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Objective: Deep brain stimulation (DBS) of the centromedian thalamic nucleus has been reportedly used to treat severe Tourette syndrome, yielding promising outcomes. However, it remains unclear how DBS electrode position and stimulation parameters modulate the specific area and related networks. The authors aimed to evaluate the relationships between the anatomical location of stimulation fields and clinical responses, including therapeutic and side effects., Methods: The authors collected data from 8 patients with Tourette syndrome who were treated with DBS. The authors selected the active contact following threshold tests of acute side effects and gradually increased the stimulation intensity within the therapeutic window such that acute and chronic side effects could be avoided at each programming session. The patients were carefully interviewed, and stimulation-induced side effects were recorded. Clinical outcomes were evaluated using the Yale Global Tic Severity Scale, the Yale-Brown Obsessive-Compulsive Scale, and the Hamilton Depression Rating Scale. The DBS lead location was evaluated in the normalized brain space by using a 3D atlas. The volume of tissue activated was determined, and the associated normative connective analyses were performed to link the stimulation field with the therapeutic and side effects., Results: The mean follow-up period was 10.9 ± 3.9 months. All clinical scales showed significant improvement. Whereas the volume of tissue activated associated with therapeutic effects covers the centromedian and ventrolateral nuclei and showed an association with motor networks, those associated with paresthesia and dizziness were associated with stimulation of the ventralis caudalis and red nucleus, respectively. Depressed mood was associated with the spread of stimulation current to the mediodorsal nucleus and showed an association with limbic networks., Conclusions: This study addresses the importance of accurate implantation of DBS electrodes for obtaining standardized clinical outcomes and suggests that meticulous programming with careful monitoring of clinical symptoms may improve outcomes.

Objective: Projections from the dentate nucleus (DN) follow a certain organized course to upper levels. Crossing and noncrossing fibers of the dentatorubrothalamic (DRT) tract terminate in the red nucleus and thalamus and have various connections throughout the cerebral cortex. We aimed to establish the microsurgical anatomy of the DN in relation to its efferent connections to complement the increased recognition of its surgical importance and also to provide an insight into the network-associated symptoms related to lesions and microsurgery in and around the region., Methods: The cerebellum, DN, and superior cerebellar peduncle (SCP) en route to red nucleus were examined through fiber dissections from the anterior, posterior, and lateral sides to define the connections of the DN and its relationships with adjacent neural structures., Results: The DN was anatomically divided into 4 areas based on its relation to the SCP; the lateral major, lateral anterosuperior, posteromedial, and anteromedial compartments. Most of the fibers originating from the lateral compartments were involved in the decussation of the SCP. The ventral fibers originating from the lateral anterosuperior compartment were exclusively involved in the decussation. The fibers from the posteromedial compartment ascended ipsilaterally and decussated, whereas most anteromedial fibers ascended ipsilaterally and did not participate in the decussation., Conclusions: Clarifying the anatomofunctional organization of the DN in relation to the SCP could improve microneurosurgical results by reducing the complication rates during infratentorial surgery in and around the nucleus. The proposed compartmentalization would be a major step forward in this effort., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The red nucleus (RN) is a large subcortical structure located in the ventral midbrain. Although it originated as a primitive relay between the cerebellum and the spinal cord, during its phylogenesis the RN shows a progressive segregation between a magnocellular part, involved in the rubrospinal system, and a parvocellular part, involved in the olivocerebellar system. Despite exhibiting distinct evolutionary trajectories, these two regions are strictly tied together and play a prominent role in motor and non-motor behavior in different animal species. However, little is known about their function in the human brain. This lack of knowledge may have been conditioned both by the notable differences between human and non-human RN and by inherent difficulties in studying this structure directly in the human brain, leading to a general decrease of interest in the last decades. In the present review, we identify the crucial issues in the current knowledge and summarize the results of several decades of research about the RN, ranging from animal models to human diseases. Connecting the dots between morphology, experimental physiology and neuroimaging, we try to draw a comprehensive overview on RN functional anatomy and bridge the gap between basic and translational research.

Normative databases allow testing of novel hypotheses without the costly collection of magnetic resonance imaging (MRI) data. Here we present the Amsterdam Ultra-high field adult lifespan database (AHEAD). The AHEAD consists of 105 7 Tesla (T) whole-brain structural MRI scans tailored specifically to imaging of the human subcortex, including both male and female participants and covering the entire adult life span (18-80 yrs). We used these data to create probability maps for the subthalamic nucleus, substantia nigra, internal and external segment of the globus pallidus, and the red nucleus. Data was acquired at a submillimeter resolution using a multi-echo (ME) extension of the second gradient-echo image of the MP2RAGE sequence (MP2RAGEME) sequence, resulting in complete anatomical alignment of quantitative, R 1 -maps, R 2 *-maps, T 1 -maps, T 1 -weighted images, T 2 *-maps, and quantitative susceptibility mapping (QSM). Quantitative MRI maps, and derived probability maps of basal ganglia structures are freely available for further analyses., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

The Red Nucleus (RN) is a large nucleus located in the ventral midbrain: it is subdivided into a small caudal magnocellular part (mRN) and a large rostral parvocellular part (pRN). These distinct structural regions are part of functionally different networks and show distinctive connectivity features: the mRN is connected to the interposed nucleus, whilst the pRN is mainly connected to dentate nucleus, cortex and inferior olivary complex. Despite functional neuroimaging studies suggest RN involvement in complex motor and higher order functions, the pRN and mRN cannot be distinguished using conventional MRI. Herein, we employ high-quality structural and diffusion MRI data of 100 individuals from the Human Connectome Project repository and constrained spherical deconvolution tractography to perform connectivity-based segmentation of the human RN. In particular, we tracked connections of RN with the inferior olivary complex, the interposed nucleus, the dentate nucleus and the cerebral cortex. We found that the RN can be subdivided according to its connectivity into two clusters: a large ventrolateral one, mainly connected with the cerebral cortex and the inferior olivary complex, and a smaller dorsomedial one, mainly connected with the interposed nucleus. This structural topography strongly reflects the connectivity patterns of pRN and mRN respectively. Structural connectivity-based segmentation could represent a useful tool for the identification of distinct subregions of the human red nucleus on 3T MRI thus allowing a better evaluation of this subcortical structure in healthy and pathological conditions.

The dentato-rubro-thalamic tract (DRTT) regulates motor control, connecting the cerebellum to the thalamus. This tract is modulated by deep-brain stimulation in the surgical treatment of medically refractory tremor, especially in essential tremor, where high-frequency stimulation of the thalamus can improve symptoms. The DRTT is classically described as a decussating pathway, ascending to the contralateral thalamus. However, the existence of a nondecussating (i.e. ipsilateral) DRTT in humans was recently demonstrated, and these tracts are arranged in distinct regions of the superior cerebellar peduncle. We hypothesized that the ipsilateral DRTT is connected to specific thalamic nuclei and therefore may have unique functional relevance. The goals of this study were to confirm the presence of the decussating and nondecussating DRTT pathways, identify thalamic termination zones of each tract, and compare whether structural connectivity findings agree with functional connectivity. Diffusion-weighted imaging was used to perform probabilistic tractography of the decussating and nondecussating DRTT in young healthy subjects from the Human Connectome Project (n = 91) scanned using multi-shell diffusion-weighted imaging (270 directions; TR/TE = 5500/89 ms; spatial resolution = 1.25 mm isotropic). To define thalamic anatomical landmarks, a segmentation procedure based on the Morel Atlas was employed, and DRTT targeting was quantified based on the proportion of streamlines arriving at each nucleus. In parallel, functional connectivity analysis was performed using resting-state functional MRI (TR/TE = 720/33 ms; spatial resolution = 2 mm isotropic). It was found that the decussating and nondecussating DRTTs have significantly different thalamic endpoints, with the former preferentially targeting relatively anterior and lateral thalamic nuclei, and the latter connected to more posterior and medial nuclei (p < 0.001). Functional and structural connectivity measures were found to be significantly correlated (r = 0.45, p = 0.031). These findings provide new insight into pathways through which unilateral cerebellum can exert bilateral influence on movement and raise questions about the functional implications of ipsilateral cerebellar efferents., (Copyright © 2018. Published by Elsevier Inc.)

