1    The history of the thalamus

Acknowledge their energy. If you condemn their violence in a violent age speak of their courage. Mock their pride when, having built as well, in as wide a compass, you have none.
Jon Stallworthy, Epilogue to an Empire (1998)

Sketch of a trireme, fourth to fifth century BC. From Casson (1971).

Galen and the origin of the word thalamus

Sir Wilfrid Le Gros Clark, one of the most distinguished of British neuroanatomists, relates in his autobiography (Clark, 1968) that reference to him as one who had “put in some good work on the thalamus,” once led to considerable amusement in an Oxford senior common room. With their classical backgrounds, those dining that evening appreciated that the Greek word thalamos (θɑƛɑμoΣ) referred not only to an inner room but commonly also to a bridal chamber or bridal couch. Used in reference to marriage, consummation, and the continuity of the tribe, the word appears commonly in Homer,¹ and later in Roman writers from Virgil² on (from whom we get thalamus). This sense has come down to us in the poetic, epithalamion. The connotation of sexual behavior was rendered very explicitly in the works of the Roman poets Ovid, Horace, Propertius, and Petronius.³ Writing later, in the sixteenth century, Rabelais⁴ called the flagship of the Pantagruelist, on their voyage to seek advice from the Oracle of the Holy Bottle regarding the virtue of Panurge’s future wife, the “Thalamège”, the name of the barge upon which Anthony and Cleopatra at the height of their love affair floated on the Nile. There can be no doubt about his meaning either. In similar vein, Don Quixote’s visions of his life to be with Dulcinea del Toboso are punctuated by soulful references to “el tálamo.”⁵ The old meaning of thalamus survives in the French synonym couche optique and was unquestionably in Burdach’s (1822) mind when he named a posterior protrusion of the human thalamus, Polster or pillow, a term that later became Latinized as pulvinar.⁶

   Thalamos for an innermost room, storeroom, sleeping chamber, or room of the women has a very old usage in Greek. The basic layout of the archaic Greek house (Fig. 1.1) was retained in farmlands and in industrial areas of cities such as Athens into Roman times; it was built around a central courtyard or aule with an open portico or pastas across its northern end. Behind the pastas opened a series of inner rooms, among which would be included thalamoi (Ryder, 1916; Quennell and Quennell, 1931; Graham, 1938; J. E. Jones et al., 1962). Thalamos, as a room connecting directly or via a passageway with the aule, appears frequently in the Odyssey,⁷

and in the description of the activities surrounding Odysseus’ return to Ithaca and his destruction of the suitors, there is so much movement in and out of inner rooms that scholars have used these passages to reconstruct the layout of a palace of Homeric times.

Fig 1.1    Typical Greek houses. Left: plan and reconstruction of a typical Greek house of the archaic period, from ruins discovered at Dystus, Euboea. The house is built around an open courtyard or aule. Behind the portico, or pastas, lie sleeping chambers and storerooms generally known as thalamoi. From Quennell and Quennell (1931). Right: reconstruction of a Greek villa of the fourth to fifth century BC at Olynthus, Chalcidice. From Graham (1938).

   The first extant anatomical usage of thalamus has been traced to Galen, who wrote in Greek in the second century AD. In applying the term, he seems to have had the concept of a storeroom in mind but appears to have applied the word to something other than the large diencephalic mass that we call the thalamus. In Book Ⅸ of his Anatomical Procedures, Galen seems to imply that he had seen the lateral geniculate body by dissecting the optic tract to it, but he does not refer to thalamus. Then, in De Usu Partium, Galen (Book 16, section 3) makes it clear that he believed that the optic tracts arose from a region where the lateral ventricles come together at the back of the diencephalon adjacent to the lateral geniculate bodies. This region, he said, is “a thalamus of the ventricles . . . made for the sake of . . . [the optic] . . . nerves.” By means of this communication with the nerves, he felt that the pneuma, or animating principle, infused with animal spirits in the rete mirabile, brain, and ventricles, could pass via a lumen that he postulated in the optic nerves, to the eyes. According to Marcus Singer, in a note to Book 8 of May’s (1968) translation of Galen’s De Usu Partium, the communication that Galen observed in the ox brain was probably the choroid fissure of the descending part of the lateral ventricle, torn open where it lies on top of the lateral geniculate body. The appearances that seem to have misled Galen can be obtained by dissecting the brain from behind, as in Fig. 1.2.

