Hypnotic manipulation of effort sense during dynamic exercise: cardiovascular responses and brain activation.

The purpose of this investigation was to hypnotically manipulate effort sense during dynamic exercise and determine whether cerebral cortical structures previously implicated in the central modulation of cardiovascular responses were activated. Six healthy volunteers (4 women, 2 men) screened for high hypnotizability were studied on 3 separate days during constant-load exercise under three hypnotic conditions involving cycling on a 1) perceived level grade, 2) perceived downhill grade, and 3) perceived uphill grade. Ratings of perceived exertion (RPE), heart rate (HR), blood pressure (BP), and regional cerebral blood flow (rCBF) distributions for several sites were compared across conditions using an analysis of variance. The suggestion of downhill cycling decreased both the RPE [from 13 +/- 2 to 11 +/- 2 (SD) units; P < 0.05] and rCBF in the left insular cortex and anterior cingulate cortex, but it did not alter exercise HR or BP responses. Perceived uphill cycling elicited significant increases in RPE (from 13 +/- 2 to 14 +/- 1 units), HR (+16 beats/min), mean BP (+7 mmHg), right insular activation (+7.7 +/- 4%), and right thalamus activation (+9.2 +/- 5%). There were no differences in rCBF for leg sensorimotor regions across conditions. These findings show that an increase in effort sense during constant-load exercise can activate both insular and thalamic regions and elevate cardiovascular responses but that decreases in effort sense do not reduce cardiovascular responses below the level required to sustain metabolic needs.     

Differential energetic response of brain vs. skeletal muscle upon glycemic variations in healthy humans

The brain regulates all metabolic processes within the organism, and therefore, its energy supply is preserved even during fasting. However, the underlying mechanism is unknown. Here, it is shown, using (31)P-magnetic resonance spectroscopy that during short periods of hypoglycemia and hyperglycemia, the brain can rapidly increase its high-energy phosphate content, whereas there is no change in skeletal muscle. We investigated the key metabolites of high-energy phosphate metabolism as rapidly available energy stores by (31)P MRS in brain and skeletal muscle of 17 healthy men. Measurements were performed at baseline and during dextrose or insulin-induced hyperglycemia and hypoglycemia. During hyperglycemia, phosphocreatine (PCr) concentrations increased significantly in the brain (P = 0.013), while there was a similar trend in the hypopglycemic condition (P = 0.055). Skeletal muscle content remained constant in both conditions (P > 0.1). ANOVA analyses comparing changes from baseline to the respective glycemic plateau in brain (up to +15%) vs. muscle (up to -4%) revealed clear divergent effects in both conditions (P < 0.05). These effects were reflected by PCr/Pi ratio (P < 0.05). Total ATP concentrations revealed the observed divergency only during hyperglycemia (P = 0.018). These data suggest that the brain, in contrast to peripheral organs, can activate some specific mechanisms to modulate its energy status during variations in glucose supply. A disturbance of these mechanisms may have far-reaching implications for metabolic dysregulation associated with obesity or diabetes mellitus.     

Production of auto-anti-idiotype antibody during the normal immune response. XI. Ficoll-induced variations in auto-anti-idiotype production during the response to 2,4,6-trinitrophenyl-Ficoll

The responses to 2,4,6-trinitrophenyl conjugates of different Ficoll preparations differ with respect to the magnitude of the accompanying auto-anti-idiotype (Id) response in both mice and chickens. Evidence is presented that reduced auto-anti-Id production in the chicken is due to the activation of suppressor activity by some preparations of Ficoll.     

Rapid and preferential activation of the c-jun gene during the mammalian UV response.

Exposure of mammalian cells to DNA-damaging agents leads to activation of a genetic response known as the UV response. Because several previously identified UV-inducible genes contain AP-1 binding sites within their promoters, we investigated the induction of AP-1 activity by DNA-damaging agents. We found that expression of both c-jun and c-fos, which encode proteins that participate in formation of the AP-1 complex, is rapidly induced by two different DNA-damaging agents: UV and H2O2. Interestingly, the c-jun gene is far more responsive to UV than any other immediate-early gene that was examined, including c-fos. Other jun and fos genes were only marginally affected by UV or H2O2. Furthermore, UV is a much more efficient inducer of c-jun than phorbol esters, the standard inducers of c-jun expression. This preferential response of the c-jun gene is mediated by its 5' control region and requires the TPA response element, suggesting that this element also serves as an early target for the signal transduction pathway elicited by DNA damage. Both UV and H2O2 lead to a long-lasting increase in AP-1 binding activity, suggesting that AP-1 may mediate the induction of other damage-inducible genes such as human collagenase.     

Regulation of TGF-beta response during T cell activation is modulated by IL-10.

