The cerebellothalamic tract, or brachium conjuntivum, originates in the dentate, interposed and fastigial cerebellar nuclei. The cerebellothalamic tract ascends through the superior cerebellar peduncle, crosses (most of the fibres) over its decussation, passes through and anteriorly to the red nucleus and then rises into the thalamus. To ease the description, we adopted a Latin nomenclature for the subthalamic fibre systems, i.e. the cerebellothalamic fibre bulk is called “fasciculus cerebellothalamicus” (fct) from the level of the red nucleus (RN) to its entrance into the thalamus.
The fct was traced on the basis of myelin stained sections, from the dorsal border of the RN to the thalamus. Overall, the trajectory of the tract can be relatively easily followed; it climbs into the thalamus with a posteromedial to anterolateral direction. On sagittal sections, the main orientation of the tract is posteroventral to anterodorsal, with a 60°–65° angle with the intercommissural plane (Fig. ). The relative stable anteroposterior position of the fct at mid-distance between the posterior commissure (pc) and midcommissural level (mcl) is recognizable in horizontal sections (Fig. ). On frontal sections, the orientation is medioventral to laterodorsal, with a 40°–45° angle with the intercommissural plane (Figs. , ). In myelin stain, the entrance of the fibres is clearly seen in the ventral division of the ventral lateral posterior (VLpv) nucleus (Fig. , sagittal planes L10.8 and L11.7) with a possible extension into the ventral lateral anterior (VLa) nucleus (e.g. Figs. a; , L9 and L9.9). On its way to the VLp, most of the fct passes ventral to the subparafascicular (sPf) nucleus, anterolaterally to the parvocellular part of the ventral posterior medial (VPMpc) and VPM nuclei, and through the ventral medial nucleus (VM) at level posterior to the subthalamic nucleus and the zona incerta (ZI) (Fig. ). It is interesting to note that at the dorsal border of the RN, a part of the fct seems to take a medial turn towards the centre médian nucleus (CM) (Fig. , section A6.0).
Fig. 5 Pallidothalamic (blue) and cerebellothalamic (orange) tracts drawn on the atlas of the human thalamus (case Hb1). The sagittal maps are arranged from medial (L4.5) to lateral (L11.7 mm) with 0.9 mm intervals. The maps are centered on the (more ...)
Fig. 6 Pallidothalamic (blue) and cerebellothalamic (orange) tracts drawn on horizontal sections of the atlas at intercommissural level (DV0) and four levels ventral to DV0 (V0.9, V1.8, V2.7, and V3.6). The horizontal planes are projected on a sagittal section (more ...)
Fig. 7 Series of frontal high-resolution proton density postmortem MRI (left column), myelin sections (middle column), and atlas maps (right column) of the same brain (Table ; Hb5), at corresponding anteroposterior levels from posterior (lower panels (more ...)
In adjacent sections stained for AChE or immunoreacted for CaBP, the fct appears generally negative, except for PV-immunoreactivity (PV-ir), which also characterizes the RN and STh, as described below.
The pallidothalamic tract was traced from its origin in the GPi and divided into two bundles according to previous descriptions (Vogt 1909
; Vogt and Vogt 1920
; Nauta and Mehler 1966
): the ansa lenticularis (al) and the fasciculus lenticularis (fl). The al, which represents the ventral division of the ansa lenticularis of von Monakow leaves the internal pallidum at its anteroventral edge and courses anteromedially around the posterior limb of the internal capsule (Figs. , ). Its origin in the pallidum appears to extend from far rostral to near the caudal end of GPi, and from both medial and lateral subdivisions of the nucleus. From the internal capsule, the al continues posterodorsally to take a sharp descending, then an ascending turn toward the thalamus where it is joined by the fibres of the fl arriving over the dorsal edge of the subthalamic nucleus. The fl (or field H2 of Forel) leaves the GPi dorsal to al (Fig. , A21.0 and A19.0; Fig. , A17.5) and represents the dorsal division of the ansa lenticularis of von Monakow. Its emergence from GPi seems to extend not as far rostrally as that of al. Although the precise course of the fl through the internal capsule cannot be determined on myelin sections as it is embedded within the capsular fibres, it seems to cross the internal capsule nearly horizontally and then runs dorsal to the subthalamic nucleus and ventral to ZI in a posteroventral direction, joining the al to form the fasciculus thalamicus (ft). The term ft thus characterizes all pallidothalamic fibres entering the ventral thalamus, regardless of their ansal or fascicular origin. The ft reaches mainly the parvocellular division of the ventral anterior (VApc) and VLa nuclei through the anterior part of the VM nucleus (Fig. , L9 and L9.9).
