2. Functional Neuroanatomy

The neuron contains four well-defined cellular parts, including the cell body, dendrites, axons, and axon terminals. The cell body, or soma, is the trophic or life center of the neuron (see Fig. 2.1). Cell bodies vary in size and shape and contain the ribonucleic acid (RNA) and deoxyribonucleic acid (DNA) of the neuron. RNA, the site of protein synthesis, transmits instructions from DNA directing the metabolic functions of the neuron. Biochemical processes of the neuron, which take place in the cytoplasm of the cell body, include the energy-producing functions, the self-reproducing functions, and the oxidating reactions, whereby energy is made available for the metabolic activities of the cell (Carlson, 2007). Destruction or damage to the cell body can result in the death of the neuron.

Dendrites branch off the cell body and receive impulses from other neurons (Carlson, 2007). Dendrites are afferent in nature and conduct nerve impulses toward the cell body. Dendritic spines are the major point of the synapse, the area of transmission from one cell to another. Individuals with cognitive retardation have fewer spines or points of contact across neurons (Klein-Tasman, Phillips, & Kelderman, 2007). Dendrites can transmit neuronal impulses across neurons through either temporal or graded potentials. In this case, as a neuron receives an impulse it can transmit this impulse if the stimulation is close in time to another impulse or if it is strong enough combined with a previous impulse.

The axon is a long projection or axis from the cell body. Most neurons have only one axon, usually efferent in nature, that conducts nerve impulses away from the cell body. Axons are typically longer than dendrites and can be as much as one yard in length. For example, giant pyramidal cells in the motor cortex send axons to the caudal tip of the spinal cord. The axon hillock is a slender process close to the cell body where action potentials arise. The axon hillock is highly excitable and is activated through electrochemical processes, thereby “turning on” the neuron (Carlson, 2007). The impulse must be of sufficient strength for the neuron to “fire.” Axons follow an “all or nothing” rule; if the impulse is not strong enough the neuron will not fire and, thus, will not transmit the message to another neuron. After the neuron fires, there is a period of time when it will not fire again as the neuron “recovers.”

Axons are covered by a myelin sheath made up of neurilemma (or Schwann cells), which surround the axon. The myelin sheath gives the axon a white appearance and constitutes most of the white matter in cortical and subcortical areas. Most axons are myelinated at birth particularly in areas necessary for survival (motor-sucking; tactile sensitivity to hot, cold, and pain; auditory, and vision). Some axons continue to myelinate throughout development with myelinization not complete in the frontal lobes until well into the third decade of life. Changes in postnatal brain weight are generally related to increases in dendritic connections and to increases in the number of glial cells that form the myelin sheath along the axon (Shepherd, 2004).

Axons allow the nerve cells to transmit impulses rapidly, particularly along the Nodes of Ranvier. The Nodes of Ranvier are gaps in the myelin and during cell activation, nerve impulses skip from node to node. Myelinated axons permit more rapid transmission of signals, and anesthetics seem to be more effective at the Nodes of Ranvier. The terminal branches of the axon end at the synaptic telodendria.

The presynaptic and postsynaptic sites are both referred to as the synapse. Synapses are specialized for the release of chemicals known as neurotransmitters. Neurotransmitters are released from synaptic knobs at the end foot of the neuron in the presynapse, and they activate neurons at the postsynapse. Neurotransmitters are released from the presynapse (neuron A), travel across the synaptic cleft, and influence the activity of the adjoining neuron (neuron B) (see Fig. 2.2 for a depiction of these activities). There is a collection of vesicles at the synaptic knob at the end of each synapse, where neurotransmitters are stored. Most neurons have thousands of synapses, and each dendritic spine serves as a synapse that is excitatory in nature, which causes neurons to fire. Synapses are quite large for motor neurons and are smaller in the cerebellum and other cortical regions. Synapses usually occur between the axon of one cell and the dendrite of another (axondendritic connections). Although they can connect onto the soma or cell body of another neuron (axosomatic connection), synapses rarely occur from axon to axon (axo-axonal connections).

