Negative Contrast Effect Research Articles

Chlordiazepoxide and the determinants of negative contrast

Previous experiments have shown that the negative contrast effect in consummatory behavior that occurs when rats are shifted from 32% to 4% sucrose is alleviated by the tranquilizer chlordiazepoxide (CDP). However, in these experiments, CDP was effective on the second postshift day but not on the first postshift day. The three experiments described in this paper suggest that this differential effectiveness of CDP is not due to the difference in preshift-postshift retention intervals on Day 1 (24 h) and Day 2 (48 h), but is due instead to the necessity of some degree of experience (about 5 min) with the postshift solution. These results, combined with those of an earlier study which showed elevated corticosterone in shifted animals on the second postshift day but not on the first postshift day, suggest that negative contrast may be a dynamic process, involving sequential processes of detection, evaluation, and conflict over the postshift period. It was further suggested that CDP becomes effective in moderating contrast only when the conflict stage is reached.

Effects of pimozide on positive and negative incentive contrast with rewarding brain stimulation.

Positive and negative contrast effects with brain-stimulation reward were inferred from significant differences in rate/intensity curves obtained by ascending, random and descending orders of current presentation. The neuroleptic drug pimozide caused a dose-related attenuation of both positive and negative contrast. A dose of 0.1 mg/kg blocked positive contrast obtained by comparing ascending and random rate/intensity curves. Negative contrast and threshold current intensities for brain-stimulation reward at sites in the ventral tegmental area were unaffected by the low dose (0.1 mg/kg) of pimozide. Higher doses of pimozide (0.25, 0.4 mg/kg) blocked both positive and negative contrast effects, and caused a significant elevation in threshold current intensities under the random order condition. Two doses (0.25, 0.4 mg/kg) of pimozide were associated with performance deficits as the response rates at the maximum current intensities were attenuated significantly with each order of current presentation. These demonstrations of both positive and negative contrast are consistent with the theoretical position linking brain-stimulation reward to incentive motivation. Furthermore the effects of the dopamine receptor antagonist pimozide are consistent with a role for dopamine in brain-stimulation reward and also raise the possibility of dopaminergic involvement in incentive contrast phenomena.

Systolic direction of right ventricular contrast trajectories in the detection of ventricular septal defect with left-to-right shunt

Abnormal systolic direction of contrast flow toward the transducer within the right ventricle was demonstrated on M-mode echocardiograms in patients with ventricular septal defect (VSD) and left-to-right shunt. The usefulness of this new technique was tested in 30 patients with VSD proved at catheterization and in 300 control subjects. In all subjects, 2-dimensional (2-D) visualization of the defect, 2-D negative contrast effect and M-mode demonstration of positive contrast within the left ventricular (LV) cavity were also performed. Sensitivity and specificity for each technique and each hemodynamic subgroup of patients were determined and compared. A sensitivity of 100% for the diagnosis of VSD by anterior right ventricular (RV) systolic direction of contrast trajectories was achieved in 20 patients with relatively small VSDs and mild to moderate elevation of RV pressure (RV-LV pressure ratio 60%) and mean pulmonary to systemic blood flow ratio of 1.7. Sensitivities of 2-D echocardiography, 2-D negative contrast technique and positive LV contrast appearance on M-mode echocardiography were 63%, 71% and 53%, respectively. Sensitivity of 100% for systolic anterior direction of contrast trajectories was also calculated in 6 patients with RV-LV pressure ratios from 61 to 80% and mean pulmonary to systemic blood flow ratio of 2.7. Sensitivities of 2-D echocardiography, 2-D negative contrast technique and positive contrast appearance in the LV cavity by M-mode echocardiography were 75%, 60% and 86%, respectively. In 4 patients with systemic or nearly systemic RV pressure, sensitivity of systolic anterior direction of RV contrast trajectories decreased drastically, to only 67%. In contrast, sensitivities of 2-D echocardiography and positive contrast appearance in the LV cavity on M-mode echocardiography increased to 100% for both techniques. This method of identifying anterior systolic RV contrast trajectories direction was useful for detecting VSDs with left-to-right shunt in adults in whom other echocardiographic methods may be inadequate.

