Biomedical subjects

H Flohr

Publications and source records attributed to H Flohr.

At least 19 recordsLinked to original sources

PubMed1999

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.

Adult↗

PubMed1998

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.

Anesthesia, General↗

PubMed1998

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.

Anesthetics, Intravenous↗

PubMed1998

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.

Adult↗

PubMed1998

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.

Adult↗

PubMed1997

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.

Adult↗

PubMed1997

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.

Adult↗

PubMed1996

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.

Adolescent↗

PubMed1996

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.

Adult↗

PubMed1995

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.

Anesthesia, General↗

PubMed1995

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.

Animals↗

PubMed1993

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.

Adaptation, Psychological↗

PubMed1992

Identification of a B-50-like protein in frog brain synaptosomes.

Vestibular compensation in the frog following unilateral labyrinthectomy is accompanied by distinct changes in the endogenous phosphoprotein patterns in total frog brain homogenate and isolated synaptosomes. The purpose of this study was to characterize one of these proteins, an acidic 45-kDa synaptosomal protein, resembling in some of its features the growth-associated protein GAP-43/B-50. Our results demonstrate by comparative analysis with purified rat B-50/GAP-43 that the 45-kDa protein (IP 4.8) in synaptosomal membranes of frog brain is phosphorylated by added purified PKC, cross-reacts with affinity-purified rabbit antibodies to rat B-50 and exhibits a Staphylococcus aureus V8 protease peptide digestion pattern corresponding to rat B-50. Therefore, we conclude that the acidic 45-kDa synaptosomal protein is a growth-associated B-50-like protein, probably involved in processes responsible for compensatory reorganization of the vestibular structures after hemilabyrinthectomy in the frog.

Animals↗

PubMed1992

Vestibular compensation affects endogenous phosphorylation of frog brain proteins.

The effect of unilateral labyrinthectomy followed by the process of vestibular compensation on the incorporation of radioactive phosphate into frog brain proteins was investigated. Phosphoproteins were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by autoradiography. The present data show that unilateral labyrinthectomy affects the incorporation of 32P into various frog brain proteins. In particular, the phosphorylation of a 20-kDa protein appeared enhanced during early stages of vestibular compensation (4-12 days). This 20-kDa protein was shown to be immunologically related to myelin basic protein and its phosphorylation was regulated by an endogenous calcium/calmodulin-dependent protein kinase. These data might indicate that in addition to neuronal components, components of glial origin are also involved in biochemical events that lead to functional recovery after neuronal lesions.

Adaptation, Physiological↗

PubMed1992

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.

Animals↗

PubMed1991

Role of the visual input in recovery of function following unilateral vestibular lesion in the goldfish. I. Short-term behavioural changes.

Vestibular compensation, i.e. the partial or complete recovery of function following lesion of a labyrinth, has been suggested to be based on a multisensory substitution process involving vestibular, visual and somatosensory information. Teleost fish would seem ideal subjects for testing this proposal, because equilibrium orientation in the intact animal is largely under the bimodal control of the vestibular and visual systems. The role of the visual input in the compensation of behavioural deficits elicited by hemilabyrinthectomy (HL) was studied in goldfish maintained over the first two postoperative hours under different lighting conditions. HL caused severe postural and locomotory symptoms, which were the same or similar under all lighting conditions. The rate at which the various deficits disappeared, however, was dependent not only on the presence of light but also on its direction of incidence. Animals maintained under overhead illumination reached the criterion of successful compensation (completion of 5-min continuous and unimpaired swimming) within 10 min, whilst under unilateral illumination (90 degrees to the vertical) the time to criterion was significantly increased; animals exposed to illumination from below or infra-red illumination showed little or no signs of compensation up to 2 h after HL. It is concluded (1) that the immediately postoperative stage of vestibular compensation in the goldfish represents an integral part of the recovery process, within which all observable deficits can be compensated with remarkable rapidity; and (2) that the visual input is both necessary and sufficient for the compensation of the immediately postoperative deficits. We term this early stage of recovery the 'acute' phase and consider it to be based on a visual substitution process, whereby the missing labyrinthine input to the (partially) deafferented vestibular neurons is functionally replaced by visual afferents.

