Cortical activation associated with midtrial change of instruction in a saccade task.

The appearance of a visual stimulus in the peripheral visual field can elicit different saccade responses depending on prior instruction. This flexibility is commonly attributed to differences in motor set. Little is known about how the brain switches between one saccade response and another. To investigate the neural processes associated with switches between saccade motor sets, we recorded event-related potentials (ERPs) in 13 subjects, in three tasks that required subjects to generate prosaccades to a visual stimulus on 75% of the trials. On 25% of the trials, the color of the fixation point (FP) changed 300 ms prior to stimulus presentation. In the "ANTI" task, the change of the FP was the instruction to generate an antisaccade; in the "NOGO" task, subjects were instructed to maintain fixation; and in the "PRO" task, subjects were instructed to generate a prosaccade. The switch in motor set from prosaccades to antisaccades in the ANTI task and the cancellation of the prosaccade motor set in the NOGO task modulated frontal and frontocentral channels. Futhermore, the ANTI task but not the NOGO task was associated with differences at central and parietal channels compared with the PRO task. We hypothesize that the frontal activation in the ANTI and NOGO task reflects inhibition and task-switching processes, whereas the parietal activation reflects the preparation of this area for the sensorimotor transformation process that is necessary for the generation of an antisaccade.

Prestimulus cortical potentials predict the performance in a saccadic distractor paradigm.

OBJECTIVE: In distractor paradigms, subjects sometimes respond to the wrong stimulus in a reflex-like manner. It is poorly understood why these errors occur. METHODS: To investigate the cortical processes possibly responsible for these errors, we recorded event-related potentials (ERPs) in human subjects performing a distractor saccade task in which subjects had to select a saccade target based on the colour of the initial fixation point and ignore a distractor on the opposite side. The initial fixation point disappeared 200 ms before the presentation of the visual stimuli (gap period). We compared the ERPs between correct trials in which subjects looked to the correct stimulus with error trials in which they looked towards the wrong stimulus. RESULTS: Correct response trials and error response trials showed a negative potential at the end of the gap period with the greatest amplitude over the fronto-central cortex. However, this potential had a lower amplitude in error response trials compared to correct response trials. CONCLUSION: These findings suggest that task-specific preparatory cortical processes in the frontal lobe prior to stimulus presentation have a major influence on the performance in distractor paradigms.

[Application of nursing care products in decubitus prevention]. / Zum Einsatz von Pflegehilfsmitteln in der Dekubitusprophylaxe.

Pathophysiological factors of decubitus development determine general risk situation of individuals. Working principle and used material of common used antidecubitus systems can have a strong influence on individual risk potential. This study gives an overview about individual advantages and disadvantages in working principle, which may be used by different technical devices for decubitus prevention.

Role of albumin and glomerular capillary wall charge distribution on glomerular permselectivity: studies on the perfused-fixed rat kidney model.

The charge-related determinants of albumin permeability are the subject of controversial discussion. To study this question we have developed an isolated perfused rat kidney model in which metabolic processes are eliminated by perfusion fixation with glutaraldehyde. The fixed kidneys were perfused with albumin solutions using the following approaches: 1. Modification of the charge of both the glomerular capillary wall (GCW) and albumin using different buffer systems in a pH range spanning the isoelectric points of albumin and the glomerular basement membrane (GBM), the extracellular matrix of the GCW. 2. Modification of the charge of the GCW by perfusing the isolated kidney with cations either before or after fixation. 3. Modification of the charge of albumin by cationization. In the model, the inulin "urine" to perfusate ratio was one. This shows that the tubules have no metabolic activity, that the glomerular filtration rate (GFR) is equal to "urine" flow rate and that the "urine" collected is identical to the ultrafiltrate. Therefore, sieving coefficients in this model can simply be calculated as the ratio between "urine" and perfusate protein concentrations. We could show that: 1. pH has a significant effect on the albumin sieving coefficient: it was maximally increased at pH 4.0 [(70.3 +/- 15.9) x 10(-3), n = 10 versus (8.7 +/- 3.7) x 10(-3), n = 11, at pH 7.4]. Only a pH as low as 4.0 should lead to a pronounced neutralization of the anionic charges of albumin and the GBM; the charge density of the GCW calculated with these data is 43 mEq/l at pH 7.4. 2. Modifying the ionic composition of the GCW with protamine before fixation with glutaraldehyde causes a bigger increase in the glomerular permeability for albumin [(51.2 +/- 22.5) x 10(-3), n = 10, glomerular charge density 21 mEq/l] than modifying the albumin charge by cationization. 3. Modifying the albumin charge by cationization increases the glomerular permeability for albumin [(20.0 +/- 6.7) x 10(-3), n = 8]. These findings support the hypothesis that at the onset of proteinuria changes in the charge and configuration of the GCW could be more important pathogenetic factors than changes in the charge of serum-derived proteins.

