Clinical Neuroanatomy, 27 ed.

CHAPTER 9. Diencephalon

The diencephalon includes the thalamus and its geniculate bodies, the hypothalamus, the subthalamus, and the epithalamus (Fig 9–1). The third ventricle lies between the halves of the diencephalon. The development of the diencephalon is reviewed in Chapter 10 (see Figs 10–110–3, and 10–4).


FIGURE 9–1 Midsagittal section through the diencephalon.

A small groove on the lateral wall of the slim third ventricle—the hypothalamic sulcus—separates the thalamus dorsally and the hypothalamus and subthalamus inferiorly.



Each half of the brain contains a thalamus, a large, ovoid, gray mass of nuclei (Fig 9–2). Its broad posterior end, the pulvinar, extends over the medial and lateral geniculate bodies. The rostral thalamus contains the anterior thalamic tubercle. In many individuals, there is a short interthalamic adhesion (massa intermedia) between the thalami, across the narrow third ventricle (see Fig 9–1).


FIGURE 9–2 Dorsal aspect of the diencephalon after partial removal of the overlying corpus callosum. The thalamus is shown in blue.

White Matter

The thalamic radiations are the fiber bundles that emerge from the lateral surface of the thalamus and terminate in the cerebral cortex. The external medullary lamina is a layer of myelinated fibers on the lateral surface of the thalamus close to the internal capsule. The internal medullary lamina is a thin vertical sheet of white matter that bifurcates in its anterior portion and thus divides the gray matter of the thalamus into lateral, medial, and anterior portions (Fig 9–3).


FIGURE 9–3 Diagrams of the thalamus. Oblique lateral and medial views.

Thalamic Nuclei

There are five major groups of thalamic nuclei, each with specific fiber connections (Figs 9–3 and 9–4Table 9–1).


FIGURE 9–4 Schematic lateral view of the thalamus with afferent fiber systems.

Table 9–1 Functional Divisions of Thalamic Nuclei.


A. Anterior Nuclear Group

This group of clusters of neurons forms the anterior tubercle of the thalamus and is bordered by the limbs of the internal lamina. It receives fibers from the mamillary bodies via the mamillothalamic tract and projects to the cingulate cortex of the cerebrum.

B. Nuclei of the Midline

These groups of cells are located just beneath the lining of the third ventricle and in the interthalamic adhesion. They connect with the hypothalamus and central periaqueductal gray matter. The centromedian nucleus connects with the cerebellum and corpus striatum.

C. Medial Nuclei

These include most of the gray substance medial to the internal medullary lamina: the intralaminar nuclei as well as the dorsomedial nucleus, which projects to the frontal cortex.

D. Lateral Nuclear Mass

This constitutes a large part of the thalamus anterior to the pulvinar between the internal and external medullary laminas. The mass includes a reticular nucleus between the external medullary lamina and the internal capsule; a ventral anterior nucleus (VA), which connects with the corpus striatum; a ventral lateral nucleus (VL), which projects to the cerebral motor cortex; a dorsolateral nucleus, which projects to the parietal cortex; and a ventral posterior (also known as ventral basal) group, which projects to the postcentral gyrus and receives fibers from the medial lemniscus and the spinothalamic and trigeminal tracts.

The ventral posterior group of thalamic nuclei is divided into the ventral posterolateral (VPL) nucleus, which relays sensory input from the body, and the ventral posteromedial (VPM) nucleus, which relays sensory input from the face. The ventral posterior nuclei project information via the internal capsule to the sensory cortex of the ipsilateral cerebral hemisphere (see Chapter 10).

E. Posterior Nuclei

These include the pulvinar nucleus, the medial geniculate nucleus, and the lateral geniculate nucleus. The pulvinar nucleus is a large posterior nuclear group that connects with the parietal and temporal cortices. The medial geniculate nucleus, which lies lateral to the midbrain under the pulvinar, receives acoustic fibers from the lateral lemniscus and inferior colliculus. It projects fibers via the acoustic radiation to the temporal cortex. The lateral geniculate nucleus is a major way station along the visual pathway. It receives most of the fibers of the optic tract and projects via the geniculocalcarine radiation to the visual cortex around the calcarine fissure. The geniculate nuclei or bodies appear as oval elevations below the posterior end of the thalamus (Fig 9–5).


FIGURE 9–5 Horizontal section through the thalamus.

Functional Divisions

The thalamus can be divided into five functional nuclear groups: sensory, motor, limbic, multimodal, and intralaminar (see Table 9–1).

