The thalamus is found on both sides of the third ventricle and consists of numerous nuclei with different functions. It is the relay station for most of the afferent pathways that ascend to the cerebral cortex. Some types of impulses (e.g., nociceptive impulses) may already be perceived, integrated, and given an affective coloring, in an imprecise way, in the thalamus, but actual conscious experiences do not seem to be generated until sensory impulses can interact with the cerebral cortex. There exist two principal types of thalamic relay nuclei, first-order nuclei (such as the lateral geniculate nucleus) that relay input from a subcortical source (i.e., retina), and higher-order nuclei (such as the pulvinar) which connect different cortical areas to another. This thalamic division is also seen in other sensory pathways and suggests an important role of these nuclei in corticocortical communication.
The most basal portion of the diencephalon is the hypothalamus, which coordinates vital bodily functions such as respiration, circulation, water balance, temperature, and nutritional intake and is thus the hierarchically uppermost regulatory organ of the autonomic nervous system. It also influences the activity of the endocrine glands by way of the hypothalamic–pituitary axis.
The autonomic nervous system is responsible for the nerve supply of the internal organs, blood vessels, sweat glands, and salivary and lacrimal glands. It is called “autonomic” because it functions largely independently of consciousness; it is alternatively (less commonly) called the vegetative nervous system. Its efferent arm in the periphery is composed of two anatomically and functionally distinct parts, the sympathetic and parasympathetic nervous systems. The afferent arm is not divided in this way.
Because of the multiplicity of functions that the diencephalon performs, diencephalic lesions can have very diverse effects, depending on their site and extent. Thalamic lesions produce hemiparesis and hemisensory deficits, movement disorders, disturbances of consciousness, and pain syndromes, while hypothalamic lesions impair various vital functions singly or in combination, and cause endocrine dysfunction.
Location. The position of the diencephalon is just oral to that of the midbrain; the diencephalon does not continue along the brainstem axis, but rather takes a rostral bend, so that it comes to lie nearly in the longitudinal axis of the cerebrum (▶Fig. 6.1). It is located in the middle of the brain, ventrally and caudally to the frontal lobe, and encloses the lower portion of the third ventricle from both sides (▶Fig. 6.2).
The thalamus forms the upper portion of the third ventricular wall, and the hypothalamus forms its lower portion. Dorsally, the diencephalon is enclosed by the corpus callosum, the lateral ventricles, and the cerebral hemispheres (▶Fig. 6.2). The roof of the third ventricle is formed by the thin tela choroidea and the attached choroid plexus. The rostral extent of the diencephalon is delimited by the lamina terminalis and anterior commissure, its caudal extent by the posterior commissure, habenular commissure, and pineal body (epiphysis). The interventricular foramen of Monro, which connects the lateral ventricle with the third ventricle, is found on either side anterior to the rostral portion of the thalamus, just below the genu of the fornix. The basal portion of the diencephalon is its only externally visible part: it can be seen on the undersurface of the brain between the optic chiasm, the optic tract, and the cerebral peduncles. The visible diencephalic structures in this area are the mamillary bodies and the tuber cinereum, together with its infundibulum (pituitary stalk), which leads downward to the pituitary gland (cf. ▶Fig. 4.8).
The two halves of the thalamus facing each other across the third ventricle are connected in 70 to 80% of cases by the interthalamic adhesion (massa intermedia) (▶Fig. 6.1). Laterally, the diencephalon is delimited by the internal capsule.
The globus pallidus is embryologically a part of the diencephalon, though it is separated from it by the internal capsule (▶Fig. 8.4) and is thus located in the basal ganglia. It will be discussed along with the rest of the basal ganglia in ▶Chapter 8. Likewise, a discussion of the hypophysis (pituitary gland), which is linked to the hypothalamus by the infundibulum, will be deferred to the section on the peripheral autonomic nervous system.
Subdivisions. The diencephalon has the following components (▶Fig. 6.1):
The hypothalamus, which is demarcated from the thalamus by the hypothalamic sulcus, contains various functionally distinct groups of neurons. It is the hierarchically uppermost center (“head ganglion”) of the autonomic nervous system; on each side, the column of the fornix descends through the lateral wall of the hypothalamus to terminate in the mamillary body (see ▶Fig. 6.8).
