The Fetal brain
Murder is a legal term: Since Roe the only time the term murder can be used to address a fetal death is if a prosecutor says so. It is for the sake of debate important to differeniate technical terms to prevent hair splitters like stringy from going off on hair splitting rabbit trails of non arguments. Medical abortions legally kill unborn babies they do not murder them.
That said~~~
Developmental Review, 20, 81-98, 1999).
FETAL BRAIN &
COGNITIVE DEVELOPMENT
Rhawn Joseph, Ph.D.
Brain Research Laboratory,
ABSTRACT
The human brainstem is fashioned around the 7th week of gestation and matures in a caudal to rostral arc thereby forming the medulla, pons, and midbrain. The medulla mediates arousal, breathing, heart rate, and gross movement of the body and head, and medullary functions appear prior to those of the pons which precede those of the midbrain. Hence, by the 9th gestational week the fetus will display spontaneous movements, one week later takes its first breath, and by the 25th week demonstrates stimulus-induced heart rate accelerations. As the pons, which is later to mature, mediates arousal, body movements, and vestibular and vibroacoustic perception, from around the 20th to 27th weeks the fetus responds with arousal and body movements to vibroacoustic and loud sounds delivered to the maternal abdomen. The midbrain inferior-auditory followed by the superior-visual colliculi is the last to mature, and in conjunction with the lower brainstem makes fine auditory discriminations, and reacts to sound with fetal heart rate (FHR) accelerations, head turning, and eye movements--around the 36th week. When aroused the fetus also reacts with reflexive movements, head turning, FHR accelerations, and may fall asleep and display rapid eye movements. Thus fetal-cognitive motor activity, including auditory discrimination, orienting, the wake-sleep cycle, FHRs, and defensive reactions, appear to be under the reflexive control of the brainstem which also appears capable of learning-related activity.
FETAL BRAIN-BEHAVIOR AND COGNITIVE DEVELOPMENT
It is now well established that the human fetus is capable of some degree of behavioral complexity. In fact, as early as the 9th week of gestation the fetus is able to spontaneously move the extremities, head, and trunk (de Vries, Visser, & Prechtl, 1985). It has also been suggested that the near term fetus may be endowed with some degree of cognitive capability (e.g., Hepper & Shahidullah, 1994; Kisilevsky, Fearson & Muir, 1998). Cognition has been inferred based on alterations in fetal heart rate (FHR) and habituation to airborne sound (Kisilevsky & Muir, 1991), response-declines to vibroacoustic stimuli (Kisilevsky et al., 1998; Kuhlman, Burns, Depp, & Sabagha, 1988), and what appears to be neonatal preferences for the maternal voice as well as melodies and stories presented up to six weeks prior to birth (DeCasper & Fifer, 1980; DeCasper & Spence, 1986; DeCasper, Lecanuet, Busnel, Granier-Deferre & Maugeais, 1994; Lecanuet, Granier-Deferre, & Busnel, 1989).
As will be detailed below, the behavior of the fetus and newborn is likely a reflection of reflexive brainstem activities which are produced in the absence of forebrain-mediated affective or cognitive processing, i.e. thinking, reasoning, understanding, or true emotionality (Joseph, 1996a, 1999; Levene, 1993; Sroufe, 1996). It is the much slower to develop forebrain which generates higher order cognitive activity and purposeful behaviors, and which is responsible for the expression and experience of true emotions including pleasure, rage, fear and joy and the desire for social-emotional contact (Joseph, 1992, 1996ab, 1999; MacLean, 1990).
At birth and for the ensuing weeks, the forebrain is so immature that its influences are limited to signaling distress in reaction to hunger or thirst; a function of the immature hypothalamus (Joseph, 1982, 1992, 1999) in conjunction with the midbrain periaqueductal gray (e.g. Larson, Yajima, & Ko, 1994; Zhang, Davis, Bandler, & Carrive, 1994). Although various limbic nuclei become functionally mature over the course of the first several postnatal months and years (Benes, 1994; Joseph, 1992, 1999), the neocortex and lobes of the brain take well over seven, ten, and even thirty years to fully develop and myelinate (Blinkov & Glezer, 1968; Conel, 1939, 1941; Flechsig, 1901; Huttenlocher, 1990; Yakovlev & Lecours, 1967).
It is rather obvious that the neonate is able to scream and cry and can even slightly lift the corners of the mouth as if smiling. However, these do not appear to be true emotions (Sroufe, 1996; however, see Izard, 1991). In fact, smiling, as well as screaming and crying can be produced from brainstem stimulation even with complete forebrain transection or destruction (Larson et al., 1994; Zhang et al., 1994; reviewed in Joseph, 1996a). Hence, neonatal and premature infant "smiling" or distress reactions to noxious stimulation (e.g. heel lance) are also likely brainstem mediated, particularly in that they may be triggered in the absence of any obvious stimulus source and following forebrain destruction or lack of development (anencephaly). However, as brainstem maturation continues in a caudal-rostral arc (Debakan, 1970; Langworthy, 1937), at term and over the following weeks and months, the immature hypothalamus (which sits atop the midbrain), and thus the forebrain, increasingly contributes to and gains control over these behaviors (Joseph, 1992, 1999).