The substantia nigra (SN), the subthalamic nucleus (STN), and the red nucleus (RN) are midbrain structures of ample interest in many neuroimaging studies, which may benefit from the availability of automated segmentation methods. The high iron content of these structures awards them high contrast in quantitative susceptibility mapping (QSM) images. We present a novel segmentation method that leverages the information of these images to produce automated segmentations of the SN, STN, and RN. The algorithm builds a map of spatial priors for the structures by non-linearly registering a set of manually-traced training labels to the midbrain. The priors are used to inform a Gaussian mixture model of the image intensities, with smoothness constraints imposed to ensure anatomical plausibility. The method was validated on manual segmentations from a sample of 40 healthy younger and older subjects. Average Dice scores were 0.81 (0.05) for the SN, 0.66 (0.14) for the STN and 0.88 (0.04) for the RN in the left hemisphere, and similar values were obtained for the right hemisphere. In all structures, volumes of manual and automatically obtained segmentations were significantly correlated. The algorithm showed lower accuracy on R 2 * and T 2 -weighted Fluid Attenuated Inversion Recovery (FLAIR) images, which are also sensitive to iron content. To illustrate an application of the method, we show that the automated segmentations were comparable to the manual ones regarding detection of age-related differences to putative iron content., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Lesions of the cerebellar dentate nucleus (DN) reduce the after-discharge duration induced by repetitive kindling stimulation and decrease seizures to a lower rank according to Racine's scale. The DN sends cholinergic and glutamatergic fibers to the red nucleus (RN), which is composed of glutamatergic and GABAergic cells. To test the participation of these neurotransmitters in seizures, we compared the levels of glutamate and gamma-aminobutyric acid (GABA) at the RN in a control condition, a kindled stage, and a kindled stage followed by DN lesions. We found that the kindled stage was associated with significant reductions in glutamate and GABA in the RN and that the lesions of the DN in kindled rats reversed the severity of seizures and restored the GABA levels. GAD 65 , a GABA-synthesizing enzyme, was increased in kindled rats and decreased after DN lesions. GAD 65 commonly appears localized at nerve terminals and synapses, and it is only activated when GABA neurotransmission occurs. Thus, it is possible that the increased expression of GAD 65 found in kindled rats could be due to an exacerbated demand for GABA due to kindled seizures. It is known that GABA maintains the inhibitory tone that counterbalances neuronal excitation. The decreased expression of GAD 65 found after the DN lesions indicated that the GABA-synthesizing enzyme was no longer required once it eliminated the excitatory glutamate input to the RN. We thus conclude that DN lesions and their consequent biochemical changes are capable of decreasing the generalized seizures induced by kindling stimulation. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

With recent developments in MR acquisition at 7T, smaller brainstem structures such as the red nuclei, substantia nigra and subthalamic nuclei can be imaged with good contrast and resolution. These structures have important roles both in the study of the healthy brain and in diseases such as Parkinson's disease, but few methods have been described to automatically segment them. In this paper, we extend a method that we have previously proposed for segmentation of the striatum and globus pallidus to segment these deeper and smaller structures. We modify the method to allow more direct control over segmentation smoothness by using a Markov random field prior. We investigate segmentation performance in three age groups and show that the method produces consistent results that correspond well with manual segmentations. We perform a vertex-based analysis to identify changes with age in the shape of the structures and present results suggesting that the method may be at least as effective as manual delineation in capturing differences between subjects., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Diffusion-weighted imaging (DWI) tractography is a technique with great potential to characterize the in vivo anatomical position and integrity of white matter tracts. Tractography, however, remains an estimation of white matter tracts, and false-positive and false-negative rates are not available. The goal of the present study was to compare postmortem tractography of the dentatorubrothalamic tract (DRTT) by its 3D histological reconstruction, to estimate the reliability of the tractography algorithm in this specific tract. Recent studies have shown that the cerebellum is involved in cognitive, language and emotional functions besides its role in motor control. However, the exact working mechanism of the cerebellum is still to be elucidated. As the DRTT is the main output tract it is of special interest for the neuroscience and clinical community. A postmortem human brain specimen was scanned on a 7T MRI scanner using a diffusion-weighted steady-state free precession sequence. Tractography was performed with PROBTRACKX. The specimen was subsequently serially sectioned and stained for myelin using a modified Heidenhain-Woelke staining. Image registration permitted the 3D reconstruction of the histological sections and comparison with MRI. The spatial concordance between the two modalities was evaluated using ROC analysis and a similarity index (SI). ROC curves showed a high sensitivity and specificity in general. Highest measures were observed in the superior cerebellar peduncle with an SI of 0.72. Less overlap was found in the decussation of the DRTT at the level of the mesencephalon. The study demonstrates high spatial accuracy of postmortem probabilistic tractography of the DRTT when compared to a 3D histological reconstruction. This gives hopeful prospect for studying structure-function correlations in patients with cerebellar disorders using tractography of the DRTT.

The 1967 paper from Hans Kuypers and Don Lawrence provided the first complete description of the projections from every major cortical area to the red nucleus and brainstem in the monkey. The study includes descriptions of some of the major cortical influences on sensory and motor circuits subserving vision, hearing and proprioception, as well as movements of the eyes, head and limbs. It also describes the detailed anatomy of the red nucleus in the monkey, and highlights species differences in this structure. It also postulates that cortical projections to the parvicellular component of the red nucleus provide a recurrent loop returning via the thalamus to the motor cortex. The findings reported in this paper helped to substantiate Kuypers' new theory on the organisation of the descending motor pathways by showing that the primary motor cortex, as well as providing a direct crossed corticospinal input to spinal circuits controlling movements of the distal extremities (hand and foot), also influenced these same circuits through ipsilateral projections to the cells of origin of the rubrospinal tract. In contrast, projections from more rostral motor, premotor and prefrontal regions terminated bilaterally in the parvicellular red nucleus, and influenced ventromedial descending pathways controlling movements of the head, neck, trunk and proximal limbs. The paper has proved of lasting value to our understanding of sensorimotor control and the contribution of different pathways to it. This article is part of a Special Issue entitled SI:50th Anniversary Issue., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Previous Diffusion Tensor Imaging studies have demonstrated that the human red nucleus is widely interconnected with sensory-motor and prefrontal cortices. In this study, we assessed red nucleus connectivity by using a multi-tensor model called non- negative Constrained Spherical Deconvolution (CSD), which is able to resolve more than one fiber orientation per voxel. Connections of the red nuclei of fifteen volunteers were studied at 3T using CSD axonal tracking. We found significant connectivity between RN and the following cortical and subcortical areas: cerebellar cortex, thalamus, paracentral lobule, postcentral gyrus, precentral gyrus, superior frontal gyrus and dentate nucleus. We confirmed that red nucleus is tightly linked with the cerebral cortex and has dense subcortical connections with thalamus and cerebellar cortex. These findings may be useful in a clinical context considering that RN is involved in motor control and it is known to have potential to compensate for injury of the corticospinal tract., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

