3. Development in the CNS

Conel (1939–1959) mapped postnatal frontal lobe development, showing rapid changes in density from birth until 15 months. Synaptic density increases until two years of age, when it is about 50 percent above that of adults, and decreases until about 16 years of age (Gazzaniga et al., Ivry, & Magnun, 2002). A decrease in the number of synapses in the frontal lobes may represent a “qualitative refinement” in the functional capacity of the neurons (Brodal, 2004). That is, cognitive complexity cannot be defined in simple quantitative terms, such as the number of synapses. These structural changes appear to correspond to the development of behaviors mediated by the frontal lobes, namely speech, executive, and emotional functions (see Table 3.1).

Using EEG data to map brain activity, Thatcher (1996) suggests that there are “growth spurts” of cortical connections from the parietal, occipital, and temporal lobes to the frontal lobes. These growth spurts occur at three intervals: (1) from age 1.5 to 5 years; (2) from 5 to 10 years, and (3) from 10 to 14 years. After age 14 the frontal lobes develop at the same rate and continue until age 45. These corticocortical connections differ between hemispheres. The left hemisphere shows a developmental sequence of gradients involving anterior-posterior and lateral-mesial regions, with lengthening of connections between posterior sensory regions, and frontal areas, while the right hemisphere involves a contraction of long-distance frontal connections to posterior sensory areas. Thatcher (1996) suggests that the expansion of the left hemisphere is due to functional differentiation of new subsystems, whereas the contraction of the right hemisphere is the functional integration of previously existing subsystems. Thus, experience and stimulation play a direct role in the process of redefining and differentiating neuroanatomy.

Studies of changes in the brain over development using Magnetic Resonance Imaging (MRI) have found differences not only by age but also by gender. Sowell, Trauner, Gamst and Jernigan (2002) found age-related increases in total brain volume as well as in white matter volume in a group of children aged 7–16. Differentiation in white matter was found during this period with increases in volume while gray matter was found to decrease in volume between childhood and adolescence. Cerebrospinal fluid (CSF) was found to show a 2 percent increase with age. Older participants had about 4 percent of the brain volume due to CSF, while younger participants had 2 percent of the total brain volume due to CSF. Additional age effects were found in the areas of the frontal lobe and anterior cingulate with increases in white matter volume in these regions. The caudate and thalamus were found to decrease in volume with age, which was gender-specific. Volumes of the caudate and putamen decreased with age for boys, but not for girls. Similarly, the cerebellum (the region of the brain responsible for fluid movement) was approximately 8 percent larger in boys. The putamen and globus pallidus (other areas deep in the brain and responsible for input of motor information) were also larger in males compared to females.

Male brains have been found to be approximately 7–10 percent larger in volume compared to females during childhood (Giedd, Castellanos, Rajapakse, Vaituzis & Rapoport, 1997; Giedd et al., 1996; Reiss, Abrams, Singer, Ross & Denckla, 1996; Sowell et al., 2002). When brain size was controlled, girls were found to show larger volumes in the gray matter of the temporal cortex, the caudate, thalamus, and regions deep inside the brain (i.e., hypothalamus). In a subsequent study, (Giedd et al., 1997) found that the amygdala (a structure involved in emotional processing) and the hippocampus (a structure involved in setting down memories) volumes increased for both genders with age. The amygdala was found to increase significantly more for males than females, while the hippocampus increased in volume more for females than for males.

Scheibel (1990) examined dendritic structures in the frontal lobe to determine the relationship between functional speech abilities and cortical development. In a series of postmortem studies, electron microscopic techniques were applied to brain tissue taken from 17 subjects between the ages of three months and six years. Structural changes in dendritic growth patterns appear related to differences in language functions across the ages and are summarized as follows:

Speech during the first 6–12 months of age is characterized by affective communication patterns, which probably are related to dendritic growth in the right frontal regions (Scheibel, 1990). As the left frontal region develops the child’s ability to understand syntax and more complex language forms improves. Development of dendritic processes in the language regions in the left hemisphere catches up to and eventually exceeds development in the right hemisphere corresponding to increases in the use and complexity of language skills. Some suggest that experience and functional differentiation go hand in hand and are necessary for further development.

Scheibel (1990) found that proximal and distal segments of the dendritic branches also differed depending on the hemisphere. Proximal segments (near the cell body) develop early, with distal segments (far) appearing later in development. Proximal segments are longer in the right hemisphere, with distal segments more pronounced in the left hemisphere. The proximal/distal ratio appears complementary, where proximal segments are longer in the absence of distal segments. The importance of distance from the cell body in determining the role of the dendritic processes is unknown. However, Scheibel (l990) does suggest that distinct dendritic processes in the two hemispheres are probably related to functional differences between the two regions.

