Btatn Research, 95 (1975) 1-24
1
,U Elsevier Scientific Pubhshmg Company, Amsterdam - Prmted m The Netherlands
Research Reports
SOME C O N N E C T I O N S OF T H E E N T O R H 1 N A L ( A R E A 28) A N D P E R I R H I N A L ( A R E A 35) C O R T I C E S OF T H E R H E S U S M O N K E Y I T E M P O R A L LOBE A F F E R E N T S *
GARY W VAN HOESEN** ANDDEEPAK N PANDYA** Hat va~d Neutologtcal Umt, Boston City Hospttal, Boston, Mass 02118 and Aphasta Research Centel, Depattment of Neurology, Boston Umverstty Medtcal School, Boston, Mass 02130 ( U S .4 )
(Accepted March 10th, 1975)
SUMMARY
In this lnvest,gatlon the efferent projections from ventral temporal neocort,cal and llmblc cortical areas to the entorhmal and penlhlnal cortices have been investigated in the rhesus monkey using Sliver ,mpregnatlon methods It was observed that virtually all ventral temporal neocortlcal areas contribute some afferents to the trans,t,onal zones of penallocortex (perlrhmal and prorhlnal cortices) forming the walls of the rhlnal sulcus These areas in turn project medially to the entorhmal cortex and h,ppocampus Addlt,onal direct sources of afferent input to the entorhlnal cortex were found to originate in Brodmann's areas 51.49 and 27, and Bonln and Ba,ley's areas TF and T H These connectmns have been characterized as final relays in multtsynaptlc cort,co-cortlcal pathways hnkmg the entorhmal cortex and, ultimately, h~ppocampus to the assoclat,on areas of the frontal, parietal, temporal, and occipital lobes
INTRODUCTION
The entorhlnal cortex (Brodmann's area 28, see ref 5) is a unique area of corte× which forms the caudal portion of the uncus Neurons of this perlallocortex g,ve rzse to the perforant pathway which terminates in the fascia dentata and hlppocampusJ, 6, 11,1.,, providing these structures with the,r prlnc,pal extr,nslc afferents and. possibly. their only cortical afferents Although these effetent connecttons are well-known, httle is known of afferent connectton~ to the entorhmal area This has largely precluded characterizing the input of the h~ppocampus, a structure postulated to play an intimate * A prehmlnary report regarding some of the findings here has been previously pubhshed36 ** Present address Harvard Neurolog,cal Umt, Beth Israel Hospital, Boston, Mass 02215, U S A
role in diverse aspects ot behavior including human memory 3' Cajal" emphasized this problem, asserting (p 175) that 'ffthe angular ganghon (entorhmal cortex) Is olfactor3, then so should Ammon's horn be olfactory If the former is optic, so is the latter, etc " In th~s report experimental neuroanatom~cal ewdence is presented which elucidates some of the sources and some of the routes wa which cortical input from the ventral temporal lobe may act upon the penrhmal (area 35) and entorhmal (area 28) cortices of the rhesus monkey MATERIALS AND METHODS
Surgtcal procedure The h~stolog~cal material described here was from the brains of 15 young-adult rhesus monkeys Each had received a undateral cortical ablation by aspiration whde under Nembutal anesthesm To expose the normally inaccessible ventro-medlal temporal lobe, 40 ml of 25 ~ manmtol (Osmltrol ®) was routinely admimstered intravenously prior to mClSmg the dura mater The use of th~s dmretlc, which temporardy decreases the overall volume of the brain, m combination with the removal of the zygomatlc arch, and the positioning of the monkey on its back or side, reduced the necessity for mechamcal retraction and minimized damage to the cortex surrounding the intended area of ablation Examinations of each hemisphere for infarcts attributable to these techmques were consistently negative
Htstologtcal procedures After a survival period of 6-12 days, the monkeys were perfused transcardlally with sahne and 10 ~ formahn The brains were removed and stored for 4-8 weeks in 1 0 ~ formalin Each brain was then divided into quadrants by longitudinal and transverse cuts and the medial, lateral, ventral, and dorsal surfaces photographed Following a week of soaking m a sucrose-formahn solution (30 ~ sucrose w/v with 10 ~ formahn), the frontal and occipital quadrants of the brain were affixed together and embedded m an albumin and gelatin matrix These blocks were cut transversely at 26 # m and stained with the Nauta 1°, Fmk-Helmer 1°, and Nlssl methods (cresyl violet). The sections were then examined hght microscopically with evidence of degeneration recorded on graph paper with the use of an X - Y recorder coupled to the two axes of the microscope stage This reformation was reconstructed onto tracings of the respective wews of the brain
Identtfieatlon of the uncal cortex tn the rhesus monkey Brodmann 5 divided the uncal cortex into area 51, the preplnform and periamygdalold cortex, and area 28, the entorhmal cortex Both tie medial to the rhmal sulcus and compnse the rostral one-half of the parahlppocampal area in the rhesus monkey (Fig 1A-C) Although some older reports dealt with primates m comparative investigations of these heterogeneous areas (cf Fdlmonov 9, and Plgache24), a definitive map of the uncus based on its cytoarchltecture is not available for the rhesus monkey Consequently, we have mapped this area using Nlssl-stamed material sectioned m the transverse, saglttal, and horizontal planes and reduced silver impregnated matertal a7
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Fig 1 A the conventional view of the ventral surface of the rhesus monkey brain is depicted, illustrating the well-defined superior temporal gyrus (stg) and the ill-defined middle (mtg) and inferior (itg) temporal gyrl The rhmal (rs) and occipltotemporal (ots) sulcl define the localization of the parahippocampal area, although its rostral component is largely hidden B this view of the rhesus monkey brain depicts the medial surface of the hemisphere and the ventro-medlal temporal lobe after the brain stem has been dissected away allowing the parahlppocampal area to be observed. The rostral portion is composed of perlallocortical areas 51 (preplrxform and perlamygdalold cortices) and 28 (entorhlnal cortex), while the caudal portion is composed of neocortlcal areas TF-TH and area prostrlata (AP) C eight sections in the transverse plane are shown and the approximate localization of temporal neocortical (TE, TG) and parahlppocampal areas (51, 28, 35, 49, and TF-TH) indicated These sections correspond numerically to the levels shown in Fig 1A Note that the perlrhlnal cortex (area 35) hes lateral to the rhmal sulcus, but is considered here to be part of the parahJppocampal area
