The Effect of Absence of the on the Position of the Hippocampus and on the Formation of Probst's Bundle

KENNETH R. MAGEE AND ROBERT N. OLSON' Kresge Neurological Research Laboratory, University of Michigan

Complete or partial agenesis of the fibers, the fimbria. Elliot Smith ('10) corpus callosum results in an alteration stressed that the position of the hippo- in anatomical developmcnt of the midline campus as the medial edge of the cerebral structures of the . The cortex is an important feature of the influence of such maldevelopment on the in the ancestors of and is prob- position of the hippocampus and its con- ably a fundamental feature in the develop- nections will be considered in this study. ment of all vertebrates. The dorsal com- In addition, agenesis of the corpus cal- missure of the contains only losum may allow structures existing in fibers of hippocampal origin (fig. 1). In normal to become more evident the bat, Nycotophilus, which represents a because they are not masked by the abun- transition from the acallosal to the callosal dant fiber distribution of the corpus cal- brain, the anterior part of the dorsal com- losum. Various other cerebral anomalies missure becomes invaded by pallial com- may often be seen in agenesis of the cor- missural fibers thus forming an anterior pus callosum but they will not be stressed extension of the dorsal commissure (Smith in this study for good reviews of the gen- 1897a). These pallial decussating fibers eral subject are available (Baker and do not develop to so great an extent as in Graves, '33; Carpenter and Druckemiller, higher animals but begin to influence the '53; Kirschbaum, '47; Bunts and Chaffee, position of the hippocampus. As in these '44; and Marburg, '49). lower forms, studies of higher mammals have demonstrated that the fibers which PERTINENT LITERATURE eventually form the corpus callosum are The embryologic and phylogenetic de- first seen as a bundle known as the tape- velopment of the midline anatomy of the turn covering the neocortical inner wall of brain will first be reviewed. In a the (Tilney, '39). When the study of , Tilney ('39) con- fibers course medialward, they are pushed cluded, ". . . in spite of its extreme primi- against the anterior side of the alveus layer tiveness it (the marsupial) follows, stage of archicortex and then invade the ante- for stage, the fundamental principles rior part of the dorsal commissure matrix which underlie the growth of the brain or commissural bed of Elliot Smith (1897a). in all mammals." Tilney noted a precal- The first parts of the corpus callosum losal stage in all the mammals (including to develop are the corpus, the genu, and man) which he examined, that eventually the rostrum as these fibers are first seen develop a corpus callosum. in this region in front of the foramen of In the marsupial, the hippocampal for- Monro and the . The mation extends from the temporal pole to increasing number of fibers causes the the olfactory peduncle and forms the me- corpus callosum to increase in bulk and dial margin of the cortex (Ariens Kappers, in length mainly posteriorly but there is Huber and Crosby, '36, pp. 1412). This also some forward extension. The back- midline arc of hippocampus has the same ward extension of the corpus callosum is cortical makeup and general consistency throughout its extent. Along its inner mar- * Student fellow, National Institute of Neuro- gin runs a longitudinal bundle of nerve logical Diseases and Blindness. 371 372 KENNETH R. MAGEE AND ROBERT N. OLSON

Fig. 1 Illustrating the position of the hippocampus on the medial surface of the hemi- sphere and the hippocampal commissure of the marsupial. Didelphis virginiuna. not accompanicd by a corresponding ex- located on its dorsal surface (Tilney, '39). pansion of the psalterium, which therefore The is therefore becomes greatly thinned at its junction rolled back, down and out into the tem- with the splenium. The posterior expan- poral pole, into close relation with the cor- sion of the corpus callosum, interposed tex of the piriform lobe (Ariens Kappers, between hippocampal formation above and Huber and Crosby, '36, pp. 1413). A mid- hippocampal commissure below, forms the line hippocampal division persists, how- splenium (Smith, 1897a and '10). Related ever, forming the induseum griseum and to the increased development of inter- the white stria of Lancisi. Thus, even hemispheral communication in , in adult forms of higher primates, the the corpus callosum is enlarged and elon- hippocampus maintains the full arc from gated, primarily in the callosal trunk. The olfactory peduncle to temporal horn. This distance between genu and splenium is supracallosal hippocampus, however, is ap- disproportionately longer than in lower parently retarded in development by the mammals. The splenium is therefore car- introduction of the corpus callosum for ried caudad in such a way as to bear it does not grow or advance in cellular with it the hippocampal commissure and, structure and remains very small in com- at the same time, cause an elongation of parison to the hippocampus associated the longitudinal fibers of the fimbria (Til- with the temporal horn. ney, '39). The corpus callosum also influences the This caudal extension of the corpus cal- development of the , as has been losum and development of the neopallial mentioned. The fornix becomes elongated regions of the hemisphere carrics with it with the pushing backward and downward the growing structures of the archicortex of the hippocampus by the corpus callosum ABSENCE OF CORPUS CALLOSUM 373