   Galen was obviously referring to a reservoir or to a funnel through which the pneuma could reach the optic nerve, so it would have been appropriate for him to use this term for what he perceived as a chamber for the distillation and storage of pneuma. Walker’s (1938a) suggestion of a term deriving from an Egyptian word for an antechamber is less plausible, although thalamus for an antechamber still sometimes appears in archeological writings. Perhaps Galen also saw the chamber at what he regarded as the commencement of the optic nerves as a center for regeneration, renewal, and continuity. Such a sense is often implied by the contexts in which Virgil used the word thalamus and is present in the occasional use of the word in botany to refer to a receptacle from which carpels arise and within which embryonic seeds may develop.

   The use of thalamus in the sense of bridal couch or bridal chamber by the classical Latin writers must have been known to Galen. For one who had referred to the corpora quadrigemina as nates and testes, the point of attachment of the pineal body as an anus, and the infundibular recess as a pelvis, it would be in character for him to introduce a note of levity in naming a new structure or region. However, it is by no means clear that this is exactly what Galen had in mind. He may also have seen in the dissection of the optic nerve springing from this chamber a fanciful resemblance to an oar of a galley springing from the inner chamber or thalamos of the vessel. Elsewhere in De Usu Partium (Book 1, section 24), he used the analogy of the different lengths of oars in a trireme in considering the functional necessity for having fingers of different lengths. The rower in what is now agreed to have been the lowest bench of an Athenian fighting trireme (trieres) of the fifth century BC was referred to as thalamite (thalamios) and his oarport as thalamia (Morrison and Williams, 1968; Sleeswyk, 1982) (Fig. 1.3). The disadvantages of occupying this position are summed up by Aristo- phanes in a rather scatological passage in the Frogs (1074–1076), a passage once commonly omitted from the more polite English translations.

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Fig 1.2    Human brain with the left temporal lobe dissected away. A preparation of this kind displays the optic tract and inferior horn of the lateral ventricle in the manner in which Galen may have seen them and in a form which may have led him to believe that the optic nerve arose from the ventricle. From Polyak (1957).

   Critical editions of the surviving Greek manuscripts of Galen (1822 and 1907/1909 editions) cast doubt on Galen’s use of  thalamos and tend instead to read thalame (θαλαμη) in the passage on the optic nerve in De Usu Partium and also in passages of this and other works in which Galen refers to the temporal fossa (De Usu Partium 11.3), orbit (De Instrumento Odoratus 5.24) or rete mirabile (De Placitis Hippocratis et Platonis 7.3.5). Moreover, the use of thalame for a cavity of the body, the orbit, or a heart chamber is attested in a number of pre-Galenic writers.⁸ Simon (1907) and Hyrtl (1880) suggested that thalamus derives from a misreading of the Arabic texts from which Latin translations of Galen entered the West in the twelfth and thirteenth centuries before discovery of the earlier Greek texts in the fourteenth century. Outside the Greek medical literature, thalame carried the meaning of a lurking place, especially the den of an animal or cave of an undersea creature.⁹ It seems less apt than thalamos as a term implying a reservoir of the pneuma. But a cave or den may have also seemed appropriate to Galen if he indeed had in mind the deepest compartment of a galley. Galen’s near contemporary Lucian, used thalame in speaking jocularly of a pretty boy emerging from his hiding place in the deeper recesses of a ship (Navigum, section 2), so the leap from thalamos to thalame may not be so great as it at first appears.

   What Galen truly had in mind and what word he actually used will probably never be known. More than a thousand years later, at the rebirth of anatomical investigation, thalamus indubitably came to mean the large mass of gray matter in the dorsal part of the diencephalon. Though still thought to be intimately associated with the optic tract and thus referred to as optic thalamus, and for a time continuing to be thought of as a reservoir from which vital spirits could flow into the optic nerve and eye, it no longer meant a part of the ventricular system.

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Fig 1.3  Modern interpretations of the arrangements of oars and rowers in a Greek trieres of the fourth to fifth century BC. The lowest seated rower was the thalamite or thalamian and his oarport a thalamia. Large figure from Morrison and Williams (1968); inset from Foley and Soedel (1981).

