The Callosal Syndromes

Joseph E. Bogen
  1. In spite of evidence affirming it, the callosal syndrome, whose principal elements were magnificently described before 1908, has been discussed, forgotten, rediscovered, denied, proven, put in doubt; it continues a subject for argument. Brion and Jedynak (1975)

  2. The corpus callosum is by far the largest of those nerve fiber collections that directly connect one cerebral hemisphere with the other and are called the cerebral commissures. These include the anterior commissure and the hippocampal commissures. Not included are the posterior and the habenular commissures as well as other commissures of the spinal cord and brainstem.

  3. When the cerebral commissures have been surgically divided (the "split-brain" operation), a variety of deficits in interhemispheric communication can be demonstrated. These make up "the syndromes of the cerebral commissures," also known as "the syndromes of brain bisection" or "the syndrome of hemisphere disconnection" (Sperry et al., 1969; Gazzaniga, 1970; Sperry, 1982; Bogen, 1987). Many of these same deficits can occur with only a partial interruption of the commissures (for example, a portion of the corpus callosum) when this partial disconnection occurs in a setting of acute, naturally occurring disease, such as a thrombosis (Geschwind, 1965). Earlier cases were often described as examples of "the anterior cerebral artery syndrome" (Foix and Hillemand, 1925a; Critchley, 1930; Ethelberg, 1951).

  4. Callosal lesions are often accompanied by damage to neighboring structures. As a result, neighborhood signs may overshadow signs of callosal disconnection. The situation can also be complicated by nonlocalizing signs, such as meningismus when the callosal lesion is caused by hemorrhage from an aneurysm, or signs of increased intracranial pressure when the callosal lesion is a tumor. Although any sign after cortical damage (in a region giving rise to callosal fibers) could be suspected of being partially callosal in origin, small lesions of the callosum rarely can be reliably correlated with any behavioral deficit.

  5. This chapter will deal with signs of hemisphere disconnection and neighborhood signs. The first section comments on terminology and etiology. Second is a synopsis of the human split-brain syndrome, to give an overall view of what is to come. Third is an historical account that will help us to understand how the disconnection signs have come to be emphasized. Next are two sections presenting detailed descriptions of the acute and the chronic syndromes that result from complete callosotomy. The sixth section describes clinical testing for callosal signs and symptoms with naturally occurring lesions. The final sections discuss a few examples of ongoing controversy.

    TERMINOLOGY AND ETIOLOGY

  6. The term split-brain has several meanings. Applied to the human, it denotes complete callosal section--with or without anterior commissurotomy--an operation which is usually performed for medically intractable, multifocal epilepsy (Reeves, 1984; Spencer et al., 1987). In the experimental animal, such as the cat or monkey, it usually implies both commissural section and a split chiasm; this makes it possible to restrict visual information to one hemisphere merely by covering one eye. In the human with intact chiasm, restriction of visual input to one hemisphere requires restriction of the visual stimuli to one or the other visual hemifield. Our own split-brain patients (Bogen and Vogel, 1962, 1975; Bogen et al., 1965, 1988) had complete cerebral commissurotomy (including anterior commissure, dorsal and ventral hippocampal commissures, and, in some cases, the massa intermedia). But it is now common to use the term split brain to refer to cases of complete callosotomy alone, since they manifest most of the same signs and symptoms.

  7. The term partial split has come into common usage because some seizure disorders respond well to section of only the anterior half or anterior two-thirds of the callosum. Moreover, partial sections have sometimes been used for surgical approaches: examples are genu section for anterior communicating aneurysm clipping, trunk sections for access to the third ventricle and environs (Apuzzo, 1987), and splenial section for approaching the pineal region. Tumors (usually gliomas) can occur anywhere in the callosum, the best studied being tumors of the genu or of the splenium. Multiple sclerosis can cause disconnection signs. Toxic and/or infectious lesions of the callosum occasionally occur. And from time to time an anterior cerebral artery aneurysm rupture results in hemorrhagic dissection of the callosum. These naturally occurring lesions usually result in eventually subsiding fractions of the complete callosotomy syndrome. Familiarity with the complete syndrome makes it easier to identify the partial or forme fruste varieties. Congenital absence of the corpus callosum (callosal agenesis) has been intensively studied; it is for the most part not accompanied by disconnection signs, a perplexity which is discussed in detail further on.

    SYNOPSIS OF THE HUMAN SPLIT-BRAIN SYNDROME

  8. When patients who have had a complete callosotomy have recovered from the acute operative effects and reach a fairly stable state, they manifest a variety of phenomena which can be grouped under four headings.

  9. Social Ordinariness

  10. One of the most remarkable results is that in ordinary social situations the patients are indistinguishable from normal. Special testing methods, usually involving the lateralization of input, are needed to expose their deficits.

  11. Lack of Interhemispheric Transfer

  12. A wide variety of situations (to be described below) have been contrived to show that the human subjects are in this respect the same as split-brain cats and monkeys. A typical example is the inability to retrieve with one hand an object palpated with the other.

  13. Hemispheric Specialization Effects

  14. The hemispheric specialization typical of human subjects results in phenomena not seen in split-brain animals. A typical example is the inability of right-handers to name or describe an object in the left hand, even when it is being appropriately manipulated.