(Ariens Kappers, Huber and Crosby, '36, systems, it would seem quite probable that pp. 1428). Although most fibers of the in agenesis of the corpus callosum: fornix are ventral to the corpus callosum, longitudinal association fibers and some fibers of the fornix (fimbria) system bundles, some of which are not are dorsal to the corpus callosum (E. usually distinguished, become more Smith, 1896, 1897a and b). Some of the fas- distinct; cicles from the medial stria of Lancisi, the location of the hippocampus cross through the corpus callosum to enter and its connections is altered; early interruption or destruction of the where they join the commissural bed can be the in the distribution of the subcallosal for- cause of true agenesis (Marburg, nix fibers. Some fibers from the hippo- '49). campal flexure (that part of the hippo- following material is mesented campus arching over the caudal part of with these obseriations in mind.L In addi- the splenium) course around the splenium tion, the composition of the so-called before they perforate the corpus callosum. Probst's bundle (longitudinal callosal bun- These fibers which perforate the corpus dle) will be noted and discussed later. This callosum to reach the fornix are called the bundle is apparent in many cases of agen- superior fornix. It is now believed that esis of the corpus callosum and appears some of these fibers may also arise from as a primarily longitudinal fiber system. the cinguli or possibly neighboring Its exact nature has been the subject of corticaI areas (Valenstein and N-auta, '59). much disagreement. There are also fibers which pass around the genu of the corpus callosum to reach DISCUSSION OF MATERIAL the septum, some of which arise from the Study 1: A 20-year-old woman had a medial striae Lancisii and become a part psychosis and jerking movements of the of the precommissural fornix (Ariens extremities. A diagnosis of Huntington's Kappers, Huber and Crosby, '36, pp. 1430). chorea was considered but not proven. As with the longitudinal fibers which Birth and developmental history and the cause of death were not available. make up the fornix systems (the fascicles Examination of the brain disclosed com- of the striae of Lancisi, etc.), the major pIete agenesis of the corpus callosum. The association bundles, which connect differ- anterior commissure was present as was ent lobes of the same hemisphere, are in the fornix which, however, was separated close anatomical relationship with the cor- throughout its full extent. Olfactory tracts pus callosum. The fibers which make up were present. The septum pellucidum was these bundles vary in number and kind absent. The gyrus cinguli was not present, (short or long association fibers) at differ- although the regions of cortex which usu- ent parts of the bundle. Longitudinal asso- ally make up this gyrus may have been ciation fibers exist which are not con- represented by portions of the convolu- densed into the bundles but run among tional pattern. Sulci radiated from what the corpus callosal fibers, being perpendic- in a normal brain wouId have been the ular to them. With the absence of such callosal . The parieto-occipital sulci a large structure as the corpus callosum, did not meet the calcarine . it is easily seen how the longitudinal fibers The hippocampal formation was of par- of the fornix longus, the fornix superior, ticular interest and had not taken its nor- and the association fibers of the hemis- mal adult position (as in the adult) but pheres may come into a close relationship remained in a more medial and dorsal posi- to form a bundle. tion, lying next to the medial wall of the Considering the ways in which the de- lateral ventricle. Figure 2 shows the hippo- velopment of the corpus callosum affects campus in this position, superior to the the position of the hippocampus and for- inferior colliculus. Some of the fibers of nix, and the manner in which develop- Probst's bundle apparently turned down- ment of this large neopallial commissure ward to the hippocampus but they were not can obscure the finer longitudinal fiber of sufficient number to account for more 374 KENNETH R. MAGEE AND ROBERT N. OLSON