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Fig 2 The parahJppocampal area and ventromedlal lobe are depicted two-dimensionally, having been pulled laterally away from the htppocampal fissure and caudally away from the hmen msulae (cf Fig 1B) to compensate for curvature The cytoarch~tectomcsubareas of the uncal cortex are further defined m the text sectioned m the transverse plane These results are summarized in Fig 2 The cytoarchitectonic subdivisions are represented on a v~ew of the ventro-medial temporal lobe as it would appear when the brain stem is dissected away and the hemisphere tilted 45 ° from the sagatal plane As depicted m Fig 2, the entorhinal area has been parcellated into 3 subareas, the classical zones 28a and 28b 5, and a sizable intermediate zone labeled 281 The cortex along the medml wall of the rhmal sulcus throughout its rostro-caudal extent ~s labeled prorhmal cortex (Pr) and set apart from the classical subareas because of its umque cyto- and fiber-architectonic features, as well as its connections 3~ Its caudal portions correspond to what we have previously called the lateral p o m o n of the lateral entorhlnal cortex 36 The perlrhlnal cortex (area 35) forms the lateral wall of the rhmal sulcus m the rhesus monkey and has been dwided into subareas, a medlally positioned area 35a, and a laterally positioned area 35b The rostral pole of the uncus (area 51) xs composed of two major subareas, the prepJrlform cortex (ppc), and the heterogenous periamygdalo~d cortex (pare) Encompassed within the latter are the nucleus of the lateral olfactory tract, Samdes and Sas' perlpaleocortex 28, and that p o m o n of uncal cortex dorsal to the amygdaloid sulcus where Cajal-Retzms fetal cells are
observed m the plextform layer 28 Areas 49 (parasubmulum) and 27 (presublculum) form the medml-most components of the parahlppocampal area E n t o , h m a l col rex
The classical subareas of entorhlnal cortex ~ are easily recognizable in the rhesus monkey Area 28a is the largest and contains the basra archltectomc prototype against whmh others are compared In the Nlssl-stamed sections (Figs 3B and 4C-D) It e\hlblts a wide cell sparse layer I (outer ple\lform zone), a neatly ahgned layer lI of large stellate cells, a wide layer lIl of medmm size pyramtdal cells, a cell sparse layer IV (lamina &ssecans or tuner plexlform layer), a narrow, but dlstmgmshable, layer V composed of smaller pyramidal and horizontal cells and a multllamlnated layer VI composed of what Cajal 6 described as polymorph and spindle shaped cells In NIssl materml, layers II and IV form the most discernible charactenstms of th~s area Th~s arrangement characterizes all levels of area 28a, but rostro-caudal and medlo-lateral gradients m cell density and laminar wzdth are observed m the rhesus monkey Area 28b has a similar overall arrangement as area 28a but can be set apart for several reasons Firstly, the stellate cells of la~er II appear smaller and more fustform, and are conspicuously arranged in small mrcular clusters Secondly, layer Ill Is less compact than that of area 28a and has an overall patchy appearance (Fig 3A) Thirdly, layer IV (lamina &ssecans) or area 28b is varmble throughout the extent of this cortex and difficult to detect except at caudal levels And fourthly, la~er VI lacks a sharp multflamlnated appearance
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4, f.F~g 3 A and B photomicrographs of NJssl-stamed transverse sechons through the uncus of the rhesus monkey, depicting the general cytoarchltectomc orgamzatlon of the entorhlnal (28) prorhmal (Pr), and perJrhmal (35) cortices at these le,~els 12
Fig 4 C and D photomicrographs of Nlssl-stamed transverse sections through the uncus of the rhesus monkey, depicting the general cytoarchltectonlc orgamzat~on of the entorhmal (28), prorhlnal (Pr), and penrhmal (35) cortices at these levels 12 In reference to further parcellatlon of the entorhinal area, Lorente de No ~s stated, 'the area entorhlnahs is constituted according to the same plan m every mammal, t e , the number of subfields is constant' (p 159) FilImonov 9 challenged thIs assertion, and proposed that in primates ~t differs considerably from that of lower forms in having a greater number of subareas Our own observations favor those of Flhmonov For example, in the rhesus monkey a sizable zone can be observed to have characterlstlcs of both classical subareas This area has been labeled 281 and m Nlssl material has the following characteristics Layer lI is composed of large Islands of stellate cells which contrast sharply with the neat uninterrupted ahgnment of these cells m area 28a and the smaller circular islands of area 28b Layer lII is less patchy than m area 28b but less compact than m area 28a Layer IV Is &scermble m area 281, a characteristic slmdar to area 28a, but unhke area 28b And lastly, layer VI appears less multllammated than in area 28a, but decidedly sharper than m area 28b Thus, area 281 mtght represent an intermediate zone, embodying some of the dlstmgmshable characteristics of both classical subareas, but lacking the definltwe characteristics of either As wall be shown below, thws area recewes input from afferent sources that project to both areas 28a and 28b The cortex forming the medial wall of the rhinal sulcus was set apart by FIIImonov 9 as a distinct zone m virtually all primates he studied. Although th~s cortex appears to vary m structure depending upon the type of entorhmal cortex ~t borders, it wall all be called prorhmal cortex in this report The lateral-most portion, which adjoins area 35, is labeled Pr2 and has a umque appearance m Nissl-stained sections (Figs 3 and 4) Layer II of Pr2 contains large elongated and deeply stained stellate
cells which appear unlike those of the other entorhlnal subareas Layers Ill, IV, V, and VI blend throughout Pr2 and lose their distractive features m the depths of the rhlnal sulcus The lamina dlssecans is seldom d~scernlble At levels rostral to area 28b, a conspicuous zone can be observed separating Pr2 from the ventralmost regions of the prepirlform and permmygdalold cortex Th~s zone has been labeled Prl and appears similar in architecture to a zone recently described in the rat z6 The architecture and connections of this area as well as area Pr2 will be dealt with more extensively in a future report The fiber architectonics of the entorhlnal cortex complement the cellular pattern described above and appear in substantial accord with those described in the cat 31 The principal new feature not described in other species ~s a dense fiber plexus encompassing the superficml layers ( I - I I ) of the prorhlnal cortex This is shown in Fig 5A-B where it can be compared with area 28a Area 28a contains a dense fiber band in layer I called the sublamlna tangentialls 3~ Deep to this layer, and extending to the inner plexfform layer, msthe wide superficial radial plexus composed of radially arranged fibers and their arborlzatlons Beneath this layer and extending to the white matter is the deep radial plexus In comparison, the prorhlnal cortex throughout the caudal levels (of Fig 5A-B) is filled with not only radial fibers but horizontal and randomly arranged fibers as well, and a particularly dense plexus is formed As will be detailed below, these laminae are the termination field for a large quantity of afferent fibers from throughout the ventral temporal lobe, and undoubtedly their arborlzatlons contribute to these fiberarchltectonlc features P e t u h m a l coJ tex Area 35 was described by Brodmann 5, and as indicated m his Fig 26 (p 49), was localized largely lateral to the depths of the rhmal sulcus in the rhesus monkey Little attention has been paid to this zone of transitional cortex since this time Lorente de N6 TM, in discussing the entorhlnal cortex of monkeys, asserted that he Included area 35 within area 28, but examination ofh~s photomicrographs (Fig 33, p 162) indicates that he was confused about the area's exact localization since he considered cortex lateral to the depths of the rhlnal sulcus temporal cortex Samdes 27 confirmed a number of Brodmann's observations in the monkey and characterized area 35 as an intermediate type of cortex (pro~socortex) positioned between the perlallocortlcal entorhlnal cortex medmlly and temporal neocortex laterally He suggested that the area be parcellated into subareas (of Figs 2, 3A-B, and 4A B) with one (35a) bearing more resemblance to entorhmal cortex and another (35b) bearing more resemblance to neocortex According to Sanldes 17, area 35a begins in the depths of the rhlnal sulcus and several features set it apart from neighboring areas For example, layer II is accentuated in width with large cells, but m contrast with this layer of entorhmal cortex, they are neither as large nor as deeply stained in Nlssl material We have observed that In rostral levels where area 35 continues beneath olfactory cortex to end in the lower bank of the Sylvlan fissure ventral to the Insular cortex, as well as at caudal levels, where the rhmal sulcus is shallow, these cells are often grouped together in small
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Fig 5 T h e upper p o l t l o n of this illustration J~ a transverse section f r o m a rhesus m o n k e y stall~ed by Vogt~s ~7 sliver i m p r e g n a t i o n m e t h o d It depicts the fiberarch]tectomc features of the e n t o r h m a l (28) a n d p r o r h m a l (Pr) cortices Especially n o t e w o r t h y is the dense fiber plexus e n c o m p a s s i n g layers 1 a n d 2 o f Pr2 15 T h e p h o t o m i c r o g r a p h s (a-c) m the lower portion o f the illustration provide a c o m p a r i s o n between these laminae m areas 28a, Pr2, a n d 35 Note the dense a n d r a n d o m arrangem e n t o f fibers in area Pr2 in c o m p a N s o n to areas 28 a n d 35 125
clusters a4 Another feature of area 35a is the absence of granule cells in layer IV This contrasts markedly with the neocortex of the temporal lobe, but is consistent with the absence of cells in layer IV of entorhlnal cortex Finally, area 35a contains a dense layer V composed of large pyramidal cells Area 35b, according to Sanldes zT, lies immediately lateral to area 35a and likewise has numerous architectonic features distinguishing it from neighboring areas Layer I I, m comparison with temporal neocortex, is accentuated with cells forming a wide compact layer A distinguishable layer IV composed of loosely packed granule cells IS apparent in this area, a feature which contrasts sharply with the total absence of these cells in area 35a and the compact layel IV of temporal neocortex Layer V of area 35b is the most readily distinguishable feature of this cortex and appears as a conspicuous island of large deeply stained pyramidal cells throughout the rostrocaudal extent of this area These cytoarchltectonlc observations may suggest that the perlrhlnal and prorhlnal cortices form transitional belts between the atypical, but well-differentiated entorhlnal cortex of the caudal uncus and the neocortex of the temporal lobe It will be shown below that these areas receive substantial neoccrtlcal afferents and in turn project medially to the entorhlnal cortex RESULTS
Ahlatlon o f aleas TG and TE The efferent cortlco-comcal connections of Bonln and Bailey's ~ areas TG and TE have been described a number of times lz,~'z as, although It remains unclear how they relate anatomically to areas 35 and 28 Only these relationships will be emphasized here since our observations of other cortlco-cortlcal connections are in accord with other results previously detailed As depicted in Fig 6A, case 1 had a large ablation of the temporal pole largely confined to area TG From this ablation degeneratzon could be traced to the rostral portions of areas TE and TA, with evidence of terminal degeneration centered In and around layer 1V of these areas Medially, degeneration could be traced to area 35 where a conspicuous widening of the terminal degeneration was observed (Fig 10a and b) Evidence of degeneration could be further traced around the depths of the rhlnal sulcus into layers I - I l l or area Pr2, but it ceased abruptly at the junction of this cortex with areas 28a and 28b Cases 2, 3, and 4 all had ablations in area TE Cases 2 and 4 (Fig 6A) had large ablations which together encompassed the entire region except the area ablated in case 3 In the larger ablations considerable damage was incurred by the white matter underlying the ablated cortex In reference to areas 35 and Pr2, the pattern of degeneration was virtually identical to that just described for case 1 Briefly, as the degeneration from the ablation was traced medially, a conspicuous widening of its laminar distribution was observed This corresponded archltectonlcally with the localization of area 35 and afforded considerable contrast with the pattern of degeneration in ne~ghborlng neocortlcal areas where it was primarily centered around layer IV Further medially, a moderate quantity of degeneration could be followed around the
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Fig 6. A this illustration depicts the topography of the ablations in cases 1-4 on a view of the ventral surface of the temporal lobe The two series of transverse sections (1-3) were taken from cases 1 and 2, and their approximate levels correspond to the numerals shown o n the ventral vaew. The general pattern of terminal degeneration observed for a case is depicted by dots B this illustration summarizes the observed projecUons to the perirlunal and prorhinal cortices after area TE and T G ablations For this illustration and those that follow, specific dots a n d arrows are not meant to imply pathways or point to pomt projections, hut only the general stte of o n g m for a projection and the cytoarchitectomcalty defined region within which It terminates
