The claustrum and its projection system in the human brain: a microsurgical and tractographic anatomical study

Laboratory investigation

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Object

The goal in this study was to examine the microsurgical and tractographic anatomy of the claustrum and its projection fibers, and to analyze the functional and surgical implications of the findings.

Methods

Fifteen formalin-fixed human brain hemispheres were dissected using the Klingler fiber dissection technique, with the aid of an operating microscope at × 6–40 magnification. Magnetic resonance imaging studies of 5 normal brains were analyzed using diffusion tensor (DT) imaging–based tractography software.

Results

Both the claustrum and external capsule have 2 parts: dorsal and ventral. The dorsal part of the external capsule is mainly composed of the claustrocortical fibers that converge into the gray matter of the dorsal claustrum. Results of the tractography studies coincided with the fiber dissection findings and showed that the claustrocortical fibers connect the claustrum with the superior frontal, precentral, postcentral, and posterior parietal cortices, and are topographically organized. The ventral part of the external capsule is formed by the uncinate and inferior occipitofrontal fascicles, which traverse the ventral part of the claustrum, connecting the orbitofrontal and prefrontal cortex with the amygdaloid, temporal, and occipital cortices. The relationship between the insular surface and the underlying fiber tracts, and between the medial lower surface of the claustrum and the lateral lenticulostriate arteries is described.

Conclusions

The combination of the fiber dissection technique and DT imaging–based tractography supports the presence of the claustrocortical system as an integrative network in humans and offers the potential to aid in understanding the diffusion of gliomas in the insula and other areas of the brain.

Abbreviations used in this paper: DT = diffusion tensor; LSA = lenticulostriate artery; MR = magnetic resonance.

Abstract

Object

The goal in this study was to examine the microsurgical and tractographic anatomy of the claustrum and its projection fibers, and to analyze the functional and surgical implications of the findings.

Methods

Fifteen formalin-fixed human brain hemispheres were dissected using the Klingler fiber dissection technique, with the aid of an operating microscope at × 6–40 magnification. Magnetic resonance imaging studies of 5 normal brains were analyzed using diffusion tensor (DT) imaging–based tractography software.

Results

Both the claustrum and external capsule have 2 parts: dorsal and ventral. The dorsal part of the external capsule is mainly composed of the claustrocortical fibers that converge into the gray matter of the dorsal claustrum. Results of the tractography studies coincided with the fiber dissection findings and showed that the claustrocortical fibers connect the claustrum with the superior frontal, precentral, postcentral, and posterior parietal cortices, and are topographically organized. The ventral part of the external capsule is formed by the uncinate and inferior occipitofrontal fascicles, which traverse the ventral part of the claustrum, connecting the orbitofrontal and prefrontal cortex with the amygdaloid, temporal, and occipital cortices. The relationship between the insular surface and the underlying fiber tracts, and between the medial lower surface of the claustrum and the lateral lenticulostriate arteries is described.

Conclusions

The combination of the fiber dissection technique and DT imaging–based tractography supports the presence of the claustrocortical system as an integrative network in humans and offers the potential to aid in understanding the diffusion of gliomas in the insula and other areas of the brain.

The claustrum is a thin sheet of gray substance located deep with respect to the insula and is present in all mammalian species examined so far.32 Although it is easily identifiable on computed tomography and MR imaging studies obtained in the human brain, it has received very little attention in the neurosurgical literature. In addition, its functional significance in the human brain is unknown.20,67,74

The implication of the fiber bundles underlying the insular cortex in the spread of gliomas of the insular region has been stressed during recent years,41,72 and an anatomical classification of insular gliomas based on white matter invasion patterns has been suggested.41 On the other hand, the infiltration of the claustrum by the diffusion of insular gliomas has been a matter of controversy, adding more uncertainties to this enigmatic structure. Whereas Yaşargil et al.76 reported the sparing of the claustrum in all but the most advanced malignant insular tumors, Zentner et al.78 and Duffau et al.17 found the claustrum invaded by the tumor in most patients.

In the cat and monkey, the claustrum is reciprocally connected with every area of the cerebral cortex, and the claustrocortical and corticoclaustral projections show a topographical organization.5,13–16,30,48–50,56 Recently, because of these widespread claustrocortical connections,68 Francis Crick, the discoverer of the DNA structure and function, and one of the most important scientists of the 20th century,62 suggested that the human claustrum is critical to binding information and speculated on the possible relationship of the claustrum to the processes that give rise to integrated conscious percepts.11 Nevertheless, the presence of claustro-cortical connections in the human brain has not been demonstrated,67 and only one report suggests the existence of those connections.46 The aim of our study was to examine the microsurgical anatomy of the claustrum, determine whether the claustrocortical system was present in the human brain, and analyze the functional and surgical implications of the findings.

Materials and Methods

The gross cross-sectional anatomy and relationships of the claustrum were examined using coronal cuts obtained in 5 formalin-fixed normal human cerebral hemispheres at the level of the anterior commissure and 5, 10, and 15 mm in front of and behind it, and axial cuts that were obtained in another 5 specimens at the level of the anterior commissure and 5, 10, and 15 mm above and below it.

Fifteen normal human cerebral hemispheres were fixed in a 10% formalin solution for ≥ 40 days and then frozen at 10 to 15°C for 14 days in preparation for the fiber dissection technique as described by Ludwig and Klinger.38 The specimens were dissected using the operating microscope (× 6–40 magnification) in a stepwise manner, beginning at the lateral surface of the hemisphere.

Magnetic resonance imaging studies of 5 normal brains were performed on a whole-body 3.0-T Signa Excite unit (General Electric Medical Systems, Inc.). Diffusion tensor imaging was performed using a single-shot multislice spin echo–echo planar sequence: diffusion sensitization 1000 seconds/mm2, TR 8700 msec, TE 71.1 msec, slice thickness 4.0 mm, no gap between slices, a field of view of 260 × 260 mm with 8-channel head coil. Six diffusion gradient directions and 1 image set without diffusion weighting (b = 0 seconds/mm2) were obtained. Acquisition coverage extended from the medulla oblongata to the brain vertex. The total DT imaging measurement required 2 minutes and 19 seconds for each study. The DT imaging data sets and anatomical MR imaging studies were analyzed with software for DT analysis and fiber tracking (VOLUME-ONE and dTV software; available free at http://volume-one.org). The specifications of this software have been extensively explained elsewhere.27–29 Fiber tracking was initiated from a manually selected seed area from which lines were propagated in both anterograde and posterograde directions according to the eigenvector at each pixel. Tracking was terminated when it reached a pixel with a fractional anisotropy < 0.18.

Results

Macroscopic Anatomy of the Claustrum

The claustrum is a thin collection of gray matter located deep with respect to the insula. Macroscopically, we divide the claustrum into 2 parts: the dorsal claustrum, also referred to as compact59,60 or insular claustrum;3,22,46,67 and the ventral claustrum, also named fragmented59,60 prepiriform, amygdalar, or temporal claustrum.22,46,67 The names dorsal and ventral claustrum were applied based on studies in animals, and this nomenclature was carried over to humans. However, in humans the dorsal claustrum is posterosuperior, and the ventral claustrum is anteroinferior, as seen on our fiber dissection (Fig. 1A and B).

Fig. 1.
Fig. 1.