Studies have also focused on the neurobehavioral correlates of frontal lobe development, specifically the emergence of “executive” functions (e.g., planning, flexibility, inhibition, and self-monitoring) that have been attributed to this area. Whereas prefrontal regions have been hypothesized to be involved primarily in executive functions, striatal regions also have been investigated (Castellanos et al., 1996; Semrud-Clikeman, Pliszka, Lancaster, & Liotti, 2006). Because there are rich connections between the frontal lobes and striatal regions (Semrud-Clikeman et al., 2006), it is reasonable to believe that these two areas are intimately involved in executive functions.

It has been strongly suggested that executive functions are subdivided between the dorsal frontal, lateral frontal, and orbital frontal anatomical regions. The dorsal frontal region may be responsible for determining how important a situation is; the lateral frontal is involved in determining if the selected action is worth the effort needed to obtain the result; and the orbital frontal is responsible for determining the social and situational appropriateness of actions. Thatcher (1991) suggests that the interaction of these three functionally relevant areas provides the behavior known as executive function.

In keeping with our transactional model, Denckla (2007) suggests that executive functions have two influences, one neuroanatomical and the other “psychodevelopmenta1,” and that these influences not only interact, but also modify each other. For example, Denckla (2007) cites the example that construct validity of executive action is demonstrated by convergent (a child of X age can do this when he or she can do that) and divergent (a child of X age can do this, but not that) validity. Some suggest that the frontal lobes of children develop rather markedly between the ages of four and seven years, with steady but less dramatic increases from 12 years of age to adulthood (Luria, 1980). Others suggest that development of executive functioning begins in adolescence and continues up to about 24 years of age (Pennington, 1991). Still others suggest that the frontal lobes develop in cycles rather than with variable development between the hemispheres (Thatcher, 1996).

Experimental studies have shown that children do exhibit behaviors thought to be mediated by the frontal lobes much earlier than adolescence or adulthood. Similar to Denckla’s (2007) convergent/divergent validity approach to executive functions, Becker, Isaac, and Hynd (1987) found age variation in skill attainment. Skills thought to be mediated by the frontal lobes were found to be mastered by 10- and 12-year-olds; these included the capability of inhibiting motor responses, remembering the temporal order of visual designs, using strategies for memory tasks, attending to relevant details and ignoring distractors, and employing verbal mediators to enhance performance. Six-year-olds had more difficulty inhibiting motor responses and remembering the temporal order of visual designs. There appeared to be a developmental shift for eight-year-olds, who were able to inhibit motor responses. While subjects at all age levels were able to verbalize directions, younger children, especially those under the age of eight, were not always able to inhibit perseverative responses.

Passler, Isaac, and Hynd (1985) also found that children progress through developmental stages showing mastery of some frontally mediated tasks at six and eight years, while other tasks were not even mastered at the age of 12. Six-year-olds gave flexible, correct responses for a verbal conflict task, but were unable to respond accurately to a nonverbal conflict task. Although eight-year-olds mastered both tasks and were also able to complete a perseveration task, they were unable to complete a series of drawings consistently or to respond correctly to verbal and nonverbal proactive inhibition tasks. Finally, even the 12-year-olds did not obtain full mastery of the verbal and nonverbal retroactive inhibition tasks.

Taken together these findings suggest that the greatest period of development for executive functions occurs between the ages of six and eight, with continued growth beyond the 12-year-old level for more complex tasks. Supporting these findings, children have been found to reach adult levels of performance by 10 years of age on measures of cognitive flexibility (the Wisconsin Card Sorting Test), but did not reach adult levels of performance on a word fluency test even by the age of 17.

