The human brain can be subdivided by many classification systems. One particular nomenclature that refers to the duality of the brain is the diencephalon. It is the caudal part of the forebrain (prosencephalon) that occupies the central region of the brain. The diencephalon is comprised of the:
- Hypophysis cerebri
In the following article we will explore these different parts of diencephalon as well as its function.
- Gross Anatomy
- The Metathalamus
- Hypophysis Cerebri
- Clinical Significance
- Related diagrams and images
Each of the components of the diencephalon has specialized functions that are integral to life. The diencephalon acts as a primary relay and processing center for sensory information and autonomic control. The plethora of communicating pathways between these structures and other parts of the body makes the diencephalon a functionally diverse area. Some of these connections include pathways to the limbic system (seat of memory and emotion), basal ganglia (motor coordination), as well as primary sensory areas, such as auditory or visual.
This article will explore the embryology of the diencephalon, as well as the gross anatomy and function of its various components. Clinically significant points relating to this region of the brain will also be discussed.
The anterior most part of the primary cerebral vesicles of the embryo gives rise to the prosencephalic portion of the foetal brain. At about the 5th week of development, the prosencephalon is further subdivided into a ventral telencephalon (that differentiates to form the cerebral hemispheres) and a caudal diencephalon (secondary cerebral vesicles). The latter originates from the median region of the prosencephalon. In utero, the region consists of two lateral alar plates (representing sensory areas), a roof plate (most dorsal part of the neural tube), and the third ventricle. The scientific community is unclear whether or not basal plates (representing motor areas) exist as it is not physically observed, but the corresponding biomarkers have been identified.
The alar plates give rise to the lateral walls of the third ventricle (and by convention, the medial walls of the thalamus). Rapid cellular proliferation results in medial projection of the thalamus into the diencephalic cavity (future space of the third ventricle), resulting in a midline fusion of a portion of the thalamus known as the massa intermedia or the interthalamic connexus (adhesions). A shallow groove known as the hypothalamic sulcus emerges and divides the walls of the diencephalon into the thalamus (dorsally) and the hypothalamus (ventrally). The roof plate is comprised of a monolayer of ependymal cells that is coated with vascular mesenchyme. This area subsequently differentiates into the choroid plexus of the third ventricle. Caudally, the roof plate differentiates into the epiphysis (pineal body).
The hypothalamus further differentiates into a variety of nuclear regions that are responsible for an eclectic collection of body functions. These include, but are not limited to, digestion, thermoregulation, and circadian regulation. Caudal to the hypothalamus is the hypophysis cerebri (pituitary gland). It originates from both ectodermal and neuroglial tissue and as a result, it can be subdivided into the adenohypophysis and the neurohypophysis.
Of note, the prosencephalon also gives rise to the optic cup and stalk, which subsequently develops into the retina of the eye.
There are several structures between the brainstem and the cerebral cortex that make up the diencephalon. These include the epithalamus, thalamus, subthalamus, metathalamus, hypothalamus, hypophysis cerebri and the third ventricle as its cavity. The medial and lateral geniculate bodies, which are collectively called the metathalamus, along with the pulvinar, are frequently regarded as an integral part of the dorsal thalamus.
The third ventricle is a narrow vertical midline cleft between and below the two lateral ventricles and in between left and right thalami. The lateral ventricles communicate with the third ventricle via the interventricular foramen of Monro. It also communicates with the fourth ventricle posteroinferiorly via the cerebral aqueduct of Sylvius.
It possesses a roof, a floor and four walls: anterior, posterior and two lateral.
- The roof is formed by the thin tela choroidea, which is a combination of two membranes, the ependyma and pia mater. Within the tela choroidea are two plexuses of blood vessels (one on either side of the middle line) that bulge downwards into the cavity of the third ventricle. These are the choroid plexuses of the third ventricle which functions as a point of production of the cerebrospinal fluid (CSF).
- The floor is made up of the optic chiasm, the tuber cinereum and infundibulum, the mammillary bodies, the posterior perforated substance and the uppermost part of the mesencephalic tegmentum.
