Test-retest reliability of electrophysiological parameters related to cognitive motor control.

Previously, the continuous performance test was demonstrated to elicit distinct electrophysiological correlates of cognitive response during execution (Go) and inhibition (NoGo) of an anticipated motor response. A robust method for topographical quantification of these brain electrical microstates has been established recently. Test reliability is crucial to allow application in the assessment of neuropsychiatric disorders. The present study evaluates the reliability of the Go and NoGo centroid locations as well as the NoGo anteriorisation (NGA) in 23 healthy individuals. Our results show supreme test-alternate retest reliabilities of Pearson's product moment correlations and intraclass correlation coefficients of r> or =0.63 (P< or =0.001) for these parameters which assert a quality well within the range reported for those of other electrophysiological standard paradigms. Go and NoGo centroid locations as well as the NGA are, therefore, reliable correlates of prefrontal motor control and may contribute to the understanding of disorders with allied impairments.

Age-related changes in the brain electrical correlates of response control.

OBJECTIVES: Previously, a quantification method was validated which, on a single case basis, allows one to assess the NoGo-anteriorisation (NGA) of the positive area of long latency event-related potential (ERP) fields elicited by a cued continuous performance test (CPT). The NGA was shown to be associated with right frontal activity. The present study was conducted to investigate the influence of age and gender on this topographical index of cognitive response control. METHODS: Thirty-seven healthy controls were investigated with 21-channel recordings during the execution of a cued CPT, and ERPs of the Go and NoGo condition were obtained. The location of the positive area centroids in a P300 range and the NGA were calculated and related to age and gender by means of correlation analysis and t tests. RESULTS: The centroid locations of the brain electrical activity during the NoGo- and the Go-condition of the CPT, were both located in more anterior brain regions with increasing age (P<0.01 and P<0.1, respectively); the NGA, however, was not correlated with the subject's age. Latencies and amplitudes of the Go- and NoGo-centroids were not correlated with age. No gender differences were found. CONCLUSIONS: The study showed that age is a source of variance for the positive area centroid locations in this Go-NoGo paradigm. The NGA, on the other hand, was robust to age and gender effects. The result is interpreted as a sign of an increasing contribution of frontal brain areas to cognitive response control during lifespan. The finding is consistent with the age-related topographical changes described in acoustic oddball-paradigms and, therefore, appears to be a general topographical ERP effect.

Electrophoretic analysis of proteases in Echinostoma Caproni and Echinostoma trivolvis.

Gelatin substrate sodium dodecyl sulfate polyacrylamide gel electrophoresis was used to analyze proteases in 14 day-old adults of Echinostoma caproni and Echinostoma trivolvis. At pH 8.0, E. caproni adults showed 2 protease bands at 36 kDa and 58 kDa, whereas E. trivolvis adults showed 6 bands at 39, 64, 77, 96, 120, and 168 kDa. Each species also showed distinct protease banding patterns in their excretory/secretory (E/S) products. The E. caproni E/S proteases were at 36 and 58 kDa, whereas those of E. trivolvis were at 120 and 168 kDa. Further characterization of E. caproni adult proteases revealed 2 bands (58 and 66 kDa) with optimal activity at pH 3.0-4.5 and 3 bands (38, 61, and 96 kDa) that were most active at pH 7.0-8.0. Four low molecular weight bands (19, 21, 25, and 30 kDa) appeared when E. caproni worm extracts were incubated in the presence of CaCl2 at pH 8.0 but were inhibited with ethylenediaminetetraacetic acid and 1,10-phenanthroline. Echinostoma caproni protease bands at 58 and 38 kDa in the whole worm samples and the E/S products and the 36-kDa band in the whole worm samples were inhibited with phenylmethylsulfonyl fluoride. By showing protease differences in addition to recent work on nucleotide differences, this study helps distinguish these 2 related allopatric species of 37-collar-spined Echinostoma.

Effects of Echinostoma caproni infections on metallic ions in the intestinal mucosa of ICR mice.

Inductively coupled plasma atomic emission spectrometry (ICP-AES) was used to study metallic ions in the intestinal mucosa of ICR mice infected with Echinostoma caproni and the mucosa of uninfected control mice. Infected mucosa (n = 9 with about 100 mg wet weight per sample) were examined at 2 weeks p.i. in mice that were infected with about 25 worms per host. Uninfected mucosa (n = 9 with about 100 mg wet weight per sample) were examined in the same time frame as the infected mucosa. Five metals were measured in the mucosa by ICP-AES analysis, as follows: calcium, potassium, magnesium, sodium and zinc. There were no significant differences (Student's t-test, P > 0.05) in the concentrations of calcium, potassium or zinc in infected versus uninfected mucosa. The concentration of sodium was significantly greater (P < 0.05) in the mucosa of infected versus uninfected mucosa, but the situation was reversed in regard to magnesium.