Fig. 2 Note the raised position of the hippocampus and its position superior to the in- ferior colliculus.

than 20% of the bundle. It is possible bers into a more compact structure. Seen that a larger number of fibers from this in each frontal plane, some of these arch- bundle entered the hippocampus and may ing fibers ran throughout the entire extent have turned into it rostra1 to the section, of the bundle to reach the fornix. These for serial sections of the brain were not “perforating” fibers thus assert their simi- available. larity to the perforating fibers of the corpus Probst’s bundle extended as a protruding c allosum. mass along the whole length of the lateral The Probst’s bundle at levels through the ventricle at the junction of the medial and posterior horn of the lateral ventricle had the dorsal portions of the wall of the ven- demonstrable connections with the occipi- tricle. At the level of the anterior nucleus tal cortex. There was also a strong con- of the thalamus, it was of greatest size and tinuity of the bundle with the fimbria of most complex structure (fig. 3). The for- the abnormally placed hippocampal forma- nix appeared as a tapering extension from tion. In other words it was a combined the ventral part of the bundle and followed fornix and association bundle. it along its whole protrusion into the ven- Study 2: This study was made on post tricle. Fibers passed not only longitudi- mortem material of the brain of a white nally but also obliquely. These oblique fi- child, who died at age two. A second cous- bers coursed from the most ventral part in was feebleminded but otherwise there of the medial cortex to the fornix, there- was no family history of neurologic dis- fore passing between the longitudinal fi- ease. Retarded physical and mental devel- bers. Fibers arising from cortex or passing opment were evident. She could not sit up to it from the bundle first appeared to form and had moderately hyperactive reflexes an arch along the upper part of the bundle, but no paralysis. The eyes were suggestive which circumscribed the longitudinal fi- of mongolism but other stigmata of this ABSENCE OF CORPUS CALLOSUM 375

Fig. 3 Illustrating Probst’s bundle at the level of the thalamus. disorder were not evident. A diagnosis of development, or family history. Four years microcephaly was made. She died of pneu- before death, he developed an embryonal monia. carcinoma (monocellular type) of the right Anatomical study showed fusion of the testicle. This eventually resulted in death frontal lobes in the anterior portion with due to massive retropcritoneal lymph node slight symmetrical cortical atrophy. The metastases with ureteral obstruction and corpus callosum was absent. In the ab- uremia. sence of the corpus callosum, there was a The brain was completely fused in both persistence of gray matter in the form of a frontal lobes with heterotopic gray masses convolution following the usual contour of scattered throughout, but mainly on either what would be considered the indusium side of the midline. The gray near the griseum over the corpus callosum in a midline resembled hippocampal tissue and normal brain (fig. 4). was in an area corresponding to the posi- Small hippocampi were also found in tion of the induseum griseum when the their adult location in the temporal lobes. corpus callosum is present (fig. 5). The The fimbriae were distorted although iden- rostrum, the genu, and the body of the tifiable. Probst’s bundle was not evident corpus callosum were absent but the splen- on either side. The entire brain was re- ium was present. The duced in size. Additional findings included was not divided as the septum pellucidum overall decrease in size of the was absent. A Y shaped single cavity was and . formed. The hippocampi were bilaterally Study 3: This is a study of the brain high and inverted (figs. 6a and b). of a man who died at 38 years of age. He Study 4: A 53-year-old female was had been hospitalized for 6 years before “simple and backward in school. Mental his death with a diagnosis of mental de- symptoms of withdrawal, hallucinations, ficiency, high imbecile grade. No informa- and aggressive behavior developed in adult tion was available about birth history, early life. Two cousins were also mentally re- 376 KENNETH R. MAGEE AND ROBERT N. OLSON