Animals↗

PubMed1991

Role of the visual input in recovery of function following unilateral vestibular lesion in the goldfish. II. Long-term behavioural changes.

Previous behavioural studies in our laboratory have demonstrated that the visual input is both necessary and sufficient for the acquisition of the acutely compensated state following hemilabyrinthectomy (HL) in the goldfish. Here we examine the role of the visual input in the maintenance of the compensated state. Exposure of acutely compensated animals to illumination from below (IFB) or infra-red illumination (IRI) elicited a decompensation: whereas IRI was no longer effective 4 days after HL, the susceptibility to IFB disappeared slowly over a number of weeks. Exposure of acutely compensated animals to unilateral illumination (UI) induced a highly asymmetrical dorsal light response 1 day after HL: tilt towards the ipsilateral side was extreme, whilst tilt towards the contralateral side was similar to preoperative values. This pronounced side difference decreased rapidly over the next 3 days and then more slowly over the following weeks and months. The findings show (1) that the maintenance of the acutely compensated state is temporarily dependent not only on the presence of light but also on its direction of incidence; and (2) that the visual-vestibular integration governing posture and locomotion is strongly biased in favour of the visual input to the lesioned side during the early postoperative period and subsequently returns to near preoperative values. The present results are compatible with the hypothesis that acute vestibular compensation in the goldfish is based on a visual substitution process. The latter is not permanent, however, the chronic course of compensation being characterized by a progressive decrease in reliance on visual cues. The observed changes in visual-vestibular integration with time are assumed to reflect modifications in inter- and/or extra-vestibular commissural systems by which the intact labyrinth gradually strengthens its control over the deafferented nuclear complex.

Animals↗

PubMed1991

Molecular mechanisms of brainstem plasticity. The vestibular compensation model.

Vestibular compensation is the process of behavioral recovery that occurs following unilateral deafferentation of the vestibular nerve fibers (unilateral labyrinthectomy, UL). Since UL results in a permanent loss of vestibular input from the ipsilateral vestibular (VIIIth) nerve, vestibular compensation is attributed to CNS plasticity and has been used as a general model of lesion-induced CNS plasticity. Behavioral recovery from the ocular motor and postural symptoms of UL is correlated with a partial return of resting activity to neurons in the vestibular nucleus (VN) on the deafferented side (the "deafferented VN"), and lesions to the deafferented VN prevent compensation; therefore, the regeneration of resting activity within the deafferented VN is believed to have a causal role in vestibular compensation. The biochemical mechanisms responsible for the adaptive neuronal changes within the deafferented VN are poorly understood. Neuropeptide hormone fragments, such as adrenocorticotrophic hormone (ACTH)-4-10, have been shown to accelerate vestibular compensation and can act directly on some VN neurons in vitro. Antagonists for the N-methyl-D-aspartate (NMDA) receptor have been shown to inhibit vestibular compensation if administered early in the compensation process. Biochemical studies in frog indicate marked alterations in the phosphorylation patterns of several proteins during compensation, and the in vitro phosphorylation of some of these proteins is modulated by ACTH-(1-24), calcium (Ca2+), and calmodulin or protein kinase C. It is therefore possible that ACTH fragments and NMDA antagonists (via their effects on NMDA receptor-mediated Ca2+ channels) modulate vestibular compensation through their action on Ca(2+)-dependent pathways within VN neurons. Recent studies have shown that some Ca2+ channel antagonists and the Ca(2+)-dependent enzyme inhibitor calmidazolium chloride facilitate vestibular compensation. How the regulation of Ca2+ may be related to the neuronal changes responsible for vestibular compensation is unclear at present.

Adrenocorticotropic Hormone↗