Handbook of the Cerebellum and Cerebellar Disorders

Preface to the Second Edition
Preface to the First Edition
Contents
About the Editors
Contributors
Part I: Cerebellar Development
1 Specification of the Cerebellar Territory
Introduction
Delineating the Cerebellar Primordium
Fate Maps of the Cerebellum
Rotation of the Cerebellar Primordium
Specification of the Cerebellar Primordium
The Midbrain-Hindbrain (MHB) Domain
Organizing Properties of the Isthmic Neuroepithelium - Fgf8
The MHB Organizer: A Molecular Network Set up at the Otx2-Gbx2 Boundary
The Otx2-Gbx2 Boundary: A Stable or Drifting Limit?
Genes Regulating the Competence of the Neuroepithelium to Develop a MHB Identity
Genes Regulating Distinct Neuroepithelium Competences on Either Sides of the MHB Boundary
Subdivisions of the Cerebellar Plate
Anteroposterior Subdivisions of the Cerebellar Plate
Dorsoventral Subdivisions of the Cerebellar Plate
Conclusions and Future Directions
References
2 Proneural Genes and Cerebellar Neurogenesis in the Ventricular Zone and Upper Rhombic Lip
Introduction
Proneural Genes in Drosophila melanogaster Development
The Roles of Proneural Genes in Vertebrate Neurogenesis
Atoh1: The Master Gene in Granule Cell Development
Atoh1 Plays a Key Role in Granule Cell Clonal Expansion
Other Glutamatergic Neurons Derive from Atoh1+ Progenitors
Late Atoh1+ Progenitors in the URL Give Rise to Unipolar Brush Cells
NeuroD: A ``Nearly Proneural´´ Gene with Key Roles in Cerebellar Development
Ascl1 in Ventricular Zone Neurogenesis
Ptf1a Is a Master Gene of Cerebellar GABAergic Neurogenesis
Ascl1 Labels the Cerebellar GABAergic Lineage
Neurogenins in Cerebellar GABAergic Development
Neurog1 and Neurog2 Are Expressed in the Ptf1a+ Ventricular Neuroepithelium
Neurog1 Is Expressed in Cerebellar GABAergic Interneuron Progenitors
Neurog2 Labels the PC Lineage and Regulates PC-Progenitor Cell-Cycle Progression and Dendritogenesis
Conclusion
References
3 Zones and Stripes: Development of Cerebellar Topography
The Architecture of the Adult Cerebellar Cortex
From Allocation to Rhombomere 1 to Two Germinal Epithelia
Purkinje Cell Birth Date, Phenotype, and Location
From Ventricular Zone to Clusters
Purkinje Cell Subtype Specification
From Embryonic Clusters to Adult Stripes
Afferent Topography
Climbing Fibers
Mossy Fibers
Interneurons
Cerebellar Topography and Circuit Function
From Zones-And-Stripes to Complex Motor Behaviors
Conclusions
References
4 Roof Plate in Cerebellar Neurogenesis
Introduction
Cellular and Molecular Mechanisms Regulating Development of the 4th Ventricle Roof Plate and Choroid Plexus Epithelium
The Role of the Roof Plate and Choroid Plexus in the Development of the Cerebellar Rhombic Lip
Roof Plate-Derived Bmp Signaling as Regulator of Rhombic Lip Development
Other Roof Plate-Derived Secreted Molecules as Regulators of Rhombic Lip Development
The Role of Roof Plate and Choroid Plexus Signaling in Development of the Cerebellar Ventricular Zone and Its Progeny
Roof Plate-Dependent Bmp and Wnt Signals as Regulators of Proliferation of the Cerebellar Ventricular Zone
Shh Signals from the Hindbrain Choroid Plexus Regulate Proliferation of Progenitors in the Late Embryonic Ventricular Zone
Contribution of Bmp Signaling to Migration of Purkinje Cells
Conclusions and Future Directions
Cross-References
References
5 Specification of Cerebellar and Precerebellar Neurons
Specification of Cerebellar Neurons
Specification of Precerebellar Neurons
Conclusions and Future Directions
Cross-References
References
6 Specification of Granule Cells and Purkinje Cells
Introduction
Territorial Allocation
Dorsoventral ``Compartments´´ and the Origin of Cell Types
Temporal Patterning and Lineage in the Rhombic Lip
Secondary Proliferation and Neurogenesis
Diversity of Granule and Purkinje Cells
An Evolutionary Perspective on Neurogenesis
Conclusions
References
7 Gliogenesis
Introduction
Origin and Differentiation of Cerebellar Astrocytes
The Phenotypic Heterogeneity of Cerebellar Astrocytes
Origin of Cerebellar Astrocytes
Lineage Relationship Between Cerebellar Astrocytes and Neurons
Postnatal Amplification of Intermediate Astrocyte Precursors
Differentiation of Cerebellar Astrocytes
Maturation of Morphological Features
Maturation of Molecular Profiles
Origin and Differentiation of Cerebellar Oligodendrocytes
Origin of Cerebellar Oligodendrocytes
Differentiation of Cerebellar Oligodendrocytes
Conclusions and Future Directions
References
8 Granule Cell Migration and Differentiation
Introduction
Granule Cells Exhibit Different Mode, Speed, and Direction of Migration at Different Cortical Layers
Mechanisms Involved in Granule Cell Migration
Control of Granule Cell Migration by Intrinsic Programs
Phase I (PI, a Period of 0-20 h In Vitro)
Phase II (PII, a Period of 20-40 h In Vitro)
Phase III (PIII, a Period of 40-60 h In Vitro)
Time-Dependent Changes in Granule Cell Migration and Morphology by Intrinsic Programs
Possible Roles of Intrinsic Programs on the Regulation of Granule Cell Migration In Vivo
Glutamate Accelerates Granule Cell Migration Through the Activation of NMDA Receptors
Reciprocal Regulation of Granule Cell Migration in the EGL and the IGL by Somatostatin
Halt of Granule Cell Migration in the PCL by PACAP
Ca2+ Spikes Control Granule Cell Migration and Its Termination
EGL
ML
PCL
IGL
Cyclic Nucleotide Signaling Plays a Role in the Control of Granule Cell Migration
Exposure to Alcohol, Methyl Mercury, and Light Alters Granule Cell Migration
Alcohol Adversely Affects Granule Cell Migration
Impairment of Granule Cell Migration by Methylmercury
Light Stimulus Controls Granule Cell Migration via Altering Insulin-Like Growth Factor 1 Signaling
Control of Granule Cell Differentiation
Conclusions and Future Directions
Cross-References
References
9 Purkinje Cell Migration and Differentiation
Introduction
The Generation of Purkinje Cells in the Ventricular Neuroepithelium
Migration of Purkinje Cells
Migration Toward the Cerebellar Cortex and Formation of the Purkinje Cell Plate
Formation of the Purkinje Cell Monolayer
Development of the Purkinje Axon
Development of the Corticofugal Purkinje Axon
Development of the Intracortical Plexus of the Purkinje Axon
Intrinsic Mechanisms and Environmental Control of Purkinje Axon Development
Development of the Purkinje Dendritic Tree
Sequential Phases of Dendritic Differentiation
Intrinsic Determinants Regulate the First Phase of Purkinje Cell Dendritogenesis
Role of ROR-Alpha in the Formation of Purkinje Cell Dendrites
Extrinsic and Intrinsic Factors That Control the Late Phase of Purkinje Dendritic Growth
Role of Parallel Fibers in the Monoplanar Disposition and Branching Pattern of Purkinje Cell Dendrites: Comparison of Control ...