  15. Compensatory Phenomena

  16. Split-brain subjects progressively acquire a variety of strategies for circumventing their interhemispheric transfer deficits. A common example is for the patient to speak out loud the name of an object palpated in the right hand; because the right hemisphere can recognize many individual words, the object can then be retrieved with the left hand.

  17. These four kinds of phenomena are discussed in detail in the section on the chronic or stabilized syndrome of hemisphere disconnection.

HISTORICAL BACKGROUND

  • The history of studies of the corpus callosum can be considered to have six periods:
  • The humoral anatomists
  • The traffic anatomists
  • The classical neurologists
  • The critics
  • The two-brain theorists
  • The revisionists
    1. Contributors not mentioned here are cited in the extensive reviews included in the bibliography."

    2. The Humoral Anatomists

    3. By "humoral anatomists" I mean those writers of antiquity whose concepts of brain function emphasized the contents of the brain cavities and the flow of various fluids such as air, phlegm, cerebrospinal fluid, blood, etc. For them, the corpus callosum seemed largely a supporting structure. Even that original Renaissance genius, Vesalius, believed that the corpus callosum served mainly as a mechanical support, maintaining the integrity of the various cavities. In 1543 he wrote:

    4. There is a part [whose] external surface is gleaming white and harder than the substance on the remaining surface of the brain. It was for this reason that the ancient Greeks called this part "tyloeides" ["callosus" in Latin] and, following their example, in my discourse I have always referred to this part as the corpus callosum. If you look at the right and left brain ... and also if you compare the front and rear, the corpus callosum is observed to be in the middle of the brain;... Indeed, it relates the right side of the cerebrum to the left; then it produces and supports the septum of the right and left ventricles; finally, through that septum it supports and props the [fornix] so that it may not collapse and, to the great detriment of all the functions of the cerebrum, crush the cavity common to the two [lateral] ventricles of the cerebrum. (Clarke and O'Malley, 1968, p. 597)

    5. The Traffic Anatomists

    6. The "traffic anatomists" took a major step forward. As indicated by Joynt (1974), it was at about the time of Willis(1664) that anatomists began thinking in terms of communication between the more solid parts of the brain. This view became quite explicit in the statement of Viq d'Azyr, who wrote in 1784:

    7. It seems to me that the commissures are intended to establish sympathetic communications between different parts of the brain, just as the nerves do between different organs and the brain itself. (Clarke and O'Malley, 1968, p.,592)

    8. For over two centuries, beliefs about callosal function consisted almost solely of inferences from its central location, widespread connections, and large size (larger than all those descending and ascending tracts, taken together, which connect the cerebrum with the outside world). Willis, de la Peyronie, and Lancisi, among others, thought the corpus callosum a likely candidate for "the seat of the soul"; or they used some other expression intended to cover that highest or ultimate liaison which brings coherent, vital unity to a complex assemblage.

    9. -Levy-Valensi, 1910; Mingazzini, 1922; Bremer et al., 1956; Bremer, 1958; Geschwind, 196.5; Unterharnscheidt et al., 1968; Bogen and Bogen, 1969; Elliot, 1969; Kuhlenbeck, 1969; Cumming et al., 1970; Doty and Negro, 1972; Berlucchi, 1972, 1990; Joynt, 1974; Selnes, 1974; Brion and Jedynak, 1975; Pandya, 1975; Reeves, 1984; Innocenti, 1986; Lepore et al., 1986; Harrington. 1987; Berlucchi and Aglioti, 1990; Trevarthen, 1990; Innocenti, 1991.

    10. The observations of the early anatomists have been supported by subsequent anatomic observations, including the large number of callosal fibers, at least 600 million of them." It seems reasonable to suppose that these fibers which interconnect so much of cerebral cortex, especially that cortex considered associative, have to do with the "highest," most educable, and characteristically human functions of the cerebrum (Bremer, 1958).

    11. Inference of function from observable structure is time honored and productive. However, such inference has its limitations. The physiological evidence has t>nly partially sustained anatomic inference. We now know from various observations (notably the split-brain) that the corpus callosum is indeed an important integrative structure; we also know it is neither sufficient nor indispensable, providing only one of a number of integrative mechanisms. Indeed, the multiplicity of mechanisms mediating between the two hemispheres is a major theme of this chapter.

    12. Behavioral deficits are now easily and clearly demonstrable in individuals who have had surgical section of the cerebral commissures. But these deficits were first recognized, by 3 number of exceptionally astute clinicians, in patients with vascular disease causing very complex and evolving syndromes.

    13. The Classical Neurologists

    14. In the closing decades of the nineteenth century (or more broadly construed, in the period between the American Civil War and the First World War), a group of neurologists emerged whose discoveries and formulations are still the core of current clinical kr~owlcdgc; many issues which they debated remain live issues today. Among them were several, including Wernicke, Liepmann, Dejerine, and Goldstein, who interpreted various neurological symptoms as resulting from disconnection, including interruption of information flow through the corpus callosum.