- The anterior wall is the delicate lamina terminalis, as well as the anterior commissure and anterior column of the fornix..
- The short posterior wall is formed by the stalk of the pineal gland, posterior commissure and the Habenular commissures.
- The lateral walls are of the cavity are formed by the medial walls of each thalami. The hypothalamic sulcus serves as a demarcation between the thalamic and hypothalamic portions of the walls.
The diencephalon is richly supplied by several blood vessels, notably the thalamogeniculate branches of the posterior cerebral artery and thalamoperforating branches of the posterior cerebral artery and posterior communicating artery.
The epithalamus lies in relation to the posterior part of the roof of the third ventricle and the little adjoining part of its lateral wall. It consists of the following parts:
- Stria medullaris
- Posterior commissure
- Habenular nuclei (medial and lateral)
- Pineal body
- Paraventricular nuclei (anterior and posterior)
The stria medullaris thalami lie close to the taenia thalami as a bundle of fibres along the junction of the medial and superior surfaces of the thalamus. It begins near the anterior pole of the thalamus and runs posteriorly toward the Habenular trigone. From the stria medullaris thalami, some fibres cross in the superior or anterior lamina of the pineal stalk to reach the Habenular nuclei of the opposite side. These fibres constitute the Habenular commissure, some of which also connect the amygdaloid and hippocampal complexes of the right and left cerebral hemispheres. The posterior commissure lies in the inferior lamina of the stalk of the pineal body. A number of small nuclei are present in relation to the commissure, such as the interstitial and dorsal nuclei of the posterior commissure, the nucleus of Darkschewitsch and the interstitial nucleus of Cajal (both nuclei communicate with the vestibular nuclei via the medial longitudinal fasciculus).
The pineal gland is a small piriform structure located in relation to the posterior wall of the third ventricle. It is an endocrine gland of considerable significance and is made up of cells called pinealocytes, which secrete melatonin in response to darkness. The pineal body also secretes a number of hormones that have important regulatory influence on many endocrine organs including the hypophysis cerebri, thyroid, parathyroids, adrenals and gonads. Hormones of the pineal gland reach the hypophysis cerebri through the blood stream and the cerebrospinal fluid (CSF). As humans age, the pineal glands become calcified and form what are known as corpora arenacea or brain sand.
The thalamus is the largest mass of grey matter of the diencephalon that is laterally related to the third ventricle. The symmetrical halves of this midline structure are located between the cerebral cortices and the midbrain. It has an anterior and a posterior pole, as well as superior, inferior, medial and lateral surfaces. Its superior part is covered by a thin layer of white matter called the stratum zonale and its lateral surface is covered by a similar layer called the external medullary lamina.
The thalamus also comprises several nuclei, such as the:
- Dorsomedial nucleus
- Midline nuclei
- Geniculate bodies (lateral and medial)
- Anterior nuclei
- Intralaminar nuclei
- Lateral dorsal nuclei
- Lateral posterior nuclei
- Ventral anterior nuclei
- Ventral posterior (medial and lateral)
- Ventral lateral nuclei
The anterior pole of the thalamus lies just behind the interventricular foramen of Monro.
Its posterior pole makes up the pulvinar, and lies just superior and lateral to the superior colliculus. The medial and lateral geniculate bodies are connected to the inferior and superior colliculi by the inferior and superior brachium quadrigeminum, respectively.
The medial surface forms the greater part of the lateral wall of the third ventricle, and is lined by ependyma. A mass of grey matter called the interthalamic adhesion (connexus) is found attached to the medial surfaces of the two thalami and this connexus interconnects the left and right thalami. Inferiorly, the medial surface is separated from the hypothalamus by the hypothalamic sulcus.
The internal capsule is related to the lateral surface of the thalamus and separates this surface from the lentiform nucleus (globus pallidus and putamen) of the basal ganglia.
The thalamostriate vein and a bundle of fibres called the stria terminalis are in close apposition to the dorsal or superior surface of the thalamus, and these structures separate the thalamus from the caudate nucleus of the basal ganglia.