Photographs of cadaveric specimens showing the anatomical correlation between the insular surface, underlying claustrum, and adjacent fiber tracts. A: The positions of the dorsal (blue) and ventral (dark green) claustrum are outlined on the insular surface. The ventral (or anteroinferior) portion of the external capsule (light green) is formed by the uncinate and the inferior occipitofrontal fascicles, which cross deep with respect to the anterior and middle short insular gyri. The ventral (or anteroinferior) claustrum consists of a group of diffuse or islandlike gray masses that are separated and fragmented by the uncinate and the inferior occipitofrontal fascicle. The dorsal (or posterosuperior) external capsule (orange) is composed predominantly of claustrocortical fibers, which are located deep with respect to the posterior short and anterior and posterior long gyri. The dorsal (or posterosuperior) claustrum is situated above and posterior to the limen insulae, posterior to the insular apex, and beneath the proximal part of the posterior short, anterior long, and posterior long gyri. The insular apex is the most prominent laterally projecting area on the insular surface. The central insular sulcus approximates the position of the center of the dorsal claustrum. B: Fiber dissection of the insular region showing the dorsal claustrum and external capsule, and the ventral claustrum and external capsule. The insular cortical gray matter and the extreme capsule have been removed. The uncinate fascicle forms most of the white matter of the limen insulae and passes beneath the anterior pole of the insula, connecting the temporal pole with the orbitofrontal region. The inferior frontaloccipital fascicle, which forms the most dorsal part of the limen insulae, is located deep with respect to the insular apex, and to the anterior and middle short gyri. It connects the frontal opercula and prefrontal region with the posterior temporal and occipital regions (panels C–F, coronal sections of the central core of the cerebral hemisphere at the level shown in panel F). The central core is the area between the insular cortex and the lateral and third ventricles. C: Cross-section of the brain immediately anterior to the limen insulae, and at the level of the insular apex (see panel F). The gray matter of the anterior segment of the uncus has been removed to expose the amygdala. The cross-section extends through the central core anterior to the dorsal claustrum. At this level the ventral claustrum extends toward the base of the frontal lobe below the putamen, adjoining the prepiriform cortex. Medially, the anteroinferior part of the putamen and the head of the caudate nucleus blend in the nucleus accumbens in the area below the anterior limb of the internal capsule. D: This section at the level of the anterior commissure crosses the dorsal and ventral claustrum, the anterior part of the amyg-dala, the uncinate fascicle, and the middle and posterior short gyri (see panel F). The dorsal claustrum is a column of gray matter situated between the insular cortex and the putamen. At the level of the limen insulae, the white fibers of the uncinate fascicle fragment the anteroinferior part of the claustrum, creating the characteristic islandlike pattern of the ventral claustrum, which at this level is located in the supraamygdalar area. The anterior segment of the uncus contains the amygdala. E: Cross-section obtained 5 mm behind the anterior commissure and crossing the posterior short gyrus and the anterior and posterior long gyri (see panel F). The dorsal claustrum has a triangular shape with its base at the inferior margin. The dorsal external capsule, situated between the dorsal claustrum and the putamen, narrows in the downward direction. At the level of the inferior margin of the dorsal claustrum, where its thickness is maximum, the dorsal external capsule is reduced to a thin layer of white matter, which covers the inferolateral surface of the putamen. F: Lateral view of the insula after removal of the opercular lips. The level of the coronal sections depicted in panels C–E is shown on the external surface of the insula. Ant. = anterior; Cap. = capsule; Caud. = caudate; Cent. = central; Comm. = commissure; Dors. = dorsal; Ext. = external; Fas. = fascicle; Front. = frontal; Glob. = glo-bus; Gyr. = gyrus; Inf. = inferior; Innom. = innominata; Int. = internal; Mid. = middle; Nucl. = nucleus; Occip. = occipital; Pall. = pallidus; Post. = posterior; Seg. = segment; Subst. = substantia; Temp. = temporal; Vent. = ventral.

The dorsal (or posterosuperior) claustrum is a continuous irregular lamina of gray matter lying between the putamen (from which it is separated by the external capsule) and the insular cortex (from which it is separated by the extreme capsule) (Fig. 1D and E). It has the form of a plate, which narrows in the upward direction and widens in the downward direction, giving it a triangular form in coronal cross-section. This contrasts with the external capsule, which is widest above and narrow in the area adjacent to the lower part of the dorsal claustrum, where it is separated from the putamen by a thin or even nonexistent external capsule (Fig. 1E).

The ventral (or anteroinferior) claustrum consists of a group of diffuse or islandlike gray masses fragmented by the uncinate and the inferior occipitofrontal fascicle. We divide the ventral claustrum in 2 parts: superior and inferior. The superior part of the ventral claustrum is continuous with the anteroinferior pole of the dorsal claustrum and extends downward toward the base of the frontal lobe below the putamen, adjoining the prepiriform cortex (Figs. 1C and 2). The inferior part of the ventral claustrum is continuous with the posteroinferior pole of the dorsal claustrum and is directed toward the amygdalar region (Figs. 1D and 2). In this area, the relationship between the ventral claustrum and the amygdala is so close that it is sometimes difficult to delimit one from the other clearly. This close anatomical relationship has been found in other ontogenetic and phylogenetic studies.22,23

Fig. 2.
Fig. 2.

Photographs of cadaveric specimens showing stepwise fiber dissection of the left insular and basal ganglia region. A: The opercular lips of the sylvian fissure have been removed to expose the insula. The central sulcus, which is the deepest insular sulcus, separates the insula into larger anterior and smaller posterior portions. The anterior portion consists of 3 short gyri (anterior, middle, and posterior) arranged in a radiating pattern that converges at the insular pole located at the anteroinferior edge of the short insular gyri. The anterior and posterior long gyri extend backward and upward from the limen insulae. The inferior limiting sulcus is positioned below the long gyri of the insula and separates the insula from the sylvian surface of the temporal lobe. The superior limiting sulcus separates the insula from the sylvian surface of the frontal and parietal lobes. B: Removal of the cortical gray matter of the long and short insular gyri exposes the extreme capsule and the claustrum. The extreme capsule has a ventral (anteroinferior) part composed of the lateral fibers of the uncinate and inferior occipitofrontal fascicles, and a thinner dorsal (posterosuperior) part formed by multiple short association fibers that connect the different insular gyri with each other and with the adjacent frontal, parietal, and temporal operculae. The claustrum has a dorsal (posterosuperior) part, composed of compact gray matter, and a ventral (anteroinferior) part, formed by islands of gray matter intermixed with and fragmented by fibers of the uncinate and inferior occipitofrontal fascicles. C: Enlarged view of the dorsal claustrum and external capsule after removal of the dorsal part of the extreme capsule. The fibers of the dorsal external capsule converge in and merge with the gray matter of the dorsal claustrum, forming a characteristic spoke-and-wheel pattern with its center at the dorsal claustrum. Thus, they are claustrocortical fibers. The fibers of the uncinate and inferior occipitofrontal fascicles traverse the most anterior and inferior parts of the claustrum to create the gray matter islands that form the ventral claustrum. D: A further step in the dissection of the claustrocortical fibers. Removal of the claustrocortical fibers of the dorsal external capsule also peels away the gray matter of the dorsal claustrum. The fibers from the posterior part of the external capsule enter the posterior part of the dorsal claustrum, and the fibers coming from the middle part enter the anterior part of the dorsal claustrum. The fibers of the anterior part of the external capsule at this level belong to the uncinate and inferior occipitofrontal fascicles and traverse the ventral claustrum. E: After removal of most of the claustrocortical fibers and dorsal claustrum, only the deepest layer of the dorsal external capsule, which faces the putamen, remains. White gliotic tissue surrounding the lateral LSAs is found between the inferomedial surface of the dorsal claustrum and the adjacent putamen. F: Removal of the dorsal claustrum and the peri-vascular white matter exposes the lateral LSAs. These vessels pass medial to the uncinate fascicle and lateral to the anteroinferior pole of the putamen. G: The putamen and the globus pallidus have been removed to expose the anterior and posterior limbs of the internal capsule. The anterior commissure runs from a medial to lateral direction. The substantia innominata is located in front of and below the anterior commissure. Islands of gray matter of the ventral claustrum are found between the fibers of the uncinate fascicle. H: Enlarged view. The most medial fibers of the uncinate fascicle merge into the ventral claustrum and amygdala. The islands of gray matter forming the ventral claustrum blend to the amygdala. The nucleus accumbens, which is situated in the septal region below the head of the caudate nucleus, has been removed. A. = artery; Cor. = corona; Extr. = extreme; Ins. = insular; Lat. = lateral; Lent. = lenticulate; Limit. = limiting; Rad. = radiata; Sup. = superior.