    15. The concept of apraxia was developed by Liepmann expressly to describe a patient who could carry out commands with one of his hands but not with the other. Liepmann and Maas (1907) described a right-hander whose callosal lesion caused a left apraxia as well as a left-hand agraphia--an inability to write--in the absence of aphasia. These disabilities have subsequently been observed many times. Unilateral apraxia and agraphia are not always present, and they may subside as a stroke victim recovers, but they remain among the cardinal signs of hemisphere disconnection.

    16. Among Liepmann's ideas were two which he considered to be necessarily connected, but whose acceptance, in fact, has waxed and waned independently. We can call them (1) the concept of callosal motor mediation or "the callosal concept" and (;2) the concept of left-hemisphere motor dominance or "motor dominance."

    17. According to the first concept, interruption of transcallosal interhemispheric communication results in apraxia. Liepmann considered the corpus callosum instrumental in left-hand responses to verbal command: the verbal instruction was comprehended only by the left hemisphere and the left hand followed instructions which were delivered not by a directly descending pathway which we now call "ipsilateral control" (cf. Brinkman and Kuypers, 1973; Jones et al., 1989) but by a route involving callosal interhemispheric tranfer from left to right and then by way of what we now call "contralateral control," that is, by right-hemisphere control of the left hand. Necessarily then, callosal interruption would result in an inability to follow verbal commands with the left hand although there would be no loss of comprehension (as expected from a left-hemisphere lesion). And there would be no weakness or incoordination of the left hand (as would usually result from a right-hemisphere lesion). This view was largely ignored or rejected (particularly in the English-speaking countries) for nearly half a century, although it is now thought to be essentially correct. Correspondingly, we now recognize the notion of spatial or pictorial instructions understood by the right hemisphere and requiring callosally mediated interhemispheric communication for correct right-hand execution. This right-to-left aspect of callosal function was not part of Liepmann's original callosal concept, although, in retrospect, it seems a natural corollary.

    18. -The 2 X 10^8 estimate of Tomasch (1954) was based on light microscopy. According to G. Innocenti (personal communication in 1991), electron microscopy will at least triple the old estimate (see also Clarke et al., 1989).

    19. Second, there was Liepmann's concept of the left hemisphere as the organizer of complex (particularly learned) motor behavior. Indeed, according to Coldstein (1953), it was Liepmann who made "the important discovery of the dominance of the left hemisphere." Unlike the callosal concept, this idea of motor dominance was readily accepted, along with the already established concept of language dominance by the left hemisphere. Almost everyone came to think of the left hemisphere as generally "the dominant hemisphere" (Benton, 1977). The reemergence in the 1960s of interest in the corpus callosum (as described below) was coincidentally accompanied by a recognition of right-hemisphere dominance for certain nonverbal processes and their motor expression. Hence, while Liepmann's callosal concept was regaining popularity, his motor dominance concept was losing some of its appeal. We have here what seems to be an example of how ideas thought by their inventor to be necessarily linked can be separated by the judgments of others. Whether, and in what way, the left hemisphere is dominant for skilled or serially programmed movements generally (and not just those linguistically related) is currently a matter of active controversy (Kimura and Archibald, 1974; Denckla, 1974; Geschwind, 1975; Albert et al., 1976; Zaidel and Sperry, 1977; Haaland et al., 1977; Mateer and Kimura, 1977; Denckla and Rudel, 1978; Zaidel, 1978b; Haaland and Delaney, 1981; Jason 1983a,b; Kimura, 1983; Hampson and Kimura, 1984; Corina et al., 1991; Leonard and Milner, 1991). For a further discussion of apraxia (including callosal apraxia) see Chapter 7.

    20. Meanwhile, Liepmann's callosal concept is now hardly doubted. But this was not always so.

    21. The Critics

    22. Even during the time of Liepmann, there were critics and doubters; they became progressively more influential in the ensuing decades. In their extensive review, Ironside and Guttmacher (1929) concluded:

    23. Taking into account the com pleteness of the case records, our series of tumour cases would lead us to believe that apraxia is not a common symptom of tumours of the corpus callosum.

    24. The symptoms in corpus callosum tumours are largely of the "neighbourhood" type and arise from involvement of, or pressure on, adjacent structures by the growth.

    25. In addition to the criticism of hemisphere disconnection as a cause of symptoms, the situation was clouded by certain distractions which we can consider briefly before returning to the central theme of disconnection.

    26. MENTAL SYMPTOMS WERE DISPUTED Distractions arose as a result of attempts to correlate lesions, especially tumors of the corpus callosum, with mental symptoms. For example, a mental callosal syndrome was formulated by Raymond et al. (1906) and their views were widely accepted for many years. They observed a certain loss of connectedness of ideas but no delirium, a difficulty with recent memory, a "bizarreness" of manner, and a lability of mood. One is impressed with the extent to which this resembles symptoms which are now commonly attributed to frontal lobe damage (Botez, 1974; Barbizet et al., 1977; Damasio, 1984; Stuss and Benson, 1986; Fuster, 1989; Levin et al., 1991).

    27. Alpers (1936) redescribed the callosal syndrome emphasizing "imperviousness": a certain indifference to stimuli as if the threshold were elevated, difficulties in concentration, and a lack of elaboration of thought.

