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Left and right visual field advantages are a function of scotopic and photopic retinal adaptation, respectively, in simple reaction time to near-threshold targets.

Modulation of stimulus luminance in a tachistoscopic face discrimination task has been found to significantly invert visual hemifield advantage in reaction time (RT) (Sergent, 1982a, Sergent, 1982b). However, there is no more physiological rationale for that than for a similar effect, say, of retinal adaptation, and it is even conceivable that the latter may have confounded the former in past experiments. The experiments reported here were therefore designed to tease out the relative contributions of stimulus luminance and of background illumination (i.e., retinal adaptation) in a simple RT task. Two equally difficult conditions of dim targets were set up, one with light-adapted subjects and one with dark-adapted subjects. Similarly, two equally difficult conditions of bright targets were set up with light and dark-adapted subjects. It was found that dim targets (near detection threshold) yielded a significant right visual field RT advantage in light-adapted subjects and that dim targets (equally near detection threshold) yielded a significant left visual field RT advantage in dark-adapted subjects. Future experiments will determine whether cone-mediated RT to detection is left hemisphere dominant and whether rod-mediated RT to detection is right hemisphere dominant.

Adaptation, Ocular↗

Sensitivity to eye gaze in prosopagnosic patients and monkeys with superior temporal sulcus ablation.

Accuracy at perceiving frontal eye gaze was studied in monkeys and human subjects using a forced-choice detection task on paired photographs of a single human face. Monkeys learned the task readily, but after bilateral removal of the banks and floor of the superior temporal sulcus (STS) they failed to perform the task efficiently. This result is consistent with the conclusion, based on recordings from single cells in awake, behaving monkeys [Perret et al., Physiological Aspects of Clinical Neuro-ophthalmology, Chapman & Hall, London, 1988] that this region of the temporal lobe is important for coding information about eye-gaze of a confronting animal. Human subjects were given identical stimuli in a task where they were asked to detect "the face that is looking straight at you". Human performance is sensitive to the degree of angular deviation from the frontal gaze position, being poorest at small angular deviations from 0 degrees. This was also true of monkeys viewing these stimuli, pre- and post-operatively. Compared with normal controls, two humans prosopagnosics were impaired at this task. However the extent of impairment was different in the two patients. These findings are related to earlier reports (including those for patients with right-hemisphere damage without prosopagnosia), to normal performance with upright and inverted face photographs, and to notions of independent subsystems in face processing.

Adult↗

Responses to activation and rest in patients with panic disorder and major depression.

Physical activity may be a trigger for panic attacks in patients with panic disorder, while exercise may have an antidepressant effect in patients with major depression. In order to examine reactions to rest as well as to exercise periods, we assessed physiological responses (heart rate, blood pressure), subjective responses on a visual analogue scale, and attentional responses with the span of apprehension test. Twenty participants met the diagnostic criteria for panic disorder, 20 patients had major depression, and 20 participants served as controls. Patients with major depression showed slower reaction times than participants in the other groups; this difference was more pronounced with increased task difficulty. Physical activation led to lower depression scores in all groups. Patients with panic disorder had elevated anxiety scores after physical activation, but also after rest. Heart rate as well as systolic blood pressure showed the expected acceleration after physical activation, but there were no differences between the groups. Activation did not seem to influence attentional performance as measured by the span of apprehension test. Results are consistent with a cognitive view of panic disorder. In contrast to patients with panic disorder, patients with major depression seem to have an attentional deficit which is more pronounced with more complex cognitive processing.

Adult↗

Transparent motion perception as detection of unbalanced motion signals. II. Physiology.