There are two basic types of neurons: efferent and afferent. Efferent neurons originate in the motor cortex of the CNS, descend through vertical pathways into subcortical regions, and culminate in the body’s muscles (Gazzaniga, Ivry, & Mangun, 2002). These large descending tracts form columns from the motor cortex connecting higher cortical regions through the brain stem and spinal cord, to the body for the activation of single muscles or muscle groups. Various motor pathways begin to develop prenatally, while postnatal development is marked by changes in primitive reflexes (the Babinski reflex) and automatic reflexes (head and neck righting) (Swaiman et al., 2006).

Afferent neurons, sensory receptors found throughout the body, transmit sensory information into specific cerebral areas. For example, afferent neurons consist of rods and cones (cells that convey information about color or black/white) in the visual system that project into the occipital cortex; hair cells (convey information about tone) in the auditory system that project into the temporal cortex, and pain, touch, temperature, and pressure sensors in the skin that project into the parietal cortex. Somesthetic senses are the first to become functional in the fetus, as early as 7–8 weeks gestation, while auditory and visual neural maturation occurs later in embryonic development (Gazzaniga et al., 2002). Other cells in the corpus callosum (a large bundle of fibers connecting the two hemispheres) and the frontal lobes do not become fully functional until the teenage years through the 20s.

The neuroglia cells serve a number of important functions in the CNS: (1) providing structural support to neurons; (2) aiding in the regeneration of injured nerve fibers; (3) occupying injured sites by producing scar tissue, and (4) transporting gas, water, and metabolites from blood, and removing wastes from nerve cells (Carlson, 2007). The three major types of neuroglia (astrocytes, oligodendroglia, and microglia) have distinct functions and serve multiple purposes in the CNS. Astrocytes have three primary functions: (1) forming the blood-brain barrier; (2) supporting the cellular structure of the brain, and (3) directing the migration of neurons during early development. Astrocytes are the largest in size and the most abundant type of neuroglia (Carlson, 2007). These star-shaped glial cells attach to capillary blood vessels and cover approximately 80 percent of each capillary. Astrocytes, found primarily in the pia matter (fine membrane on the surface of the brain), cover large blood vessels. When injury occurs to the spinal cord or to the brain, through either disease or trauma, astrocytes go into hypertrophy (Morris, Krawiecki, Kullgren, Ingram, & Kurczynski, 2000). These cells multiply quickly, forming a glial scar that fills in gaps in the cellular structure caused by injury. Astrocytes may also serve a phagocytic function by removing destroyed tissue and cleaning up the site of injury. Astrocytoma, a type of primary neoplasm that frequently reoccurs after surgery, is the second most common brain tumor in adults (Hunter et al., 2005); though rare, astrocytomas do occur in children as well.

Astrocytomas in childhood most frequently occur in the cerebellum and the brain stem. These tumors are found equally in males and females. Although astrocytomas can occur at any age, the most frequent incidence is between five and nine years of age (Hunter et al., 2005). Oligodendroglia cells form and maintain the myelin sheath and, when injured, swell in size. Tumors rarely occur in oligodendroglia cells; when they do they grow slowly and are found primarily in the cortex and white matter. While about 40–60 percent of these tumors can be detected by skull X-rays after they calcify (Cohen & Duggner, 1994), radionuclide brain scans, angiography, and computed tomography scans have been helpful in the diagnostic phase of tumor processes. Finally, microglia cells are predominantly found in the gray matter (Carlson, 2007). Following disease or injury, microglia proliferate, move to the site of injury, and perform a phagocytic function by cleaning up damaged tissue. Tumors rarely occur in microglia cells.

These cells develop at different rates depending on location in the brain, experience of the baby, and genetic programming. In order to understand difficulties children have in development it is first important to understand how a typical brain develops. The following section provides a brief overview of the course of neuronal development.

The ventricles, large cavities filled with cerebrospinal fluid (CSF), reside in various regions of the brain. The fourth ventricle, also referred to as the aqueduct of Sylvius, resides in the brain stem at the level of the pons and the medulla. The third ventricle is located in the diencephalon, and the lateral ventricles are found in the forebrain region (see Fig. 2.3). Ventricles provide equilibrium as well as the CSF transporting nutrients and wastes throughout the brain. When these ventricles appear enlarged, a diagnosis of a tumor or disease processes, including hydrocephalus, encephalitis, and meningitis, may be made.