Purkinje Cells as the Organizers of the Architecture and Projectional Arrangement of the Cerebellum
Failure in the Differentiation of Purkinje Cells Leads to the Apparent Disappearance of the Cerebellum
Purkinje Cells Stimulate Granule Cell Neurogenesis
Modular Organization of the Input/Output Projections in the Cerebellum: The Olivocerebellar System
Adult Cerebellum: Purkinje Cell Biochemical Heterogeneity, Parasagittal Stripes of Protein Expression
One Congruent Map or Several Independent Maps?
Organization of the Cerebellar Cortical Layering; Transient Biochemical Heterogeneity of Purkinje Cells and Inferior Olivary N...
Organization of the Three-Dimensional Architecture of the Projectional Maps; Validation of the ``Matching Hypothesis´´ with th...
Conclusions
References
10 Development of Cerebellar Nuclei
Introduction
Overview of Cerebellar Development
Patterning and Morphogenesis
Cerebellar Neuron Subtypes Are Produced Sequentially
Development of the Cerebellar Nuclei in Mammals
Cerebellar Morphogenesis Leading to the Formation of CN
Formation of Deep Cerebellar Neurons: Differentiation, Cellular Migration, and Transcription Factor Expression
Differentiation and Migration of CN GABAergic Neurons
Differentiation and Migration of CN Glutamatergic Neurons
Anatomical and Molecular Classifications of CN Neurons
Efferent Projections: Molecular Determinants for Axonal Guidance
Development of Human Cerebellar Nuclei
Cerebellar Nuclei Abnormalities
Cerebellar Nuclei Defects: Mouse Mutant Phenotypes
Cerebellar Nuclei Defects: Insights from Human Malformations
Joubert Syndrome
Rhombencephalosynapsis
Thanatophoric Dysplasia
Pontocerebellar Hypoplasia
Autism
Conclusions and Future Directions
References
11 Specification and Development of GABAergic Interneurons
Introduction
Cerebellar Inhibitory Interneurons: A Surprisingly Diverse Ensemble
Origins of Cerebellar GABAergic Interneurons
Ptf1a And the Delineation of Cerebellar GABAergic Interneurons
The Deep Cerebellar Mass/Nascent White Matter of the Cerebellar Anlage: An Instructive Environment?
Terminal Differentiation and Synaptic Integration of Postmigratory Precursors of GABAergic Interneurons
Maturation of GABAergic Interneurons Resident in the Molecular Layer
Inhibitory Interneurons of the Granule Cell Layer
Differentiation of Subsets of Golgi Cells and of Non-Golgi GABAergic Interneurons of the Granule Cell Layer
Concluding Remarks
Cross-References
References
12 Development of Glutamatergic and GABAergic Synapses
Introduction
The Mossy Fibers and the Glomeruli
Parallel Fibers
Climbing Fibers
Molecular Specificity of PF and CF Synapses and Heterosynaptic Competition
GABAergic Interneurons of the Molecular Layer: Stellate and Basket Cells
Golgi Cells
Other Inhibitory Interneurons
The Axon Collaterals of Purkinje Cells
Deep Cerebellar Nuclei
Conclusions
Cross-References
References
13 Synaptic Remodeling and Neosynaptogenesis
Introduction
Climbing Fiber-Purkinje Cell Synaptogenesis
Initial Interactions Between Climbing Fibers and Purkinje Cells
Somatodendritic Translocation of Climbing Fiber Terminals
Selective Synapse Elimination Is Based on Homosynaptic Competition
Selective Synapse Elimination Requires Heterosynaptic Competition
Purkinje Cell Function Within the Synaptic Network Regulates Climbing Fiber Refinement
Remaining Questions
Differential Effects of Climbing Fiber and Purkinje Cell Maturation on Selective Axon-Target Interactions
Reinnervation of Purkinje Cells After Mechanical Lesion in the Early Postnatal Period
Climbing Fiber Reinnervation of Mature Purkinje Cells
Post-lesion Reinnervation of Maturing Purkinje Cells: Similarities and Differences from Neonatal Reinnervation
Purkinje Cell Reinnervation After Partial Olivary Lesion by 3-Aminopyridine (3-AP)
Differential Maturation of Synaptic Partners Alter Climbing Fiber - Purkinje Cell Interactions
Mature Climbing Fibers Multi-innervate Immature Purkinje Cells
Prior Purkinje Cell Synaptogenesis Determines the Capacity for Neosynaptogenesis
A Critical Period for Synapse Elimination?
Conclusions
References
14 Synaptogenesis and Synapse Elimination
Introduction
Climbing Fiber Synaptogenesis on Immature Purkinje Cells
Functional Differentiation and Selective Strengthening of Single Climbing Fiber Inputs
Dendritic Translocation of Single Climbing Fibers
Early Phase of Climbing Fiber Synapse Elimination
Late Phase of Climbing Fiber Synapse Elimination
Heterosynaptic and Homosynaptic Competition in Purkinje Cell Synaptic Wiring
Conclusions and Future Directions
References
15 Genes and Cell Type Specification in Cerebellar Development
Introduction
Cerebellar Structure and Early Development
Cerebellar Germinal Zones and Lineage Specification
Ventricular Zone and Cell Type Specification Within GABAergic Lineages
Rhombic Lip and Cell Type Specification Within Glutamatergic Lineages
Cerebellar Glial Cells
Bioinformatic Strategies to Identify Novel Genes in the Specification of Cells During Cerebellar Development
Cerebellar Gene Regulation in Time and Space (CbGRiTS)
The FANTOM5 Consortium
Conclusion and Looking Forward
References
16 Hormones and Cerebellar Development
Introduction
Thyroid Hormone and Cerebellar Development
Molecular Mechanisms of Thyroid Hormone Action
The Effect of Thyroid Hormone on the Developing Cerebellum
Animal Models to Study Thyroid Hormone Action in the Developing Cerebellum
Steroid Hormones and Cerebellar Development
General Overview
Adrenal Steroid Hormones and Cerebellar Development
Gonadal Hormones and Cerebellar Development
Conclusions and Future Directions
Cross-References
References
17 Development of Physiological Activity in the Cerebellum
Introduction
Neuronal Development
Cerebellar Physiology
Early Influences of Adult Firing Patterns
What Influences Physiological State of Developing Purkinje Cells?
