Disorders of the cerebellum: ataxia, dysmetria of thought, and the cerebellar cognitive affective syndrome
01 Aug 2004-Journal of Neuropsychiatry and Clinical Neurosciences (American Psychiatric Publishing)-Vol. 16, Iss: 3, pp 367-378
TL;DR: The cerebellar cognitive affective syndrome (CCAS) includes impairments in executive, visual-spatial, and linguistic abilities, with affective disturbance ranging from emotional blunting and depression, to disinhibition and psychotic features.
Abstract: Many diseases involve the cerebellum and produce ataxia, which is characterized by incoordination of balance, gait, extremity and eye movements, and dysarthria. Cerebellar lesions do not always manifest with ataxic motor syndromes, however. The cerebellar cognitive affective syndrome (CCAS) includes impairments in executive, visual-spatial, and linguistic abilities, with affective disturbance ranging from emotional blunting and depression, to disinhibition and psychotic features. The cognitive and psychiatric components of the CCAS, together with the ataxic motor disability of cerebellar disorders, are conceptualized within the dysmetria of thought hypothesis. This concept holds that a universal cerebellar transform facilitates automatic modulation of behavior around a homeostatic baseline, and the behavior being modulated is determined by the specificity of anatomic subcircuits, or loops, within the cerebrocerebellar system. Damage to the cerebellar component of the distributed neural circuit subserving sensorimotor, cognitive, and emotional processing disrupts the universal cerebellar transform, leading to the universal cerebellar impairment affecting the lesioned domain. The universal cerebellar impairment manifests as ataxia when the sensorimotor cerebellum is involved and as the CCAS when pathology is in the lateral hemisphere of the posterior cerebellum (involved in cognitive processing) or in the vermis (limbic cerebellum). Cognitive and emotional disorders may accompany cerebellar diseases or be their principal clinical presentation, and this has significance for the diagnosis and management of patients with cerebellar dysfunction.
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TL;DR: The thesis of this Review is that the encephalopathy of prematurity is a complex amalgam of primary destructive disease and secondary maturational and trophic disturbances.
Abstract: Brain injury in premature infants is of enormous public health importance because of the large number of such infants who survive with serious neurodevelopmental disability, including major cognitive deficits and motor disability. This type of brain injury is generally thought to consist primarily of periventricular leukomalacia (PVL), a distinctive form of cerebral white matter injury. Important new work shows that PVL is frequently accompanied by neuronal/axonal disease, affecting the cerebral white matter, thalamus, basal ganglia, cerebral cortex, brain stem, and cerebellum. This constellation of PVL and neuronal/axonal disease is sufficiently distinctive to be termed "encephalopathy of prematurity". The thesis of this Review is that the encephalopathy of prematurity is a complex amalgam of primary destructive disease and secondary maturational and trophic disturbances. This Review integrates the fascinating confluence of new insights into both brain injury and brain development during the human premature period.
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TL;DR: An activation likelihood estimate (ALE) meta-analysis of neuroimaging studies reporting cerebellar activation in selected task categories provided support for an anterior sensorimotor vs. posterior cognitive/emotional dichotomy in the human cerebellum.
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TL;DR: The results suggest that participation in MBSR is associated with changes in gray matter concentration in brain regions involved in learning and memory processes, emotion regulation, self-referential processing, and perspective taking.
Abstract: article i nfo Therapeutic interventions that incorporate training in mindfulness meditation have become increasingly popular, but to date little is known about neural mechanisms associated with these interventions. Mindfulness-Based Stress Reduction (MBSR), one of the most widely used mindfulness training programs, has been reported to produce positive effects on psychological well-being and to ameliorate symptoms of a number of disorders. Here, we report a controlled longitudinal study to investigate pre-post changes in brain gray matter concentration attributable to participation in an MBSR program. Anatomical magnetic resonance (MR) images from 16 healthy, meditation-naive participants were obtained before and after they underwent the 8-week program. Changes in gray matter concentration were investigated using voxel-based morphometry, and compared with a waiting list control group of 17 individuals. Analyses in a priori regions of interest confirmed increases in gray matter concentration within the left hippocampus. Whole brain analyses identified increases in the posterior cingulate cortex, the temporo-parietal junction, and the cerebellum in the MBSR group compared with the controls. The results suggest that participation in MBSR is associated with changes in gray matter concentration in brain regions involved in learning and memory processes, emotion regulation, self-referential processing, and perspective taking.
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TL;DR: Neuroimaging and neuropsychological data supply compelling support for the view that a closed-loop circuit represents the major architectural unit of cerebro-cerebellar interactions and provides the cerebellum with the anatomical substrate to influence the control of movement and cognition.
Abstract: Does the cerebellum influence nonmotor behavior? Recent anatomical studies demonstrate that the output of the cerebellum targets multiple nonmotor areas in the prefrontal and posterior parietal cortex, as well as the cortical motor areas. The projections to different cortical areas originate from distinct output channels within the cerebellar nuclei. The cerebral cortical area that is the main target of each output channel is a major source of input to the channel. Thus, a closed-loop circuit represents the major architectural unit of cerebro-cerebellar interactions. The outputs of these loops provide the cerebellum with the anatomical substrate to influence the control of movement and cognition. Neuroimaging and neuropsychological data supply compelling support for this view. The range of tasks associated with cerebellar activation is remarkable and includes tasks designed to assess attention, executive control, language, working memory, learning, pain, emotion, and addiction. These data, along with the revelations about cerebro-cerebellar circuitry, provide a new framework for exploring the contribution of the cerebellum to diverse aspects of behavior.
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TL;DR: Functional topography is considered 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.
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Cites background from "Disorders of the cerebellum: ataxia..."
