•Cerebrocerebellar connections confer functional topography on cerebellar organization.•Sensorimotor processing is represented principally in the cerebellar anterior lobe.•Anterior lobe damage causes ...the motor syndrome of gait ataxia and limb dysmetria.•Cognition and emotion are subserved by the cerebellar posterior lobe.•Posterior lobe lesions cause the cerebellar cognitive affective syndrome (CCAS).•The CCAS scale can identify and rate degree of impairment in clinical contexts.•The cerebellar role in behavioral neurology / neuropsychiatry continues to evolve.
What the cerebellum does to sensorimotor and vestibular control, it also does to cognition, emotion, and autonomic function. This hypothesis is based on the theories of dysmetria of thought and the universal cerebellar transform, which hold that the cerebellum maintains behavior around a homeostatic baseline, automatically, without conscious awareness, informed by implicit learning, and performed according to context. Functional topography within the cerebellum facilitates the modulation of distributed networks subserving multiple different functions. The sensorimotor cerebellum is represented in the anterior lobe with a second representation in lobule VIII, and lesions of these areas lead to the cerebellar motor syndrome of ataxia, dysmetria, dysarthria and impaired oculomotor control. The cognitive / limbic cerebellum is in the cerebellar posterior lobe, with current evidence pointing to three separate topographic representations, the nature of which remain to be determined. Posterior lobe lesions result in the cerebellar cognitive affective syndrome (CCAS), the hallmark features of which include deficits in executive function, visual spatial processing, linguistic skills and regulation of affect. The affective dyscontrol manifests in autism spectrum and psychosis spectrum disorders, and disorders of emotional control, attentional control, and social skill set. This report presents an overview of the rapidly growing field of the clinical cognitive neuroscience of the cerebellum. It commences with a brief historical background, then discusses tract tracing experiments in animal models and functional imaging observations in humans that subserve the cerebellar contribution to neurological function. Structure function correlation studies following focal cerebellar lesions in adults and children permit a finer appreciation of the functional topography and nature of the cerebellar motor syndrome, cerebellar vestibular syndrome, and the third cornerstone of clinical ataxiology – the cerebellar cognitive affective syndrome. The ability to detect the CCAS in real time in clinical neurology with a brief and validated scale should make it possible to develop a deeper understanding of the clinical consequences of cerebellar lesions in a wide range of neurological and neuropsychiatric disorders with a link to the cerebellum.
The cognitive neuroscience of the cerebellum is now an established multidisciplinary field of investigation. This essay traces the historical evolution of this line of inquiry from an emerging field ...to its current status, with personal reflections over almost three decades on this journey of discovery. It pays tribute to early investigators who recognized the wider role of the cerebellum beyond motor control, traces the origins of new terms and concepts including the dysmetria of thought theory, the universal cerebellar transform, and the cerebellar cognitive affective syndrome, and places these developments within the broader context of the scientific efforts of a growing community of cerebellar cognitive neuroscientists. This account considers the converging evidence from theoretical, anatomical, physiological, clinical, and functional neuroimaging approaches that have resulted in the transition from recognizing the cerebellar incorporation into the distributed neural circuits subserving cognition and emotion, to a hopeful new era of treatment of neurocognitive and neuropsychiatric manifestations of cerebellar diseases, and to cerebellar-based interventions for psychiatric disorders.
Clinical, experimental and neuroimaging studies indicate that the cerebellum is involved in neural processes beyond the motor domain. Cerebellar somatotopy has been shown for motor control, but ...topographic organization of higher-order functions has not yet been established. To determine whether existing literature supports the hypothesis of functional topography in the human cerebellum, we conducted an activation likelihood estimate (ALE) meta-analysis of neuroimaging studies reporting cerebellar activation in selected task categories: motor (
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7 studies), somatosensory (
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2), language (
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11), verbal working memory (
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8), spatial (
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8), executive function (
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8) and emotional processing (
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9). In agreement with previous investigations, sensorimotor tasks activated anterior lobe (lobule V) and adjacent lobule VI, with additional foci in lobule VIII. Motor activation was in VIIIA/B; somatosensory activation was confined to VIIIB. The posterior lobe was involved in higher-level tasks. ALE peaks were identified in lobule VI and Crus I for language and verbal working memory; lobule VI for spatial tasks; lobules VI, Crus I and VIIB for executive functions; and lobules VI, Crus I and medial VII for emotional processing. Language was heavily right-lateralized and spatial peaks left-lateralized, reflecting crossed cerebro-cerebellar projections. Language and executive tasks activated regions of Crus I and lobule VII proposed to be involved in prefrontal-cerebellar loops. Emotional processing involved vermal lobule VII, implicated in cerebellar-limbic circuitry. These data provide support for an anterior sensorimotor vs. posterior cognitive/emotional dichotomy in the human cerebellum. Prospective studies of multiple domains within single individuals are necessary to better elucidate neurobehavioral structure–function correlations in the cerebellar posterior lobe.