We investigated how the primate visual system solves the difficult problem of representing multiple motion vectors in the same part of the visual space--the problem of motion transparency. In the preceding companion article we reported that displays with locally well-balanced motion signals in opposite directions are perceptually nontransparent (i.e., one does not see two coherent moving surfaces) and that transparent displays always contain locally unbalanced motion signals. This is exemplified by our paired and unpaired dot patterns. Although both types of stimuli contain two sets of dots moving in opposite directions, the former is locally well balanced and appears like flicker while the latter gives a perception of two transparent surfaces. In this article we report our physiological recordings from areas V1 and MT of behaving monkeys, comparing single-cell responses to the paired and the unpaired dot patterns. Although a small proportion of directionally selective V1 cells responded differently to the two types of patterns, the average V1 responses could not reliably distinguish between the paired and the unpaired stimuli. A large fraction of MT cells, on the other hand, responded significantly better to the unpaired dot patterns than to the paired ones. Furthermore, the average response of all MT cells to the unpaired dot patterns was significantly higher than that to the paired dot patterns. These results demonstrate a neural correlate of the perceptual transparency at the level of MT. On the other hand, V1 cells do not generally discriminate between the transparent and nontransparent stimuli, indicating that V1 activity is not well correlated with the perception of motion transparency. Our results are consistent with a two-stage model for motion processing: the first stage measures local motion and the second stage introduces suppression if different directions of motion are present at a local region of the visual field. The first stage is located primarily in V1 and the second stage primarily in MT. Finally, we found a strong and negative correlation between the degree of the opponent-direction suppression of MT cells and their responses to flicker noise stimuli. This result suggests that one of the fundamental roles of the opponent-direction suppression in MT is noise reduction.

Animals↗

Relationship between cortical lamination and texture sensitivity in complex neurones of the striate cortex in cats.

The present study provides detailed anatomical evidence that the strongly texture-sensitive complex neurones of the cat's striate cortex constitute a discrete subset of all complex neurones, and lie in two bands, deep in lamina III and in lamina V. Physiological properties of simple and complex striate cortical neurones were characterized extracellularly in lightly anaesthetized cats by use of micropipettes filled with 12% Fast Green FCF dye in 2.0 M sodium chloride. Complex neurones were further subdivided on the basis of their length-summating properties for an optimally oriented bar into "standard," "special," or "intermediate" categories and on the basis of their tuning and degree of sensitivity to motion of random texture. Extracellular dye marks were made at strategic locations along each microelectrode track, especially at the site of recording from strongly texture-sensitive complex neurones. Tracks were reconstructed with the aid of the histologically recovered dye marks in sections counterstained with cresyl violet to reveal cortical lamination. The results confirm and refine the inference made by Hammond and MacKay (Exp. Brain Res. 22:427-430, '75; Exp. Brain Res. 30:275-296, '77) and the gross observations from 2-deoxyglucose uptake studies by Wagner, Hoffmann, and Zwerger (Brain Res. 224:31-43, '81) concerning the laminar distribution of texture-sensitive complex neurones in the cat's striate cortex.

Animals↗

Multidimensional rhythm disturbances as a precursor of sustained ventricular tachyarrhythmias.

Cardiac cycle dynamics reflect underlying physiological changes that could predict imminent arrhythmias but are obscured by high complexity, nonstationarity, and large interindividual differences. To overcome these problems, we developed an adaptive technique, referred to as the modified Karhunen-Loeve transform (MKLT), that identifies an individual characteristic ("core") pattern of cardiac cycles and then tracks the changes in the pattern by projecting the signal onto characteristic eigenvectors. We hypothesized that disturbances in the core pattern, indicating progressive destabilization of cardiac rhythm, would predict the onset of spontaneous sustained ventricular tachyarrhythmias (VTAs) better than previously reported methods. We analyzed serial ambulatory ECGs recorded in 57 patients at the time of VTA and non-VTA 24-hour periods. The disturbances in the pattern were found in 82% of the recordings before the onset of impending VTA, and their dimensionality, defined as the number of unstable orthogonal projections, increased gradually several hours before the onset. MKLT provided greater sensitivity and specificity (70% and 93%) compared with the best traditional method (68% and 67%, respectively). We present a theoretical analysis of MKLT and describe the effects of ectopy and slow changes in cardiac cycles on the disturbances in the pattern. We conclude that MKLT provides greater predictive accuracy than previously reported methods. The improvement is due to the use of individual patterns as a reference for tracking the changes. Because this approach is independent of the group reference values or the underlying clinical context, it should have substantial potential for predicting other forms of arrhythmic events in other populations.