The medulla is a continuation of the spinal cord and contains nerve tracts similar to those found in the spinal cord. Groups of sensory and motor nuclei are arranged in ascending (i.e., afferent-sensory tracts) or descending (i.e., efferent-motor tracts) cell columns. Projections of the major cranial nerves occur at the level of the medulla, including the hypoglossal (tongue), the glossopharyngeal (pharynx and larynx), and the accessory (neck muscles) nerves. The sensory and motor tracts cross over into the opposite side of the brain at the level of the medulla. The somatosensory (touch, pressure, pain, and temperature) and the motor systems are organized in contralateral fashion, such that sensory information and movement on the right side of the body are primarily controlled by the left hemisphere. Conversely, the left side of the body is controlled by the right hemisphere. The auditory and visual systems also cross in the medulla. These functional systems will be discussed in more detail later in this chapter.

The reticular activating system (RAS) comprises a major portion of the medulla, extends into the midbrain region, and has numerous connections and functions (Brodal, 2004). The RAS, considered the arousal system, plays an important role in maintaining consciousness and attentional states for the entire brain. The RAS has been hypothesized as one of the critical mechanisms involved in ADHD (Sagvolden & Archer, 1989). For example, some RAS functions control blood pressure, blood volume in organs, and heart rate, whereas others regulate sleep and wakefulness.

The RAS receives input from most sensory systems and connects to all levels of the CNS. Because the RAS is directly or indirectly connected to much of the CNS, it can modulate CNS activity. Selective stimuli activate the RAS, which then alerts the cortex to incoming stimuli. Researchers espousing a bottom-up model hypothesize that the RAS may be filtering too much sensory information, thereby not allowing stimulation to reach the higher cortical regions that are necessary for adequate direction and maintenance of attention. When enough information reaches the RAS, it signals the cortex and produces cortical arousal and wakefulness. Thus, in children with ADHD this subcortical filter may not allow sufficient stimuli to reach higher cortical regions. This theory and others will be explored in later chapters.

Secretion of serotonin takes place at the pons, probably in the raphe system. The raphe nuclei are cells located across the medulla, pons, and midbrain regions, with afferent connections to the hypothalamus and limbic system (Brodal, 2004). This region also contains the locus ceruleus (LC), which produces 70 percent of norepinephrine in the brain, and serves as a modulator for other neurotransmitters (Carlson, 2007). The norepinephrine-rich cells in the locus ceruleus connect with the serotonin-rich cells in the raphe nuclei, and each type has a reciprocal affect on the other. Norepinephrine plays a role in vigilance, arousal, filtration of stimuli, and habituation. Finally, the continuation of the RAS at the pontine level appears to mediate sleep.

Serotonin inhibits arousal of the RAS, which then allows the thalamus to bring the cortex to a slow-wave sleep state (Carlson, 2007). Anesthetics appear to depress the RAS, which ultimately depresses the cortex. Fibers in the RAS also project to the limbic system and serve behavioral and emotional mechanisms for the control of pain. Morphine and opiate-like drugs may produce analgesic actions most likely in the raphe system (Shepherd, 2004).

The pons, between the medulla and midbrain and above the cerebellum, serves as a bridge across the right and the left hemispheres. Major sensory and motor pathways move through the pons, a continuation from the spinal cord and brainstem regions, and enter into higher cortical areas. The pons, in coordination with the cerebellum, receives information concerning movements from the motor cortex and helps modulate movements (Brodal, 2004). Information from the visual cortex is also received at the pontine level, which serves to guide visually determined movements. Finally, information from the hypothalamus and the limbic system converge in the pons and may influence the impact of emotional and motivational factors on motor activity (Brodal, 2004). A number of cranial nerves converge in the pontine region. Cranial nerves innervating the face and head receive sensory information and transmit signals in the pons for swallowing and chewing (trigeminal nerve), moving facial muscles, and affecting the hearing and equilibrium in the inner ear. Cranial nerves innervating the eye muscles (abducens) also pass through the pons.

The most anterior region of the brainstem is the midbrain or mesencephalon. The midbrain serves a major relay function for sensory-motor fibers. The two major divisions in the midbrain are the tegmentum, which falls below the ventricle and is separated by the substantia nigra, and the tectum, which comprises the superior colliculi (upper region involved in vision) and the inferior colliculi (lower region involved in the integration of auditory and kinesthetic impulses). The RAS also continues into the midbrain region. Several cranial nerves are located in the midbrain region. The oculomotor nerve moves the eye (lateral and downward gaze), and regulates the size of the pupil and the shape of the lens. The trigeminal nerve also resides in the midbrain area and serves as the major sensory nerve of the face.

