Cerebellar Topography Research Articles

Social cognition and the cerebellum: A meta-analytic connectivity analysis.

This meta-analytic connectivity modeling (MACM) study explores the functional connectivity of the cerebellum with the cerebrum in social cognitive processes. In a recent meta-analysis, Van Overwalle, Baetens, Mariën, and Vandekerckhove (2014) documented that the cerebellum is implicated in social processes of "body" reading (mirroring; e.g., understanding other persons' intentions from observing their movements) and "mind" reading (mentalizing, e.g., inferring other persons' beliefs, intentions or personality traits, reconstructing persons' past, future, or hypothetical events). In a recent functional connectivity study, Buckner et al. (2011) offered a novel parcellation of cerebellar topography that substantially overlaps with the cerebellar meta-analytic findings of Van Overwalle et al. (2014). This overlap suggests that the involvement of the cerebellum in social reasoning depends on its functional connectivity with the cerebrum. To test this hypothesis, we explored the meta-analytic co-activations as indices of functional connectivity between the cerebellum and the cerebrum during social cognition. The MACM results confirm substantial and distinct connectivity with respect to the functions of (a) action understanding ("body" reading) and (b) mentalizing ("mind" reading). The consistent and strong connectivity findings of this analysis suggest that cerebellar activity during social judgments reflects distinct mirroring and mentalizing functionality, and that these cerebellar functions are connected with corresponding functional networks in the cerebrum.

The compartmental restriction of cerebellar interneurons

The Purkinje cells (PC's) of the cerebellar cortex are subdivided into multiple different molecular phenotypes that form an elaborate array of parasagittal stripes. This array serves as a scaffold around which afferent topography is organized. The ways in which cerebellar interneurons may be restricted by this scaffolding are less well-understood. This review begins with a brief survey of cerebellar topography. Next, it reviews the development of stripes in the cerebellum with a particular emphasis on the embryological origins of cerebellar interneurons. These data serve as a foundation to discuss the hypothesis that cerebellar compartment boundaries also restrict cerebellar interneurons, both excitatory [granule cells, unipolar brush cells (UBCs)] and inhibitory (e.g., Golgi cells, basket cells). Finally, it is proposed that the same PC scaffold that restricts afferent terminal fields to stripes may also act to organize cerebellar interneurons.

Phospholipase cβ4 expression reveals the continuity of cerebellar topography through development

Mediolateral boundaries divide the mouse cerebellar cortex into four transverse zones, and within each zone the cortex is further subdivided into a symmetrical array of parasagittal stripes. Various expression markers reveal this complexity, and detailed maps have been constructed based on the differential expression of zebrin II/aldolase C in a Purkinje cell subset. Recently, phospholipase (PL) Cbeta4 expression in adult mice was shown to be restricted to, and coextensive with, the zebrin II-immunonegative Purkinje cell subset. The Purkinje cell expression of PLCbeta4 during embryogenesis and postnatal development begins just before birth in a subset of Purkinje cells that are clustered to form a reproducible array of parasagittal stripes. Double label and serial section immunocytochemistry revealed that the early PLCbeta4-immunoreactive clusters in the neonate are complementary to those previously identified by neurogranin expression. The PLCbeta4 expression pattern can be traced continuously from embryo to adult, revealing the continuity of the topographical map from perinatal to adult cerebella. The only exception, as has been seen for other antigenic markers, is that transient PLCbeta4 expression (which subsequently disappears) is seen in some Purkinje cell stripes during the second postnatal week. Furthermore, the data confirm that some adult Purkinje cell stripes are composite in origin, being derived from two or more distinct embryonic clusters. Thus, the zone and stripe topography of the cerebellum is conserved from embryo to adult, confirming that the early- and late-antigenic markers share a common cerebellar topography.