Event-related potentials and saccadic reaction times: effects of fixation point offset or change.

Previous studies have shown that saccadic reaction times (SRTs) are reduced if the initial fixation point (FP) disappears 200 ms (gap period) before a peripheral target is presented. This gap saccade task is associated with a negative cortical potential at the end of the gap period. To determine whether the neural processes underlying this potential account for the reduction of SRTs during gap saccade tasks, we recorded event-related potentials (ERPs) in 19 subjects performing a gap saccade task (gap duration 200 ms), a warning saccade task (the color of the FP changed 200 ms prior to target appearance) and an overlap task (the FP remained visible during the trial). SRTs were shortest during the gap task, longest during the overlap task and intermediate during the warning task. The gap and warning tasks were accompanied by the same widespread negative cortical potential with a maximum at the time of stimulus presentation. These findings indicate that the warning effect mediated by the disappearance of the FP during gap saccade tasks is responsible for the gap negativity which was observed by several authors. Our findings of shorter SRTs during the gap task than the warning task, however, suggest that the gap has an additional effect that probably depends on subcortical mechanisms.

Accuracy of visually and memory-guided antisaccades in man.

Primary saccades to remembered targets are generally not precise, but rather undershoot target position. The major source of this saccadic undershoot may be (a) a memory-related process or (b) a poor spatial resolution in those processes which transfer the retinotopic target information into an intermediate memory-linked representation of space. The aim of this study was to investigate whether distortions of eye positions in the antisaccade task, which are characterized by inherent co-ordinate transformation processes, may completely account for the spatial inaccuracies of memory-guided antisaccades. The results show that the spatial inaccuracy of primary and secondary eye movements in the visually guided antisaccade task was comparable to that in the memory-guided antisaccade task. In both conditions, the direction error component was less dysmetric than the amplitude error component. Secondary eye movements were significantly corrective. This increase of eye position accuracy was achieved by reducing the amplitude error only. It is concluded from this study that at least some of the distortion of memory-guided saccades is due to inaccuracies in the sensorimotor co-ordinate transformations.

7-Nitro indazole enhances methohexital anesthesia.

7-nitro indazole, a selective inhibitor of the neuronal nitric oxide (NO) synthase dose-dependently prolongs the duration of methohexital narcosis in the rat. This effect can be antagonized stereoselectively by the NO-synthase substrate l-arginine (l-Arg). The results support the assumption that the potentiation of the anesthetic state by NO-synthase inhibitors is due to a specific effect on brain NO-synthase and a disruption of synaptic NO signalling pathways. These results are also in accordance with predictions that follow from recent hypotheses proposing that a modification of the NMDA receptor function is the final common pathway of anesthetic action.

Event-related potentials associated with correct and incorrect responses in a cued antisaccade task.

