The Forebrain (Organization of the Central Nervous System) Part 4

Other Major Pathways of The Forebrain

Internal Capsule

The internal capsule contains descending fibers from the cerebral cortex to the brainstem and spinal cord as well as ascending fibers from the thalamus to the cerebral cortex. As noted previously, the fibers contained within the internal capsule play critical roles in sensorimotor functions. It should be recalled that, when viewed in a horizontal section (Fig. 13-2), the internal capsule has three components: an anterior limb, posterior limb, and genu. The frontopontine fibers are contained within the anterior limb, the corticobulbar fibers are contained within the genu, and the corticospinal fibers are present within the posterior limb. The internal capsule also serves as an important anatomical landmark, separating the thalamus from the globus pallidus and the caudate nucleus from the putamen (Fig. 13-2).

Anterior Commissure

The anterior commissure, which lies just rostral to the descending column of the fornix (Fig. 13-1), contains olfactory fibers that pass from the anterior olfactory nucleus to the contralateral olfactory bulb as well as some fibers that originate in parts of the temporal lobe, including the amygdala.

Clinical Considerations

Vascular and other lesions of the forebrain are considered in all of the succeeding topics that relate to discussion of forebrain structures. For this reason, disorders of different regions of the forebrain are discussed only briefly at this time.


As a result of a thalamic infarct, frequently involving its posterior aspect, the patient feels a very painful and unpleasant sensation. When the pain persists generally as a burning sensation, it is referred to as a thalamic pain syndrome.


Because the hypothalamus mediates a variety of auto-nomic, visceral, and emotional responses, damage to different groups of hypothalamic nuclei can result in disorders in eating, endocrine function, temperature regulation, aggression and rage, and sympathetic dysfunction. An example of one such disorder is diabetes insipidus, which results from damage to vasopressin neurons located in the supraoptic or paraventricular nuclei and is characterized by the flow of large amounts of urine coupled with drinking of large quantities of fluids.

Basal Ganglia

Diseases of the basal ganglia are characterized by abnormal, involuntary movements at rest, referred to collectively as dyskinesia and by abnormal changes in muscle tone. Parkinson’s disease, an example of a hypokinetic disorder, is associated with tremor, rigidity, and akinesia. The disorder results from a loss of dopamine released from the substantia nigra that supplies the neostriatum. Other disorders include chorea, which is a hyperkinetic disorder associated with a loss of gamma-aminobutyric acid in the striatum, characterized by brisk involuntary movements of the extremities and hemiballism, which involves damage to the subthalamic nucleus, resulting in abnormal flailing movements of the arm and leg on the contralateral side of the body.

Limbic Structures

Because of their relationships with the hypothalamus and midbrain PAG, disruptions of limbic structures resulting from vascular lesions or tumors frequently are associated with marked changes in emotional behavior, irritability, impulsivity, and rage. Structures most closely associated with these effects include the amygdala, hippocampal formation, and the prefrontal cortex. Other disorders include loss of short-term memory functions, particularly after damage to the hippocampal formation; a decrease in cognitive ability and flatness in emotional responsiveness after damage to the prefrontal cortex; and seizure disorders associated most commonly with damage to temporal lobe structures.

Cerebral Cortex

In brief, some of these disorders are mentioned here and usually result from tumors or vascular lesions. These disorders include: (1) upper motor neuron paralysis associated with damage of the precentral and premotor cortices; (2) several forms of aphasias (inability to express or understand language) associated with damage to the ventrolateral aspect of the premotor region or borderline region of the temporal and parietal lobes; (3) apraxias (inability to produce a motor act correctly even though sensory and motor circuits are intact) associated with damage to the premotor cortex or to the posterior parietal cortex; (4) loss of somatosensory and auditory discrimination ability after damage to the postcentral and superior temporal gyri, respectively; and (5) partial blindness after damage to the region of the cal-carine fissure of the occipital cortex.

Clinical Case


John is a 36-year-old man who had fallen forwards off a tractor at the age of 10 years, sustaining a blow to the front of his head. Ever since then, John suffered behavioral problems. In school, he had difficulty concentrating and paying attention. His behavior toward other students was often inappropriate, with the inability to suppress impulsive actions with lack of emotional reaction. Although he was ultimately promoted every year, he was given a diagnosis of attention deficit disorder and learning disability. Methylphenidate (Ritalin) and behavioral therapy did not make a major impact on his behavior, but he was able to advance in school and graduate.

As he reached adulthood, John had more difficulty controlling his impulsive behavior. He lacked appropriate social inhibition as well as awareness of the abnormal behavior. For example, after a woman rejected his advances, he drove to her house and washed his car in her driveway for 4 hours, until she finally called the police. He also became involved in meaningless activities such as collecting small objects. He often made inappropriate comments, causing him to lose several jobs. John was unable to respond appropriately to emotional situations such as laughing upon hearing that his father suffered a serious injury.


When evaluated by a neuropsychologist, John was found to be somewhat emotionally bland. He further made comments about the examiner, which lacked appropriate inhibition,such as,"Only a stupid person would administer this test." When asked to describe situations observed in standardized drawings, he described the literal meaning of the drawing, while missing the more conceptual or abstract aspect of the meaning. For example, when asked what was wrong with a picture of two children pouring water on the floor of a kitchen and throwing eggs on the floor, he described the picture as showing these actions. However, when asked if there was something wrong with what they were doing, he stated that the materials were on the floor, but there was nothing wrong with the children’s behavior. He was noted to have slight grasping responses and had a tendency to imitate the examiner. John was referred for a magnetic resonance imaging (MRI) scan to determine if there were any new problems since his original injury.