Returning ‘cafeteria-fed’ rats to a chow diet: Negative contrast and effects of obesity on feeding behaviour

Two experiments examined the feeding behaviour and body weight changes of rats returned to a standard chow diet after prolonged periods of cafeteria feeding. In the first, both overweight (ad lib fed) and ‘normal’ weight (fed a restricted ration of cafeteria foods) cafeteria rats became hypophagic compared to chow-fed rats following their return to chow feeding. However, the overweight rats' hypophagia was initially more severe and was longer lasting. In the second experiment, analysis of meal patterns recorded throughout the first 4 weeks on chow after 26–32 weeks of ad lib cafeteria feeding showed that the hypophagia was due to a reduction in mean meal size (MMS) and meal frequency (MF). Food intake and MMS subsequently recovered to within control levels (by 2–3 weeks), but MF remained persistently low. There was a decrease and then a recovery in eating rate (ER) which paralleled the changes in MMS. The previously cafeteria-fed rats lost only 60% of their excess body weight. These findings are interpreted in terms of a negative contrast effect (changes in MMS and ER) and an inhibitory action of increased adiposity on feeding (affecting mainly MF).

Correlation of corticosterone elevation and negative contrast varies as a function of postshift day

In three experiments, rats shifted from 32% to 4% sucrose consumed less of the 4% sucrose than did rats that had received only the 4% solution. Experiment 1 showed that this negative contrast effect was not accompanied by a corticosterone elevation on the first day subsequent to the shift. Experiments 2 and 2a showed that corticosterone levels were substantially elevated on the 2nd postshift day and that there was a tendency for degree of elevation in corticosterone to be related to degree of lick suppression. These results are discussed in terms of other data suggesting that anxiolytic drugs and disinhibitory stimuli are more effective in alleviating contrast on the 2nd postshift day than on the 1st postshift day. It is suggested that, in the present paradigm, reaction to stimulus change may be the primary determinant of contrast on the 1st postshift day, but emotional processes related to reward loss and/or conflict develop by the 2nd postshift day.

Functional and anatomical correlates in atrial septal defect. An echocardiographic analysis.

The results of cross sectional echocardiography, intracardiac contrast echocardiography, and balloon sizing techniques and conventional haemodynamic assessment were correlated in 40 consecutive patients evaluated for an isolated left to right shunt at atrial level. Echo free areas along the septum were identified in 23 of 25 patients with a secundum defect, but not in two with a fenestrated defect, and in the upper atrial septum in three of four patients with a sinus venosus defect. No false positive results occurred in 11 patients with a probe patent foramen ovale. Saline contrast injection into the left atrium showed significant left to right shunting in all patients with atrial septal defect; inferior vena caval injection produced right to left shunting in 15 of 29 patients and a negative contrast effect in eight of 29 patients with an atrial septal defect, although neither correlated quantitatively with defect diameter or magnitude of the left to right shunt. Echocardiographic assessment of defect size as small, moderate, or large showed a highly significant correlation with balloon measurement of defect diameter, although some overlap between the groups was evident. In contrast, the correlation between defect diameter and pulmonary to systemic blood flow ratio was poor, mainly because of highly variable shunting in patients with an anatomically large defect. Cross sectional echocardiography has high sensitivity and specificity in the diagnosis of the non-fenestrated atrial septal defect and provides quantitative information about defect diameter. Contrast studies do not add to the diagnostic value of imaging from the subcostal position. The poor correlation between defect size and the measured shunt suggests that the latter may not be the best criterion for surgical management and that size could be an important factor likely to influence both the long term prognosis and the decision for closure.

Detection of intracardiac shunt flow in atrial septal defect using a real-time two-dimensional color-coded Doppler flow imaging system and comparison with contrast two-dimensional echocardiography

