of sensory-specific information (1). Here we report findings from a study in which subjects learned a set of picture and sound items and were then given a recall test during which they vividly remembered the items while imaged by using event-related functional MRI. Regions of visual and auditory cortex were activated differentially during retrieval of pictures and sounds, respectively. Furthermore, the regions activated during the recall test comprised a subset of those activated during a separate perception task in which subjects actually viewed pictures and heard sounds. Regions activated during the recall test were found to be represented more in late than in early visual and auditory cortex. Therefore, results indicate that retrieval of vivid visual and auditory information can be associated with a reactivation of some of the same sensory regions that were activated during perception of those items.

Neural correlates of episodic retrieval success.

Episodic memory retrieval involves multiple component processes, including those that occur when information is correctly remembered (retrieval success). The present study employed rapid-presentation event-related functional MRI that allowed different trial types with short intertrial intervals to be sorted such that the hemodynamic response associated with retrieval success could be extracted. Specifically, in an old/new episodic recognition task, hit trials (correctly recognized old items) and correct rejection trials (correctly rejected new items) were directly compared. The comparison revealed a mostly left-lateralized set of brain regions. Differential activation was most robust in left lateral parietal cortex and medial parietal cortex. Additional regions of differential activation included left anterior prefrontal cortex at or near Brodmann area 10, anterior insula, thalamus, anterior cingulate cortex, frontal cortex along inferior frontal gyrus, premotor cortex, and presupplementary motor area. These results suggest that left frontal and parietal regions modulate activity based on the successful retrieval of information from episodic memory. We discuss these findings in the context of several recent investigations that provide converging results as well as prior studies that have failed to detect these changes.

Cognitive neuroscience of episodic memory encoding.

This paper presents a cognitive neuroscientific perspective on how human episodic memories are formed. Convergent evidence from multiple brain imaging studies using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) suggests a role for frontal cortex in episodic memory encoding. Activity levels within frontal cortex can predict episodic memory encoding across a wide range of behavioral manipulations known to influence memory performance, such as those present during levels of processing and divided attention manipulations. Activity levels within specific frontal and medial temporal regions can even predict, on an item by item basis, whether an episodic memory is likely to form. Furthermore, separate frontal regions appear to participate in supplying code-specific information, including distinct regions which process semantic attributes of verbal information as well as right-lateralized regions which process nonverbal information. We hypothesize that activity within these multiple frontal regions provides a functional influence (input) to medical temporal regions that bind the information together into a lasting episodic memory trace.

Attention and the detectability of weak taste stimuli.

Subjects detected weak solutions of sucrose or citric acid under conditions in which attention was directed toward one of the tastants or the other. Detection thresholds were measured using an adaptive, forced-choice procedure, with a three-down one-up rule, which computer simulations suggest should be more reliable than the popular two-down one-up rule. The thresholds were modestly but systematically lower for attended tastants than for unattended ones. Similar results have been reported in other sense modalities, including vision (greater sensitivity to stimuli presented to attended versus unattended spatial locations) and hearing (greater sensitivity to stimuli presented at attended versus unattended sound frequencies). Taken together, the findings are consistent with a general hypothesis regarding attention in sensory systems: gains or losses in detectability occur when a central attentional mechanism (or, conceivably, a preattentive mechanism) selectively and preferentially monitors signals arising from particular subsets of peripheral neural inputs.

Focused attention and the detectability of weak gustatory stimuli. Empirical measurement and computer simulations.