Fig. 4 Note small convolution corresponding to the area where the induseum griseum would be found in a callosal brain. tarded. Examinations, shortly before death, words. She could never walk. Neurologic disclosed organic mental deficiency with examination disclosed, in addition to se- a superimposed psychotic reaction. The vere mental retardation, spasticity of all neurologic examination was otherwise nor- extremities with contractures in her joints. mal. The patient died of chronic myo- She died of bronchopneumonia. On rou- c arditis. tine autopsy, a congenital absence of the Post mortem examination of the brain gall bladder was found. disclosed an agenesis of the corpus callo- The convolutional pattern was abnor- sum. The hippocampi were in normal lo- mal; macrogyria were present in the fron- cation but were small. Probst’s bundle was tal and the parietal lobes and microgyria present. Fibers were seen entering it from in the . The parieto-occipital the cingulate gyrus. The connections of did not meet the calcarine fissure. Probst’s bundle were the same in study 1 The sulci in the parietal and the occipital (fig. 7). regions radiated from the callosal sulcus. Study 5: A 7-year-old child, who had The cingulate gyrus was not present al- had a normal birth and no family history though there were longitudinal gyri in the of neurologic disease, showed early re- which were interrupted by tarded mental and physical development. short shallow sulci. The occipital lobe was At the age of 7, she could say only a few larger than normal (fig. 8). There was no ABSENCE OF CORPUS CALLOSUM 377

Fig, 5a and b Note gray matter dorsal to the lateral ventricle in the area where the induseum griseum would be expected in a callosal brain. anterior commissure or septum pelluci- present between the Probst’s bundle and dum. The fornix was present but divided. other parts of the frontal cortex. Longi- A Probst’s bundle was present and ex- tudinal fibers in this bundle were not so tended along the dorsomedial portion of great as in the other cases but perforating the lateral ventricle. It also extended along fibers were abundant. the medial margin of the ventricle forming At the lateral border of the roof of the with the fornix, which tapered from its ventricle and extending down the lateral ventral surface, an arch around the lower surface was a bundle of longitudinally part of the lowest convolutions of the me- running fibers. This bundle, evident in this dial cortex. Fibers coursing between the brain, but not in all of the others, was com- Probst’s bundle and the cingulate gyrus posed of association fibers and represented were abundant. Connections were also the fibers normally seen in the superior 378 KENNETH R. MAGEE AND ROBERT N. OLSON

Fig. 6a and b Note the high in1rerted position of the hippocampi. occipito-frontal fasciculus. The into the Probst’s bundle but was a separate and the stratum subcallosum could not be recognizable fiber fasciculus close to it. identified. The findings in this brain indicate that DISCUSSION the composition of the Probst’s bundle may The brains in studies 1, 2 and 3 illus- vary, depending on how close the fibers trate that, in agenesis of the corpus callo- group together in the absence of the corpus sum, abnormal accumulations of gray mat- callosum. Here the superior occipito- ter were present in an area corresponding frontal fasciculus was not incorporated to the location of the induseum griseum in ABSENCE OF CORPUS CALLOSUM 379

Fig. 7 Note agenesis of the corpus callosum with a well-formed Probst’s bundle in the dorsolateral wall of the lateral ventricle. It is best seen on the right. The convolution on the left in the same area as the bundle on the right resembles the hippocampus but its connec- tions could not be traced adequately.