Ion Channels
Sodium Channels
Potassium Channels
Calcium Channels
Ion Channels Summary
Other Regulators of Physiological Activity During Development
Calcium Buffers
Synapses
Other Influences of Normal Developmental Physiology
Development Gone Awry: Disease States
Autism Spectrum Disorders
Ataxia
Early-Onset Ataxias
Altered Cerebellar Development in Late-Onset Ataxias?
Conclusions and Future Directions
Cross-References
References
18 Epigenetic Regulation of the Cerebellum
A Brief Introduction to Epigenetic Mechanisms
Genome-Wide Changes in the Epigenetic Landscape in the Developing Cerebellum
Families of Epigenetic Regulators in Mouse Cerebellar Development
ATP-Dependent Chromatin Remodeling Enzymes
Histone Tail Modifiers
DNA Methylation
Perspectives on Epigenetic Regulators in the Mouse Cerebellum
Epigenetic Control of Cerebellar-Dependent Behavior
Epigenetics in Human Disease
Conclusions and Future Directions
References
19 Analysis of Gene Networks in Cerebellar Development
Introduction
Transcription Factor Targetomes
En2 (Engrailed-2)
Atoh1 (Math1)
Rora (RORα)
Physiological and Metabolic Control of Development
Cell Type Specific Genes and Gene Networks
Conclusions and Future Directions
References
Part II: Anatomy, Connections, and Neuroimaging of the Cerebellum
20 Vascular Supply and Territories of the Cerebellum
Overview
Posterior Inferior Cerebellar Arteries (PICAs)
Anterior Inferior Cerebellar Arteries (AICAs)
Superior Cerebellar Arteries (SCAs)
References
21 Vestibulocerebellar Functional Connections
Introduction
Vestibular Primary Afferent Fibers Project to Vestibular Nuclei and Vermal Lobules IX-Lobule X
Vestibular Secondary Mossy Fiber Afferents Terminate Bilaterally in the Cerebellum
Vestibular Climbing Fibers Project to Vermal Lobules IX-X
Purkinje Neurons Generate Two Different Action Potentials
Vestibular Stimulation Modulates the Discharge of CSs and SSs Antiphasically
CSs and SSs Are Aligned in Sagittal Zones in Vermal Lobules IX-X
Granule Cells and Unipolar Brush Cells (UBCs) Discharge in Phase with Mossy and Climbing Fibers
Stellate and Golgi Cells Are Oppositely Modulated by Vestibular Stimulation
A Unilateral Microlesion of β-Nucleus Reduces Vestibular Modulation of Contralateral CSs and SSs
Microlesions of ß-Nucleus Reduce the Modulated Discharge of Contralateral Stellate and Golgi Cells
A Unilateral Labyrinthectomy (UL) Blocks Vestibular Primary Afferent Input to Ipsilateral Vermal Lobules IX-X, but Leaves Inta...
Vestibularly Modulated Discharge of Stellate and Golgi Cells Is Reduced by a Contralateral UL
Functions of Climbing and Mossy Fiber Circuitry
Three Distinct Climbing Fiber-Evoked Pauses in the Discharge of SSs
Cerebellar Functions
Abnormal Cerebellar Function
Conclusions and Future Directions
References
22 Cerebellar Nuclei and the Inferior Olivary Nuclei: Organization and Connections
Introduction
The Cerebellar Nuclei
Subdivision of the Inferior Olive
Afferent Connections of the Inferior Olive
Projections from Spinal Cord, Trigeminal Nuclei, and Dorsal Column Nuclei
Ventral Spino-Olivary Pathways
Projections from the Sensory Nuclei of the Trigeminal Nerve
Projections from the Dorsal Column Nuclei
Optokinetic and Vestibular Projections to the Inferior Olive
Afferents from Tectum and Pretectum
Nuclei at the Mesodiencephalic Border: The Central and Medial Tegmental Tracts
The Corticonuclear and Olivocerebellar Projections
The Corticonuclear Projection
The Olivocerebellar Projection
The Nucleo-Olivary Pathway
Olivocerebellar and Corticonuclear Projections in Primates
The Cerebellar Nuclei: Efferent Connections and Recurrent Climbing Fiber Paths
The Fastigial Nucleus
Anterior Interposed Nucleus
Posterior Interposed Nucleus and Interstitial Cell Groups
Dentate Nucleus
Cross-References
References
23 Axonal Trajectories of Single Climbing and Mossy Fiber Neurons in the Cerebellar Cortex and Nucleus
Introduction
Axonal Trajectories of Single Olivocerebellar Axons
Distribution of CFs
Thin Collaterals of OC Axons
Relationship Between the Longitudinal Distribution of CFs of Single OC Axons and Aldolase C Bands in the Cx
Compartmentation of the CN and Its Relationship to the Cortical Compartments
Morphology of Single Mossy Fibers
Lateral Reticular Nucleus Neurons
General Features of Axonal Trajectories of Single LRN Neurons
Distribution of Terminals of Single LRN Axons in the Cx
Morphology of Collaterals Terminating in the Cerebellar and Vestibular Nuclei
Dorsal Column Nucleus Neurons
Pontine Nucleus Neurons
Spinal Cord Neurons
General Features of Axonal Projection Patterns of Single CF and MF Neurons
Functional considerations: Conclusions
Cross-References
References
24 Visual Circuits from Cerebral Cortex to Cerebellum; The Link Through Pons
Which Cells in the Cerebral Cortex Have an Axon that Projects to the Pons?
Which Areas of Cortex Project to the Pons?
What Is the Pathway of the Cortical Projection to the Pons?
Where Do Corticopontine and Collicular Fibers Terminate in the Pons?
Demagnification
Fibers from the Cerebral Cortex and Colliculus Give off Collaterals
What Are the Receptive Field Properties of Pontine Visual Cells?
Where and how Do the Axons of Pontine Cells Terminate on the Cerebellum?
