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[The effect of dilantin on the neuronal reactions of the sensorimotor cortex and hippocampus during learning].

After dilantin (D) administration in a dose which reduced posttetanic potentiation (according to the data of literature), probability of movements to light flashes (conditioned signal of a defensive reflex) did not change. Weak but stable disinhibition of motor reactions to flashes was observed when they were presented at the background of continuous light as a conditioned inhibitor. Activation of neurons of the sensorimotor cortex in response to reinforced and non-reinforced light flashes increased under D action (as it had been earlier observed in neurons of the visual cortex), and activatory reactions to pain reinforcement decreased. In hippocampal neurons increase of the rate of impulsation in response to reinforced flashes under the action of D disappeared. On the basis of the data obtained it can be concluded that PTP in the neocortex does not participate in long-term memory storage of the biological significance of activating stimulus.

Animals↗

Operant conditioning and discrimination of alpha: some methodological limitations inherent in response-discrimination experiments.

Studies on the operant conditioning of central nervous system activity have produced results interpreted as demonstrating that responses, certain properties of responses, or response-produced stimuli can function as discriminative stimuli. It is assumed that the feedback stimulus in biofeedback makes the subject aware of the internal response and that by becoming aware of the response, the subject can acquire voluntary control over it. In this context, awareness is operationally defined as the ability to use the response as a discriminative stimulus. Since direct evidence for the assumed relationship between control and discrimination is lacking, an attempt was made to test the hypothesis that discrimination of a response automatically leads to control over that response. The discriminative stimuli were the presence and absence of occipital alpha electroencephalograph (EEG) activity. Data from two experiments are reported. The first study, employing naive subjects, was designed to answer the following questions: (a) Since pilot data indicated that subjects seemed to match their responses to the more probable type of trial, would increases in the probability of a correct response result when the probabilities of alpha and nonalpha trials were held near .50? (b) If correct responding does increase, would performance of these subjects in an alpha feedback task be enhanced relative to that of subjects not previously given discrimination training? and (c) If subjects could not learn the discrimination task, would feedback training enhance their performance in a subsequent discrimination task? Results from this study indicate that holding the probabilities of alpha and nonalpha discrimination trials near .50 results in an absence of learning curves, but leaves open the possibility that sophisticated subjects are capable of discriminating alpha and nonalpha activity. The second study deals with two questions: (a) Can sophisticated subjects learn to discriminate occipital alpha activity from nonalpha activity? and (b) Does the procedure of providing subjects with salient stimuli, contingent on the presence and absence of alpha activity, establish stimulus control of the presence and absence of alpha activity? Results indicate that it is not possible to conclude that subjects can learn to discriminate alpha and nonalpha activity. However, learning to increase percent-time nonalpha or decrease percent-time alpha with respect to baseline levels by means of EEG-contingent stimulation provides subjects with the ability to suppress percent-time alpha in the absence of feedback. Information gained in both studies through subject interviews indicates that subjects most often acquired their control of alpha activity during feedback by a specific strategy and then used the strategy during the stimulus-control tests.

Alpha Rhythm↗

Hypertension and the kidney: lessons learned from transplantation.

This review discusses the analogies between some experimental models of arterial hypertension and some probable causes of hypertension in kidney-transplanted patients. Some subgroups of these patients have striking similarities with some animal models: Data suggest that the genetic predisposition to hypertension can be transmitted with the kidney, similar to the transplantation experiments in genetically hypertensive rat stains. Patients with graft artery stenosis, if previously binephrectomized, present the same puzzling sequence of events in the development of hypertension as the one-kidney one-clip Golblatt hypertension animal models. "Native kidney" hypertension can be related to a state of chronic angiotensin excess as in the chronically angiotensin-infused animals. Confounding variables include chronic steroid therapy, chronic rejection, and the possible role of renal nerve regeneration. There are also animal models available for these contributing factors that allow us to understand the many facets of post transplant hypertension better.

Angiotensin II↗

Learning multiple evolutionary pathways from cross-sectional data.