The sensory nuclei (ventral posterior group including VPL and VPM, and the lateral and medial geniculate bodies) are involved in relaying and modifying sensory signals from the body, face, retina, cochlea, and taste receptors (see Chapter 14). The thalamus is thought to be the crucial structure for the perception of some types of sensation, especially pain, and the sensory cortex may give finer detail to the sensation.

The thalamic motor nuclei (ventral anterior and lateral) convey motor information from the cerebellum and globus pallidus to the precentral motor cortex. The nuclei have also been called motor relay nuclei (see Chapter 13).

Three anterior limbic nuclei are interposed between the mamillary nuclei of the hypothalamus and the cingulate gyrus of the cerebral cortex. The dorsomedial nucleus receives input from the olfactory cortex and amygdala regions and projects reciprocally to the prefrontal cortex and the hypothalamus (see Chapter 19).

The multimodal nuclei (pulvinar, posterolateral, and dorsolateral) have connections with the association areas in the parietal lobe (see Chapter 10). Other diencephalic regions may contribute to these connections.

Other, nonspecific thalamic nuclei include the intralaminar and reticular nuclei and the centrum medianum; the projections of these nuclei are not known in detail. Interaction with cortical motor areas, the caudate nucleus, the putamen, and the cerebellum has been demonstrated.



The hypothalamus, which serves a number of autonomic, appetitive, and regulatory functions, lies below and in front of the thalamus; it forms the floor and lower walls of the third ventricle (see Fig 9–1). External landmarks of the hypothalamus are the optic chiasm; the tuber cinereum, with its infundibulum extending to the posterior lobe of the hypophysis; and the mamillary bodies lying between the cerebral peduncles (Fig 9–6).


FIGURE 9–6 Diencephalon from below, with adjacent structures.

The hypothalamus can be divided into an anterior portion, the chiasmatic region, including the lamina terminalis; the central hypothalamus, including the tuber cinereum and the in-fundibulum (the stalk connecting the pituitary to the hypothalamus); and the posterior portion, the mamillary area (Fig 9–7).


FIGURE 9–7 Coronal sections through the diencephalon and adjacent structures. A: Section through the optic chiasm and the anterior commissure. B: Section through the tuber cinereum and the anterior portion of the thalamus. C: Section through the mamillary bodies and middle thalamus. D: Key to the section levels.

The right and left sides of the hypothalamus each have a medial hypothalamic area that contains many nuclei and a lateral hypothalamic area that contains fiber systems (eg, the medial forebrain bundle) and diffuse lateral nuclei.

Medial Hypothalamic Nuclei

Each half of the medial hypothalamus can be divided into three parts (Fig 9–8): the supraoptic portion, which is farthest anterior and contains the supraoptic, suprachiasmatic, and paraventricular nuclei;the tuberal portion, which lies immediately behind the supraoptic portion and contains the ventromedial, dorsomedial, and arcuate nuclei in addition to the median eminence; and the mamillary portion, which is the farthest posterior and contains the posterior nucleus and several mamillary nuclei. There is also the preoptic area, a region that lies anterior to the hypothalamus, between the optic chiasm and the anterior commissure.


FIGURE 9–8 The human hypothalamus, with a superimposed diagrammatic representation of the portal-hypophyseal vessels. (Reproduced, with permission, from Ganong WF: Review of Medical Physiology, 22nd ed. McGraw-Hill, 2005.)


The thalamic syndrome is characterized by immediate hemianesthesia, with the threshold of sensitivity to pinprick, heat, and cold rising later. When a sensation, sometimes referred to as thalamic hyperpathia, is felt, it can be disagreeable and unpleasant. The syndrome usually appears during recovery from a thalamic infarct; rarely, persistent burning or boring pain can occur (thalamic pain).

Afferent Connections

Consistent with its autonomic and regulatory functions, the hypothalamus receives inputs from limbic structures, thalamus and cortex, visceral and somatic afferents, and sensors such as osmoreceptors, which permit it to monitor the circulation.

Afferent connections to the hypothalamus include part of the medial forebrain bundle, which sends fibers to the hypothalamus from nuclei in the septal region, parolfactory area, and corpus striatum;thalamohypothalamic fibers from the medial and midline thalamic nuclei; and the fornix, which brings fibers from the hippocampus to the mamillary bodies. These connections also include the stria terminalis, which brings fibers from the amygdala; pallidohypothalamic fibers, which lead from the lentiform nucleus to the ventromedial hypothalamic nucleus; and the inferior mamillary peduncle, which sends fibers from the tegmentum of the midbrain. A small number of ganglion cells from throughout the retina (less than 1% of the total number of retinal ganglion cells) send axons that provide visual input to the suprachiasmatic nucleus via the retinohypothalamic tract. These and other connections are shown in Table 9–2.