The progression in behavioral complexity that begins with spontaneous fetal movements and which culminates with presumed preferences for the sound of mother's voice, also appear to reflect maturational events taking place in the brainstem, followed by forebrain structures. Indeed, the brainstem is first fashioned around the 33rd day of gestation (Bayer, 1995; Marin-Padilla, 1988; Sidman & Rakic, 1982) and nearly completes its cycle of development and myelination around the 7th gestational month (Gilles, Leviton, & Dooling, 1983; Langworthy, 1937; Yakovlev & Lecours, 1967). However, in contrast to the forebrain, the brainstem is incapable of cognition such as reasoning, comprehension, or thought (Joseph, 1996c), but instead reflexively reacts to a variety of stimuli in an exceedingly complex, albeit stereotyped fashion (Blessing, 1997; Cohen, Rossignol & Gillner, 1988; Cowie, Smith, & Robinson,1994; Steriade & McCarley, 1990).
FETAL BRAIN DEVELOPMENT: OVERVIEW
Fetal brain development can be divided into ten stages (Joseph, 1996a)
1. The generation of the neuroectoderm from ectoderm, and the formation of the neural preplate.
2. The splitting of the preplate thereby forming the neural plate.
3. The rising up and the inward folding of the sides of the neural plate which arch together and create a neural tube.
4. The generation of neuroepithelium which gives birth to immature nerve cells, the neuroblasts which migrate and grow leading axonal appendages, and then aggregate in specific, genetically determined locations beginning with what will become the brainstem and spinal cord.
5. The division of the neuroepithelium into ventricular and subventricular zones which produce separate waves of migrating neuroblasts.
6. Flexure of the neural tube which ascends, twists, and bends due to continued neuroblast generation and neuron division, thereby forming three (medulla, pons, forebrain), then later two additional cerebral vesicles (midbrain, telencephalon).
7. The aggregation, differentiation, and division of neurons which form the nuclei of the medulla, then the pons, midbrain, hypothalamus, thalamus, and later the limbic system, striatum, and later, layers I and VII (VIa,b) of the neocortex.
8. The establishment of neocortical layers II through VI as successive waves of neuroblasts are generated and form columns and layers as they sandwich themselves between neocortical layers I and VII (VIa,b).
9. Neuronal differentiation, dendritic growth, the establishment of synapses, and the myelination of activated brainstem axons which have established dendritic synaptic connections.
10. Functional development of the medulla, followed by the pons, then the midbrain, the lastly, the forebrain which does not begin to functionally mature until near term.
THE BRAINSTEM: A FUNCTIONAL OVERVIEW
The brainstem consists of phylogenetically older neurons and nuclei and is organized in a somewhat similar manner across a host of species ranging from fish to woman and man (Aitkin, 1986; Joseph, 1996c; Vertes, 1990) The brainstem is an exceedingly complex structure, consisting of a variety of nuclei and subdivisions which perform an array of divergent as well as interrelated sensory and reflexive motor functions (Blessing, 1997; Klemm, 1990; Skinner & Garcia-Rill, 1990; Vertes, 1990). These include the mediation and control of arousal, orienting, the sleep cycle, heart rate, breathing, gross axial, limb, head and eye movement (Blessing, 1997; Cowie et al., 1994; Masino, 1992; Steriade & McCarley, 1990), as well as visual, somesthetic, gustatory, and acoustic perception and sound production such as screaming and crying (Aitkin, 1986; Davidson & Bender,1991; Larson & Yajima, 1994; Zhang et al., 1994).
Given its exceedingly long and ancient evolutionary history, not surprisingly, many brainstem functions are present before birth and occur without the aid of thinking, reasoning, or even forebrain/neocortical participation (Blessing, 1997; Joseph, 1996cd; Steriade & McCarley, 1990). That is, the motor programs which subserve many basic and vital functions, such as the regulation of heart rate, the sleep cycle, and respiration, are essentially genetically hardwired, reflexively initiated, and produced in accordance with the brainstem's synaptic organization and internally generated rhythms which have been acquired and molded over the course of evolution. Because so many brainstem functions occur in a rhythmic, diurnal, and/or reflexive fashion, they do not require the assistance of the forebrain (Blessing, 1997; Cohen et al., 1988; Joseph, 1996c; Klemm, 1990; Steriade & McCarley, 1990).
