Dentate nucleus: a review and implications for dentatotomy.

PURPOSE: The dentate nucleus (DN) is the largest, most lateral, and phylogenetically most recent of the deep cerebellar nuclei. Its pivotal role encompasses the planning, initiation, and modification of voluntary movement but also spans non-motor functions like executive functioning, visuospatial processing, and linguistic abilities. This review aims to offer a comprehensive description of the DN, detailing its embryology, anatomy, physiology, and clinical relevance, alongside an analysis of dentatotomy. METHODS AND RESULTS: We delve into the history, embryology, anatomy, vascular supply, imaging characteristics, and clinical significance of the DN. Furthermore, we thoroughly review the dentatotomy, emphasizing its role in treating spasticity. CONCLUSIONS: Understanding the intricacies of the anatomy, physiology, vasculature, and projections of the DN has taken on increased importance in current neurosurgical practice. Advances in technology have unveiled previously unknown functions of the deep cerebellar nuclei, predominantly related to non-motor domains. Such discoveries are revitalizing older techniques, like dentatotomy, and applying them to newer, more localized targets.

Motor and higher-order functions topography of the human dentate nuclei identified with tractography and clustering methods.

Deep gray matter nuclei are the synaptic relays, responsible to route signals between specific brain areas. Dentate nuclei (DNs) represent the main output channel of the cerebellum and yet are often unexplored especially in humans. We developed a multimodal MRI approach to identify DNs topography on the basis of their connectivity as well as their microstructural features. Based on results, we defined DN parcellations deputed to motor and to higher-order functions in humans in vivo. Whole-brain probabilistic tractography was performed on 25 healthy subjects from the Human Connectome Project to infer DN parcellations based on their connectivity with either the cerebral or the cerebellar cortex, in turn. A third DN atlas was created inputting microstructural diffusion-derived metrics in an unsupervised fuzzy c-means classification algorithm. All analyses were performed in native space, with probability atlas maps generated in standard space. Cerebellar lobule-specific connectivity identified one motor parcellation, accounting for about 30% of the DN volume, and two non-motor parcellations, one cognitive and one sensory, which occupied the remaining volume. The other two approaches provided overlapping results in terms of geometrical distribution with those identified with cerebellar lobule-specific connectivity, although with some differences in volumes. A gender effect was observed with respect to motor areas and higher-order function representations. This is the first study that indicates that more than half of the DN volumes is involved in non-motor functions and that connectivity-based and microstructure-based atlases provide complementary information. These results represent a step-ahead for the interpretation of pathological conditions involving cerebro-cerebellar circuits.

Ventralis intermedius nucleus anatomical variability assessment by MRI structural connectivity.

The ventralis intermedius nucleus (Vim) is centrally placed in the dentato-thalamo-cortical pathway (DTCp) and is a key surgical target in the treatment of severe medically refractory tremor. It is not visible on conventional MRI sequences; consequently, stereotactic targeting currently relies on atlas-based coordinates. This fails to capture individual anatomical variability, which may lead to poor long-term clinical efficacy. Probabilistic tractography, combined with known anatomical connectivity, enables localisation of thalamic nuclei at an individual subject level. There are, however, a number of confounds associated with this technique that may influence results. Here we focused on an established method, using probabilistic tractography to reconstruct the DTCp, to identify the connectivity-defined Vim (cd-Vim) in vivo. Using 100 healthy individuals from the Human Connectome Project, our aim was to quantify cd-Vim variability across this population, measure the discrepancy with atlas-defined Vim (ad-Vim), and assess the influence of potential methodological confounds. We found no significant effect of any of the confounds. The mean cd-Vim coordinate was located within 1.88 mm (left) and 2.12 mm (right) of the average midpoint and 3.98 mm (left) and 5.41 mm (right) from the ad-Vim coordinates. cd-Vim location was more variable on the right, which reflects hemispheric asymmetries in the probabilistic DTC reconstructed. The method was reproducible, with no significant cd-Vim location differences in a separate test-retest cohort. The superior cerebellar peduncle was identified as a potential source of artificial variance. This work demonstrates significant individual anatomical variability of the cd-Vim that atlas-based coordinate targeting fails to capture. This variability was not related to any methodological confound tested. Lateralisation of cerebellar functions, such as speech, may contribute to the observed asymmetry. Tractography-based methods seem sensitive to individual anatomical variability that is missed by conventional neurosurgical targeting; these findings may form the basis for translational tools to improve efficacy and reduce side-effects of thalamic surgery for tremor.

Dentate Nucleus: Connectivity-Based Anatomic Parcellation Based on Superior Cerebellar Peduncle Projections.