To evaluate the noninvasive detection of shunt flow using a newly developed real-time 2-dimensional color-coded Doppler flow imaging system (D-2DE), 20 patients were examined, including 10 with secundum atrial septal defect (ASD) and 10 control subjects. These results were compared with contrast 2-dimensional echocardiography (C-2DE). Doppler 2DE displayed the blood flow toward the transducer as red and the blood flow away from the transducer as blue in 8 shades, each shade adding green according to the degree of variance in Doppler frequency. In the patients with ASD, D-2DE clearly visualized left-to-right shunt flow in 7 of 10 patients. In 5 of these 7 patients, C-2DE showed a negative contrast effect in the same area of the right atrium. Thus, D-2DE increased the sensitivity over C-2DE for detecting left-to-right shunt flow (from 50% to 70%). However, the specificity was slightly less in D-2DE (90%) than C-2DE (100%). Doppler 2DE could not visualize right-to-left shunt flow in all patients with ASD, though C-2DE showed a positive contrast effect in the left-sided heart in 9 of 10 patients with ASD. Thus, D-2DE is clinically useful for detecting left-to-right shunt flow in patients with ASD.

Incentive Value of Free-Response Reward Schedules

(VI-30 s) schedule, to FR-1, and then to VI-30 s. Performance in the runway varied as a function of the schedules in effect in the goal box. No evidence for a successive positive contrast effect was obtained. In the second experiment, running speeds were compared across groups that were trained under fixed interval schedules (FI-0 s, FI-10 s, or FI-60 s) in the goal box. Runway performance and bar press rate varied as a function of the interval length employed. Group differences occurred at different points in training in running speeds and bar press rates. When groups that were trained under the FI-0 s or FI-60 s schedules were shifted to an FI-10 s schedule, no evidence of a positive or negative contrast effect was obtained. These results were compared with the effects obtained in the traditional runway using delayed reward and partial reinforcement. It is concluded that interval schedules are more similar to delayed than to partial reward and that running speed and bar press rate represent different indices of the conditioning process. Many training procedures have been devised to isolate the controlling dimensions of free-response reward schedules to define the basic processes underlying their effects on behavior. All of the intermittent schedules incorporate a delay between reinforced responses and are characterized by a high proportion of unrewarded responses. Therefore, on free response schedules, responding is both partially reinforced and reward is delayed if the ratio contingency is greater than one or the interval value selected is greater than 0 s. Intermittent free response schedules combine several reward conditions typically studied in the straight alley paradigm and may be viewed as relatively complex contingencies. Although running speed and bar press rate have been described as indices of response strength, the relationship of these measures to the same reinforcement procedure has not been clearly established. The present set of experiments was de

Interevent anticipation of liquid and solid sucrose rewards

Albino rats were trained in a straight runway under two different series of reward magnitude each day. In one three-run series (a trial), reward was given on the first and third runs (R-N-R), and in the other, reward was given only on the first run (R-N-N). The interval between trials was approximately 40 min, and the interval between runs within a trial was approximately 30 sec. For one group of rats, reward was 10 45-mg sucrose pellets. For the other group, reward was 1 ml of 30% liquid sucrose mixed by weight with tap water. With both reward types, running on the second run of a trial was faster if the third run was rewarded (R-N-R) than if it was not (R-N-N). This result suggests that the animals were in some way anticipating the reward amount for an upcoming run while running a current run. After 26 training days, the third run of the R-N-R trial was shifted to nonreward for 12 additional days. Times slowed on Runs 2 and 3 in the shifted trial, but there was no evidence of a successive negative contrast effect. The implications of the anticipation result for the interpretation of differences between sugar and ordinary food rewards in paradigms that suggest reward anticipation are discussed.

Medial and lateral amygdalectomy differentially influences consummatory negative contrast

Rats shifted from a 32% to 4% sucrose solution consume substantially less 4% sucrose than unshifted animals that experience only the 4% solution. This negative contrast effect was found to be attenuated by lesions of the lateral aspects of the amygdala (basolateral, lateral, and basomedial nuclei) and eliminated by lesions of the medial aspects of the amygdala (corticomedial and central nuclei). The results are discussed in terms of the possible role the amygdala may play in some of the proposed determining factors mediating consummatory negative contrast (e.g., emotionality, neophobia, memory).