Indeed, these same reflexive and rhythmic activities are demonstrated by anencephalic infants who may possess only a brainstem, i.e. respiration, sleeping, waking, crying, leg kicking, rudimentary smiling, and even rapid eye movements while sleeping. Rather, it is only later life that the maturing forebrain begins to exert significant influence on brainstem functioning.
By the 7th gestational month the medulla and pons have nearly completed their cycle of myelination and most of the various descending spinal-motor fiber tracts have reached target tissues and established their synaptic interconnections (Gilles et al., 1983; Langworthy, 1937; Yakovlev & Lecours, 1967). However, because the fetal brainstem matures in a caudal to rostral arc, and as different nuclei mature and myelinate at different rates, fetal-brainstem reflexes are initially triggered infrequently or in isolation, and thus emerge gradually and in an irregular fashion (Debakan, 1970).
For example, around the 10th week of gestation the fetus may take a single "breath" over a 24 hour time period, whereas by the 40th week "breathing" occurs much more frequently with some degree of regularity in regard to chest and abdominal movement (de Vries et al., 1985; Natale, Nasello-Paterson & Connors, 1988). However, it's not until birth that the breathing (inhalation - exhalation) response occurs in a continual fashion; a function of increasingly mature brainstem development.
Nevertheless, the brainstem continues to mature well after birth, and correspondingly, brainstem reflexes emerge and disappear at different time periods over the course of the first three to six months of postnatal life (Debakan, 1970; see also Capute, Palmer, Accardo, Wachtel, Ross & Palmer, 1984; Piper & Darrah, 1994). For example, initially, vital functions such as heart rate and respiration are irregular, body temperatures fluctuate, and swallowing is precarious. In addition, reflexes such as sneezing, yawning, sweating, salivation, and urination are almost hypersensitive and easily triggered. Moveover, similar to those with forebrain destruction or transection, newborn infants can make stepping, walking, running, crawling and even swimming movements. Neonates can also involuntary grope and reflexively grasp with their hands. These same behaviors are also demonstrated by anencephalics.
Over the ensuing months these reflexes become subject to increasing neurological maturational control and either become stable or incorporated and subsumed by the forebrain, or they disappear and are suppressed; albeit at different time periods in accordance with the maturational events still taking place throughout the brainstem as well as the forebrain. However, if the forebrain were destroyed many of these same primitive reflexes will reappear, including the sucking, head turning, groping, grasping, tonic neck, labyrinthine, supporting, placing, and stepping reflexes.
THE DEVELOPMENT OF THE MEDULLA: A FUNCTIONAL OVERVIEW
Broadly considered, the brainstem consists of the medulla, pons, and midbrain, and matures in a caudal to rostral arc--a process that begins around the 6th to 7th week of gestation and continues well into the first year of postnatal life (Debakan, 1970; Gilles et al., 1983; Sidman & Rakic, 1982; Yakovlev & Lecours, 1967). Hence, the nuclei of the medulla generally emerge and myelinate prior to those of the pons which precede those of the midbrain. As noted above, this pattern of functional development is also demonstrated behaviorally in the fetus and neonate.
For example, in addition to its many subnuclei, the medulla gives rise to a variety of descending spinal-motor tracts which reflexively trigger limb and body movement. It also sprouts five cranial nerves, the acoustic (VIII), glossopharyngeal (IX), vagus (X), accessory (XI) and hypoglossal (XII), which exert tremendous influences on gross body movement, heart rate, respiration, and head turning. Specifically, the hypoglossal nerve and nucleus, controls the tongue and influences body movement. The spinal accessory nerve and nucleus controls shoulder elevation and head turning. The vagus, glosopharyngeal nerve, and nucleus solitarious control respiration and heart rate.
In regard to heart rate, the nucleus of the solitary tract interacts with and is also coextensive with the medullary respiratory and vasomotor centers. Together with the vagus and glosopharyngeal nerve and in conjunction with the "autonomic nervous system" these nuclei act to excite and depress cardiovascular functioning (Aminoff, 1996; Blessing, 1997; Joseph, 1996c). As per the medulla, control over the cardiovascular system is accomplished via pre- and post-ganglionic vagal fibers which project to the atrial muscle and the sinoatrial and atrioventicular nodes of the heart. However, in regard to fetal development and heart rate, the differential developmental rates of the parasympathetic system vs the sympathetic system, also appear to exert significant influences on the different maturational patterns of FHR deceleration and acceleration (see Kisilevsky & Low, 1998; Sorokin, Dierker, Pillay, Zador, Schreiner, & Rosen, 1982; Wheeler & Murrills, 1978).