11 depths of the rhlnal sulcus m layers I - I I I of Pr2 (Fig 10c) Cases hawng area TE ablations were also observed to contribute a moderate projection to the parahlppocampal areas T F - T H Ablation o f alea TF-TH Bonm and Badey 4 identified in the rhesus monkey two areas caudal to the entorhlnal cortex (areas T F and TH) in what we regard as the neocortical port~on of the parahlppocampal area Three ablations were successfully placed m area T F - T H and are dlustrated In Fig 7A Case 5 had a discrete ablatmn locahzed medial to the rostral t~p of the OCClpltotemporal sulcus Case 6 had a more medially located ablatmn which extended to the border of this area w~th areas 49 and 27 U n h k e case 5, the underlying white matter was invaded, causing a partial disruption of the temporal extension of the cmgulum Case 7 had a larger more caudally placed ablation whIch encroached into the rostral levels of area OA on the ventral surface of the hemisphere In all of these cases a strong rostral and lateral spread of degeneration could be observed Into areas TE, 35, Pr2, 28a, and 281 In each of these areas, however, the laminar distribution of degeneration differed In area TE, it was centered almost exclusively around layer IV In area 35, all layers contained moderate to heavy degeneration, with the heaviest quantities occurring along the caudal one third of the rhmal sulcus in layers I I I - V (Fig 10d) In Pr2, degeneration was observed m moderate quantities and was distributed predominantly to layers I - I I I Unhke the pattern of degeneration following area T G and TE ablations, a moderate quantity of degeneratIon was also observed in layers I and II of areas 28a and 281 In all 3 cases (Fig 10e) These observations imply that while all ventral temporal neocortlcal areas project to the perlrhmal and prorhlnal cortices, only area T F - T H projects m addition to a classical entorhmal cortex subarea The last neocortlcal region of the parahlppocampal area, area prostrlata, was partially ablated in case 8 This ablatlon also encroached into areas OA and OB on the ventral aspect of the occipital lobe (Fig 7A) No projectmns were observed from th~s ablation to either areas 28 or 35, but as IS summarized m Fig 7A, a heavy and diffuse projectmn to area T F - T H was observed Ablatton o f area 35 Of the 8 cases described to this point, only those having ablations of area T F - T H were observed to contribute afferents directly to the entorhlnal cortex All of the other ventral temporal neocortlcal areas, Including area T F - T H as well, had projections to the prorhmal and perlrhinal areas bordering the rhinal sulcus In lieu of the apparent convergence of input to these areas, 3 ablations are described which damaged area 35 Case 9 (Fig 8A) had a small ablation located along the caudal one-third of the rhlnal sulcus This ablation extended to the depths of the rhlnal sulcus but did not invade areas Pr2, 28a, and 28b Area TE lateral to the rhlnal sulcus was damaged as well as area T F - T H caudal to the entorhlnal cortex This neocortlcal damage, however, overlapped with that previously described in which there was no involvement of area 35 Case 10 had a large ablation lateral to the rhlnal sulcus The middle one-third of this
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Fig 7 A this illustration depicts the topography of the ablations m cases 5-8 on the ventral surface of the temporal lobe The two series of transverse sections (1-3) were taken from cases 5 and 6, and thetr approximate levels correspond to the numerals shown on the ventral view The general pattern of terminal degeneration observed for a case is depicted by dots B thts dlustratlon summarlzes the observed projections to the entorhmal, penrhmal and prorhlnal cortices after area TFT H ablations
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Fig 8 A this illustration depicts the t o p o g r a p h y of the ablations in cases 9-11 on the ventral surface of the temporal lobe The two series of transverse sections (I 3) were taken f r o m cases 9 and 10, and their approximate levels correspond to the numerals shown on the ventral view The general pattern of terminal degeneratton observed for a case is depicted by dots B this illustration summarizes the observed projections to the entorhlnal cortex after a b l a u o n s that damaged area 35
14 ablation extended into the depths of the rhmal sulcus and directly damaged or undercut areas 35a and 35b Case 1 l had a small ablation on the medial surface ol the temporal pole dorsal to the temporal preplnform cortex and ventral to the insular cortex Th~s ablation encroached into area TG, but also damaged the rostral p o m o n s of area 35a Unhke cases having only temporal neocomcal ablations, these cases all contained degeneration m areas 28a, 28~, and 28b At levels near the ablation, the pattern of degeneration was heavy, but decreased as the distance from the ablation mcreased For example, case 1t had projections directed to the rostral levels ot areas 28b and 28~ with only a hght amount of degeneration m area 28a Case 10 had projections to the entorhlnal areas near the ablation with decreasing amounts of degeneration rostralty and caudally Case 9 had heavy degeneration m areas 28a (F~g 10f), 28~, and caudal 28b, but the quantity decreased markedly as area 28b was followed rostrally These observations suggest that area 35 projects locally to contiguous levels of entorhmal cortex and not topographically to mdwldual subareas
Dtsrupttons of the cmgulum A potential confounding feature of ablations near the rhmal sulcus, and especially those in the caudal parahlppocampal area, can be the disruption of the cingulum since it forms a sizable component of the white matter m this region of the brain The majority of the cases having area 35 and area T F - T H ablations did not have heavy white matter involvement, but some involvement was unavoidable to the superficml components of the whtte matter m a number of cases (cf cases 6 and 9) We would hke to emphasize m this regard that m independent cases the cmgulum has been disrupted above and below the splemum of the corpus callosum, and a laminar pattern of degeneration duphcatlng that following either an area 35 or area T F - T H ablation has never been observed z3 Our observations indicate that the cmgulum m the rhesus monkey terminates almost exclusively in the presublculum (area 27) and to a lesser extent in the deeper lamina (V-VI) of area 28a An additional light and diffuse pattern of degeneration of presumed cmgulum o n g m has also been observed in Pr2
Ablatton of area 51 Afferent projections to the entorhmal cortex from area 51 have been described in rats 7,16,25, rabbits 7, and cats 7,1~ These well-documented observations are opposed to Adey and Meyer's 2 negative observations in the monkey where large ablations were made in the rostral uncal cortex including the amygdala. We have made an ablation in Brodmann's area 51 using a surgical approach across the r o o f of the orbit Case 12 (Fig 9) had an ablation m the rostral uncus which damaged the p r e p m f o r m and periamygdalold cortices as well as the ventral-most portions of the medial and lateral components of the basal amygdalold nucleus This ablation did not encroach into the entorhlnal cortex or its subjacent white matter L~kewme, the orbltofrontal cortex was free of damage F r o m the ablation, a strong caudotateral spread of degeneration was observed with heavy quantities m layers I - I I I of areas 28b (Fig 10g), 281, and Pr2, as well as hght evidence of terminal degeneration in area 35 Degenerating fibers emanating from the ablation appeared to reach these areas via both the plexlform