Distinct neurophysiological mechanisms for manic and cycloid psychoses: evidence from a P300 study on manic patients.

Pathologically asymmetrical P300 fields with right lateralized peaks were described in core schizophrenia as an expression of left-temporal functional deficits, while higher than normal amplitudes were found in cycloid psychosis. This latter finding appeared to be specific for cycloid psychosis and was explained by a generalized cerebral hyperarousal. Based on some psychopathological analogies with cycloid psychosis, and on the comparable pharmacological treatment of the acute episodes, a group of 19 manic patients was investigated immediately after remission and clinical stabilization of an episode. Patients with psychotic features were excluded to avoid overlaps with cycloid psychosis. Patients showed normal P300 amplitudes and no pathological asymmetries of the field, but more posterior positive areas compared to age- and sex-matched controls. This indicates that the neurophysiological changes underlying mania are different from both core schizophrenia and cycloid psychosis. Based on previous three-dimensional source location studies, this finding indicates that disinhibition due to reduced frontal lobe activity, and not hyperarousal, is the basic functional mechanism of manic disorders.

Loss of functional hemispheric asymmetry in Alzheimer's dementia assessed with near-infrared spectroscopy.

In a total of 10 patients with dementia of the Alzheimer-type (DAT) and in 10 healthy controls near-infrared spectroscopy (NIRS), a new non-invasive optical method, was used to measure the changes of concentrations of oxy- (O2HB) and deoxyhemoglobin (HHB) in left and right hemispheric prefrontal brain tissue areas during performance of the Verbal Fluency Test (VFT). On a neuropsychological level, the healthy subjects performed better in the VFT than patients with DAT. Statistical analysis of the relative concentrations of O2HB and HHB measured with NIRS during performance of the VFT revealed a significant interaction of the hemispheric effects with the diagnosis. A possible interpretation of this finding is that a good performance in the VFT relies on a predominantly left hemispheric activation observed in controls, whereas a low number of correct responses is associated with a loss of this asymmetric activation in patients with DAT. Although both, patients and controls, performed better in the category version of the VFT, the metabolic effects of this task were significantly less pronounced than in the letter version. This indicates that different energy demands, according to the type of access to the memory stores, may be interpreted as the result of a less energy-demanding access to categorically stored information and adds further evidence to the view that memory departments in humans are organized according to categorical principles.

Neurophysiological correlates of mental imagery in different sensory modalities.

Mental Imagery is supposed to be a basic phenomenon of conscious mental operations, which is exerted in any sensory modality. The aim of the present study was to investigate neurophysiological correlates of mental imagery in the visual, the acoustic and tactile modality. For that purpose, word lists were created based on their power to evoke mental imagery in these modalities. Nine young healthy volunteers were included. Words were presented on a computer screen with 3-s intervals. Evoked electrical activity was recorded simultaneously with a 21-channel system. After inspection for artifacts and off-line averaging, further analysis was performed in a time range of 250-450 ms, corresponding to the P300 component. Within this range, six topographically stable segments were found. A repeated measures ANOVA was significant for the left-right directions of the positive and of the negative centroid, but not for the anterior-posterior directions. The posterior centroid was most right-located in the visual sensory modality and most left-located for tactile imagery; in the acoustic modality it had a midline-position. These differences in centroid locations during mental imagery in different sensory modalities can be explained by the underlying activity of different neural generator ensembles, possibly involving modality specific primary cortical areas.

Observations on Echinostoma revolutum and Echinostoma trivolvis in single and concurrent infections in domestic chicks.