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.

Blood Supply by the Superior Cerebellar Artery and Posterior Inferior Cerebellar Artery to the Motor and Nonmotor Domains of the Human Dentate Nucleus.

BACKGROUND: The human cerebellum plays an important role in motor and nonmotor coordination. Any functional loss of the dentate nucleus can result in interruption of the cerebellar efferent pathway based on its somatotopy. However, understanding of the vascular supply to the dentate nucleus remains inadequate. METHODS: The origin of the perforators to the dentate nucleus was investigated by microscopic anatomic dissection of 14 human cerebellar hemispheres. The dentate nuclei were divided dorsoventrally, rostrocaudally, and mediolaterally to identify which cerebellar artery dominated which part of the dentate nucleus. RESULTS: The average number of perforators from the superior cerebellar artery (SCA) to the dentate nucleus was 2.2 ± 0.9. The average number of perforators from the posterior inferior cerebellar artery (PICA) was 1.8 ± 0.7. The anterior inferior cerebellar artery did not provide perforators to the dentate nucleus. The dorsal, rostral, and lateral halves of the dentate nucleus were more frequently dominated by the SCA than by the PICA. The ventral and medial halves of the dentate nucleus were more frequently dominated by the PICA than by the SCA. The dorsal rostrolateral and the ventral caudomedial sections were mainly supplied by the SCA and PICA, respectively. CONCLUSIONS: These findings in combination with findings of previous imaging studies suggest that the SCA is mainly associated with the motor activity and the PICA is mainly associated with the nonmotor activity of the dentate nucleus.

Corollary discharge in precerebellar nuclei of sleeping infant rats.

In week-old rats, somatosensory input arises predominantly from external stimuli or from sensory feedback (reafference) associated with myoclonic twitches during active sleep. A previous study suggested that the brainstem motor structures that produce twitches also send motor copies (or corollary discharge, CD) to the cerebellum. We tested this possibility by recording from two precerebellar nuclei-the inferior olive (IO) and lateral reticular nucleus (LRN). In most IO and LRN neurons, twitch-related activity peaked sharply around twitch onset, consistent with CD. Next, we identified twitch-production areas in the midbrain that project independently to the IO and LRN. Finally, we blocked calcium-activated slow potassium (SK) channels in the IO to explain how broadly tuned brainstem motor signals can be transformed into precise CD signals. We conclude that the precerebellar nuclei convey a diversity of sleep-related neural activity to the developing cerebellum to enable processing of convergent input from CD and reafferent signals.

Cerebellar modules in the olivo-cortico-nuclear loop demarcated by pcdh10 expression in the adult mouse.

Topographic connection between corresponding compartments of the cerebellar cortex, cerebellar nuclei, and inferior olive form parallel modules, which are essential for the cerebellar function. Compared to the striped cortical compartmentalization which are labeled by molecular markers, such as aldolase C (Aldoc) or zebrin II, the presumed corresponding organization of the cerebellar nuclei and inferior olivary nucleus has not been much clarified. We focused on the expression pattern of pcdh10 gene coding cell adhesion molecule protocadherin 10 (Pcdh10) in adult mice. In the cortex, pcdh10 was strongly expressed in (a) Aldoc-positive vermal stripes a+//2+ in lobules VI-VII, (b) paravermal narrow stripes c+, d+, 4b+, 5a+ in crus I and neighboring lobules, and (c) paravermal stripes 4+//5+ across all lobules from lobule III to paraflocculus. In the cerebellar nuclei, pcdh10 was expressed strongly in the caudal part of the medial nucleus and the lateral part of the posterior interposed nucleus which project less to the medulla or to the red nucleus than to other metencephalic, mesencephalic, and diencephalic areas. In the inferior olive, pcdh10 was expressed strongly in the rostral and medioventrocaudal parts of the medial accessory olive which has connection with the mesencephalic areas rather than the spinal cord. Olivocerebellar and corticonuclear axonal labeling confirmed that the three cortical pcdh10-positive areas were topographically connected to the nuclear and olivary pcdh10-positive areas, demonstrating their coincidence with modular structures in the olivo-cortico-nuclear loop. We speculate that some of these modules are functionally involved in various nonsomatosensorimotor tasks via their afferent and efferent connections.

Parrots have evolved a primate-like telencephalic-midbrain-cerebellar circuit.