Fig. 8 Note agenesis of the corpus callosum and the distorted convolutional pattern. 380 KENNETH R. MAGEE AND ROBERT N. OLSON the normal brain. Such remnants of gray the may contribute to the adult matter were quite likely hippocampal tis- position of the hippocampus. sue which has not been carried into its Other authors have noted hippocampal normal adult position by the developing tissue near the medial surface of the hemi- corpus callosum. Added evidence that such sphere in acallosal brains. Shryock, Bar- aberrant tissue is hippocampal in origin nard and Knighton (’40) demonstrated a is afforded by the first brain where the large aberrant mass of cortical tissue taken clearly identifiable hippocampus can be across the of an acallosal seen rising, from its normal position in brain that clearly resembled the hippo- the temporal horn of the ventricle, to a campus. Kuhlenbeck and Globus (’36) location dorsal and medial to the wall of presented a somewhat different anomaly the lateral ventricle (fig. 2). - arhinencephaly with extreme eversion It is unfortunate that the material avail- of the end-brain in which the corpus cal- able was not accompanied by sufficient in- losum was rudimentary and a clearly formation to allow judgment as to whether formed supracallosal hippocampus was evident. Kirschbaum (‘47) described hetero- the cerebral malformation was of genetic topic gray matter forming a bridge between origin or due to birth trauma or a similar the frontal olfactory and the hippocampal secondary process. system. He commented that this case had From the location of the hippocampal certain features in common with the ar- tissue, one might hope to determine rangement of olfactory cortex in lower whether the absence of the corpus cal- mammals but he tended to doubt that con- losum was a true agenesis or whether genital anomalies represented reversions this commissure had secondarily degen- to the ancestral condition. Lichtenstein erated after once forming. In the latter and Maloney (’54) also described two situation, one would expect the hippo- cases where failure of migration of the campus to retain its final position at the hippocampus were evident in the anoma- temporal pole of the ventricle. If the cor- lous brains. pus callosum had never formed or the The origin of Probst’s bundle (longitudi- commissural plate had been destroyed nal callosal bundle, Balkenlangsbiindel of early in development, varying degrees of Probst (’01)) has been in dispute. Accord- hippocampal tissue might be expected in ing to some observers the bundle is a the more primitive position on the medial normal structure which becomes more dis- hemispheric surface. Bruce (1889) and tinctly visible with the lack of callosal fi- 0. Marburg (’49) have given criteria for bers. This implies that the bundle is com- determining when the defect has occurred. posed of association pathways between Marburg stated that true agenesis of the various lobes of the hemisphere which ap- corpus callosum occurs during the first pear unrelated when the corpus callosum 14 days of life, but developmental defects is well developed. Other investigators have of the corpus callosum occur during the felt that the bundle consists of aberrant second half of fetal life and a complete callosal fibers which, instead of crossing agenesis does not occur. to the other hemisphere, assume a sagittal Although absence of the corpus callosum direction. The most detailed account of the has been shown to alter the position of the bundle in the English language is that of hippocampus as described above, it is deLange (’25). After a careful review of equally true that in some cases of absence the subject, deLange presented a brain of the corpus callosum where there is no with partial agenesis of the corpus callo- obvious evidence to suggest a degenerative sum in which, instead of a splenium, there process, the hippocampus finds its way to was a “pseudosplenium,” fibers of which the adult position. Even in the cases de- radiated to the cortex in a manner similar scribed in this paper varying amounts of to that of a normal splenium and which hippocampal tissue were observed in the had a position comparable to a longitudi- normal position. This would indicate that nally running Probst’s bundle. She con- additional factors besides the development cluded, therefore, that the Probst’s bundle of the corpus callosum and expansion of contained aberrant, uncrossed fibers of the ABSENCE OF CORPUS CALLOSUM 381 corpus callosum. Recently, Akert, Puletti, correlates with the hypothesis in the pre- and Erickson (’54), suggested that a band ceding paragraph. of heterotopic in the post- central gyrus of an acallosal brain repre- ACKNOWLEDGMENT sented misdirected callosal fibers. They We wish to acknowledge with deep grati- also suggest that Probst’s bundle is of the tude the guidance and assistance of Dr. same origin. Cameron (’07) and Douglas- Elizabeth C. Crosby throughout this study. Crawford (’06) described acallosal brains which have a Probst’s bundle and persist- LITERATURE CITED ance of gray matter on the medial surface Akert, K., F. Puletti and T. C. Erickson 1954 Abnormalities of the associ- of the hemisphere from the to the ated with agenesis of corpus callosum and fo- olfactory region. They suggested that these cal cortical . Trans. Am. Neur. Assoc., structures are representatives of the limbic 79: 151-153. lobe and that the longitudinal fibers of Ariens Kappers, C. U., G. C. Huber and E. C. Crosby 1936 The comparative anatomy of Probst’s bundle are related to the fornix the nervous system of vertebrates, including system, the longitudinal stria and connec- man. The MacMillan Co., New York. tions of the cortex with the . Baker, R. C., and G. 0. Graves 1933 Partial agenesis of the corpus callosum. Arch. New. Cameron also suggested that some of these Psychiat., 29: 1054-1065. fibers are a condensation of the normal Bruce, A. 1889 On the absence of the corpus long longitudinal intrahemispheric connec- callosum in the , with the descrip- tions. tion of a new case. Brain, 12: 171-190. Bunts, A. T., and J. S. Chaffee 1944 Agenesis It is difficult to accept the conclusion of the corpus callosum with possible poren- that fibers that normally cross and provide cephaly: review of the literature and a report interhemispheral communication assume of a case. Arch. Neur. Psychiat., 51: 35-53. instead a long aberrant longitudinal course Cameron, J. L. 1907 A brain with complete absence of the corpus callosum. J. Anat. and end indiscriminately in various regions Physiol., 41: 293-301. on the same side of the brain. It seems Carpenter, M. B., and W. H. Druckemiller 1953 more probable that association fibers be- Agenesis of the corpus callosum diagnosed dur- tween different regions of the same hemi- ing life. A.M.A. Arch. Ncur. Psychiat., 69: 305- sphere which are masked or separated 322. DeLange, C. 1925 On brains with total and from each other in the normal brain by partial lack of the corpus callosum and on the the fibers of the corpus callosum, when nature of the logitudinal callosal bundle. J. the latter structure does not exist, come Nerv. Ment. Dis., 62: 449-476. into closer relationship to each other. Thus Douglas-Crawford, D. 1905 A case of absence of the corpus callosum. J. Anat. Physiol., 40: a tract (Probst’s bundle), not recognizable 57-62. in the normal brain, is formed. That many Kirschbaum, W. R. 1947 Agenesis of the cor- of these fibers arise from areas similar to pus callosum and associated malformations. the fibers of the corpus callosum is not dis- J. Neuropath. Exp. Neur., 6: 78-94. turbing for this most likely occurs in the Kuhlenbeck, H., and J. H. Globus 1936 Arhin- encephaly with extreme eversion of the end- normal brain. It is suggested, therefore, brain. Arch. Neur. Psychiat., 36: 58-74. that Probst’s bundle is composed of at least Lichtenstein, B. W., and J. E. Maloney 1954 the following systems: (1) Septal-hippo- Malformation of the forebrain with comments campal, hippocampal-septa1 fibers and pos- on the so-called dorsal cyst. The corpus cal- losum, and the hippocampal structures. J. sible other fornix components; (2) the Neuropath. Exp. Neur., 13: 117-128. superior fornix of Elliot Smith; (3) associ- Marburg, 0. 1949 So-called agenesia of the ation fibers between various parts of other corpus callosum (Callosal defect) : Anterior cortical areas. cerebral dysraphism. Arch. Neur. Psychiat., 61: 297-312. The material presented showed that at Probst, M. 1901 Ueber den Bau des vollstandig least some of the fibers in Probst’s bundle balkenlosen Grosshirns sowie iiber Mikrogyrie are projection fibers of the hippocampus and Heterotopie der grauen Substanz. Arch. or septum pellucidum. It is obvious that Psychiat., 34: 709-786.