Some Further Speculations on the Role of the Cortico-Ponto-Cerebellar System
Behavioral Evidence of the Function of the Corticopontine Link
Collateral Fibers and the Corollary Discharge
Receptive Fields and Visual Guidance; the Appearance of the Ground to a Walking Cat
Cerebellum and Kinesie Paradoxale
Cerebellar Localization and Current Problems
References
25 Cerebellar Connections with Limbic Circuits: Anatomy and Functional Implications
Introduction
Defining the Limbic System
Cerebellar Connections with the Limbic System
Cerebellar-Hypothalamic Circuits
Cerebellar Connections with Paralimbic and Neocortical Association Areas
Observations from Neuroimaging Studies
Functional Topography in the Cerebellum
Cerebellum and Pain Modulation
Autonomic Influences
Indirect Limbic Inputs
The Cerebellum Is Implicated in Autism Spectrum Disorders (ASD)
Implications of a Cerebellar Role in Emotional Processing
Therapeutic Implications
Conclusions and Future Directions
References
26 Cerebellar Influences on Descending Spinal Motor Systems
Introduction
The Cerebellar Nuclei
Medial and Lateral Descending Motor Systems from the Brainstem
Reticulospinal Tracts
Medial Cerebellar Nucleus
The Posterior Interposed Nucleus and the Interstitial Cell Groups
The Anterior Interposed Nucleus and the Dorsolateral Hump
The Lateral Cerebellar Nucleus
Vestibulospinal Tracts
Cerebellar Corticovestibular Projections
Cerebellar Nucleo-Vestibular Connections
Rubrospinal Tract
Cerebellar Projections to the Red Nucleus
Tectospinal Tract
Cerebellar Nucleo-Tectal Connections
Interstitiospinal Tract
Cerebellar Projections to the Interstitial Nucleus of Cajal
Cerebellar Projections to Other Areas
Divergence of Cerebellar Projections
Convergence of Cerebellar Projections
Functional Implications
Clinical Implications
Hypotonia
Ataxia
Intention Tremor
Conclusions and Future Directions
Cross-References
References
27 Cerebellar Thalamic and Thalamocortical Projections
Introduction
Cyto- and Chemoarchitecture of the Motor Thalamus
Afferents of the Motor Thalamus
Motor Thalamic Projections to Cortex
Projections to MI
Projections to SMA and Pre-SMA
Projections to the Premotor Cortex
Projections to Other Cortical Areas
General Topography of Projections
Conclusions and Future Directions
References
28 Cerebellar Outputs in Non-human Primates: An Anatomical Perspective Using Transsynaptic Tracers
Introduction
Cerebellar Output Channels
Macro-Architecture of Cerebro-Cerebellar Loops
The Cerebellum Is Interconnected with the Basal Ganglia
Summary and Conclusions
References
29 Delineation of Cerebrocerebellar Networks with MRI Measures of Functional and Structural Connectivity
Introduction
Functional Connectivity
ROI-Based fcMRI of the Dentate Nucleus
ROI-Based fcMRI of the Cerebellar Cortex
ROI-Based fcMRI of the Cerebral Cortex
ICA fcMRI
Tractography
Conclusions and Future Directions
References
30 Radiographic Features of Cerebellar Disease: Imaging Approach to Differential Diagnosis
Introduction
Congenital
Cerebellar Agenesis, Hypoplasia, and Atrophy
Cerebellar Dysplasia and Malformations of Cortical Development
Congenital Posterior Fossa Cysts and Related Disorders (Poretti et al. 2016a)
Acquired
Cerebrovascular
Ischemic Changes
Hemorrhage
Vascular Pathologies
Traumatic
Infectious
Genetic
Autoimmune
Neurodegenerative
Neoplastic
Toxic and Miscelaneous Disorders
Conclusions
References
31 Imaging Vascular Anatomy and Pathology of the Posterior Fossa
Introduction
Vascular Anatomical Overview
Ischemic Diseases of the Posterior Fossa
Brainstem Ischemic Syndromes
Medullary Ischemic Syndromes
Pontine Ischemic Syndromes
Midbrain Ischemic Syndromes
Basilar Artery Occlusion
Cerebellar Ischemic Syndromes
Posterior Inferior Cerebellar Artery Infarction
Anterior Inferior Cerebellar Artery Infarction
Superior Cerebellar Artery Infarction
Hemorrhagic Diseases of the Posterior Fossa
Aneurysmal Disease
Saccular Aneurysms
Fusiform Aneurysms
Distal Cerebellar Aneurysms
High-Flow Vascular Malformations
Pial Arteriovenous Malformations
Dural Arteriovenous Fistulas
Imaging Approach for Posterior Fossa Neurovascular Disease
Conclusion and Future Directions
References
32 MR Spectroscopy in Health and Disease
Introduction
Neurochemicals Detectable by 1H MRS
Technical Challenges of MR Spectroscopy in the Cerebellum
Neurochemical Profile of the Cerebellum
MRS of the Cerebellum in Neurodegenerative Diseases
MRS of the Cerebellum in Cancer
MRS of the Cerebellum in Metabolic Disorders
Other Applications of MRS of the Cerebellum
Conclusions and Future Directions
References
33 Functional Topography of the Human Cerebellum Revealed by Functional Neuroimaging Studies
Introduction
Functional Connectivity Data Reveal Different Functional ``Zones´´ in the Cerebellum
Activation During Sensorimotor Tasks
Fractured Somatotopy: Cerebellar Activation During Simple Sensorimotor Tasks
Eye Movements
Complex Sensorimotor Tasks: Motor Learning, Tool Use
Cerebellar Activation During Cognitive Tasks
Language and Reading
Spatial Processing
Executive Function Tasks, Including Working Memory
Social/Emotional/Affective Processing
Cross-domain Relative Topography
Meta-analyses of Neuroimaging Literature
Multidomain Imaging Studies
Within-Task Topography
Multiple Representations of Motor, Cognitive, and Affective Function in the Cerebellar Cortex
Conclusions and Future Directions
References
Part III: Neurotransmission, Neuromodulation, and Physiology
34 Cerebellar Granule Cell
Introduction
Granule Cell Ontogenesis and Connectivity
Granule Cell Neurobiology: Receptors and Transduction Pathways
Intrinsic Electroresponsiveness
Fast Synaptic Transmission at Glomerular Synapses
Long-Term Synaptic Plasticity
Granule Cell Activity In Vivo
Granule Cell Models
New Views on the Granule Cell Function: Transformations of Signals in Time, Frequency, and Space
Pathologies of the Granule Cells
Conclusions and Future Directions
References
35 Purkinje Neurons: Synaptic Plasticy
Introduction
PF-LTD
Involvement of Intracellular Ca2+ Increase
Decrease of Functional Postsynaptic AMPA Receptor Number at PF-PC Synapses
Kinase and Phosphatase Signaling Pathways
Role of Presynaptic Receptors at PF-PC Synapses
Transcription Factors, Protein Synthesis
PF-LTP
Additional Forms of PC Synaptic Plasticity
Conclusions and Future Directions
References
36 Stellate Cells: Synaptic Processing and Plasticity
Introduction
Physiological Properties of Molecular Layer Interneurons
Function of Molecular Layer Interneurons
Synaptic Plasticity of Molecular Layer Interneurons
Conclusions and Future Directions
Cross-References
References
37 Golgi Neurons
Introduction