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,U Elsevier Scientific Pubhshmg Company, Amsterdam - Prmted m The Netherlands
Research Reports
SOME C O N N E C T I O N S OF T H E E N T O R H 1 N A L ( A R E A 28) A N D P E R I R H I N A L ( A R E A 35) C O R T I C E S OF T H E R H E S U S M O N K E Y I T E M P O R A L LOBE A F F E R E N T S *
GARY W VAN HOESEN** ANDDEEPAK N PANDYA** Hat va~d Neutologtcal Umt, Boston City Hospttal, Boston, Mass 02118 and Aphasta Research Centel, Depattment of Neurology, Boston Umverstty Medtcal School, Boston, Mass 02130 ( U S .4 )
(Accepted March 10th, 1975)
SUMMARY
In this lnvest,gatlon the efferent projections from ventral temporal neocort,cal and llmblc cortical areas to the entorhmal and penlhlnal cortices have been investigated in the rhesus monkey using Sliver ,mpregnatlon methods It was observed that virtually all ventral temporal neocortlcal areas contribute some afferents to the trans,t,onal zones of penallocortex (perlrhmal and prorhlnal cortices) forming the walls of the rhlnal sulcus These areas in turn project medially to the entorhmal cortex and h,ppocampus Addlt,onal direct sources of afferent input to the entorhlnal cortex were found to originate in Brodmann's areas 51.49 and 27, and Bonln and Ba,ley's areas TF and T H These connectmns have been characterized as final relays in multtsynaptlc cort,co-cortlcal pathways hnkmg the entorhmal cortex and, ultimately, h~ppocampus to the assoclat,on areas of the frontal, parietal, temporal, and occipital lobes
INTRODUCTION
The entorhlnal cortex (Brodmann's area 28, see ref 5) is a unique area of corte× which forms the caudal portion of the uncus Neurons of this perlallocortex g,ve rzse to the perforant pathway which terminates in the fascia dentata and hlppocampusJ, 6, 11,1.,, providing these structures with the,r prlnc,pal extr,nslc afferents and. possibly. their only cortical afferents Although these effetent connecttons are well-known, httle is known of afferent connectton~ to the entorhmal area This has largely precluded characterizing the input of the h~ppocampus, a structure postulated to play an intimate * A prehmlnary report regarding some of the findings here has been previously pubhshed36 ** Present address Harvard Neurolog,cal Umt, Beth Israel Hospital, Boston, Mass 02215, U S A
role in diverse aspects ot behavior including human memory 3' Cajal" emphasized this problem, asserting (p 175) that 'ffthe angular ganghon (entorhmal cortex) Is olfactor3, then so should Ammon's horn be olfactory If the former is optic, so is the latter, etc " In th~s report experimental neuroanatom~cal ewdence is presented which elucidates some of the sources and some of the routes wa which cortical input from the ventral temporal lobe may act upon the penrhmal (area 35) and entorhmal (area 28) cortices of the rhesus monkey MATERIALS AND METHODS
Surgtcal procedure The h~stolog~cal material described here was from the brains of 15 young-adult rhesus monkeys Each had received a undateral cortical ablation by aspiration whde under Nembutal anesthesm To expose the normally inaccessible ventro-medlal temporal lobe, 40 ml of 25 ~ manmtol (Osmltrol ®) was routinely admimstered intravenously prior to mClSmg the dura mater The use of th~s dmretlc, which temporardy decreases the overall volume of the brain, m combination with the removal of the zygomatlc arch, and the positioning of the monkey on its back or side, reduced the necessity for mechamcal retraction and minimized damage to the cortex surrounding the intended area of ablation Examinations of each hemisphere for infarcts attributable to these techmques were consistently negative
Htstologtcal procedures After a survival period of 6-12 days, the monkeys were perfused transcardlally with sahne and 10 ~ formahn The brains were removed and stored for 4-8 weeks in 1 0 ~ formalin Each brain was then divided into quadrants by longitudinal and transverse cuts and the medial, lateral, ventral, and dorsal surfaces photographed Following a week of soaking m a sucrose-formahn solution (30 ~ sucrose w/v with 10 ~ formahn), the frontal and occipital quadrants of the brain were affixed together and embedded m an albumin and gelatin matrix These blocks were cut transversely at 26 # m and stained with the Nauta 1°, Fmk-Helmer 1°, and Nlssl methods (cresyl violet). The sections were then examined hght microscopically with evidence of degeneration recorded on graph paper with the use of an X - Y recorder coupled to the two axes of the microscope stage This reformation was reconstructed onto tracings of the respective wews of the brain
Identtfieatlon of the uncal cortex tn the rhesus monkey Brodmann 5 divided the uncal cortex into area 51, the preplnform and periamygdalold cortex, and area 28, the entorhmal cortex Both tie medial to the rhmal sulcus and compnse the rostral one-half of the parahlppocampal area in the rhesus monkey (Fig 1A-C) Although some older reports dealt with primates m comparative investigations of these heterogeneous areas (cf Fdlmonov 9, and Plgache24), a definitive map of the uncus based on its cytoarchltecture is not available for the rhesus monkey Consequently, we have mapped this area using Nlssl-stamed material sectioned m the transverse, saglttal, and horizontal planes and reduced silver impregnated matertal a7
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Fig 1 A the conventional view of the ventral surface of the rhesus monkey brain is depicted, illustrating the well-defined superior temporal gyrus (stg) and the ill-defined middle (mtg) and inferior (itg) temporal gyrl The rhmal (rs) and occipltotemporal (ots) sulcl define the localization of the parahippocampal area, although its rostral component is largely hidden B this view of the rhesus monkey brain depicts the medial surface of the hemisphere and the ventro-medlal temporal lobe after the brain stem has been dissected away allowing the parahlppocampal area to be observed. The rostral portion is composed of perlallocortical areas 51 (preplrxform and perlamygdalold cortices) and 28 (entorhlnal cortex), while the caudal portion is composed of neocortlcal areas TF-TH and area prostrlata (AP) C eight sections in the transverse plane are shown and the approximate localization of temporal neocortical (TE, TG) and parahlppocampal areas (51, 28, 35, 49, and TF-TH) indicated These sections correspond numerically to the levels shown in Fig 1A Note that the perlrhlnal cortex (area 35) hes lateral to the rhmal sulcus, but is considered here to be part of the parahJppocampal area
