Ronald E. Myers

Two patterns of perinatal brain damage and their conditions of occurrence

Abstract Term monkey fetuses may be subjected to episodes of total asphyxia characterized by complete stoppage of respiratory gas exchange. Such animals, after resuscitation and extended survival, exhibit damage to structures in their brainstems. This injury pattern fails to resemble that found after perinatal damage in the human being. Term monkey fetuses subjected to episodes of partial asphyxia, on the other hand, exhibit injury to structures in the hemispheres. This damage, when severe, may consist of a total bilateral hemispheral necrosis. With less severe injury, the necrosis may be restricted to the middle third of the paracentral region and/or to the basal ganglia. After prolonged survival, areas of necrosis are transformed into areas of nodular cortical atrophy, white matter sclerosis, and status marmoratus of the basal ganglia. These eventual long-term, static lesions closely compare to the lesions of human perinatal injury or cerebral palsy. Episodes of in utero fetal partial asphyxia may be brought about in a variety of ways, many of which, in one fashion or another, reduce maternal blood flow through the placenta. Retardation of placental intervillous space perfusion, in turn, diminishes the net exchange of respiratory gases between the mother and the fetus and leads to varying degrees of hypoxia, hypercarbia, and acidosis. Episodes of fetal bradycardia and hypotension following uterine contractions (Type II dips) may appear with severe asphyxia. Such hypotensive episodes may be associated with impairments of cerebral perfusion which, when repeated, may contribute to fetal brain injury. Maternal stimulation with exogenous or endogenous catecholamines leads to fetal asphyxia by producing maternal visceral vasoconstriction, thereby reducing maternal blood flow to the uterus. The tendency for perinatal asphyxia to be associated with myocardial injury and heart failure is emphasized. More babies die of cardiovascular failure secondary to myocardial injury than survive less severe disturbances in heart action to exhibit brain damage.

COMPARATIVE NEUROLOGY OF VOCALIZATION AND SPEECH: PROOF OF A DICHOTOMY

The existence of a dichotomy between those behaviors and body movements which are volitional and those which are emotional has been recognized in clinical neurology for many years. The neurologist, in examining his patient, requests him to “show his teeth” with all his strength. In response to this command, the patient strongly bares his teeth. If a weakness appears in the action of one or both sides of the face the neurologist concludes the patient has a paralysis of volitional use of the face-if no evidence exists of a lesion of the facial nerve or its nucleus. The neurologist also waits for occasions when the patient smiles or laughs in response to any amusing situation. He again takes care to determine whether the patient shows any asymmetry in action of the two sides of his face. If such an asymmetry appears and the patient does not also show evidence of a volitional paralysis, the neurologist concludes that the patient has a weakness in the emotional use of the opposite side of the face. Again, such a paralysis can be bilateral or entirely one-sided. These timehonored methods of investigating the motor activity of the face may serve us as the basis for an operational definition of the terms “volitional” and “emotional.” Those unintended facial movements (or vocal utterances) which arise as a part of an instinctual reaction to an appropriately evocative situation may be regarded as emotional or involuntary, whereas those facial movements (or vocal emissions) which are clearly intended by the individual or requested of him may be considered volitional. The neurologist has long recognized that large lesions which affect the precentral gyrus, the internal capsule, or the corticospinal tracts of one or the other hemisphere may cause a paralysis of the voluntary use of the opposite side of the body. If, however, such lesions are restricted to inferior portions of the precentral convolution or to a small part of the internal capsule, they may cause a paralysis restricted to the opposite side of the face. Lesions affecting the left hemisphere in such locations also often cause disorders of speech. The association of right facial weakness with speech difficulties is common and excites no special attention in the literature, particularly since such right-sided motor symptomatologies associated with speech disorders have been described since the early 1800s. See, for example, Broca’s 1865 description of the occurrence of speech disorders following lesions of the posterior portion of the left inferior frontal convolution. I It took neurologists a longer time to recognize that isolated paralyses of the emotional use of the face may occur. However, by the middle 1800s, the possibility of such paralyses was well recognized, and from that period through the 1920s numerous papers describing this phenomenon appeared under a variety of titles.2-4 In contrast to the ready recognition of a relation between paralyses of volitional movement and the corticospinal system, it has been difficult to define a precise neurologic basis for paralyses affecting emotional expression. This has been true

Maternal psychological stress and fetal asphyxia: a study in the monkey.