Algorithms↗

Steroid hormones and excitability in the mammalian brain.

Adrenocortical and gonadal steroid hormones can pass the blood-brain barrier and bind to intracellular receptors in the brain. In addition to steroid hormones binding to intracellular steroid receptors, metabolites of these steroids and steroid hormones produced in the brain (neurosteroids) are thought to bind to membrane recognition sites. Actions mediated by the intracellular receptors are generally delayed in onset and are of prolonged duration, whereas the hormones binding to membrane recognition sites induce fast effects. Both fast and delayed actions by steroid hormones potentially alter the electrical properties of neuronal membranes and thus the firing patterns of neurons carrying receptors for the hormones. We here review the fast and delayed actions by steroid hormones on single cell electrical properties in the mammalian nervous system. In general, fast effects by corticosteroids-presumably mediated by membrane receptors-induce inhibitory effects on cellular firing, although regional differences seem to exist. Delayed effects by corticosteroid hormones via mineralocorticoid receptors serve to maintain or enhance fast transmission in the brain, while modulatory inputs are suppressed. By contrast, corticosteroids acting through glucocorticoid receptors suppress transmission carried by amino acids, particularly when the activity is elevated in comparison to resting level; modulatory inputs are enhanced. Prolonged activation of glucocorticoid receptors can implicate the integrity of neuronal circuits by allowing considerable influx of calcium ions during depolarization. Of the gonadal hormones, estradiol mainly exerts excitatory actions, in both a rapid and a delayed mode. Progesterone on the other hand is predominantly inhibitory, usually with a short delay in onset. The effect of androgens on neuronal excitability has not yet been studied in great detail. Finally, neurosteroids and A-ring reduced steroids in general induce rapid effects on firing patterns, probably by acting on ligand gated ion channels. The diverse actions of steroid hormones on single cell activity have consequences for the excitability in local circuits in which these cells participate. This is illustrated in this review for two processes that depend on circuit rather than single cell function, i.e., long term potentiation and epilepsy. The diverging character of steroid hormones with regard to the time frame, space, and nature of their effects is also reflected in the functional processes that are linked to the activity of the networks responding to steroids. In this way steroid hormones add an essentially new aspect to the regulation of functional processes in the brain, during physiological conditions but also when networks are implicated during diseases and disorders. Future research on steroid modulation of cellular excitability will gain considerably from attempts to either link the changed excitability to the underlying molecular events or study the effects on cellular activity in close connection with behavioral functions.

Animals↗

Thalidomide as an anti-cancer agent.

Thalidomide is a glutamic acid derivative initially introduced as a sedative hypnotic nearly forty years ago. It was withdrawn following numerous reports linking it to a characteristic pattern of congenital abnormalities in babies born to mothers who used the drug for morning sickness. It has gradually been re-introduced into clinical practice over the past two decades, albeit under strict regulation, since it was found to be useful in the management of erythema nodosum leprosum and HIV wasting syndrome. Recognition of its anti-angiogenic effect led to its evaluation in the treatment of various malignancies, where angiogenesis has been shown to play an important role. Numerous clinical trials done over the past four years have confirmed the significant anti-myeloma activity of this drug. It has also shown promise in preliminary trials in the treatment of a variety of different malignant diseases. The mechanisms of its antineoplastic effects continue to be the focus of ongoing research. It has become clear that even though its anti angiogenic effects play a significant role in the anti-tumor activity, there are other properties of this drug which are responsible as well. It also possesses anti-TNF alpha activity, which has led to its evaluation in several inflammatory states. In this concise review, we briefly describe the historical background and pharmacological aspects of this drug. We have concisely reviewed the current knowledge regarding mechanisms of its anti-neoplastic activity and the results of various clinical trials in oncology.

Antineoplastic Agents↗

ESS, eye stimulator system for VVIS facility (Visual and Vestibular Investigation System).