   The first of the new identifications of the thalamus may have been by Mondinus in the fourteenth century. Mondinus, perhaps the best of the pre-Vesalian anatomists, referred to structures shaped like anche (haunches or thighs) between the lateral ventricles and the third ventricle. Singer, in his English translation of Mondinus (Mondinus Da Luzzi (Fl. 1315), read this word as anchae and translate it as buttocks, a usage which Hyrtl (1880) had suggested may date to Galen. Galen had also called the superior colliculi the nates or buttocks, but in the relevant passage of Mondinus the distinction between the anche and the superior colliculi seems clear, although by no means unequivocally so.¹⁰

   The thalamus, corpus striatum, and internal capsule are clearly depicted in the horizontal sections of the head seen in plates 7 and 8 of Book Ⅶ of Vesalius’s Fabrica (1543). However, the drawing of this part of the brain has a curiously unfinished look and the structures are not named. This probably misled Walker (1938a) into believing that Vesalius had not observed the thalamus. Colombus, a few years after Vesalius, certainly saw the thalami, likening (“not very elegantly” he says) their posterior surfaces and the intervening third ventricle to a female pubis and vulva.¹¹

   The thalamus is clearly visible, although unlabeled, in several of the plates found in Book Ⅹ of Casserius’ posthumous (1627) Tabulae Anatomicae. In some, the habenulae and striae medullares can be identified but they are also unlabeled. The most complete views are Plate Ⅴ, Fig. Ⅱ and Plate Ⅶ, Fig. Ⅰ. The thalamus can also be discerned in Plate 14, Fig. 2 of Highmore’s (1651) Disquisitions on the Anatomy of the Human Body (Fig. 1.4), although drawn from an apparently much autolysed brain and in a form that may also have misled earlier historians of the thalamus. In this, Highmore reversed the names nates and testes, applying the former to the inferior and the latter to the superior colliculi. Like Casserius, he did not name the thalamus.

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Fig 1.4   Highmore’s dissection of a human brain with the right hemisphere removed to reveal the brainstem and diencephalon. The transected right thalamus, although not named, is seen at H. The left thalamus would be located deep to O. Also visible are the pineal gland (h), superior (C) and inferior (D) colliculi, the infundibular stalk (I) and pituitary (K). From Highmore (1651).

1.2     Thomas Willis

Thalamus became entrenched in Western medical literature following the writings of Thomas Willis (1664, 1681). Willis consistently referred to it as thalamus nervorum opticorum, an expression that on at least two occasions he attributed to Galen. Possibly, he had obtained the name and the attribution indirectly through Jan Riolan the younger, who had made a similar comment in 1610. In Samuel Pordage’s English version of Willis’ Latin text (1681), thalamus nervorum opticorum was translated as the “chamber of the optic nerves.” To Willis, the “oblong marrow” (medulla oblongata or brainstem) was a Y-shaped structure with the arms of the Y (the crura, or “shanks of the oblong marrow”) inserted into the cerebral hemispheres and ending there as the corpora striata (“streaked or chamfered bodies”). In using crura or shanks, Willis was likely looking back at Mondinus’ anche. Below, “where the streaked bodies end, the chambers or Thalami, as they are termed, of the Optick Nerves, possesseth the next part to the oblong marrow; to wit, in this place, its shanks rise into unequal prominences, out of the ridges of which the Optick Nerves arise . . .” Below the thalami in the stem of the Y come the nates and testes (superior and inferior colliculi). The thalamus was clearly illustrated in four views of human or sheep brains drawn as seen from behind by Christopher Wren and there can be no doubt that it is the thalamus of modern anatomy that is being depicted (Fig. 1.5). In two of the plates, what are probably the geniculate eminences are also seen.

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Fig 1.5   One of Christopher Wren’s drawings of a human brain for Thomas Willis’ Cerebri Anatomie, showing the thalami (E), which Willis located in “the shanks of the oblong marrow.” Out of these arise (and situated further out of sight) the “streaked bodies” (corpora striata). From Willis (1664).