John’s case is an example of bilateral frontal lobe dysfunction. Frontal lobe lesions, especially those of the inferior and prefrontal regions, tend to result in disorders of initiative, apathy, abulia (lack of motor activity), primitive grasp responses like those seen in infants, inappropriate behavior, and lack of social inhibition. If the lesion is sufficiently posterior to involve the motor cortex, upper motor neuron weakness may also be observed. These properties were noted in patients who had undergone prefrontal lobotomies for mental illness in earlier periods of the 20th century and are the reason why this procedure was abandoned.

In John’s case, the MRI showed atrophy (shrinkage) of the anterior frontal lobes bilaterally, which provided evidence that the initial injury remained. Subsequent MRI scans could be used to determine if this condition was, indeed, progressive. However, usually they are not necessary due to easy clinical evaluations.


Major Forebrain Nuclei and Pathways



Principle Relationships



Anterior nucleus

Receives inputs from hippocampal formation and mammillary bodies and sends information to cingulated gyrus;function: memory

Dorsomedial nucleus

Receives inputs from prefrontal cortex and several limbic nuclei and major output includes prefrontal region of cortex; function: affective processes and emotional behavior

Ventral anterior and ventrolateral nuclei

Inputs: Globus pallidus and cerebellum; output: motor regions of cerebral cortex; function: motor functions

Ventral posterolateral and ventral posteromedial nuclei

Receive somatosensory inputs from the body and head, respectively, and transmit this information to somatosensory cortex

Pulvinarand lateral posterior nuclei

Receive and integrate sensory inputs and appear to be associated with cognitive functions

Medial geniculate nucleus

Auditory relay nucleus, receives auditory inputs from inferior colliculus and transmits this information to auditory cortex

Lateral geniculate nucleus

Relay nucleus for visual inputs from retina and transmits these signals to visual cortex

Intralaminar nuclei: reticular nucleus and centro-median nucleus

Receive inputs from varieties of thalamic and other neurons and modulate cortical activity by widespread projections to the cerebral cortex


Habenular complex and stria medullaris

Receives inputs from parts of basal forebrain via stria medullaris and projects axons to ventromedial midbrain via habenulo-peduncular tract

Pineal gland

Attached to roof of posterior diencephalon-midbrain juncture; contains specialized secretory cells (pinealocytes), secreting biogenic amines


Subthalamic nucleus and zona incerta

Subthalamic nucleus is anatomically and functionally linked to motor functions of the basal ganglia; functions of the zona incerta are largely unknown


Lateral hypothalamus

Receives inputs from limbic structures and projects to brainstem nuclei; plays important roles in drinking and predatory functions

Medial hypothalamus

Receives inputs from limbic structures and projects to midbrain PAG; regulates visceral functions such as feeding, affective processes, including rage, and activity of the sympathetic nervous system

Supraoptic-paraventricu-lar nuclei

Synthesize vasopressin and oxytocin, which are transported to posterior pituitary

Mammillary bodies

Receive inputs from hippocampal formation and project axons to anterior thalamic nucleus (via mammillothalamic tract) and to midbrain (mamillary peduncle)

Basal Ganglia

Caudate nucleus and putamen

Main receiving areas of basal ganglia for information from cerebral cortex, thalamus, and substantia nigra

Globus pallidus

Primary region for outputs of information from basal ganglia




Principle Relationships

Basal Ganglia

Related pathways:

Ansa lenticularis and lenticular fasciculus transmit information from different aspects of globus pallidus to thalamus; thalamic fasciculus includes the coalescence of fibers from the dentate nucleus of cerebellum (dentatothalamic fibers), ansa lenticularis,and lenticular fasciculus

Limbic System

Hippocampal formation

Major component of limbic system situated within temporal lobe; projects to septal area and hypothalamus via the fornix and is associated with the regulation of autonomic and other visceral functions, including hormonal functions of hypothalamus; emotional behavior; and short-term memory

Septal area

Major relay nucleus of hippocampal formation; projects axons to hypothalamus; associated with regulatory functions of hypothalamus

Bed nucleus of stria terminalis

Receives major inputs from amygdala; projects axons to hypothalamus and brainstem regions associated with autonomic and endocrine functions

Nucleus accumbens

Receives major inputs from dopaminergic neurons of the ventral tegmentum of midbrain; believed to integrate motor responses associated with affective behavior and with functions related to addictive processes

Substantia innominata

Sometimes viewed as an extension of amygdala; reciprocally connected with amygdala and projects to hypothalamus and to wide areas of cerebral cortex; projections to cortex are cholinergic, and their loss may contribute to Alzheimer’s disease


Major component of limbic system contained in rostral aspect of temporal lobe; major functions include regulation of visceral, behavioral, and affective processes associated with hypothalamus and midbrain PAG; major output pathway includes stria terminalis, which projects directly to medial hypothalamus from medial amygdala

Other pathways

Internal capsule: Anterior limb, genu, posterior limb

Internal capsule contains fibers passing mainly from cerebral cortex to thalamus, brainstem and spinal cord; anterior limb contains frontopontine fibers ultimately destined to supply cerebellum;fibers in genu contain fibers that supply brainstem and, in particular, nuclei of cranial nerves, thus controlling cranial nerve functions; posterior limb contains corticospinal fibers that control movements of the limbs

Anterior commissure

Commissure in rostral forebrain containing olfactory fibers passing from anterior olfactory nucleus to contralateral olfactory bulb as well as temporal lobe fibers passing from one temporal lobe to the other, including those that supply the amygdala

PAG = periaqueductal gray matter.

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