Shrvock.I, E. H.. ,- .T. F. Barnard and R. S. Knighton the bundle, when present as a distinct en- 1940 Agenesis of the corpus callosum associ- tity, is not composed Of just One group of ated with porencephaly: report of a case. Bull. fibers but of fibers of various types. This LOS Angeles Neur. SOC.,5: 146-163. 382 KENNETH R. MAGEE AND ROBERT N. OLSON

Smith, G. Elliot 1896 The “fornix superior.” - 1910 Some problems relating to the J. Anat. Physiol., 31: 80-94. evolution of the brain. Lancet.. I: 1-6. 1897a The Origin Of the ‘Orpus Tilney, F. 1939 The hippocampus and its re- losum: a comparative study of the hippocam- lations to the corpus callosum, J. N~~~,Merit. pal region of the cerebrum of Marsupialia and Dis,, 89: 433-513. certain Cheiroptera. Tr. Linnean SOC. Lond. Zoology 2nd. Ser., 7: 47-69. Valenstein, E. S., and W. J. H. Nauta 1959 A 1897b The relation of the fornix to the comparison of the distribution of the fornix margin of the cerebral cortex. J. Anat. Physiol., system in the rat, guinea pig, cat, and monkey. 32: 23-58. J. Comp. Neur., 113: 337-363.