We introduce a mixture model of trees to describe evolutionary processes that are characterized by the ordered accumulation of permanent genetic changes. The basic building block of the model is a directed weighted tree that generates a probability distribution on the set of all patterns of genetic events. We present an EM-like algorithm for learning a mixture model of K trees and show how to determine K with a maximum likelihood approach. As a case study, we consider the accumulation of mutations in the HIV-1 reverse transcriptase that are associated with drug resistance. The fitted model is statistically validated as a density estimator, and the stability of the model topology is analyzed. We obtain a generative probabilistic model for the development of drug resistance in HIV that agrees with biological knowledge. Further applications and extensions of the model are discussed.

Algorithms↗

Spatial EEG correlates of nonassociative and associative olfactory learning in rabbits.

Recent studies have shown that spatially distributed olfactory bulbar activity correlates with odor-specific behavioral responding (Coopersmith & Leon, 1984; Freeman & Grajski, 1987; Freeman & Schneider, 1982; Freeman & Viana di Prisco, 1986; Grajski, Breiman, Viana di Prisco, & Freeman, 1986; Gray, Freeman, & Skinner, 1986; Sullivan & Leon, 1986; Viana di Prisco & Freeman, 1985). The present studies established olfactory bulbar spatial electroencephalogram (EEG) correlates of nonassociative and associative learning in odorant stimulation in rabbits. Behavior was quantified by measuring magnitude and probability of the sniff response. It was shown that (a) olfactory bulbar spatial EEG amplitude patterns do not simply reflect odor (peripheral) stimulation, (b) repeated presentations of a nonreinforced odor initially reveal a transient EEG pattern change but the pattern change does not recur after the subject has habituated to the odor, and (c) repeated presentations of a reinforced odor (mild cutaneous shock), with a second nonreinforced odor serving as a control, reveal that coexisting, odor-specific spatial EEG amplitude patterns emerge with the acquisition of differential behavioral responding.

Animals↗

Pyrogens specifically disrupt the acquisition of a task involving cognitive processing in the rat.

In addition to changes in body temperature and other metabolic and physiological responses corresponding to immune activation, pyrogens can induce profound behavioral changes referred to collectively as sickness behavior. One feature of sickness behavior, sometimes reported in clinical settings, but rarely exposed to experimental analysis, is depressed cognitive functioning. The present series of five experiments sought to demonstrate the existence of specific cognitive deficits in rats, independently of any confounding performance effects of pyrogen injections. The behavioral task used, called autoshaping, consisted of presenting hungry Wistar rats with a stimulus (introduction of a retractable lever) that predicted food delivery. Control rats quickly learned to press the lever, although this response does not influence the probability of food delivery. When pyrogens (250 micrograms/kg lipopolysaccharide, 4 micrograms/rat interleukin-1 beta, or 300 mg/rat yeast) were injected to rats during acquisition of this task, they severely disrupted acquisition while the pyrogen was active. The same treatments were, however, without effect on performance when injected later, when performance had stabilized. It is argued that these results demonstrate specific, performance-independent effects of pyrogens on the cognitive processes needed for the acquisition of this task. The results are discussed in terms of the relationship between these effects and the cytokines induced in the brain by pyrogens, and in terms of the exact nature of the cognitive process likely to be affected.

Animals↗

Predicting the success of cataract surgery.

Fifty-four elderly patients with cataracts were tested with a questionnaire and a series of visual-motor learning and performance tasks immediately before, 7 weeks after, and 16 weeks after cataract surgery. The goal was to learn whether postoperative performance and questionnaire responses could be predicted from the preoperative tasks. Twenty-two elderly people without diagnosed cataracts did the same tasks at comparable intervals to establish normal performance levels and reliabilities. The amount of activity before surgery (walking, shopping, gardening, sewing, etc.) and the ability to learn a new visual-motor coordination were positively correlated with successful recovery as assessed by several measures including spontaneously expressed satisfaction.

Aged↗

How do surgeons' probability estimates of operative mortality compare with a decision analytic model?