    28. After reviewing the relevant literature, and on the basis of personal cases, Brihaye (in Bremer et al., 1956) agreed with the observation of Le Beau (1943) that "there is a certain apathy, that is to say, a clouding without somnolence which is possibly very specific." When we actually read Le Beau, we find that the rest of his sentence is, "but this, in any case, is insufficient to permit more than a clinical suspicion of localization in the corpus callosum. Most of the time, there is nothing of the sort" (p. 1370). And on the very first page of his extensive article, Le Beau says, "The clinical diagnosis of these tumors is hardly possible, because there is no callosal syndrome (p. 1365). And in his summary, "in particular there is no characteristic mental deficit and no apraxia" (p. 1381).

    29. Patients with anterior callosal lesions often do have "a certain apathy." This imperviousness" occurs in patients with acute or progressive callosal lesions--especially the malignancy that is sometimes called a "butterfly glioma" because it spreads its wings into both frontal lobes. The patient who is impervious to instructions will eventually respond, and often appropriately (but sometimes incompletely), but only after repeated requests and considerable delay. We are now inclined to attribute this symptom not to involvement of the genu of the corpus callosum (which is, to be sure, involved) but rather to involvement of the medial aspects of the frontal lobes including the anterior cingulate gyri. And we suppose the imperviousness to be a milder form of akinesia, often approaching a mute immobility, of a patient who has what is sometimes called the "subfrontal syndrome" consequent to bleeding from an anterior cerebral artery aneurysm, or with a third ventricle tumor. (Also, see Chapters 10 and 12 on the neglect syndrome and the frontal lobes, respectively.) In any event, imperviousness can be a useful sign of anterior callosal lesions, although it is probably not a result of callosal interruption.

    30. Neighborhood signs have also been noted with posterior callosal lesions, with involvement of the hippocampi. Translating Escourolle et al. (1975):

    31. A certain number of our tumors of the splenium [twice as common as genu gliomas] were accompanied by memory dysfunction, whereas the anterior tumors were more often manifested by akinetic states with mutism, probably because of bilateral anterior cingulate involvement (p. 48)

    32. DISCONNECTION SIGNS WERE NOT OFTEN SEEN

    33. The eclipse of Liepmann's understanding of the corpus callosum was only partly attributable to clouding of the issue with neighborhood signs: mainly it was from an unwillingness to accept as meaningful such disconnection signs as unilateral apraxia, unilateral agraphia, and hemialexia. The objections which were raised included the following six points:

    34. 1. Callosal lesions are rarely if euer isolated, so that deficits attributed to such lesions may well result, at least in part, from associated damage.

    35. This problem is real enough; the only solution is to obtain a sufficient variety of cases so that one can reasonably attribute to their common anatomic aspects those clinical features which they also have in common. This is reminiscent of the generally accepted attitude among scientists that a belief becomes more secure through the convergence of widely differing lines of evidence.

    36. 2. Signs attributable to callosal lesions often subside 07 disappear altogether.

    37. This criticism is correct, especially for younger patients with unimanual dyspraxia and unimanual dysgraphia. But it does not apply to all callosal signs, notably the unilateral anemia and the hemialexia following callosotomy. Even if it did, subsidence does not mean that a sign was without significance, any more than the frequent subsidence of aphasia means that it is not a reliable sign (in right-handers) of a left-hemisphere lesion. Progressive compensation following focal damage is one of the most characteristic features of the brain.

    38. 3. In numerous cases of callosal disease the erpected disconnection signs are not elicited.

    39. This included cases of toxic degeneration of the corpus callosum (such as Marchia fava-Bignami disease) as well as the far more common cases of callosal tumor or cal losal infarction. In the massive revised edition of his neurology text, Gowers (1903) reasonably concluded:

    40. we do not yet know of any symptoms that are the result of the damage to the callosal fibers. (p.314)

    41. S.A.K. Wilson, in his definitive neurology text (Wilson and Bruce, 1940), reaffirmed, on the basis of tumor cases, much the same conclusion. Wilson mentioned apraxia as an inconstant symptom, emphasized certain mental symptoms such as lack of spontaneity, and concluded:

    42. In fact, the claim might be advanced that all "callosal" symptoms are of a neighboring or distant kind. (p. 1235)

    43. Wilson's discussion refers to studies by Bristowe, Ransom, Tooth, Guillain, Alpers and Grant, Voriz and Adson, Dyke and Davidoff, and the book by Mingazzini (1922), as well as the article by Ironside and Guttmacher (1929) quoted above in the introduction to this subsection on the critics. He does not refer to Liepmann. This insular tradition of disprizing callosal disconnection as a source of symptoms persists (Rudge and Warrington, 1991).

    44. In retrospect, these negative findings can often be attributed to a lack of looking; it is not everyone's routine to look for dysgraphia in the left hand or even for an anomia; and hemialexia in the left half-field can be even more elusive, particularly if no precautions are taken to prevent shift of gaze (such as using a tachistoscope so that stimuli appear, in one visual half-field or the other, for only a fraction of a second). In addition, disconnection signs may not be demonstrable because patients with callosal tumors or toxic degeneration are often too obtunded to be appropriately tested.