The inferior surface of the thalamus is related to the hypothalamus.
The thalamus and caudate nucleus form the floor of the central part of the lateral ventricles. However, the medial part of the superior surface of the thalamus is separated from these ventricles by the fornix, and by a fold of pia mater called the tela choroidea. At the junction of the medial and lateral surfaces of the thalamus the ependyma of the third ventricle is reflected from the lateral wall to the roof. The line of reflection is marked by a line called the taenia thalami, underneath which there is a narrow bundle of fibres called the stria medullaris thalami.
Characteristics & Components
The subthalamus refers to the part of the diencephalon that lies below the posterior part of the thalamus just behind and lateral to the hypothalamus. It includes nuclei and grey matter such as the zona incerta, reticular nucleus, and the perigeniculate nucleus. The zona incerta provides gamma-aminobutyric acid stimulation (GABAergic) to the thalamus; while the reticular nucleus provides GABAergic regulation to the thalamocortical pathway. Collectively, the pre-geniculate nucleus and the lateral geniculate nucleus form the lateral geniculate complex.
The subthalamus is continuous with the upper ends of the red nucleus and substantia nigra of the tegmentum of the midbrain inferiorly. Laterally it reaches the lowest part of the internal capsule.
The pre-geniculate nucleus has connections similar to the lateral geniculate nucleus and includes fibres from the retina, pretectal region and superior colliculus, thus playing a role in vision and eye movements. The zona incerta has strong connections with the reticular nucleus of the thalamus which it connects as a thin lamina of grey matter. It is believed to be involved in the regulation of visceral activities such as sexuality, hydration and food intake as well as cardiovascular activity.
Fibres emerging from the dorsal thalamus (thalamus proper) traverse the ventral thalamus through the reticular nucleus. These fibres give the nucleus a reticulated appearance, hence the name. The reticular nucleus is made of a thin layer of neurons covering the lateral aspect of the dorsal thalamus, and is also related to the internal capsule. Inferiorly it becomes partially continuous with the zona incerta. The main efferent fibers of the reticular nucleus pass to the dorsal thalamus; however afferents reach it from the nucleus cuneiformis (in the reticular formation of the midbrain).
Other connections of the subthalamus include afferents from the cerebral cortex, putamen, globus pallidus, trigeminal nuclei, cerebellar nuclei and pretectal region. These afferents reach the reticular nucleus and zona incerta through which it sends efferent fibers to those structures and the spinal cord. The ventral thalamus also has connections with the dentate nucleus, cerebral peduncle, fasciculus lenticularis, ansa lenticularis, pre-rubral field and thalamic fasciculus.
The metathalamus consists of two oval eminences (the geniculate bodies) on the caudal surface of the diencephalon, just inferior to the caudal end of the dorsal thalamus. The lateral and medial geniculate bodies function as primary thalamic relay stations for the auditory and optic system, respectively.
Medial Geniculate Body
The medial geniculate body receives tonotopically (arrangement of sound based on frequency on the brain) organized auditory information from the inferior colliculus of the quadrigemini, via the brachium of the inferior colliculus. Processed information from the medial geniculate body is then relayed via the auditory radiation to the primary auditory cortex on the transverse gyrus of Heschel (i.e. the superior temporal gyrus). The medial geniculate body consists of three major divisions:
- the dorsal division, consisting of the posterior part of the parvocellular nucleus
- the medial division, or magnocellular nucleus
- the ventral division, consisting of the ventral part of the parvocellular nucleus.
Lateral Geniculate Body
The lateral geniculate body receives retinotopic (mapping of visual input on the brain) input from the contralateral visual field via the optic tract. Information is relayed from the lateral geniculate in a topographic manner via the optic radiation (Meyer’s loop) to the primary visual cortex surrounding the calcarine sulcus in the occipital lobe. The lateral geniculate body consists of layers of neurons, and the visual information received is divided among the various layers.