Table 9–2 Principal Pathways to and from the Hypothalamus.


Affective and emotional inputs from the prefrontal cortex reach the hypothalamus via a polysynaptic pathway that passes through the dorsomedial nuclei of the thalamus. In addition, visceral information from the vagal sensory nuclei, gustatory messages from the nucleus solitarius, and somatic afferent messages from the genitalia and nipples are relayed to the hypothalamus.

Efferent Connections

Efferent tracts from the hypothalamus include the hypothala-mohypophyseal tract, which runs from the supraoptic and paraventricular nuclei to the neurohypophysis (see the next paragraph); the mamillotegmental tract (part of the medial forebrain bundle) going to the tegmentum; and the mamillothalamic tract (tract of Vicq d’Azyr), from the mamillary nuclei to the anterior thalamic nuclei. There are also the periventricular system, including the dorsal fasciculus to the lower brain levels; the tuberohypophyseal tract, which goes from the tuberal portion of the hypothalamus to the posterior pituitary; and fibers from the septal region, by way of the fornix, to the hippocampus (see Chapter 19).

There are rich connections between the hypothalamus and the pituitary gland. The pituitary has two major lobes: the posterior pituitary (neurohypophysis) and anterior pituitary (adenohypophysis). Neurons in the supraoptic and paraventricular nuclei send axons, via the hypothalamohypophyseal tract, to the neurohypophysis. These axons transport Herring bodies, which contain precursors of the hormones oxytocin and vasopressin (also known as antidiuretic hormones, or ADHs) to the posterior pituitary. Oxytocin and vasopressin are released from axon endings in the posterior pituitary and are then taken up by a rich network of vessels that transports them to the general circulation (Figs 9–8 and 9–9).


FIGURE 9–9 Schematic view of the pituitary portal system of vessels and neurohypophyseal pathways. The portal hypophyseal vessels serve as a vascular conduit that carries various hypophyseotropic hormones from their sites of release from hypothalamic neurons, in the median eminence on the pituitary stalk, to the anterior pituitary. In contrast, the axons of supraoptic and paraventricular neurons run all the way to the posterior pituitary, where they release vasopressin and oxytocin.

Neurons in other hypothalamic nuclei regulate the adenohypophysis via the production of a group of hypophyseotropic hormones that control the secretion of anterior pituitary hormones (Fig 9–10). The hypophyseotropic hormones include releasing factors and inhibitory hormones, which, respectively, stimulate or inhibit the release of various anterior pituitary hormones.


FIGURE 9–10 Effects of hypophyseotropic hormones on the secretion of anterior pituitary hormones. CRH, corticotropin-releasing hormone; TRH, thyrotropin-releasing hormone; GnRH, gonadotropin-releasing hormone; GRH, growth hormone-releasing hormone; GIH, growth hormone-inhibiting hormone; PRH, prolactin-releasing hormone; PIH, prolactin-inhibiting hormone. (Reproduced, with permission, from Ganong WF: Review of Medical Physiology, 22nd ed. McGraw-Hill, 2005.)

Communication between the hypothalamus and adeno-hypophysis involves a vascular circuit (the portal hypophy-seal system) that carries hypophyseotropic hormones from the hypothalamus to the adenohypophysis. After their synthesis in the cell bodies of neurons located in the hypothalamic nuclei, these hormones are transported along relatively short axons that terminate in the median eminence and pituitary stalk. Here they are released and taken up by capillaries of the portal hypophyseal circulation. The portal hypophyseal vessels form a plexus of capillaries and veins that carries the hypophyseotropic hormones from the hypothalamus to the anterior pituitary. After delivery from the portal hypophyseal vessels to sinusoids in the anterior pituitary, the hypophyseotropic hormones bathe the pituitary cells and control the release of pituitary hormones. These pituitary hormones, in turn, play important regulatory roles throughout the body (Fig 9–11).


FIGURE 9–11 Anterior pituitary hormones. ACTH, adrenocorticotropic hormone; TSH, thyroid-stimulating hormone; FSH, folliclestimulating hormone; LH, luteinizing hormone; ß-LPH, beta-lipotropin (function unknown). In women, FSH and LH act in sequence on the ovary to produce growth of the ovarian follicle, ovulation, and formation and maintenance of the corpus luteum. In men, FSH and LH control the functions of the testes. Prolactin stimulates lactation. (Reproduced, with permission, from Ganong WF: Review of Medical Physiology, 22nd ed. McGraw-Hill, 2005.)