Neurochemical and Morphological Diversity of Golgi Cells: Toward a Functional Classification
Golgi Cells and Lugaro Cells Represent Two Different Types of Neurons
Organization of the Golgi Cells´ Inhibitory Input onto Granule Cells
Golgi Cells Are a Neurochemically Heterogenous Group of Cells
Synaptic Inputs onto Golgi Cells
Excitatory Synaptic Inputs to Golgi Cells
Mossy Fiber Inputs
Granule Cell Inputs
Climbing Fibers Preferentially Target Lugaro Cells
Inhibitory Synaptic Inputs to Golgi Cells
Lugaro Cells Are Master Inhibitory Interneurons of the Cerebellar Cortex
Purkinje Cells Contact Lugaro, but Not Golgi Cells
In Vivo Studies
Golgi Cell Spontaneous Activity in Anesthetized Animals Is Characterized by Slow Irregular Firing
Golgi Cells Display a Complex Triphasic Response to Peripheral Stimulations
Golgi Cells Display Large Receptive Fields and Modulated Discharge Patterns during Motor Behavior
Golgi Cell Excitability and Granular Layer Dynamics: Gain Control and Oscillations
Role of the Cerebellum in Oscillatory Motor Control
Gap-Junctional Coupling of Firing Golgi Cells Generates Beta-Band Resonant Population Oscillations
Feedback Inhibition and Oscillations in Models of the Granule Cell Layer
Conclusions and Future Directions
References
38 Glutamate Receptor Auxiliary Subunits and Interacting Protein Partners in the Cerebellum
Introduction
Glutamate Receptors in Cerebellar Neurons and Glia
AMPARs and Plasticity in the Cerebellum
Glutamate Receptor Auxiliary and Interacting Protein Partners in the Cerebellum
Transmembrane AMPAR Regulatory Proteins: TARPs
Cornichon Homologues Interact with AMPARs
PICK1, GRIP, and ABP: Intracellular Protein Partners of AMPARs
N-Ethylmaleimide Sensitive Fusion Protein Interacts with GluA2
AMPAR Interaction with Synapse-Associated Scaffolding Proteins (SAPs)
The Cadherin-Catenin Cell-Adhesion Complex
Kainate Receptor Interacting Proteins in the Cerebellum
NETO2
KRIP6
Conclusions
References
39 GABA and Synaptic Transmission in the Cerebellum
Introduction
Purkinje Cells
Basket and Stellate Cells
Golgi Cells
Other Types of Neurons in the Cerebellar Cortex
GABAergic Neurons in the Cerebellar Nuclei
GABA Receptors in the Cerebellum
Regulation of Glutamatergic Synaptic Inputs to GABAergic Neurons
Regulation of GABAergic Synapses
Behavioral Abnormality Caused by Alteration of GABAergic Synaptic Transmission
GABA in Cerebellar Ataxia
Conclusion and Future Directions
Cross-References
References
40 Norepinephrine and Synaptic Transmission in the Cerebellum
Introduction
Anatomical Considerations
Physiology of NE in Cerebellum
Noradrenergic Receptors in Cerebellum
Cerebellar Dysfunction in Aging
Conclusions and Future Directions
References
41 Serotonin and Synaptic Transmission in the Cerebellum
Introduction
Serotonergic Fiber Innervation of the Cerebellum
Serotonergic Modulation in the Cerebellar Cortex
Serotonergic Modulation in the Deep Cerebellar Nuclei
Conclusions and Future Directions
References
42 Cannabinoids and Synaptic Transmission in the Cerebellum
Introduction
The Endocannabinoid System
Endocannabinoid Biosynthesis and Degradation
Targets of Endocannabinoids
CB1 Cannabinoid Receptors
Retrograde Endocannabinoid Signaling
Autocrine Signaling and Regulation of Neuronal Excitability
Endocannabinoid Release in Purkinje Cells
DSE and DSI: Global Endocannabinoid Signaling
Synaptically Evoked Suppression of Excitation (SSE): Local Endocannabinoid Signaling
Long-Term Depression (LTD)
Long-Term Potentiation (LTP)
Endocannabinoid Signaling in Cerebellar Circuitry
Parallel Fiber to Stellate Cell and Basket Cell Synapses
Parallel Fiber to Golgi Cell Synapses
The Spread of Endocannabinoids in the Cerebellar Cortex
Endocannabinoid Signaling and Information Flow Through the Cerebellar Cortex
The Endocannabinoid System and Cerebellar Function
Human Studies
Animal Models
Endocannabinoid Signaling in Other Cerebellar Circuits
Conclusion
References
43 Nitric Oxide and Synaptic Transmission in the Cerebellum
Introduction
The Sources of NO and cGMP
Nitric Oxide Synthases
Soluble Guanylyl Cyclases
Downstream cGMP Effectors
Ion Channels
Phosphodiesterases
cGMP-Dependent Protein Kinases
NO and Synaptic Transmission in the Cerebellum
Granule Cells as a Central Player in Cerebellar NO Signaling
Mossy Fiber-Granule Cell Synapses
Parallel Fiber (PF)-Purkinje Cell Synapses
Vesicle Recycling as a Target of NO/cGMP/cGK Signaling to Regulate Synaptic Transmission
Conclusions and Future Directions
Cross-References
References
44 Purinergic Signaling in the Cerebellum
Introduction
ATP (P2) Receptors
P2 Receptor Expression in the Cerebellum
Functional Effects of P2 Receptor Activation in the Cerebellum
Synaptic Actions of ATP
Role of ATP in Glial Signalling
Extracellular Metabolism of ATP
Adenosine Signalling in the Cerebellum
Adenosine (P1) Receptors in the Cerebellum
Adenosine Release
Does the Extracellular Adenosine Tone Arise from Extracellular ATP Metabolism?
Release of Adenosine in Cerebellar Cultures
Release of Adenosine in Cerebellar Slices
Molecular Layer Stimulation: Is Adenosine a Neurotransmitter?
Do Climbing Fibers Release ATP or Adenosine?
Breakdown and Uptake of Adenosine
Hypoxia and Ischemia
The Role of Purinergic Signalling in the Cerebellum and in Motor Control
Conclusions and Future Directions
Cross-References
References
45 Modulatory Role of Neuropeptides in the Cerebellum
Introduction
Corticotropin-Releasing Factor Family of Peptides
Distribution
CRF Receptors in the Cerebellum
Functional Roles of CRF in the Cerebellum
Ligand-Receptor Mismatch
Functional Role of UCN in the Cerebellum
Conclusions
References
46 Taurine in the Cerebellum
Introduction
Cellular Actions of Taurine
Effects of Taurine Neuronal Circuits
Taurine Induced Biochemical Alterations in the Brain
Taurine Enhances the Neuroendocrine Interaction Between the Brain and the Pancreas
Conclusion
References
47 Biological Actions of Neurosteroids in the Growth and Survival of Purkinje Cells During Cerebellar Development
Introduction
Discovery of the Purkinje Cell as a Major Site for Neurosteroidogenesis
Biosynthesis of Neurosteroids in the Purkinje Cell
Biological Actions of Progesterone, Allopregnanolone, and Estradiol Produced in the Purkinje Cell on the Growth and Survival o...
Mode of Action of Progesterone and Estradiol Produced on Purkinje Cell Growth During Cerebellar Development
Discovery of the Pineal Gland as a Major Site for Neurosteroidogenesis
Identification of Major Neurosteroids Produced in the Pineal Gland
Biological Action of Allopregnanolone Produced in the Pineal Gland in the Survival of Purkinje Cells During Cerebellar Develop...
