Higher Brain Centers Research Articles

Effects of androgen administered to neonatal male rats on hypophyseal gonadotropin content, secretion and response to LHRH at adulthood.

Supraphysiologic doses (1.75-3.50 mg) of testosterone propionate (TP) administered to male rats on the day of birth and 24 h later resulted in markedly reduced serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in adult males castrated for 16 days. These effects diminished as androgen was injected on succeeding postnatal days. Since exogenous dihydrotestosterone and testosterone were similarly effective, aromatization to estrogen is not required to elicit these effects. No build-up of either gonadotropin occurred in the pituitaries of TP-treated animals; pituitary LH content was appreciably reduced, while FSH remained unchanged. These data imply that hypophyseal synthesis and secretion of gonadotropins are curtailed in adult castrated males who have been androgenized neonatally. Pituitaries of such neonatally treated animals, however, were capable of increased secretion of LH in response to a challenge of luteinizing hormone-releasing hormone. These findings are compatible with a model in which an androgen suppressible event occurs at a suprahypophyseal level, e.g., hypothalamus or higher brain centers, in the male rat during a restricted neonatal period, which is responsible for programming the development of mechanisms involved in accumulation and secretion of gonadotropins.

Prediction of methylphenidate (Ritalin) responsiveness through sensory integrative testing.

Seventeen children previously judged to be good or poor responders to methylphenidate (Ritalin) were tested on sensory integrative measures while in the off-drug state. The tester was unaware of the children's drug response category. Results showed that children who were poor responders to Ritalin showed prolonged scores on and an adverse reaction to the Southern California Postrotary Nystagmus Test and had poorer equilibrium reactions and lower double tactile stimuli scores than the children judged good responders to Ritalin. These findings suggest that it might be possible to identify good and poor responders to Ritalin before the medication is given, something not previously thought possible. The current method for making this distinction is through a drug trial. These findings also indicate that there are at least two discernible types of hyperactivity associated with attention deficit disorders (ADD) that are theoretically related to differences in vestibular processing: one related to underaroused or overinhibited lower brain centers, and another related to deficient inhibition from higher brain centers. The good responders to Ritalin appear to be the underaroused group, the same population that responds to sensory integrative occupational therapy techniques. This implies that perhaps occupational therapy could be used to reduce the medication needs of these children.

Delayed puberty caused by hyperthyroidism in ram lambs is not a result of suppression in body growth.

Over a period of 8 weeks ram lambs (16 weeks old) were made hyperthyroidal (serum thyroxine approximately equal to 150 ng/ml, compared with control approximately equal to 48 ng/ml) by daily subcutaneous injections of thyroxine or maintained at a constant body weight by restriction of the feed intake. Hyperthyroidal and restricted-intake lambs remained at a constant body weight during the period of treatment whilst control rams gained body weight. Testicular growth was normal in restricted-intake lambs but was suppressed in hyperthyroidal animals. Hyperthyroidism, but not feed restriction, was also associated with decrease in LH pulse frequency (1.3 +/- 0.3/12 h compared with controls 4.8 +/- 0.9/12 h. Hyperthyroidal lambs showed normal LH responses to exogenous LHRH. After cessation of treatment testicular growth continued to be suppressed for up to 16 weeks in previously hyperthyroidic rams; thereafter testes began to increase in size but at 30 weeks after treatment were still smaller than those of control rams. It is concluded that elevated thyroxine concentrations directly influence sexual maturation in ram lambs through actions at hypothalamic and/or higher brain centres which control LH secretion. Transient hyperthyroidism during sexual maturation may cause permanent impairment of sexual development.