It is widely accepted that parrots show remarkable cognitive abilities. In mammals, the evolution of complex cognitive abilities is associated with increases in the size of the telencephalon and cerebellum as well as the pontine nuclei, which connect these two regions. Parrots have relatively large telencephalons that rival those of primates, but whether there are also evolutionary changes in their telencephalon-cerebellar relay nuclei is unknown. Like mammals, birds have two brainstem pontine nuclei that project to the cerebellum and receive projections from the telencephalon. Unlike mammals, birds also have a pretectal nucleus that connects the telencephalon with the cerebellum: the medial spiriform nucleus (SpM). We found that SpM, but not the pontine nuclei, is greatly enlarged in parrots and its relative size significantly correlated with the relative size of the telencephalon across all birds. This suggests that the telencephalon-SpM-cerebellar pathway of birds may play an analogous role to cortico-ponto-cerebellar pathways of mammals in controlling fine motor skills and complex cognitive processes. We conclude that SpM is key to understanding the role of telencephalon-cerebellar pathways in the evolution of complex cognitive abilities in birds.

Different contributions of preparatory activity in the basal ganglia and cerebellum for self-timing.

The ability to flexibly adjust movement timing is important for everyday life. Although the basal ganglia and cerebellum have been implicated in monitoring of supra- and sub-second intervals, respectively, the underlying neuronal mechanism remains unclear. Here, we show that in monkeys trained to generate a self-initiated saccade at instructed timing following a visual cue, neurons in the caudate nucleus kept track of passage of time throughout the delay period, while those in the cerebellar dentate nucleus were recruited only during the last part of the delay period. Conversely, neuronal correlates of trial-by-trial variation of self-timing emerged earlier in the cerebellum than the striatum. Local inactivation of respective recording sites confirmed the difference in their relative contributions to supra- and sub-second intervals. These results suggest that the basal ganglia may measure elapsed time relative to the intended interval, while the cerebellum might be responsible for the fine adjustment of self-timing.

Structural and functional connectivity of the nondecussating dentato-rubro-thalamic tract.

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.

Improved Neuroimaging Atlas of the Dentate Nucleus.

The dentate nucleus (DN) of the cerebellum is the major output nucleus of the cerebellum and is rich in iron. Quantitative susceptibility mapping (QSM) provides better iron-sensitive MRI contrast to delineate the boundary of the DN than either T2-weighted images or susceptibility-weighted images. Prior DN atlases used T2-weighted or susceptibility-weighted images to create DN atlases. Here, we employ QSM images to develop an improved dentate nucleus atlas for use in imaging studies. The DN was segmented in QSM images from 38 healthy volunteers. The resulting DN masks were transformed to a common space and averaged to generate the DN atlas. The center of mass of the left and right sides of the QSM-based DN atlas in the Montreal Neurological Institute space was -13.8, -55.8, and -36.4 mm, and 13.8, -55.7, and -36.4 mm, respectively. The maximal probability and mean probability of the DN atlas with the individually segmented DNs in this cohort were 100 and 39.3%, respectively, in contrast to the maximum probability of approximately 75% and the mean probability of 23.4 to 33.7% with earlier DN atlases. Using QSM, which provides superior iron-sensitive MRI contrast for delineating iron-rich structures, an improved atlas for the dentate nucleus has been generated. The atlas can be applied to investigate the role of the DN in both normal cortico-cerebellar physiology and the variety of disease states in which it is implicated.

Transformation of spatiotemporal dynamics in the macaque vestibular system from otolith afferents to cortex.

Sensory signals undergo substantial recoding when neural activity is relayed from sensors through pre-thalamic and thalamic nuclei to cortex. To explore how temporal dynamics and directional tuning are sculpted in hierarchical vestibular circuits, we compared responses of macaque otolith afferents with neurons in the vestibular and cerebellar nuclei, as well as five cortical areas, to identical three-dimensional translational motion. We demonstrate a remarkable spatio-temporal transformation: otolith afferents carry spatially aligned cosine-tuned translational acceleration and jerk signals. In contrast, brainstem and cerebellar neurons exhibit non-linear, mixed selectivity for translational velocity, acceleration, jerk and position. Furthermore, these components often show dissimilar spatial tuning. Moderate further transformation of translation signals occurs in the cortex, such that similar spatio-temporal properties are found in multiple cortical areas. These results suggest that the first synapse represents a key processing element in vestibular pathways, robustly shaping how self-motion is represented in central vestibular circuits and cortical areas.

PECULIARITIES OF THE CEREBELLUM NUCLEI IN AGED PERSONS.

