Maternal corticotropin-releasing hormone and habituation in the human fetus.

Elevated concentrations of maternal corticotrophin-releasing hormone (CRH) during the 2nd and early 3rd trimester of human pregnancy are associated with spontaneous preterm birth, but the effects of maternal CRH on the fetus are unknown. Maternal plasma was collected for analysis of CRH concentration, m = 156.24 +/- 130.91 pg/ml, from 33 pregnant women during Weeks 31-33 of gestation. Immediately after collection of plasma, fetal heart rate (FHR) measures were obtained in response to a challenge with a series of vibroacoustic stimuli. Fetuses of mothers with highly elevated CRH did not respond significantly to the presence of a novel stimulus in a repeated series, p = 0.016. These effects on the FHR response were not related to parity, fetal gender, medical (antepartum) risk, or eventual birth outcomes. Impaired dishabituation in these fetuses of mothers with high concentrations of CRH suggests that neurological systems rich with CRH receptors that support learning and memory, such as parahippocampal regions, may be targets for maternal/placental CRH, with implications for fetal neurological development.

Is P50 suppression a measure of sensory gating in schizophrenia?

BACKGROUND: Abnormal P50 response has been hypothesized to reflect the sensory gating deficit in schizophrenia. Despite the extensive literature concerning the sensory filtering or gating deficit in schizophrenia, no evidence has been provided to test the relationship of the P50 phenomenon with patients' experiences of perceptual anomalies. METHODS: Sixteen drug-free DSM-IV diagnosed schizophrenic patients who reported moderate to severe perceptual anomalies in the auditory or visual modality were examined as compared to 16 schizophrenic patients who did not report perceptual anomalies, and 16 normal subjects. Both control groups were age- and gender-matched with the study group. RESULTS: Patients reporting perceptual anomalies exhibited P50 patterns that did not differ from normal subjects. In contrast, patients who did not report perceptual anomalies showed the abnormal P50 ratios previously found to be associated with schizophrenia. CONCLUSIONS: These paradoxical findings do not support the hypothetical relationship between the P50 and behavioral measures of sensory gating, suggesting that additional studies are needed to further explore the clinical correlates of the P50.

Human fetal heart rate dishabituation between thirty and thirty-two weeks gestation.

Few studies of human fetal habituation have included dishabituation procedures (i.e., assessment of the reemergence of a habituated response) to determine if response decrements are the result of reevaluation of information (a brain process) or fatigue of peripheral receptors. The purpose of this study is to describe the ability of the human fetus to learn and recall information with procedures to assess the central nervous system. Fetal heart rate (FHR) of 84 fetuses between 30 and 32 weeks gestational age was examined in response to 3 series of vibroacoustic (VA) stimuli presented at pseudorandom intervals of 25-45 s over the head of the fetus. Responses to the first series of 15 stimuli (S1) were compared with an identical second series of 15 stimuli (S1) presented over the head of the fetus. Between the 2 series, a novel (dishabituating) VA stimulus (S2) was presented, differing from S1 in intensity and frequency. The third series of S1s was applied to the mother's thigh as a control for possible maternal responses to the stimulus. Prestimulus FHR was computed during a 5 s interval before each stimulus, and mean FHR was computed during the intertrial interval (average FHR). The response to S1 during the first series of trials (1-15) produced a sustained rise in both prestimulus and average FHR, r(83) = .90, p < .001. After the novel S2 (trial 16) the rate of change was attenuated for average FHR, r(83) = .12, ns, to S1 for trials 17-31 but not prestimulus FHR, r(83) = .50, p < .001. The decrease in FHR response was reestablished when stimulation was applied to mother's thigh, trials 32-41, r(83) = .92, p < .001. A significant habituation pattern across trials was observed for the first series of S1s when prestimulus HR was subtracted from each preceding average FHR value (delta FHR). After the single novel stimulus (S2), the FHR response to S1 reemerged. All combinations of beginning and ending series slopes were compared, and only the rate of change during the last 4 trials of the initial presentation of S1 and the first 4 trials after the novel stimulus was significant, F(1, 82) = 9.21, p < .003. Uterine contractions collected from the continuous record were not related to the presentation of the novel stimulus, chi 2(1, N = 84) = 0.59, p < .50, ns, or delta FHR slope after the novel stimulus, chi 2(9, N = 84) = 10.52, p < .50, ns. These results established that the 32 week human fetus is capable of detecting, habituating, and dishabituating to an external stimulus and support the premise that areas of the human fetal central nervous system critical for detecting and discriminating information and for learning and memory have developed by the early third trimester.

Evidence for terminal decline in the event-related potential of the brain.

Precipitous decline (terminal decline) characterizes changes in the elderly just prior to death. The neurological and temporal parameters of terminal decline are not defined. The present study compared sensitive changes in the brain event-related potential (ERP) in 7 subjects who died within 1 year of evaluation with matched controls. Cross-correlation of annual ERPs revealed disorganization within and between subjects in response to memory dependent conditions but not in response to a novel stimulus (oddball). Motor reaction time to targets was not sensitive to decline. The changes associated with impending death were restricted to decline in reliability of the ERP within 1 year of death.

Neonatal exposure to a high level of ACTH4-10 impairs adult learning performance.