...V) and lobule VIII are predominantly sensorimotor, whereas lobules VI and VII (including Crus I and II and lobule VIIB) contribute to higher-level processes (Schmahmann, 1991, 1996, 2004, 2009)....
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References
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TL;DR: The results suggest that, in normal individuals, nonconscious biases guide behavior before conscious knowledge does, and without the help of such biases, overt knowledge may be insufficient to ensure advantageous behavior.
Abstract: Deciding advantageously in a complex situation is thought to require overt reasoning on declarative knowledge, namely, on facts pertaining to premises, options for action, and outcomes of actions that embody the pertinent previous experience. An alternative possibility was investigated: that overt reasoning is preceded by a nonconscious biasing step that uses neural systems other than those that support declarative knowledge. Normal participants and patients with prefrontal damage and decision-making defects performed a gambling task in which behavioral, psychophysiological, and self-account measures were obtained in parallel. Normals began to choose advantageously before they realized which strategy worked best, whereas prefrontal patients continued to choose disadvantageously even after they knew the correct strategy. Moreover, normals began to generate anticipatory skin conductance responses (SCRs) whenever they pondered a choice that turned out to be risky, before they knew explicitly that it was a risky choice, whereas patients never developed anticipatory SCRs, although some eventually realized which choices were risky. The results suggest that, in normal individuals, nonconscious biases guide behavior before conscious knowledge does. Without the help of such biases, overt knowledge may be insufficient to ensure advantageous behavior.
3,265 citations
TL;DR: A constellation of deficits is suggestive of disruption of the Cerebellar modulation of neural circuits that link prefrontal, posterior parietal, superior temporal and limbic cortices with the cerebellum, called the 'cerebellar cognitive affective syndrome'.
Abstract: Anatomical, physiological and functional neuroimaging studies suggest that the cerebellum participates in the organization of higher order function, but there are very few descriptions of clinically relevant cases that address this possibility. We performed neurological examinations, bedside mental state tests, neuropsychological studies and anatomical neuroimaging on 20 patients with diseases confined to the cerebellum, and evaluated the nature and severity of the changes in neurological and mental function. Behavioural changes were clinically prominent in patients with lesions involving the posterior lobe of the cerebellum and the vermis, and in some cases they were the most noticeable aspects of the presentation. These changes were characterized by: impairment of executive functions such as planning, set-shifting, verbal fluency, abstract reasoning and working memory; difficulties with spatial cognition including visual-spatial organization and memory; personality change with blunting of affect or disinhibited and inappropriate behaviour; and language deficits including agrammatism and dysprosodia. Lesions of the anterior lobe of the cerebellum produced only minor changes in executive and visual-spatial functions. We have called this newly defined clinical entity the 'cerebellar cognitive affective syndrome'. The constellation of deficits is suggestive of disruption of the cerebellar modulation of neural circuits that link prefrontal, posterior parietal, superior temporal and limbic cortices with the cerebellum.
2,640 citations
TL;DR: Retrograde transneuronal transport of herpes simplex virus type 1 was used to identify subcortical neurons that project via the thalamus to area 46 of the primate prefrontal cortex, defining an anatomical substrate for the involvement of basal ganglia and cerebellar output in higher cognitive function.
Abstract: The possibility that neurons in the basal ganglia and cerebellum innervate areas of the cerebral cortex that are involved in cognitive function has been a controversial subject. Here, retrograde transneuronal transport of herpes simplex virus type 1 (HSV1) was used to identify subcortical neurons that project via the thalamus to area 46 of the primate prefrontal cortex. This cortical area is known to be involved in spatial working memory. Many neurons in restricted regions of the dentate nucleus of the cerebellum and in the internal segment of the globus pallidus were labeled by transneuronal transport of virus from area 46. The location of these neurons was different from those labeled after HSV1 transport from motor areas of the cerebral cortex. These observations define an anatomical substrate for the involvement of basal ganglia and cerebellar output in higher cognitive function.
1,273 citations
TL;DR: 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.
1,002 citations
TL;DR: The adaptive role of the cerebellar cortex would appear to be specialized for combining simpler elements of movement into more complex synergies, and also in enabling simple, stereotyped reflex apparatus to respond differently, specifically, and appropriately under different task conditions.
Abstract: Based on a review of cerebellar anatomy, neural discharge in relation to behavior, and focal ablation syndromes, we propose a model of cerebellar function that we believe is both comprehensive as to the available information (at these levels) and unique in several respects. The unique features are the inclusion of new information on (a) cerebellar output--its replicative representation of body maps in each of the deep nuclei, each coding a different type and context of movement, and each appearing to control movement of multiple body parts more than of single body parts; and (b) the newly assessed long length of the parallel fiber. The parallel fiber, by virtue of its connection through Purkinje cells to the deep nuclei, appears optimally designed to combine the actions at several joints and to link the modes of adjacent nuclei into more complex coordinated acts. We review the old question of whether the cerebellum is responsible for the coordination of body parts as opposed to the tuning of downstream executive centers, and conclude that it is both, through mechanisms that have been described in the cerebellar cortex. We argue that such a mechanism would require an adaptive capacity, and support the evidence and interpretation that it has one. We point out that many parts of the motor system may be involved in different types of motor learning for different purposes, and that the presence of the many does not exclude an existence of the one in the cerebellar cortex. The adaptive role of the cerebellar cortex would appear to be specialized for combining simpler elements of movement into more complex synergies, and also in enabling simple, stereotyped reflex apparatus to respond differently, specifically, and appropriately under different task conditions. Speed of learning and magnitude of memory for both novel synergies and task-specific performance modifications are other attributes of the cerebellar cortex.
1,001 citations