Attentional processes can modulate the detectability of weak stimuli; for example, the detectability of visual or auditory signals can depend on whether attention is allocated to the appropriate spatial location (vision) or acoustic frequency (hearing). Earlier attempts in the first author's laboratory to find analogous effects of focused attention on the detectability of taste stimuli were equivocal, in part it seems because human gustatory sensitivity can fluctuate substantially over time, a serious problem when using procedures that track sensitivity (d') to a constant stimulus concentration. To circumvent this problem, we adopted an adaptive psychophysical procedure, the transformed up-down method, using a 3-down/1-up rule to determine how the threshold to detect weak concentrations of sucrose and citric acid depended on whether the stimulus presented in a given two-alternative, forced-choice trial was expected or unexpected. The results showed threshold sensitivity to be slightly but consistently poorer when the test stimulus was unexpected (e.g., sucrose presented when citric acid was expected) than it was when the test stimulus was expected (e.g., sucrose presented when sucrose was expected). In this attentional paradigm, the unexpected stimulus must perforce be presented on only a small fraction of the trials. In selecting a procedure, we chose a 3-down/1-up adaptive rule rather than the more popular 2-down/1-up rule, a choice that turned out to be in line with results of Monte Carlo computer simulations. These simulations suggest that across a wide range of conditions (starting stimulus concentrations, step sizes), the variability in threshold measurements can be smaller with a 3-down/1-up rule than with a 2-down/1-up rule, even when the total number of trials is the same and not very great.

Inhibitors of sterol synthesis. Characterization of beta,gamma-unsaturated analogs of 3 beta-hydroxy-5 alpha-cholest-8(14)-en-15-one and their effects on 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in CHO-K1 cells.

Treatment of 3 beta-hydroxy-5 alpha-cholest-8(14)-en-15-one (1), a potent regulator of cholesterol metabolism, with perchloric acid in methanol resulted in its partial isomerization to the beta,gamma-unsaturated 15-ketosterols, 3 beta-hydroxy-5 alpha,14 beta-cholest-8-en-15-one (2) and 3 beta-hydroxy-5 alpha,14 beta-cholest-7-en-15-one (3), which were easily separated from 1 by chromatography. Isomers 1, 2, and 3 could be distinguished by their chromatographic retention times as well as by their physical and spectral properties. Reduction of 2 with sodium borohydride gave 5 alpha,14 beta-cholest-8-ene-3 beta,15 beta-diol (4), for which the C-15 configuration was established from the lanthanide-induced shifts of its 3 beta-tert-butyldimethylsilyl ether. 1H and 13C NMR chemical shift differences between 2, 3, and 4 indicated the involvement of variable populations of conformers that differ in the flexible C-D ring system and in the side chain. Compounds 2, 3, and 4 lowered the levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in CHO-K1 cells.

Cultured human endothelial cells stimulated with cytokines or endotoxin produce an inhibitor of leukocyte adhesion.

Activation of cultured human endothelial cells (HEC) by inflammatory stimuli, such as interleukin 1 (IL-1), tumor necrosis factor (TNF), and bacterial endotoxin (lipopolysaccharide, LPS), increases their surface adhesiveness for blood leukocytes and related cell lines. We now report that activated HEC also generate a soluble leukocyte adhesion inhibitor (LAI), which accumulates in conditioned media from IL-1-, TNF-, or LPS-treated, but not sham-treated, HEC cultures. LAI significantly inhibits the adhesion of PMN and monocytes to activated, but not unactivated, HEC. In contrast, LAI has no effect on the adhesion of lymphocytes, the promyelocytic cell line HL-60 or the monocyte-like cell line U937 to HEC monolayers. LAI appears to act directly on the leukocyte, but does not inhibit either agonist-induced responses in PMN (membrane depolarization, changes in cytosolic calcium concentration, superoxide production) or PMN attachment to serum-coated plastic surfaces. Endothelial generation of LAI is blocked by actinomycin D but not by aspirin or indomethacin. Preliminary biochemical characterization indicates that LAI is a soluble, protein-containing molecule that is heat- and acid-stable. Fractionation by HPLC gel filtration yields a single peak of LAI activity (14,000 less than Mr greater than 24,000). Thus, in addition to proadhesive cell surface changes, the endothelium may also actively contribute to the regulation of endothelial-leukocyte interactions at sites of inflammation in vivo through the production of soluble adhesion inhibitors such as LAI.

Physiological changes in hemostasis associated with acute exercise.