Fiber Dissection of the Insular and Basal Ganglia Region

The dissection begins with a detailed inspection of the topography of the insula, observing the pattern of its gyri and sulci, and identifying the insular apex and the limen insulae. The insular apex is the most prominent laterally projecting area on the insular convexity. The limen insulae is a slightly raised, arched ridge located at the junction of the sphenoidal and operculoinsular compartments of the sylvian fissure, which extends from the temporal pole to the orbital surface of the frontal lobe (Fig. 2A).

Removal of the cortical gray matter of the long and short insular gyri exposes the extreme capsule, which is composed of multiple short association fibers that connect the insular gyri with each other, and with the adjacent frontal, parietal, and temporal operculae. Some of these short fibers emerge from the gray matter digitations of the claustrum, which conform to the shape of the overlying posterior short and long insular gyri (Fig. 2B).

Removal of the fibers of the extreme capsule exposes the gray matter of the dorsal claustrum located above and posterior to the limen insulae, posterior to the insular apex, and beneath the proximal part of the posterior short and long insular gyri (Figs. 1A and B and 2A and B). At this level, the fibers of the dorsal (or posterosuperior) external capsule appear at the periphery of the dorsal claustrum, forming a characteristic spoke-and-wheel pattern with its center at the dorsal claustrum (Fig. 2C and D). Interestingly, the central insular sulcus crosses at or near to the center of the dorsal claustrum (Fig. 1A). Removal of the cortical gray matter overlying the limen insulae exposes the thick uncinate fascicle, with its characteristic hooklike shape, connecting the temporal pole with the orbitofrontal area (Figs. 1A and B and 2B–G) and forming the anterior part of the limen insulae. The posterior-most fibers at the level of the limen insulae belong to the inferior occipitofrontal fascicle, which is located deep with respect to the insular apex, and to the anterior and middle short gyri (Figs. 1A and B and 2B–G). The diffuse or islandlike gray masses that composed the ventral claustrum are embedded in these white matter tracts (Fig. 2B–G). The lateral fibers of these tracts belong to the extreme capsule, whereas the most medial ones form part of the external capsule. The dorsal claustrum is positioned above these tracts (Fig. 2C and D). As the dissection of the external capsule progresses, the radiation pattern of its fibers from the claustrum (and/or toward it) to the corona radiata (and/or from it) becomes more evident (Fig. 2C and D). A detailed and delicate dissection of these fibers, proceeding in a centripetal manner, starting at the periphery of the external capsule, where the fibers join or become a part of the corona radiata, reveals several important facts. First, most fibers converge in and merge with the gray matter of the dorsal claustrum (Fig. 2C–E). Second, the fibers from the posterior part of the corona radiata enter the posterior part of the dorsal claustrum, the fibers from the middle part of the corona radiata enter the anterior part of the dorsal claustrum, and the fibers from the uncinate and inferior occipitofrontal fascicles (located in the most anterior part of the corona radiata) enter, cross, and fragment the anteroinferior part of the claustrum, forming the typical islandlike pattern of the ventral claustrum (Fig. 2C and D). Third, removal of the white fibers is associated with removal of the gray matter of the dorsal claustrum, so that as the dorsal external capsule is being removed, the dorsal claustrum is also being removed (Fig. 2D and E). Fourth, removing all the fibers from the external capsule that merge in the dorsal claustrum leads to removal of the dorsal claustrum, leaving the putamen exposed, without a lateral covering. Only a few white fibers adherent to the external surface of the putamen remain, and the most lateral LSAs are exposed at the outer and lower surface of the putamen (Fig. 2E and F). Anterior and inferior to the putamen, the fibers of the uncinate and inferior occipitofrontal fascicles and the islands of gray matter of the ventral claustrum can be identified. The fibers from the uncinate and inferior occipitofrontal fascicles form the ventral (or anteroinferior) part of the external capsule (Fig. 2E and F).

The putamen can be removed using either suction72 or thin spatulas. Its resection exposes the globus pallidus and the internal capsule at its medial border. The gray matter that connects the caudate and putamen is identified in the anterior limb of the internal capsule (Fig. 2G and H). Gently removing the globus pallidus exposes the entire internal capsule. At the anterior and basal pole of the globus pallidus, the anterior commissure is found, traversing from medial to lateral, with a slightly anteroposterior direction. The substantia innominata (or basal forebrain), located in front of and beneath the anterior commissure (Fig. 2G and H), and above the anterior perforated substance, is the site of the basal nucleus of Meynert, the main cholinergic input of the cortex.6,42 Medially, the substantia innominata is continuous with the base of the septal region, which contains the nucleus accumbens, an intermediate nucleus between the extrapyramidal and the limbic system (Fig. 2G and H).6,51 The complete dissection of the fibers of the uncinate fascicle reveals the close relationship of the amygdala, ventral claustrum, and substantia innominata (Fig. 2H).

Tractography Study of the Claustrum and the External Capsule

Using the 3 spatial MR imaging planes and applying the anatomical knowledge acquired by the microsurgical dissections, we localized the region of the claustrum and external capsule and selected 3 different and equidistant seed points: anterior, middle, and posterior. The seed points were all located within the anteroposterior boundaries of the insular region, lateral to the putamen and medial to the insular cortex (Fig. 3).

Fig. 3.
Fig. 3.

Diffusion tensor imaging–based tractography studies and cadaveric specimens showing the anatomical–radiological correlation between the tractography and fiber dissection studies of the claustrum and external capsule. A: A DT imaging–based tractography study obtained with the seed point at the level of the anterior part of the insular region (inset). The uncinate fascicle runs from the orbitofrontal to the anterior temporal region, and the inferior occipitofrontal fascicle from the prefrontal to the posterior temporal and occipital regions to form the ventral part of the external capsule. B: A DT imaging–based tractography study obtained with the seed point at the level of the middle part of the insular region (inset). Multiple fibers originating from the superior frontal, precentral, and postcentral gyri converge in the area just above the uncinate and occipitofrontal fascicles, which, as shown in the fiber dissections, corresponds to the area of the dorsal claustrum. These fibers form the anterior part of the dorsal external capsule. C: A DT imaging–based tractography study obtained after selecting the seed point at the posterior part of the insular region (inset). Several loops interconnect the superior parietal lobule and parietooccipital region and the area of the dorsal claustrum. These fibers form the posterior part of the dorsal external capsule. Some displayed tracts are continuing toward the prefrontal and orbitofrontal region. Based on the fiber dissection findings, we think this continuation reflects an artifact of the tractography study. D: A DT imaging–based tractography study showing the ventral and dorsal portions of the external capsule. The latter contains the claustrocortical projection system, which has a topographical organization. E: Axial section of a left cerebral hemisphere cut 15 mm above the anterior commissure. The upper part of the dorsal claustrum is identified as a thin sheet of gray matter located between the extreme and external capsule. The 3 seed points (colored rings in panels E and F) selected in the tractography studies are displayed F: White fiber dissection of the left insular region showing the 3 seed points selected for the tractography studies. The fibers of the dorsal external capsule, which come from the superior frontal, pre-central, postcentral, superior parietal, and parietooccipital regions, converge in the dorsal claustrum. The fibers of the inferior occipitofrontal and uncinate fascicles form the ventral external capsule. Lob. = lobule; Orb. = orbital; Par. = parietal; Prefront. = prefrontal; Proj. = projection.

