New techniques in the field of neuroscience are now being applied to the study of how the human brain develops under normal or abnormal circumstances. These are exciting developments that will have a tremendous impact on our understanding of childhood psychiatric disorders, and how we care for these children. As child psychiatrists, it is important to appreciate some of the recent advances in these areas. I have chosen to discuss how neuroimaging techniques are allowing researchers to get a much more refined definition of how the brain works, and how recent advances in genetics permit us to understand the underlying molecular basis of many neuropsychiatric disorders. The practice of child and adolescent psychiatry and allied professions will certainly be shaped by this new knowledge, and it will become increasing important for us to link new findings from laboratory research and the consulting room.
 A key controversy in child psychiatry over the past fifty years has been the dispute over whether nature or nurture are more important for determining child development. Few topics have aroused more passion or displayed such swings of the pendulum as the debate over genetic and environmental influences on how the brain develops. Which one reigns supreme in its contribution to the normal or abnormal growth of our children?
 The history of research on autism is an excellent area to get a feel for the intensity of this debate. The core symptoms of this disorder were first described by Leo Kanner in 1943. He speculated that the core symptoms of autistic children had a biological basis. Perhaps the inability to develop social attachments was an innate neurological feature.
 However, he also commented on the parents of autistic children, who occasionally displayed peculiar personality traits. Unfortunately, it was his commentary on the parents of autistic children that led others to theorize that inadequate parenting could cause autism. Thus begin an era in which “refrigerator mothers” were held responsible for inducing autistic behaviors in their offspring. During the 1970s and 1980s however, the pendulum slowly swung back as genetic studies suggested that other factors contributed to the etiology of autism.
 Today, the question is no longer whether nature or nurture is more important in the expression of childhood neuropsychiatric disorders. Both are viewed as critically important. It is clear that some genetic mutations are so disruptive that regardless of environment the brain is destined to develop abnormally. More typically, however, it is the interplay between these two factors that determines whether a child will develop normally or abnormally. Similarly, there are times when the extent of environmental deprivation is so extreme that neurological impairments emerge despite the adequacy of the underlying genetic plan. For the typical family and typical child, it is the interplay between these two factors that shapes the development of the CNS and the unfolding of cognitive and social skills over the first few decades of life.
 Some of the strongest arguments for the contribution of both genetic and environmental factors to neurological development come from twin studies. Monozygotic twins have much higher concordance rates when compared to dizygotic twins for many physical traits, cognitive skills, and the development of psychiatric disorders. However, it is rare for the concordance rate among monozygotic twins to exceed 50% suggesting that environmental factors are also etiologically important.
 One type of neurological disorder which both environmental and genetic factors clearly contribute is autoimmune disorders that affect the CNS. Recently, there have been several reports suggesting that some cases of Tourette syndrome and obsessive compulsive disorder are autoimmune disorders that result from prior exposure and immune responses to streptococci infection. Although these individuals produce antibodies against streptococci in a normal fashion, the antibodies also cross-react with proteins in the CNS in addition to the streptococci specific molecules. As a consequence of this cross-reactivity with self antigens, the CNS is compromised and neurological symptoms emerge. This mechanism for causing autoimmune related diseases has more generally been referred to as the molecular mimicry hypothesis. It has been speculated that repeated infections in vulnerable individuals can exacerbate clinical symptoms, and this is one explanation for why symptoms in these disorders often wax and wane. However, the evidence for this hypothesis has not been generated yet in the laboratory, and we must await these results before subscribing to this particular theory.
 The neuroscientist and the clinician share a fascination with how to link the inner world of the child with emerging knowledge on how the brain develops its capacity for thought, feelings, and expression. Over the past two decades, our basic understanding of the biological and environmental factors that influence brain development has grown dramatically. The clinician no longer has to choose between nature and nurture, but can appreciate their interaction in the understanding of normal or abnormal development. In this new age, basic neuroscience techniques have begun to reveal the continuous interplay between the child’s unfolding genetic program and the complexities of experience and activity-mediated changes in the cells of the brain.
 High resolution neuroimaging techniques such as functional magnetic resonance imaging (fMRI) show us the changes in neuronal activity within brain nuclei, the concentrations of different neurotransmitters and other neuromodulators while an individual is speaking, listening or learning new tasks. We have reached a new level of understanding of how complex brain functions are localized in normal individuals, and individuals who have different disorders. These techniques are being applied to children with disorders such as Tourette syndrome or dyslexia, and the results are helping investigators determine what neural networks may be involved.