Mode of Action of Pineal Allopregnanolone on Purkinje Cell Survival During Cerebellar Development
Conclusions
Cross-References
References
48 Inferior Olive: All Ins and Outs
Development of the Inferior Olive and Climbing Fibers
The Origin of Inferior Olivary Neurons
Migration of Inferior Olivary Neurons
Inferior Olivary Subdivisions and Cell Types
Climbing Fiber Outgrowth and Elimination
Ultrastructure of the Inferior Olivary Neuropil
Glomeruli and Gap Junctions
Inputs and Origin
Neurotransmitters and Receptors
Cell Physiology of Inferior Olivary Neurons
Subthreshold Oscillations and Spike Timing
Electrical Synapses in the Inferior Olive
Synaptic Modification of Oscillations and Coupling
Action Potential Waveforms
Models of the Olivary Neurons
Single-Cell Models
Network Models
Climbing Fiber Patterns and Behavioral Consequences
Spatiotemporal Patterns
Behavioral Consequences
Functional Models of the Olivocerebellar System
Marr-Albus-Ito Learning Models
Motor Timing Models
Pathology of Inferior Olive
Conclusions
References
49 Dynamics of the Inferior Olive Oscillator and Cerebellar Function
Introduction
Basic Features of the Inferior Olive
Excitable Properties of IO Neurons
Subthreshold Oscillations
Gap Junctions and Synchrony
Oscillations and Olivary Output
Extrinsic Control of Oscillations
Rhythmicity and Synchrony in the Climbing Fiber System
Conclusion
References
50 Feedback Control in the Olivocerebellar Loop
Introduction
Anatomical Features of the NO Pathway
Neurophysiological Properties of the NO Pathway
Functions of the NO Pathway
Regulation of Spontaneous Purkinje Cell Activity
Regulation of Cerebellar Learning
Regulation of Electrotonic Coupling in the Inferior Olive
Indirect Cerebellar Control of Olivary Excitability
Conclusion
Acknowledgments
References
51 Neurons of the Deep Cerebellar Nuclei
Introduction
Projection Neurons
Large Glutamatergic Projection Neurons
Small, GABAergic Projection Neurons
Glycinergic Projection Neurons: Nucleocortical and Nucleovestibular
Interneurons
GABAergic/Glycinergic Interneurons
Non-GABAergic (Putatively Glutamatergic) Interneurons
Summary
References
52 Cerebellar Nuclei and Cerebellar Learning
Introduction
Functional Considerations
Cellular Properties and Synaptic Integration in the CN
Modulation of Spike Rate
Activation of Rebound Firing
The Eyeblink Conditioning Paradigm as a Blueprint for Learning Mechanisms in the CN
Adaptation of the Vestibulo-Ocular Reflex (VOR) Gain Shares Many Features with Eyeblink Conditioning
Learning Limb Movements Does Not Take Place in the CN but Submovement Coordination May
Cellular Plasticity in the CN
Plasticity in the Mossy Fiber Inputs to CN Neurons
Plasticity in the Purkinje Cell CN Pathway
Other Forms of Plasticity in the CN
Conclusion and Future Directions
Cross-References
References
53 Cerebro-cerebellar Connections
Introduction
Descending Projections to the Cerebellum
Cerebro-Pontocerebellar Pathways
Cerebro-Olivocerebellar Pathways
Conclusions and Future Directions
Cross-References
References
54 Cerebellar Control of Eye Movements
Introduction
Floccular Complex
Neuronal Responses
Nodulus and Uvula
Neuronal Responses
Oculomotor Vermis and Fastigial Oculomotor Region
Motor Learning in Eye Movements by the Cerebellar Cortex
Models of Eye Movement Control of the Cerebellum
Conclusions and Future Directions
References
55 Cerebellum and Eyeblink Conditioning
Introduction
Critical Neural Circuitry
Eyeblink Conditioning and Cerebellar Dysfunction
Conclusions and Future Directions
References
56 Purkinje Neurons During Eye Blink Conditioning and New Mechanisms of Cerebellar Learning and Timing
Introduction
Pause Responses in Purkinje Cells During Conditioning
Correspondences Between Overt CRs and Purkinje Cell CRs
Acquisition and Extinction
Temporal Properties of Purkinje Cell CRs
Minimum CS-US Interval
Cellular Mechanisms of Simple Spike Suppression and Timing
Conclusions and Future Directions
Cross-References
References
57 Cerebellar Control of Speech and Song
Introduction
Anatomical Substrates
Internal Models
Laterality
Cerebellum and Working Memory
Verbal Fluency
Grammar Processing
Linguistic Deficits in Cerebellar Patients
Conclusions and Perspectives
References
58 Cerebellum and Timing
History/Background
Cerebellar Function in Sensorimotor Timing: Neuropsychological Studies
Cerebellar Function in Sensorimotor Timing: Neuroimaging and TMS Studies
Cerebellar Contributions to Perceptual Timing: Neuropsychological Studies
Cerebellar Contributions to Perceptual Timing: Neuroimaging Studies
Cerebellar Timing Function in Sensorimotor Learning
The Range of Cerebellar Timing
The Cerebellum as an Event Timer
Conclusions
References
59 Cerebellar Control of Posture
Introduction
Anatomical Aspects
Historical Aspects
Postural Disturbances After Cerebellar Lesions
Animal Data
Postural Deficits in Cerebellar Patients
Genetic Aspects
Plasticity in Cerebellum
Role of Cerebellum in Learning
Cerebellum and Learning Postural Tasks
Conclusion
References
60 Channelopathies and Cerebellar Disease
Introduction
Channels and Channelopathy
SCA6 (CACNA1A)
SCA13 (KCNC3)
SCA15/29 (ITPR1)
SCA19 (KCND3)
SCA41 (TRPC3)
SCA42 (CACNA1G)
SCA44 and SCAR13 (GRM1)
SCAR18 (GRID2)
EA1 (KCNA1)
EA5 (CACNB4)
EA6 (SLC1A3)
Clinical Overview
Treatment of Channelopathy
Conclusions and Future Directions
References
61 Disruption of the Microbiota-Gut-Brain (MGB) Axis and Mental Health of Astronauts During Long-Term Space Travel
Introduction
The Microbiota-Gut-Brain (MGB) Axis in a Nutshell
The Role of the Cerebellum in the Gut-Brain Axis: A Gut-Cerebellar Brunch
Examples of Clinical and Animal Data Supporting the Concept of Disrupted MGVHB Axis in Space