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Fig 2 The parahJppocampal area and ventromedlal lobe are depicted two-dimensionally, having been pulled laterally away from the htppocampal fissure and caudally away from the hmen msulae (cf Fig 1B) to compensate for curvature The cytoarch~tectomcsubareas of the uncal cortex are further defined m the text sectioned m the transverse plane These results are summarized in Fig 2 The cytoarchitectonic subdivisions are represented on a v~ew of the ventro-medial temporal lobe as it would appear when the brain stem is dissected away and the hemisphere tilted 45 ° from the sagatal plane As depicted m Fig 2, the entorhinal area has been parcellated into 3 subareas, the classical zones 28a and 28b 5, and a sizable intermediate zone labeled 281 The cortex along the medml wall of the rhmal sulcus throughout its rostro-caudal extent ~s labeled prorhmal cortex (Pr) and set apart from the classical subareas because of its umque cyto- and fiber-architectonic features, as well as its connections 3~ Its caudal portions correspond to what we have previously called the lateral p o m o n of the lateral entorhlnal cortex 36 The perlrhlnal cortex (area 35) forms the lateral wall of the rhmal sulcus m the rhesus monkey and has been dwided into subareas, a medlally positioned area 35a, and a laterally positioned area 35b The rostral pole of the uncus (area 51) xs composed of two major subareas, the prepJrlform cortex (ppc), and the heterogenous periamygdalo~d cortex (pare) Encompassed within the latter are the nucleus of the lateral olfactory tract, Samdes and Sas' perlpaleocortex 28, and that p o m o n of uncal cortex dorsal to the amygdaloid sulcus where Cajal-Retzms fetal cells are
observed m the plextform layer 28 Areas 49 (parasubmulum) and 27 (presublculum) form the medml-most components of the parahlppocampal area E n t o , h m a l col rex
The classical subareas of entorhlnal cortex ~ are easily recognizable in the rhesus monkey Area 28a is the largest and contains the basra archltectomc prototype against whmh others are compared In the Nlssl-stamed sections (Figs 3B and 4C-D) It e\hlblts a wide cell sparse layer I (outer ple\lform zone), a neatly ahgned layer lI of large stellate cells, a wide layer lIl of medmm size pyramtdal cells, a cell sparse layer IV (lamina &ssecans or tuner plexlform layer), a narrow, but dlstmgmshable, layer V composed of smaller pyramidal and horizontal cells and a multllamlnated layer VI composed of what Cajal 6 described as polymorph and spindle shaped cells In NIssl materml, layers II and IV form the most discernible charactenstms of th~s area Th~s arrangement characterizes all levels of area 28a, but rostro-caudal and medlo-lateral gradients m cell density and laminar wzdth are observed m the rhesus monkey Area 28b has a similar overall arrangement as area 28a but can be set apart for several reasons Firstly, the stellate cells of la~er II appear smaller and more fustform, and are conspicuously arranged in small mrcular clusters Secondly, layer Ill Is less compact than that of area 28a and has an overall patchy appearance (Fig 3A) Thirdly, layer IV (lamina &ssecans) or area 28b is varmble throughout the extent of this cortex and difficult to detect except at caudal levels And fourthly, la~er VI lacks a sharp multflamlnated appearance
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4, f.F~g 3 A and B photomicrographs of NJssl-stamed transverse sechons through the uncus of the rhesus monkey, depicting the general cytoarchltectomc orgamzatlon of the entorhlnal (28) prorhmal (Pr), and perJrhmal (35) cortices at these le,~els 12
Fig 4 C and D photomicrographs of Nlssl-stamed transverse sections through the uncus of the rhesus monkey, depicting the general cytoarchltectonlc orgamzat~on of the entorhmal (28), prorhlnal (Pr), and penrhmal (35) cortices at these levels 12 In reference to further parcellatlon of the entorhinal area, Lorente de No ~s stated, 'the area entorhlnahs is constituted according to the same plan m every mammal, t e , the number of subfields is constant' (p 159) FilImonov 9 challenged thIs assertion, and proposed that in primates ~t differs considerably from that of lower forms in having a greater number of subareas Our own observations favor those of Flhmonov For example, in the rhesus monkey a sizable zone can be observed to have characterlstlcs of both classical subareas This area has been labeled 281 and m Nlssl material has the following characteristics Layer lI is composed of large Islands of stellate cells which contrast sharply with the neat uninterrupted ahgnment of these cells m area 28a and the smaller circular islands of area 28b Layer lII is less patchy than m area 28b but less compact than m area 28a Layer IV Is &scermble m area 281, a characteristic slmdar to area 28a, but unhke area 28b And lastly, layer VI appears less multllammated than in area 28a, but decidedly sharper than m area 28b Thus, area 281 mtght represent an intermediate zone, embodying some of the dlstmgmshable characteristics of both classical subareas, but lacking the definltwe characteristics of either As wall be shown below, thws area recewes input from afferent sources that project to both areas 28a and 28b The cortex forming the medial wall of the rhinal sulcus was set apart by FIIImonov 9 as a distinct zone m virtually all primates he studied. Although th~s cortex appears to vary m structure depending upon the type of entorhmal cortex ~t borders, it wall all be called prorhmal cortex in this report The lateral-most portion, which adjoins area 35, is labeled Pr2 and has a umque appearance m Nissl-stained sections (Figs 3 and 4) Layer II of Pr2 contains large elongated and deeply stained stellate
cells which appear unlike those of the other entorhlnal subareas Layers Ill, IV, V, and VI blend throughout Pr2 and lose their distractive features m the depths of the rhlnal sulcus The lamina dlssecans is seldom d~scernlble At levels rostral to area 28b, a conspicuous zone can be observed separating Pr2 from the ventralmost regions of the prepirlform and permmygdalold cortex Th~s zone has been labeled Prl and appears similar in architecture to a zone recently described in the rat z6 The architecture and connections of this area as well as area Pr2 will be dealt with more extensively in a future report The fiber architectonics of the entorhlnal cortex complement the cellular pattern described above and appear in substantial accord with those described in the cat 31 The principal new feature not described in other species ~s a dense fiber plexus encompassing the superficml layers ( I - I I ) of the prorhlnal cortex This is shown in Fig 5A-B where it can be compared with area 28a Area 28a contains a dense fiber band in layer I called the sublamlna tangentialls 3~ Deep to this layer, and extending to the inner plexfform layer, msthe wide superficial radial plexus composed of radially arranged fibers and their arborlzatlons Beneath this layer and extending to the white matter is the deep radial plexus In comparison, the prorhlnal cortex throughout the caudal levels (of Fig 5A-B) is filled with not only radial fibers but horizontal and randomly arranged fibers as well, and a particularly dense plexus is formed As will be detailed below, these laminae are the termination field for a large quantity of afferent fibers from throughout the ventral temporal lobe, and undoubtedly their arborlzatlons contribute to these fiberarchltectonlc features P e t u h m a l coJ tex Area 35 was