Abstract
Recognition of key concepts of structural and functional anatomy of the cerebellum can facilitate image interpretation and clinical correlation. Recently, the human brain mapping literature has increased our understanding of cerebellar anatomy, function, connectivity with the cerebrum, and significance of lesions involving specific areas.
Both the common names and numerically based Schmahmann classifications of cerebellar lobules are illustrated. Anatomic patterns, or signs, of key fissures and white matter branching are introduced to facilitate easy recognition of the major anatomic features. Color-coded overlays of cross-sectional imaging are provided for reference of more complex detail. Examples of exquisite detail of structural and functional cerebellar anatomy at 7 T MRI are also depicted.
The functions of the cerebellum are manifold with the majority of areas involved with non-motor association function. Key concepts of lesion–symptom mapping which correlates lesion location to clinical manifestation are introduced, emphasizing that lesions in most areas of the cerebellum are associated with predominantly non-motor deficits. Clinical correlation is reinforced with examples of intrinsic pathologic derangement of cerebellar anatomy and altered functional connectivity due to pathology of the cerebral hemisphere. The purpose of this pictorial review is to illustrate basic concepts of these topics in a cross-sectional imaging-based format that can be easily understood and applied by radiologists.
Introduction
The structural and functional anatomy of the cerebellum is complex, but demonstrates reproducible spatial organization. Detail of cerebellar pathologic derangement is often underemphasized in radiology education and reports, but recognition of key concepts and patterns can facilitate image interpretation and clinical correlation. In recent decades, advances in the human brain mapping literature has increased our understanding of anatomy, function, and the clinical significance of lesions involving specific areas of the cerebellum. The purpose of this pictorial review is to illustrate basic concepts of these imaging topics to facilitate application to clinical practice and to the appraisal of human brain mapping research. To do this, key patterns, or signs, of white matter branching and fissure prominence, configuration, and orientation are presented to depict the major anatomic features. Color-coded overlays are provided for reference of further anatomic detail. A brief introduction to relevant embryology and correlation to general vascular territories are provided. Functional organization is presented with blood oxygen level dependent (BOLD) fMRI signal and introduction of lesion–symptom mapping.
Overview of cross-sectional anatomy
The cerebellum broadly consists of cortex, central white matter, and deep nuclei. The cortex lacks areas of highly distinct cytoarchitecture analogous to the Brodmann areas of the brain. However, differences in biochemistry and function occur within sagittally oriented segments that have been divided into zones/stripes and modules with a medial to lateral gradient of connectivity to the inferior olives and deep nuclei.1 The trilaminar cortical layers can be remembered with the pneumonic MPG (superficial to deep: molecular, Purkinje, and granular); the molecular and granular layers have been visualized in vivo with specialized techniques at 7 T, but are not routinely visualized in current clinical practice.2 The Purkinje layer is too small to visualize in vivo with current techniques, but serves as the cortical output to the deep nuclei.
The central white matter (corpus medullare) has distinct branching patterns (arbor vitae); of these several particularly prominent white matter stems can be used to identify key anatomic areas. The deep nuclei give rise to the major efferent white matter fibers. While the dentate nucleus is commonly visualized at 1.5 or 3 T MRI, the interposed and fastigial nuclei are more challenging to visualize even at higher field strength.3,4
Side-to-side, the cerebellum is divided into two hemispheres with a midline vermis. Both the hemispheres and the vermis are typically divided into three lobes. In turn, fissures subdivide the lobes into numerous lobules (Figures 1–5). Importantly, the designation of ‘anterior’ and ‘posterior’ location for both the lobes and axis of development (below) reflect ‘cranial’ and ‘caudal’ location respectively rather than designations by conventional clinical MRI terminology. While the radiologist may be familiar with the common names of the lobes and lobules, numerous nomenclature schemes and definitions exist which can create some confusion. To address this variability, Schmahmann et al proposed a numerical nomenclature which is commonly used in the human brain mapping literature and emerging in the imaging literature.5,6 Assessment of this level of detail can be important since function and predisposition to certain pathology varies amongst the lobules. Recognition of lobule anatomy also facilitates assessment of congenital anomalies. The Schmahmann classification simplifies lobule nomenclature as the lobules are arranged in numerical order (I–X) radially in the sagittal plane. In many locations, the lobule can be identified quickly on cross-sectional imaging by the relationship to patterns, or signs, of key fissures or white matter stems presented in the figures of this essay. Several methods of automated parcellation of the cerebellar lobules which could aid visual identification and assessment have been described, but these are not yet widely evaluated or implemented in clinical practice.7
Embryology
The development of the cerebellum is highly complex and the details are beyond the scope of this review. Barkovich et al have provided an in-depth analysis with a comprehensive classification system of congenital anomalies.8 In brief, both the cerebellum and brainstem (pons and medulla) are derived from the rhombencephalon. The fissures appear in sequence, with the primary and posterolateral fissures (separating the lobes) developing first while those separating lobules VI, VIIA, and VIIB (which are the only lobules to share a common white matter stem in the vermis) are the last to form.6 Understanding this sequence can facilitate interpretation of expected findings on prenatal imaging and avert a misdiagnosis of hypoplasia prior to final differentiation of the lobules.6 There is both anteroposterior (craniocaudal) and dorsoventral hindbrain patterning; abnormalities of these processes can lead to deranged anatomy along the respective axes.8 Importantly, lobular development does not occur in the numeric sequence outlined in the Schmahmann classification. Further, the vermis does not arise from fusion of the cerebellar hemispheres, but is derived from dedicated primordium, with the anterior and posterior segments arising separately.6 These concepts can account for numerous categories of deranged anatomy including the existence of segmental vermian abnormalities and the isolated presence of the posterior vermis in some cases of rhomboencephalosynapsis.6 Examples of these concepts are included in Figure 6.