Fig. 8 Anterior continuation of the series shown in Fig. to illustrate MRI correlations of pallidothalamic fibre tracts (al, fl, and ft), thalamic nuclei, and basal ganglia. Same conventions as in Fig. . Scale bars (left column): 10 mm (more ...)
Fig. 9 a Illustration of the pallidal emergence of al in horizontal and b frontal sections stained for myelin. The levels are 4.5 mm ventral to the intercommissural plane (in a) and 22 mm anterior to pc (in b). Note the relatively large anteroposterior (more ...)
In relation to the classic nomenclature, Forel field H2 corresponds to the emergence of fl fibres from the internal capsule. The field H1, on the other hand, is more difficult to relate with the al or fl because it contains both fibre bundles. The most medial component of the ft seems to arise from al more than fl (Fig. , L4.5, L5.4, and L6.3), which in turn joins the ft more laterally (Fig. , L7.2 and L8.1). Whether this apparent mediolateral gradient persists at the entrance of the tract into the thalamus cannot be determined at this point. At most posterior and medial levels (e.g. Fig. , L7.2), the pallidothalamic fibres form the so-called “H1 + H2” field of Forel. At this level, the ft is not yet joined by all of the fl fibres. The transition between this part of ft and the ansa, as well as with ft proper containing both fl and al fibres, is unclear and cannot be identified on the basis of the present data. As best seen in the horizontal plane, the ft tract comes close to the mammillothalamic (mtt) tract which courses toward the anteroventral (AV) nucleus. This close vicinity of the two tracts occurs near midcommissural level (mcl; Fig. , sagittal planes L4.5 and L5.4; Fig. ).
The al, fl, and ft are generally unstained with different markers, except for slight PV-ir in ft at subthalamic level (Fig. d). At pallidal level, the “negative” staining of al is clearly in contrast with the very intense CR-ir in the sublenticular area, associated with the extended amygdala defined by others (Heimer et al. 1997
; Alheid 2003
), as well as with enhanced CB-ir in the GPi (see Fig. c, d). The CR-ir fibre tract ascending into the thalamus at the same level and which is continuous with the sublenticular CR-ir fibres (Fig. d) corresponds to the ansa peduncularis (ap) known to connect the amygdala to the mediodorsal (MD) and reticular (R) thalamic nuclei.
Fig. 10 Multiarchitectonic characteristics of the pallidal and subpallidal areas on photomicrographs of frontal sections stained for a myelin, b AChE or c immunoreacted for CB and d CR. Note the clear contrast between al (only moderately stained) and the GPi (more ...)
Striatonigral and pallidosubthalamic fibres
Two other fibre systems related to the basal ganglia are the pallidosubthalamic and striatonigral fibres, which are part of the so-called “comb system” (Nauta and Mehler 1966
). Pallidosubthalamic fibres form the fasciculus subthalamicus, which was associated with the middle division of the ansa lenticularis of von Monakow (1895
) and connects the external pallidum (GPe) to the STh. The tract cannot be distinguished from the fl at its emergence from the GPi, but further posteriorly and medially, can be seen as thick myelin bundles coming into the STh, ventral to the fl and dorsal to al (Figs. a, a). In contrast to fl and al, which remain largely unstained, some of pallidosubthalamic fibres are characterized by enhanced PV-ir and can be traced through the internal capsule up to the level of the subthalamic nucleus, which itself contains very high level of PV (Figs. d, d). Interestingly, these PV-ir fibres appear in negative contrast to the thick myelinated fibres seen at the same level (Figs. a, a). The tract corresponding to this position contained very dense degenerated fibres after lesion of GPe (Morel et al. 2001
Fig. 11 Photomicrographs of adjacent frontal sections 15 mm anterior to the posterior commissure stained for a myelin, c AchE, and b immunostained for the calcium-binding proteins CB and d PV. Pallidothalamic fibres (fl, ft) are darkly stained for myelin, (more ...)