Although the hypothalamus is small (weighing 4 gm, or about 0.3% of the total brain weight), it has important regulatory functions, as outlined in Table 9–3.

Table 9–3 Principal Hypothalamic Regulatory Mechanisms.


A. Eating

A tonically active feeding center in the lateral hypothalamus evokes eating behavior. A satiety center in the ventromedial nucleus stops hunger and inhibits the feeding center when a high blood glucose level is reached after food intake. Damage to the feeding center leads to anorexia (loss of appetite) and severe loss of body weight; lesions of the satiety center lead to hyperphagia (overeating) and obesity.

B. Autonomic Function

Although anatomically discrete centers have not been identified, the posterolateral and dorsomedial areas of the hypothalamus function as a sympathetic (catecholamine) activating region, whereas an anterior area functions as a parasympathetic activating region.

C. Body Temperature

When some regions of the hypothalamus are appropriately stimulated, they evoke autonomic responses that result in loss, conservation, or production of body heat. A fall in body temperature, for example, causes vasoconstriction, which conserves heat, and shivering, which produces heat. A rise in body temperature results in sweating and cutaneous vasodilation. Normally, the hypothalamic set point, or thermostat, lies just below 37 °C of body temperature. A higher temperature, or fever, is the result of a change in the set point, for example, by pyrogens in the blood.

D. Water Balance

Hypothalamic influence on vasopressin secretion within the posterior pituitary is activated by osmoreceptors within the hypothalamus, particularly in neurons within a “thirst center” located near the supraoptic nucleus. The osmoreceptors are stimulated by changes in blood osmolarity. Their activation results in the generation of bursts of action potentials in neurons of the supraoptic nucleus; these action potentials travel along the axons of these neurons, to their terminals within the neurohypophysis, where they trigger the release of vasopressin. Pain, stress, and certain emotional states also stimulate vasopressin secretion. Lack of secretion of vasopressin caused by hypothalamic or pituitary lesions can result in diabetes insipidus, which is characterized by polyuria (increased urine excretion) and polydipsia (increased thirst).

E. Anterior Pituitary Function

The hypothalamus exerts a direct influence on secretions of the anterior pituitary and an indirect influence on secretions of other endocrine glands by releasing or inhibiting hormones carried by the pituitary portal vessels (see Fig 9–9). It thus regulates many endocrine functions, including reproduction, sexual behavior, thyroid and adrenal cortex secretions, and growth.

F. Circadian Rhythm

Many body functions (eg, temperature, corticosteroid levels, oxygen consumption) are cyclically influenced by light intensity changes that have a circadian (day-to-day) rhythm. Within the hypothalamus, a specific cell group, the suprachiasmatic nucleus, functions as an intrinsic clock. Within these cells, there are “clock genes,” including two genes called clock and per, that turn on and off with a circadian, onceper-day, rhythm (Fig 9–12). Thus, cells within the suprachiasmatic nucleus show circadian rhythms in metabolic and electrical activity, and in neurotransmitter synthesis, and appear to keep the rest of the brain on a day-night cycle. A retinosuprachiasmatic pathway carries information about the light intensity and can “entrain” the suprachiasmatic clock in order to synchronize its activity with environmental events (eg, the light-dark day-night cycle). In the absence of any sensory input, the suprachiasmatic nucleus itself can function as an independent clock with a period of about 25 hours per cycle; lesions in this nucleus cause the loss of all circadian cycles.


FIGURE 9–12 Clock genes turn on and off, once per daily cycle, within neurons of the suprachiasmatic nucleus. Top panels show that transcription of the Per1 gene peaks at about mid-day (Per1 mRNA within suprachiasmatic neurons appears black). Bottom panels show Per1 protein, which is produced after a delay of about 6 hours, peaking in the early evening. Per1 protein appears light. (Reproduced, with permission, from Mendoza J, Challet E: Neuroscientist 2009;5:480.)

G. Expression of Emotion

The hypothalamus is involved in the expression of rage, fear, aversion, sexual behavior, and pleasure. Patterns of expression and behavior are subject to limbic system influence and, in part, to changes in visceral system function (see Chapters 19 and 20).



The subthalamus is the zone of brain tissue that lies between the dorsal thalamus and the tegmentum of the midbrain. The hypothalamus lies medial and rostral to the subthalamus; the internal capsule lies lateral to it (see Fig 9–7C). The subthalamic nucleus, or body of Luys, lies dorsolateral to the upper end of the substantia nigra; it extends posteriorly as far as the lateral aspect of the red nucleus.