Diffusion tensor imaging (DTI) and tractography of white Matter
DTI can depict areas of afferent and efferent white matter tracts of the cerebellum as well as some of the major white matter stems within the cerebellum. However, tractography techniques are needed for detailed delineation of the afferent and efferent tracts. Karavasilis et al report that both crossed and uncrossed components of the afferent tracts [fronto-ponto-cerebellar (FPC), parieto-ponto-cerebellar (PPC), occipito-ponto-cerebellar (OPC) tracts] to the cerebral hemispheres can be identified with tractography.9 In distinction, the uncrossed fibers of the dentato-rubro-thalamo-cortical tract (DRTC) are most consistently depicted with current DTI and tractography techniques, although crossed fibers are more numerous (Figure 7).9 This is important because the cerebellum and DRTC have a role in many tremor conditions and mapping the DRTC can facilitate functional neurosurgical treatment.
Overview of functional anatomy
The cerebellum contributes to diverse distinct central nervous system functions including motor, language, working memory, executive function, autonomic, and affect. In general, such function demonstrates organization in a medial to lateral distribution and in a radial distribution amongst the lobules. To a first approximation, both motor and association cerebellar function demonstrate mirror-image organization about the Crus I/II expansion.10 There is also evidence of a small tertiary map near lobule IX.10 As exceptions, some data indicate lack of cerebellar connectivity to the primary visual and primary auditory cortex.10 During routine clinical fMRI, cerebellar BOLD activity may be identified within the cerebellum at 3 or 7 T. Additionally, special coils and techniques to specifically assess cerebellum BOLD activity at 7 T have been described (Figure 8).11
Motor function, and corresponding BOLD activity on fMRI examinations, is largely found in the anterior lobe, with additional motor function within the ventral cerebellum (particularly lobules VIII) and deep cerebellar nuclei. This motor activity demonstrates somatotopic organization both within the cerebellar hemispheres and the dorsal dentate nucleus (the ventral dentate nucleus is thought to serve largely non-motor function). Key motor function of the cerebellar cortex is medially located within the anterior lobe.
The majority of the cerebellum specializes in non-motor functions with connectivity to multimodal association areas of cerebral cortex (Figure 9). The bulk of the cerebellum is comprised of the posterior lobe and the lateral and peripheral most regions are formed by Crus I/II. The relatively expansive Crus I/II lobules demonstrate connectivity to association cerebral cortex. Overall, the size of regional connections between the cerebellum and cerebrum are relatively proportionate.10 Specific regions of the cerebellum have been found to participate in intrinsic connectivity networks of the brain such as the default mode, salience, and executive networks.12,13
Language function localizes to the posterior lobe contralateral to the language dominant cerebral hemisphere, usually the right posterior lobe of the cerebellum.14 Similarly, whereas the right cerebral association areas have a prominent role in visuospatial function, this function localizes to the left posterior cerebellar hemisphere. There is also evidence that working memory function maps to the left posterior cerebellar hemisphere.
The deep cerebellar nuclei (Figure 10) also demonstrate mediolateral and rostral-caudal functional organization. In general amongst the nuclei, motor function is located medially, with truncal motor control closest to midline and lower extremity control present more off midline. Further, somatotopic organization of motor function has been described within the dorsal dentate nucleus with a rostral (foot activation) to caudal (finger activation) gradient at 7 T on group analysis, although some overlap occurred.15
Lesion–symptom mapping
Lesion involving specific regions of the cerebellar hemispheres or deep nuclei can result in specific clinical findings (Figure 11). However, such findings can be more subtle and variable than with lesions of the cerebral hemispheres and clinically detectable deficit may be absent. Studies in the human brain mapping literature have correlated the area of lesion overlap and involvement to clinical deficits in groups of patients.16,17 In general, the resultant clinical manifestations can be predicted by knowledge of cerebellar functional topology.