described by Brodmann 5, and as indicated m his Fig 26 (p 49), was localized largely lateral to the depths of the rhmal sulcus in the rhesus monkey Little attention has been paid to this zone of transitional cortex since this time Lorente de N6 TM, in discussing the entorhlnal cortex of monkeys, asserted that he Included area 35 within area 28, but examination ofh~s photomicrographs (Fig 33, p 162) indicates that he was confused about the area's exact localization since he considered cortex lateral to the depths of the rhlnal sulcus temporal cortex Samdes 27 confirmed a number of Brodmann's observations in the monkey and characterized area 35 as an intermediate type of cortex (pro~socortex) positioned between the perlallocortlcal entorhlnal cortex medmlly and temporal neocortex laterally He suggested that the area be parcellated into subareas (of Figs 2, 3A-B, and 4A B) with one (35a) bearing more resemblance to entorhmal cortex and another (35b) bearing more resemblance to neocortex According to Sanldes 17, area 35a begins in the depths of the rhlnal sulcus and several features set it apart from neighboring areas For example, layer II is accentuated in width with large cells, but m contrast with this layer of entorhmal cortex, they are neither as large nor as deeply stained in Nlssl material We have observed that In rostral levels where area 35 continues beneath olfactory cortex to end in the lower bank of the Sylvlan fissure ventral to the Insular cortex, as well as at caudal levels, where the rhmal sulcus is shallow, these cells are often grouped together in small
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Fig 5 T h e upper p o l t l o n of this illustration J~ a transverse section f r o m a rhesus m o n k e y stall~ed by Vogt~s ~7 sliver i m p r e g n a t i o n m e t h o d It depicts the fiberarch]tectomc features of the e n t o r h m a l (28) a n d p r o r h m a l (Pr) cortices Especially n o t e w o r t h y is the dense fiber plexus e n c o m p a s s i n g layers 1 a n d 2 o f Pr2 15 T h e p h o t o m i c r o g r a p h s (a-c) m the lower portion o f the illustration provide a c o m p a r i s o n between these laminae m areas 28a, Pr2, a n d 35 Note the dense a n d r a n d o m arrangem e n t o f fibers in area Pr2 in c o m p a N s o n to areas 28 a n d 35 125
clusters a4 Another feature of area 35a is the absence of granule cells in layer IV This contrasts markedly with the neocortex of the temporal lobe, but is consistent with the absence of cells in layer IV of entorhlnal cortex Finally, area 35a contains a dense layer V composed of large pyramidal cells Area 35b, according to Sanldes zT, lies immediately lateral to area 35a and likewise has numerous architectonic features distinguishing it from neighboring areas Layer I I, m comparison with temporal neocortex, is accentuated with cells forming a wide compact layer A distinguishable layer IV composed of loosely packed granule cells IS apparent in this area, a feature which contrasts sharply with the total absence of these cells in area 35a and the compact layel IV of temporal neocortex Layer V of area 35b is the most readily distinguishable feature of this cortex and appears as a conspicuous island of large deeply stained pyramidal cells throughout the rostrocaudal extent of this area These cytoarchltectonlc observations may suggest that the perlrhlnal and prorhlnal cortices form transitional belts between the atypical, but well-differentiated entorhlnal cortex of the caudal uncus and the neocortex of the temporal lobe It will be shown below that these areas receive substantial neoccrtlcal afferents and in turn project medially to the entorhlnal cortex RESULTS
Ahlatlon o f aleas TG and TE The efferent cortlco-comcal connections of Bonln and Bailey's ~ areas TG and TE have been described a number of times lz,~'z as, although It remains unclear how they relate anatomically to areas 35 and 28 Only these relationships will be emphasized here since our observations of other cortlco-cortlcal connections are in accord with other results previously detailed As depicted in Fig 6A, case 1 had a large ablation of the temporal pole largely confined to area TG From this ablation degeneratzon could be traced to the rostral portions of areas TE and TA, with evidence of terminal degeneration centered In and around layer 1V of these areas Medially, degeneration could be traced to area 35 where a conspicuous widening of the terminal degeneration was observed (Fig 10a and b) Evidence of degeneration could be further traced around the depths of the rhlnal sulcus into layers I - I l l or area Pr2, but it ceased abruptly at the junction of this cortex with areas 28a and 28b Cases 2, 3, and 4 all had ablations in area TE Cases 2 and 4 (Fig 6A) had large ablations which together encompassed the entire region except the area ablated in case 3 In the larger ablations considerable damage was incurred by the white matter underlying the ablated cortex In reference to areas 35 and Pr2, the pattern of degeneration was virtually identical to that just described for case 1 Briefly, as the degeneration from the ablation was traced medially, a conspicuous widening of its laminar distribution was observed This corresponded archltectonlcally with the localization of area 35 and afforded considerable contrast with the pattern of degeneration in ne~ghborlng neocortlcal areas where it was primarily centered around layer IV Further medially, a moderate quantity of degeneration could be followed around the
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Fig 6. A this illustration depicts the topography of the ablations in cases 1-4 on a view of the ventral surface of the temporal lobe The two series of transverse sections (1-3) were taken from cases 1 and 2, and their approximate levels correspond to the numerals shown o n the ventral vaew. The general pattern of terminal degeneration observed for a case is depicted by dots B this illustration summarizes the observed projecUons to the perirlunal and prorhinal cortices after area TE and T G ablations For this illustration and those that follow, specific dots a n d arrows are not meant to imply pathways or point to pomt projections, hut only the general stte of o n g m for a projection and the cytoarchitectomcalty defined region within which It terminates