The subthalamus, which mainly consists of the subthalamic nucleus (corpus luysii, ▶Fig. 6.2) and is located beneath the thalamus and dorsolateral to the mamillary body.
Flanking the third ventricle, on either side of the brain, there is a large, ovoid complex of neurons measuring about 3 × 1.5 cm in diameter. This complex, the thalamus, is not a uniform cluster of cells but rather a conglomerate of numerous, distinct nuclei, each with its own function and its own afferent and efferent connections. Each half of the thalamus (left and right) is divided into three major regions by sheetlike layers of white matter taking the form of a Y (the internal medullary laminae, ▶Fig. 6.3). The anterior nuclei sit in the angle of the Y, the ventrolateral nuclei laterally, and the medial nuclei medially. The ventrolateral nuclei are further subdivided into ventral and lateral nuclear groups. The ventral nuclei include the ventral anterior nucleus (VA), the ventral lateral nucleus (VL), the ventral posterolateral nucleus (VPL), and the ventral posteromedial nucleus (VPM). The lateral nuclei consist of a lateral dorsal nucleus and a lateral posterior nucleus. Further caudally, one finds the pulvinar, with the medial and lateral geniculate bodies attached to its underside. There are a few small groups of neurons within the internal medullary laminae (the interlaminar nuclei), as well as one larger, centrally located cell complex, the centromedian nucleus (or centre médian). Laterally, the external medullary lamina separates the thalamus from the internal capsule; the reticular nucleus of the thalamus is a thin layer of cells that is separated from the thalamus by the external medullary lamina (▶Fig. 6.2).
The three major nuclear groups (anterior, ventrolateral, and medial) have been cytologically and functionally subdivided into about 120 smaller nuclei, the most important of which are shown in ▶Fig. 6.3. There is still no uniform standard for the subdivision and nomenclature of the thalamic nuclei; the nomenclature followed in ▶Fig. 6.3 is that found in Nomina Anatomica.
In the preceding chapters, the pathways that ascend from the spinal cord, brainstem, and cerebellum to the cerebral cortex have been traced upward as far as the thalamus. The thalamus is the last major relay station for all ascending impulses (except olfactory impulses) before they continue, via thalamocortical fibers, to the cortex. ▶Fig. 6.4 shows the termination of various afferent pathways of distinct thalamic nuclei, which then project to corresponding cortical areas (for further details, see below).
Like the spinal cord and brainstem (e.g., the medial lemniscus), the thalamic nuclei of the ventral group and their thalamocortical projections maintain a strict point-to-point somatotopic organization.
Specific and nonspecific projections. Thalamic nuclei that receive input from circumscribed areas of the body periphery and transmit impulses to the corresponding circumscribed cortical areas (primary projective fields) are called specific thalamic nuclei (or primary thalamic nuclei). Thalamic nuclei projecting to the unimodal and multimodal cortical association areas (secondary and tertiary thalamic nuclei) are also counted among the specific nuclei. The distinguishing feature of the specific nuclei is thus a direct projection to the cerebral cortex.
In contrast, nonspecific thalamic nuclei receive their afferent input from multiple, distinct sense organs, usually after an intervening synapse in the reticular formation and/or one of the primary thalamic nuclei. They project only indirectly to the cerebral cortex (e.g., by way of the basal ganglia), including the association fields.
Ventral posterolateral nucleus (VPL) and ventral posteromedial nucleus (VPM). All somatosensory fibers ascending in the medial lemniscus, spinothalamic tract, trigeminothalamic tract, etc., terminate in a relay station in the ventroposterior nuclear complex of the thalamus. The ventral posterolateral nucleus is the relay station for the medial lemniscus, while the ventral posteromedial nucleus is the relay station for trigeminal afferents. These nuclei, in turn, project fibers to circumscribed areas of the somatosensory cortex (areas 3a, 3b, and 2, ▶Fig. 6.4).