Studies were done to determine specific differences between adults of Echinostoma revolutum and Echinostoma trivolvis grown singly and concurrently in domestic chicks. Worm recovery at 10-21 days post-infection (p.i.) of E. revolutum and E. trivolvis in singly infected chicks was 21 and 17%, respectively; in concurrent infections, worm recovery for E. revolutum and E. trivolvis was 21 and 16%, respectively. The body area of E. trivolvis was 1.5-2.0 times greater than that of E. revolutum at 10-21 days p.i. Most body organ measurements of the suckers and gonads at 10, 14 and 21 days p.i. were significantly greater in E. trivolvis compared with those of E. revolutum. The mean dry weight/worm at 14 days p.i. was 2.5 mg for E. trivolvis and 1.0 mg for E. revolutum. In single infections, E. revolutum was found only in the rectum and E. trivolvis mainly in the lower ileum, and in concurrent infections worms of both species were found in the rectum. Contrary to a previous report that stated that the body size of adult worms is not a reliable taxonomic indicator between E. revolutum and E. trivolvis, the findings reported here show that body area and organ size can be used to distinguish these closely related species.

Decreased EEG microstate duration and anteriorisation of the brain electrical fields in mild and moderate dementia of the Alzheimer type.

Spatially oriented segmentation allows researchers to break down the continuous stream of the ongoing EEG into microstates with stable topography of the brain electrical landscapes. The resulting microstates were shown to be related to conscious mental experience as well as to psychiatric disorders typically associated with thought disorders. In the present study, the microstates of the resting EEG of patients presenting with mild or moderate probable dementia of the Alzheimer type (DAT) were investigated. A significant anteriorisation of the centers of gravity of the microstate fields, an increase of the microstates' optimal window size and a reduced duration of sustained microstates were found. These differences were statistically more robust than the typical changes in the frequency domain (diffuse slowing) and were significantly correlated with the cognitive decline. The adaptive spatial segmentation into microstates is discussed as a method to extract meaningful EEG parameters for the early diagnosis and staging of Alzheimer's disease.

Band 3 Memphis: a widespread polymorphism with abnormal electrophoretic mobility of erythrocyte band 3 protein caused by substitution AAG----GAG (Lys----Glu) in codon 56.

Band 3 Memphis (b3M) is a variant of the erythrocyte band 3 protein detected in individuals of virtually all ethnic groups and characterized by a reduced mobility of proteolytic fragments derived from the N-terminus of the cytoplasmic domain of band 3 (cdb3). We have sequenced band 3 cDNA corresponding to cdb3 in 12 heterozygotes for the b3M polymorphism including one white, one black, one Chinese, one Philippino, one Malay, and seven Melanesian subjects. In all individuals, we found a single-base substitution in codon 56 of one band 3 allele changing lysine to glutamic acid (AAG----GAG) which, in some of them, was linked with an additional mutation in cdb3. Since the change of codon 56 from AAG to GAG was the only mutation in the studied individuals found within the cDNA segment coding for the abnormally migrating fragment of cdb3, we conclude that it represents the underlying molecular basis of the b3M polymorphism. We further support this conclusion by showing that electrophoresis in the presence of 4 mol/L urea abolished the difference in migration between proteolytic products of b3M and normal band 3, and that a fusion protein prepared from cDNA coding for the b3M allele again exhibits reduced electrophoretic mobility compared with the normal fusion protein. Finally, since most of the previously cloned mouse, rat, and chicken band 3 and band 3-related proteins contain glutamic acid in the position corresponding to amino acid 56 in the human band 3, we propose that the Memphis variant is the evolutionarily older form of band 3.

Spatial zones of binocular rivalry in central and peripheral vision.

This paper presents results from psychophysical experiments on human binocular rivalry in central and peripheral vision. Results show that the incidence of periods of exclusive visibility of a given eye's rival target increased with decreasing target size, and for a given sized target exclusive visibility increased with retinal eccentricity. Control measures confirmed that these results were not attributable solely to reduced peripheral acuity, to Troxler's effect, or to spatial frequency. We computed the minimum-sized stimulus that would lead to a criterion level of exclusive visibility of one or the other eye; this we term the spatial zone of binocular rivalry. The change in estimated size of spatial zones of rivalry with eccentricity compares favorably with estimates of human cortical magnification. We propose a model that assumes concentrically organized zones of rivalry. These zones do not function independently, but instead exhibit a high degree of mutual excitatory cooperativity. The model has multiple solutions for the foveal zone size, but the best fits predict a diameter of 5.3 or 7.3 min of visual angle; these values dovetail nicely with our empirical estimates of the foveal zone size.

Rheologic properties of senescent erythrocytes: loss of surface area and volume with red blood cell age.