11 depths of the rhlnal sulcus m layers I - I I I of Pr2 (Fig 10c) Cases hawng area TE ablations were also observed to contribute a moderate projection to the parahlppocampal areas T F - T H Ablation o f alea TF-TH Bonm and Badey 4 identified in the rhesus monkey two areas caudal to the entorhlnal cortex (areas T F and TH) in what we regard as the neocortical port~on of the parahlppocampal area Three ablations were successfully placed m area T F - T H and are dlustrated In Fig 7A Case 5 had a discrete ablatmn locahzed medial to the rostral t~p of the OCClpltotemporal sulcus Case 6 had a more medially located ablatmn which extended to the border of this area w~th areas 49 and 27 U n h k e case 5, the underlying white matter was invaded, causing a partial disruption of the temporal extension of the cmgulum Case 7 had a larger more caudally placed ablation whIch encroached into the rostral levels of area OA on the ventral surface of the hemisphere In all of these cases a strong rostral and lateral spread of degeneration could be observed Into areas TE, 35, Pr2, 28a, and 281 In each of these areas, however, the laminar distribution of degeneration differed In area TE, it was centered almost exclusively around layer IV In area 35, all layers contained moderate to heavy degeneration, with the heaviest quantities occurring along the caudal one third of the rhmal sulcus in layers I I I - V (Fig 10d) In Pr2, degeneration was observed m moderate quantities and was distributed predominantly to layers I - I I I Unhke the pattern of degeneration following area T G and TE ablations, a moderate quantity of degeneratIon was also observed in layers I and II of areas 28a and 281 In all 3 cases (Fig 10e) These observations imply that while all ventral temporal neocortlcal areas project to the perlrhmal and prorhlnal cortices, only area T F - T H projects m addition to a classical entorhmal cortex subarea The last neocortlcal region of the parahlppocampal area, area prostrlata, was partially ablated in case 8 This ablatlon also encroached into areas OA and OB on the ventral aspect of the occipital lobe (Fig 7A) No projectmns were observed from th~s ablation to either areas 28 or 35, but as IS summarized m Fig 7A, a heavy and diffuse projectmn to area T F - T H was observed Ablatton o f area 35 Of the 8 cases described to this point, only those having ablations of area T F - T H were observed to contribute afferents directly to the entorhlnal cortex All of the other ventral temporal neocortlcal areas, Including area T F - T H as well, had projections to the prorhmal and perlrhinal areas bordering the rhinal sulcus In lieu of the apparent convergence of input to these areas, 3 ablations are described which damaged area 35 Case 9 (Fig 8A) had a small ablation located along the caudal one-third of the rhlnal sulcus This ablation extended to the depths of the rhlnal sulcus but did not invade areas Pr2, 28a, and 28b Area TE lateral to the rhlnal sulcus was damaged as well as area T F - T H caudal to the entorhlnal cortex This neocortlcal damage, however, overlapped with that previously described in which there was no involvement of area 35 Case 10 had a large ablation lateral to the rhlnal sulcus The middle one-third of this
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Fig 7 A this illustration depicts the topography of the ablations m cases 5-8 on the ventral surface of the temporal lobe The two series of transverse sections (1-3) were taken from cases 5 and 6, and thetr approximate levels correspond to the numerals shown on the ventral view The general pattern of terminal degeneration observed for a case is depicted by dots B thts dlustratlon summarlzes the observed projections to the entorhmal, penrhmal and prorhlnal cortices after area TFT H ablations
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Fig 8 A this illustration depicts the t o p o g r a p h y of the ablations in cases 9-11 on the ventral surface of the temporal lobe The two series of transverse sections (I 3) were taken f r o m cases 9 and 10, and their approximate levels correspond to the numerals shown on the ventral view The general pattern of terminal degeneratton observed for a case is depicted by dots B this illustration summarizes the observed projections to the entorhlnal cortex after a b l a u o n s that damaged area 35
14 ablation extended into the depths of the rhmal sulcus and directly damaged or undercut areas 35a and 35b Case 1 l had a small ablation on the medial surface ol the temporal pole dorsal to the temporal preplnform cortex and ventral to the insular cortex Th~s ablation encroached into area TG, but also damaged the rostral p o m o n s of area 35a Unhke cases having only temporal neocomcal ablations, these cases all contained degeneration m areas 28a, 28~, and 28b At levels near the ablation, the pattern of degeneration was heavy, but decreased as the distance from the ablation mcreased For example, case 1t had projections directed to the rostral levels ot areas 28b and 28~ with only a hght amount of degeneration m area 28a Case 10 had projections to the entorhlnal areas near the ablation with decreasing amounts of degeneration rostralty and caudally Case 9 had heavy degeneration m areas 28a (F~g 10f), 28~, and caudal 28b, but the quantity decreased markedly as area 28b was followed rostrally These observations suggest that area 35 projects locally to contiguous levels of entorhmal cortex and not topographically to mdwldual subareas
Dtsrupttons of the cmgulum A potential confounding feature of ablations near the rhmal sulcus, and especially those in the caudal parahlppocampal area, can be the disruption of the cingulum since it forms a sizable component of the white matter m this region of the brain The majority of the cases having area 35 and area T F - T H ablations did not have heavy white matter involvement, but some involvement was unavoidable to the superficml components of the whtte matter m a number of cases (cf cases 6 and 9) We would hke to emphasize m this regard that m independent cases the cmgulum has been disrupted above and below the splemum of the corpus callosum, and a laminar pattern of degeneration duphcatlng that following either an area 35 or area T F - T H ablation has never been observed z3 Our observations indicate that the cmgulum m the rhesus monkey terminates almost exclusively in the presublculum (area 27) and to a lesser extent in the deeper lamina (V-VI) of area 28a An additional light and diffuse pattern of degeneration of presumed cmgulum o n g m has also been observed in Pr2
Ablatton of area 51 Afferent projections to the entorhmal cortex from area 51 have been described in rats 7,16,25, rabbits 7, and cats 7,1~ These well-documented observations are opposed to Adey and Meyer's 2 negative observations in the monkey where large ablations were made in the rostral uncal cortex including the amygdala. We have made an ablation in Brodmann's area 51 using a surgical approach across the r o o f of the orbit Case 12 (Fig 9) had an ablation m the rostral uncus which damaged the p r e p m f o r m and periamygdalold cortices as well as the ventral-most portions of the medial and lateral components of the basal amygdalold nucleus This ablation did not encroach into the entorhlnal cortex or its subjacent white matter L~kewme, the orbltofrontal cortex was free of damage F r o m the ablation, a strong caudotateral spread of degeneration was observed with heavy quantities m layers I - I I I of areas 28b (Fig 10g), 281, and Pr2, as well as hght evidence of terminal degeneration in area 35 Degenerating fibers emanating from the ablation appeared to reach these areas via both the plexlform
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