The ESS (Eye Stimulation System) is one of four main Subsystems of the Visual and Vestibular Investigation System ( VVIS ), Facility developed in the field of EDEN program and aimed to the research in the area of neurosensors physiology under microgravity conditions. In particular, the ESS is an Optokinetic Stimulator that stimulates the Subject's eyes with moving black and yellow patterns, in order to allow, by another main Subsystem, video recording of the pupil movement and, successively, to elaborate the relevant data of the neurovestibular experiment. This Stimulator was designed by the Officine Galileo as Subcontractor of Aerospatiale, leader of the VVIS facility, developed under ESA contract and successfully flown in April 1998 aboard the Neurolab mission. The Eye Stimulation System, on the frame of the VVIS Facility, is used in conjunction with the Body Rotating Device and the Eye Movement and Recording System, in order to fulfill all operations that lead to carry-out the experiments proposed. The Subject, seated on the Rotating Chair, observes the stimuli on a display monitor through a set of lenses, mounted on a proper box, fixed to a main structure of the unit. The stimuli patterns are showed on a display, placed on a movable support in order to fix it in a proper position, depending on the optical characteristics of the Subject. The experiments are repeated with different kind of patterns. All the main components of the visual system are mounted on a structural base plate, that gives also the mechanical I/F with the other system, supporting the ESS.

Computer Graphics↗

Electro-physiological investigation of edge-selective mechanisms of human vision.

This study investigates the spatial and temporal characteristics of human visual mechanisms that respond selectively to the polarity of edges. The technique was to record steady-state visual evoked-potentials (VEPs) while visually stimulating with a sawtooth waveform (a series of edges of the same polarity) periodically reversing in contrast (and hence edge-polarity) at a suitable frequency. To ensure that phase-locked VEPs resulted from polarity reversal (rather than local luminance modulation) the stimuli were randomly jittered to a new position between each contrast reversal. The jittered stimulus elicited strong and reliable second-harmonic modulation, usually about one-fifth the amplitude of standard VEPs under similar conditions. The amplitude and extrapolated thresholds of polarity-specific VEPs (relative to standard VEPs) did not vary with eccentricity (up to 10 degrees) or with stimulus orientation. The dependency on spatial frequency was similar to that of standard VEPs, but the polarity-specific VEPs tended to peak at lower temporal frequencies. Perhaps the clearest difference in the two types of VEPs was in the estimated response latency, about 140 msec for the polarity VEPs, compared with 90 msec for standard VEPs.

Contrast Sensitivity↗

How patterns of bleached rods and cones become visual perceptual experiences: a proposal.

In an attempt to increase information about how mammalian visual systems create a perceptual experience out of a retinal photochemical bleach pattern, this article brings together recent rat physiological data acquired with large electrodes, an old cat behavioral experiment, and two complex human behaviors: reading and the reversible blindness people experience when the scene being viewed is stabilized on the retinal surface. The outcome suggests this juxtaposition of disparate data sets has been logical, reasonable, and informative. The link between rats and reading is the fact that both rat and human retinas convert bleach patterns into ganglion cell volleys 3 times a second. The probable trigger for these episodic retinal volleys is a more or less abrupt change in the pattern of bleached rods and cones, and we claim the absence of this trigger when the image is stabilized is responsible for the blindness. The cat behavioral experiment correlates performance on visual discrimination tasks with the number of nerve fibers remaining after lesions of the optic tract. The analysis of the result, which shows that as few as 2% of the normal number of nerve fibers supports perfect performance of such tasks, prompts the concept of a second dynamic visual system, operating in parallel with the anatomical nervous system pictured in the textbooks. The dynamic visual system model, which brings into the foreground important old facts that have been neglected and integrates them with new data, offers a synthesis that may be useful in interpreting classical visual behavioral phenomena.

Animals↗

Effects of sex steroids on women's health: implications for practitioners.