Anterior Seed Point (Anterior Part of the Insular Region)

The tractography study displayed the uncinate fascicle running from the orbitofrontal region to the temporal pole and temporomesial region, and the inferior occipitofrontal fascicle running from the orbitofrontal and prefrontal region toward the posterior temporal and occipital region. These fascicles form the ventral or anteroinferior part of the extreme and external capsules (Fig. 3A), which, as we saw with the microsurgical dissections, are related to the ventral claustrum.

Middle Seed Point (Middle Part of the Insular Region)

The tractography study showed multiple loops of fibers originating in the superior frontal, precentral, and postcentral gyri, and converging together in an area located just above the uncinate and occipitofrontal fascicles, which, as we saw with the fiber dissection, corresponds to the area of the dorsal claustrum (Fig. 3B).

Posterior Seed Point (Posterior Part of the Insular Region)

The tractography study showed multiple loops of fibers coming from the superior parietal lobule and parietooccipital region, converging in the area of the dorsal claustrum (Fig. 3C). These tracts converged in the dorsal claustrum in a more posterior location than the tracts displayed using the middle seed point. Some depicted tracts are continuing toward the prefrontal and orbitofrontal region. Based on the fiber dissection findings, we think this continuation reflects an artifact of the tractography study.

Tractographically Examined Relationship Between the External and Internal Capsules

We selected 2 seed points, one at the region of the external capsule, and the other at the posterior limb of the internal capsule. These examinations, in which the external capsule was separated from the internal capsule by the putamen, showed the structure found in the fiber dissections in which the fibers arising from the region of the dorsal claustrum radiated toward the cortex. The fibers of the external capsule joined the fibers of the internal capsule at the superior edge of the putamen to blend together in the corona radiata, but we did not find any connection fibers between the external and internal capsule at the inferior end of the putamen (Fig. 4).

Fig. 4.
Fig. 4.

Diffusion tensor imaging–based tractography studies and cadaveric specimens showing anatomical–radiological correlations between the tractography and fiber dissection studies of the external and internal capsules. A: Coronal view of DT imaging–based tractography study obtained with 2 seed points, one at the external capsule and the other at the posterior limb of the internal capsule. The yellow tract corresponds to the external capsule, and the red one to the internal capsule. The putamen is located below and between where the fibers converge. The fibers of the external capsule join those of the internal capsule at the superior edge of the putamen, together forming the corona radiata. The fibers of the external and internal capsules do not join at the lower edge of the putamen. B: Coronal section of the right hemisphere cut 5 mm behind the anterior commissure. As we showed with the tractography study (panel A), the external capsule joins the internal capsule at the superior edge of the putamen to form the corona radiata. The external capsule is wider at the superior edge of the claustrum and narrows as it descends along the medial edge of the structure, leaving only a thin layer of fibers at the inferior edge of the putamen, where only a thin layer of white tissue surrounding the lateral LSAs remains. C: Coronal view of a different tractography study of the external and internal capsules. The fibers of the dorsal external capsule converge in the dorsal claustrum, the presumed site of the gray matter and nerve cells giving rise to the fibers. D: Fiber dissection of the left hemisphere. The superior part of the dorsal external capsule has been removed to show the relationship between the dorsal claustrum and external capsule, the putamen, and the corona radiata. The internal capsule is located deep with respect to the putamen. E: Left sagittal view of the tractography study shown in panel A. Anatomical–radiological correlation with panel D. The tractography study permits the visualization of fiber tracts, as in the internal and external capsules, at different depths. Cort. = cortico.

Discussion

Although more than a century ago Déjérine12 and Tro-lard70 stated that the external capsule contains fibers from the claustrum, the recent studies of the white fiber tracts, in which the fiber dissection technique57,65,71,72 or DT imaging–based tractography was used,7,8,34,35,40,43,58,73 have neglected this important fact, as have current neuroanatomical texts.6,51,67,77

During our recent fiber dissection studies about the optic radiations10,61,63 we also noted that most fibers of the external capsule converged into the claustrum. Additional fiber dissection of the claustrum and the external capsule region revealed that the fibers of the external capsule merged with the gray matter of the claustrum. Ture et al.72 stated that “the external capsule consists mostly of deeper fibers of the occipito-frontal fascicle” and “it is joined to the internal capsule at both ends of the putamen.” Our study shows that the occipitofrontal and uncinate fascicles, including their deepest fibers, form exclusively the ventral (or anteroinferior) part of the external and extreme capsules, whereas the corticoclaustral projection fibers form the dorsal (or poste-rosuperior) part of the external capsule (Figs. 1 and 2). Our tractography studies showed that the latter is composed of multiple fiber bundles coming from the superior frontal, precentral, postcentral, superior parietal, and parietooccipital regions, converging in the area of the dorsal claustrum. Thus, the dorsal external capsule is mainly composed of projection (intrahemispheric corticosubcortical) and not association (intrahemispheric interlobar corticocortical) fibers. Furthermore, the tractography studies revealed a topographical organization in the dorsal claustrum and external capsule, where posterior cortical areas project into the posterior part of the dorsal claustrum, and more anterior cortical areas converge in the anterior part (Fig. 3). In addition, we show that the fibers of the external capsule join the internal capsule at the upper but not the lower margin of the putamen (Fig. 4).

Schmahmann and Pandya,64 using definitive radioactive isotope tracing methods, have demonstrated that the external capsule of the nonhuman primate is composed of corticoputaminal and corticoclaustral fibers, which is in accordance with our findings in humans. In addition, our fiber dissections revealed that the corticoputaminal component of the external capsule is much smaller than the corticoclaustral part. Supporting our findings, Lehericy and colleagues36,37 have provided the first demonstration of corticoputaminal connections in humans running not in the external, but predominately in the internal capsule.

Morys et al.46 performed histological studies of the claustrum in 9 human brains with prominent bilateral microgyria. These authors observed severe neuronal loss in the anterior part of the claustrum when the pathological lesions involved the frontal cortex, and in the central and posterior part of the claustrum when the lesions affected the parietal and occipital cortices. They concluded that “our results strongly suggest that in man, as in other mammals, the claustrum is connected extensively with the neocortex, and that these connections are topographically organized.” Based on tracing studies conducted in nonhuman primates, Pearson et al.56 concluded that the frontal cortex is related to the more anterior part of the claustrum, the parietal cortex is connected with its central and posterior parts, and the occipital and temporal cortices are related to the posterior and inferior margins of the claustrum. Our results are in agreement with these studies, which reveal a topographical organization in the claustrocortical projection system.

In relation to the possible functional role of the claustrocortical projection system, a positron emission tomography study24 revealed the involvement of the claustrum in cross-model matching in tasks that require the simultaneous evaluation of information from > 1 sensory domain (that is, visual–tactile, audio–visual, and so on), and a functional MR imaging study4 detected claustral activation specifically during the unimodal phases of the bimodal–unimodal contrasts. In the aforementioned study, given the anatomical separation and lack of direct connections between the auditory and visual cortices, and the absence of any additional contribution from a possible intersensory region during the bimodal condition, the question arose as to how the auditory and visual signals are combined. Ettlinger and Wilson21 suggested a system whereby the senses could access each other directly via an interconnecting structure such as the claustrum.

