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Objective: The purpose of this study was to examine the circadian distribution of creatinine and uric acid clearances in subjects with Multiple Sclerosis., Materials and Methods: Eleven subjects with MS, 6 women (48+/-7y) and 5 men (58+/-5y) volunteered for this circadian study. Thirteen healthy females (39+/-11y) served as controls. Data of seven healthy male controls (64+/-8 y) were extracted from a similar circadian study conducted previously. Each MS patient, and each male control had blood samples drawn around the clock, at 3h intervals (8/24h), and each collected urines over 3h periods (8/24h). Each female control contributed only one blood sample and one complete 24h urine collection. Blood and urine samples were analyzed for a number of relevant analytes: ELAM, IL-6, NO, insulin, ACTH, aldosterone, cortisol, electrolytes, lymphocytes, monocytes including creatinine and uric acid clearances. Those were standardized to an average body surface area of 1.73 m2., Results: The relevant analytes demonstrated increased synthesis of insulin, IL-6, ELAM, monocytes, and reduced concentrations of serum NO. The creatinine clearances were significantly lower in MS females than in female controls, 63+/-22 vs.108+/-18 ml/min. They were also lower than those of MS males and male controls, 107.8+/-17, 97.5+/-8.2 ml/min. Uric acid clearances in MS females were also lower 6.9+/-2.4 vs. 10.5+/-4.4 ml/min. The uric acid clearance in MS males was higher than in male controls, 7.0+/-4.5 vs. 4.0+/-1.0 ml/min., Conclusions: The alterations in selected relevant analytes and the reduced creatinine and uric acid clearances in females but not in males, suggest a renal dysfunction in MS females. These observations may contribute to understanding better the mechanism of renal dysfunction in female patients and perhaps this may be an additional factor contributing to greater frequency of MS in females than in male subjects.

Aim: We examined the circulating levels of iron and ferritin in serum of seven healthy and three insulin non-dependent diabetic (Type 2) males in order to compare their circadian characteristics., Methods: Blood samples were collected every 3h over a 24h period and were analyzed for serum iron and ferritin., Results: The mean Fe level was significantly higher in healthy than in diabetic subjects: 80.0 +/- 3.3 vs. 63.0 +/- 3.7 microg/dL. The ferritin level was significantly lower in healthy than in diabetic men: 79.8 +/- 4.7 vs. 186.3 +/- 110.5 microg/L. A significant (p < 0.001) time-effect was found by ANOVA and circadian rhythm was detected at p < 0.001 in all data sets when a 24h cosine was fitted to the normalized data. Acrophases were located in mid to late morning for Fe (11:30, vs. 09:22h) and for ferritin (11:10 vs. 11:46h)., Discussion: We concluded that there is significant circadian variation in both serum Fe and ferritin, with predictable peaks in the mid to late morning.

56 student volunteers (mean age 21 yr.) participated in a study designed to assess how the Stroop procedure and delayed auditory feedback affect cardiac activity when they are used individually as well as when they are combined in the same task. In a preliminary study, listening to tape-recorded instructions on how to relax produced a significant decrease in cardiac activity. In the major study, when used individually, both the Stroop procedure and delayed auditory feedback produced significant increases in cardiac activity. The largest increase, however, occurred with systolic blood pressure and was induced by delayed auditory feedback. When the Stroop procedure was used in combination with delayed auditory feedback, systolic blood pressure again increased, but this effect was no greater than when delayed auditory feedback was used alone. This pattern of results implies that, when combined, the Stroop procedure and delayed auditory feedback have largely independent effects on cardiac activity and that, when tested under similar conditions, delayed auditory feedback has the larger effect.