For example, lower limb ataxia can result from lesions of lobules III–IV and upper limb ataxia from lesions of lobules IV–VI. Dysarthria can result from lesions of lobules V and VI and eyeblink conditioning is altered by lesions of lobule VI and Crus I. Lesions of the deep cerebellar nuclei can also be subdivided, with lesions of the fastigial and interposed nuclei predisposing to truncal ataxia and lesions of the interposed and dentate nuclei predisposing to limb ataxia. In general, there seems to be less recovery of function in the chronic state with lesions of the deep nuclei relative to the cortex.16,17
Isolated acute cerebellar infarcts can provide insight into cerebellar function due to acute onset, lack of opportunity to adapt, and defined anatomic extent of pathology. Anterior lobe infarcts, which approximately correspond to the superior cerebellar artery (SCA) territory, can result in predominantly motor symptoms including dysarthria and upper and/or lower limb ataxia depending on location (Figure 11). The SCA also typically supplies the dorsal (motor) portions of the dentate nucleus whereas the posterior inferior cerebellar artery (PICA) supplies the inferior (non-motor dentate); accordingly evidence indicates the SCA infarcts with dentate involvement are associated with impaired hand gripping tests whereas PICA infarcts with dentate involvement are not.18 However, the majority of cerebellar infarcts involve the posterior lobe (approximately anterior inferior cerebellar artery–PICA territory), which may be associated with predominantly nonspecific symptoms including nausea, headache, and confusion. Although the correlation of loss of function to area of isolated cerebellar infarct somewhat variable, in general limb ataxia and dysarthria are most common with SCA infarcts whereas gait ataxia can be seen with SCA or PICA infarcts, in particular with involvement of the vermis.16,19,20
Lesion–symptom mapping can also be predicated upon longstanding pathology and the effects of surgical resection. For example, there is evidence that resection of tumors from the posterior lobes can result in impaired cognition, affect, and pain processing and that resection of medulloblastomas of the left posterior cerebellar lobe is associated with decreased working memory.21,22 Schmahmann et al described the cerebellar cognitive affective disorder, which encompasses a variety of executive function and behavioral symptoms due to lesions of the posterior lobes.17 This can include planning, reasoning, working memory, language, personality, affect, and altered behavior.
Pathologic derangement
With symptom–lesion mapping, study of normal function and structure can facilitate an understanding of clinical manifestations of pathology. Both intrinsic derangement within the cerebellum itself and altered functional connectivity due to pathology of the cerebral hemisphere are possible. Altered structure and function can be on either an acquired or a congenital basis (Figures 12–13).
Key take home points
Advances in the human brain mapping literature in recent decades have substantially improved the understanding of cross-sectional and functional anatomy of the cerebellum.
Numerical lobule designation per the Schmahmann classification is arranged radially in the sagittal plane. Most lobules of the vermis are identified by an independent white matter stem, whereas lobules VI, VIIA, and VIIB have a common dorsally directed stem and are the last to differentiate.
The main anatomic features of the cerebellum on MRI can be recognized by relationship to several typical white matter stem and fissure configurations, orientations, and/or prominence. Key signs include the ‘intraculminate X sign’ just anterior to the deep primary fissure and the ‘crus I bowtie sign’ amongst many others described herein.
Lesion–symptom mapping reports indicate that lesions of the anterior lobe can result predominantly in motor deficits and specific forms of ataxia corresponding to homunculus involvement whereas lesions of the larger posterior lobe can result in nonmotor symptoms such as cerebellarcognitive affective disorder and impaired working memory. Nonetheless, lesions of the cerebellum often result in a variety of non-specific symptoms. Lesions of the deep nuclei are important to recognize since there is generally less recovery of function over time compared to other regions of the cerebellum.
The cerebellum plays a role in tremor syndromes and DRTC tractography, including that of uncrossing fibers, can facilitate functional neurosurgical treatment.
Normal and pathologic anatomy and function of the cerebellum is intertwined with the brainstem and cerebrum via circuits. Cerebellar pathology can arise from insults primary to these other locations such as malformations of cerebral cortical development.
Footnotes
Acknowledgment: The authors acknowledge the assistance of Sonia Watson, PhD, in editing the manuscript.
Conflicts of Interest: TJK: Consult for SpineThera and stock option ownership, not relevant to current work; all other authors have no conflicts of interest to declare.
Contributor Information
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