Detection of atrial septal defect by right sternal border echocardiography

The atrial septum can be visualized by right sternal border 2-dimensional echocardiography (2-D echo). To evaluate the usefulness of this approach in the evaluation of atrial septal defect (ASD), 50 patients who underwent cardiac catheterization were studied by 2-D echo. Twenty-one patients (Group A) had ASD (3 ostium primum, 18 ostium secundum) and 29 (Group B) had mitral valve disease and an intact atrial septum. Subcostal and right sternal border approaches were used to visualize the atrial septum. Both approaches identified the 3 cases of ostium primum ASD; secundum ASD was identified using the subcostal approach in 11 patients and using the right sternal border approach in 13. In 15 patients the ASD was imaged at least by 1 of the 2 approaches. Two-dimensional contrast echocardiography showed a positive or negative contrast effect in 13 of 18 cases (12 with standard approaches, 11 with right sternal border approach). In all patients in Group B, the right sternal border approach showed an intact atrial septum. Thus, the right sternal border approach is a useful approach that increases the sensitivity of 2-D echo in the diagnosis of ASD.

Sucrose Pellet Reduction and Runway Performance

Summary To establish the reliability of the finding that runway-trained rats show clear preshift superiority if the reward is 12 sucrose pellets, as opposed to one, but do not show the successive negative contrast effect (SuNCE) when reward is reduced, albino rats were trained for 24 days, two trials per day, in a runway for one or 12 sucrose (92.4%) Noyes 45-mg pellets. A four-day postshift period followed in which all animals received 10 trials per day with the one-pellet reward. The changed postshift reward conditions eliminated a preshift superiority of the 12-pellet reward yet did not produce the SuNCE.

The Goal Units Dimension in Negative Contrast Failures with Sucrose

Summary To pursue the possibility that the usual failure to obtain the successive negative contrast effect (SuNCE) with sucrose rewards is an indirect consequence of the liquid medium in which sucrose is usually delivered, Experiment 1 was designed to look for the SuNCE with sucrose pellets. Food-deprived rats were trained for 20 preshift days, two trials/day in a runway for either one or 12 45-mg Noyes pellets of either sucrose or standard formula. During six postshift days, 10 trials/day, all rats were given the one-pellet reward of the same preshift type, and the SuNCE appeared in the standard but not sucrose groups. A second experiment produced single-alternation patterning in the discrete-trial lever pressing of rats given four two-trial sequences of one or 10 sucrose or standard pellets each day for 102 days. The patterning was potentiated with a change, for the remaining 28 days, from the one-pellet reward to nonreward, but in no case throughout the experiment was the strength of patterning any dif...

Ultrasonic contrast studies for the detection of cardiac shunts

Contrast echocardiography has achieved importance in the diagnosis of cardiac shunt lesions. The technique provides information about flow patterns and serves as an adjunct to identifying communications that may be too small to image, even with high resolution real time scanning. This report reviews clinical applications and experiences in the use of standard, peripherally injected echocardiographic contrast agents for the detection of atrial septal defect, ventricular septal defect and patent ductus arteriosus. The importance and development of transpulmonary contrast agents capable of crossing the pulmonary capillary bed to opacify the left ventricle are reviewed and experience with a variety of experimental echocardiographic contrast agents is presented. Agents opacifying the left ventricle after intravenous injection are capable of providing direct ultrasonic contrast imaging of congenital left to right shunts. Further, recent experience with an experimental standardized, gas-producing contrast agent in an open chest animal model with an experimentally produced ventricular septal defect suggests that a combination of an experimental right heart agent that produces a measurable and reproducible amount of contrast effect, with a videodensitometric system capable of quantifying both positive and negative contrast effects, may provide an ultrasonic method for evaluating the magnitude of cardiac shunts.

Repeated successive contrast in consummatory behavior with repeated shifts in sucrose concentration

Contrast in consummatory behavior was investigated following repeated shifts from 32% to 4% sucrose. In Experiment 1, contrast in licking and in open-field measures of activity occurred following the second and third downshifts. In Experiments 2a and 2b, equivalent contrast effects occurred following the first and second downshifts in sucrose. In Experiment 3, negative contrast remained unabated following nine downshifts in animals shifted between 32% and 4% sucrose on alternate days. Similar results were found for five downshifts in animals shifted every 2 days. In both of these latter conditions, positive contrast occurred over the first few shifts and was then lost as the 32% control group reached asymptote. These data show that repeated negative contrast effects in consummatory behavior are robust and enduring and occur under several different sets of experimental parameters. The results are discussed in terms of reinforcement level and emotional interpretations of contrast effects, and the possibility was suggested that the causal mechanism of contrast changes with repeated shifts.

