Practice Flashcards: Nervous System Organization

Clinical Case Study of Stroke and the Implications of Brain Injury

The case of R.S. illustrates the profound impact of localized brain damage on behavior and cognitive function. R.S., a former manager and owner of a movie theater, possessed an encyclopedic knowledge of cinema until a stroke, defined as an interruption of blood flow to the brain that kills brain cells and results in sudden behavioral changes, significantly altered his life. While repairing his garage roof, R.S. experienced numbness in his left hand and subsequently collapsed. A CT scan revealed damage to his right frontal cortex caused by ischemia, which is a deficiency of blood flow resulting from the functional constriction of a blood vessel by a clot. According to the U.S. Centers for Disease Control and Prevention, stroke is the third-leading cause of death and the leading cause of long-term disability in the United States, with a stroke occurring every $40$ seconds. While stroke rates are declining in developed countries due to reduced smoking, dietary improvements, and blood pressure control, the condition remains a primary concern for medical researchers.

Following his stroke, R.S. suffered permanent behavioral changes. Although rehabilitation restored his ability to walk with a stiff left leg, his left arm remained rigid and flexed. His family observed a total lack of interest in his previous passions, such as gardening, business, and cinema. This apathy is a common neuropsychological symptom following frontal cortex damage. In terms of medical intervention, ischemic strokes can often be treated using tissue plasminogen activator ($t\text{-PA}$) if administered within $3$ hours of the onset. This drug breaks up clots to restore normal blood flow. However, R.S. did not receive this treatment because the attending physician could not determine if his fall was the cause or the result of the stroke; administering such anticlotting drugs to a patient with a hemorrhagic stroke—caused by a burst vessel bleeding into the brain—would aggravate cell death rather than mitigate it. Modern research continues to seek ways to stimulate reparative processes in the brain and develop behavioral therapies to address the debilitating apathy experienced by patients like R.S.

Fundamental Biological Complexity and Neuroplasticity

The human brain is a structure of immense complexity, housing approximately $8.6 \times 10^{10}$ neurons dedicated to information processing. Each of these neurons can make up to $30,000$ individual connections with other neurons. Supporting these units are roughly $8.5 \times 10^{10}$ glial cells that maintain neuronal functioning. These cells are organized into layers or clusters called nuclei—from the Latin for “nut”—which perform specific functions in mediating behavior. When neurons are situated close together, they form dense local connections, but they also establish long-distance connections through fiber pathways or tracts, a term derived from the Old French for “path.” This anatomical architecture varies between species and between individual humans, contributing to the behavioral differences observed across the population.

A central principle of neuropsychology is the concept of neuroplasticity, which refers to the brain's ability to undergo enormous changes throughout a lifespan. This plasticity allows neurons to change their connections, and the brain to lose or gain neurons and glia in response to development, experience, and learning. It also facilitates compensation following damage. While the common architecture of the brain is determined by the genotype, epigenetic influences mediate individual phenotypic plasticity. This is demonstrated by studies on genetically identical mice clones that express different physical and behavioral phenotypes because their mothers were fed different dietary supplements during pregnancy. Such environmental influences lead to varied body structures and eating behaviors despite identical genetic code.

Systems of Anatomical Orientation and Nomenclature

Describing locations within the brain requires a standardized reference frame consisting of three main perspectives. The first perspective relates to other body parts: rostral (toward the beak or head), caudal (toward the tail), dorsal (toward the back), and ventral (toward the stomach). In certain contexts, the terms superior and inferior are used to replace dorsal and ventral respectively. The second perspective is based on the face: anterior or frontal refers to the front, posterior refers to the back, lateral refers to the sides, and medial refers to the center or midline. The third perspective is the viewer's section: a coronal section is a vertical cut from the crown down revealing a frontal view, a horizontal section is cut along the horizon revealing a dorsal view, and a sagittal section is cut lengthways from front to back revealing a medial view.

Symmetry is a fundamental feature of the nervous system. Structures on the same side are termed ipsilateral, while those on opposite sides are contralateral. If a structure exists in each of the two hemispheres, it is called bilateral. Depth is described using the terms proximal (close to) and distal (far from). Direction of movement relative to a structure is described as afferent (toward a structure, such as sensory input to the brain) or efferent (away from a structure, such as motor output from the brain). These naming conventions often include historical and descriptive terms. For example, the precentral gyrus, responsible for R.S.'s motor deficits, is also known as the motor strip, Jackson’s strip (after John Hughlings-Jackson), the primary motor cortex ($M1$), or area pyramidalis. Other names are derived from flora, such as the amygdala (almond), or mythology, such as Ammon’s horn for a part of the hippocampus.