Recently, Crick and Koch,11 after > 20 years devoted to the problem of consciousness,62 suggested that the claustrum is critical to binding information. Using their words, “in biology, if seeking to understand function, it is usually a good idea to study structure.” Our study shows the claustrum connecting with many cortical areas and suggests the existence of a distant transcortical interconnection through the claustrum, with a peculiar topographical organization. It also shows the close relationship between the claustrum and other subcortical structures involved in the limbic system, such as the amygdala and the prepiriform cortex. We suggest, as Crick did, that the information from, say, a visual cortical region, would be combined with information from the limbic system, or information from the somato-sensory cortex would be integrated with information from the motor cortex, by the corticoclaustral network. This observation supports Crick's hypothesis about the function of the claustrum in integrating information at the fast time-scale, which represents an essential characteristic of consciousness.11

Concerning the clinical repercussions of claustral lesions, Morys et al.47 reported that in all the patients in their study who had unilateral vascular lesions of the central claustrum (referred to as the anterior segment of the dorsal claustrum in our study), the cortical somatosensory evoked potentials were absent contralaterally to the side of the lesion and ipsilaterally to the stimulated nerve. In contrast, Duffau et al.19 showed the absence of permanent sensori-motor or cognitive disorders after unilateral resection of the claustrum in cases of insular gliomas, thus demonstrating that its functional role can be compensated after unilateral lesions, and supporting a connectionist view of the claustrum as a part of a large-scale network, rather than as an essential epicenter.

On the other hand, selective bilateral lesions of the claustrum and external capsule have been reported in patients with herpes simplex encephalitis,31 ingestion of the Sugihiritake mushroom,55 and lesions with unknown origins.66 In all of the reported cases, patients developed a severe encephalopathy with disturbance of consciousness, seizures, and psychotic symptoms. The reversibility of both neurological symptoms and radiological signs in one case indicated a close association of epilepsy, behavior, and the claustrum.66 In addition, it was recently suggested that the claustrum could be involved in seizure generalization.79 The claustrum may also show pathological changes in Alzheimer disease45 and aging.44

The microsurgical anatomy of the white matter tracts and gray nuclei underlying the insula is of special interest in glioma surgery in the insular region. Interestingly, Duffau et al.18 reported that intraoperative stimulation at the level of the ventral (or anteroinferior) part of the external capsule during glioma surgery elicited semantic paraphasias. This area anatomically corresponds to the inferior occipitofrontal fascicle, which forms the so-called ventral semantic pathway. In this study we show, not only the anatomy of its fibers, but also its correlation with the insular apex and the anterior and middle insular gyri (Fig. 3), which is of evident interest during insular surgery.

The diffusion of gliomas along the white fiber tracts is well established,1,72,74,75 and recently the uncinate and arcuate fascicles but not the external capsule have been implicated in the spreading of insular gliomas.41 Our studies suggest that the dorsal external capsule (that is, the claustrocortical system) can be responsible for the diffusion of insular gliomas toward the superior and posterior margins of the insula and the claustrum. Yaşargil et al.76 noted the sparing of the claustrum and other medial structures, such as the putamen, in all but the most advanced malignant insular gliomas, and other authors affirmed that these tumors replace the external and extreme capsules.26 By contrast, others found the claustrum and the lentiform nucleus to be invaded by the tumor in most patients.17,78 This discrepancy may reflect the different stages of diffusion of the gliomas through the claustrocortical projection system.

In addition, the constant finding of the most lateral LSAs running medial to the uncinate fascicle and to the lower part of the dorsal claustrum can be of surgical importance. Damage to these arteries is the principal source of surgical morbidity in insular glioma surgery.17,33,76,78 For this reason, Yaşargil et al.76 and Lang et al.33 recommended early identification of the lateral LSAs arising from the middle cerebral artery to define the deepest plane of dissection that avoids these arteries. Along the same lines, Tanriover et al.69 described the limen recess, which lies between the medial border of the limen insulae and the site at which the most lateral LSA enters the anterior perforated substance, and suggest that the resection should not extend beyond the medial edge of the recess to avoid injuries to the LSAs. Moreover, Yaşargil et al. stated the occasional necessity of leaving a layer of tumor tissue along the uncinate bundle, so as to preserve these vessels. Because the claustrum can usually be identified during the resection of insular glio-mas,17,76 we suggest that not only the medial layer of the uncinate fascicle but also the medial and lower part of the dorsal claustrum could serve as internal landmarks to aid in the preservation of those essential arteries.

In this study we used the old but revitalized fiber dissection technique and the new and promising tractography. The latter has proven valuable in pre- and intraoperative planning and in reducing surgery-related morbidity during intracerebral surgery25 as a result of its ability to localize the corticospinal tract,2,28,52–54 primary motor area,27 optic radiations,29,52 and language pathways.25 In addition, it has made important contributions to human neuroanatomy and neuroscience.9,36,37,39

As we show in this study, the combination of both techniques is reciprocally enriched, because one solves the limitations of the other. The fiber dissection technique is limited because of the complex relationships of the fiber systems, so the demonstration of one fiber system often results in the destruction of other fiber systems.72 This is avoided with DT imaging–based tractography, which can show at the same time the complex relationships between the fiber systems. On the other hand, the main limitation of tractography studies occurs when the axons are not oriented in a coherent fashion, so that then the voxel-averaged estimate of orientation cannot accurately summarize the orientation of the underlying fibers,8 assuming continuity between the fibers where there is none.64 To avoid this problem, in addition to the development of new techniques to analyze those voxels containing multiorientational fiber populations,8 an accurate knowledge of the anatomy of the fiber systems, acquired by means of the fiber dissection technique, allows correct interpretation of the tracts displayed by the tractography studies. Thus, we think that the combination of both techniques should be used not only in neurosurgical training and operative planning but also as an alternative and complementary method of neuroanatomical research.

Conclusions

The combination of the fiber dissection technique and DT imaging–based tractography has proven valuable in understanding the anatomy of the claustrum and its projections. These studies also aid in our understanding of the diffusion of insular gliomas and may help explain some of the neurophysiological deficits found when the area of the claustrum and external capsule is affected by tumors, spontaneous hematomas, ischemic accidents, or vascular malformations. Further research is needed to delineate definitively the role of the claustrocortical network in the integrative process. Fiber dissections, done in conjunction with tractography or other techniques for studying neural pathways, can provide confirmatory evidence that can be used in planning neurosurgical procedures.

Acknowledgments

We thank Robin Barry for her assistance in preparation of the figures and Laura Dickinson for helping with the manuscript. We acknowledge Maria J. Bolado for her constant support to complete this project.