The aim of this study is to compare surgeons' estimates of operative mortality of patients with an abdominal aneurysm (= dilation of the aorta) with the operative mortality derived from a decision analytic model and to determine how surgeons use clinical information. Four experienced surgeons are asked to estimate, among other things, the operative mortality of 137 patients. Results concerning the accuracy of surgeons' estimates show that surgeons' average operative mortality estimates are quite accurate as compared to the calculated mortalities. The standard deviations of surgeons' estimates are lower than the standard deviation of the model, however, indicating that the surgeons are not as good in distinguishing the high and low risk patients. Furthermore, surgeons show substantial inconsistencies in the weighing of the clinical information, and also differ from the model in how clinical information is weighed. Finally, when comparing the operative mortalities of the patients who died and those who did not, the model shows a modest, but higher discrimination than the surgeons. Physicians' performance seems to be influenced by the difficulty of the task (i.e. the unpredictability of the event and the multidimensionality of the task). In order to improve physicians' probability estimates, the calculations of the decision model can be used as learning tool.

Aortic Aneurysm, Abdominal↗

Knowledge-based battery design of short-term tests based on dose information.

A construction of batteries of short-term tests (STTs) is described which is based on a classification of 73 chemicals in regard to their carcinogenicity. The 73 chemicals were studied within the U.S. National Toxicology Program (Ashby and Tennant, 1988). The batteries are validated using the classification of 35 additional chemicals. They are defined by logically structured combinations of rules. The single rules are defined by the z-scores of the logarithmic values of the limiting doses obtained from the 4 in vitro STTs used in the study by Ashby and Tennant. The limiting dose is defined as the lowest effective dose or the highest ineffective dose (Waters et al., 1987). The batteries are constructed by minimizing the number of disagreements with the classification by Ashby and Tennant. Compared with the results obtained from single STTs, 2 batteries of 3 STTs have higher concordances with the carcinogenicity data, namely 70% for the NTP data and 74-77% for the independent test data. In addition, a theoretical result shows that the proposed battery design, for a large enough learning set of chemicals, leads to results which are replicated with high probability on a large enough validation set. Based on the first results obtained with a limited number of chemicals it is concluded that the knowledge-based battery design is worth further development.

Animals↗

Implantation of encapsulated glial cell line-derived neurotrophic factor-secreting cells prevents long-lasting learning impairment following neonatal hypoxic-ischemic brain insult in rats.

OBJECTIVE: Implantation of encapsulated glial cell line-derived neurotrophic factor-secreting cells into brain parenchyma reduces histological brain damage following hypoxic-ischemic stress in neonatal rats. We examined the effect of glial cell line-derived neurotrophic factors on long-term learning and memory impairment and morphological changes up to 18 weeks after hypoxic-ischemic stress in neonatal rats. STUDY DESIGN: Baby hamster kidney cells were transfected with expression vector either including (glial cell line-derived neurotrophic factor-hypoxic-ischemic group; n = 10) or not including (control-hypoxic-ischemic group; n = 8) human glial cell line-derived neurotrophic factor cDNA, encapsulated in semipermeable hollow fibers, and implanted into the left brain parenchyma of 7-day-old Wistar rats. Two days after implantation the rats received hypoxic-ischemic stress, and their behavior was then examined in several learning tasks: the 8-arm radial maze, choice reaction time, and water maze tasks, which examine short-term working memory, attention process, and long-term reference memory, respectively. The rats were killed 18 weeks after the hypoxic-ischemic insult for evaluation of brain damage. Two additional control groups were used: the control group (n = 15), which underwent no treatment, and the glial cell line-derived neurotrophic factor group (n = 6), which underwent implantation of the glial cell line-derived neurotrophic factor capsule but did not undergo hypoxic-ischemic stress. RESULTS: The decrease in the size of the cerebral hemisphere was significantly less in the glial cell line-derived neurotrophic factor-hypoxic-ischemic group, compared with the control-hypoxic-ischemic group, and improved performance was observed in all three tasks for the glial cell line-derived neurotrophic factor-hypoxic-ischemic group: for the control-hypoxic-ischemic group versus the glial cell line-derived neurotrophic factor-hypoxic-ischemic group, respectively, in the 8-arm radial maze test, average number of correct choices was 6.2 +/- 0.1 versus 6.9 +/- 0.1 ( P < .01); in the choice reaction time test, average reaction time for a correct response was 2.35 +/- 0.1 seconds versus 1.97 +/- 0.09 seconds ( P < .01); in the water maze test, average swimming length was 1120.0 +/- 95.2 cm versus 841.6 +/- 92.1 cm ( P < .01). All results for the glial cell line-derived neurotrophic factor group were similar to those for the control group. CONCLUSION: Glial cell line-derived neurotrophic factor treatment is effective in not only reducing brain damage but also inhibiting learning and memory impairment, following hypoxic-ischemic insult in neonatal rats. No adverse effects in learning and memory tests were observed in the glial cell line-derived neurotrophic factor group.