    45. When patients with toxic malfunction of the corpus callosum are testable, and appropriately tested, such signs as unilateral anemia and dyspraxia have been found (Lhermitte et al., 1977; Barbizet et al., 1978). Disconnection signs have likewise been found with appropriate testing of tumor/infarction cases, as was so well demonstrated in the now classic paper of Geschwind and Kaplan (1962) (see also Barbizet et al., 1974).

    46. 4. Patients with agenesis of the corpus callosum (andlor ca2losal lipoma) do not manifest most of the so-called callosal signs.

    47. Levy-Valensi (1910) was an ardent admirer of Liepmann, gave him the credit for the concept of apraxia, and said, "... apraxia is part of the callosal syndrome." But he, like so many others, was particularly troubled by callosal agenesis and admitted, "The physiologist is no less embarrassed than the anatomist by these disconcerting cases." A sizable number of callosal agenesis patients have been seen in the past few years; and a few deficits in interhemispheric transfer have seemed to be present (Jeeves, 1965, 1991; Lehmann and Lampe, 1970; Dixon and Jeeves, 1970; Kinsbourne and Fisher, 1971; Sadowsky and Beeves, 1975; Milner and Jeeves, 1979; Lassonde et al., 1981; Sauerwein ct al., 1981; Milner, 1982).

    48. But there has been no disconnection syndrome typical of the split-brain in such patients. This observation cannot be explained away on methodological grounds since it is true even with the most extensive, systematic testing (Saul and Sperry, 1968; Ettlinger et al., 1974; Ferriss and Dorsen, 1975; Reynolds and Jeeves, 1977; Cott and Saul, 1978; Jeeves, 1979; Lassonde et al., 1988, 1991).

    49. The presence of interhemispheric transfer in spite of callosal agenesis has been attributed to various causes, most notably the use of other commissural systems such as the anterior commissure. There may also be a duplication of function (such as speech in each hemisphere) or the compensatory appearance, during brain development, of unusually effective ipsilateral fiber tracts, or cerebellopetal pathways (Voneida, 1963; Glickstein, 1990).

    50. The anterior commissure explanation is appealing because the available postmortem evidence indicates that individuals with callosal agenesis (if they reach an age sufficient for psychological testing) all have anterior commissures, sometimes larger than normal (Bruce, 1890; Segal, 1935; Reeves and Courville, 1938; Kirschbaum, 1947; Slager et al., 1957; Leeser and Alvord, 1968; Bossy, 1970; Ito et al., 1972; Sheremata et al., 1973; Shoumura et al., 1975; Carleton ct al., 1976; Jeret et al., 1987)."

    51. The anterior commissure has been shown in animal experiments to serve visual transfer nearly as well as the splenium (Downer, 1962; Black and Myers, 1964; Doty and Overman, 1977; Sullivan and Hamilton, 1973a; Doty et al., 1986, 1988; Mishkin and Phillips, 1990). And it is now known that in the chronic, stabilized state, the splenium can effect sufficient interhemispheric exchange to avoid signs of disconnection. This conclusion is based on cases having extensive but incomplete commissurotomy, that is, section of the anterior commissure and all of the corpus callosum except for the splenium. Later in this chapter an extensive list of deficits reliably found after a complete commissurotomy is presented; few of these deficits can be found after surgery if the splenium is spared (Gordon et al., 1971; Cazzaniga et al., 1975; Ozgur et al., 1977; Cobben et al., 1978; Benes, 1982; Apuzzo et al., 1982; Greenblatt et al., 1980; Bogen, 1987; Oepen et al., 1988; Purves et al., 1988; Gordon, 1990; Oguni et al., 1991). Certain transfer deficits found with various partial callosal interruptions are discussed at the end of this chapter.

    52. Two points deserve emphasis:

    53. a. An apparent lack of callosal symptoms in cases of long-standing partial lesion (and probably of callosal agenesis) is largely due to the compensatory capabilities of the remaining fibers.

    54. b. Partial lesions are not usually compensated immediately. Hence, disconnection symptoms are more likely to occur after a sudden partial lesion (such as a stroke) or in the presence of progressive lesions (such as tumors) where the deficit is increasing faster than it can be compensated.

    55. The paucity of disconnection deficits in patients with callosal agenesis is not wholly explained by the presence of the anterior commissure. It should be kept in mind that compensation for loss of the splenium, by the anterior commissure, has been imperfect in animal experiments (Butler, 1979; Ringe et al., 1991). Nor does the anterior commissure compensate very well for splenial loss in humans, as shown by the hemialexia usually persisting after splenial section (Trescher and Ford, 1937; Maspes, 1948; Gazzaniga and Freedman, 1973; Iwata et al., 1974; Sugishita et al., 1986).