OBJECT The dentatorubrothalamic tract (DRTT) is the major efferent cerebellar pathway arising from the dentate nucleus (DN) and decussating to the contralateral red nucleus (RN) and thalamus. Surprisingly, hemispheric cerebellar output influences bilateral limb movements. In animals, uncrossed projections from the DN to the ipsilateral RN and thalamus may explain this phenomenon. The aim of this study was to clarify the anatomy of the dentatorubrothalamic connections in humans. METHODS The authors applied advanced deterministic fiber tractography to a template of 488 subjects from the Human Connectome Project (Q1-Q3 release, WU-Minn HCP consortium) and validated the results with microsurgical dissection of cadaveric brains prepared according to Klingler's method. RESULTS The authors identified the "classic" decussating DRTT and a corresponding nondecussating path (the nondecussating DRTT, nd-DRTT). Within each of these 2 tracts some fibers stop at the level of the RN, forming the dentatorubro tract and the nondecussating dentatorubro tract. The left nd-DRTT encompasses 21.7% of the tracts and 24.9% of the volume of the left superior cerebellar peduncle, and the right nd-DRTT encompasses 20.2% of the tracts and 28.4% of the volume of the right superior cerebellar peduncle. CONCLUSIONS The connections of the DN with the RN and thalamus are bilateral, not ipsilateral only. This affords a potential anatomical substrate for bilateral limb motor effects originating in a single cerebellar hemisphere under physiological conditions, and for bilateral limb motor impairment in hemispheric cerebellar lesions such as ischemic stroke and hemorrhage, and after resection of hemispheric tumors and arteriovenous malformations. Furthermore, when a lesion is located on the course of the dentatorubrothalamic system, a careful preoperative tractographic analysis of the relationship of the DRTT, nd-DRTT, and the lesion should be performed in order to tailor the surgical approach properly and spare all bundles.

Nucleus ruber is known as an important supraspinal center that controls forelimb movements in tetrapods, and the rubral homologue may serve similar functions in fishes (motor control of pectoral fin). However, two apparently different structures have been identified as 'nucleus ruber' in actinopterygians. One is nucleus ruber of Goldstein (1905) (NRg), and the other nucleus ruber of Nieuwenhuys and Pouwels (1983) (NRnp). It remains unclear whether one of these nuclei (or perhaps both) is homologous to tetrapod nucleus ruber. To resolve this issue from a phylogenetic point of view, we have investigated the distribution of tegmental neurons retrogradely labeled from the spinal cord in eight actinopterygian species. We also investigated the presence/absence of the two nuclei with Nissl- or Bodian-stained brain section series of an additional 28 actinopterygian species by comparing the morphological features of candidate rubral neurons with those of neurons revealed by the tracer studies. Based on these analyses, the NRg was identified in all actinopterygians investigated in the present study, while the NRnp appears to be absent in basal actinopterygians. The phylogenetic distribution pattern indicates that the NRg is the more likely homologue of nucleus ruber, and the NRnp may be a derived nucleus that emerged during the course of actinopterygian evolution., (© 2016 S. Karger AG, Basel.)

During the execution of the skilled reaching task, naïve rats bring their elbow to the midline of their body to aim at the food target, perform the arpeggio movement to grasp it and supinate the paw to bring the food to their mouth. Red nucleus lesions in the rat interfere with each of these three movement elements of reaching. On the other hand, lesions to the rubrospinal tract, which originate from the magnocellular subdivision of the red nucleus, only interfere with the arpeggio movement. This latter evidence strongly suggests that impairment in aiming and supinating could be under the control of the parvocellular subdivision of the red nucleus. In order to test this hypothesis, rats were trained on the skilled reaching task and then received either complete lesions of the red nucleus or lesions restricted to its parvo- or magnocellular subdivision. In line with previous data, complete excitotoxic lesions of the red nucleus compromised limb aiming, arpeggio and supination. Lesions restricted to the parvocellular division of the red nucleus abolish supination and interfere with aiming, although the latter result did not reach significance. The results are discussed in terms of the distinct connectivity and functional significance of these two architectonic subdivisions of the red nucleus., (Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.)

We characterize the contrast behavior of substantia nigra (SN) in both magnetization transfer (MT) imaging, which is believed to be sensitive to neuromelanin (NM), and susceptibility weighted imaging (SWI). Images were acquired with a MT prepared dual echo gradient echo sequence. The first echo was taken as the MT contrast image and the second was used to generate the SWI image. SN volumes were segmented from these two types of images using a thresholding method. The spatial and signal characteristics of the extracted SWI and MT volumes were compared. Both images showed the presence of SN but the volumes of the SN identified in the two are spatially incongruent. The MT volume was more caudal than the SWI volume and with only a 12% overlap between the two volumes. Considering the SN volumes in each hemisphere separately, the average distances between the centers of mass of the volumes from the two types images are 5.1±1.1mm and 4.1±1.2mm, respectively. The frequency offsets (homodyne filtered phase/echo time) for the volumes derived from MT (NM) images and SWI images are 0.09±0.32radians/s and -1.12±0.57radians/s (p<0.0001), respectively. The MT contrasts for the two volumes are 0.16±0.02 and 0.10±0.03 (p<0.001), respectively. Our results indicate that the two contrasts are sensitive to different portions of the SN, with MT seeing the more caudal portion of the SN than SWI, likely due to variations of NM and iron content in the SN. Despite the small overlap, these regions are complementary. Our results provide a new understanding of the contrast behavior of the SN in the two imaging approaches commonly used to image it and indicate that using both may yield a more comprehensive visualization of the SN., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Up till the 1840s, gross dissection was the only method available to study the tracts and fascicles of the white matter of the human brain. This changed dramatically with the introduction by Stilling (1842, 1843, 1846) of the microscopy of serial sections and his demonstration of the discriminative power of this method. The decussation of the brachium conjunctivum (the superior cerebellar peduncle) (International Anatomical Terminology (1998)) originally was known as the horseshoe-shaped commissure of Wernekinck. The first use of this name and the first illustrations of this commissure date from a book by Wernekinck’s successor, Wilbrand (1840).Using gross dissection, he concluded that the commissure connects the dentate nucleus with the contralateral inferior olive. A few years later, Stilling (1846), using microscopy of serial sections through the human brain stem, illustrated the entire course of the brachium conjunctivum, its decussation,and its crossed ascending branch, up to the red nucleus. From his work, it became clear that Wernekinck and Wilbrand had included the central tegmental tract in their commissure, and that they had failed to identify its ascending branch.

Objective: To study the possibility of Chinese visible human (CVH) head datasets as brain atlas for locating the subthalamic nucleus (STN) before deep brain stimulation (DBS) surgery., Methods: Optimal head axial and coronal 3.0T, T2-weighted magnetic resonance images (MRI) of 30 patients were obtained. Cross-sectional head images of four CVH head datasets were chosen to establish an average CVH model. All MRI sequences were registered to the CVH model via fiducials in X-, Y-, and Z-direction, respectively, within the same stereotactic space. The correlations between red nucleus (RN) and fiducials, the accuracy of MRI-to-CVH registration, and the coordinate value differences of RN gravity center between MRI and CVH were tested., Results: The mean gravity center coordinate values and ranges of STN in CVH were measured; The X coordinate value of RN positively correlates with the most anterior point of putamen(PU-A), the lateral edges of putamens (PU-L), and width of the third ventricle, negatively correlated with the patients' age; The minimal mean errors were when no fiducials were used when locating RN between the MRI and the CVH average model; There were no significant differences of RN in X- and Y-direction between MRI sequences and CVH., Conclusion: CVH head datasets can be used as brain atlas for Chinese STN localization. Moreover, average coordinate values of the gravity center and the ranges of STN in CVH can be considered as references for locating STN.