This study compared the results of reflex modification (RM)--an objective technique for assessing brainstem sensorineural processing--with those of auditory brainstem response (ABR) for a group of high-risk infants at comparable postconceptional ages. For the RM procedure, an eyeblink-eliciting tap to the glabella was presented either alone or accompanied by a brief 90dB SPL tone. 37 high-risk infants were tested with both RM and ABR at a mean postconceptional age of 37.3 weeks. Seven had an increased brainstem conduction time ('failed ABR') and eight did not exhibit significant reflex augmentation ('failed RM'), seven of whom also failed the ABR. These data provide evidence that sensory stimuli which affect the neural mechanisms responsible for the organization of the startle response and auditory processing share essential neural components.

The onset and development of the delayed blink response, elicited by a tap to the glabella, and its modification by an acoustic stimulus (tone), were studied longitudinally in 36 healthy preterm and 43 term infants. Blink amplitude increased with gestational age. By term postconceptional age, the responses of the preterm infants to tap alone, and to both tap and tone, were not significantly different from those of the term infants. These results suggest that neurological development, as reflected by the blink reflex and its modification, proceeds in an orderly, sequential fashion and that the mechanisms affecting these brainstem processes are not altered by environmental influences.

Ducklings (5 to 28 days old) were trained to peck a pole on fixed-ratio, fixed-interval, and multiple schedules using brief presentation of an imprinting stimulus as the response-contingent event. Other ducklings of the same age were trained similarly except that reinforcement consisted of access to water. With water reinforcement the typical fixed-ratio ("break-run"), fixed-interval ("scallop"), and multiple schedule response patterns were readily established and consistently maintained. With the imprinting stimulus these schedule effects were inconsistent in some subjects and virtually nonexistent in others, despite extended training. Schedule control with the imprinting stimulus was not improved by the use of a reinforcement signaling procedure which enhances responding reinforced by electrical brain stimulation on intermittent schedules. However, the overall rates of responding and the extinction functions generated after reinforcement with water versus the imprinting stimulus were comparable. These findings imply that control by temporal and discriminative stimuli may be relatively weak when a young organism's behavior is reinforced by presentation of an imprinting stimulus.

Newly hatched Khaki Campbell ducklings (Anas platyrhynchos domesticus) were initially housed in pairs and subsequently transferred to isolated housing conditions. Subjects living with another bird displayed filial behavior and little aggression upon encountering another duckling in a test arena. In contrast, ducklings housed in isolation exhibited aggressive pecking in addition to filial behavior when another duckling was subsequently encountered. In Experiment 2, ducklings were housed with an imprinting object (i.e., an object that elicits attachment behavior), but they were otherwise isolated from other birds. These subjects displayed little aggression when they were subsequently reunited with a conspecific, indicating that the aggression-precluding effects of social housing are not limited to the particular social stimulus with which the ducklings are housed. In Experiment 3, ducklings were again housed with an imprinting object, but this time the object was behind glass, thereby precluding tactile contact with it. Since these birds also exhibited little aggression when reunited with a conspecific, it is apparent that visual stimulation from an imprinting object is sufficient in itself to preclude subsequent aggression. These findings suggest that stimulation that elicits attachment behavior is the critical factor mediating isolation-induced aggression.

The human eyeblink, elicited by a tap to the glabella, can be inhibited if a relatively weak acoustic signal precedes the tap by approximately 100 msec. The work reported here was designed to explore the surprising fact that more inhibition occurs when the acoustic prestimulation is presented monaurally than when it is presented binaurally. The present studies revealed that (a) given equally loud binaural inputs, a reduction of about 40 dB(A) in one of them is sufficient to produce inhibition comparable to that produced by a monaural signal, (b) the difference between nonaural and binaural inhibition remains constant as the intensity of prestimulation is varied, and (c) the simultaneous offset of a tone in one ear and onset of a tone in the other ear produces more inhibition than either monaural offest or onset alone. These findings suggest that the specific attributes of a given acoustic signal make independent contributions to the inhibition produced by that signal.