 One area of active research relates to the development of higher cognitive skills. In an effort to better understand normal cognitive development, researchers often study abnormal development. For example, to better understand the development of language, investigators have turned to individuals with normal hearing as well as individuals who are born deaf. What leads to certain parts of the brain being dedicated to certain cognitive skills?  In dear individuals, what happens to brain regions that are normally dedicated to auditory processing?  Does it simply disappear, never having developed properly, or do they get taken over and dedicated to other sensory modalities?
 Functional MRIs have allow this question to be addressed. This neuroimaging technique allows researchers to measure the amount of activity that occurs in different regions of the brain. If a certain brain region is metabolically active while a subject performs a particular cognitive or motor activity, it is presumed that the brain area is critical for that task. The experiments must be carefully designed to assure that one is actually measuring what it is you want to measure and not an associated feature.
 When normal individuals are asked to listen to spoken language, areas that light up intensely are Heschl’s gyrus and the associated Brocca’s and Wernicke’s areas. These regions either within or close to the temporal lobes has been known for many years to be involved in the processing of language. Therefore, it was of interest to know what happens to this area if you are born deaf. Research in the laboratory of Helen Neville has looked at this question. It turns out that there is an increase in visually evoked responses in these regions. By studying how these changes come about in infancy, it has been determined that young infants normally show visually evoked responses over large areas of the cortex, and these become restricted to classical visual areas during the first 2-3 years of life. This does not occur in children born deaf. There is no significant decrease in Heschl’s volume, rather, the region is rededicated to processing visual information.
 If deafness occurs after this plastic period, however, deaf individuals do not show visually evoked activity in auditory areas. This underscores an important maxim developmental neuroscience which states that there are critical periods during which neuronal growth and synaptic connections normally form and become stabilized. At the extreme of this idea is that abnormal sensory inputs during infancy can substantially alter the types of connections that are established.
 Neurobiologists have long been interested in determining how this occurs. The early development of the brain involves the following important steps. Neurons are born early during gestation and soon differentiate into their final cellular type. They then begin to migrate to their final brain destinations, and grow axons roughly to the appropriate targets. These events occur during gestation and are mostly complete by birth. They rely primarily on intrinsic factors within the CNS and are largely independent of environmental events. This is not to say that environmental factors such as drugs, alcohol, and viral illnesses cannot disrupt normal brain development. They can if they occur during critical periods of neurogenesis and migration while the fetus is growing.
 After birth, the next phase of neurological development begins. This consists of the laying done of proper synaptic connections between interacting neurons. Environmental factors become critically important during this stage of brain maturation. In humans and other mammals, following birth there is a dramatic increase in the number of synapses. The specificity of neuronal connections is then refined during early postnatal life. Experimental data have shown conclusively that neuronal activity is critical for refining and stabilizing correct synaptic connections. Thus, once the initial circuitry of the CNS is guided by intrinsic factors into roughly correct patterns, sensory inputs drive patterns of neural activity that further specify connections between neurons.
 A very important series of experiments were conducted in the nineteen sixties and seventies by the Torsten Wiesel and David Hubel, for which they received the Nobel Prize in 1981. The most important result of their work was that early visual experiences are critical factors for the eventual organization of the adult visual cortex. The primary visual cortex receives input from the two eyes via a relay in the thalamic visual area. Like all cortex, the primary visual cortex is a layered structure, with visual input forming synapses on neurons in layer 4. Initially, synaptic input into the visual cortex is homogeneous. As visual input occurs, there is a clear separation of input from the right and left eyes into alternative bands that Hubel and Wiesel called ocular dominance columns.
 The early work on the visual cortex demonstrated that the normal segregation of inputs that is present later in adult brains requires visual input, and that this activity must occur during a particular window of time. If the animal grows with input from only one eye, than the neurons in layer 4 respond only to that eye and not at all to the other. As a result, very little territory will be dedicated to the unused eye.
 Another critical result of this work was to demonstrate that this ability to reorganize the pattern of inputs is limited over time. Restricting vision to only one eye in adult animals has little effect on the organization of inputs to the primary visual cortex. Moreover, a return to normal, binocular visual experience in the adult cannot repair the abnormal organization of inputs to visual cortex resulting from early visual deprivation. The period of time during which the normal establishment of ocular dominance columns may be disrupted is called the “critical period.”