Fiber Connections

The subthalamus receives fibers from the globus pallidus and projects back to it (see Chapter 13); the projections from the globus pallidus to the subthalamic nucleus form part of the efferent descending path from the corpus striatum. Fibers from the globus pallidus also occupy the fields of Forel, which lie anterior to the red nucleus and contain cells that may be a rostral extension of reticular nuclei. The ventromedial portion is usually designated as field H, the dorsomedial portion as field Hj, and the ventrolateral portion as field H2. The fasciculus lenticularis (field H2) runs medially from the globus pallidus and is joined by the ansa lenticularis, which bends acutely in field H. The thalamic fasciculus extends through field Hj to the anterior ventral nucleus of the thalamus. The zona incerta is a thin zone of gray substance above the fasciculus lenticularis.


Several clinical problems related to dysfunction of the hypothalamus have been discussed previously in this chapter. Lesions in the hypothalamus are most often caused by tumors that arise from either the hypothalamus itself (eg, glioma, hamartoma, germinoma) or adjacent structures (eg, pituitary adenoma, craniopharyngioma, thalamic glioma). Somnolence or even coma may be the result of bilateral lesions of the lateral hypothalamus and its reticular formation components (see Chapter 18). Even relatively minor destruction in the hypothalamus can cause a considerable loss of function.

A vasopressin deficiency produces a syndrome of diabetes insipidus, usually in the setting of damage to the hypothalamus because of neoplastic invasion, trauma, or vascular or infectious lesions (25% of cases are idiopathic). Diabetes insipidus is characterized by polyuria (passage of large amounts of dilute urine) and polydipsia (the drinking of large amounts of fluids).

The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) results from inappropriate hypersecretion of vasopressin. The syndrome is characterized by hyponatremia with low plasma osmolality; increased urinary sodium excretion; absence of volume depletion; and normal renal, hepatic, and adrenal function. SIADH can result from inappropriate hypersecretion of vasopressin by hypothalamic neurons as a result of intracranial trauma, brain tumors, and central nervous system infections or from the inappropriate production of vasopressin by neoplastic cells in a variety of tissues, including the lungs.


The epithalamus consists of the habenular trigones on each side of the third ventricle, the pineal body (pineal gland or epiphysis cerebri), and the habenular commissure (see Fig 9–1).

Habenular Trigone

The habenular trigone is a small triangular area in front of the superior colliculus. It contains the habenular nuclei, which receive fibers from the stria medullaris thalami and are joined via the habenular commissure. The habenulointerpeduncular tract extends from the habenular nucleus to the interpeduncular nucleus in the midbrain. The function of these structures is not known.

Pineal Body

The pineal body is a small mass that normally lies in the depression between the superior colliculi (Figs 9–1 and 9–13). Its base is attached by the pineal stalk. The ventral lamina of the stalk is continuous with the posterior commissure and the dorsal lamina with the habenular commissure. At their proximal ends, the laminas of the stalk are separated, forming the pineal recess of the third ventricle. The pineal body is said to secrete hormones that are absorbed into its blood vessels.


FIGURE 9–13 Location of the circumventricular organs. There is no blood-brain barrier in these organs (see Chapter 11).


Several small areas, termed the circumventricular organs, located in or near the wall of the third ventricle, the aqueduct, and the fourth ventricle, may be of functional importance with regard to cerebrospinal fluid composition, hormone secretion into the ventricles, and the maintenance of normal cerebrospinal fluid pressure (see Fig 9–13). Most research on the circumventricular organs has been performed on experimental animals.


Lesions in the subthalamic nucleus can result in hemiballismus, a motor disorder that affects one side of the body, causing coarse flailing of the arm or leg. (In rare cases, the lesions cause ballismus, affecting both sides.) Flailing of the affected extremities may lead to severe trauma or fractures.


A 21-year-old postal worker was referred for evaluation of severe headaches of 6 months’ duration. He reported that the pain was not constant but had become more pronounced during the past month, and he felt that his eyesight had deteriorated in the past few weeks. He also stated that he now often felt cold, even in warm weather.

Neurologic examination showed partial (incomplete) bitemporal hemianopia. There was no clear papilledema, but the disks had become flattened and slightly pale. The patient had indicated that he was sexually inactive; further examination showed underdeveloped testes and the absence of pubic and axillary hair.

What is the differential diagnosis? Which imaging procedures are needed? What is the most likely diagnosis?

Cases are discussed further in Chapter 25.


A tumor in the pineal region may obstruct the cerebral aqueduct or cause inability to move the eyes in the vertical plane (Parinaud’s syndrome). One type of tumor (germinoma) produces precocious sexual development, and interruption of the posterior commissure abolishes the consensual light reflex.


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