Anatomical, clinical and imaging findings suggest that the cerebellum is engaged in cognitive and affective functions as well as motor control. Evidence from converging modalities also indicates that ...there is a functional topography in the human cerebellum for overt control of movement vs. higher functions, such that the cerebellum can be divided into zones depending on connectivity with sensorimotor vs. multimodal association cortices. Using functional MRI, we show that regions active during overt movement differ from those involved in higher-level language, spatial processing and working memory tasks. Nine healthy participants each completed five tasks in order to determine the relative activation patterns for the different paradigms. Right-handed finger-tapping activated right cerebellar lobules IV–V and VIII, consistent with descriptions of the cerebellar homunculi. Verb generation engaged right cerebellar lobules VI-Crus I and a second cluster in lobules VIIB–VIIIA. Mental rotation activation peaks were localized to medial left cerebellar lobule VII (Crus II). A 2-back working memory task activated bilateral regions of lobules VI–VII. Viewing arousing vs. neutral images did not reliably activate the cerebellum or cerebral limbic areas in this study. The cerebellar functional topography identified in this study reflects the involvement of different cerebro-cerebellar circuits depending on the demands of the task being performed: overt movement activated sensorimotor cortices along with contralateral cerebellar lobules IV–V and VIII, whereas more cognitively demanding tasks engaged prefrontal and parietal cortices along with cerebellar lobules VI and VII. These findings provide further support for a cerebellar role in both motor and cognitive tasks, and better establish the existence of functional subregions in the cerebellum. Future studies are needed to determine the exact contribution of the cerebellum – and different cerebro-cerebellar circuits – to task performance.
► We investigated cerebellar functional topography for motor and cognitive tasks. ► Subjects completed motor, language, working memory, spatial, and affective tasks. ► Overt movement activated the anterior lobe and lobule VIII. ► Cognitive measures activated topographically distinct areas in lobules VI and VII. ► Findings are consistent with the localization of cerebro-cerebellar loops.
Background
Cerebellar mutism (CM), pseudobulbar palsy, posterior fossa syndrome (PFS), and cerebellar cognitive affective syndrome (CCAS) are terms that have been used, sometimes interchangeably, to ...refer to the complex neurological constellation that occurs following surgical removal of cerebellar and fourth ventricular tumors, mostly in children, but also sometimes in adults.
Methods
This paper reviews the origins of what is now regarded as pediatric post-operative cerebellar mutism, the cerebellar cognitive affective syndrome, and the neurological manifestations of injury to or disruption of brainstem and cerebellar structures. It examines the specific components of each of these phenomena in the context of the evolving understanding of the role of the cerebellum in nervous system function.
Results
Children undergoing surgical management of tumors in the posterior cranial fossa are at risk of experiencing cranial neuropathies, corticospinal damage, cerebellar ataxia and related motor disorders, neuropsychiatric and cognitive changes, and in some patients, mutism. These clinical presentations are differentiated from each other and examined in the context of the relevant anatomical structures and distributed neural circuits. The term posterior fossa syndrome is not sufficiently helpful in distinguishing the different elements of the clinical phenomena from each other, and because of this lack of precision and specificity, there is consensus among investigators in the international Posterior Fossa Society that the designation be retired.
Conclusions
Using contemporary brain imaging methods and guided by careful clinical observation and meticulous definition of clinical phenomenology, it is now feasible to perform detailed structure function correlation analyses to achieve two critical goals in the care of children with tumors in the posterior cranial fossa. The first goal is to identify and understand the neural circuits responsible for the different manifestations—arousal, cranial neuropathies, long tract signs, cerebellar motor syndrome, cerebellar vestibular syndrome, cerebellar cognitive affective syndrome including emotional dyscontrol, and mutism. The second goal is to transform this knowledge into practical clinical intervention, preventing the complications inherent in the necessary surgery whenever possible, and develop new approaches to treatment with methods including brain modulation targeting interconnected nodes of the damaged neural circuits.
Patients with cerebellar damage often present with the cerebellar motor syndrome of dysmetria, dysarthria and ataxia, yet cerebellar lesions can also result in the cerebellar cognitive affective ...syndrome (CCAS), including executive, visual spatial, and linguistic impairments, and affective dysregulation. We have hypothesized that there is topographic organization in the human cerebellum such that the anterior lobe and lobule VIII contain the representation of the sensorimotor cerebellum; lobules VI and VII of the posterior lobe comprise the cognitive cerebellum; and the posterior vermis is the anatomical substrate of the limbic cerebellum. Here we analyze anatomical, functional neuroimaging, and clinical data to test this hypothesis. We find converging lines of evidence supporting regional organization of motor, cognitive, and limbic behaviors in the cerebellum. The cerebellar motor syndrome results when lesions involve the anterior lobe and parts of lobule VI, interrupting cerebellar communication with cerebral and spinal motor systems. Cognitive impairments occur when posterior lobe lesions affect lobules VI and VII (including Crus I, Crus II, and lobule VIIB), disrupting cerebellar modulation of cognitive loops with cerebral association cortices. Neuropsychiatric disorders manifest when vermis lesions deprive cerebro-cerebellar-limbic loops of cerebellar input. We consider this functional topography to be a consequence of the differential arrangement of connections of the cerebellum with the spinal cord, brainstem, and cerebral hemispheres, reflecting cerebellar incorporation into the distributed neural circuits subserving movement, cognition, and emotion. These observations provide testable hypotheses for future investigations.
A central principle for understanding the cerebral cortex is that macroscale anatomy reflects a functional hierarchy from primary to transmodal processing. In contrast, the central axis of motor and ...nonmotor macroscale organization in the cerebellum remains unknown. Here we applied diffusion map embedding to resting-state data from the Human Connectome Project dataset (n = 1003), and show for the first time that cerebellar functional regions follow a gradual organization which progresses from primary (motor) to transmodal (DMN, task-unfocused) regions. A secondary axis extends from task-unfocused to task-focused processing. Further, these two principal gradients revealed novel functional properties of the well-established cerebellar double motor representation (lobules I-VI and VIII), and its relationship with the recently described triple nonmotor representation (lobules VI/Crus I, Crus II/VIIB, IX/X). Functional differences exist not only between the two motor but also between the three nonmotor representations, and second motor representation might share functional similarities with third nonmotor representation.
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