Altered Gut Microbiota and Gut Structure in Space Environment
Vagus Nerve Signaling and Heart Abnormalities in Astronauts
Changes in Brain Structure and Behavior
Impact of Space Environmental Factors on the MGVHB Axis
Diet
Gravity
Radiation
Stress
Sexually Dimorphic Nature of the MGVHB Axis, as a Factor in Selection of Women Versus Men for Long-Term Space Travel
Possible Means of Minimizing the Effects of the Environment of Space Travel on Astronauts´ MGVHB Axis and Mental Health
Concluding Remarks
Cross-References
References
62 Cerebellum-Like Structures
Introduction
Cerebellum-Like Structures in Different Vertebrate Groups
Circuitry of Cerebellum-Like Structures
Comparison of the Local Circuitries of Cerebellum-Like Structures and the Cerebellum
Patterns of Gene Expression in Cerebellum-Like Structures and the Cerebellum
Evolution of Cerebellum-Like Structures and the Cerebellum
Sensory Predictions in Cerebellum-Like Structures
Plasticity at Parallel Fiber Synapses in Cerebellum-Like Structures and the Cerebellum
Adaptive Function in Cerebellum-Like Structures Versus the Cerebellum
Predictions in the Cerebellum
Conclusions and Future Directions
References
Part IV: Computational Models of Cerebellar Function
63 Cerebellum and Internal Models
Introduction
Internal Models and the Central Nervous System
Internal Models for Motor Control and the Cerebellum
Motor Deficits in Patients with Cerebellar Disease
Functional Imaging Studies
Noninvasive Cerebellar Stimulation
Electrophysiological Investigations
Cerebellar Internal Models for Tool Use
Cerebellar Internal Models Beyond Motor Function
Conclusion and Future Directions
Cross-References
References
64 State Estimation and the Cerebellum
Introduction
Internal Models
Behavioral Evidence of State Estimation
State Estimation and the Cerebellum
Prediction Error and Adaptative Learning
Conclusions and Future Directions
References
65 Adaptive Filter Models
Introduction
Model Alterations
Molecular Layer Interneurons
Spike-Timing-Dependent Plasticity
Initial Plausibility of Altered Model
Problems with LTD
Possible Solutions
Importance of LTP
Problems in Characterizing LTD
In Vivo LTD
Conclusions
References
66 Cerebellum and Human Evolution: A Comparative and Information Theory Perspective
Introduction
Comparative Changes in the Cerebellum and Information Processing
Estimated Comparative Changes in the Volume Fraction of the Neocerebellum
Comparative Changes in the Number of Granule-Cell-Purkinje-Cell (gcPc) Synapses in Mammals
Summary
The Role of the Cerebellum in Complex and Adaptive Behavior
Adaptive Behavior and the Cerebellum: Action Perception and Learning and Memory
Complex Behavior and the Cerebellum: Information Coding and Processing Capacity
Comparative Changes of the Cerebellum and Behavior
Cerebellum and Human Evolution
Conclusions and Future Directions
References
67 Computational Structure of the Cerebellar Molecular Layer
Introduction
Motor Control as the Computational Context for Cerebellar Theory
Linking Function to Structure
What Do Parallel Fibers Do to Purkinje Cells?
Uncovering Function from Structure
Functional and Algorithmic Implications for the Cerebellar Molecular Layer
Implications for Previous Models of Cerebellar Function
A New Cortical Computational Algorithm
Conclusions and Future Directions
References
68 Recursive Genome Function of the Cerebellum: Geometric Unification of Neuroscience and Genomics
Introduction
Agenda: The Cerebellum as the Platform for the Unification of Neuroscience and Genomics by the Geometric School of Biophysics
Recursion in the Cerebellum
Review: Philosophies, Theories, and Computational Models as Foundations of the School of Cerebellar Recursion
The Concept of Coordinates and Their Recursion as Basics of Tensor Network Theory of Cerebellar Neural Nets
Generalization of Recursion from Cerebellar Neuroscience to Genomics; Covariant and Contravariant RNA Functors and Their Eigen...
Recursive Algorithms Rule Both Vector-Matrix and Fractal Representations
Tensor Network Theory: Vector-Matrix Recursion as Basis of the Cerebellum Acting as a Sensorimotor Metric Tensor
Fractals Are Pervasive in Nature; Both the Cerebellar Brain Cells and the DNA are Fractal Objects
The Zipf-School Suspected that the DNA Contained a Fractal Language
The Genome is Fractal: Grosberg-School Suspected that the DNA Showed Fractal Folding
The Perez-School Shows that the DNA is Fractal at DNA, Codon- and Full Chromosome Set and Whole Genome Levels
Fractals to DNA Numerical Decoding: Toward the Golden Ratio
The ``Fractal Chaos´´ Artificial Neural Network
``DNA SUPRACODE´´ Overview
In Single-Stranded DNA Human Genome, Codons Population are Fine-Tuned in Golden Ratio Proportions
A Strange Meta-Architecture Organizes Our 24 Human Chromosomes
Unifying All Biological Components of Life: DNA, RNA, Proteins
Neural Net Elements are Fractal: Purkinje Neuron Fractal Model
The Genome is Fractal! Proof of Concept and the Basis of Generalization: Whole Genome Analysis Reveals Repetitive Motifs Confo...
Conclusions
Neuronal and Genomic Systems are Governed by Recursive Algorithms of Massively Parallel Networks, Not Only Including, but Surp...
Application of Fractal Genomics is Already Here
Friedreich Spinocerebellar Ataxia
Application of Fractal Genomics for Cancer
Future Directions
Theory of Recursive Algorithms
Neural Net Algorithms Comprise Massively Parallel and Coordinated Genome Function
Integration of Neural Net and Fractal Algorithms
Develop and Integrate Quantum Theory of Neuroscience and Genomics
Public Domain Agenda in Industrialization of Genomics: Local and Global Fractal Dimension as a Standard Definition for Optimal...