As the medullary reticular formation constitutes the core of the medulla this portion of the brainstem is also able to stimulate and thus activate the spinal cord, as well as the more rostral portions of the brain including the forebrain and neocortex (Blessing, 1997; Steriade & McCarley, 1990). However, as the medulla matures in advance of more rostral structures, reflexive movements of the head, body, extremities, as well as "breathing" movements and alterations in heart rate, appear in advance of other functions.
SPONTANEOUS HEART RATE CHANGES, BODY AND BREATHING MOVEMENTS
The neural tube is first fashioned three weeks after conception and by the 7-8th week of gestation the major structures of the medulla have been established (Gilles et al., 1983; Sidman & Rakic, 1982). These include the hypoglossal, spinal accessory, vagus, and glosopharyngeal cranial nuclei, and the neurons of the reticular activating system. As noted, these nuclei and activating pathways subserve arousal, generalized body movements, head turning, shoulder elevation, heart rate, and breathing.
Likewise, beginning as early as the 7th week of gestation, the infant will display spontaneous movements, which by the 9th week come to include the extremities, the trunk, and the head (de Vries et al., 1985). Soon thereafter the fetus will take its first "breath" and by the 10th week of gestation spontaneous "breathing" (chest and abdominal) movements are observed (de Vries et al.,1985).
Initially these "breathing" movements remain rather irregular, variable, and isolated events, such that perhaps one breath might be observed over the course of an hour. Over the ensuing weeks and months these breathing movements occur more frequently and by 24 weeks they may be observed about 14% of the time. By 40 weeks the fetus will breath about 30% of the time over a 24 hour period (de Vries et al. 1985; Natale et al., 1988; Patrick, Campbell, Carmichael, Natale, & Richardson,1980).
As there is no free oxygen which may be inhaled, these "breathing" movements are brainstem reflexes which tend to be produced during periods of brainstem activity and heightened arousal (e.g., Pillai & James, 1990). Thus the aroused fetus (Pillai & James, 1990; Sorokin et al., 1982) not only will take a "breath" but will demonstrate alterations in heart rate and spontaneous movements which are also produced secondary to high levels of brainstem activity --as it is the brainstem which mediates arousal. Thus, during high levels of brainstem arousal, the fetus will spontaneously move its head, trunk, and extremities (de Vries et al., 1985), whereas heart rate may dramatically accelerate (Sorokin et al., 1982).
Moreover, just as breathing occurs more frequently as the medulla matures, spontaneous movements are observed more frequently as well. By 10 weeks spontaneous body movements occur about 14% of the time, whereas by 19 weeks the fetus is active more than 50% of the time (de Vries et al., 1985). That does not mean that FHR acceleration, breathing, and body movements are strictly coupled. For example, after 20 weeks there is an increase in the percentage of FHR acceleration and movement (DiPietro, Hodgson, Costigan, Hilton, & Johnson, 1996), until around 30 weeks at which point body movements decline (Natale, Nasello-Paterson, & Turlink, 1985). By contrast, a decrease in fetal "breathing" is not observed until two days before labor onset (Patrick et al., 1980), which, however, may be due to mechanisms initiating labor rather than maturation per se.
By term, heart rate fluctuations and accelerations again occur in tandem with spontaneous body movements and heightened arousal (Timor-Tritch, Dierker, Hertez, Deagan, & Rosen, 1978); a likely function of maturational changes occuring within the medulla and throughout the brainstem.
However, just as heightened brainstem activity is associated with labored breathing, but a general lack of movement during "paradoxical" sleep (Steriade & McClure, 1990), alterations in brainstem arousal may produce fetal "breathing" but a lack of movement during "quiet" states. As in "deep sleep," "quiet" periods may be due to heightened brainstem inhibitory influences over the spinal cord and cranial nerves; for electrophysiologically, during "deep sleep," the brain is in fact highly active (Steriade & McClure, 1990). Hence the term "paradoxical" sleep; a seemingly "quiet" period associated with a lack of limb, head, or whole body movement other than jerks and twitches, lateral eye movements, and labored breathing.
That these fetal reflexes are produced by an immature and still maturing brainstem and do not reflect cognitive processing or purposeful movement activity is suggested by the fact that breathing and spontaneous movements actually decrease as the fetus nears term (Kozuma, Nemota, Okal, & Mizuno, 1991; Patrick et al., 1980; Patrick, Campbell, Carmichael, Natale, & Richardson, 1982; Trudinger, Aust, & Knight, 1985), though again the contributions of mechanisms related to labor initiation cannot be ruled out. Thus, as the medulla myelinates, stabilizes, and matures, these spontaneous reflexes are not as easily triggered, but begin to be governed by the more stable intrinsic activities generated within the brainstem. Hence, at birth the infant takes its first real breath which is then sequentially repeated without interruption. Likewise, as the brainstem continues to mature after birth, brainstem regulated functions, such as heart rate and breathing, become increasingly stabilized over the ensuing weeks and months.