The diencephalon, the superior region of the brain stem, contains major relay and integrative centers for all the sensory systems except smell. The diencephalon is not clearly demarcated, but includes the thalamus, the hypothalamus, the pituitary gland, the internal capsule, the third ventricle, and the optic nerve (Brodal, 2004). The thalamus receives input from several sensory sources, including: (1) the visual system (projecting into the lateral geniculate body of the thalamus); (2) the auditory system (projecting into the medial geniculate body), and (3) sensory receptors in the skin for pain, pressure, touch, and temperature.

The hypothalamus, anterior and inferior to the thalamus, plays a role in controlling the autonomic nervous system, including eating, sexual functions and dysfunctions, drinking, sleeping, temperature, rage, and violence. With connections to the limbic system, the hypothalamus influences motivational mechanisms of behavior. The pituitary, following directions from the hypothalamus, secretes hormones that regulate bodily functions. The internal capsule, situated lateral to the thalamus, contains fibers connecting the cortex to lower brain regions including the brainstem and the spinal cord. Major fibers comprise the internal capsule and connect the frontal cortical regions to the thalamus and to the pons. Finally, the optic nerve converges in the diencephalon and forms the optic chiasma (Brodal, 2004). Fibers from the optic nerve cross at the chiasma and project to the lateral geniculate body in the thalamus via the optic tract (Brodal, 2004). Figure 2.6 shows these structures.

The cerebellum or hindbrain, behind the brain stem, connects to the midbrain, pons, and medulla. The cerebellum receives sensory information about where the limbs are in space and signals where muscles should be positioned. The cerebellum receives information from the semicircular canals (in the inner ear) concerning orientation in space. The cerebellum is involved in the unconscious adjustment of muscles in the body for coordinated, smooth, and complex motor activity. Injury of the cerebellum can result in dystaxia (movement disorders), dysarthria (slurred speech), nystagmus (blurred vision and dizziness), and hypotonia (loss of muscle tone) (Swaiman et al., 2006). Though still relatively uncommon, subtentorial tumors involving the cerebellum and the fourth ventricle are the most frequent type of brain tumor affecting young children (Konczak, Schoch, Dimitrova, Gizewski, & Timmann, 2005).

The neocortex, often referred to simply as the cortex, comprises the highest functional division of the forebrain and makes up about 80 percent of the human brain. The cortex is wrinkled in appearance, with various elevated ridges and convolutions. Ridges are referred to as gyri, the deepest indentations are called fissures, and the shallower indentations are called sulci. The configuration of fissures and large sulci can be identified on visual inspection of the cortex (see Fig. 2.6). The lateral or Sylvian fissure separates the frontal lobe from the temporal lobe, and the central sulcus (fissure of Rolando) separates the frontal from the parietal lobe. The central sulcus is a prominent landmark separating the motor cortex (anterior to the central sulcus) from the sensory cortex (posterior to the central sulcus). The surface areas of posterior temporal and parietal locations are not clearly defined from the occipital regions. Finally, the calcarine sulcus extends from the occipital pole below to the splenium of the corpus callosum. The following sections will describe the structures and functions of the cortex. This brief overview of the structure, function, and development of neurons serves as a foundation for understanding the basic structure of the CNS and will be explored in more detail in a discussion of brain tumors and head trauma (Chapter 10) and in the discussion of psychopharmacology (Chapter 11). In the following sections, the basic divisions of the nervous system will be explored.

Large bundles of myelinated fibers connect various intra- and interhemispheric regions. The two hemispheres are connected via several transverse commissures or pathways, including the corpus callosum, the anterior commissure, and the posterior commissure. The corpus callosum, comprising the rostrum, the genu, the body, and the splenium, contains approximately 300 million nerve fibers for rapid interhemispheric communication (Carlson, 2007). The genu connects rostral portions of the right and left frontal lobes, while the body has interconnections between the frontal and parietal regions across the two hemispheres. The splenium connects temporal and occipital regions and is reportedly larger in females (Semrud-Clikeman, Fine, & Bledsoe, 2008). The splenium has been implicated in various childhood disorders, including ADHD (Hynd, Semrud-Clikeman, Lorys, Novey, & Eliopulos, 1991; Semrud-Clikeman et al., 1994) and dyslexia (Fine, Semrud-Clikeman, Keith, Stapleton, & Hynd, 2006). The anterior commissure is smaller than the corpus callosum and connects the temporal lobes of the right and left hemispheres (Kolb & Whishaw, 2003).