In an antisaccade task, subjects are instructed to inhibit a reflexive saccade towards a peripheral stimulus flash and to generate a saccade in the opposite direction. It has been shown recently that normal subjects will generate a high number of incorrect prosaccades in an antisaccade task if the fixation point is extinguished 200 ms before the stimulus appears and if a valid cue for the subsequent antisaccade is given during this gap period. In the present study we recorded cerebral event-related potentials from 19 scalp electrodes from normal subjects prior to correct and incorrect responses in a cued antisaccade task to investigate the neural processes associated with correct antisaccades and incorrect prosaccades in this task. Correct antisaccades and incorrect prosaccades were associated with a negative potential with a maximal amplitude around stimulus onset over the dorsomedial frontal cortex. This potential was higher prior to correct antisaccades than prior to incorrect prosaccades. The execution of a correct antisaccade was preceded by a shift of a negative potential from the parietal hemisphere contralateral to the visual stimulus towards the parietal hemisphere ipsilateral to the stimulus. These results support the view that the supplementary eye fields participate in the inhibition of incorrect saccades in a cued antisaccade task and show that the parietal cortex participates in generating a neural representation of the visual stimulus in the hemifield ipsilateral to the stimulus before generating a motor response.

The role of the NMDA synapse in general anesthesia.

A theory of anesthesia is presented. It consists of four hypotheses. (1) The occurrence of states of consciousness causally depends on the formation of transient higher-order, self-referential mental representations. The occurrence of such states is identical with the appearance of conscious phenomena. Loss of consciousness will occur, if the brain's representational activity falls below a critical threshold. (2) Higher-order mental representations are instantiated by neural cell assemblies. (3) The formation of such assemblies involves the activation of the NMDA receptor channel complex. The activation state of this receptor determines the rate at which such assemblies are generated. (4) Modification of NMDA-dependent computational processes is the final common pathway of anesthetic action. Agents that directly inactivate the NMDA synapse necessarily have anesthetic properties; agents that do not directly affect the NMDA synapse will exert an anesthetic action, if they inhibit NMDA-dependent processes.

Influence of pre-target cortical potentials on saccadic reaction times.

Saccades elicited by suddenly appearing targets show a broad distribution of reaction times. This may depend on variations in the subject's state of preparation before target onset. To test this hypothesis, we recorded scalp event-related potentials from eight human subjects to investigate whether differences in saccadic reaction times (SRTs) are related to differences in cortical slow potentials prior to target onset. Compared with trials with medium SRTs (180-230 ms), trials with fast SRTs (130-180 ms) were found to be preceded by a more negative slow potential and trials with slow SRTs (230-280 ms) were found to be preceded by a more positive slow potential. These results support the hypothesis that cortical activation prior to target appearance influences SRTs.

Cortical potentials preceding pro- and antisaccades in man.

The antisaccade task has been used widely to assess a frontal lobe deficit. In the present study cortical potentials preceding prosaccades and antisaccades were recorded in 7 healthy subjects with 19 scalp electrodes according to the international 10-20 system. The main results were as follows: (1) In both saccade types, a slow presaccadic negative shift was observed at dorso-medial frontal recording sites. The integral over these potentials was significantly greater for antisaccades at the C3, C4 and Cz location than in prosaccades. (2) The integral over presaccadic positivity was significantly lower for antisaccades compared with prosaccades at the Cz location. It is concluded that these results support an important role of the supplementary eye fields in generating antisaccades.

Cortical potentials during the gap prior to express saccades and fast regular saccades.

When a temporal gap is introduced between the offset of the central fixation point and the appearance of a new target, saccadic reaction time is reduced (gap effect) and a special population of extremely fast saccades occurs (express saccades). It has been hypothesized that the gap triggers a readiness signal, which is responsible for the reduced saccadic reaction times. Here, we recorded event-related potentials during the gap to investigate the central processes associated with the generation of fast regular saccades and express saccades. Prior to the execution of fast regular saccades, subjects produced a slow negative shift, with a maximum at frontal and central channels that started 40 ms after fixation offset. This widespread negativity is similar to a readiness potential. Anticipatory saccades were preceded by an increased frontal and parietal negativity. Prior to express saccades, a frontal negativity was observed, which started 135 ms after the disappearance of the fixation point. It is assumed that the frontal negativity prior to express saccades corresponds to the fixation-disengagement discharge described in the frontal eye field of monkeys. Therefore, we hypothesize that fast regular saccades are the result of an increased readiness signal, while express saccades are the result of specific preparatory processes.

Hypometric primary saccades of schizophrenics in a delayed-response task.