Furthermore, gustatory fibers from the nucleus of the tractus solitarius terminate in the medial tip of the ventral posteromedial nucleus, which, in turn, projects to the postcentral region overlying the insula (▶Fig. 6.4).
Medial and lateral geniculate bodies. The medial and lateral geniculate bodies, too, are among the specific nuclei of the thalamus. The optic tract terminates in the lateral geniculate body, which relays visual impulses retinotopically, by way of the optic radiation, to the visual cortex (area 17). Auditory impulses are carried in the lateral lemniscus to the medial geniculate body and relayed tonotopically, by way of the auditory radiation, to the auditory cortex (transverse temporal gyri of Heschl, area 41) in the temporal lobe (▶Fig. 6.5).
Ventral oral nuclei and ventral anterior nucleus. The ventral oral posterior nucleus (a portion of the ventral lateral nucleus) receives input from the dentate nucleus and red nucleus by way of the dentatothalamic tract (▶Fig. 6.4) and projects to the motor cortex (area 4), while the ventral oral anterior nucleus and the ventral anterior nucleus (VA), both of which also belong to the ventral nuclear group, receive input from the globus pallidus and project to the premotor cortex (areas 6aα and 6aβ) (▶Fig. 6.4).
The anterior nucleus, the medial nucleus, and the pulvinar are secondary and tertiary higher-order thalamic nuclei (▶Fig. 6.5, ▶Fig. 6.6), i.e., specific thalamic nuclei projecting to the unimodal and multimodal cortical association fields. These nuclei mostly receive their input not from the periphery but rather after a synaptic relay, which is usually located in one of the primary thalamic nuclei described. Connections with the cerebral cortex are reciprocal: thus, the cortex can directly affect the relaying function of the thalamus. Ventral portions are connected to visual areas, dorsal portions to temporo-parieto-frontal areas. The most commonly postulated functions so far of these nuclei are visual attentiveness and visuo-motor integration, but more recent studies also suggest involvement in multimodal sensorimotor integration and cognitive functions.
Anterior nucleus. The anterior nucleus (▶Fig. 6.6) is reciprocally connected to the mamillary body and fornix through the mamillothalamic tract (of Vicq d’Azyr); it possesses bidirectional, point-to-point connections with the cingulate gyrus (area 24) and is thus an integral part of the limbic system, whose structure and function are described in ▶Chapter 7.
Medial nucleus. The medial nucleus of the thalamus has bidirectional, point-to-point connections with the association areas of the frontal lobe and the premotor region. It receives afferent input from other thalamic nuclei (ventral and intralaminar nuclei), and from the hypothalamus, midbrain nuclei, and globus pallidus (▶Fig. 6.5).
Destruction of the medial nucleus by a tumor or other process causes a frontal lobe syndrome with personality changes (loss of self-representation, as described by Hassler), just as has been described after frontal leukotomy—a psychosurgical procedure, now rarely, if ever, performed, in which a lesion is made in the deep white matter of the frontal lobe. The visceral impulses that reach this nucleus by way of the hypothalamus exert an influence on the affective state of the individual, leading to a sense of well-being or uneasiness, good or bad mood, etc.
Pulvinar. The pulvinar possesses reciprocal, point-to-point connections with the association areas of large parts of the cortices (▶Fig. 6.5). These association areas are surrounded by the primary somatosensory, visual, and auditory cortices and thus probably play a major role in the binding of these different types of incoming sensory information. The pulvinar also receives neural input from other thalamic nuclei, especially the intralaminar nuclei. The so-called “visual pulvinar” includes the inferior and lateral pulvinar, which have been shown to be involved in higher-order visual functions such as allocation of spatial attention. The medial pulvinar has widespread connections with nonsensory or association parts of the cortex, and the anterior portion of the pulvinar is connected tothe somatosensory system, thus pointing to a role in sensorimotor (eye–hand) and possibly multimodal integration.
Lateral nuclei. The lateral dorsal nucleus and the lateral posterior nucleus do not receive any neural input from outside the thalamus and are connected only to other thalamic nuclei. They are thus known as integrative nuclei.