   Although he remarked upon the lack of an obvious cavity in the chambers of the Optick Nerves, and did not describe the penetration of the optic nerves into these chambers, Willis leaves us in no doubt about his adherence to the Galenic view of a flow of psychic spirit into the nerves. “. . . these Nerves are inserted into the medullar trunk, as branches of a Tree to the stock, that so they may receive by that means the influence of the Spirits . . .” He noted the disproportionately large size of the diencephalon in relation to the cerebral hemispheres in birds and fish. This led him to remark that “. . . in this place, the animal spirits seem to have their chief Mart or Empory in a most large medullar chamber, or the Sphere of their Expansion. And so, when from hence the animal Spirits are derived from so full and plentiful a Store-house, it is for this reason that Fowls are furnished with so curious an Eye, and with so highly perspicacious and acute a sight.” To Willis, the whole oblong marrow was permeated by the animal spirits, which flowed from there into the various nerves arising from its different parts:

We have already shewed that the animal Spirits are procreated only in the Brain and Cerebel, from which they continually spring forth, inspire and fill full the medullar Trunk: (like the Chest of a musical Organ, which receives the wind to be blown into all the Pipes) but those Spirits being carried from thence into the Nerves, as into so many Pipes hanging to the same, blow them up and actuate them with a full influence; then what flow over or abound from the Nerves, enter the Fibres dispersed every where in the Membranes, Muscles, and other parts, and so impart to those bodies, in which the nervous Fibres are interwoven, a motive and sensitive or feeling force. And these Spirits of every part are called Implanted, forasmuch as they flow not within the Nerves, as the former, with a perpetual flood; but being something more stable and constant, stay longer in the subject bodies; and only as occasion serves, viz. according to the impressions inwardly received from the Nerves, or impressed outwardly by the objects, are ordained into divers stretching or carryings out for the effecting of motion or sense either of this or that manner or kind.

1.4  Recognition of the thalamic nuclei

In the 150 years following the publication of Willis’s work, the thalamus was illustrated many times, the internal capsule was dissected past it, and some ascending tracts were dissected towards it. Several authors noted the anterior tubercle of the thalamus, thrown up by the underlying anterior nuclei, and the pulvinar can often be seen in their drawings (Vieussens, 1685; Soemmering, 1778; Vicq d’Azyr, 1786; Gall and Spurzheim, 1809, 1810; Luys, 1865) (Figs. 1.6 and 1.7). The geniculate bodies had also been recognized since Willis, though often joined together, and the term geniculate seems to have been first applied by Santorini (1724, 1775), who traced the optic tract to the lateral member of the pair. Occasional synonyms for thalamus were introduced, such as colliculus nervorum opticorum (Monro, 1783), and Sehnervenhügel or Sehhügel in the German literature; however, apart from couche optique in France, none supplanted thalamus.

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Fig 1.6   Drawings of 1 mm thick horizontal (left) and frontal (right) sections of human thalami, cut after prior fixation in chromic acid. From Luys (1865).

Fig 1.7   Plates copied by Alexander Knox from Gall and Spurzheim (1810) (A) and Vicq d’Azyr (1786) (B) showing the thalamus (13 in A) and related blood vessels and other structures (B). In (B) note the striae medullares (15–18) and massa intermedia (13, 14). From Knox (1832).

   The first clear indications of nuclear subdivisions in the thalamus were given by Karl Friedrich Burdach (1822), one of the major figures in the history of neuroanatomy, but until publication of Alfred Meyer’s Historical Aspects of Cerebral Anatomy (1971), probably not adequately recognized for his seminal contributions. By examining slices of alcohol-hardened human brains with a hand lens, Burdach identified the internal medullary lamina and recognized that it divided the thalamus into superior (anterior), internal (medial), and external (lateral) nuclei. He also clearly recognized that what he called the external and internal geniculate bodies were parts of the thalamus. He seemed to have gained at least a superficial impression of lamination in the lateral geniculate body and he traced the optic tract as well as the brachium of the superior colliculus to it. Burdach named the pulvinar and also a stratum corneum, which seems to correspond to the external medullary lamina and possibly to the reticular nucleus. The reticular nucleus (stratum reticulatum) received its name later from Arnold (1838). Burdach’s plates are elegantly simple lithographs that mostly illustrate surface features of the brain. Only one, Plate Ⅸ, shows, at relatively low magnification, a view of a parasagittal section of the thalamus. In this, the ventral, and the lateral geniculate nuclei and the pulvinar can be discerned.