A key role for the HLH transcription factor EBF2COE2,O/E-3 in Purkinje neuron migration and cerebellar cortical topography

Early B-cell factor 2 (EBF2) is one of four mammalian members of an atypical helix-loop-helix transcription factor family (COE). COE proteins have been implicated in various aspects of nervous and immune system development. We and others have generated and described mice carrying a null mutation of Ebf2, a gene previously characterized in the context of Xenopus laevis primary neurogenesis and neuronal differentiation. In addition to deficits in neuroendocrine and olfactory development, and peripheral nerve maturation, Ebf2 null mice feature an ataxic gait and obvious motor deficits associated with clear-cut abnormalities of cerebellar development. The number of Purkinje cells (PCs) in the Ebf2 null is markedly decreased, resulting in a small cerebellum with notable foliation defects, particularly in the anterior vermis. We show that this stems from the defective migration of a molecularly defined PC subset that subsequently dies by apoptosis. Part of the striped cerebellar topography is disrupted due to cell death and, in addition, many of the surviving PCs, that would normally adopt a zebrin II-negative phenotype, transdifferentiate to Zebrin II-positive, an unprecedented finding suggesting that Ebf2 is required for the establishment of a proper cerebellar cortical map.

Whole-mount immunohistochemistry: a high-throughput screen for patterning defects in the mouse cerebellum.

Large-scale mouse mutagenesis experiments now under way require appropriate screening methods. An important class of potential mutants comprises those with defects in the development of normal cerebellar patterning. Cerebellar defects are likely to be identified often because they typically result in ataxia. Immunohistochemistry (IHC) is commonly used to reveal cerebellar organization. In particular, the antigen zebrin II (=aldolase C), expressed by stripes of Purkinje cells, has been valuable in revealing cerebellar pattern abnormalities. The development of whole-mount procedures in Drosophila, chick, and Xenopus embryos allows complex patterns to be studied in situ while preserving the integrity of the structure. By combining procedures originally designed for embryonic and early postnatal tissue analyses, we have developed a whole-mount IHC protocol using anti-zebrin II, which reveals the complex topography of Purkinje cells in the adult mouse cerebellum. Furthermore, the procedure is effective with a number of other antigens and works well on both perfusion-fixed and immersion-fixed tissue. By use of this approach, normal adult murine cerebellar topography and patterning defects caused by mutation can be studied without the need for three-dimensional reconstruction.

Three-Dimensional MRI Atlas of the Human Cerebellum in Proportional Stereotaxic Space

We have prepared an atlas of the human cerebellum using high-resolution magnetic resonance-derived images warped into the proportional stereotaxic space of Talairach and Tournoux. Software that permits simultaneous visualization of the three cardinal planes facilitated the identification of the cerebellar fissures and lobules. A revised version of the Larsell nomenclature facilitated a simple description of the cerebellum. This atlas derived from a single individual was instrumental in addressing longstanding debates about the gross morphologic organization of the cerebellum. It may serve as the template for more precise identification of cerebellar topography in functional imaging studies in normals, for investigating clinical–pathologic correlations in patients, and for the development of future probabilistic maps of the human cerebellum.

Comparing motion- and imagery-related activation in the human cerebellum: A functional MRI study

Cerebellar activation during execution and imagination of a finger movement was compared. Functional magnetic resonance imaging was used to detect cerebellar activation during execution and imagination of an untrained self-paced finger-to-thumb movement (left and right hand separately). The four fingers were opposed to the thumb in changing sequences freely chosen by the subjects. The activation maps of 10 right-handed healthy subjects were averaged after transformation into a common coordinate space. Averaged activation maps revealed strong motion-related bilateral activation in the anterior lobe of the cerebellum and in the paravermal regions of the posterior lobe. Ipsilateral activity predominated significantly. Compared to motion, imagination of the same task produced lower signal changes, and foci were more variable in position and strength. The averaged activation maps showed activity in the same regions as in motion. Activation in the posterior cerebellar lobe was more prominent extending into the lateral hemispheres. Ipsilateral dominance was significant for right-hand imagery. The left-hand task only showed marginally stronger ipsilateral activation. The activation pattern observed during execution of the finger-to-thumb movement is in agreement with theories of functional cerebellar topography. For imagery, activation at a comparable location may reflect common functionality, e.g., motor preparation and/or timing. Additional activation in the lateral hemispheres may be related to an imagery-specific function.

An antigenic map of cerebellar topography

An antigenic map of cerebellar topography