Intralaminar nuclei. The intralaminar nuclei are the most important component of the nonspecific thalamic projection system. These nuclei are located within the internal medullary lamina, and the largest among them is the centromedian nucleus. These cell complexes receive their afferent input through ascending fibers from the brainstem reticular formation and the emboliform nucleus of the cerebellum, as well as from the internal pallidal segment and other thalamic nuclei. They project not to the cerebral cortex but rather to the caudate nucleus, putamen, and globus pallidus (▶Fig. 6.6). They probably also send efferent impulses diffusely to all nuclei of the thalamus, which then, in turn, project to widespread secondary areas of the cerebral cortex. The centromedian nucleus is an important component of the intralaminar cell complex, which constitutes the thalamic portion of the ARAS (or arousal system). Another portion of this arousal system probably involves the subthalamus and hypothalamus.
Furthermore, it is a relay station for all impulses arising in cutaneous and visceral sensory receptors, for visual and auditory impulses, and for impulses from the hypothalamus, cerebellum, and brainstem reticular formation, all of which are processed in the thalamus before being transmitted onward to other structures. The thalamus sends a small efferent component to the striatum, but most of its output goes to the cerebral cortex. All sensory impulses (other than olfactory impulses) must pass through the thalamus before they can be consciously perceived. Thus, the thalamus was traditionally called “the gateway to consciousness,” though the conscious perception of smell implies that this conception is flawed and perhaps misleading.
The thalamus, however, is not merely a relay station, but an important center for integration and coordination, in which afferent impulses of different modalities, from different regions of the body, are integrated. A neural substrate of certain elementary phenomena such as pain, displeasure, and well-being is already present in the thalamus before being transmitted upward to the cortex.
Some thalamic nuclei are also components of the ARAS, a specific arousal system originating in nuclei that are diffusely located throughout the brainstem reticular formation. Activating impulses from the ARAS are relayed by certain thalamic nuclei (ventral anterior nucleus, intralaminar nuclei [particularly the centromedian nucleus], reticular nuclei) to the entire neocortex. An intact ARAS is essential for normal consciousness.
Lesions of intralaminar nuclei. The ventral anterior (VA), intralaminar, and reticular nuclei are nonspecific “activating” nuclei. They project diffusely to the frontal lobes (ventral anterior nucleus, cf. ▶Fig. 6.4) and the entire neocortex (intralaminar nuclei), and they serve to modulate cortical responses. These pathways are components of the ARAS. Lesions in this area, particularly bilateral lesions, cause disturbances of consciousness and attention, and, if they extend to the midbrain tegmentum, vertical gaze palsy. Less commonly, paramedian lesions can cause agitation, dysphoria, or acute confusion. Lesions in this area, particularly bilateral lesions, cause disturbances of consciousness and attention, and, if they extend to the midbrain tegmentum, vertical gaze palsy. Less commonly, paramedian lesions can cause agitation, dysphoria, or acute confusion. Isolated lesions of the left anterior nuclei have been reported to cause anomia, word-finding difficulties, and memory impairments; right-sided lesions in this area have also been reported to cause more complex disturbances of mood, e.g., manic state and logorrhea, or, alternatively, delirium with confabulations and inappropriate behavior. Bilateral medial thalamus lesions can cause transient amnesia with or without anosognosia.
This 51-year-old male schoolteacher was attending a friend’s funeral when he suddenly fell and complained of nausea and a pulsatile headache. He had been standing in the hot sun during the eulogy, and the other funeral attendees at first thought he had simply fainted. When he was still unable to get up unaided and continued to complain of headache 10 minutes later, they called an ambulance. The emergency physician on the scene found an arterial blood pressure of 220/120 mm Hg and weakness of the left hand and the entire left lower limb, and the patient was transported to the hospital. Examination on admission revealed central-type left hemiparesis with increased deep tendon reflexes, as well as hypesthesia and hypalgesia near the midline, pallanesthesia, and a mild deficit of position sense on the left side of the body. A CT scan revealed an acute hemorrhage in the right basal ganglia and thalamus (▶Fig. 11.30).