Structural Protection and Cerebrovascular Irrigation

The central nervous system ($CNS$), consisting of the brain and spinal cord, is encased in bone—the skull and the vertebrae. While the peripheral nervous system ($PNS$) lacks this protection, it has a superior capacity for self-repair through the regrowth of axons and dendrites. Within the bony casing, the $CNS$ is protected by the meninges, a triple-layered membrane system. The outermost layer is the tough dura mater (hard mother), the middle is the delicate, spider-web-like arachnoid membrane, and the innermost layer is the pia mater (soft mother) which clings to the brain's surface. Between these layers and within the four ventricles of the brain flows the cerebrospinal fluid ($CSF$). This fluid cushions the brain against shock. A blockage in the flow of $CSF$ can lead to hydrocephalus (water brain), resulting in built-up pressure that causes intellectual impairment or death.

The brain also features a blood-brain barrier created by astroglia, which stimulate capillary cells to form tight junctions that exclude toxins and infections from the $CNS$. The vascular supply to the brain is provided by two internal carotid arteries and two vertebral arteries. These branch into three major cerebral arteries: the anterior cerebral artery ($ACA$), irrigating the medial and dorsal cortex; the middle cerebral artery ($MCA$), irrigating the lateral surface; and the posterior cerebral artery ($PCA$), irrigating the ventral and posterior surfaces. Some individuals possess anastomoses, which are connections between arteries that provide alternative blood routes if a clot occurs. Venous blood returns to the heart via external and internal cerebral and cerebellar veins, which do not follow the same paths as the arteries.

Cellular Origins and Classification of Neuronal Types

All brain cells originate from undifferentiated multipotential neural stem cells located in the subventricular zone surrounding the ventricles. These stem cells divide to produce progenitor cells, which then give rise to blasts. Neuroblasts differentiate into various neurons, while glioblasts differentiate into glial cells. Neurons are characterized into three major functional categories. Sensory neurons include bipolar neurons (found in the retina) and somatosensory neurons (which projects from bodies to the spinal cord without passing through the cell body to speed up conduction). Interneurons, such as stellate, pyramidal, and Purkinje cells, connect sensory and motor activity and feature extensive dendritic branching. Motor neurons, often described as the “final common path,” project from the brainstem and spinal cord to command muscle movement.

There are five primary types of glial cells: ependymal cells, which line the ventricles and secrete $CSF$; astroglia, which provide support, nutrition, and maintain the blood-brain barrier; microglial cells, which serve a defensive immune function and remove debris; oligodendroglia, which form insulating myelin around axons in the $CNS$; and Schwann cells, which provide the same myelination for the $PNS$. The physical appearance of the brain tissue reflects its composition: gray matter is made of cell bodies and capillaries; white matter consists of axons insulated by fatty myelin; and reticular matter, like that found in the brainstem, is a netlike mixture of both.

Developmental Anatomy and the Five-Division Model

The central nervous system begins as a tube that develops into a three-chambered structure consisting of the prosencephalon (front brain for olfaction), the mesencephalon (middle brain for vision/hearing), and the rhombencephalon (hindbrain for movement/balance). In mammals, this further subdivides into five regions. The prosencephalon becomes the telencephalon (cerebral hemispheres) and the diencephalon (thalamus/hypothalamus). The mesencephalon remains the midbrain. The rhombencephalon subdivides into the metencephalon (cerebellum and pons) and the myelencephalon (medulla). Functional levels generally assign cognitive processes to the forebrain, regulatory functions to the brainstem, and reflexive motor functions to the spinal cord.

Functional Organization of the Spinal Cord and Spinal Nerves

The spinal cord is organized into segments corresponding to five anatomical regions: cervical ($C$), thoracic ($T$), lumbar ($L$), sacral ($S$), and coccygeal. There are $31$ segments in total, each corresponding to a dermatome, or ring-shaped body region. The Bell-Magendie law states that the posterior (dorsal) roots of the spinal cord are sensory (afferent), while the anterior (ventral) roots are motor (efferent). This principle was discovered through the experiments of François Magendie and Charles Bell. Spinal cord injury leads to loss of function below the site of the cut, resulting in paraplegia (loss of leg control) or quadriplegia (loss of arm and leg control). While adult mammals cannot naturally regrow severed spinal fibers, research into pharmacological treatments, glial implants, and brain-computer interfaces ($BCI$) seeks to restore functionality.

The spinal cord produces reflexes, which are specific movements elicited by sensory stimulation. Flexion reflexes are produced by pain and temperature receptors, pulling the limb toward the body. Extension reflexes are produced by fine touch and muscle receptors, extending the limb outward to maintain contact with a surface and support body weight. These circuits can operate even when separated from the brain, as demonstrated by the work of Charles Sherrington. Higher coordination, such as stepping, involves the cooperation of multiple thoracic and lumbar segments to coordinate movement across all four limbs in quadrupeds.