Precise temporal and spatial sequences of synaptogenesis occur in the cerebellar system, as in other synaptic circuits of the brain. In postmortem brain sections of 172 human fetuses and neonates, synaptophysin immunoreactivity was studied in nuclei of the Guillain-Mollaret triangle: dentato-olivo-rubro-cerebellar circuit. Synaptophysin demonstrates not only progressive increase in synaptic vesicles in each structure, but also shows the development of shape from amorphous globular neuronal aggregates to undulated nuclei. Intensity of synaptophysin reactivity is strong before the mature shape of these nuclei is achieved. Accessory olivary and deep cerebellar nuclei are intensely stained earlier than the principal olivary and dentate nuclei. The dorsal blades of both form earlier than the ventral, with reactivity initially peripheral. Initiation of synaptophysin reactivity is at 13 weeks in the inferior olive (r6, r7) and at 16 weeks in the dentate (r2). Initial synaptic vesicles are noted at 13 weeks in the red nucleus (r0); synapses form initially on the small neurons at 13 weeks but thereafter simultaneously on small and large neurons. Form and reactivity follow caudorostral, dorsoventral and mediolateral gradients in the axes of the rhombencephalon. This study provides control data to serve as a basis for interpreting aberrations in synaptogenesis in malformations of the cerebellar system, genetic disorders and acquired insults to the cerebellum and brainstem during fetal life, applicable to tissue sections and complementing biochemical and molecular techniques., (Copyright © 2013 S. Karger AG, Basel.)

Three-dimensional MRI is typically performed with the same orientation for radiofrequency slab excitation and slab select phase encoding. We introduce independent slab excitation and encoding to create a new degree of freedom in three-dimensional MRI, which is the angular relationship between the prescribed excitation volume and the voxel encoding grid. By separating the directions of slab excitation and slab phase encoding, the independent slab excitation and encoding method allows choice of optimal voxel orientation, while maintaining volume excitation based on anatomic landmarks. The method requires simple pulse sequence modifications and uses standard image reconstruction followed by removal of aliasing and image reformatting. The independent slab excitation and encoding method enables arbitrary oblique angle imaging using fixed voxel encoding gradients to maintain similar eddy current, concomitant field, or magnetic dipole effects independent of the oblique angle of excitation. We apply independent slab excitation and encoding to phase and susceptibility-weighted imaging using fixed voxel encoding aligned with the main magnetic field to demonstrate its value in both standardizing and improving image contrast, when using arbitrary oblique imaging volumes., (Copyright © 2011 Wiley Periodicals, Inc.)

The human red nucleus consists of the well-developed parvicellular red nucleus (pNr) and the rudimentary magnocellular red nucleus (mNr). It is believed that the human pNr is separated from the nucleus accessorius medialis of Bechterew (NB), which, generally speaking, is located in the ventral central gray. It was initially suggested that the "rolled sheet" model of the human pNr that we proposed included the view that the human NB does not occupy the ventral central gray but is placed in the dorsomedial part of the red nucleus. It is perhaps more appropriate to state that the NB, the origin of the medial tegmental tract (MTT), over time became displaced from the ventral central gray and was in part shifted to the adjacent reticular formation. The majority of the MTT tract however remained in its established location. Evolutionarily speaking, this separation of the NB and the nucleus of Darkschewitsch (ND), and the translocation of the position of the NB just referred to, might have begun within the lineage of the apes prior to the emergence of man. Furthermore it is generally believed that the human mNr consists of a scattered few groups of giant-to-large neurons situated among the fiber bundles of the superior cerebellar peduncle at the level of the oculomotor nerve fibers. It has long been considered impossible to clearly draw an outline of the human mNr such that it could be seen as a self-contained structural entity. However, we now demonstrate just such an outline of the rudimentary human adult mNr through employment of the concepts of the so-called "Mannen's closed nucleus" and "Ogawa's human mNr": descriptions that exclude the associated area that contains neurons which possess melanin pigment. Interestingly, recent studies have shown that the human fetus and newborns have a well-developed semilunar mNr, and this observation raises the possibility that the associated transient but well-developed rubrospinal tract seen in the perinatal state might have had an important role for the development of upright bipedalism in hominids. The well-developed human prefrontal-NB-olivo-lateral cerebellar circuit might possibly have resulted in the emergence of language., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: To investigate the optimal pulse sequences of commonly used 1.5-tesla MRI for identifying the red nucleus (RN) to aid targeting of the subthalamic nucleus (STN)., Methods: Forty-six healthy adults were enrolled for this prospective study. All subjects underwent MR studies of 5 sequences: diffusion-weighted imaging (DWI), T(1)-weighted fluid-attenuated inversion recovery (T1IR), fast spin echo T(2)-weighted imaging (FSE-T2WI), T(2)-weighted fluid-attenuated inversion recovery (T2FLAIR) and T(2)*-weighted gradient-echo (T2*-GRE) sequences. The clearness of the RN contour was analyzed., Results: Overall, the RN was identified in 98% subjects without gender and age differences. The RN was demarcated on a 5-mm slice relatively better in T2FLAIR (93.5%), followed by FSE-T2WI (78.3%), T2*-GRE (65.2%) and DWI (43.5%) sequences, but was completely invisible on the T1IR image. Generally, the signal intensity in all MR sequences decreased mildly on 2-mm slices with a similar identifying power. The detecting power on 5-mm slices was in favor of T2FLAIR with 94% sensitivity, 10% specificity, and 1.89 odds ratio compared to FSE-T2WI. In addition, the scanning time of T2FLAIR was longer in comparison to the FSE-T2WI study., Conclusion: T2FLAIR is an alternative to FSE-T2WI that can readily demarcate the RN to help target the STN., (Copyright © 2012 S. Karger AG, Basel.)

The rubrospinal tract (RST) is an extrapyramidal motor pathway in the human brain. In this study, using diffusion tensor tractography (DTT), we attempted to identify the RST in the normal human brain. Twenty-one healthy volunteers were recruited for this study. A 1.5-T scanner was used for scanning of diffusion tensor images, and the RSTs were isolated by DTT using FMRIB software. Values of fractional anisotropy (FA), mean diffusivity (MD), and tract volume of the RSTs were measured. Among 42 hemispheres of 21 subjects, RSTs were isolated in 27 hemispheres (64.28%) of 15 subjects. All identified tracts originated from the red nucleus and crossed the midline via ventral tegmental decussation. Then, they passed through the area between the inferior olivary nucleus and the inferior cerebellar peduncle in the contralateral medulla. The tracts finally descended through the lateral funiculus of the upper spinal cord. Mean values of FA, MD, and tract volume did not differ significantly between the left and right hemispheres (P>0.05). We believe that the methodologies used and the results of this study would be helpful to researchers interested in the function of the human RST and its clinical implications., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Introduction: The dentatorubrothalamic tract (DRTT) originates from the dentate nucleus in the cerebellum and terminates in the contralateral ventrolateral nucleus (VL) of the thalamus after decussating to the contralateral red nucleus. Identification of the DRTT is difficult due to the fact that it is a long, multisynaptic, neural tract crossing to the opposite hemisphere. In the current study, we attempted to identify the DRTT in the human brain using a probabilistic tractography technique of diffusion tensor imaging., Methods: Diffusion tensor imaging was performed at 1.5-T using a synergy-L sensitivity encoding head coil. DRTTs were obtained by selection of fibers passing through three regions of interest (the dentate nucleus, the superior cerebellar peduncle, and the contralateral red nucleus) from 41 healthy volunteers. Probabilistic mapping was obtained from the highest probabilistic location at 2.3 mm above the anterior commissure-posterior commissure level., Results: DRTTs of all subjects, which originated from the dentate nucleus, ascended through the junction of the superior cerebellar peduncle and the contralateral red nucleus and then terminated at the VL nucleus of the thalamus. The highest probabilistic location for the DRTT at the thalamus was compatible with the location of the VL nucleus., Conclusions: We identified the DRTT in the human brain using probabilistic tractography. Our results could be useful in research on movement control.