Over the next 6 months, the patient’s hemiparesis and hemisensory deficit largely resolved, and he was able to resume playing tennis. In the same period of time, however, he began to experience repeated bouts of paroxysmal pain and dysesthesia in the previously hypesthetic areas on the left side of the body. These abnormal sensations were partly electric in character. An MRI scan of the head at this time revealed only a small remnant of the initial hemorrhage, with formation of a cyst in the right thalamus. The pain improved considerably on treatment with carbamazepine and amitriptyline but returned promptly as soon as the patient tried to stop taking these medications. They could finally be discontinued with a slow taper after a further 3 years.
Lesions of the ventral nuclei. As described, the ventral posterior nuclei are relay stations for specific sensory impulses, which are then sent onward to the corresponding primary cortical areas. Lesions of these nuclei produce specific deficits of one or more sensory modalities, as follows.
Lesions of the ventral posterolateral nucleus produce contralateral impairment of touch and proprioception, as well as paresthesias of the limbs, which may feel as if they were swollen or abnormally heavy.
Lesions affecting the basal portion of the ventral posterolateral and/or posteromedial nucleus can produce severe pain syndromes in addition to the sensory deficits just described (“thalamic pain,” sometimes in anesthetic areas—“anesthesia dolorosa”; see ▶Case Presentation 6.1).
Lesions of the ventral lateral nucleus have mainly motor manifestations, as this nucleus is mainly connected to the primary and secondary motor areas of the cerebral cortex, and to the cerebellum and basal ganglia.
Acute lesions of the ventral lateral nucleus and the neighboring subthalamic region can produce severe central “weakness,” in which direct peripheral testing reveals no impairment of raw muscle strength (e.g., against resistance) (“thalamic astasia”). The patient falls to the side opposite the lesion and may be unable to sit unaided. Such manifestations appear either in isolation or in conjunction with transient thalamic neglect, in which both sensory and motor function is neglected on the side opposite the lesion. Thalamic neglect, due to involvement of the pulvinar and/or thalamocortical fibers projecting to the parietal lobe, is usually short-lasting and almost always resolves completely.
Lesions affecting the dentato-rubro-thalamic projections of the ventral lateral nucleus (VL) produce contralateral hemiataxia with action tremor, dysmetria, dysdiadochokinesia, and pathological rebound. Such findings may give the erroneous impression of a cerebellar lesion.
The thalamus is supplied by four arteries. Interruption of the arterial blood supply in each of these distributions causes a characteristic syndrome, as described in ▶Arteries of the Posterior Fossa, Chapter 11.
The epithalamus consists of the habenula with its habenular nuclei, the habenular commissure, the stria medullaris, and the epiphysis. The habenula and the habenular nuclei constitute an important relay station of the olfactory system. Afferent olfactory fibers travel by way of the stria medullaris thalami to the habenular nuclei, which emit efferent projections to the autonomic (salivatory) nuclei of the brainstem, thus playing an important role in nutritional intake.
Epiphysis (pineal gland). This gland contains specialized cells, called pinealocytes. Calcium and magnesium salts are deposited in the epiphysis from approximately age 15 years onward, making this structure visible in plain radiographs of the skull (an important midline marker before the era of CT and MRI). Epiphyseal tumors in childhood sometimes cause precocious puberty; it is thus presumed that this organ inhibits sexual maturation in some way, and that the destruction of epiphyseal tissue can remove this inhibition. In lower vertebrates, the epiphysis is a light-sensitive organ that regulates circadian rhythms. In primates, light cannot penetrate the skull, but the epiphysis still indirectly receives visual input relating to the light–dark cycle. Afferent impulses travel from the retina to the suprachiasmatic nucleus of the hypothalamus, from which, in turn, further impulses are conducted to the intermediolateral nucleus and, via postganglionic fibers of the cervical sympathetic chain, to the epiphysis.