TGF-beta1 is an important pleiotropic cytokine that has been described to have both stimulatory and inhibitory effects on cell growth and differentiation. For several cell types, the effect of TGF-beta1 was found to correlate with the differentiation stage of the cells and the presence of other cytokines. In this report, we address the influence of TGF-beta1 on CD4(+) T cell activation by evaluating the effect of TGF-beta1 on the proliferative and cytokine responses of purified resting and activated human or mouse CD4(+) T cells. TGF-beta1 inhibits proliferation and cytokine secretion on resting CD4(+) T cells but has no inhibitory effect on activated T cells. Moreover, TGF-beta1 unresponsiveness of activated T cells was correlated with a down-regulation in the expression of the TGF-beta receptor type II. Interestingly, IL-10 addition enhances TGF-beta receptor type II expression and restores TGF-beta responsiveness on activated T cells. These results indicated that TGF-beta responsiveness is sequentially regulated on T cells by the modulation of the of TGF-beta receptor type II chain expression. Moreover, we have identified a novel regulatory role of IL-10 on TGF-beta-dependent T cell growth that can explain the control of T cell activation on chronic vs acute inflammatory sites.     

Properties of Go cells: variations in the proliferative response following isoprenaline.

The proliferative behaviour induced in the acinar cells of the rat submaxillary gland in response to isoprenaline has been used to examine the transit time of cells from a quiescent (Go) state into the S phase. Cumulative 3H-TdR labelling index curves were constructed to determine the mean time interval (Gis time) between stimulation with isoprenaline and entry into the S phase. Data were collected for the proliferative wave induced by three sequential injections of isoprenaline, and the effects of varying the interval between the second and third injections of isoprenaline, and of changing the dose of the drug, were examined. Intervals of 28, 52 and 76 hr between isoprenaline injections resulted in mean Gis times of 16-2, 20-9 and 25-6 hr respectively. It was concluded that the Gis time depended on the recent history of cells with respect to stimulation, but not division. The results are considered in terms of two models, in one of which the time to leave Go is variable, whilst in the other the cells leave Go immediately the stimulus is applied.     

Specific activation of brain cortical areas in response to stimulation of the support receptors in healthy subjects and patients with focal lesions of the CNS

The space medicine data on the nature of motor disorders suggest an important role of the support inputs in the control of mammalian tonic and postural systems. Progress in functional magnetic resonance tomography (fMRT) makes it possible to perform in vivo analysis of various brain areas during stimulation of the support afferentation. Under these conditions, specific activation of the brain cortical areas was studied in 19 healthy subjects (with the mean age of 38 ± 15.13 years) and 23 patients (with the mean age of 53 ± 9.07 years) with focal CNS lesions (cortical-subcortical ischemic stroke). During scanning of subjects, the support areas of the soles of the feet were stimulated using a block design to simulate slow walking. In healthy subjects, significant activation was recorded (p < 0.05 at the cluster level) in the primary somatosensory cortex, premotor and dorsolateral prefrontal cortex, and insular lobe. In patients that had had a stroke, activation of the locomotion-controlling supraspinal systems clearly depended on the stage of the disease. In patients with a cortical-subcortical stroke, the pattern of contralateral activation of the sensorimotor locomotion predominated during motility rehabilitation.     

Model of the bacterial flagellar motor: response to varying viscous load.

A model of bacterial flagellar drive by cytomembrane streaming is described and applied to experiments of bacterial propulsion under varying viscous load. The theory predicts a linear dependence of the reciprocal propulsion velocity on the viscosity of the suspension medium, if the velocity of cytomembrane streaming far from the basal body of the flagella is assumed independent of the external viscosity. The theoretical predictions are in good agreement with experiments on free-swimming and on tethered bacteria. From comparison of the theory with experiments, the surface viscosity of the bacterial cytomembrane is evaluated for different bacterial species and turns out to be in the range observed experimentally on lipid monolayers.     

Pheromone reception: A complex map of activation in the brain.

Recent studies of the projection pattern made by sensory neurons involved in mammalian pheromone reception have shown that there is a map of activation in the brain, but this pheromone map appears far more complex than the equivalent map in the main olfactory system responsible for the sense of smell.     

Three-dimensional tomography of event-related potentials during response inhibition: evidence for phasic frontal lobe activation

Objectives: Spatial analysis of the evoked brain electrical fields during a cued revealed an extremely robust anteriorization of the positivity of a P300 microstate in the NoGo compared to the Go condition (NoGo-anteriorization in a prevailing study). To allow a neuroanatomical interpretation the NoGo-anteriorization was investigated with a new three-dimensional source tomography method (LORETA) was applied.Methods: The test contains subsets of stimuli requiring the execution (Go) or the inhibition (NoGo) of a cued motor response which can be considered as mutual control conditions for the study of inhibitory brain functions. 21-channel ERPs were obtained from 10 healthy subjects during a cued CPT, And analyzed with LORETA.Results: Topographic analyses revealed significantly different scalp distributions between the Go and the NoGo conditions in both P100 and P300 microstates, indicating that already at an early stage different neural assemblies are activated. LORETA disclosed a significant hyperactivity located in the right frontal lobe during the NoGo condition in the P300 microstate.Conclusions: The results indicate that right frontal sources are responsible for the NoGo-anteriorization of the scalp P300 which is consistent with animal and human lesion studies of inhibitory brain functions. Furthermore, it demonstrates that frontal activation is confined to a brief microstate and time-locked to phasic inhibitory motor control. This adds important functional and chronometric specificity to findings of frontal activation obtained with PET and Near-Infrared-Spectroscopy studies during the cued CPT, and suggests that these metabolic results are not due to general task demands.     