The large fibre bundles characterized by high CB-ir and AChE staining reaching the substantia nigra (SN) correspond to the striatonigral fibres described previously (Morel et al. 2002
). In the subthalamic area, these fibres run ventral to the STh and to the fasciculus subthalamicus to continue posteriorly toward the SN, as shown in Fig. b. Through not illustrated in the present report, these fibres can be followed from their origin in the striatum (mostly from the posterior two-third of the putamen), through the two pallidal segments and the internal capsule, to their entry in the pars reticulata (SNr). The striatonigral fibres are also enhanced in SMI-32-ir, while only moderately for PV- and CR-ir (Figs. c, e; d). They appear largely unstained in myelin (Fig. a), which is presumably related to their smaller size.
High-resolution proton density MRI was obtained from one brain (Hb5, Table ; see also MRI acquisition protocole in “Materials and methods
”) prior to guillotine sectioning and histological processing. After MRI acquisition, one hemisphere was cut in the frontal plane and the other in the horizontal plane. The MRI slices (1.3-mm thick) were correlated with the closest myelin stained sections and drawings of the same brain. Examples of these correlations are shown on frontal sections in Figs. and , at different anteroposterior levels of the thalamus. On these high-resolution MRI, several thalamic and basal ganglia subdivisions can be well recognized: the striatum (PuT, Cd), both segments of the pallidum (GPe/GPi) separated by the internal medullary lamina (Fig. , A20–A15), medial, lateral, and anterior thalamic nuclei (AV, LD, MD, LP, and the intralaminar CM and CL nuclei). The reticular nucleus (R) is also distinguishable between the internal capsule and the lateral nuclei (Fig. , A5–A7.5). The fct tract is illustrated in Fig. at three anteroposterior levels (A7.5, A5.0, and A2.5), highlighting its entrance into the thalamus. The course of the pallidothalamic fibres is shown in Fig. , from their emergence from the internal part of the pallidum (A20.0 and A17.5 for the al and A17.5 and A15.0 for the fl) up to their entry in the thalamus (A12.25). At levels A17.5 and A15.0, the course of the tract in the subthalamic area and the most medial extension of the al just before merging with the fl to form the ft are also clearly recognized. Other fibre tracts such as the fornix (fx), the mtt and the optic tract (ot) are strongly contrasted.
Stereotactic localization and interindividual variability
The stereotactic position of the cerebello- and pallidothalamic tracts was determined in six hemispheres (three brains; cases Hb1, Hb4, and Hb5; Table ). As seen on sagittal and horizontal planes (Figs. , ), the fct enters the thalamus more posterior and lateral than the ft, but the two come into close proximity at several mediolateral levels (e.g. Fig. , L7.2–L9) and in horizontal planes, ventral to the intercommissural level (e.g. Fig. , level V0.9). Nevertheless, there is a gap between the two tracts, as best seen in sagittal sections stained for myelin or immunoreacted for PV (arrows in Fig. a, d) and the bulks of the fct and ft are clearly separated. The position of the two tracts in different brains is illustrated on sagittal and horizontal atlas sections in Fig. . The fct, ft, and fl from two different brains (Hb1 in red and Hb4 in gray) are compared on sagittal sections (L7 and L8) in upper panels. In these representations, the tracts show similar dorsoventral and anteroposterior positions. More variations are seen in the mediolateral axis, as best illustrated on horizontal section (lower panel) where the fiber tracts from four different brains (Hb1, Hb2, Hb3, and Hb5) are superposed. The area of maximal overlap between three of the four cases (represented in yellow) is located in the medial more than the lateral part of the tracts. This is related to overall differences in mediolateral width of the thalamus and subthalamic area in the different brains (as also reported in Morel 2007
). As seen on sagittal planes (upper panels of Fig. ), the dorsoventral variation of the position of the two tracts is similar to that of the ventral part of the thalamus (e.g. CM, VPMpc, and ventral limit of VLpv and VM), but much smaller than the variation of dorsal thalamic nuclei (e.g. LD, dorsal extent of VLpd, MD, and CL). In order to evaluate more quantitatively the variability of the cerebello- and pallidothalamic tracts, the mediolateral and anteroposterior stereotactic coordinates of the bulk centers of the two tracts were determined on sagittal planes of two different brains (Hb1 and Hb4). In every sagittal map, the anteroposterior coordinate of the center of the fibre bulks was measured at their intersecting point with the DV0, V1, and V2 horizontal planes, respectively. The mediolateral and anteroposterior coordinates of the ft, fl, and fct are plotted in Fig. for the three dorsoventral levels.