The dynamic interaction between steroids and gonadotropins in the mammalian ovulatory cycle

The interrelationship between steroid hormone secretion and gonadotropin secretion during the human menstrual cycle is a set of complex interactions. The temporal relationship between estradiol and progesterone secretion, the preovulatory surge of gonadotropins and the time of ovulation, has been studied extensively. The median time interval between the first rise of estradiol, progesterone, LH and FSH, and ovulation has been estimated to be 82.5 hr, 7.8 hr, 32 hr and 21.1 hr, respectively. The median time interval between peak blood concentrations of estradiol, LH and FSH, and the time of ovulation is estimated to be 24, 16.5 and 15.3 hr. There is considerable individual variation in the above mentioned estimates. The rising levels of blood estradiol that are secreted by the maturing ovarian follicles appear to be the primary trigger for the surge of gonadotropins leading to ovulation. In the experimental animal, the estrogen effect takes place at the level of the hypothalamus in the release of LHRH and at the level of the pituitary in increasing its sensitivity to LHRH. There appears to be a good correlation between the nuclear translocation of occupied estrogen receptors in the hypothalamus and the pituitary and the manifestation of estrogen effects. In the human, a rise in progesterone begins to take place after the first rise in LH has occurred. Progesterone appears to have both a stimulatory and inhibitory effect on gonadotropin secretion in the experimental animal and the human. Thus it exerts a fine-tune modulatory influence of estrogen effects which include enhancement of the estradiol induced gonadotropin surge, and perhaps the initiation of the midcycle FSH surge in the human. The abrupt termination of the preovulatory gonadotropin surge is difficult to explain because the pituitary gland is not depleted of its gonadotropin content or its capacity to secrete gonadotropins. Preliminary results suggests that progesterone by exerting its inhibitory influence may be responsible for the termination of the gonadotropin surge. This hypothesis, however, needs careful confirmation. The effects of progesterone may be manifested at higher brain centers, the hypothalamus and the pituitary, and may involve not only the release of LHRH but also an alteration of the pulsatile pattern of release of LHRH. The recognition of these components, along with the presence and control of LHRH degrading enzymes in the hypothalamus and the pituitary, emphasize the complexity of the system and the need for further work to gain a better understanding of the steroidal regulation of gonadotropin secretion.

Cobalt-immunocytochemical identification of peptidergic neurons in Calliphora innervating central and peripheral targets.

Certain neurons of the blowfly, Calliphora erythrocephala, show immunoreactivity to anti-gastrin/cholecystokinin (CCK) COOH terminal specific antisera. However, as is common to immunocytochemical staining, much of the structure of the immunoreactive neurons escapes detection. We describe here whole-neuron identification by backfilling with Co2+ and subsequent silver reduction, combined with immunocytochemistry of the filled cells. Cobalt-silver filled neurons can be examined directly by fluorescence microscopy for the presence of a secondary, rhodamine-conjugated antibody linked to the primary one. Two peptide-containing pathways have been resolved, one leading out of the brain to the corpus cardiacum, the other innervating certain higher brain centres, such as the central body. Both arise from neurosecretory cells of the mid-brain. Immunoreactive peptidergic neurons leading, respectively, to the corpus cardiacum and to the central body have been matched to single nerve cells visualized by Golgi impregnation, cobalt backfilling or focal injection of cobalt into the brain.

Central and peripheral influences on retention of postural asymmetry in rats.

Four studies were conducted to delineate potential neural processes involved in retention of a peripherally induced postural asymmetry. In the first experiment, dorsal and ventral spinal root section following varying intervals of stimulation successfully abolished peripherally induced hindlimb asymmetry. Experiment 2 revealed that 50 min of ventral root stimulation, in the absence of central connection, was not effective in producing asymmetry persistence. In an attempt to more closely delineate the time parameters involved in peripherally induced asymmetry retention, Experiment 3 was conducted. Asymmetry was found to consistently outlast a spinal transection if 40 min of stimulation was given. Finally, possible modulatory higher brain center influences on the retention processes were demonstrated in Experiment 4. Asymmetry persistence was consistently observed in animals that received 10, 20, 30, 40, or 50 min of hindlimb stimulation if 50 min were allowed to elapse between the onset of stimulation and spinal section. These results, when coupled with the findings of earlier studies, suggest an active involvement of spinal reflex centers in the fixation process. In addition, these studies indicate that the manner in which reflex activity is altered is not crucial as long as underlying time parameters are adhered to. Finally, the present studies demonstrate that higher center influences can modulate retention of a postural asymmetry in a complex manner.

The chemical control of respiration.