The study of the clinical anatomy and functional features of the cortex, subcortical and conductive pathways of the cerebellum is necessary for clinicians for elaboration rational surgical approaches to these formations, for determination the localization of pathological processes associated with these formations. Cerebellar nucleus neurons are crucial to the olivo-cerebellar circuit as they provide the sole output of the entire cerebellum. The relationship between mobility and cognition in aging is well established, but the relationship between mobility and the structure and function of the aging brain is relatively unknown. In connection with the above, the purpose of our study was detection of the morphological characteristics of the cerebellum nuclei in aged persons. Study was performed on 48 specimens of the cerebellum from people (24 male and 24 female), who died at the age from 75 to 99 years due to diseases, which were not related to the central nervous system damaging. Formalin-fixed human hemispheres were dissected with the Ludwig and Klingler fiber dissection technique under x6 to x40 magnifications of binocular microscope Olympus BX41 (Japan). The morphological features of the human cerebellar nuclei were established. Namely, on the series of sections of the cerebellum in the horizontal, frontal and sagittal planes, as well as on the macro-microscopic preparations of the cerebellar nuclei location, their relative position, shape, linear dimensions, weight and volume were described. The features of macro-microscopic and histological structure of the nuclei of the cerebellum were made own classification of the gyri and teeth of the dentate nucleus of the cerebellum was offered. Macro-microscopic dissection of persons died after 75 years old show no significant variability of linear dimensions of cerebellar nuclei with their specific location and options. Simultaneously, reliable reducing of cellular density was detected for Purkinje, granule and basket neurons more pronounced in male for Purkinje cells.

Dentatorubrothalamic tract localization with postmortem MR diffusion tractography compared to histological 3D reconstruction.

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.

Anatomical and functional relationships between deep cerebellar nuclei and cerebellar cortical Crus II in vivo in mice.

We previously reported that an air-puff stimulation on the ipsilateral whisker pad evoked responses in molecular layer (ML) and Purkinje cell (PC) layer in cerebellar cortex folium Crus II. We used anterograde tracing and electrophysiological methods to investigate the anatomical and functional relationships between the trigeminal tactile response area in the cerebellar cortex Crus II and deep cerebellar nuclei (DCN) in living mice. We found that the axons of tactile activated PCs projected in anterior part (IntA) and posterior part (IntP), and dorsolateral hump (IntDL) of ipsilateral interposed cerebellar nucleus (ICN). In ICN, the tactile stimulus evoked-field potential expressed a sequence of two negative components N1 and N2, while extracellular recordings from ICN neurons revealed that an increase in spike frequency in response to tactile stimulus. When the duration of facial air-puff stimulus were ≥ 30 ms, stimulation off response (Roff) were observed in the ICN, but an increase in the duration of facial air-puff stimulation did not significantly affect the amplitude of Ron (N1 and N2) and Roff. The latency and time to peak of N1 in ICN were significantly shorter than that of N1 in the ML, but the latency and time to peak of N2 in ICN were significantly later than that of P1 in the ML. The present results suggest that the facial sensory information, at least in part, is transferred to ICN by PC axons from Crus II, which evokes excitation in ICN neurons.

The nondecussating pathway of the dentatorubrothalamic tract in humans: human connectome-based tractographic study and microdissection validation.

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.

A probabilistic atlas of the cerebellar white matter.

Imaging of the cerebellar cortex, deep cerebellar nuclei and their connectivity are gaining attraction, due to the important role the cerebellum plays in cognition and motor control. Atlases of the cerebellar cortex and nuclei are used to locate regions of interest in clinical and neuroscience studies. However, the white matter that connects these relay stations is of at least similar functional importance. Damage to these cerebellar white matter tracts may lead to serious language, cognitive and emotional disturbances, although the pathophysiological mechanism behind it is still debated. Differences in white matter integrity between patients and controls might shed light on structure-function correlations. A probabilistic parcellation atlas of the cerebellar white matter would help these studies by facilitating automatic segmentation of the cerebellar peduncles, the localization of lesions and the comparison of white matter integrity between patients and controls. In this work a digital three-dimensional probabilistic atlas of the cerebellar white matter is presented, based on high quality 3T, 1.25mm resolution diffusion MRI data from 90 subjects participating in the Human Connectome Project. The white matter tracts were estimated using probabilistic tractography. Results over 90 subjects were symmetrical and trajectories of superior, middle and inferior cerebellar peduncles resembled the anatomy as known from anatomical studies. This atlas will contribute to a better understanding of cerebellar white matter architecture. It may eventually aid in defining structure-function correlations in patients with cerebellar disorders.

Increased Signal Intensity in the Dentate Nucleus on Unenhanced T1-Weighted Images After Gadobenate Dimeglumine Administration.