 Deficits in our ability to see occur if we do not experience normal vision during these early months and years of our lives. A dramatic example of this is seen in infants who are born with congenital cataracts. These children do not have normal visual inputs through the affected eye. If the cataract is not removed early but is allowed to remain in place for several years before it is removed, the child will never be able to see through that eye, a condition referred to as amblyopia. This is obviously in contrast to what happens in adult life. The adult who develops a cataract late in life slowly loses sight through that eye. However, once it is removed normal vision returns.
 The visual cortex has been the most extensively studied area of the cerebral cortex. It is reasonable to ask whether other regions of the brain develop in similar ways, and require neural activity to develop normally. We discussed earlier how in brains of deaf children regions that normally belong to the auditory system now respond to visual inputs. A second example comes from children who are bilingual from an early age.
 The acquisition of language during the first several years of life underscores how important early activity is to the organization of the brain. Functional MRIs have been used to determine the spatial relationship of language centers in individuals who have learned their own language as well as a second language. If a child learns a second language early in life, both the native and second language are represented in the same cortical region. In contrast, when a second language is acquired as an adult, a new language center is established in the cortex that is clearly separated from the native language center. Although these findings do not yet explain why young children are able to learn a new language more easily than older individuals, it does support the findings that early experiences affect the way the brain develops.
 The work from a number of laboratories have provided compelling evidence that certain growth factors may play and important role in much of the activity-dependent growth and development of neuronal structure. These small signaling molecules have long been known to play critical roles in their ability to promote neuronal survival, and for their ability to guide axonal growth. More recent investigations have demonstrated that the same growth factors are able to regulate the extent of dendritic growth, and whether particular neurons will be pruned away. Much of the strengthening of neuronal contacts appears to be mediated by growth factors. This is an area that is only now being explored, and is one mechanism by which an environmental factor (visual input for example) will influence the pattern of cortical growth, presumable leading to strengthening certain cognitive skills.
 It appears then that if you do not reinforce certain synaptic connections early in development, they are unlikely to develop later in life. Although much of this work as been performed in the visual and somatosensory areas of the cortex, it is reasonable to assume that similar patters are established in other brain regions.
 What happens if you stimulate synaptic growth early during development by exposing the child to novel or different experiences?  Does exposing our children to ’enriched’ experiences early in life lead to smarter adults?
 Researchers in Fred Gage’s laboratory have begun to answer these questions. What is the extent of neuroanatomical plasticity that occurs in the brains of mice reared in an enriched environment?  Mice have been raised in special cages that contain a number of additional items, such as wheels, toys, and tunnels. There is little doubt that this type of enrichment is very different from their normal environment in the wild. However, it is a considerable improvement over the starkness of the control cages.
 The brains of the animals raised in the “enriched environment” were compared to the brains of litter mates raised in the control conditions. A number of significant morphological changes in brain growth were found in the hippocampi of mice raised in the enriched environments. These included an increase not only in the number of neurons present, but also in the overall volume of the hippocampus. The experimental animals were also found to have improved ability to learn new tasks. Similar experiments have shown an increase in the extent of dendritic arborization and the number of supporting glial cells in enriched environment can have a substantial effect on how the hippocampus develops and wires itself during critical periods of maturation.
 The review has focused mainly on environmental factors. We are now beginning to appreciate the importance of genetic factors in neurological development. Recent work in several developmental disorders has led to the isolation of the genes that are thought to cause these disorders. One example of this is fragile X syndrome which is the most common form of inherited mental retardation. The gene that causes this disorder was recently isolated, and studies are now underway in several laboratories to determine the function of the protein that it encodes. Other examples of developmental disorders that have a known genetic cause include Prader-Willi syndrome, Angelman syndrome, and several forms of lissencephaly. A number of laboratories have reported that they are close to isolating genes that contribute to autism, Tourette syndrome, and some forms of dyslexia.
 We are entering a new age in child psychiatry in which it is becoming important to become familiar with recent developments in neuroscience, especially if one is interested in understanding the etiology of various childhood neuropsychiatric disorders. Many of us were not interested in neuroimaging techniques, in molecular biology, or in neural networks when we began our life long interest in children and their psychiatric difficulties. It is becoming clear, however, we will need to pay attention to these studies that are going to clarify the intricacies of both normal and abnormal development during the first years of life.
 Portions of this article were adapted from a series of columns on development and neuroscience that has appeared in the Journal of the American Academy of Child and Adolescent Psychiatry.