Association fibers connect cortical regions within each hemisphere (Kandel, Schwartz, & Jessell, 2000b). Association pathways allow for rapid communication within hemispheric regions for the perception and integration of stimuli and to organize complex output (e.g., emotional responses to stimuli). Short association fibers connect one to another, and longer fibers connect one lobe to another. For example, the arcuate fasciculus connects the frontal and temporal lobes; the longitudinal fasciculus connects the temporal and the occipital lobes with the frontal lobe; the occipitofrontal fasciculus connects the frontal, temporal, and occipital lobes, and the angular gyms connects the parietal and the occipital lobes (Kandel, Schwartz, & Jessell, 2000a). Dysfunction of these pathways can result in a variety of behavioral, cognitive, and personality manifestations including reading, spelling, and computational disorders in children (Zaidel, Iacoboni, Zaidel, & Bogen, 2003).

The frontal lobes are the most anterior cortical structures and comprise the primary motor cortex, the premotor cortex, an area of expressive language (Broca's area), the medial cortex, and the prefrontal cortex (Damasio & Anderson, 2003). Whereas the primary and premotor areas of the frontal lobes have major motor functions, the prefrontal cortex mediates reasoning and planning and monitors other cortical and subcortical functions. The prefrontal cortex matures the most slowly of all of the areas of the lobes.

Lesions or damage to the primary motor cortex can result in paralysis to the contralateral side of the body, whereas lesions to the premotor cortex can produce more complex coordination problems because this region directs the execution of the primary motor area (Kolb & Whishaw, 2003). Lesions or damage to the prefrontal cortex, with its intricate connections to other brain regions, including thalamic, hypothalamic, and limbic areas, often result in affective dissociations, impaired executive functions and judgment, and intellectual deficits (Lezak, Howieson, & Loring, 2004).

The parietal lobe is separated from the frontal regions by the central sulcus and from the temporal lobe by the lateral fissure. The parietal lobes play a central role in the perception of tactile sensory information, including the recognition of pain, pressure, touch, proprioception, and kinesthetic sense. The parietal lobe is comprised of three areas: the primary sensory projection area, the secondary somatosensory area, and the tertiary or association area (Carlson, 2007).

The most posterior region of the cortex comprises the occipital lobe (primary visual cortex), which is further divided into dorsal (superior) and ventral (inferior) areas. The inferior and superior regions are divided by the lateral-occipital sulcus, while the calcarine fissure extends from the occipital pole into the splenium of the corpus callosum (see Fig. 2.7). The visual cortex receives projections from the retina in each eye via the lateral geniculate nucleus in the thalamus (see Fig. 2.8). The rods and cones in the retina respond to photic stimulation, and photochemical processes result in nerve impulses in the optic nerve (Carlson, 2007). Once inside the cerebrum, the optic nerve forms the optic chiasm. The optic chiasm is where nerve fibers partially cross, project to the lateral geniculate in the thalamus, and converge in the visual cortex. Damage anywhere along this pathway can produce a variety of visual defects.

The occipital lobe comprises primary, secondary, and tertiary or association regions (Kolb & Whishaw, 2003). The primary occipital cortex receives afferent input from the thalamus, which passes through the temporal cortex. Damage to this tract, even if it occurs in the temporal lobe, can produce visual field defects. The association region is involved with complex visual perception, relating past visual stimuli to present stimuli for the recognition and appreciation of what is being seen. Damage to the association region, particularly in the right hemisphere, can produce a variety of visual deficits, including recognition of objects, faces, and drawings.