In this study, the execution of delayed saccades in 15 DSM-III-R-schizophrenic patients and 15 normal subjects was investigated. While looking at a central fixation cross, a peripheral target was randomly presented at 10 degrees eccentricity. Subjects were instructed to saccade to the target when the fixation cross was switched off after 500 ms. Two experiments were conducted: (a) a delayed-saccade task and, (b) a memory-guided saccade task, that is, the peripheral target was switched off together with the fixation cross. In the delayed-saccade task, amplitudes of regular saccades did not differ between schizophrenic patients and normals. In the memory-guided saccade task, schizophrenic subjects showed marked hypometric saccades. Incorrect delayed saccades (while the fixation cross was on) were also hypometric in schizophrenics, but not in normal controls. The final eye position, i.e., the position reached after the execution of correction saccades, however, did not differ between patients and controls. This means that schizophrenics show a deficit in the programming of primary saccades, if the fixation point and the peripheral target are (a) both visually presented or (b) both memorized. The results support the hypothesis that these saccades are the result of an averaging effect between the fixation point and the peripheral target. It is further hypothesized that these deficits might be explained by a lack of prefrontal inhibition of ocular fixation areas.

Sensations and brain processes.

A hypothesis on the physiological conditions of consciousness is presented. It is assumed that the occurrence of states of consciousness causally depends on the formation of complex representational structures. Cortical neural networks that exhibit a high representational activity develop higher-order, self-referential representations as a result of self-organizing processes. The occurrence of such states is identical with the appearance of states of consciousness. The underlying physiological processes can be identified. It is assumed that neural assemblies instantiate mental representations; hence consciousness depends on the rate at which large active assemblies are generated. The formation of assemblies involves the activation of the N-methyl-D-aspartate receptor channel complex which controls different forms of synaptic plasticity including rapid changes of the connection strengths. The various causes of unconsciousness (e.g., anaesthetics or brain stem lesions) have a common denominator: they directly or indirectly inhibit the formation of assemblies.

An information processing theory of anaesthesia.

A theory of anaesthesia is presented. It consists of four hypotheses: (1) The occurrence of states of consciousness causally depends on the formation of transient higher-order, self-referential mental representations. The occurrence of such states is identical with the appearance of conscious phenomena. Loss of consciousness will occur, if and only if the brain's representational activity falls below a critical threshold. (2) Mental representations are instantiated by neural cell assemblies. (3) The formation of assemblies involves the activation of the NMDA receptor channel complex. The activation state of this receptor determines the rate at which assemblies are generated. (4) General anaesthetics have a common operative mechanism: they directly or indirectly affect the function of the NMDA system.

Role of NMDA receptors in lesion-induced plasticity.

The effect of the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 on the acquisition and maintenance of a compensated state following unilateral labyrinthectomy was investigated in two species, grass frog and goldfish. MK-801: 1) inhibits the acquisition of a compensated state, and 2) causes a loss of compensation in early phases of the compensation process, but 3) has no such effect to the long-term maintenance of compensation. It is concluded that NMDA receptors perform a transient function by inducing a sensory or functional substitution process in the deafferented vestibular system. A hypothesis is presented explaining the lesion-induced adaptive process as a result of a self-organizing process in a neural net using Hebb-like algorithms to organize the strength of connections.

The physiological and pathophysiological basis of glomerular permeability for plasma proteins and erythrocytes.

The barrier function of glomerular capillaries in vivo, which prevents the leakage of plasma proteins and cellular elements, depends on the basic morphological and electro-chemical fine structure of the glomerular capillary wall, and on a functional barrier maintained by components obtained from blood, which effect the definitive barrier against the leakage of plasma proteins and cellular elements. The functional component of the barrier may explain the variability and some of the phenomena known as functional proteinuria. A certain size and number of morphological "defects" are thought to represent the normal condition, but under pathological conditions they may increase in size and number, resulting in a shift to an increasing permeability for higher molecular mass proteins; also an increase of the size and number of larger defects may enable more red cells to pass the barrier compared with the normal condition. These defects are different from the minimal glomerular lesions which are due to charge defects in the glomerular capillary membrane, primarily the lamina rara interna and the lamina rara externa of the basement membrane.