The rheologic properties of senescent erythrocytes have been examined using two models of red blood cell (RBC) aging. In the rabbit, aged erythrocytes were isolated after biotinylation, in vivo aging, and subsequent recovery on an avidin support. Aged RBCs from the mouse were obtained using the Ganzoni hypertransfusion model that suppresses erythropoiesis for prolonged periods of time allowing preexisting cells to age in vivo. In both cases, the aged erythrocytes were found by ektacytometry to have decreased deformability due to diminished surface area and cellular dehydration. The aged rabbit erythrocytes were further characterized by micropipette methods that documented an average surface area decrease of 10.5% and a volume decrease of 8.4% for the cells that were 50 days old. Because both the surface area and volume decreased with cell age, there was little change in surface-to-volume ratio (sphericity) during aging. The aged cells were found to have normal membrane elasticity. In addition, human RBCs were fractionated over Stractan density gradients and the most dense cells were found to have rheologic properties similar to those reported for the aged RBCs from rabbits and mice, although the absolute magnitude of the changes in surface area and volume were considerably greater for the human cells. Thus, stringent density fractionation protocols that result in isolation of the most dense 1% of cells can produce a population of human cells with rheologic properties similar to senescent cells obtained in other species. The data indicate that progressive loss of cell area and cell dehydration are characteristic features of cell aging.

Acquired flatfoot secondary to tibialis posterior dysfunction: biomechanical aspects.

The biomechanical implications of the normally-functioning tibialis posterior muscle and tendon unit, pathomechanics of its dysfunction, and its diagnosis are presented. The interaction of the tibialis posterior tendon with the rearfoot ligamentous system is discussed. An anatomic consideration of the glenoidal ligaments of the talonavicular joint new to the English literature is presented. A plan for staging the disease of tibialis posterior dysfunction and classifying its etiology is considered to be a prerequisite for proper treatment.

Frequencies of Band 3 variants of human red cell membranes in some different populations.

A variant of Band 3, the major protein of the erythrocyte membrane, was observed by Mueller and Morrison in 1977 in 6-7% of healthy blood donors on sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of erythrocyte membranes treated with pronase. Pronase treated red cells containing this first recognized variant [here designated 'Band 3-Memphis (m)'] section had two bands of about 63,000 and 60,000 Mr while pronase treated normal cells had only the lighter Mr band. The present study includes data on the frequency of variants resembling Band 3-Memphis in patients of different ethnic groups and on random donors obtained earlier in Memphis. These variants were detected by the original method of Mueller and Morrison and were not associated with recognized clinical or haematological abnormalities. Significantly higher gene frequencies for the variants of the (m) type were observed in American Indians, African Americans and Filipinos than in Caucasians; putative heterozygotes and homozygotes were identified among each of these groups. The frequency of silent Band 3 polymorphisms in different populations should be considered in the interpretation of clinical findings associated with the presence of Band 3 variants.

A physiological model of binocular rivalry.

This paper presents a modified reciprocal inhibition model for the temporal dynamics of binocular rivalry. The model is based on neurophysiological mechanisms and is derived from human psychophysical data. A simple reciprocal inhibition oscillator may be described with a set of four coupled differential equations with a neurophysiological interpretation. However, such a circuit does not account for some aspects of the temporal behavior of binocular rivalry, including the effects of contrast change on alternation rate and on the magnitudes of changes in duration of the suppressed and dominant phases. To better account for these phenomena, the equations and their stimulation are modified to include three new components: (1) presynaptic inhibition of the reciprocal inhibition by the input, (2) the motor delays that occur when a human observer tracks rivalry and (3) a minimum threshold for each neuron's state variable. The result is a much improved fit to psychophysically-obtained data on the temporal behavior of binocular rivalry. Finally, the model is incorporated into a larger model to suggest how rivalry might occur in a network that usually exhibits binocular fusion.

A fresh look at the temporal dynamics of binocular rivalry.

Human observers viewed dichoptic orthogonal sine-wave gratings and indicated when exclusive visibility occurred in either eye. Contrast was held constant in one eye and was increased or decreased in the other eye for a number of alternation cycles (continuous presentation) or for only the duration of a single period of exclusive visibility (synchronous presentation). The synchronous presentation condition allowed us to identify the differing effects of contrast during the suppressed and during the dominant periods. Mixed phases were recorded as distinct from suppressed and dominant phases, and new classifications of compound-dominant and compound-suppressed phases are defined. The results indicate that binocular rivalry responds to stimulus contrast in two ways. 1) The duty-cycle of dominance and suppression is determined by the relative image contrast between the two eyes, with dominance of the higher contrast image being favored, and 2) the overall rate of alternation is driven by monocular image contrast during the suppressed phase (increased monocular contrast increases the alternation rate) and to a lesser extent by monocular contrast during the dominant phase (increased monocular contrast decreases the rate). A model is developed to reflect these ideas. These results support a reciprocal inhibition oscillator as the underlying mechanism of binocular rivalry.