Arterial blood gas tensions are maintained at appropriate levels through a feedback system which adjusts ventilation and has multiple inputs and outputs. Inputs to the system arise mainly from peripheral and central chemoreceptors, but there are other inputs from mechanoreceptors and higher brain centers. Output from the system travels to chest wall and upper airway muscles. Need to conserve energy consumption by the respiratory system may also affect controller activity. The response times of the system may be important clinically but are not measured by conventionally used tests of respiratory control. Instability in respiratory control may contribute to the recurrent periods of apnea seen during sleep.

Regulation of Growth Hormone Release: Evidence against Negative Feedback in Rat Pituitary Cells*

To determine if the anterior pituitary gland is the site of negative feedback inhibition of GH release, we studied the effect of GH and multiplication-stimulating activity (MSA), a member of the somatomedin family, on isolated rat anterior pituitary cells in primary culture. The effect of GH was examined in two ways: 1) by adding to the cultures human GH (10 ng/ml to 20 microgram/ml) which was biologically active in the rat but not cross-reactive in the rat GH (rGH) RIA, and 2) by comparing rGH secretion in cultures of different cell densities. No suppression of either basal or prostaglandin E1-stimulated rGH release was found. An enhancement observed in serum-free conditions at high human GH concentrations was interpreted as a nonspecific response to protein, because bovine serum albumin produced the same effect. When added in the presence of serum, MSA (1--500 ng/ml) had no effect on rGH secretion. In the absence of serum, there were 71% and 30% increases in the basal and prostaglandin E1-stimulated rates of hormone release, respectively, possibly attributable to a trophic effect of MSA. Six other hormones having structural or functional similarity to either GH or somatomedin also failed to inhibit rGH secretion. Our results do not support the hypothesis that GH or somatomedin exerts a negative feedback effect on GH release directly on the anterior pituitary gland. Most likely, the hypothalamus or a higher brain center is the site for such regulation.

Glycine high affinity uptake and strychnine binding associated with glycine receptors in the frog central nervous system

Accumulation of [ 3H]glycine into synaptosomal fractions occurs by high affinity systems in cerebral cortex, optic tectum, brain stem and spinal cord of the frog. Specific [ 3H]strychnine binding which appears associated with postsynaptic glycine receptors is also demonstrable in these regions. By contrast, only very low levels of strychnine binding and high affinity glycine uptake occur in higher centers of the rat central nervous system. The relative potencies of small neutral amino acids in competing for [ 3H]strychnine binding are similar in frog brain and spinal cord. No evidence for a high affinity accumulation of [ 3H]taurine by synaptosomal fractions of frog spinal cord can be demonstrated. These observations favor glycine rather than taurine as an inhibitory transmitter in frog spinal cord. Moreover, these findings suggest that glycine may have a synaptic role in higher brain centers in the frog.

Effects of Aging on the Hypothalamic-Hypophyseal-Gonadal Axis in Female Rats

The failure of reproductive function in aged rats could be due to deficiencies at the level of the ovary, pituitary, hypothalamus, or higher brain centers. The classic explanation that the ovary is depleted of follicles does not receive adequate support on the basis of histologic studies of aged ovaries. Basal serum gonadotropin levels change with increasing age in female rats. Serum follicle-stimulating hormone (FSH) levels rise while serum luteinizing hormone (LH) levels fall. Likewise, the characteristic response to castration is markedly altered in aged female rats with a reduced secretion of FSH and a minimal elevation of LH. However, the pituitaires of these animals are still caapable of responding to exogenous LH-releasing hormone with a delayed LH response whose magnitude simulates that seen in younger female animals. With increasing age there is decreased pituitary and/or hypothalamic sensitivity to the feedback action of estradiol. These data are consistent with the postulation that there is an altered hypothalamic-hypophyseal function in aged rats.

Electroencephalography of the olfactory bulb in relation to prespawn homing.