   Burdach made relatively little comment about the possible functions of the thalamus, although he seemed to have regarded it mainly as a sensory, especially visual, center. However, all views of the functional significance of the thalamus in that era were extremely vague. In one of the most influential British textbooks of physiology, William Carpenter (1853) described the thalamus, basal ganglia, and brainstem as parts of an integrated “automatic apparatus” responsible for sensation and motion, essentially on the basis of reflex activity. According to Carpenter, projections downward from the cerebral cortex imposed upon the automatic apparatus the “guidance of reason” and, thus, the generation of conscious experiences. These he called “ideomotor” when accompanied by ideas and “emotional” when accompanied by sensation. The lumping together of thalamus and basal ganglia as a more or less common entity was typical of the time. Full recognition of the important role of the thalamus as a sensory way station en route to the cerebral cortex had to wait until later in the century.

   After Burdach, perhaps the next significant contributions on the anatomy of the thalamus were made by Luys (1865), whose focus was clearly on sensory functions. In the interim, Stein (1834) had published what Walker (1938a) and Fulton (1949) regarded as the first thesis on the thalamus, the title page of which served as the frontispiece to Walker’s book. Luys studied the thalamus in carmine-stained slices of brain, previously fixed in chromic acid (Fig. 1.6), a method that had only recently been introduced (Gerlach, 1858). Luys emphasized the subdivision of the thalamus into four centers, each of which he felt was isolated from its neighbors and made up of nerve cells communicating with special groups of afferent fibers. Basing his interpretation on comparative and pathological anatomy, he believed that the centers were independent foci through which different kinds of sensory impression were relayed to the cerebral hemisphere. From dissections of the brain, he recognized that the different centers were connected by white matter tracts to different regions of the cerebral hemisphere, although these were not very specifically nor, from a modern standpoint, very accurately identified.

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Fig 1.7   (cont.)

   Luys identified four thalamic centers (Fig. 1.8). (1) The centre antérieur was equivalent to the anterior nuclei. He noted the relatively large size of the anterior thalamic tubercle in macrosmatic animals and felt that it was connected to the basal olfactory areas via the stria terminalis; he, therefore, considered it to be olfactory in function. (2) The centre moyen, from his illustration, was clearly equivalent to the internal (medial) nucleus of Burdach, but it was regarded by Luys as the terminus of the optic tracts and, therefore, visual in function. (3) The centre médian was discovered by Luys in the human brain and still bears this name, although in his figure probably including part of the mediodorsal nucleus. He considered it to be the center for “the condensation of sensory impressions” (i.e., the terminus of the somatic sensory pathways). Destructive lesions affecting it, he noted, were associated with contralateral hemianesthesia. (4) Finally, the centre postérieur, seemingly a part of the pulvinar in his illustration, was regarded by him as auditory in function, mainly because it appeared degenerated in the brains of two deaf mutes. Luys also recognized the central gray matter component of the thalamus, considering it a continuation of the gray matter of the spinal cord and probably containing ascending sensory fibers. This was a not uncommon belief, dating at least to Gall and Spurzheim. Luys’ illustrations also delineated Burdach’s external (lateral) nucleus, but, curiously, he simply labeled this “couche optique” and did not mention it further. Image not available in HTML version

   Luys’ scheme of the “sensori-motor processes of cerebral activity.” 1 is the thalamus and 4, 9, and 14 its centers for relaying auditory (4), somatic sensory (9), and visual (14) impressions to the sensorium (5, 10, 15). From the sensorium, the large cells convey messages to the corpus striatum (2) and its corresponding centers (12) for the initiation of muscular activity. From Luys (1881).

   With a characteristic lack of modesty, Luys wrote in his English book (1881) “. . . I have insisted on the fact, which ten years ago I was the first in France to bring to light, namely, that the optic thalamus, with the isolated grey ganglions of which it is composed, represents a place of passage and reinforcement for excitations radiated from the sensorial periphery, while the corpus striatum, with its different compartments, and arches one within another, is on the contrary directly related to the passage of voluntary–motor excitations.” “The isolated ganglions of the optic thalamus are so many independent departments for each kind of sensorial impressions, and the destruction of each of them may lead to the disappearance or alteration of the function to which it is specially devoted.” He went on to say: “From a physiological standpoint, the optic thalami are intermediary regions interposed between the purely reflex phenomena of the spinal cord and the activities of psychical life . . .” Finally, he wrote:

By their isolated and independent ganglions they serve as points of condensation for each order of sensorial impressions that finds in their network of cells a place of passage and a field for transformation.