Androgen excess in women is manifested typically by clinical features that may include hirsutism, acne, central obesity, male-pattern baldness, upper torso widening, increased waist-to-hip ratio, clitoral hypertrophy, and deepening of the voice. The differential diagnosis includes androgen-producing ovarian and adrenal neoplasms, Cushing's syndrome, polycystic ovary syndrome, and the intake of exogenous androgens. Physicians treating patients for one symptom of androgen excess must be alert for other symptoms and signs. The cosmetic manifestations of androgen excess belie the serious health risks associated with this condition, including cardiovascular disease, intravascular thrombosis, and insulin resistance. Prompt clinical recognition of androgen excess, understanding of the androgen-related biochemical abnormalities underlying the risks associated with this condition, and implementation of risk modification can reduce the incidence of associated morbidity and mortality. An interdisciplinary approach to management is strongly recommended. Risk reduction strategies include correction of dyslipidemias, low-dose aspirin for primary prevention of myocardial infarction, maintenance of ideal weight, smoking cessation, exercise, use of oral contraceptives containing a low-androgenic progestin, and postmenopausal estrogen replacement. Combination oral contraceptives containing low-androgenic progestins are effective not only in reducing signs of androgen excess but also in potentially retarding the progression of long-term sequelae such as cardiovascular disease.

Cardiovascular Diseases↗

Conformationally constrained analogues of diacylglycerol (DAG). 16. How much structural complexity is necessary for recognition and high binding affinity to protein kinase C?

The design of potent protein kinase C (PK-C) ligands with low nanomolar binding affinities was accomplished by the combined use of pharmacophore- and receptor-guided approaches based on the structure of the physiological enzyme activator, diacylglycerol (DAG). Earlier use of the former approach, which was based on the structural equivalence of DAG and phorbol ester pharmacophores, identified a fixed template for the construction of a semirigid "recognition domain" that contained the three principal pharmacophores of DAG constrained into a lactone ring (DAG-lactones). In the present work, the pharmacophore-guided approach was refined to a higher level based on the X-ray structure of the C1b domain of PK-Cdelta complexed with phorbol-13-O-acetate. A systematic search that involved modifying the DAG-lactone template with a combination of linear or branched acyl and alpha-alkylidene chains, which functioned as variable hydrophobic "affinity domains", helped identify compounds that optimized hydrophobic contacts with a group of conserved hydrophobic amino acids located on the top half of the C1 domain where the phorbol binds. The hydrophilic/hydrophobic balance of the molecules was estimated by the octanol/water partition coefficients (log P) calculated according to a fragment-based approach. The presence of branched alpha-alkylidene or acyl chains was of critical importance to reach low nanomolar binding affinities for PK-C. These branched chains appear to facilitate important van der Waals contacts with hydrophobic segments of the protein and help promote the activation of PK-C through critical membrane interactions. Molecular modeling of these DAG-lactones into an empty C1b domain using the program AutoDock 2.4 suggests the existence of competing binding modes (sn-1 and sn-2) depending on which carbonyl is directly involved in binding to the protein. Inhibition of epidermal growth factor (EGF) binding, an indirect PK-C mediated response, was realized with some DAG-lactones at a dose 10-fold higher than with the standard phorbol-12, 13-dibutyrate (PDBU). Through the National Cancer Institute (NCI) 60-cell line in vitro screen, DAG-lactone 31 was identified as a very selective and potent antitumor agent. The NCI's computerized, pattern-recognition program COMPARE, which analyzes the degree of similarity of mean-graph profiles produced by the screen, corroborated our principles of drug design by matching the profile of compound 31 with that of the non-tumor-promoting antitumor phorbol ester, prostratin. The structural simplicity and the degree of potency achieved with some of the DAG-lactones described here should dispel the myth that chemical complexity and pharmacological activity go hand in hand. Even as a racemate, DAG-lactone 31 showed low namomolar binding affinity for PK-C and displayed selective antitumor activity at equivalent nanomolar levels. Our present approach should facilitate the generation of multiple libraries of structurally similar DAG-lactones to help exploit molecular diversity for PK-C and other high-affinity receptors for DAG and the phorbol esters. The success of this work suggests that substantially simpler, high-affinity structures could be identified to function as surrogates of other complex natural products.

4-Butyrolactone↗

Sex differences in chronic stress effects on memory in rats.