Models of the neuropsychological basis of emotions indicate that the frontal lobes play a central role in the processing of emotional responses (Semrud-Clikeman, 2007). The two hemispheres appear differentially involved in adults, with damage to the left hemisphere resulting in depression and catastrophic reactions; whereas damage to the right hemisphere results in inappropriate emotional reactions, including indifference or euphoria (Heilman, Blonder, Bowers, & Valenstein, 2003). Developmental patterns have documented that the left hemisphere may be more reactive to emotional stimuli in younger children (9 years of age) than adolescents (14 years of age) and adults (Davidson, 1994). As the right hemisphere matures, it has a modulating effect on the more reactive left hemisphere (Heilman, Watson, & Valenstein, 2003). Moreover, as the corpus callosum matures, the right hemisphere can inhibit or control the left hemisphere more effectively. Thus, depression in children and adults may be a function of underactivation of the frontal regions, or the right hemisphere may be overactivated. It may well be that it is the ratio of activation between the two hemispheres that is important rather than the level of activation of either one. Neurodevelopmental patterns may help to explain why depression seems to increase around puberty, which corresponds to the time when later-developing corpus callosal structures are becoming mature (Zaidel et al., 2003). The temporal lobes may also be important for the perception of emotions (e.g., facial or tonal), and differences between the anterior/posterior regions may be just as important as the right/left hemisphere differences in the control of emotions. For example, posterior regions of the temporal lobe are important for recognition of facial expressions while anterior regions may be implicated in understanding and recalling the labels for such expressions (Semrud-Clikeman, 2007).

Although it is assumed that the sensory systems are functional prior to birth, very little is known about tactile-sensory development. Whereas evidence suggests that somesthetic senses are the first to develop embryonically, the course of development in infancy and early childhood is less understood. Proton magnetic resonance spectroscopy technology has been used to measure brain metabolism in order to determine regional differences in brain development from childhood into early adulthood (Hashimoto et al., 1995). There was a significant correlation between age and metabolic activity in the right parietal regions, suggesting rapid brain maturation in this region from one month up to the age of two or three years. The frontal regions showed less metabolic activation during the same time frame, suggesting slower development of these regions. The frontal lobes, dense with gray matter, are slower to myelinate and to form synaptic and dendritic connections than the more posterior brain regions.

The course of development for tactile perception has been most thoroughly researched for hemispheric asymmetries. Tactile form perception increases with age (from 8 to 12 years); children usually show a slight superiority in scores using their preferred hand (dominant hand), and scores on the non-preferred hand were much more variable than on the preferred (Baron, 2004). For the 12- to 14-year-old group, children show a more even range of scores and reach adult-like performance on these measures. Tactile finger localization develops more slowly, and most preschool children are unable to name or point to the finger that has been touched (Baron, 2004). This is a difficult task for most seven-year-old children, but by the age of nine few errors are present. When errors do appear, they occur more frequently on adjacent fingers (37.5%), which is four times higher than for adults. Thus, children respond differentially to tactile localization tests on the right and left hands, depending on the type of response mode required (Baron, 2004). Verbal responses seem to increase accuracy when identifying touch to the right hand, whereas nonverbal responses enhance accuracy with the left hand. Witelson and Pallie (1973) found that children do recognize nonsense forms better with the left hand, but recognition of letter shapes does not appear to have a right or left hand advantage.

The visual system is slow to develop in humans. Myelination of the optic tract is moderately developed at six weeks of age, but is heavily developed by three months (Brodal, 2004). The myelination of the optic radiation is somewhat slower, with minimal development at three months of age and mild development at six weeks. However, heavy myelination occurs in the optic radiation at about the same time as the optic tract. Developmental trends in visual asymmetries have also been investigated in children. Kolb and Fantie (1989) found that the right hemisphere may be specialized for facial recognition in children as young as four years of age, and shows a steady increase in accuracy up to age five, with slower acceleration after this age. Kolb and Fantie hypothesize that the structural hardwire of the brain is sufficiently mature by age five and that further growth in accuracy is dependent on experience. While the six-year-old is adept at facial recognition, matching expressions to situations is not well developed until about 14 years of age. This finding implies that the later task may also require frontal lobe maturation as well as posterior cortical development.

Developmental patterns have also been investigated for hemispheric asymmetry in the temporal lobes. Asymmetries of the temporal lobe appear to have some relationship between cortical maturation and the development of the corpus callosum (Brodal, 2004). There is sufficient evidence that the left planum temporale is larger than the right and that these differences are present at birth (Witelson & Kigar, 1988). This developmental course is likely related to functional differences between the two hemispheres in their ability to process information. Infants appear to discriminate speech sounds early on, as young as 1–4 months of age (Molfese & Molfese, 2002). Further, researchers have found functional lateralization of the left hemisphere for speech sounds in infants (Molfese & Molfese, 2002) and for music and non-speech sounds in the right hemisphere in infants. See Table 3.2 for a summary of developmental ages when asymmetry between the two hemispheres appears.