    56. Interhemispheric transfer of discriminative information via the anterior commissure seems to be, in surgical cases, incomplete (Goldstein and Joynt, 1969; Goldstein et al., 1975). Even if the anterior commissure is responsible for visual transfer in cases of callosal agenesis, how are we to explain the somesthetic transfer in such cases? One consideration is that agenesis cases typically have a large longitudinal bundle of fibers along the medial aspect of each hemisphere (the bundle of Probst, 1973). As pointed out by R. Saul (personal communication) this bundle might make available to the anterior commissure some types of information which it does not ordinarily transfer. In any event, the presence of Probst's bundle fits the view that brains with callosal agenesis differ from normal brains in ways other than disconnection.

    57. "I am aware of only one report, brought to my attention by Dr. Maryse Lassonde, of a person reaching adulthood and at autopsy considered to have absence of the anterior commissure (Harcourt-Webster and Rack, 1965).

    58. Also implying that such a brain is peculiar in its principles of operation is the notion of increased function of ipsilaterally descending or ascending fiber tracts. In this regard, Dennis (1976) confirmed that callosal agenesis is accompanied by deficits within each hemisphere, appearing as a loss of finely differentiated tactile localization and individual finger movements. This loss was attributed to a lack of inhibitory action by the corpus callosum during early development of the brain. The corpus callosum, in this view, oridnarily suppresses information contained in uncrossed pathways. Somewhat related are the suggestions (1) that unilateralization of language (and other engrams) depends on callosal inhibition active at the time of engram acquisition (Doty et al., 1973; but see Temple et al., 1989; Lassonde et al., 1990; Leonard et al., 1991) and (2) that the development of hemispheric specialization depends on competitive interaction between the hemispheres during early childhood (Galin, 1977).

    59. Some reservation is necessary with respect to the interpretation of intrahemispheric deficits in callosal agenesis, since the condition is so often associated with other anomalies. Hence, any deficit in intrahemispheric function might easily be coincidental, not a direct result of the absence of commissures. Further evidence might be expected from animal experiments in which the cerebral commissures are severed shortly after birth (Jeeves and Wilson, 1969; Sechzer et al., 1976; Elberger, 1980; Ptito and Lepore 1983). Recent results include the finding that callosotomy in kittens seems to interfere with the normal development of a variety of visual functions (Elberger, 1988, 1990).

    60. 5. Callosal section in animal experiments does not produce significant deficits.

    61. The negative experiments of Zinn (1748); Magendie, Muratow, Roussy, Franck, and Pitres; Koranyi, Dotto, and Pusateri; Lo Monaco; and Baldi were all reviewed by Levy-Valensi (1910), whose own monkey experiments were (to his dismay) also negative, as were the experiments (cited by Bremer et al., 1956) of Lafora and Prados (1923), Hartmann and Trendelenberg (1927), Seletzky and Cilula (1928), and Kennard and Watts (1934).

    62. In retrospect, these negative results can be attributed to a lack of relevant testing (as will be discussed further on). Besides, the more striking signs and symptoms seen in human patients are attributable to hemispheric specialization which is less evident in rats, cats, dogs, or even monkeys (Warren and Nonneman, 1976; Doty and Overman, 1977; Hamilton, 1977; Stamm et al., 1977; Dewson, 1977; Harnad et al., 1977; Denenberg, 1981; Overman and Doty, 1982; Hamilton and Vermeire, 1982, 1988; Petersen et al., 1984).

    63. 6. Surgical section of the corpus callosum is often asymptomatic.

    64. Waiter Dandy went so far as to say in 1936:

    65. The corpus callosum is sectioned longitudinally ... no symptoms follow its division. This simple experiment puts an end to all of the extravagant hypotheses on the functions of the corpus callosum.

    66. Even more persuasive was the negative testing by Akelaitis (1944; 1944-1945) of patients who had callosal section. These results were admitted by Tomasch (1954, 1957), whose interest in the corpus callosum and anterior commissure led him to make his widely known estimates of their fiber content. Of the Akelaitis results he wrote:

    67. They showed very clearly and in accordance with some earlier authors like Dandy, Foerster, Meagher and Barre, whose material however was not so extensive, that the corpus callosum is hardly connected with any psychological functions at all.

    68. Ethelberg (1951), after an extensive review, concluded:

    69. It may be premature to consider the recent clinical, surgical, and experimental observations an obituary of Liepmann's concepts as to the role played by the corpus callosum in the development of "true" apraxia. But they certainly suggest the need of some hesitance in accepting them. (p. 117)

    70. About the same time, Fessard (1954) summarized the view which was then generally accepted:

    71. there is a great deal of data showing [that] sections of important associative white tracts such as the corpus callosum does not seem to affect mental performances. Other similar observations in man or animals are now accumulated in great number and variety. These results are so disturbing that one may be tempted to admit the irrational statement that a heterogeneous system of activities in the nervous system could form a whole in the absence of any identified liaison.

    72. Fessard relied on the foregoing when he emphasized the importance of the brainstem reticular formation not only for wakefulness (Moruzzi and Magoun, 1949; Magoun, 1958) but also as a constituent of Penfield's proposal of a "centrencephalon":

    73. An area in which those mechanisms are to be found which are prerequisite to the existence of intellectual activity and prerequisite to the initiation of the patterned stream of efferent impulses that produce the planned action of the conscious man. [and] It may be suggested at once that the intralaminar systems of the thalamus and the reticular formation of the brain stem and the non-specific projection systems which have widespread connections with the cortex of both sides satisfy the definition. (Penfield, 1954, pp. 286-287)

    74. When considering this anatomical description, it is well to recall that there are two thalami, as well as that the corpus callosum is now known to play an important role in both intellectual activity and planned action. The split-brain observations put a damper on enthusiasm for the "centrencephalon." In 1977, Doty asserted that they "speak quite strongly that the unification of consciousness is not at the brainstem level.''