Regulation of oxygen transport during brain activation: stimulus-induced hemodynamic responses in human and animal cortices

BACKGROUND: The correlation between regional changes in neuronal activity and changes in hemodynamics is a major issue for noninvasive neuroimaging techniques such as functional magnetic resonance imaging (fMRI) and near-infrared optical imaging (NIOI). A tight coupling of these changes has been assumed to elucidate brain function from data obtained with those techniques. In the present study, we investigated the relationship between neuronal activity and hemodynamic responses in the occipital cortex of humans during visual stimulation and in the somatosensory cortex of rats during peripheral nerve stimulation. METHODS: The temporal frequency dependence of macroscopic hemodynamic responses on visual stimuli was investigated in the occipital cortex of humans by simultaneous measurements made using fMRI and NIOI. The stimulus-intensity dependence of both microscopic hemodynamic changes and changes in neuronal activity in response to peripheral nerve stimulation was investigated in animal models by analyzing membrane potential (fluorescence), hemodynamic parameters (visible spectra and laser-Doppler flowmetry), and vessel diameter (image analyzer). RESULTS: Above a certain level of stimulus-intensity, increases in regional cerebral blood flow (rCBF) were accompanied by a decrease in regional cerebral blood volume (rCBV), i.e., dissociation of rCBF and rCBV responses occurred in both the human and animal experiments. Furthermore, the animal experiments revealed that the distribution of increased rCBF and O2 spread well beyond the area of neuronal activation, and that the increases showed saturation in the activated area. CONCLUSIONS: These results suggest that above a certain level of neuronal activity, a regulatory mechanism between regional cerebral blood flow (rCBF) and rCBV acts to prevent excess O2 inflow into the focally activated area.     

Effects of mandibular advancement on brain activation during inspiratory loading in healthy subjects: a functional magnetic resonance imaging study.

Oral appliances have been a popular treatment option for subjects with obstructive sleep apnea. However, little information is available on how brain activation induced by respiratory challenge is modulated by mandibular advancement with these appliances. We hypothesized that the brain activation caused by respiratory stress may be alleviated by mandibular advancement. Respiratory stress was induced in 12 healthy subjects by resistive inspiratory loading. The effects of mandibular advancement during resistive inspiratory loading were assessed subjectively by using a visual analog scale. These effects were also evaluated objectively by using blood oxygenation level-dependent functional magnetic resonance imaging. The score for the visual analog scale significantly decreased with mandibular advancement. Cortical deactivation, in association with mandibular advancement, was localized to several specific regions, including the left cingulate gyrus and the bilateral prefrontal cortexes. These regions are known to be involved in respiratory control. Our results suggest that mandibular advancement with an oral appliance appears to be useful for reducing respiratory stress, based on both subjective and neuronal criteria.     

Interferon: effects on the immune response and the mechanism of activation of the cellular response.

The discovery of interferon in 1957 by Drs. Isaacs and Lindenmann led to major revisions in the concepts of man's defenses against viral infections. There are at least two types of interferon. Along with their antiviral properties, they have recently been shown to exert a suppressive effect on the humoral and cellular immune response; they affect both B and T lymphocytes. A variety of substances, including virus, polyribonucleotides, and mitogens for T lymphocytes, are good interferon inducers. T lymphocytes seem to be necessary for these inducers to exert their immunosuppressive effects. The immunosuppressive effects of interferon inducers suggests that interferons may be mediators of suppressor T lymphocyte effects. In the virus system, interferon does not exert its antiviral effects by direct action on the virus, but rather derepresses a cell gene that results in the production of an antiviral protein. This antiviral protein is probably the mediator of inhibition of virus replication. This is a complex sequence of events that results in the interaction of interferon with the cell membrane and the resulting production of the antiviral state in the cell. This review will examine the various steps of this involved process.     

Effects of attention and emotion on face processing in the human brain: an event-related fMRI study.

We used event-related fMRI to assess whether brain responses to fearful versus neutral faces are modulated by spatial attention. Subjects performed a demanding matching task for pairs of stimuli at prespecified locations, in the presence of task-irrelevant stimuli at other locations. Faces or houses unpredictably appeared at the relevant or irrelevant locations, while the faces had either fearful or neutral expressions. Activation of fusiform gyri by faces was strongly affected by attentional condition, but the left amygdala response to fearful faces was not. Right fusiform activity was greater for fearful than neutral faces, independently of the attention effect on this region. These results reveal differential influences on face processing from attention and emotion, with the amygdala response to threat-related expressions unaffected by a manipulation of attention that strongly modulates the fusiform response to faces.