Acute exercise enhances fibrinolytic (FA), factor VIII coagulant and factor VIII ristocetin cofactor activities, and increases the concentration of factor VIII-related antigen. Little is known concerning the mechanisms of these changes. To investigate possible relationships between exercise-induced changes in blood lactate, 2,3-diphosphoglycerate (DPG), and the hemostatic variables, a branching multistage treadmill protocol was used to exercise male volunteers to a maximum effort. Blood samples were drawn before, immediately post-, and 8 min postexercise. All hemostatic variables were significantly (P less than 0.05) increased postexercise. Highest values for factor VIII coagulant, factor VIII-related antigens and factor VIII ristocetin cofactor were observed at 8 min postexercise. Significant (P less than 0.001) correlations were found postexercise for lactate with factor VIII coagulant (r = 0.64), while no association between pre-, post-, or 8 min postexercise. Postexercise lactate demonstrated a significant correlation (r = +0.81), which was strengthened by including the preexercise high-density lipoprotein (HDL) concentrations (r = +0.87). Consequently, the expected postexercise FA may be calculated from the observed values for postexercise lactate and preexercise HDL. The correlations of lactate with postexercise FA and with postexercise factor VIII coagulant may reflect a common stimulus for these exercise-induced changes.

Interleukin-1 activation of vascular endothelium. Effects on procoagulant activity and leukocyte adhesion.

Interleukin-1 (IL-1), an inflammatory/immune mediator, acts directly and selectively on cultured human vascular endothelial cells to alter two important functional properties. First, IL-1 induces endothelial cell biosynthesis and surface expression of a tissue factor-like procoagulant activity. Second, IL-1 dramatically increases the adhesiveness of the endothelial cell surface for human peripheral blood polymorphonuclear leukocytes (6-42-fold increase) and monocytes (2-5-fold increase), as well as the related leukocyte cell lines HL-60 and U937. These IL-1 effects are concentration-dependent (maximum, 5-10 U/ml), time-dependent (peak 4-6 hours), and reversible. Cycloheximide and actinomycin D block these IL-1 actions on endothelium, which suggests the requirement for de novo protein synthesis. Human-monocyte-derived IL-1, cell-line--derived IL-1, and recombinant IL-1 exhibited comparable biologic activities in our assays, whereas two other mediators, IL-2 and immune interferon, were without effect. IL-1 stimulated procoagulant activity and leukocyte adhesion in human endothelial cells cultured from both umbilical veins and adult saphenous veins but not in other cultured cell types, including SV-40-transformed human endothelial cells and human dermal fibroblasts. Similar actions of IL-1 on vascular endothelium in vivo may contribute to the development of intravascular coagulation and enhanced leukocyte--vessel wall adhesion at sites of inflammation.

Interleukin 1 acts on cultured human vascular endothelium to increase the adhesion of polymorphonuclear leukocytes, monocytes, and related leukocyte cell lines.

Increased leukocyte adhesion to the endothelial lining of blood vessels is an essential event in inflammation and the pathogenesis of certain vascular diseases. We have studied the effect of interleukin 1 (IL-1), an inflammatory/immune mediator, on endothelial-leukocyte adhesion using quantitative in vitro assays. Selective pretreatment of cultured human umbilical vein endothelial monolayers with IL-1 (5 U/ml, 4 h) resulted in an 18.3 +/- 2.6-fold increase in human peripheral blood polymorphonuclear leukocyte (PMN) adhesion (mean +/- SEM, n = 16) and a 2.6 +/- 0.3-fold increase in monocyte adhesion (n = 7) over basal levels. IL-1-treated endothelial monolayers also supported increased adhesion of the promyelocytic cell line HL-60 and the monocytelike cell line U937 (33.0 +/- 6.0-fold, n = 6 and 4.9 +/- 0.5-fold, n = 15, respectively). In contrast, selective IL-1 pretreatment of leukocytes, or the addition of IL-1 during the adhesion assay, did not alter endothelial-leukocyte adhesion. Conditioned medium from IL-1-treated endothelial cultures also did not promote leukocyte adhesion to untreated monolayers. IL-1 induction of endothelial adhesivity was concentration dependent (maximum, 10 U/ml), time dependent (peak, 4-6 h), and reversible, was blocked by cycloheximide (10 micrograms/ml) or actinomycin D (5 micrograms/ml) but not by acetylsalicylic acid (100 microM), and occurred without detectable endothelial cell damage. IL-1 treatment of SV40-transformed human endothelial cells and dermal fibroblasts did not increase their adhesivity for leukocytes. These data suggest that IL-1 can act selectively on human vascular endothelium to increase its adhesivity for circulating blood leukocytes, and thus to localize leukocyte-vessel wall interactions at sites of inflammation in vivo.