    75. The "centrencephalon" will reemerge later when we consider the revisionists. Meanwhile, we now realize that most of the negative findings after surgical section of the corpus callosum resulted from two sources:

    76. a. As already mentioned, when surgical section of the commissures is incomplete, a remarkable capacity for maintaining cross-communication between the hemi spheres may be retained with commissural remnants, particularly when the part remaining is the splenium.

    77. b. Negative findings often result from the use of inappropriate or insensitive testing techniques. What one finds depends on what one looks for; whereas Dandy (1936) said that callosal section produces no observable deficits, among his own patients was the one reported by Trescher and Ford to have hemialexia.

    78. The Two-Brain Theorists

    79. In the nineteenth century, considering the cerebrum to be a "double brain" was espoused by Wigan (1844), Jackson (1874), and a multitude of others, as described in detail by Harrington (1987). Jackson (1874) advised:

    80. I use the word brain to include the cerebral hemisphere and the subjacent motor and sensory tract. I use the word encephalon to include all parts of the nervous system within the skull.

    81. But such ideas, along with Liepmann's callosal concept, fell far out of favor by the end of World War I and remained so for many decades. A distinct reversal of opinion occurred during the 1960s, following publication of the "split-brain" experiments, and the concept of a "double brain" again became popular (Dimond, 1972).

    82. Current views on callosal function are attributable in large part to studies, under the aegis of R. W. Sperry, of our patients with surgical section of the cerebral commissures. These patients are indeed without, in Dandy's words, "any deficits" in the ordinary social situation, or even as determined by most of a routine neurological examination (Bogen and Vogel, 1975; Botez and Bogen, 1976). In specially devised testing situations, however, they can be shown to have a wide variety of deficits in interhemispheric communication (Gazzaniga et al., 1962, 1963, 1965, 1967; Gazzaniga, 1970; Sperry, 1968, 1970, 1974, 1982; Sperry and Cazzaniga, 1967; Sperry et al., 1969; Zaidel, 1973, 1983; Bogen, 1987; Zaidel et al., 1990b).

    83. The split-brain humans confirmed in a particularly striking way the importance of commissural fibers for interhemispheric communication. But the essential fact had already been described in animal experiments during the 1950s, initiated by Myers and Sperry (1953, 1958; Myers, 1956). It was found that each hemisphere of a cat or monkey could learn solutions to a problem different from (even conflicting with) the solutions learned by the other hemisphere. This made it clear that effective functioning could occur independently in the two hemispheres. As Sperry (1961) put it:

    84. Callosum-sectioned cats and monkeys are virtually indistinguishable from their normal cagemates under most tests and training conditions. [But] if one studies such a "split-brain" monkey more carefully, under special training and testing conditions where the inflow of sensory information to the divided hemispheres can be separately restricted and controlled, one finds that each of the divided hemispheres now has its own independent mental sphere or cognitive system--that is, its own independent

    85. perceptual, learning, memory and other mental processes.., it is as if the animals had two separate brains. (p. 1749)

    86. it is important to understand that the duality of minds seen after hemisphere disconnection is not an inference solely from certain striking clinical cases, and a handful of surgical patients, as sometimes said. Split-brain experiments have been carried out with many different species by hundreds of investigators around the world. They are virtually unanimous in concluding that each of the disconnected hemispheres can act independently of the other (Bogen, 1977). Let us consider two examples of variation on the basic idea that the cerebrum is double.

    87. 1. One of the most reliable signs of a bilateral prefrontal lobectomy in monkeys is their inability to do delayed-alternation tasks (Jacobsen and Nissen, 1937; Mishkin, 1957; Iversen and h3ishkin, 1970; Pribram et al., 1977; Markowitsch et al., 1980; Fuster, 1989; Sawaguchi and Goldman-Rakic, 1991). It was long supposed that this inability might be explained as the result of the hyperactivity and/or distractibil ity which is also characteristic of such monkeys. This supposition can be tested in a split-brain monkey, where each hemisphere can function separately. If one hemisphere has a prefrontal lobectomy, it performs poorly on the delayed-alter nation task. This poor performance by the lobectomized hemisphere is not accom panied by hyperactivity or distractibility. Apparently, the remaining frontal lobe keeps the monkey quiet and attentive even though the intact hemisphere is not participating in the recognition of various stimuli or the evaluation of their signif icance (Clickstein et al., 1963).