It is evident that the bulbar EEG is a complex response which can be influenced by several methodological and stimulant variables. What EEG patterns tell us about actual behavior remains obscure. The bulbar EEG which is evoked by homestream water is not necessarily a reflection of olfactory memory. The evoked bulbar EEG also does not necessarily demonstrate the salmon has distinguished the home-water from another water in terms of migrational orientation. Despite lack of absolute specificity, a correlation between bulbar EEG and actual behavioral performance has been observed even though some non-home waters evoke responses similar to that of the home water. In general it has been found that the home water response can be distinguished from the response to other natural waters. Failure to obtain complete specificity may be due to a variety of variables which have been alluded to earlier in this section. Thus considering that the evoked EEG is a reflection of the integration of a diverse afferent input, further electrical and computer analyses may eventually permit the decoding of the EEG in terms of behavior. However, if the EEG proves to be more a quantitative rather than qualitative reflection of brain activity, relating EEG to behavior will prove to be of limited value. Since afferent responses in the olfactory bulb are influenced by impulses from higher brain centers, studies on centrifugal aspects during olfactory stimulation may be useful in gaining some qualitative understanding of the home water evoked EEG of the olfactory bulb.

Signal stabilization and noise suppression in neural systems

Neural activity is viewed as a stochastic point process, in which information resides in the modulation of a background of spontaneous activity. Characteristic features of the spatial and temporal mapping of sensory signals are discussed. One of the puzzling aspects of neural functioning is the integrity of the signal in its passage toward higher brain centers, in view of the fundamentally noisy response of the individual neuron. It is shown, that a process, we call image stabilization, is a direct consequence of the particular mapping function exemplified by lateral inhibition and adaptation.

Cardioinhibitor nerves in Limulus

When dorsal nerves 7 or 8 arising from the Limulus accessory brain are sectioned, cardioacceleration results; direct stimulation of these nerves produces cardioinhibition. These findings demonstrate a cardioinhibitory function. The results of forebrain lesions suggest that these inhibitors may be activated by higher brain centers.

Transformation of cortical motor signals in spinal cord

A review of the neuronal organization of the corticospinal (pyramidal) system is presented. Parameters of pyramidal tract fibers are described; special attention is paid to the existence of pyramidal neurons with fast- and slow-conducting axons which have different locations of somata over the sensorimotor cortex, different locations of terminals on spinal neurons, and different parameters of impulse activity. Two types of pyramidal descending action are considered: direct action of corticifugal signals upon motor units, and control of sensory flow to motor units and higher brain centers. Corticifugal motor signals produce predominantly excitatory postsynaptic potentials in flexor and inhibitory ones--in extensor motoneurons. The following types of connections between pyramidal fibers and motoneurons are distinguished: 1) monosynaptic connections (only in primates), 2) connections via propriospinal interneurons localized in the external basilar region and specialized for transmission of pyramidal fiber activity only, and 3) connections via interneurons of the internal basilar region and intermediate zone which transmit both segmental afferent and pyramidal activity. Evidence is presented that the activity of fast-conducting pyramidal fibers via the first two types of connections creates phasic synaptic processes in motoneurons while slow-conducting fibers via the third type render the tonic action. Properties of corresponding interneuronal groups are specialized for transmission of phasic and tonic signals. The types of pyramidal control of sensory flow considered are: 1) postsynaptic facilitation and inhibition of interneurons of segmental reflex arcs, 2) postsynaptic facilitation and inhibition of transmission via ascending pathways, 3) presynaptic inhibition of primary afferent activity, and 4) postsynaptic influences on γ-motoneurons.

Current status of research on the control of fertility

The last decade has witnessed the introduction of methods of contraception, based for the first time on means other than mechanical blockade of spermatozoa in order to prevent their ascent to the fallopian tube. Oral contraceptives, estrogen and progestin, either in combination tablets or sequentially administered, are inhibitors of ovulation. The effect on ovulation is subsequent to suppression of pituitary gonadotropin release which, in turn, is the result of an action by the administered steroids at the hypothalamus or higher brain center. There is now considerable evidence to support the concept that the steroid feedback system, controlling the release of gonadotropins, operates at the level of the central nervous system. Harris and Michael (1964), Lisk (1962) and others have demonstrated that the implantation of crystals of estrogens or progestins in specific regions of the hypothalamus results in the cessation of gonadotropin release, and, secondarily, prevents ovulation. The specific compound used in one of the contraceptive pills, chlormadinone, has been found by Gellert and Exley (1966) to prevent post-copulatory ovulation in rabbits, under experimental conditions which suggest an action at a brain level higher than the hypothalamus. It is interesting to note that electroencephalographic changes have been reported for women on contraceptive pills (Matsumoto, 1966). Studies of this type have made it abundantly clear, that the entire axis of ovary-pituitary-central nervous system must function in concert and in balance in order to produce an ovum. These anatomical units and their humoral products then provide potential targets for controlled interference with reproduction through the ultimate effect of suppressing ovulation. Important progress has been made in the last few years in our comprehension of the manner in which the neuroendocrine link at the hypothalamus operates. Hypothalamic releasing factors, which regulate the release of follicle-stimulating hormone and luteinizing hormone have been identiXed (Schally, 1964). They appear to be dialyzable substances of relatively low molecular weight. The precise