The temporal lobe has three major divisions: (1) the posterior region of the superior temporal gyrus, which is referred to as Wernicke's area in the left hemisphere; (2) the inferior temporal region, including the occipitotemporal association region, and (3) the mesial temporal aspect, including the hippocampal and amygdala regions (Tranel, 1992). The temporal lobe has complex interconnections, with afferent fibers coming from the parietal lobe, efferent fibers projecting into the parietal and frontal lobes, and the corpus callosum and the anterior commissure connecting the right and left temporal lobes (Kolb & Whishaw, 2003). Three major pathways connect the temporal lobe with other cortical regions for complex integrated functions. The arcuate fasciculus connects the frontal and temporal lobes, the superior longitudinal fasciculus connects the temporal to the occipital and frontal cortices (i.e., the sensory and motor regions of Wernicke's and Broca's areas), and the occipitofrontal fasciculus connects the frontal-temporal-occipital regions.

The anatomical complexity, including large association regions, suggests that the temporal lobes have diverse functions, including the perception of auditory sensations, the analysis of affective tone in auditory stimuli, and long-term memory storage. Although the temporal lobe has primary auditory perception and association functions related to speech and language processing, it also plays a significant role in memory functions and in facial (prosopagnosia) and object recognition (Bauer & Demery, 2003).

The primary temporal cortex is involved with the perception of speech sounds, particularly in the left hemisphere, and nonverbal tonal sequences, particularly in the right hemisphere, while the secondary and association regions are more complex and varied in function. The secondary and association regions add the affective quality to stimuli that is essential for learning to take place. When positive, negative, or neutral affective qualities are attached to stimuli, information takes on motivational or emotional importance to the learner. Without this association, all stimuli would be judged as equal and we would respond to all stimuli with the same affect or emotion (Heilman, Blonder, Bowers, & Valenstein, 2003).

The mesial temporal region, including the adjoining hippocampus and amygdala, appears to be linked to memory processes and plays a role in learning or acquiring new information (Tranel, 1992). Lesions in this area result in impaired retention of new memories, as this region appears to be related to the process by which new memories are stored or are retrieved from storage (Lezak et al., 2004). Asymmetry of functions is evident in the temporal lobes. Memory functions appear to be lateralized. The recall of verbal information, including stories and word lists presented either orally or visually, is stored in the left hemisphere, whereas nonverbal recall for geometric drawings, faces, and tunes is stored in the right hemisphere (Kolb & Whishaw, 2003).

The olfactory system is the only sensory system that converges in the telencephalon. The olfactory bulb receives sensory information concerning smell directly from the olfactory nerve and converges with the olfactory tract; at this juncture, axons cross to the bulb in the opposite hemisphere via the anterior commissure. The olfactory tract projects to the primary olfactory cortex to a small region called the uncus, close to the end of the temporal lobe (Brodal, 2004). Although olfactory assessment is often ignored, the sense of smell is frequently associated with various neuropsychiatric disturbances found in adults, particularly schizophrenia, Parkinson's disease, multiple sclerosis, subfrontal tumors, and some brain injuries (Heilman & Valenstein, 2003).

The limbic system is a complex deep collection of structures in the forebrain comprising the hippocampus, amygdale, septum, and cingulate gyms (Kolb & Whishaw, 2003). The limbic system has widespread connections with the neocortex and with the autonomic and endocrinological systems, and is considered a primitive brain structure involved with the olfactory senses. It resides between two brain regions (diencephalon and telencephalon) and serves as an intermediary to cognitive and emotional functions (Wilkinson, 1986). In humans the limbic system has less to do with the olfactory system than with emotional and memory functions that are essential for the survival of the species. It also has preservation functions for the individual.

Wilkinson (1986) describes a number of important functions of the limbic system, including:

Autonomic responses (e.g., heart rate, breathing, blood pressure, and digestive functions) can be influenced by limbic structures, especially the cingulate gyrus. Aggressive reactions and social indifference have been associated with the cingulate gyrus. The cingulate gyrus has also been associated with error checking and self-monitoring of behavior (Semrud-Clikeman, Pliszka, Lancaster, & Liotti, 2006). Feelings of anxiety, deja vu experiences, rage, and fear have been associated with functions of the amygdala (Gazzaniga et al., 2002). With its connections with other limbic and cortical structures, the hippocampus has broad functions involving learning and memory. Seizure activity in limbic structures, particularly the hippocampus, sometimes includes temporal lobe structures as well (Lockman, 1994). Seizures at this site may result in a temporary loss of consciousness and loss of memory.