Recent studies in rodent models and in humans have shown that the status of both the gonadal and adrenal axes (hypothalamic-pituitary-gonadal, HPG and hypothalamic-pituitary-adrenal, HPA, respectively) can influence learning and memory function. In this article, the effects of activating the HPA axis (stress) on performance of memory tasks in rats are reviewed. More importantly, results are presented which show that chronic stress has a different impact on performance of these tasks depending upon the sex of the rat. These observations are novel and potentially important since few studies, animal or human, have utilized females as subjects in studies of the stress response. Sex differences in the effects of chronic stress on memory were investigated in rats using an object recognition task and two spatial memory tasks, radial arm maze and object location. Given the same chronic stress--21 days of restraint for 6 h each day--males were impaired in all of the memory tests while females showed enhanced performance of the spatial memory tasks and no changes in object recognition performance. Levels of neurotransmitters and metabolites were measured in brain areas important for cognition in the subjects in order to determine neural systems that may respond to stress and mediate the cognitive responses. These results show that responses of monoamine and amino acid containing neural systems may contribute to or underlie sex differences in stress effects on cognition. Stress decreased dopaminergic activity in the frontal cortex and amygdala of males but not females; whereas, in CA3 of the hippocampus, stress increased levels of 5-HT and norepinephrine in females, but not males, and increased GABA in males, but not females. Finally, a possible role for estradiol in mediating sexually differentiated responses to stress was examined. Behavioral and neurochemical evaluations in ovariectomized, stressed females, with or without estrogen replacement, suggest that sex differences in response to stress are influenced by both the organizing and activating effects of estradiol. A few, recent studies in humans, that show sexually dimorphic relationships between chronic stress and cognition, are also highlighted. These results in humans are consistent with the pattern of results in rats. Clearly, further studies are necessary to substantiate sex differences in stress effects on memory function in humans and to understand mechanisms whereby estrogen may influence the stress response in rats. Nonetheless, recent studies show sexually differentiated cognitive responses to chronic stress and underline the importance of considering the sex/gender of subjects when studying the stress response.

Animals↗

Boosting bit rates and error detection for the classification of fast-paced motor commands based on single-trial EEG analysis.

Brain-computer interfaces (BCIs) involve two coupled adapting systems--the human subject and the computer. In developing our BCI, our goal was to minimize the need for subject training and to impose the major learning load on the computer. To this end, we use behavioral paradigms that exploit single-trial EEG potentials preceding voluntary finger movements. Here, we report recent results on the basic physiology of such premovement event-related potentials (ERP). 1) We predict the laterality of imminent left- versus right-hand finger movements in a natural keyboard typing condition and demonstrate that a single-trial classification based on the lateralized Bereitschaftspotential (BP) achieves good accuracies even at a pace as fast as 2 taps/s. Results for four out of eight subjects reached a peak information transfer rate of more than 15 b/min; the four other subjects reached 6-10 b/min. 2) We detect cerebral error potentials from single false-response trials in a forced-choice task, reflecting the subject's recognition of an erroneous response. Based on a specifically tailored classification procedure that limits the rate of false positives at, e.g., 2%, the algorithm manages to detect 85% of error trials in seven out of eight subjects. Thus, concatenating a primary single-trial BP-paradigm involving finger classification feedback with such secondary error detection could serve as an efficient online confirmation/correction tool for improvement of bit rates in a future BCI setting. As the present variant of the Berlin BCI is designed to achieve fast classifications in normally behaving subjects, it opens a new perspective for assistance of action control in time-critical behavioral contexts; the potential transfer to paralyzed patients will require further study.

Algorithms↗

Time domain processing of electric organ discharge waveforms by pulse-type electric fish.

