Kaplan + Sadock's Synopsis of Psychiatry, 11e

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Chapter 1: Neural Sciences

superficial to the neural tube becomes the neural crest, which gives rise to the PNS. The formation of these structures requires chemical communication between the neighboring tissues in the form of cell surface molecules and diffusible chemical signals. In many cases, an earlier-formed structure, such as the notochord, is said to induce the surrounding ectoderm to form a later structure, in this case the neural plate (see Color Plate 1.2-6). Identification of the chemical mediators of tissue induction is an active area of research. Investigators have begun to examine whether failures of the interactions of these mediators and their receptors could underlie errors in brain development that cause psychopathology. Neuronal Migration and Connections The life cycle of a neuron consists of cell birth, migration to the adult position, extension of an axon, elaboration of dendrites, synaptogenesis, and, finally, the onset of chemical neurotransmis- sion. Individual neurons are born in proliferative zones generally located along the inner surface of the neural tube. At the peak of neuronal proliferation in the middle of the second trimester, 250,000 neurons are born each minute. Postmitotic neurons migrate outward to their adult locations in the cortex, guided by radially oriented astrocytic glial fibers. Glia-guided neuro- nal migration in the cerebral cortex occupies much of the first 6 months of gestation. For some neurons in the prefrontal cortex, migration occurs over a distance 5,000 times the diameter of the neuronal cell body. Neuronal migration requires a complex set of cell–cell interactions and is susceptible to errors in which neurons fail to reach the cortex and instead reside in ectopic positions. A group of such incorrectly placed neurons is called a heterotopia. Neuronal heterotopias have been shown to cause epilepsy and are highly associated with mental retardation. In a neuropathological study of the planum temporale of four consecutive patients with dyslexia, heterotopias were a common finding. Recently, hetero- topic neurons within the frontal lobe have been postulated to play a causal role in some cases of schizophrenia. Many neurons lay down an axon as they migrate, whereas others do not initiate axon outgrowth until they have reached their cortical targets. Thalamic axons that project to the cortex initially synapse on a transient layer of neurons called the sub- plate neurons. In normal development, the axons subsequently detach from the subplate neurons and proceed superficially to synapse on the true cortical cells. The subplate neurons then degenerate. Some brains from persons with schizophrenia reveal an abnormal persistence of subplate neurons, suggesting a failure to complete axonal pathfinding in the brains of these persons. This finding does not correlate with the presence of schizophrenia in every case, however. A characteristic branched dendritic tree elaborates once the neuron has completed migra- tion. Synaptogenesis occurs at a furious rate from the second trimester through the first 10 years or so of life. The peak of synaptogenesis occurs within the first 2 postnatal years, when as many as 30 million synapses form each second. Ensheathment of axons by myelin begins prenatally; it is largely complete in early childhood, but does not reach its full extent until late in the third decade of life. Myelination of the brain is also sequential. Neuroscientists are tremendously interested in the effect of experi- ence on the formation of brain circuitry in the first years of life. As noted earlier, many examples are seen of the impact of early sensory experi- ence on the wiring of cortical sensory processing areas. Similarly, early

In one study of right-handed males, lesions of the right prefrontal cortex eliminated the tendency to use internal, associative memory cues and led to an extreme tendency to interpret the task at hand in terms of its immediate context. In contrast, right-handed males who had lesions of the left prefrontal cortex produced no context-dependent interpreta- tions and interpreted the tasks entirely in terms of their own internal drives. A mirror image of the functional lateralization appeared in left- handed subjects. This test thus revealed the clearest known association of higher cortical functional lateralization with the subjects’ dominant hand. Future experiments in this vein will attempt to reproduce these findings with functional neuroimaging. If corroborated, these studies suggest a remarkable complexity of functional localization within the prefrontal cortex and may also have implications for the understanding of psychiatric diseases in which prefrontal pathology has been postu- lated, such as schizophrenia and mood disorders. The heavy innervation of the frontal lobes by dopamine-containing nerve fibers is of interest because of the action of antipsychotic medica- tions. At the clinical level, antipsychotic medications may help to organ- ize the rambling associations of a patient with schizophrenia. At the neurochemical level, most typical antipsychotic medications block the actions of dopamine at the D 2 receptors. The frontal lobes, therefore, may be a major therapeutic site of action for antipsychotic medications. Development The nervous system is divided into the central and peripheral nervous systems (CNS and PNS). The CNS consists of the brain and spinal cord; the PNS refers to all the sensory, motor, and autonomic fibers and ganglia outside the CNS. During develop- ment, both divisions arise from a common precursor, the neural tube, which in turn is formed through folding of the neural plate, a specialization of the ectoderm, the outermost of the three lay- ers of the primitive embryo. During embryonic development, the neural tube itself becomes the CNS; the ectoderm immediately Figure 1.2-5 The life mask and skull of Phineas Gage. Note damage to the fron- tal region. “A famous case illustrating the result of frontal lobe dam- age involves Phineas Gage, a 25-year-old railroad worker. While he was working with explosives, an accident drove an iron rod through Gage’s head. He survived, but both frontal lobes were severely damaged. After the accident, his behavior changed dramatically. The case was written up by J.M. Harlow, M.D., in 1868, as fol- lows: [Gage] is fitful, irreverent, indulging at times in the gross- est profanity (which was not previously his custom), manifesting but little deference for his fellows, impatient of restraint or advice when it conflicts his desires…His mind was radically changed, so decidedly that his friends and acquaintances said he was ‘no lon- ger Gage.’” (Courtesy of Anthony A. Walsh, Ph.D.)