Rosen, Galaburda, and Sherman (1990) investigated the ontogeny of lateralization and have generated hypotheses about the mechanisms of asymmetry. In these studies, symmetry in the brain was found to be related to the size of the planum temporale in the right hemisphere. In brains with normal patterns of asymmetrical organization, there was a corresponding decrease in the size of the right hemisphere. This correspondence was not observed in brains that were symmetrical, as there was an abundance of neurons in the temporal regions of the right hemisphere. Further, the corpus callosum in symmetrical brains is larger than in those with normal patterns of asymmetry (Rosen et al., 1990). Rosen et al. (1990) hypothesize that this variation in volume is likely a result of “pruning” of the axons in the corpus callosum that takes place in early developmental stages. Asymmetry may be related to withdrawal of neurons in the corpus callosum, while ipsilateral connections are maintained. Numerous factors impinge upon normal brain development, affecting the manner in which neural systems function and how traits and behaviors are expressed. Genetic as well as environmental factors influence neurodevelopment. These factors will be reviewed briefly in the following sections.

With the advent of X-ray technology in the 1920s and 1930s, it became apparent that the developing fetus was susceptible to various environmental agents known as teratogens. Critical periods during the embryonic (second to eighth week of development) and the fetal stage (9th week to birth) appear particularly susceptible to exposure of teratogens. The central nervous system appears to be particularly vulnerable from the 5th week of embryonic development up to birth. The most detrimental environmental influences affecting neurodevelopment prenatally include alcohol, narcotics, pollutants, maternal disease, and malnutrition (Streissguth et al., 2004)

In addition to numerous prenatal factors that place the developing child at risk for neurological complications, maternal stress, malnutrition, poor health, and age also play a role in the ultimate expression of these risk factors (van den Bergh, Mulder, Mennes & Glover, 2005). Extreme maternal stress is known to increase levels of stress in the fetus and has been associated with low birth weight babies and irritable, restless, colicky infants. Maternal stress may create vasoconstriction reducing circulation that ultimately produces fetal asphyxia, which is known to cause brain damage in the developing fetus. Some findings have indicated that prenatal stress may have long-term consequences with problems in coping and learning, particularly for males, and an increased incidence of mood disorders and schizophrenia (King, Laplante, & Joober, 2005; Mueller & Bale, 2007).

Maternal health during pregnancy is generally monitored to ensure normal fetal development. Maternal hypotension may have an adverse affect on the fetal brain as it may result in circulation failures in the developing brain (Martens et al., 2003). Fibromyeline plaques or lesions form in cortical areas called “watershed regions.” These ischemic-induced alterations, caused by a temporary loss of blood (perfusion), have been found in the brains of individuals with dyslexia (Duane, 1991).

Ischemia may also be induced by maternal or fetal autoimmune mechanisms. The extent to which these morphological variations are related to or contribute to reading disability will be explored in later chapters. The important point here is that maternal health directly affects the developing fetal brain. Glial cells and specific molecules that direct the migration of cells may be involved in such a way as to alter the cortical architecture of the child’s brain (Duane, 1991).

Another maternal health factor that has known effects on the developing brain is rubella (German measles), which often results in deafness in babies if the mother contracts this disease in the first trimester of pregnancy. Eye and heart involvement are other likely outcomes if rubella occurs in the first eight weeks of pregnancy, whereas deafness is more likely to occur if the illness occurs between five and 15 weeks. Maternal herpes simplex 2 is also known to produce mental retardation and learning difficulties because this virus attacks the developing central nervous system of the fetus (Hutchinson & Sandall, 1995).

Concerns have recently been raised about the effects of acquired immune deficiency syndrome (AIDS) on the developing fetus. In the past birth defects including microcephaly as well facial deformities were found with mortality frequently present within five to eight months of symptom onset (Cotter & Potter, 2006). Prior to the new drug regimes, central nervous system involvement was found to be as high as 78–93 percent of children with human immunodeficiency virus (HIV), with signs of motor, visual-perceptual, language, and reasoning delays (Cotter & Potter, 2006; Suy et al., 2006).

Mothers who are likely to contract AIDS often come from high risk populations, including intravenous drug abusers, so other health factors may play a role in the manifestation of symptoms. The extent to which other psychosocial factors play a role in the long-term outcome for children with congenital HIV infection needs further study. When health, poverty, and psychological factors are controlled, infants born to teenagers and mothers over 35 do not appear to be at higher risk for complications (Cotter & Potter, 2006).

Many of the prenatal risk factors mentioned previously (infant nutritional deficiencies, maternal stress, etc.) continue to have an effect on the developing brain in the postnatal period.