Background and Purpose: Dysfunction of DA neurotransmission from the SN and VTA has been implicated in neuropsychiatric diseases, including Parkinson disease and schizophrenia. Unfortunately, these midbrain DA structures are difficult to define on clinical MR imaging. To more precisely evaluate the anatomic architecture of the DA midbrain, we scanned healthy participants with a 7T MR imaging system. Here we contrast the performance of high-resolution T2- and T2*-weighted GRASE and FFE MR imaging scans at 7T., Materials and Methods: Ten healthy participants were scanned by using GRASE and FFE sequences. CNRs were calculated among the SN, VTA, and RN, and their volumes were estimated by using a segmentation algorithm., Results: Both GRASE and FFE scans revealed visible contrast between midbrain DA regions. The GRASE scan showed higher CNRs compared with the FFE scan. The T2* contrast of the FFE scan further delineated substructures and microvasculature within the midbrain SN and RN. Segmentation and volume estimation of the midbrain SN, RN, and VTA showed individual differences in the size and volume of these structures across participants., Conclusions: Both GRASE and FFE provide sufficient CNR to evaluate the anatomy of the midbrain DA system. The FFE in particular reveals vascular details and substructure information within the midbrain regions that could be useful for examining structural changes in midbrain pathologies.

Background: Though the adult human magnocellular Red nucleus (mNr) is essentially vestigial and its boundaries with neighbouring structures have never been well demarcated, human studies in utero have shown a well developed semilunar mNr wrapping around the caudal parvicellular Red nucleus (pNr), similar to what is seen in quadrupeds. In the present study, we have sought to better delineate the morphological determinants of the adult human Red nucleus (ahRn)., Methods and Findings: Serial sections of ahRn show fine myelinated fibers arising from pNr and turning toward the central tegmental tract. DiI was deposited within a well restricted region of ahRn at the fasciculus retroflexus level and the extent of label determined. Nissl-stained serial sections allowed production of a 3-D mNr model, showing rudimentary, vestigial morphology compared with its well developed infant homologue. DiI within this vestigial mNr region at the level of the oculomotor nerve showed labeled giant/large mNr neurons, coarse fiber bundles at the ventral tegmental decussation and lateral lemniscal label., Conclusions: Large amounts of DiI and a long incubation time have proven useful in aged human brain as a marker of long axons and large cell bodies of projecting neurons such as the rubrospinal projection and for clarifying nuclear boundaries of closed nuclei (e.g., the large human pNr). Our 3D model of adult human mNr appeared shrunken in shape and axially rotated compared with the infant mNr, the rotation being a common feature among mammalian mNr.

Few imaging studies have been devoted to the structural and functional connectivity of the red and inferior olivary nuclei although these two nuclei represent two main targets of the cerebellum within the brainstem. However, the RN is anatomically and functionally related to a widespread sensorimotor, limbic, and executive brain network. It projects massively onto the principal olive with which it contributes to a cerebello-rubro-olivo-cerebellar loop modulated by cortical and subcortical afferents. Despite a minor role in planning and execution of rhythmic movements, the red nucleus in conjunction with the inferior olive, more specifically involved in the detection of "unexpected" events, contributes to sensorimotor, sensory and, likely, cognitive higher functions.

Objective: The aim of this study was to evaluate the differences in normal brain MRI findings between under 3.0 Tesla (T) and 1.5T MRI conditions with the use of the fluid attenuated inversion recovery (FLAIR) sequences., Materials and Methods: Eleven normal adults underwent imaging with the use of the FLAIR sequences on both 1.5T and 3.0T scanners. Two neuroradiologists compared the signal intensity (SI) of the centrum semiovale (CS), pulvinar thalami (PT) and normal iron deposit structures (IDSs) on the 3.0T and 1.5T FLAIR images, and they evaluated three MRI findings qualitatively: high SI of CS; low SI of PT; low SI of IDS. We also evaluated signal-to-noise ratios (SNRs) for the CS, PT, red nucleus and cerebellar dentate nucleus on the FLAIR images., Results: Based on qualitative analyses, the 3.0T FLAIR images showed all three MRI findings for all cases. Low SI for the PT in seven cases (64%), high SI of the CS in one case (9%) and low SI of the cerebellar dentate nucleus in one case (9%) were visualized only on 3.0T FLAIR images. The mean SNRs of the PT, red nucleus and dentate nucleus in patients where 3.0T FLAIR imaging was performed were significantly lower as compared with the SNRs on 1.5T FLAIR images. The SNR of the CS was not significantly different between under the two magnetic field strengths (p > 0.05)., Conclusion: We have demonstrated that normal, high and low SIs of the CS, PT and IDS on 3.0T FLAIR images were depicted more frequently and more prominently as compared with those on 1.5T FLAIR images in normal adult brains.

Background: The human red nucleus (Nr) is comparatively less well-studied than that of cats or monkeys. Given the functional importance of reticular and midbrain structures in control of movement and locomotion as well as from an evolutionary perspective, we investigated the nature and extent of any differences in Nr projections to the olivary complex in quadrupedal and bipedal species. Using neuroanatomical tract-tracing techniques we developed a "neural sheet" hypothesis allowing us to propose how rubro-olivary relations differ among the three species., Methods and Findings: Wheat germ agglutinin-horseradish peroxidase staining supports findings that the cat's nucleus accessories medialis of Bechtrew (NB) projects mainly to the lateral bend of the principal olive. We clarified boundaries among nucleus of Darkschewitsch (ND), NB and parvicellular red nucleus (pNr) of the cat's neural sheet. The macaque's ND-medial accessory olivary projection is rostro-caudally organized and the dorsomedial and ventrolateral parts of the macaque's pNr may project to the principal olive's rostral and caudal dorsal lamella; in cat it projects as well to pNr. Myelin- and Nissl-stained sections show that a well-developed dorsomedial part of the human Nr consists of densely packed cells, deriving small myelinated fibers that continue into the medial central tegmental tract., Conclusions: Based on these findings we suggest there are distinct bipedal-quadrupedal differences for Nr projections to the olivary complex. We propose the Nr of cats and monkeys comprise the ND, NB and pNr in a zonal sheet-like structure, retaining clear nuclear boundaries and an isolated, well-developed mNr. The human NB may be distinguished from its more specialised ND (ND lies alongside a well-developed pNr) in the human central gray. Phylogenetically, the NB may have been translocated into a roll-shaped Nr in the reticular formation, the dorsomedial portion of which might correspond to the cat's and monkey's NB.

Introduction: Aqueductus mesencephali is the biggest part of the ventricular system and that is why it is the most common place of intraventricular obstruction of cerebrospinal fluid. This study was done in order to study topographic characteristics of aqueduct more thoroughly., Materials and Methods: Transversal sections of mesencephalon were made in three levels. The first section was made caudally immediately from the posterior commissure. The second section was made in the middle part of the superior colliculi, and the third section was made in the rostral parts of the caudal sections of the superior colliculi. Distances of the aqueduct from structures of mesencephalon, obtained on the second section, are: 1. The distance of the aqueduct from the superior colliculi - 6.96 mm; 2. The distance of the aqueduct from the red nucleus - 6.02 mm; 3. The distance of the aqueduct from the substantia nigra - 12.29 mm; 4. The distance of the aqueduct from the interpeduncular fossa - 10.22 mm., Conclusion: Knowledge of the anatomy of the aqueductus mesencephali is very important because of interpretation of patogenesis of hidrocefalus as well as of other syndromes that occure in some pathological processes in the system of ventricles.