Male offspring of Sprague-Dawley dams were injected with 25 micrograms of ACTH4-10 or the vehicle on days 2 through 7 postpartum. Peptide treated animals exhibited a marked motor response to the peptide injection. Adrenal weights of these animals were consistently heavier than littermate controls in both the developing and adult animals. ACTH4-10 treated neonates exhibited significantly poorer learning performance in the shuttle box and were slower to acquire the reversal learning problem of a visual discrimination task under light shock levels. In addition, these animals also exhibited an exaggerated startle response and a stronger thigmotaxis response in the open field than controls. These results indicate that exposing the developing nervous system to relatively high levels of ACTH4-10 can produce marked long-term effects on behavior.

Rapid auditory evoked vascular response in man.

Plethysmographic signals were recorded in four body regions (fingertip, forearm, cerebral cortex, and ophthalmic artery) of normal, healthy subjects during the presentation of brief auditory tones. Tones were presented during either systolic or diastolic phases of the cardiac cycle. Using data processing techniques similar to those employed in cortical evoked potential studies, averaged waveforms were derived which revealed the presence of a polyphasic volumetric response beginning as early as 150 ms (after onset of tones) in some subjects. Grand average waveforms suggested a similar morphology in all four body regions. The rapid onset argued for neural mediation of this response which may represent a sudden, transient flexure of vascular smooth muscle. The presence of this evoked vascular response in the brain suggests a previously unreported responsiveness of the cerebral vasculature in man to simple auditory stimulation.

Effects of melatonin on startle reflex in rat.

In two experiments the effects of melatonin were investigated on the motor, cardiac and emotional components of the startle reflex induced by an intense acoustic stimulus. Melatonin inhibited the motor movements and significantly decreased the HR responses of rats pretested with these procedures. Melatonin decreased the HR responses to stimulation whereas the HR responses of the rats treated with the vehicle solution increased. Melatonin treatment also inhibited the startle-induced defecation compared with the vehicle injection. These findings suggest that melatonin exerts inhibitory effects on the CNS, on sensory reflex and on stress responses.

Voluntary control of electrogastric activity.

The tonic component of the electrogastrogram (EGG) has been shown to differentiate duodenal ulcer patients from healthy individuals (15). It has therefore been of considerable interest to investigate the possibility that individuals can learn to modify electrogastric activity. Using a discriminative conditioning paradigm with analogue feedback (Experiment I), subjects were generally unsuccessful at controlling tonic EGG activity. However, when the conditioning paradigm was altered (Experiment II) it was clear that subjects were able to modify specific electrogastric changes. In addition to EGG, heart rate, respiration, abdominal muscle activity, and digital blood flow were measured in order to assess the physiological concomitants of learned control of gastrointestinal activity. Subjects who evidenced discriminative control also showed the least amount of abdominal muscle activity and reported being the most relaxed. The results of these studies suggest that exploration of the physiological processes underlying the electrical activity of the gastrointestinal system and the ability of individuals to modify this activity may lead to significant clinical and theoretical advances.

Discriminative control of the vaginal vasomotor response.

With use of a discriminative control procedure and operant techniques, women significantly increased their vaginal pulse amplitude (produced vaginal vasodilation) but did not significantly decrease vaginal pulse amplitude (produce vaginal vasoconstriction). Acquisition of vaginal pulse amplitude control was rapid with no significant improvement over trials or the 5 experimental days. Specificity of vaginal pulse amplitude control occurred in relation to the other vasomotor responses, including vaginal blood volume and digital pulse amplitude. Vagnial pulse amplitude changes were not related to somatic-muscular, respiratory, or heart-rate changes. Women who used oral contraceptives were better able to control vaginal pulse amplitude than women who used other forms of birth control. Although the sexual behavior of these two groups and did not differ, women in the latter group tended to be more clitorally oriented.

Operant autonomic conditioning and rod-and-frame test performance.

Forty subjects were administered the portable rod-and-frame test (RFT) before and after operant autonomic conditioning training or control experiences. Ten subjects were assigned to each of four groups: a heart rate conditioning group; a false heart rate feedback group; a galvanic skin-response conditioning group; and a control group. Half of the subjects in the three experimental groups were informed of the response-reinforcement contingencies, and half were not informed. Informed subjects in the conditioning groups exhibited significantly lower portable RFT scores after conditioning. The results suggest that awareness of and control over autonomic functioning may be an important determinant of RFT performance.

Some questions related to melanocyte-stimulating hormone.

A number of questions remain unsettled about the release of melanocyte-stimulating hormone (MSH) and about its function. Even though relatively few investigators are studying this area, some generalities have emerged during the last 10 years. It now seems that release of MSH from the pituitary is inhibited by a substance present in the hypothalamus. The structure of this physiologic inhibitor of MSH release may still not be considered an established entity but there is evidence for additional mechanisms capable of exerting a fine control on the release of MSH. Contrary to some opinions, the release of MSH does not always occur together with the release of ACTH, and the release of the two hormones can be dissociated in several laboratory and clinical situations. In addition, many studies have shown that the pituitary peptide, MSH, exerts behavioral and electroencephalographic effects in both the rat and man. The hypothalamic peptide Pro-Leu-Gly-NH2 (MIF-I) also has direct effects on the central nervous system that may include alleviation of the symptoms of Parkinson's disease.