Membrane skeletal alterations during in vivo mouse red cell aging. Increase in the band 4.1a:4.1b ratio.

We have examined membrane protein profiles for alterations during red blood cell aging. To obtain populations of in vivo-aged red cells, we maintained mice in a state of continuous erythropoietic suppression for up to 8 wk using serial hypertransfusion. The circulating t1/2 of red cells from mice which had been erythropoietically suppressed for 8 wk was less than 1 d compared with a t1/2 of 15 d for red cells from normal animals. The most obvious alteration in membrane proteins was an increase in the ratio of the membrane skeletal components 4.1a:4.1b from 0.3 for the normal red cell population to greater than 1 for these old cells. The 4.1a:4.1b ratio thus appears to be a useful index of red cell age. Analyses of the density profile of cells aged in the hypertransfused mice disclosed that these old cells had a density range similar to that of controls, suggesting that cell density does not increase significantly with red cell age in the mouse.

The role of erythropoietin in the production of principal erythrocyte proteins other than hemoglobin during terminal erythroid differentiation.

Erythropoietin (EP) controls the terminal phase of differentiation in which proerythroblasts and their precursors, the colony forming units-erythroid (CFU-e), develop into erythrocytes. Biochemical studies of this hormone-directed terminal differentiation have been hindered by the lack of a homogeneous population of erythroid cells at the developmental stages of CFU-e and proerythroblasts that will synchronously differentiate in response to EP. Such a population of cells can be prepared from the spleens of mice with the acute erythroblastosis resulting from infection with anemia-inducing Friend virus (FVA). Using these FVA-infected erythroid cells, which were induced to differentiate with EP, four proteins other than hemoglobin that have key functions in mature erythrocytes were monitored during the 48-hour period of terminal differentiation. Synthesis of spectrin and membrane band 3 proteins were determined by immunoprecipitation and SDS-polyacrylamide gel electrophoresis; accumulation of the cytoskeletal protein band 4.1 was monitored by immunoblotting; carbonic anhydrase activity was measured electrometrically. Band 3 synthesis and band 4.1 accumulation could be detected only after exposure of the cells to EP. Spectrin synthesis was ongoing prior to culture with EP, but it did increase after exposure to the hormone. Carbonic anhydrase-specific activity changed very little throughout the terminal differentiation process. These results reveal at least three patterns of production of principal erythrocyte proteins during EP-mediated terminal differentiation of FVA-infected erythroid cells. Depending on the specific protein examined, de novo synthesis can be induced by EP, an ongoing production can be enhanced by EP, or the production of a protein can be completed at a developmental stage prior to EP-mediated differentiation in these cells.

Catabolism of the anion transport protein in human erythrocytes.

We identified the catabolic products of protein 3 in human erythrocytes. Protein 3, the major protein of the erythrocyte membrane, functions in anion transport and reacts covalently with tritiated 4,4'-diisothiocyano-1,2-diphenylethane-2,2'-disulfonic acid ([3H]DIDS), a very selective inhibitor of anion transport. In this study, [3H]DIDS was used to label protein 3 in the membranes of normal cells and those from a donor heterozygous for a variant of protein 3, defined by its elongated amino-terminal end. Both types of cells contained [3H]DIDS-labeled peptides other than protein 3. A protein fragment of 60K molecular weight was found in normal cells, whereas both 60K and 63K fragments were identified in cells from the heterozygote. These peptides are identical with those generated by treatment of intact erythrocytes with Pronase or chymotrypsin. A polyclonal rabbit antibody specific for the purified 60K fragment of protein 3 was used to detect this protein and its products in the erythrocyte membrane. Autoradiographs of membrane peptides that were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred to nitrocellulose, and allowed to react with the monospecific antibody showed, in addition to protein 3, a 60K fragment and fragments in the 40K region and in the 20-30K region. Cells containing the protein 3 variant yielded two fragments showing a 3K difference in molecular weight in all three regions, demonstrating that degradation of protein 3 is identical in normal erythrocytes and those heterozygous for the variant. This observation also confirms the common derivation of the fragments from protein 3.(ABSTRACT TRUNCATED AT 250 WORDS)