Effect of brain stem transections on blood pressure responses to medullary stimulation

1. Electrical stimulation in the posterior medulla of the unanesthetised rabbit shows diffuse distribution and intermingling of pressor and depressor points.2. Transverse transections, caudally of the hypothalamus, convert the majority of bulbar pressor responses into depressor reactions. This effect is similar to the barbiturate-induced reversal of hypertensise responses.3. It is assumed that medullary pressor neurons act mainly through higher brain centers, while the bulbar depressor elements have chiefly descending connections to the spinal cord, in addition to some ascending links.

Neuromuscular mechanisms of jaw and tongue movement

The masticatory process has a complex physiological background. Particular at­ tention has been given to the neurophysiological characteristics of this proc­ ess. Most of the studies on neuromuscular mechanisms have been concerned with limb muscles. However, there are distinct differences between jaw movements and limb movements. The mandibular joints are bilateral joints that function simul­ taneously. Movements of the jaw are varied and complex, being influenced by the anatomy of the teeth. Most of the jaw muscles are innervated by the trigem­ inal nerve. The nuclei of this nerve are widely distributed. They are found in the midbrain, pons, bulb and rostral spinal cord. T he descending neural pathways from the higher brain centers are not al­ ways similar to those of the limb muscles. This suggests that there exists a separate neural system for the jaw and tongue. The purpose of this article is to re­ view briefly the present physiological con­ cepts of the mechanisms of jaw and tongue movements. JA W M O V EM EN T AND FU N C T IO N O F JA W M U SC L E S

The correction of cross-eye.

Cross-eye does not always involve an impairment of the eye muscle. The synergism between the higher brain centers controlling convergence and divergence also may be a causative factor. Operation is frequently the most dependable remedy, but surgical results cannot be accurately predicted. The value of nonsurgical procedures should not be overlooked.

Anomalous physical signs of bodily disease in mental deficiency.

It was recognized long before the birth of Freud and of psychoanalysis that the mental attitude of the patient has an important if not a decisive influence on the course of bodily disease. Milton expresses the almost universal striving for life in spite of the sufferings of illness when he says:“And that must end us : that must be our cure—To be no more. Sad cure ! for who would lose,Though full of pain, this intellectual being,Those thoughts that wander through eternity,To perish rather, swallowed up and lostIn the wide womb of uncreated Night,Devoid of sense and motion? ”In more recent times, almost the whole of the work of Pavlov (1928), and particularly that of his pupil Bykov, is devoted to emphasizing the role of the cortex and higher brain centres in the determination of bodily reactions.

SIGNIFICANCE OF ANISEIKONIA IN AVIATION

THE word aniseikonia is derived from the Greek roots ἄνισος and eἰκών meaning literally image. It may be defined as that condition of the binocular visual apparatus in which the ocular images as seen by the two eyes are unequal in either size or shape or in both. The term ocular image does not refer to the retinal image, but it is applied to the final impression which reaches consciousness in the higher brain centers. Aniseikonia is of two principal types: (1) over-all difference, in which one image is larger than the other in all meridians, and (2) meridional difference, in which one image is larger than the other in one meridian. Combinations of the two forms may occur. If the ocular images are markedly unequal in size and shape, there may be a disturbance of binocular vision, which may or may not be apparent to the patient. ANISEIKONIA