    88. 2. A truly dramatic example occurs when only one hemisphere of a split-brain mon key has had a temporal lobectomy. A bitemporal monkey manifests the Kliiver Bucy syndrome, which includes difficulties in the visual identification of objects, orality (often mouthing inappropriate objects), hypersexuality, hypomotility, and tameness in the presence of humans. When the intact hemisphere can see, the split-brain rhesus monkey behaves in the usual rhesus manner, manifesting a fierce fear of humans. But if only the temporal lobectomized hemisphere receives the visual information, the split-brain animal acts like a Kliiver-Bucy monkey, partic ularly as regards its relative tameness. When this was reported (Downer, 1961), 1962) it was so amazing that many of us doubted it, although we were already convinced of the duality of mind in the split-brain monkey. Little room for doubt remains because this finding has, in its essentials, been reported by a number of other investigators (Bossom et al., 1961; Barrett, 1969; Horel and Keating, 1972; Doty et al., 1971, 1973; Doty and Overman, 1977).

    89. It was knowledge of the split-brain experiments in laboratory animals that alerted Geschwind and Kaplan (1962) to the possibility of a hemisphere-disconnection syndrome in the human. When a suitable patient appeared, they searched for the disconnection effects. From a complex, evolving picture, they teased out the relevant phenomena .

    90. One of the first things Ceschwind and Kaplan found was that although the patient wrote clearly with his right hand, he wrote "aphasically" with his left (and was astonished by what he had written). Among other things they found that an object placed in his left hand was handled correctly and was correctly retrieved by feel, but it could not be named; nor could it be retrieved by feel with his right hand. In their words:

    91. ... He behaved as if his two cerebral hemispheres were functioning nearly autonomously. Thus, we found that so long as we confined stimulation and response within the same hemisphere, the patient showed correct performance.

    92. In contrast, the patient performed incorrectly when the stimulus was provided to one hemisphere and the response required from the other. They concluded that the best explanation was to suppose that his hemispheres were disconnected by a lesion of the corpus callosum. Their anatomic prediction was eventually confirmed by autopsy. And their conclusions were soon amply confirmed by the surgical cases whose description we will come to further on.

    93. Liepmann's callosal concept has been resurrected. There is now widespread acceptance of an idea long ignored. It is an interesting example of what Kuhn (1962) called a paradigm shift. Geschwind (1974) wrote:

    94. What was astonishing was the fact that this work had been so grossly neglected ... that important confirmed scientific observations could almost be expunged from the knowledge of contemporary scientists.

    95. As Harrington (1987) put it, ways of thinking about the brain (i.e., laterality and duality) which seem natural enough now had "vanished from the working world view" for nearly 50 years. Chapter 9 of her book is devoted to the causes of this halfcentury eclipse. These included "neurology's rediscovery of the 'whole"' led by Marie (1906), Head (1926), Goldstein (1939), and, in the laboratory, Lashley (1929, ]951). She is particularly critical of Henry Head, whose highly selective reference to Jackson "borders on intellectual dishonesty." Concurrent was a "trend toward psychologism in psychiatry" including the work of Bleuler(lS11) and, especially, Freud.

    96. Geschwind has suggested in correspondence that there was a widespread revulsion against attempts to link brain to behavior, associated with the rise of psychoanalysis; and he had another, sociological explanation:

    97. Henry Head had been shrewd enough to point out that much of the great German growth of neurology had been related to their victory in the Franco-Prussian war. He was not shrewd enough to apply this valuable historical lesson to his own time and to realize that perhaps the decline of the vigor and influence of German neurology was strongly related to the defeat of Germany in World War I and the shift of the center of gravity of intellectual life to the English-speaking world, rather than necessarily to any defects in the ideas of German scholars. (Geschwind, 1964)

    98. But there were other factors. One thing missing was a widespread conviction that the essential facts could be observed repeatedly in humans under controlled, prospective circumstances. Such observations (to be described below) are possible with persons who have had a complete cerebral commissurotomy or, short of that, a complete callosotomy.

    99. Meanwhile, it is useful to mention briefly some objections to the two-brain view which have been resurrected in the past few years.

    100. The Revisionists

    101. The two-brain view, recognizing a significant degree of cerebral hemisphere independence (including in cats and monkeys) and conspicuous hemispheric specialization (in most humans) caught the public eye in the 1970s. The media pushed the popularity of the "right brain/left brain" story to fad proportions reaching an almost frenzied peak by 1980. This led not only to simplistic degradation, probably inevitable with popularization, but also to exploitation. Commercially motivated entrepreneurs promised to educate peoples' right hemispheres in short order, sometimes even overnight, ignoring the lengthy, arduous training necessary for any mature competence. This was followed by a reaction or backlash which itself served to confuse nonspecialists hoping to distinguish replicable fact from speculation. Much of the reaction involved the debunking of extravagant claims. Some of it, however, was more revisionist. That is, there are some writers who have challenged the basic observations by emphasizing limitations on hemispheric independence and by pointing out the variable degree of hemispheric specialization, as well as by emphasizing the obvious point that for intact individuals, most activities involve hemispheric interaction. A notable example is the recent extreme denigration of hemispheric specialization by Efron (1990). By now, it may be useful to offer some evaluation of the backlash, concentrating on the revisionist views of a few acknowledged experts who are familiar with the technical details. Such evaluations are presented in the final sections of this chapter. Since they presuppose some familiarity with both clinical and experimental data, these will be presented next.