Background and Purpose: The mesencephalon is involved in a number of human neurodegenerative disorders and has been typically imaged with T1-, T2- and T2*-weighted methods. Our aim was to collect high-contrast susceptibility-weighted imaging (SWI) data to differentiate among and within the basic mesencephalic structures: namely, the red nucleus, substantia nigra, and crus cerebri., Materials and Methods: High-resolution SWI, 3D T1-weighted, and T2-weighted data were collected to study contrast in the mesencephalon at 1.5T and 4T. Contrast between structures was calculated for SWI high-pass (HP)-filtered-phase, T1 gradient-echo, and spin-echo T2-weighted data., Results: SWI HP-filtered-phase data revealed similar contrast for the red nucleus and substantia nigra when compared with T2-weighted imaging. However, SWI was able to show structures within the red nucleus, substantia nigra, and medial geniculate body that were invisible on T2-weighted imaging. T1-weighted imaging, on the other hand, did not reveal measurable contrast for any of the structures of interest. SWI HP-filtered-phase data at 4T agreed well with india ink-stained cadaver brain studies, which appear to correlate with capillary density., Conclusions: With SWI, it is possible to create better anatomic images of the mesencephalon, with improved contrast compared with conventional T1- or T2-weighted sequences.

To analyse the effect of ageing on the projection of the anterior interposed nucleus to the red nucleus, we injected the retrograde tracer fluorogold in the red nucleus of 3-, 6- and 12-month-old mice. The number of labelled neurones in the anterior interposed nucleus fell by 9% between 3 and 6 months and by another 9% between 6 and 12 months (all P < 0.001). This suggests that loss of neurones from the cerebellar nuclei starts well before old age.

A quantitative analysis of the distribution of corticorubral fibers was performed after precise electrolytic lesioning of the lateral and medial margins of the posterior sigmoid gyrus--the motor representations of the fore-and hindlimbs respectively--in cats. The cortical representations of the forelimbs were found to project to the whole of the rostrocaudal extent of the red nucleus (RN). The number of efferent fibers terminating at the rostral margin of the RN was almost twice that terminating in the caudal third of the RN. Efferent fibers of the cortical representation of the hindlimbs did not project to the rostral two thirds of the RN but ended in its caudal third; the number of projecting corticorubral fibers was the same as the number running from the cortical representation of the forepaws to the caudal third of the RN. The significantly (almost double) greater number of fibers running from the cortical representation of the forelimbs in comparison with the number directed from the representation of the hindlimbs found in the present study is probably evidence of the greater functional importance of corticorubral connections in movement reactions performed by the forelimbs.

Morphology of the human parvocellular red nucleus (RNp) was investigated in 14 fetuses aged from 12 to 39 weeks of gestation (WG). The brains were processed into celloidin-embedded serial sections. At 12 WG, the anlage of RNp was observed as an ovoid mass of immature neurons clustering into some groups. Lobular appearance in cross-sectional images was conspicuous during the early stages (12-23 WG), particularly at rostral levels. The fasciculus retroflexus of Meynert was seen as a prominent bundle of fibers surrounded by the most rostral part of RNp. Two types of neurons were identified: large and small neurons. Large neurons were earlier observed at 16 WG, and had a polygonal or multipolar perikaryon with abundant Nissl bodies from 28 WG onwards. Small neurons later appeared among large neurons at 21 WG, and had a triangular or ovoid perikaryon with scanty Nissl bodies. The volume of RNp showed an exponential increase with age during 20-39 WG. The mean of neuronal perikaryonal areas showed a linear increase with age in both types during 16-39 WG, although the degree of change was much greater in large neurons than small neurons. The current study has clearly demonstrated the presence of two neuronal populations and their differential growth in developing human RNp., (2008 S. Karger AG, Basel.)

Introduction: The aims of this study were: (1) to test whether higher spatial resolution diffusion tensor images and a higher field strength (3 T) enable a more accurate delineation of the anatomical tract within the brainstem, and, in particular, (2) to try to distinguish the different components of the corticopontocerebellar paths in terms of their cortical origins., Methods: The main tracts of the brainstem of four volunteers were studied at 3 T using a probabilistic diffusion tensor imaging (DTI) axonal tracking. The resulting tractograms enabled anatomical well-delineated structures to be identified on the diffusion tensor coloured images., Results: We tracked corticopontine, corticospinal, central tegmental, inferior and superior cerebellopeduncular, transverse, medial lemniscal and, possibly, longitudinal medial fibres. Moreover, DTI tracking allowed a broad delineation of the corticopontocerebellar paths., Conclusion: Diffusion tensor coloured images allow a rapid and reliable access to the white matter broad parcellation of the brainstem and of the cerebellum, which can be completed by fibre tracking. However, a more accurate and exhaustive depiction of the anatomical connectivity within the brainstem requires the application of more sophisticated techniques and tractography algorithms, such as diffusion spectrum imaging.

Organization of the fibers in the descending tracts of the dorsolateral funiculus of the cervical spinal cord was investigated in cats. The spinal cord was penetrated with microelectrodes at 400 mum intervals in the medio-lateral direction at the c5/c6 and c6/c7 segmental borders. Silicon substrate microelectrodes with a linear arrangement of activated iridium contacts were used. The stimulus consisted of a 20 ms train of charge balanced biphasic current pulses at 330 Hz. The evoked activities from selected forelimb muscles were acquired into computer. Only the data points with an activation threshold of less than 35 muA were considered in the analysis. Muscle contractions were mostly in the form of short twitches. In both spinal segments, an area of high threshold was found in the middle of the dorsolateral funiculus. Majority of the muscles studied had a dorsal or ventral concentration of activation points. The distal muscles were mostly activated in the ventro-lateral aspect of the funiculus, while the elbow muscle maps spread to both dorsal and ventral sides. These results show a functional organization in both cervical segments studied, with overlapping regions between the areas dedicated for each forelimb muscle.

Introduction: Previous studies in apes and monkeys have shown that the red nucleus receives projections from the sensorimotor and premotor cortices, whereas other experiments carried out with injured human brains have found corticorubral projections issuing from associative areas. Therefore, we reassessed in vivo the human anatomical projections from the cerebral cortex to the red nucleus using diffusion tensor imaging (DTI) axonal tracking., Methods: The connectivity between the cerebral cortex and the red nuclei of seven volunteers was studied at 1.5 T using streamlined DTI axonal tracking., Results: Trajectories were constantly tracked between the red nuclei and the ipsilateral pericentral and prefrontal cortices, as well as the temporal cortex and the striatum in two subjects. Within the cerebral trunk, trajectories also include the superior cerebellar peduncle and the central tegmental tract., Conclusion: The human red nucleus receives its main afferences from the sensorimotor and prefrontal cortices.