Fifteen pregnant rhesus monkeys near term were anesthetized with pentobarbital. Catheters were placed into the right femoral arteries of the mother and fetus, the fetuses being retained in utero. After repair of all incisions, the mothers were placed on their sides and allowed to recover from anesthesia. As they awakened, their fetuses regularly developed blood chemical and, frequently, vital signs changes indicative of deepening asphyxia. In eight cases, anesthesia was reinstated with intravenous pentobarbital, 30 mg. per kilogram. This caused an immediate and significant improvement in oxygenation of the fetus in all instances. The remaining animals were transferred to restraining chairs where the blood chemical and cardiovascular statuses of the mothers and fetuses were followed over the next 3 to 72 hours. During this time, the mothers, fully awake, were subjected to both contrived and incidental episodes of psychological stress stimulation. In the majority of instances, these periods of stress to the mothers caused episodes of bradycardia and hypotension in their fetuses. These induced vital signs changes of the fetuses appeared regularly about 50 seconds after the beginning of the periods of stress stimulation of the mother. Similarly, the vital signs changes frequently began returning toward more normal values with 1 to 2 minutes after the alleviation of maternal stress. Blood samples drawn in single cases before, during, and after recovery from bradycardia identified an associated increase in asphyxia of the fetuses. These episodic aggravations of the already existent fetal asphyxia of the fetuses. These episodic aggravations of the already existent fetal asphyxia brought about by stress stimulation of the mother are interpreted as resulting from activation of the maternal sympathetic nervous system causing vasoconstriction throughout the abdominal viscera and an accompanying retardation in intervillous space perfusion.

Production of fetal asphyxia in the rhesus monkey by administration of catecholamines to the mother

Abstract The effects of the administration of epinephrine and norepinephrine to the pregnant rhesus monkey near term has been investigated with particular regard to alterations in the performance of the cardiovascular system and in the acid-base state of the fetus. It was found that either of the catecholamines can produce severe asphyxia of the fetus when given in amounts that elicit a distinct increase in maternal blood pressure. When spontaneous activity of the uterus was high, both agents (but particularly norepinephrine) increased the work output of the organ. The quiescent uterus, on the other hand, relaxed further during the administration of epinephine. Vasoconstriction in the uterine circulation was identified as the central factor responsible for the impairment in fetal oxygenation, since administration of catecholamines directly to the fetus produced no adverse effects on fetal acid-base state, and fetal asphyxia could be produced in the presence of a decrease in uterine activity.

Predictability of the state of fetal oxygenation from a quantitative analysis of the components of late deceleration

Abstract The relationship between the various components of late decelerations of the fetal heart rate (type II dips) and the pH, P o 2, and hemoglobin saturation with oxygen of the fetal arterial blood was investigated in 15 anesthetized near-term rhesus monkeys. These fetuses were asphyxiated by markedly lowering the arterial blood pressure in the distal third of the maternal aorta. Strong uterine contractions occurred spontaneously in all animals. Correlational studies demonstrated that: (1) the latency period (time from onset of uterine contraction to onset of late deceleration), (2) the rate of development, and (3) the magnitude of the late decelerations were all three good predictors of the fetal oxygenation (the P o 2 and per cent saturation of hemoglobin with oxygen of the fetal blood). The correlations between these variables were further improved when the durations of the uterine contractions were also taken into consideration. Although the values of these three components of late deceleration accurately reflected the state of fetal oxygenation, they bore no relation to the fetal blood pH. In the presence of normal uterine contractions, late decelerations never occurred in association with normal fetal oxygenation. When late decelerations did appear in relation to contractions of normal duration, they reflected the development of marked impairments in fetal oxygenation in every instance.

Loss of social group affinity following prefrontal lesions in free-ranging macaques

Abstract Five free-ranging rhesus monkeys underwent resections of prefrontal cortex anterior to the frontal eyefields. Four others sustained bilateral ablations of the cingulate gyrus. Four of the 5 prefrontal animals failed to rejoin their social group on release and remained solitary until their deaths. The one animal to rejoin the social group was a yearling. All prefrontal animals except the yearling exhibited increased levels of aimless pacing activity. Three of the 4 animals with bilateral cingulate lesions returned to the social group and appeared largely unchanged by the extensive cerebral lesions. The fourth animal, a 5-year-old male, remained solitary until his early death 2–3 days later. However, abandonment of social group and adoption of a temporary solitary state occurs frequently among males of this age group on Cayo Santiago. Ten control animals trapped from the group all returned to the social group and appeared unaffected. The present results support the hypothesis that the prefrontal and the anterior temporal cortical regions both contribute importantly to the control and regulation of social behavior in the subhuman primate.