Overview of Cranial Nerves and Autonomic Control

There are $12$ pairs of cranial nerves providing sensory and motor links for the head, neck, and internal organs. The olfactory nerve ($1$) mediates smell; the optic ($2$) mediates vision; and the oculomotor ($3$), trochlear ($4$), and abducens ($6$) nerves control eye movement. The trigeminal ($5$) nerve handles facial sensation and masticatory movements. The facial ($7$) nerve is for facial expressions and taste on the anterior two-thirds of the tongue, while the auditory vestibular ($8$) nerve is for hearing and balance. The glossopharyngeal ($9$) nerve mediates taste on the posterior third of the tongue. The vagus ($10$) nerve connects to the heart, blood vessels, and viscera. The spinal accessory ($11$) nerve controls neck muscles, and the hypoglossal ($12$) nerve controls tongue movements. Dysfunction in these nerves leads to specific symptoms like anosmia (loss of smell), anopsia (loss of vision), diplopia (double vision), or facial paralysis.

The autonomic nervous system ($ANS$) regulates internal organs through the sympathetic and parasympathetic divisions. The sympathetic system arouses the body for “fight or flight,” using a chain of ganglia parallel to the spinal cord. The parasympathetic system calms the body for “rest and digest,” with ganglia located near target organs. The vagus nerve is a major contributor to parasympathetic control. A phenomenon known as referred pain occurs because internal organs lack their own sensory representation in the spinal cord; pain from these organs is perceived as coming from the somatic dermatome, such as heart pain being felt in the left shoulder and arm.

The Brainstem and Diencephalon

The brainstem is composed of the hindbrain, midbrain, and diencephalon. The hindbrain includes the cerebellum, which contains $80.00\%$ of all brain cells and is gathered into folds called folia; it coordinates motor learning and equilibrium. The reticular formation within the hindbrain core maintains consciousness and general arousal. The pons bridges the cerebellum to the brain, while the medulla regulates vital breathing and cardiovascular functions. The midbrain consists of the tectum (roof), containing the superior colliculi (visual orienting) and inferior colliculi (auditory orienting), and the tegmentum (floor), which includes the red nucleus (limb movement), the substantia nigra (reward and movement), and the periaqueductal gray matter ($PAG$) for pain modulation and species-typical behaviors.

The diencephalon, or “between brain,” contains the hypothalamus, thalamus, and epithalamus. The hypothalamus consists of $22$ nuclei that regulate motivated behaviors like feeding, sleeping, and sexual activity. The thalamus contains $20$ nuclei acting as a relay hub for sensory information; specifically, the lateral geniculate body ($LGB$) for vision, the medial geniculate body ($MGB$) for audition, and the pulvinar for interconnecting cortical areas. The epithalamus includes the pineal gland, which secretes melatonin for biorhythms, and the habenula, which regulates hunger and thirst.

The Telencephalon: Basal Ganglia, Limbic System, and Neocortex

The telencephalon includes the basal ganglia, the limbic system, and the neocortex. The basal ganglia (caudate nucleus, putamen, and globus pallidus) regulate movement fluidity and associative habit learning. Disorders here include Huntington disease (excessive chorea), Tourette syndrome (tics), and Parkinson disease (loss of movement and rigidity). The limbic system, once called the “smell-brain” or rhinencephalon, includes the amygdala (emotion), hippocampus (spatial navigation and memory), and cingulate cortex (executive function). James Papez proposed the Papez circuit to explain how emotion is generated through the mammillary bodies, thalamus, cingulate cortex, and hippocampus.

The neocortex is a $6$-layered sheet of gray matter about $1.5$ to $3.0\,mm$ thick with an area of $2500\,cm^2$. It is folded into gyri (ridges) and sulci (shallow clefts), or fissures (deep clefts). The four lobes—frontal, parietal, temporal, and occipital—are organized into primary regions (direct input/output), secondary regions (interpretation), and tertiary/association regions (complex functions like language). Layers $I$-$III$ are for integrative functions, Layer $IV$ is the afferent sensory input layer (granular cortex), and Layers $V$-$VI$ are for efferent output. Korbinian Brodmann mapped $52$ distinctive cytoarchitectonic areas based on cell organization. Modern FACT (Function, Anatomy, Connectivity, Topography) analysis, utilized by the Human Connectome Project, suggests there are up to $180$ distinct cortical areas per hemisphere.

Hemispheric Specialization and the Crossed Brain

A defining characteristic of the brain is its crossed organization. Each hemisphere primarily responds to contralateral sensory stimulation and controls contralateral musculature. In humans, visual information is split such that the left hemisphere receives input from the right visual field of both eyes, while the right hemisphere receives input from the left visual field. This differs from animals like rats, where about $95.00\%$ of optic fibers cross, compared to only $50.00\%$ in humans. Motor and somatosensory fibers show roughly $90.00\%$ decussation (crossing) at the midline. This anatomical arrangement explains why damage to the right hemisphere, as seen in R.S., causes motor and sensory impairments on the left side of the body. Interhemispheric communication is facilitated by commissures, primarily the corpus callosum and the anterior commissure, which zip together the representations of the world formed in each hemisphere.