Application of 2-dimensional contrast studies during pericardiocentesis

Two-dimensional echocardiographic contrast studies were performed in 16 patients with pericardial effusion. A 4-chamber view was obtained by positioning the transducer at the apex. The exploratory needle was visualized in 9 patients. Five milliliters of saline solution were injected through the exploring needle and a cloud of echoes indicated its position. Microbubbles were seen in all 16 patients. This technique enabled the operator to identify that the needle was inadvertently in the left ventricle in 2 patients and in the right ventricle in 1. Furthermore, in 2 patients, when fluid could not be aspirated, the contrast study confirmed that the needle was in the pericardial sac; in both cases, pericardial fluid could be aspirated with slight manipulation of the needle. In a patient with a stab wound a negative contrast effect indicated the probable site of laceration. Thus, 2-dimensional contrast echocardiography was useful in locating needle position, which facilitated pericardiocentesis.

Effect of varying sucrose concentration on macrobehavioral aspects of licking in the rat.

Rats (eight male, eight female) were trained to lick 32% and 4% sucrose solutions for three minutes per day on four consecutive days. Measures of the number of licks revealed robust positive and negative contrast effects. Analysis of the burst-pause pattern of licking revealed that the decrease in licking characteristic of the negative contrast effect resulted from a decrease in the number of bursts, while the increase in licking characteristic of the positive contrast effect was the result of a shortening of the interburst interval.

Systematic analysis of contrast echocardiograms

Contrast echocardiography was first described in 1968. Since then, many reports have described clinical and experimental uses for the technique. Contrast echocardiography is performed at least occasionally in most echocardiography laboratories, but most physicians use this technique merely to determine the presence of a shunt or, more rarely, for structure identification. Contrast echocardiography can provide much more information. Some different types of information available from contrast echocardiographic records are discussed, including timing of contrast appearance within the cardiac cycle, relative timing of appearance in different cardiac structures, relative intensity of contrast opacification, cyclical changes in contrast opacification, negative contrast effect, slope of contrast trajectories on M-mode contrast echocardiography, and clearance times.

Incentive relativity effects reduced by exogenous insulin

In two experiments rats shifted from 32% to 4% sucrose consumed less of the 4% than rats maintained on the 4% solution. This negative contrast effect was eliminated if the rats were injected with insulin (5.4 U/kg) on the shift day. This insulin dose reduced blood glucose levels to less than 50% of control levels, but the brief access period to 4% sucrose just before blood sampling reliably increased blood glucose levels. The results were discussed in terms of the effects of deprivation conditions on incentive relativity.

Detection of ostium secundum atrial septal defects by transoesophageal cross-sectional echocardiography.

Transoesophageal cross-sectional echocardiography has special advantages when investigating the interatrial septum which is imaged perpendicularly without echo dropouts from an oesophageal transducer position. The technique was successfully used in 19 out of 20 patients (95%) with an ostium secundum atrial septal defect and in 30 control subjects. In all of the latter the interatrial septum was visualised as a continuous echo structure separating the atria, whereas a distinct discontinuity representing the septal defect was apparent in all patients with atrial septal defect. Echocardiographic measurement of the defect size correlated well with surgical findings in 11 patients who underwent open heart surgery in the course of this study. In a comparative transthoracic examination, adequate recordings were obtained in 18 of the 20 patients and in 26 of the 30 control subjects. Direct subcostal visualisation of the defect was reliable in 10 of 18 patients. Peripheral venous contrast studies were also performed with the transoesophageal as well as the transthoracic technique. Echo contrast remained confined to the right heart in the control subjects. Left sided contrast appearance diagnostic of an interatrial communication was shown in the patients using the transoesophageal technique (100% sensitivity), with an additional right atrial negative contrast apparent in seven patients. The transthoracic approach, on the other hand, showed left sided echo contrast in 14 of 18 patients and an additional negative contrast effect in two of the 14. It is concluded that transoesophageal is superior to transthoracic cross-sectional echocardiography as a highly sensitive method for the detection and evaluation of ostium secundum atrial septal defects.