As the name suggests, the hypothalamus is the part of the diencephalon that lies below the thalamus. Like the thalamus, it comprises several subdivisions and nuclei, including the periventricular zone, the medial zone and the lateral zone. On the medial side, it forms the wall of the third ventricle below the level of the hypothalamic sulcus. Posteriorly, the hypothalamus merges with the ventral thalamus, and through it with the tegmentum of the midbrain.
Anteriorly, it extends up to the lamina terminalis, and merges with certain olfactory structures in the region of the anterior perforated substance. Inferiorly, the hypothalamus is related to structures in the floor of the third ventricle. These are the tuber cinereum, the infundibulum, and the mammillary bodies, which are considered part of the hypothalamus.
Nuclei & Areas
The hypothalamus also includes the:
- Preoptic area - involved in thermoregulation
- Mammillary nuclei - aid in memory and cognition as part of the circuit of Papez
- Paraventricular nucleus - an important autonomic control centre
- Suprachiasmatic nucleus - circadian rhythm control
- Arcuate (or infundibular) nucleus - provides inhibition of prolactin secretion by the pituitary gland and control of hunger
- Posterior nucleus - involved in thermoregulation
- Anterior nucleus - forms a part of the hippocampal system for episodic memory
- Dorsomedial nucleus - aids in circadian rhythm regulation
- Ventromedial nucleus - serves as the satiety centre for regulation of feeding behaviour and body weight
- Lateral hypothalamus - aids in coordinating swallowing. Lesions in this area lead to aphagia and adipsia
- Supra-optic nucleus - facilitates secretion of vasopressin for osmoregulation
- Tuberomammillary nucleus - single source of histamine neurons
- Lateral tuberal nucleus - involved in regulation of feeding and metabolism
- Intermediate nucleus - regulates sleep
Functionally the hypothalamus is involved in the control of several cognitive behaviours, mainly owing to its connections with anatomical areas responsible for or involved in these activities. However the main functions attributed to the hypothalamus include the regulation of eating and drinking behaviour, regulation of sexual activity and reproduction, and the control of autonomic activity. Other activities of the hypothalamus include regulation of emotional behaviour, control of several endocrine activities, response to stress, temperature regulation, as well as the control of circadian rhythms.
The small projection from the ventral aspect of the base of the brain is often called the pituitary gland, but is otherwise known as the hypophysis cerebri. This 12 mm by 8 mm ovoid structure is a continuation of the infundibulum of the hypothalamus. It is encased by the sella turcica of the sphenoid bone in the middle cranial fossa and crossed superiorly by the optic chiasm.
The pituitary gland has dual embryonic origins and is consequently also divided based on the functionality of each component. The highly vascular adenohypophysis (which originated from ectoderm) is responsible for the synthesis of trophic hormones such as adrenocorticotropic, follicle-stimulating hormone, growth hormone, luteinizing hormone and others. The neurohypophysis is a derivative of neuroglial cells and is responsible for storing hormones produced by the hypothalamus.
Diencephalic (Russell’s) Syndrome
It should be noted that a lesion (vascular or neoplastic) of any part of the diencephalon may result in a deficit in the function associated with that component. For example, an insult to the supraoptic nucleus of the hypothalamus can impair the production and subsequent release of vasopressin.
Diencephalic (Russell’s) syndrome is a rare disorder characterized by:
- severe emaciation with normal caloric intake
- locomotor hyperactivity
- non-anaemic pallor
Neoplastic insults of the optic and hypothalamic region are the primary cause of this disorder. The syndrome is one of the major causes of failure to thrive among paediatric patients. Fortunately, it seldom prohibits the patient from achieving their developmental milestones.
Global deficiency of pituitary hormones is clinically classified as a panhypopituitarism syndrome. This may result from either local impairment of the gland or dysregulation of the hypothalamus. Iatrogenic insults to the pituitary gland (radiation therapy), postpartum pituitary necrosis and traumatic brain injury can also result in hypopituitarism.
Patient presentation is dependent on which hormone(s) is (are) predominantly deficient. For example, a deficiency in growth hormone will result in failure to thrive in children; while low levels of thyroid stimulating hormone would cause hypothyroidism.