References

Article Information

Address correspondence to: Albert L. Rhoton Jr., M.D., Department of Neurological Surgery, University of Florida, P.O. Box 100265, Gainesville, Florida 32610-0265. email: rhoton@neurosurgery.ufl.edu.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    Photographs of cadaveric specimens showing the anatomical correlation between the insular surface, underlying claustrum, and adjacent fiber tracts. A: The positions of the dorsal (blue) and ventral (dark green) claustrum are outlined on the insular surface. The ventral (or anteroinferior) portion of the external capsule (light green) is formed by the uncinate and the inferior occipitofrontal fascicles, which cross deep with respect to the anterior and middle short insular gyri. The ventral (or anteroinferior) claustrum consists of a group of diffuse or islandlike gray masses that are separated and fragmented by the uncinate and the inferior occipitofrontal fascicle. The dorsal (or posterosuperior) external capsule (orange) is composed predominantly of claustrocortical fibers, which are located deep with respect to the posterior short and anterior and posterior long gyri. The dorsal (or posterosuperior) claustrum is situated above and posterior to the limen insulae, posterior to the insular apex, and beneath the proximal part of the posterior short, anterior long, and posterior long gyri. The insular apex is the most prominent laterally projecting area on the insular surface. The central insular sulcus approximates the position of the center of the dorsal claustrum. B: Fiber dissection of the insular region showing the dorsal claustrum and external capsule, and the ventral claustrum and external capsule. The insular cortical gray matter and the extreme capsule have been removed. The uncinate fascicle forms most of the white matter of the limen insulae and passes beneath the anterior pole of the insula, connecting the temporal pole with the orbitofrontal region. The inferior frontaloccipital fascicle, which forms the most dorsal part of the limen insulae, is located deep with respect to the insular apex, and to the anterior and middle short gyri. It connects the frontal opercula and prefrontal region with the posterior temporal and occipital regions (panels C–F, coronal sections of the central core of the cerebral hemisphere at the level shown in panel F). The central core is the area between the insular cortex and the lateral and third ventricles. C: Cross-section of the brain immediately anterior to the limen insulae, and at the level of the insular apex (see panel F). The gray matter of the anterior segment of the uncus has been removed to expose the amygdala. The cross-section extends through the central core anterior to the dorsal claustrum. At this level the ventral claustrum extends toward the base of the frontal lobe below the putamen, adjoining the prepiriform cortex. Medially, the anteroinferior part of the putamen and the head of the caudate nucleus blend in the nucleus accumbens in the area below the anterior limb of the internal capsule. D: This section at the level of the anterior commissure crosses the dorsal and ventral claustrum, the anterior part of the amyg-dala, the uncinate fascicle, and the middle and posterior short gyri (see panel F). The dorsal claustrum is a column of gray matter situated between the insular cortex and the putamen. At the level of the limen insulae, the white fibers of the uncinate fascicle fragment the anteroinferior part of the claustrum, creating the characteristic islandlike pattern of the ventral claustrum, which at this level is located in the supraamygdalar area. The anterior segment of the uncus contains the amygdala. E: Cross-section obtained 5 mm behind the anterior commissure and crossing the posterior short gyrus and the anterior and posterior long gyri (see panel F). The dorsal claustrum has a triangular shape with its base at the inferior margin. The dorsal external capsule, situated between the dorsal claustrum and the putamen, narrows in the downward direction. At the level of the inferior margin of the dorsal claustrum, where its thickness is maximum, the dorsal external capsule is reduced to a thin layer of white matter, which covers the inferolateral surface of the putamen. F: Lateral view of the insula after removal of the opercular lips. The level of the coronal sections depicted in panels C–E is shown on the external surface of the insula. Ant. = anterior; Cap. = capsule; Caud. = caudate; Cent. = central; Comm. = commissure; Dors. = dorsal; Ext. = external; Fas. = fascicle; Front. = frontal; Glob. = glo-bus; Gyr. = gyrus; Inf. = inferior; Innom. = innominata; Int. = internal; Mid. = middle; Nucl. = nucleus; Occip. = occipital; Pall. = pallidus; Post. = posterior; Seg. = segment; Subst. = substantia; Temp. = temporal; Vent. = ventral.

  • View in gallery

    Photographs of cadaveric specimens showing stepwise fiber dissection of the left insular and basal ganglia region. A: The opercular lips of the sylvian fissure have been removed to expose the insula. The central sulcus, which is the deepest insular sulcus, separates the insula into larger anterior and smaller posterior portions. The anterior portion consists of 3 short gyri (anterior, middle, and posterior) arranged in a radiating pattern that converges at the insular pole located at the anteroinferior edge of the short insular gyri. The anterior and posterior long gyri extend backward and upward from the limen insulae. The inferior limiting sulcus is positioned below the long gyri of the insula and separates the insula from the sylvian surface of the temporal lobe. The superior limiting sulcus separates the insula from the sylvian surface of the frontal and parietal lobes. B: Removal of the cortical gray matter of the long and short insular gyri exposes the extreme capsule and the claustrum. The extreme capsule has a ventral (anteroinferior) part composed of the lateral fibers of the uncinate and inferior occipitofrontal fascicles, and a thinner dorsal (posterosuperior) part formed by multiple short association fibers that connect the different insular gyri with each other and with the adjacent frontal, parietal, and temporal operculae. The claustrum has a dorsal (posterosuperior) part, composed of compact gray matter, and a ventral (anteroinferior) part, formed by islands of gray matter intermixed with and fragmented by fibers of the uncinate and inferior occipitofrontal fascicles. C: Enlarged view of the dorsal claustrum and external capsule after removal of the dorsal part of the extreme capsule. The fibers of the dorsal external capsule converge in and merge with the gray matter of the dorsal claustrum, forming a characteristic spoke-and-wheel pattern with its center at the dorsal claustrum. Thus, they are claustrocortical fibers. The fibers of the uncinate and inferior occipitofrontal fascicles traverse the most anterior and inferior parts of the claustrum to create the gray matter islands that form the ventral claustrum. D: A further step in the dissection of the claustrocortical fibers. Removal of the claustrocortical fibers of the dorsal external capsule also peels away the gray matter of the dorsal claustrum. The fibers from the posterior part of the external capsule enter the posterior part of the dorsal claustrum, and the fibers coming from the middle part enter the anterior part of the dorsal claustrum. The fibers of the anterior part of the external capsule at this level belong to the uncinate and inferior occipitofrontal fascicles and traverse the ventral claustrum. E: After removal of most of the claustrocortical fibers and dorsal claustrum, only the deepest layer of the dorsal external capsule, which faces the putamen, remains. White gliotic tissue surrounding the lateral LSAs is found between the inferomedial surface of the dorsal claustrum and the adjacent putamen. F: Removal of the dorsal claustrum and the peri-vascular white matter exposes the lateral LSAs. These vessels pass medial to the uncinate fascicle and lateral to the anteroinferior pole of the putamen. G: The putamen and the globus pallidus have been removed to expose the anterior and posterior limbs of the internal capsule. The anterior commissure runs from a medial to lateral direction. The substantia innominata is located in front of and below the anterior commissure. Islands of gray matter of the ventral claustrum are found between the fibers of the uncinate fascicle. H: Enlarged view. The most medial fibers of the uncinate fascicle merge into the ventral claustrum and amygdala. The islands of gray matter forming the ventral claustrum blend to the amygdala. The nucleus accumbens, which is situated in the septal region below the head of the caudate nucleus, has been removed. A. = artery; Cor. = corona; Extr. = extreme; Ins. = insular; Lat. = lateral; Lent. = lenticulate; Limit. = limiting; Rad. = radiata; Sup. = superior.

  • View in gallery

    Diffusion tensor imaging–based tractography studies and cadaveric specimens showing the anatomical–radiological correlation between the tractography and fiber dissection studies of the claustrum and external capsule. A: A DT imaging–based tractography study obtained with the seed point at the level of the anterior part of the insular region (inset). The uncinate fascicle runs from the orbitofrontal to the anterior temporal region, and the inferior occipitofrontal fascicle from the prefrontal to the posterior temporal and occipital regions to form the ventral part of the external capsule. B: A DT imaging–based tractography study obtained with the seed point at the level of the middle part of the insular region (inset). Multiple fibers originating from the superior frontal, precentral, and postcentral gyri converge in the area just above the uncinate and occipitofrontal fascicles, which, as shown in the fiber dissections, corresponds to the area of the dorsal claustrum. These fibers form the anterior part of the dorsal external capsule. C: A DT imaging–based tractography study obtained after selecting the seed point at the posterior part of the insular region (inset). Several loops interconnect the superior parietal lobule and parietooccipital region and the area of the dorsal claustrum. These fibers form the posterior part of the dorsal external capsule. Some displayed tracts are continuing toward the prefrontal and orbitofrontal region. Based on the fiber dissection findings, we think this continuation reflects an artifact of the tractography study. D: A DT imaging–based tractography study showing the ventral and dorsal portions of the external capsule. The latter contains the claustrocortical projection system, which has a topographical organization. E: Axial section of a left cerebral hemisphere cut 15 mm above the anterior commissure. The upper part of the dorsal claustrum is identified as a thin sheet of gray matter located between the extreme and external capsule. The 3 seed points (colored rings in panels E and F) selected in the tractography studies are displayed F: White fiber dissection of the left insular region showing the 3 seed points selected for the tractography studies. The fibers of the dorsal external capsule, which come from the superior frontal, pre-central, postcentral, superior parietal, and parietooccipital regions, converge in the dorsal claustrum. The fibers of the inferior occipitofrontal and uncinate fascicles form the ventral external capsule. Lob. = lobule; Orb. = orbital; Par. = parietal; Prefront. = prefrontal; Proj. = projection.