Background: In deep brain stimulation the way to define and localize the optimal target for the individual patient is still under debate. The objective of our study was to investigate the reliability of atlas derived data by comparing them with direct targeting on MR images., Method: We investigated 28 STN targets in 14 volunteers. The stereotactic coordinates of the dorso-lateral subthalamic nucleus (STN), were determined in 5 different ways for both STNs of each individual volunteer: 1. directly, on axial T2WI spin echo slices, 2. directly, on coronal T2WI spin echo slices and after fusion of data sets: 3. indirectly, on an axial atlas plate, 4. indirectly, on a coronal atlas plate, 5. indirectly, 12 mm lateral, 3 mm posterior and 3 mm inferior to mid-AC-PC., Findings: The differences between MRI derived targets on axial vs. coronal slices were not statistically significant. After detection of the atlas derived targets the resulting x-coordinates were found more lateral than after direct detection on both, axial and coronal T2-weighted images (p < 0.001). On axial images y-coordinates were located more anterior (p = 0.240) on atlas derived targets and more posterior when target localizations were compared on coronal slices (p < 0.001). z-Coordinates were more superior after atlas targeting compared to MRI targeting (p < 0.001). Differences up to 6.21 mm occurred., Conclusions: Despite the limitations concerning image distortions and slice thickness, direct target planning on MRI, regarding our results, is more reliable than targeting solely based on atlas derived data. Only MRI gives us detailed information about the individual configurations of central structures in every single patient. However, targets, which are not detectable on MRI like the nucleus ventralis intermedius have to be planned using stereotactic atlas information. In these cases intra-operative micro-electrode recording might help to better define the target region.

Background: In the search for a better preoperative knowledge of the position of probes and electrodes, we assessed the feasibility and the usefulness of transcranial sonography during surgery for the implantation of stimulation electrodes into the subthalamic nucleus (STN) of patients with Parkinson's disease., Methods: Transcranial sonography was carried out during stereotactic surgery in 8 patients with Parkinson's disease who had a suitable temporal bone window on the side receiving the electrode. Test stimulation parameters were 130 Hz, 0.1 ms, up to 0 to 4.5 V., Results: The test probe with a diameter of 0.8 mm was visualized through the temporal preauricular window. The correct anatomic position of the electrode tip could be indirectly assessed thanks to the topographic relationship of the STN with the hyperechogenic substantia nigra and the nucleus ruber. The tip position of the final electrode was easily documented. A laterality of 10.5 to 11.5 mm, verified by teleradiographic ventriculography and plain films, was correlated with the best response of symptoms of Parkinson's disease to electrical impulses delivered to the STN., Conclusions: Transcranial sonography is easily feasible during stereotactic surgery. In combination with the clinical effects of electrostimulation on the symptoms of Parkinson's disease and with stereotactic x-ray images, it enables the assessment and the documentation of the correct position of implanted STN electrodes in real time.

In 1865, Jules Luys (1828-1897) described the 'accessory band of the superior olive' (red nucleus). In 1877, A. Forel completed the description and gave the name of Corpus Luysii (CL) to this grey sub-thalamic formation. In 1927, P. Martin's attribute the Hemiballismus to the destruction of the C.L. and specifies the function of the nucleus foreseen by Luys, which play a crucial role in the synthesis of automatic motor action. The new stimulation techniques of this nucleus in the treatment of Parkinson's disease would have opened a third life for the C.L. if its name hade not be changed into 'nucleus subthalamicus'. Jules Luys, a good anatomist, one of the pioneers in France of microscope and photography, ruined his reputation by his ramblings on hysteria and hypnosis which allowed the 'action of medications at distance', the 'storage of cerebral activities within magnetic crowns' and gave prominence to 'brain emanations'.

In an effort to understand better the function of the zona incerta of the thalamus, this study has examined the organisation of its connections with the red nucleus of the midbrain. Injections of the tracers biotinylated dextran (BD) or cholera toxin subunit B (CTb) were made into either the zona incerta or red nucleus of Sprague Dawley rats and the resultant labelling was examined. The results indicate that there are strong connections between the zona incerta and red nucleus; further, that these connections make distinct patterns in each nucleus. After incertal injections, labelling is found mainly within the smaller parvocellular lamina of the red nucleus, leaving the larger magnocellular lamina barren of labelling. After rubral injections, labelling is seen across all of the four distinct sectors of the zona incerta, but with a concentration within the medial region of each. Overall, the results indicate that the zona incerta is in a position to influence the motor related functions of the parvocellular lamina of the red nucleus. It is suggested that these results, when taken together with recent reports of a large interpositoincertal pathway, render the zona incerta as a synaptic interface between cerebellar and rubral circuits.

Traditionally, the red nucleus of the cat is divided into two parts: a large-celled, magnocellular, division (RNm) and a small-celled, parvicellular, division (RNp). The RNm projects to the spinal cord and receives input from the cerebellar interpositus nucleus. The RNp projects to the inferior olive and receives input from the cerebellar dentate nucleus. In this report, we reexamine the connections of the red nucleus using the bidirectional tracer wheat germ agglutinin-horseradish peroxidase (WGA-HRP). Our findings demonstrate that the cat RNp has a large caudal and lateral region that projects to contralateral spinal cord and not to the inferior olive. The spinally projecting region of RNp receives input from the dentate nucleus and a lateral segment of anterior interpositus. Cervical projections from the red nucleus show a topography with the rostral portion of RNp favoring upper segments and the caudal portion of RNm favoring lower segments. The results show that dentate output can influence spinal activity without passing through the cerebral cortex. For the control of movements such as reaching and grasping, we suggest that RNp and dentate focus on the control of proximal limb musculature, whereas RNm and the anterior interpositus focus on the control of distal limb musculature. We also suggest that other species are likely to have a small-celled area of red nucleus projecting to the spinal cord.

Background and Purpose: The human red nucleus is not a uniform structure. It is composed of caudally located magnocellular and rostrally located parvicellular subnuclei. In fact, the latter forms the bulk of the human red nucleus and can be subdivided histologically by two medullary lamellae into three parts. Because iron is deposited in the human red nucleus and gradient-echo sequences are more sensitive than spin-echo sequences in the detection of iron, a high-resolution gradient-echo MR sequence was used in this study to determine whether the medullary lamellae of the normal human red nucleus could be detected in vivo., Methods: Ten healthy volunteers (seven men and three women, 27-48 years old) were examined with a high-resolution T2-weighted gradient-echo MR sequence using a 1.9-T MR imager. The scanning parameters were 60/40/15 (TR/TE/excitations) with a flip angle of 20 degrees , a pixel size of 1 x 1 mm, and a slice thickness of 5 mm., Results: The medullary lamellae were depicted in all subjects in three imaging planes: coronal, oblique axial, and oblique sagittal. The signal intensity of the lamellae was consistently higher than that of other parts of the red nucleus on all images. With the lamellae, the parvicellular subnucleus of the human red nucleus can be divided into its subdivisions., Conclusion: High-resolution gradient-echo MR imaging is capable of depicting the medullary lamellae of the normal human red nucleus in vivo.

The red nucleus is a prominent brainstem nucleus in mammals which is thought to be involved in production of skilled limb movements. The presence of the red nucleus and associated rubrospinal tract in animals that do not produce skilled limb movements, however, suggests that these structures might also be involved in control of more general limb actions, such as those occurring during locomotion. The present study investigates this question by measuring the three-dimensional ground reaction forces produced by locomoting rats with unilateral excitotoxic lesions of the red nucleus. Twenty-four to 48 h after the lesion, rats moved with an asymmetric gait during which abnormal braking and propulsive forces were produced during the dual contact time of the forelimb contralateral to the lesion and the ipsilateral hindlimb. Rats did not recover normal symmetrical locomotion within the 55-day duration of the study. The persistent asymmetry produced by red nucleus ablation provides the first unequivocal demonstration that the red nucleus plays a role in ongoing overground locomotion in the rat. Species differences in phylogeny and connectivity of the red nucleus are discussed, as well as the possibility that there is a general compensatory response to unilateral CNS injury in the rat.