The human eyeblink elicited by a mechanically produced tap to the glabella was inhibited by a mild acoustic stimulus presented 200 msec prior to the tap and was augmented when the same acoustic stimulus was presented simultaneously with the tap. Monaural presentation of the acoustic stimulus prior to the tap yielded more reflex inhibition than when that same stimulus was presented binaurally. Binaural presentation of the acoustic stimulus simultaneously with the tap yielded more reflex augmentation than when that same stimulus was presented monaurally. These findings lend credence to the proposition that reflex inhibition and reflex augmentation are mediated by separate neural pathways.

A series of seven experiments related amplitude and latency of the pigeon's startle response, elicited by an intense visual stimulus, to antecedent auditory and visual events in the sensory environment. The data indicated that (a) within broad limits the amplitude of the reflex is a positive function of the intensity of the sensory background prevailing at the time of startle elicitation, (b) a change in the sensory environment occurring 15-2,000 msec prior to the startle-eliciting stimulus inhibits the amplitude of the response, and (c) a change in the sensory environment less than 10 msec prior to the startle-eliciting stimulus reduces the latency of the response. These findings are consistent with previous research on acoustic elicited startle in the rat. The overall configuration of the results suggests that a pathway including the reticulospinal tract and the bulbopontine reticular nuclei could be the major mediator of startle. In these terms, latency-reduction effects would occur because of partial activation of this pathway, amplitude inhibition would occur because of cerebellar influence, and amplitude facilitation would reflect cerebral or striatal influences.

In laboratory rats (as in humans) a low-intensity tone that precedes a high-intensity burst of noise by approximately 100 ms can reduce the amplitude of the startle reaction elicited by the burst of noise. A series of four experiments with rats investigated the relation between the inhibitory effects of tonal frequency change and the length of the silent period (gap) preceding it. The major findings were the following: (a) A gap in an otherwise continuous pure tone inhibited startle when the gap occurred approximately 100 ms prior to the noise burst. (b) Although an increase in gap duration increased the inhibition afforded by the gap, the maximum inhibition was yielded by gaps of 100 ms and greater; this maximum was equivalent to the inhibition yielded by the presentation of a postgap tone alone. (c) A shift in tonal frequency across a 10-ms gap yielded more inhibition than did the same gap with no frequency shift; again the shift yielded equivalent inhibition to the presentation of the postgap tone alone. (d) An increase in the frequency shift increased inhibition when the shift occurred across a 10-ms gap, but not when the shift occurred across a 100-ms gap.

The present study uses the glabellar reflex and reflex modification procedures to assess acoustic and tactile sensory processing capabilities in the human neonate. Fourteen term infants and 28 clinically stable preterm infants were given identical test paradigms. Augmentation testing consisted of a 16 V dc tap presented simultaneously with a 90 dB SPL tone; inhibition testing consisted of a 16 V tap preceded 900 msec. by an identical tap. All 14 term infants showed augmentation with 8 of 14 at p less than 0.05 level and eleven of 14 showed significant inhibition at the 900 msec intertap interval. However, only 12 of 28 preterm infants demonstrated significant augmentation and none showed reliable inhibition. These data indicate that areas of the central nervous system that process sensory stimuli are not fully developed at the time of birth even in the term infant. Further, the neural system for augmentation and inhibition may be independent of each other.

A brief stimulus presented to various regions of the visual field inhibited the eyeblink elicited by a subsequent tap to the skin between the eyebrows. Subjects were able to switch their attention toward or away from the target area without moving their eyes. In doing so they changed the amount of inhibition.