  • View in gallery

    Diffusion tensor imaging–based tractography studies and cadaveric specimens showing anatomical–radiological correlations between the tractography and fiber dissection studies of the external and internal capsules. A: Coronal view of DT imaging–based tractography study obtained with 2 seed points, one at the external capsule and the other at the posterior limb of the internal capsule. The yellow tract corresponds to the external capsule, and the red one to the internal capsule. The putamen is located below and between where the fibers converge. The fibers of the external capsule join those of the internal capsule at the superior edge of the putamen, together forming the corona radiata. The fibers of the external and internal capsules do not join at the lower edge of the putamen. B: Coronal section of the right hemisphere cut 5 mm behind the anterior commissure. As we showed with the tractography study (panel A), the external capsule joins the internal capsule at the superior edge of the putamen to form the corona radiata. The external capsule is wider at the superior edge of the claustrum and narrows as it descends along the medial edge of the structure, leaving only a thin layer of fibers at the inferior edge of the putamen, where only a thin layer of white tissue surrounding the lateral LSAs remains. C: Coronal view of a different tractography study of the external and internal capsules. The fibers of the dorsal external capsule converge in the dorsal claustrum, the presumed site of the gray matter and nerve cells giving rise to the fibers. D: Fiber dissection of the left hemisphere. The superior part of the dorsal external capsule has been removed to show the relationship between the dorsal claustrum and external capsule, the putamen, and the corona radiata. The internal capsule is located deep with respect to the putamen. E: Left sagittal view of the tractography study shown in panel A. Anatomical–radiological correlation with panel D. The tractography study permits the visualization of fiber tracts, as in the internal and external capsules, at different depths. Cort. = cortico.

References

1

Berger MS: Comment on: Türe U, Yaşargil MG, Friedman AH, Al-Mefty O: Fiber dissection technique: lateral aspect of the brain. Neurosurgery 47:4264272000

2

Berman JIBerger MSMukherjee PHenry RG: Diffusion-tensor imaging-guided tracking of fibers of the pyramidal tract combined with intraoperative cortical stimulation mapping in patients with gliomas. J Neurosurg 101:66722004

3

Brand S: A serial section Golgi analysis of the primate claustrum. Anat Embryol (Berl) 162:4754881981

4

Calvert GABrammer MJBullmore ETCampbell RIversen SDDavid AS: Response amplification in sensory-specific cortices during crossmodal binding. Neuroreport 10:261926231999

5

Carman JBCowan WMPowell TPS: The cortical projection upon the claustrum. J Neurol Neurosurg Psychiatry 2:46511964

6

Carpenter MBSutin J: Human Neuroanatomy ed 8BaltimoreWilliams & Wilkins1983

7

Catani MFfytche DH: The rises and falls of disconnection syndromes. Brain 128:222422392005

8

Catani MHoward RJPajevic SJones DK: Virtual in vivo dissection of white matter fasciculi in the human brain. Neuroimage 17:77942002

9

Catani MJones DKDonato RFfytche DH: Occipito-temporal connections in the human brain. Brain 126:209321072003

10

Choi CRubino PAFernandez-Miranda JCAbe HRhoton AL Jr: Meyer's loop and the optic radiations in the transsylvian approach to the mediobasal temporal lobe. Neurosurgery 59:4 SupplONS228ONS2362006

11

Crick FCKoch C: What is the function of the claustrum?. Philos Trans R Soc Lond B Biol Sci 360:127112792005

12

Déjérine J: Anatomie des Centres Nerveux ParisRueff et Cie 11895. 807809

13

Druga R: Claustro-neocortical connections in the cat and rat demonstrated by HRP tracing technique. J Hirnforsch 23:1912021982

14

Druga R: Corticoclaustral connections. I. Frontoclaustral connections. Folia Morphol (Praha) 14:3913991966

15

Druga R: Cortico-claustral connections. II. Connections from the parietal, temporal, and occipital cortex to the claustrum. Folia Morphol (Praha) 16:1421491968

16

Druga R: Efferent projections from the claustrum (an experimental study using Nauta's method). Folia Morphol (Praha) 20:1631651972

17

Duffau HCapelle LLopes MFaillot TSichez JPFohanno D: The insular lobe: physiopathological and surgical considerations. Neurosurgery 47:8018102000

18

Duffau HGatignol PMandonnet EPeruzzi PTzourio-Mazoyer NCapelle L: New insights into the anatomo-functional connectivity of the semantic system: a study using cortico-subcortical electrostimulations. Brain 128:7978102005

19

Duffau HMandonnet EGatignol PCapelle L: Functional compensation of the claustrum: lessons from low-grade glioma surgery. J Neurooncol 81:3273292007

20

Edelstein LRDenaro FJ: The claustrum: a historical review of its anatomy, physiology, cytochemistry, and functional significance. Cell Mol Biol 50:6757022004

21

Ettlinger GWilson WA: Cross-modal performance: behavioural processes, phylogenetic considerations and neural mechanisms. Behav Brain Res 40:1691921990

22

Filimonoff IN: The claustrum, its origin and development. J Hirnforsch 8:5035281966

23

Filimonoff IN: Homologies of the cerebral formations of the mammals and reptiles. J Hirnforsch 7:2292511964

24

Hadjikhani NRoland PE: Cross-modal transfer of information between the tactile and the visual representations in the human brain: a positron emission tomographic study. J Neurosci 18:107210841998

25

Henry RGBerman JINagarajan SSMukherjee PBerger MS: Subcortical pathways serving cortical language sites: initial experience with diffusion tensor imaging fiber tracking combined with intraoperative language mapping. Neuroimage 21:6166222004

26

Hentschel SJLang FF: Surgical resection of intrinsic insular tumors. Neurosurgery 57:1 Suppl1761832005

27

Kamada KSawamura YTakeuchi FKawaguchi HKuriki STodo T: Functional identification of the primary motor area by corticospinal tractography. Neurosurgery 56:981092005

28

Kamada KTodo TMasutani YAoki SIno KTakano T: Combined use of tractography-integrated functional neuronavigation and direct fiber stimulation. J Neurosurg 102:6646722005

29

Kamada KTodo TMorita AMasutani YAoki SIno K: Functional monitoring for visual pathway using real-time visual evoked potentials and optic radiation tractography. Neurosurgery 57:1211272005

30

Kemp JMPowell TPS: The corticostriate projection in the monkey. Brain 93:5255461970

31

Kimura SNezu AOsaka HSaito K: Symmetrical external capsule lesions in a patient with herpes simplex encephalitis. Neuropediatrics 25:1621641994