Analysis of Variance↗

Selective attention to human voice enhances brain activity bilaterally in the superior temporal sulcus.

Regional cerebral blood flow was measured with positron emission tomography (PET) in 10 healthy male volunteers. They heard two binaurally delivered concurrent stories, one spoken by a male voice and the other by a female voice. A third story was presented at the same time as a text running on a screen. The subjects were instructed to attend silently to one of the stories at a time. In an additional resting condition, no stories were delivered. PET data showed that in comparison with the reading condition, the brain activity in the speech-listening conditions was enhanced bilaterally in the anterior superior temporal sulcus including cortical areas that have been reported to be specifically sensitive to human voice. Previous studies on attention to non-linguistic sounds and visual objects, in turn, showed prefrontal activations that are presumably related to attentional control functions. However, comparisons of the present speech-listening and reading conditions with each other or with the resting condition indicated no prefrontal activity, except for an activation in the inferior frontal cortex that was presumably associated with semantic and syntactic processing of the attended story. Thus, speech listening, as well as reading, even in a distracting environment appears to depend less on the prefrontal control functions than do other types of attention-demanding tasks, probably because selective attention to speech and written text are over-learned actions rehearsed daily.

Adult↗

Autoantibodies to citrullinated proteins in rheumatoid arthritis: clinical performance and biochemical aspects of an RA-specific marker.

Rheumatoid arthritis (RA) is a common, systemic autoimmune disease of which the exact etiology is not known. In the past 10 years, substantial progress has been made in the identification of the antigens specifically recognized by the autoantibodies of RA patients. A central factor in this respect is citrullination, a form of post-translational modification that is strongly associated with autoimmunity in RA. Here, we summarize and discuss our current knowledge on (i) autoantibody systems in RA, (ii) the occurrence of peptidylarginine deiminases and (iii) citrullinated proteins in natural and diseased environments, and (iv) genetic factors involved in RA that may influence the generation and presentation of citrullinated proteins and the resulting antibody production against these modified proteins. Citrullination of proteins may play a key role in the initiation and/or the progression of RA. The onset of citrulline-specific autoimmunity in RA is probably mediated by both environmental and genetic factors, and future studies will learn whether therapeutic intervention at the level of citrullination may provide new possibilities to treat RA.

Antibody Specificity↗

Event-related neural activity associated with habit and recollection.

The neural activity associated with conscious recollection and habit was examined using event-related brain potentials. In a training phase, participants learned A-B, A-C word associations in which the probability of specific responses was varied. Once a habit was established, participants studied and were tested on a series of short lists consisting of word pairs seen in training. The process-dissociation procedure was used to estimate the contribution of habit and recollection to memory performance. Habit estimates reflected the probability with which information was presented in training but recollection estimates did not show this effect. Recollection was associated with sustained negativity over the parieto-occipital region, which was opposite in polarity over the frontal regions. Indices of habit strength were associated with a sustained positivity over left fronto-temporal regions and a sustained negativity over right fronto-central regions. Partial-least squares analyses revealed two significant latent variables that distinguished recollection and habit, consistent with the distinction between consciously controlled and automatic influences of memory.

Adult↗