Reciprocal transmembranous receptor-cytoskeleton interactions in concanavalin A-activated platelets.

Concanavalin A (Con A) has been used to activate platelets, inducing a specific interaction between the glycoprotein IIb-IIIa complex and the cytoskeleton of the activated platelet. In agreement with this, we have shown that Con A activates human platelets, initiating phosphorylation, secretion, and cytoskeletal formation. Con A and cytochalasin B were used to demonstrate a reciprocal interaction of the glycoprotein complex with the platelet cytoskeleton. Additionally, we have shown that a similar reciprocity is provided by the multivalent fibrin-fibrinogen platelet interaction found in the thrombin-induced clot. Con A differs from other activators in precipitating an apparent cytoskeletal core despite a complete inhibition of platelet activation by prostaglandin E1. We suggest, from this result, that Con A may be cross-linking a membrane-associated cytoskeletal complex present in the unactivated platelet.

Retention of the glycoprotein IIb-IIIa complex in the isolated platelet cytoskeleton. Effects of separable assembly of platelet pseudopodal and contractile cytoskeletons.

To investigate the association of the putative platelet fibrinogen receptor (glycoprotein IIb-III(a) with the cytoskeleton, 125I-surface labeled human platelets washed by gel-filtration were activated under conditions which allow selective assembly of the platelet cytoskeleton. The four conditions were activation with arachidonate or phorbol 12-myristate 13-acetate (PMA) with and without pretreatment with cytochalasin E. Activation with arachidonate generates a complete cytoskeletal core (pseudopodal and contractile elements) while PMA activation forms only an actin plus actin-binding protein pseudopodal core. Pretreatment with cytochalasin E leads to actomyosin contractile core formation if arachidonate activated, and essentially blocks cytoskeletal development if PMA activated. Cytoskeletal cores from arachidonate or PMA-activated platelets retained 26 (+/- 3%) of the total 125I-IIIa. Pretreatment with cytochalasin E followed by arachidonate or PMA activation reduced the 125I-IIIa retention to near control levels (unactivated platelets: 4 +/- 2%). The role of aggregation vs. receptor occupancy in the retention of IIb-IIIa was assessed by activation of platelets with arachidonate in the presence of fibrinogen fragment D (0.6-12 mg/ml). Aggregation was blocked by increasing concentrations of fragment D reagent while cytoskeletal assembly was not altered. The IIIa retention correlated with extent of aggregation with maximal retention corresponding to full aggregation. To determine if cytoskeletal development is necessary for the expression of the fibrinogen binding site, binding studies were performed with unlabeled platelets and 125I-fibrinogen. The mean number of binding sites and the mean dissociation constant were not significantly different among the four activation conditions. Although the development of a platelet cytoskeletal core is not required for the expression of the fibrinogen binding site, the retention of the glycoprotein IIb-IIIa complex is dependent on fibrinogen-supported aggregation as well as the formation of the pseudopodal cytoskeleton.

Adductor tenotomy-obturator neurectomy.

A 3.7-year follow-up study of 25 cerebral palsied children with 41 adductor tenotomies and obturator neurectomies showed significant improvement in hip abduction and acetabular development.

Naloxone administration and ventilation in awake cats.

Naloxone, an opiate antagonist, was administered to unrestrained awake cats to determine whether endogenous opioids tonically inhibit breathing. Whole body plethysmography was used to assess ventilation. Minute ventilation, tidal volume and breathing frequency were determined in each of 4 cats before and after 0.4 and 4.0 mg/kg naloxone. Analysis of variance did not show a significant difference between ventilatory values obtained before and after naloxone administration. Similarly, end-tidal pCO2 did not change systematically throughout a given trial.

S-C joint disruption in an infant.

An anterosuperior sternoclavicular disruption in a 7 month old female was caused by trauma. Good results were observed by concervative managment.