Behavioral and physiological work in animals and adult humans have established the sensitivity of various procedures and allowed delineation of the neuroanatomical pathways involved in sensory processing. Herein we used the glabellar reflex and reflex modification procedures to assess acoustic sensory processing capabilities in the term newborn infant. The eyeblink-eliciting device consisted of a miniature solenoid which could deliver a controlled tap. A photoreflective densitometer attached to a TDH-39 earphone assessed the eyeblinks. A total of 98 term infants was studied to determine how a response to a reflex-eliciting event (tap) was modified (either augmented or inhibited) by a mild exteroceptive stimulus (tone) which was presented at an appropriate lead interval. Ninety adult subjects were given identical testing procedures and their data were compared to that of the infants. The results of this study showed that newborn infants reliably exhibited an eyeblink response after a tap to the glabella. With fixed intensity tones, frequencies from 1 to 4 kHz produced equivalent amounts of reflex augmentation in infants and adult subjects. Blink amplitude increased as a function of increased tap and tone intensity in both infants and adults. State change was shown to affect the amplitude of the reflexive eyeblink, but not the augmentation effect. However, neonates failed to show inhibition to either acoustic lactile stimuli at an interstimulus interval that produced significant inhibition in the adult. These data indicate that reflex modification procedures provide an objective assessment of acoustic sensory processing in the term neonate.(ABSTRACT TRUNCATED AT 250 WORDS)

Male hooded and albino rats were exposed to a light flash followed at various temporal intervals by a startle-eliciting 117 db. (re 20 muN/m2) burst of white noise. The visual stimulus engendered startle response inhibition (maximally when the lead time was 64-250 msec) as well as startle response latency reduction (maximally when the lead time was 2-8 msec). The temporal functions for the effects of visual stimuli paralleled those previously reported for startle modification by acoustic events. Further study revealed that, given optimal lead times, inhibition is produced reliably by weaker visual stimuli (3 X 10-6 cd-sec/cm2) than latency reduction (3 X 10-4 cd-sec/cm2). This differential sensitivity to visual stimuli is also analogous to previously reported findings for events in the acoustic environment. It reveals that the neural mechanisms that mediate latency reduction and inhibition can be engaged by either acoustic or visual stimulation.

Airpuff-elicited eyeblink, like many other reflexes, may be inhibited when an auditory stimulus precedes the reflex-eliciting stimulus by approximately 100 milliseconds. This inhibition is greater when the auditory stimulus is delivered to one ear than when it is presented binaurally.

The amplitude of the human eyeblink elicited by a mild tap between the eyebrows can be increased if a brief tone is presented simultaneously with the tap. In two experiments we examined how this reflex augmentation effect varies with changes in the frequency characteristics of the tone and with changes in the intensity of the tap. We also examined how these effects change in the course of development. For newborn infants and for adults, fixed intensity tones with frequencies of either 1, 2, or 4 kHz produced equivalent amounts of reflex augmentation. Furthermore, while blink amplitude was an increasing function of tap intensity in both populations, the amount of reflex augmentation engendered by a simultaneously presented tone was independent of the intensity of the tap.

The reflexive eyeblink, elicited by a tactile stimulus, is inhibited if an auditory stimulus precedes the eliciting stimulus by 100 msec. With adult subjects the threshold for this effect was found to be sufficiently low to suggest that reflex inhibition may be useful in objective audiometry. A preliminary investigation with infants and children showed that the inhibitory process is present, though variable, in children as young as 6 weeks olds.

Newly hatched Khaki Campbell ducklings (Anas platyrhynchos domesticus) were exposed to a moving object that immediately suppressed distress vocalizations occurring in a novel environment. The static visual and auditory features of this object acquired the ability to suppress distress vocalizations after eight 20-min sessions of exposure to the object in motion. The acquired suppressive properties of these features were found to persist throughout thirty 20-min sessions given over 10 days. During these sessions, the ducklings were continually exposed to the static features in the absence of visual movement. In a second experiment, the ability of these features in the absence of visual movement. In a second experiment, the ability of these features to serve as reinforcement for a pecking response was shown to persist for up to 56 hr. In one duckling, presentations of the static visual features did not maintain pecking behavior. However, it was shown that pecking responses could be re-instated in this duckling by introducing novel stimuli to the environment.