The present study examined the circuitry of the red nucleus of the Sprague-Dawley rat and the freshwater pond turtle, Chrysemys picta, by using intracellular cell filling combined with anterograde tract tracing. Although both species have a well-developed cerebellorubral system, they differ in that the red nucleus of rats receives direct input from the motor areas of the cerebral cortex, whereas turtles do not. However, a direct descending projection from the hypothalamus to the red nucleus of turtles has been described. The aim of this study was to elucidate the relative functional contributions of the cerebellum and descending inputs to motor signal generation in the red nucleus. The results show that the cellular distribution of cerebellar inputs on rubrospinal neurons is similar between the rat and turtle; these projections are observed on the soma and the proximal and distal dendrites. In contrast, the hypothalamic inputs in turtles occupy mainly the more distally located dendrites, similar to the position of the cortical inputs in rats. These findings suggest that, first, the cerebellar inputs are not spatially segregated from the cortical or hypothalamic inputs in rats or turtles, as far as can be determined by light microscopy. Second, there is specificity of input from the cortex in rats and hypothalamus in turtles onto the distal portions of the dendrites. The similarity in the organizational features of the mammalian and non-mammalian cerebellorubrospinal systems has implications for interpretations of the relative roles of the cerebellum and cerebral cortex in motor control., (Copyright 2000 Wiley-Liss, Inc.)

Five cats were trained to perform a forelimb conditioned response to a paired tone CS/shock UCS. Rubrospinal tract section ipsilateral to the trained limb was carried out following criterion CR performance. Lesion sites were identified histologically and further confirmed by observation of cellular changes in the red nucleus contralateral to the trained limb. Tractotomy resulted in total or near-total loss of the CR. Prolonged postoperative training resulted in no increase in CR performance levels. The UCR remained unaffected, as did limb placing, accuracy of striking at moving objects, grooming, running and walking. Training of the opposite limb in two subjects resulted in mean scores of 90 and 85% within three sessions. Control lesions in those subjects resulted in no changes in CR performance scores. The red nucleus receives a substantial input from sensorimotor cortex and cerebellum, both of which have been shown to represent essential parts of the brain circuitry involved in associative learning and memory. Since pyramidotomy has no effect on limb CR performance [Vonedia TJ. Exp Neurol 1976;19:483-493], the possible role of the red nucleus/rubrospinal tract is discussed in terms of a critical trigger area for the expression of a learned motor response.

Purpose: High resolution MR images obtained from a normal human volunteer at 8 T are utilized to describe the appearance of iron-containing deep gray nuclei at this field strength., Method: High resolution (1,024 x 1,024 matrix) near-axial gradient echo images of the deep gray nuclei were acquired on a human volunteer by using an 8 T scanner. The images were acquired using a transverse electromagnetic resonator operating in quadrature. The following parameters were utilized: TR = 750 ms, TE = 17 ms, flip angle = 45 degrees, receiver bandwidth = 50 kHz, slice thickness = 2 mm, FOV = 20 cm. The 8 T images were reviewed and correlated to the known anatomy of the deep nuclei by comparing them with images observed at lower field strength, published diagrams, and histologic sections. In addition, the appearance of the nuclei was related to the known imaging characteristics of brain iron at lower fields., Results: The caudate, globus pallidus, putamen, thalami, substantia nigra, and red nuclei were clearly identified. The structures with the highest levels of iron, the globus pallidus, substantia nigra, and red nuclei, demonstrated significantly decreased signal, providing a map of iron distribution in the human brain., Conclusion: Preliminary imaging at 8 T demonstrates the ability to acquire ultra high resolution images of the deep nuclei, with signal characteristics believed to represent the distribution of brain iron. This may prove to be important in the early diagnosis of several neurodegenerative disorders.

Purpose: The purpose of this work is to discuss radio frequency (RF) penetration and its relevance to imaging the human head and to acquire images containing intricate structures located at the center of the brain with ultra high field MRI (UHFMRI)., Method: A simple plane wave analysis of RF penetration was performed based on Maxwell equations as a function of frequency up to 900 MHz. Gradient-recalled images were acquired at 8 T (340 MHz) using an RF resonator operating in quadrature. Typical acquisition parameters were as follows: TR = 750 ms, TE = 17 ms, slice thickness = 2 mm, FOV = 20 x 20 cm, matrix = 1,024 x 1,024. The specific absorption rate was well below 1 W/kg., Results: A simple analytical treatment, for a plane wave up to 900 MHz, reveals a lack of decreasing penetration depth with frequency beyond 200 MHz. Gradient-recalled echo images acquired from the human head displayed good contrast, homogeneity, and resolution. Importantly, excellent structural detail was observed on the resulting MR images, demonstrating that RF penetration is not a problem at 8 T. Images reveal excellent detail including the red nucleus, anterior commissure, fornix, mamillary body, pineal gland, and ependymal lining of the fourth ventricle., Conclusion: Structures located at the center of the human brain can be clearly visualized at 8 T with no detectable loss in signal intensity arising from RF penetration. The ability to examine these structures with UHFMRI will provide a powerful new modality for diagnostic radiology.

The afferents to the red nucleus from visual and nonvisual forebrain centers have been investigated in the lizard Podarcis hispanica by using both retrograde and anterograde transport of tracers. Because the red nucleus constitutes a key structure in the limb premotor system, these sensory afferents probably are involved in visuomotor and other forms of sensorimotor integration. After tracer injections aimed at the red nucleus, retrograde labeling was found in the reticular thalamus, the subthalamus, the nucleus of the posterior commissure, as well as in two retinorecipient nuclei, namely, the ventral lateral and pretectal geniculate nuclei, where labeled cells are especially abundant. These geniculorubral projections have been confirmed by means of anterograde tracing with dextranamine injections. On the other hand, small injections of tracers in the retina demonstrated that its projections to the ventral lateral and pretectal geniculate nuclei are organized in a point-to-point fashion. Moreover, small tracer injections into the optic tectum of Podarcis indicated that the ventral lateral geniculate nucleus also receives a precisely organized tectal afferent. Taken together, these results strongly suggest that geniculorubral projections might constitute the neuroanatomical substrate for the generation of quick locomotor responses to appropriate visual stimuli. Additional ventral thalamic, subthalamic, and pretectal afferents to the red nucleus are likely to subserve other kinds of sensorimotor integration. These results help to clarify the organization of the reptilian motor system, including the telencephalic control of motor responses, and to unravel some of the major trends in the evolution of the limb premotor network of tetrapodian vertebrates., (Copyright 1999 Wiley-Liss, Inc.)

Recently, feline studies have shown that a lesion in the retrorubral area, which includes the dopaminergic A8 cell group, produces motor programming deficits inherent to a hypofunction of the A9 system. A hypofunction in the striatal terminal area of A9 fibers, in turn, is known to produce a hypofunction of its first-order output station, namely the substantia nigra pars reticulata (SNR). The integrity of the SNR allows animals to execute (1) 'postural adjustments that rely on proprioceptive stimuli that originate in body parts at rest' and (2) 'non-externally guided' targeting movements. In view of these considerations, the (dys)function of the SNR of cats with a bilaterally 6-hydroxydopamine lesion of A8 cells in the retrorubral area was tested in an experimental set-up that allows the assessment of changes in these functions. The A8 lesion produced: (a) a short-lasting increase in the number of accurate targeting movements as well as an increase in the time required for the collection of six pellets: these deficits disappeared 4-7 days after the lesion; (b) a long-lasting disappearance of (1) 'postural adjustments that rely on proprioceptive stimuli that originate in body parts at rest' and (2) 'non-externally guided targeting movements'; and (c) a long-lasting display of a new strategy that allowed the lesioned cat to collect its pellets despite of its other deficits. These data led to the conclusion that a lesion of A8 cells even disrupts the function of the SNR, being one of the outputstations of the A8 cell group.