We explored coastal streams, rivers, and swamps in the Guianas of South America and found eleven species of gymnotiform fishes with pulse discharges. Each species has a characteristic electric organ discharge (EOD) waveform of 0.5-5 ms duration; at least two species appear to have a natural sex difference in their EODs which is apparent when comparing large adult males and females. Three sensory coding mechanisms are proposed to explain how electric fish might be able to determine species and sex identity from such short electrical pulses. Spectral Coding: electroreceptors tuned to different frequencies encode the spectrum of the EOD as a cross-fiber stimulation pattern. Temporal Coding: EODs are encoded as a volley of nerve spikes patterned in the time domain. Scan Sampling: a receiver detects a signaler's EOD as an amplitude modulation or 'beat' set up by the combination of its own discharge with the signaler's. The receiver uses the modulation envelope to assess the signaler's EOD waveform. To distinguish between these three coding mechanisms, we tested the ability of one pulse gymnotiform, Hypopomus beebei, to discriminate one electric waveform from another by comparing the acceleration of the discharge rate to different stimuli. Stimuli are presented under two conditions: when the stimulus pulse train is free-running compared to the fish's pulse train, and when the stimulus train is phase-locked to the fish's discharge pulse train. Under the former condition scan sampling may be used; under the latter it will be impossible. Hypopomus discriminates the polarity of a single period sinusoidal stimulus under scanning conditions but does not discriminate under clamped conditions. Hypopomus gives the strongest response to single period sine waves of 670 Hz and weaker responses to sinusoids of lower and higher frequencies. Free-running and phase-locked stimuli evoke similar responses. Under free-running conditions, Hypopomus discriminates a series of EOD-like stimuli that have been phase-shifted by varying amounts, but under phase-locked conditions does not. Scan sampling is presented as a possible waveform recognition mechanism for pulse-discharging gymnotiform fishes.

Animals↗

Temporal recognition of sperm autoantigens by IgM and IgG autoantibodies after vasectomy and vasovasostomy.

Temporal patterns of IgM and IgG autoantibodies to sperm proteins were studied by western blot analysis at intervals after bilateral vasectomy, vasectomy followed one month later by vasovasostomy, or sham operations. Responses were detected to eight major autoantigens at 21-23, 36, 41, 51, 57, 63, 68-71 and 75-83 kDa, by study of staining patterns of sequential serum samples from individual animals and by analysis of the incidence of reaction to each protein. The four lower molecular weight antigens (21-23, 36, 41 and 51 kDa) provoked mainly IgG responses. The strongly stained set of higher molecular weight antigens (57, 63, 68-71 and 75-83 kDa) tended to show more clearly defined temporal patterns of IgM followed by IgG response, including a high incidence of IgM antibody at the 2-week interval. Three of the larger peptides (57, 63 and 68-71 kDa) appeared highly immunogenic, since some reactions were detected even in sham-operated rats. The classical patterns of IgM and IgG antibody responses to the majority of the dominant sperm autoantigens are in accord with the hypothesis that vasectomy mimics immunization with spermatozoa. The high incidence of IgM antibodies in the earliest sample, taken 2 weeks after vasectomy, suggests that the initial immunizing event takes place within about a week after the operation. Vasovasostomy did not bring about a decrease in antisperm antibodies. Instead, some animals demonstrated an increased reaction to certain antigens after reversal of vasectomy, even though the vasovasostomies were anatomically successful.

Animals↗

Evidence for independent processing of subjective contour brightness and sharpness.

Subjective contours have been of considerable interest because of their importance to theories and physiological models of form perception. In particular, they have recently been characterized as the result of magnocellular cortical processing. There is, however, a paucity of parametric data relating to basic psychophysical parameters in this field. Two experiments are reported in which the roles of subjective contour size, retinal eccentricity, and flicker rate in subjective contour salience were investigated. Eleven observers estimated subjective contour magnitude using an Ehrenstein configuration. Configurations ranging in size from 0.25 to 3 deg were presented to three retinal loci (fovea, 2 deg, and 4 deg) at flicker rates ranging from 5 to 15 Hz. Subjective contour brightness and distinctness were measured separately. Brightness was greatest at a subjective contour size of about 1.25 deg, at flicker rates of 5-7 Hz, and at 3 deg peripheral for all flicker rates and all but the smallest stimulus sizes. Distinctness decreased with eccentricity and flicker, but remained high at small diameters (thus implicating spatially sensitive mechanisms). Taken together, the results support a magnocellular processing of subjective contours with respect to brightness, but also suggest that there is a parvocellular contribution to subjective contour sharpness.

Adult↗