This research asked whether the reflexive eyeblink elicited by a tap to the glabella (the flat region of skin between the eyebrows) is modified by acoustic signals which either precede or accompany the tap. Five experiments employing identical reflex modification procedures on neonates and adults suggest developmental differences in processing auditory stimuli. Neonates failed to exhibit reflex inhibition by either prior acoustic or tactile stimuli. Adults exhibited robust reflex inhibition to these same stimuli. Neonates, however, exhibited reliable reflex augmentation when mild (70 dB re: 0.0002 dyne/cm2) tones were presented simultaneously with the tap. For adults, tone intensities of at least 90 dB were necessary to obtain reliable reflex augmentation. The developmental processes implied by these findings are discussed.

Reflex modification procedures were used to test sensory processing in premature infants to examine the relationship between respiratory abnormalities and brainstem neuronal function. A total of 73 premature infants at risk for apnea and/or infants receiving methylxanthine therapy was given a 12-h pneumocardiogram and reflex modification test at a comparable postconceptional age, before discharge. Reflex modification was tested using a controlled eyeblink-eliciting tap to the glabella presented either alone or with a 1 kHz 90-dB SPL tone. The amplitude of the glabellar tap eyeblink and acoustically modified blink were lower in infants discharged on cardiac/apnea monitors (n = 36) than in the unmonitored group (1.44 and 1.59 volts versus 2.15 and 2.39 V, p less than 0.005, respectively). At follow-up, 12 monitored infants had clinically significant apnea after discharge. The records of this subgroup of infants revealed a significantly lower augmentation of the glabellar eyeblink response when compared to all infants screened for respiratory abnormalities and to the other monitored babies (p less than 0.01). The data suggest that abnormalities of the ventilatory pattern and occurrence of clinical apnea in preterm infants may in some measure be related to acoustic sensory processing, implying an alteration of brainstem neuronal function and organization.

When either the intensity or frequency spectrum of an approximately 70-db. SPL narrow-band noise was abruptly changed by a small amount, the rat's response to a startle stimulus presented 64 msec later was inhibited. When similar small frequency changes preceded the startle stimulus by ony 5 msec, the latency of the startle response was reduced, but even relatively large changes in intensity of the antecedent stimulus had no effect on response latency. These findings provide added support for the generalization that the neural processes associated with startle are engaged by small changes in the auditory environment. They also point to a measure of separation between the processes responsible for inhibition and those responsible for latency shift.

In human adults the eyeblink elicited by a given stimulus can be inhibited if that stimulus is preceded by another stimulus at an appropriate lead interval. In the present work, pairs of eyeblink-eliciting stimuli separated by 300-1200 msec were presented to sleeping preterm and full-term infants as well as to adults. Preterm infants did not exhibit reliable inhibition at any interval. Full-term infants did so, but they required longer interstimulus intervals than were needed for inhibition in the adult subjects. Results imply that the neural systems that mediate reflex inhibition are functional at birth, but that they are relatively slow to act.

Three years ago a tone ending in unavoidable electrical shock was periodically presented to pigeons while they pecked a key for food. When pecking was disrupted by tone, shock was disconnected and the training tone as well as tones of different frequencies were presented. At first, all tones caused a reduction in the rate of pecking, but as testing proceeded, suppression began to extinguish and the gradient narrowed. In the present work, testing was resumed after a 2(1/2)-yr interruption. Analysis of the gradients obtained just before and just after the interruption yielded no evidence of changes with the passage of time. As testing proceeded, however, extinction of suppression continued and the gradient all but disappeared. In subsequent experiments with these subjects (Ss) it was found that the presentation of free shocks caused a reappearance of the gradient and that this effect persisted in reduced amount for several sessions after the shock condition was terminated.

A tone ending with unavoidable electrical shock was periodically presented to pigeons while they pecked a key for food. A second group of birds was exposed to these tone-shock contingencies and also to a second tone which never ended with shock. The gradient of stimulus generalization following training to a single stimulus was symmetrical, whereas the gradient following discrimination training was asymmetrical, but there was no evidence of peak shift. During testing, suppression to all tones gradually extinguished and in both groups the slope of the gradient increased markedly. A second experiment with the discrimination birds revealed that free shock caused a recovery of the gradient, but the asymmetry persisted.