Social behavior deficits of free-ranging monkeys after anterior temporal cortex removal: a preliminary report

50KODA, J., Subcortical structures controlling lateral geniculate transmission, Tohoku J. exp. ivied., 76 (1962) 350-364. 6 SAKAKURA, H., Spontaneous and evoked unitary activities of cat lateral geniculate neurons in sleep and wakefulness, Jap. J. Physiol., 18 (1968) 23-42. 7 STERIADE, M., AND DEMETRESCU, M., Unspecific system of inhibition and facilitation of potentials evoked by intermittent light, J. Neurophysiol., 23 (1960) 602-617. 8 SUMITOMO, 1., IDE, K., IWAMA, K., AND ARIKUNI, T., Conduction velocity of optic nerve fibers innervating lateral geniculate body and superior colliculus in the rat, Exp. Neurol., 25 (1969) 378-392. 9 SuzuKi, H., AND KATO, E., Binocular interaction at cats lateral geniculate body, J. Neurophysiol., 29 (1966) 909 920. 10 SUZUKI, H., AND TAIRA, M., Effects of reticular stimulation upon synaptic transmission in cats lateral geniculate body, Jap. J. Physiol., II (1961) 641 655.

Fetal brain damage following maternal carbon monoxide intoxication: an experimental study.

Abstract. Techniques of fetal monitoring, including fetal blood sampling in utero, were employed to study the physiological effects of acute maternal carbon monoxide intoxication upon the fetal rhesus monkey. Nine term‐pregnant female monkeys were exposed to 0.1‐0.3 % inspired CO over 1‐3 hours. The mothers tolerated car‐boxyhemoglobin (COHb) levels exceeding 60 % without clinical sequelae. The fetuses promptly developed profound hypoxia upon exposure of the mothers to CO. However, the fetal COHb levels rose only gradually over the 1‐3 hours and thus contributed only slightly to the development of the early fetal hypoxia. Fetal hypoxia was associated with bradycardia, hypotension, and metabolic and, later, respiratory acidosis. A close correlation was noted between the severity of intrauterine hypoxia and the appearance of brain damage. Severe brain damage (brain swelling associated with hemorrhagic necrosis of the cerebral hemispheres) appeared only in those fetuses whose arterial O2 content had fallen below 2.0 ml/100 ml for at least 45 min during the maternal CO intoxication.

Role of forebrain structures in emotional expression in opossum

Alterations in emotional behavior were studied following the bilateral removal of forebrain structures in opossums. Structures separately ablated in different animals included the neocortex en toto, the olfactory bulbs, the pyriform cortex, the amygdala, the hippocampus, the caudate nucleus, the septum and the area innominata. n nThe opossums prominent open-mouthed threat gesture, as elicited by artificial test stimulations, diminished greatly after bilateral removals either of amygdala or of hippocampus, but was enhanced after lesions of caudate nucleus. Hyperreactivity to these test stimulations also appeared in subjects following bilateral total neocortical and olfactory bulb ablations. Bilateral pyriform cortex removals facilitated animal aggressiveness, whereas amygdalectomy extinguished its expression completely. n nThe present results reveal the amygdala to be the forebrain structure most prominently involved in controlling emotional behavior, this especially in relation to facial threat and attack.

Age effects on social behavior deficits following prefrontal lesions in monkeys

Abstract Prolonged observation of rhesus monkey social behavior has shown no deficits among infants and yearlings which have undergone bilateral ablation of the prefrontal cortex. However, the behavioral deficits common to prefrontal lobectomy did appear with an increasing severity among 2- and 3-year-old juveniles and in adults. These deficits include decreased use of face and voice for communication, alterations in aggressiveness and patterns of grooming, decreased participation in play activity and frequent aimless hyperactivity. It appears that a certain degree of maturation is required for the social effects of prefrontal lobectomy to be expressed. Rhesus infants operated on at 2 weeks, 5 months and 12 months of age show minimal, if any, deficits. Older juveniles and adults, however, do not maintain most behavioral patterns of social interaction. Harlows results regarding deficits in intellectual development on learning performance tests are discussed. It is concluded that the appearance of social awareness and of intellectual maturity may occur at different times in a monkeys development.