OBJECTIVES: The aim of this study was to compare changes in signal intensity (SI) ratios of the dentate nucleus (DN) to pons and cerebrospinal fluid (CSF) on unenhanced T1-weighted magnetic resonance imaging (MRI) scans between the first and last MRI using the linear gadolinium-based contrast agent gadobenate dimeglumine. MATERIALS AND METHODS: The study was approved by the ethical committee of the University of Heidelberg (S-324/2014), and written informed consent was waived due to the retrospective character of the study. Fifty patients who underwent at least 5 consecutive MRI examinations (plus an additional last MRI for reference) with the exclusive use of gadobenate dimeglumine were analyzed retrospectively. The difference of DN-to-pons and DN-to-CSF mean SI ratios was calculated on unenhanced T1-weighted images between the first and last examination. Results were compared with previously published data on gadopentetate dimeglumine and gadoterate meglumine. RESULTS: Signal intensity ratio differences for DN-to-pons and DN-to-CSF were significantly greater than 0 (pons: 0.0399 ± 0.0307, P < 0.001; CSF: 0.1439 ± 0.1524, P < 0.001). No control variable consistently predicted the SI ratio difference for the DN-to-pons and the DN-to-CSF ratio. Compared with previously published data, the difference in SI increase between gadopentetate dimeglumine and gadobenate dimeglumine was not significant for the DN-to-pons ratio (P = 0.906). In contrast, the DN-to-CSF ratio difference was significantly lower (P < 0.001) for gadobenate dimeglumine. Dentate nucleus-to-pons (P < 0.001) and DN-to-CSF (P = 0.017) ratio differences were both significantly higher for gadobenate dimeglumine than for gadoterate meglumine. CONCLUSIONS: The present study found an increase in SI in the DN after serial injections of gadobenate dimeglumine. Further studies are needed to clarify the potential of different linear gadolinium-based contrast agents to cause SI increase in the DN.

White Matter Integrity of Specific Dentato-Thalamo-Cortical Pathways is Associated with Learning Gains in Precise Movement Timing.

The dentato-thalamo-cortical tract (DTCT) connects the lateral cerebellum with contralateral motor and nonmotor areas, such as the primary motor cortex (M1), the ventral premotor cortex (PMv), and the dorsolateral prefrontal cortex (DLPFC). As the acquisition of precisely timed finger movements requires the interplay between these brain regions, the structural integrity of the underlying connections might explain variance in behavior. Diffusion tensor imaging was used to 1) reconstruct the DTCT connecting the dentate nucleus with M1, PMv, and DLPFC and 2) examine to which extent their microstructural integrity (tract-related fractional anisotropy) relates to learning gains in a motor-sequence learning paradigm consisting of a synchronization and continuation part. Continuous DTCT were reconstructed from the dentate nucleus to all cortical target areas. We found that the microstructural integrity of the DTCT connecting the left dentate nucleus with the right DLPFC was associated with better early consolidation in rhythm continuation (R = -0.69, P = 0.02). The present data further advances the knowledge about a right-hemispheric timing network in the human brain with the DLPFC as an important node contributing to learning gains in precise movement timing.

The dentate nucleus and its projection system in the human cerebellum: the dentate nucleus microsurgical anatomical study.

BACKGROUND: Neurosurgical management of cerebellar lesions remains challenging. Thus, it is important to have sound knowledge of the microsurgical anatomy of the cerebellum and dentate nucleus (DN) and to define different types of exposure in a variety of surgical interventions. OBJECTIVE: To examine the anatomy of the DN from a neurosurgical viewpoint using fiber tracking techniques. METHODS: Ten formalin-fixed human hemispheres were dissected with the Ludwig and Klingler fiber dissection technique under × 6 to × 40 magnification. Anatomic images were created with 3-dimensional diffusion tensor imaging. The relationships of the DN to tentorium and suboccipital and lateral surfaces of the cerebellum and its spatial positioning relative to different surgical approaches in the cerebellum and fourth ventricle were examined. The fiber tracts terminating at and surrounding the DN were defined. RESULTS: The DN is at greater risk of being injured in the transvermian and supratonsillar approaches to the cerebellum and fourth ventricle, with lesser risk in the telovelar and subtonsillar approaches. Superior approaches are safer compared with other approaches. CONCLUSION: The DN represents an important anatomic structure in surgical interventions involving the posterior fossa, particularly in the elderly because of the common occurrence of atrophy-related problems in this age group. Functionally and anatomically, the DN is closely related to the superior and middle cerebellar peduncles. The inferior cerebellar peduncle poses positional risks because it follows an anterior and superior course relative to the DN. The telovelar approach is a safer procedure for interventions involving the pathological lesions of the fourth ventricle floor.