32

Kowianski PDziewiatkowski JKowianska JMorys J: Comparative anatomy of the claustrum in selected species: a morphometric analysis. Brain Behav Evol 53:44541999

33

Lang FFOlansen NEDeMonte FGokaslan ZLHolland ECKalhorn C: Surgical resection of intrinsic insular tumors: complication avoidance. J Neurosurg 95:6386502001

34

Lazar MWeinstein DMTsuruda JSHasan KMArfanakis KMeyerand ME: White matter tractography using diffusion tensor deflection. Hum Brain Mapp 18:3063212003

35

Le Bihan D: Looking into the functional architecture of the brain with diffusion MRI. Nat Rev Neurosci 4:4694802003

36

Lehericy SDucros MKrainik AFrancois CVan de Moortele PFUgurbil K: 3-D diffusion tensor axonal tracking shows distinct SMA and pre-SMA projections to the human striatum. Cereb Cortex 14:130213092004

37

Lehericy SDucros MVan de Moortele PFFrancois CThivard LPuopon C: Diffusion tensor fiber tracking shows distinct corticostriatal circuits in humans. Ann Neurol 55:5225292004

38

Ludwig EKlinger J: Atlas Cerebri Humani BaselKarger1956

39

Makris NKennedy DNMcInerney SSorensen AGWang RCaviness VS Jr: Segmentation of subcomponents within the superior longitudinal fascicle: a quantitative, in vivo, DT-MRI study. Cereb Cortex 15:8548692005

40

Mamata HMamata YWestin CFShenton MEKikinis RJolesz FA: High-resolution line scan diffusion tensor MR imaging of white matter fiber tract anatomy. AJNR Am J Neuroradiol 23:67752002

41

Mandonnet ECapelle LDuffau H: Extension of paralimbic low grade gliomas: toward an anatomical classification based on white matter invasion patterns. J Neurooncol 78:1791852006

42

Mesulam MMGeula C: Nucleus basalis (Ch4) and cortical cholinergic innervation in the human brain: observations based on the distribution of acetylcholinesterase and choline acetyltransferase. J Comp Neurol 275:2162401988

43

Mori SCrain BJChacko VPvan Zijl PC: Three dimensional tracking of axonal projections in the brain by magnetic resonance imaging. Ann Neurol 45:2652691999

44

Morys JBerdel BMaciejewska BKrol JDziewiatkowski J: Loss of neurons in the claustrum of aging brain. Folia Neuropathol 34:971011996

45

Morys JBobinski MWegiel JWisniewski HMNarkiewicz O: Alzheimer's disease severely affects areas of the claustrum connected with the entorhinal cortex. J Hirnforsch 37:1731801996

46

Morys JNarkiewicz OWisniewski HM: Neuronal loss in the human claustrum following ulegyria. Brain Res 616:1761801993

47

Morys JSloniewski PNarkiewicz O: Somatosensory evoked potentials following lesions of the claustrum. Acta Physiol Pol 39:4754831988

48

Narkiewicz O: Connections of the claustrum with the cerebral cortex. Folia Morphol (Warsz) 25:5555611966

49

Narkiewicz O: Degenerations in the claustrum after regional neo-cortical ablations in the cat. J Comp Neurol 123:3353561964

50

Narkiewicz O: Frontoclaustral interrelations in cats and dogs. Acta Neurobiol Exp (Warsz) 32:1411501972

51

Niewenhuys RVoogd Jvan Huijzen C: The Human Central Nervous System BerlinSpringler-Verlag1988

52

Nimsky CGanslandt OFahlbusch R: Implementation of fiber tract navigation. Neurosurgery 58:2 Suppl2923032006

53

Nimsky CGanslandt OHastreiter PWang RBenner TSorensen AG: Intraoperative diffusion-tensor MR imaging: shifting of white matter tracts during neurosurgical procedures—initial experience. Radiology 234:2182252005

54

Nimsky CGanslandt OHastreiter PWang RBenner TSorensen AG: Preoperative and intraoperative diffusion tensor imaging-based fiber tracking in glioma surgery. Neurosurgery 56:1301372005

55

Nishizawa M: Acute encephalopathy after ingestion of “sugihiratake” mushroom. Rinsho Shinkeigaku 45:8188202005

56

Pearson RCBrodal PGatter KCPowell TP: The organization of the connections between the cortex and the claustrum in the monkey. Brain Res 234:4354411982

57

Peuskens Dvan Loon Jvan Calenbergh Fvan den Bergh RGoffin JPlets C: Anatomy of the anterior temporal lobe and the frontotemporal region demonstrated by fiber dissection. Neurosurgery 55:117411832004

58

Poupon CClark CAFrouin VRegis JBloch ILe Bihan D: Regularization of diffusion-based direction maps for the tracking of brain white matter fascicles. Neuroimage 12:1841952000

59

Rae AS: The connections of the claustrum. Confin Neurol 14:2112191954

60

Rae AS: The form and structure of the human claustrum. J Comp Neurol 100:15391954

61

Rhoton AL Jr: The cerebrum. Neurosurgery 51:SupplS1S512002

62

Ridley M: Francis Crick: Discoverer of the Genetic Code New YorkHarperCollins2006. 204210

63

Rubino PARhoton AL JrTong XOliveira E: Three-dimensional relationships of the optic radiation. Neurosurgery 57:Suppl2192272005

64

Schmahmann JDPandya DN: Fiber Pathways of the Brain New YorkOxford University Press2006. 36

65

Sincoff EHTan YAbdulrauf SI: White matter dissection of the optic radiations of the temporal lobe and implications for surgical approaches to the temporal horn. J Neurosurg 101:7397462004

66

Sperner JSander BLau SKrude HScheffner D: Severe transitory encephalopathy with reversible lesions of the claustrum. Pediatr Radiol 26:7697711996

67

Standring SCrossman ARTurlough FitzGerald MJCollins PNeuroanatomy. Standring S: Gray's Anatomy: the Anatomical Basis of Clinical Practice ed 39New YorkElsevier Churchill Livingstone2005. 403

68

Stevens CF: Crick and the claustrum. Nature 435:104010412005

69

Tanriover NRhoton AL JrKawashima MUlm AJYasuda A: Microsurgical anatomy of the insula and the sylvian fissure. J Neurosurg 100:8919222004

70

Trolard P: Au sujet de l'avantmur. Rev Neurol 13:106810711905. (Fr)

71

Ture UYaşargil DCAl-Mefty OYaşargil MG: Topographic anatomy of the insular region. J Neurosurg 90:7207331999

72

Ture UYaşargil MGFriedman AHAl-Mefty O: Fiber dissection technique: lateral aspect of the brain. Neurosurgery 47:4174262000

73

Wakana SJiang HNagae-Poetscher LMvan Zijl PCMori S: Fiber tract-based atlas of human white matter anatomy. Radiology 230:77872004

74

Yaşargil MG: StuttgartGeorg Thieme1994. Vol IVA:68

75

Yaşargil MGTure UYaşargil DC: Impact of temporal lobe surgery. J Neurosurg 101:7257382004

76

Yaşargil MGvon Ammon KCavazos EDoczi TReeves JDRoth P: Tumors of the limbic and paralimbic systems. Acta Neurochir (Wien) 118:40521992

77

Young PAYoung PH: Basic Clinical Neuroanatomy Balti-moreWilliams & Wilkins1997

78

Zentner JMeyer BStangi ASchramm J: Intrinsic tumors of the insula: a prospective surgical study of 30 patients. J Neurosurg 85:2632711996

79

Zhang XHannesson DKSaucier DMWallace AEHowland JCorcoran ME: Susceptibility to kindling and neuronal connections of the anterior claustrum. J Neurosci 21:367436872001

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