Fig. 12 Variability of the fibre tracts in the subthalamic area in sagittal (upper panels) and horizontal (lower panel) atlas maps of different brains. In sagittal sections (upper panels, L7 and L8), red contours and filling correspond to brain Hb1 and black (more ...)
Fig. 13 Spatial relationship between the fct, ft, and fl. In each diagram, the x-axis represents the distance (mm) to the posterior commissure and the y-axis, the distance to the medial thalamic border. The distances were measured at three different dorsoventral (more ...)
The smallest anteroposterior distance between fct and ft centers is similar (2.4 mm) in both Hb1 and Hb4, when considering the three dorsoventral planes. At V2 level, the median anteroposterior value of ft is 11 mm in Hb1 and 12.7 mm in Hb4. In terms of mediolateral extension, there is a significant difference between the two cases with an extension from L4.5 to L9 for Hb1, and from L2 to L5 for Hb4. The position of the fl is more anterior to ft in both cases (median values of 15.6 and 15.2 mm anterior to pc for Hb1 and Hb4, respectively), and the mediolateral extension varies from 6.3 to 8.1 mm in case Hb1, and from 3 to 6 mm in case Hb4. For the fct, anteroposterior median value is 6.8 mm in Hb1 and 6.7 mm in Hb4. The mediolateral extension is from L4.5 to L14 in Hb1, and from L2 to L10 in Hb4. As already shown in Fig. , the variations of the tracts in the different cases are not homogeneous in the three planes, with smallest variations in anteroposterior and dorsoventral axes, and largest variations in mediolateral axis.
Implications for stereotactic surgery
According to the orientations and stereotactic positions of the cerebello- and pallidothalamic tracts (Figs. , , ), and because of the electrode trajectory restrained by a precoronal approach, our surgical targeting in PD and in ET are determined at 2 mm ventral to intercommissural plane (V2). The anteroposterior and mediolateral coordinates for the pallidothalamic tractotomy (PTT) are at midcommissural (mcl) level and 7 mm lateral to ventricular border, respectively. For the cerebellothalamic tractotomy (CTT), these are 5–6 mm posterior to mcl and 8 mm lateral to ventricular border, respectively. This strategy has been developed for (1) best inclusion of both fl and ft in PD, with minimum involvement of STh and keeping a safe distance between the RFL and the internal capsule and mtt (see also Aufenberg et al. 2005
), and (2) to take the cerebellothalamic tract between RN and the thalamus, but avoid the risk of encroaching on the trigeminal thalamic relay VPM nucleus (more “eloquent” structure than VPMpc) by remaining relatively medial. The locations of the targeted PTT and CTT in relation to the variability of the positions of the pallido- and cerebellothalamic tracts are represented in Fig. on sagittal (upper panels) and horizontal (lower panel) atlas maps. The use of anteroposterior mcl level, instead of the pc level, and of physiological control for depth assessment, allows adjusting the site for RFL in different patients. For mediolateral coordinates, some correction can be made according to the width of the thalamus and subthalamic area assessed by the border of the internal capsule. However, corrections are minimized by the fact that targeting is directed at more medial portions of the two tracts where interindividual variations are less marked (Morel 2007
; see also Fig. , lower panel). Figure illustrates PTT of fl and ft, and CTT of fct in two patients with PD and ET, respectively, on 2-day postoperative axial T1-weighted MRI (panels a and b) and projections onto a horizontal section of the atlas (panel c). The PD patient suffered from a tremor dominant unilateral form of the disease and at 1-year follow-up, benefited from a complete tremor relief, without arising of new symptoms. He experienced a strong improvement of his quality of life and daily activities. The ET patient manifested at the 1.5-year follow-up, a complete control of both the postural and kinetic components of his prominent action tremor.
Fig. 14 Targeting in functional neurosurgery. a, b Postoperative T1-weighted axial MRI and c atlas reconstruction of pallidothalamic (PTT) and cerebellothalamic (CTT) tractotomies in two patients with PD and ET, respectively (see text for more detail). The horizontal (more ...)