The subthalamus is found immediately caudal to the thalamus at an early stage of embryological development and then moves laterally as the brain develops. It comprises the subthalamic nucleus, part of the globus pallidus (see ▶Nuclei, Chapter 8), and various fiber contingents that pass through it on their way to the thalamus, including the medial lemniscus, the spinothalamic tract, and the trigeminothalamic tract. All of these tracts terminate in the ventroposterior region of the thalamus (▶Fig. 6.4). The substantia nigra and red nucleus border the subthalamus anteriorly and posteriorly. Fibers of the dentatothalamic tract travel in the prerubral field H1 of Forel to terminate in the ventro-oral posterior nucleus of the thalamus (a part of the ventral lateral nucleus, VL); fibers from the globus pallidus travel in the lenticular fasciculus (Forel’s fasciculus H2) to the ventro-oral anterior nucleus (another part of VL) and the ventral anterior nucleus (VA). These tracts are joined more rostrally by the ansa lenticularis. The subthalamus also contains the zona incerta, a rostral continuation of the midbrain reticular formation. The major connections of the putamen, pallidum, subthalamus, and thalamus are depicted in ▶Fig. 6.7.
Function. The subthalamic nucleus (corpus Luysii) is, functionally speaking, a component of the basal ganglia and has reciprocal connections with the globus pallidus (see ▶Nuclei, Chapter 8). Lesions of the subthalamic nucleus produce contralateral hemiballism.
The hypothalamus (▶Fig. 6.8) is composed of gray matter in the walls of the third ventricle from the hypothalamic sulcus downward and in the floor of the third ventricle, as well as the infundibulum and the mamillary bodies. The posterior pituitary lobe, or neurohypophysis, is also considered part of the hypothalamus; this structure is, in a sense, the enlarged caudal end of the infundibulum. The anterior pituitary lobe, on the other hand, is not derived from the neuroectoderm at all, but rather from Rathke’s pouch, an outcropping of the rostral end of the primitive alimentary tract. The two pituitary lobes, though adjacent to each other, are not functionally connected. Remnants of Rathke’s pouch in the sellar region can grow into tumors, e.g., craniopharyngioma.
The columns of the fornix, as they descend through the hypothalamus to the mamillary bodies on either side, divide the hypothalamus of each side into a medial and a lateral segment (▶Fig. 6.8). The lateral segment contains various groups of fibers, including the medial forebrain bundle, which runs from basal olfactory areas to the midbrain. It also contains the lateral tuberal nuclei. The medial segment, in contrast, contains a number of more or less clearly distinguishable nuclei (▶Fig. 6.8), which are divided into an anterior (rostral), a middle (tuberal), and a posterior (mamillary) nuclear group.
Anterior nuclear group. The important members of this group are the preoptic, supraoptic, and paraventricular nuclei (▶Fig. 6.8). The latter two nuclei project, by way of the supraopticohypophyseal tract, to the neurohypophysis (see ▶Fig. 6.10 and ▶Fig. 6.11).
Middle nuclear group. The important members of this group are the infundibular nucleus, the tuberal nuclei, the dorsomedial nucleus, the ventromedial nucleus, and the lateral nucleus (or tuberomamillary nucleus) (▶Fig. 6.8).
Posterior nuclear group. This group includes the mamillary nuclei (the supramammillary nucleus, the mamillary nucleus, the intercalate nucleus, and others) and the posterior nucleus (▶Fig. 6.8). This area has been termed a dynamogenic zone (Hess), from which the autonomic nervous system can be immediately called into action, if necessary.
The neural connections of the hypothalamus (▶Fig. 6.9 and ▶Fig. 6.10) are multifarious and complex. In order to carry out its function as the coordinating center of all autonomic processes in the body (see ▶Functions of the Hypothalamus), the hypothalamus must communicate via afferent and efferent pathways with very many different areas of the nervous system. Information from the outside world reaches it through visual, olfactory, and probably also auditory pathways. The presence of cortical afferents implies that the hypothalamus can also be influenced by higher centers. The major connections of the hypothalamus are to the cingulate gyrus and frontal lobe, the hippocampal formation, the thalamus, the basal ganglia, the brainstem, and the spinal cord.