Proprietary Agenda in Industrialization of Genomics
Hybrid Computation on Private Clouds
Consumer Genomics in Continuous Customer Care
References
Part V: Animal Models to Study Cerebellar Function
69 Animal Models: An Overview
Introduction
Non-mammallian Animal Models
Non-vertebrate Animal Models
Fish Models
Amphibian and Reptile Models
Avian Models
Rodent Models
Mouse Models for Inherited Ataxia
Non-mouse Rodent Models
Non-rodent Mammal Models
Primate Models
Cat Models
Conclusions and Future Directions
Cross-References
References
70 Cerebellar Development and Neurogenesis in Zebrafish
Introduction
The Cerebellar Anatomy and Architecture
Cerebellar Cell Layers, Cell Types, and Circuitry
Cerebellar Afferents and Efferents
Cerebellar Development
Positioning of the Midbrain-Hindbrain Boundary and Role of the Isthmic Organizer in Establishing the Cerebellar Territories
Cerebellar Germinal Zones and Progenitor Domains
Cerebellar Neurogenesis
Adult Neurogenesis and Regenerative Potential of the Zebrafish Cerebellum
Conclusions and Future Directions
References
71 Teleost Fish
Introduction
Gross Morphology of the Teleost Cerebellum
Cellular Organization and Neural Circuit
Cerebellar Efferent Neurons in Teleost
Afferent and Efferent Fiber Connections with Other Brain Regions
Functions of Teleost Cerebellum
Conclusions and Future Directions
References
72 Robotic Mouse
Introduction
Phenotype, Neuropathology, and Behavior
Genetic and Molecular Basis
AF4, the Mutated Disease Protein, Abnormally Accumulates in Robotic PCs
AF4: A Cofactor of Transcriptional Elongation and Chromatin Remodeling
Downregulation of the IGF-1 Signaling Pathway Causes PC Degeneration in the Robotic Cerebellum
Conclusions and Future Directions
Cross-References
References
73 Lurcher Mouse
Introduction
Morphological and Cellular Changes in the Lurcher Mutant Central Nervous System
Pathogenesis of the Neurodegeneration in Lurcher Mice
Lurcher Mutation
Etiology of the Degeneration and Role of GluRδ2
Cell Death Mechanisms
Neurochemical Abnormalities and Changes of Brain Metabolism
Abnormalities of Neurotransmitters and Receptors Systems
Abnormalities in the Endocrine and Immune Systems of Lurcher Mice
Behavioral Characteristics of Lurcher Mice
Motor Functions
Cognitive Functions
Other Behavioral Characteristics
Experimental Influencing of Lurcher Mice
Effects of Cerebellectomy
Lurcher Mice in Neurotransplantation Research
Enforced Physical Activity and Enriched Environment
Pharmacological Influencing
Breeding and Colony Maintenance
Conclusions and Future Directions
Cross-References
References
74 Tottering Mouse
Introduction
Tottering Mouse as a Model of a Human Calcium Channelopathy
Behavioral Phenotype
Morphological and Histochemical Alterations
P/Q-Type Channel Dysfunction in Tottering
Altered Synaptic Transmission in Tottering
Purkinje Cell Dysfunction in Tottering
Upregulation of L-Type Ca2+ Channels in Tottering
Role of Cerebellum in Episodic Dystonia
Cerebellar Contribution to Absence Seizures
Low-Frequency Oscillations in Tottering
Triggers of Episodic Dystonia
Conclusions and Future Directions
References
75 Rolling Nagoya Mouse
Introduction
Phenotypic Description of the Rolling Nagoya Mouse
CaV2.1 Channels and the Rolling Nagoya Mutation in Cacna1a
Histological Analyses of Rolling Nagoya Brain Areas
Effect of the Rolling Nagoya Mutation on CaV2.1 Channel Electrophysiology
Effects of the Rolling Nagoya Mutation on Cellular Neurophysiological Behavior
Aberrant Action Potential Firing Pattern in Cerebellar Purkinje Cells
Dysfunction of Cerebellar Synapses and the Neuromuscular Junction
The Rolling Nagoya Mouse as a Model for Human CaV2.1 Channelopathies?
Ataxia
Migraine
Lambert-Eaton Myasthenic Syndrome
Conclusions and Future Directions
Cross-References
References
76 Ataxic Syrian Hamster
Introduction
Origin of Discovery and Hereditary Mode
Breeding and General Properties
Histology
Genetics
Possible Applications
pcd Mutation in Mice
Comparison to pcd Mutant Mice
Conclusions and Future Directions
Cross-References
References
77 Moonwalker Mouse
Introduction
The mGluR1-TRPC3 Pathway in Cerebellar Ataxia
The Moonwalker Mutation
Pathophysiology
Behavioral Phenotype
Morphological Changes
Loss of Cells
Impaired Dendritic and Synaptic Development
Conclusions and Future Directions
References
78 Hemicerebellectomy
Introduction
The Hemicerebellectomy Model
HCb and Experimentally Induced Neuroplasticity
HCb as a Model for Studying Axotomy-Induced Neurodegeneration
HCb and Endocannabinoids
HCb and Neuron-Glia Crosstalk in Neurodegeneration
HCb at Various Developmental Stages and Motor Recovery
HCB and Maze Learning
HCB and Changes in Motor Cortical Physiology
Conclusions and Future Directions
References
Part VI: Symptoms of Cerebellar Disorders in Human
79 Role of Cerebellum in Gaze-Holding Disorders
Introduction
Physiology of Gaze Holding: The Neural Integrator
Gaze-Evoked Nystagmus: Abnormal Function of Ocular Motor Neural Integrator
Vestibular Neural Integrator and the Velocity Storage
Gravity-Dependent Nystagmus
Periodic Alternating Nystagmus (PAN)
Vertical Nystagmus
Oculopalatal Tremor
References
80 Cerebellar Motor Disorders
Introduction
Contributions of Luciani, Babinski, and Holmes
Symptoms
Oculomotor Disturbances
Dysarthria and Other Speech Deficits
Dysphagia
Ataxia of Limbs
Ataxia of Stance and Gait
Topography of Clinical Deficits
References
81 Lesion-Symptom Mapping of the Human Cerebellum
Introduction
Human Cerebellar Lesion Conditions
Cerebellar Stroke
Cerebellar Tumors
Cerebellar (Cortical) Degeneration
Lesion-Symptom Mapping
Focal Cerebellar Disorders
Structural MRI Sequences and Delineation of Focal Lesions
Chronic Cerebellar Lesions
Acute Cerebellar Lesions
Cerebellar Nuclei
Normalization of the Cerebellar Cortex and Nuclei
Statistical Analysis in Focal Cerebellar Lesions
Superimposition of Lesions in Patients Showing the Same Disorder
Comparing Lesion Site in Two Groups of Patients
Voxel-Wise (Inferential) Statistical Mapping
Cerebellar (Cortical) Degeneration
Volumetric Analysis of the Cerebellum
Voxel-Based Morphometry (VBM)
Structural Connectivity of Cerebellar Pathways
Atlases of the Cerebellar Cortex and Nuclei
Atlas of the Cerebellar White Matter Tracts
Conclusions and Future Directions
Cross-References
References
82 Deficits of Grasping in Cerebellar Disorders
Introduction
Deficits of Reaching and Grasping
Predictive and Reactive Control of Grasping Forces
Internal Forward Models
Living Without a Cerebellum
Case Description
Deficits of Grasping Force Control
Deficits of Higher-Order Motor Control Related to Grasping?
References
83 Ataxic Hemiparesis
Introduction
A Brief History of AH
Core Symptoms of AH
Variations of AH
Painful AH
Sensory AH
Other Variations
The Severity of AH
Nonischemic AH
Hemorrhagic Stroke Causing AH
Other Causes of AH
Frequency of AH
Mechanisms and Topography of AH Lesions Following IS
Cerebral Cortex
Subcortical Lesions
Thalamus and Internal Capsule
Basal Ganglia
Brainstem and Cerebellum
The Role of Afferent and Efferent Pathways
Etiology of Stroke Associated with AH
Diagnostic Testing for AH
Treatment for AH
Prognosis of AH
Conclusions and Future Directions
References
84 Cerebellum and Cognition
Introduction
Evolution
Congenital Malformations of the Posterior Fossa
Abnormalities of Cerebellar Volumes and Structure
Pre- and Perinatally Acquired Cerebellar Problems
Acquired Problems During Childhood
Late-Onset Cerebellar Problems
Functional Neuroimaging
Conclusion
References
85 Cerebellar Sequencing for Cognitive Processing
Introduction
Somatosensory Processing
Cognition
Scripts
Acquisition of Procedures
Visuospatial Processing
Language
Sequencing for Language Processing
Sequencing for Writing
Conclusion and Future Directions
Cross-References
References
86 The Cerebellar Cognitive Affective Syndrome and the Neuropsychiatry of the Cerebellum
Introduction
Anatomical Connections: Overview
Topographic Arrangement of Anatomical Connections
Imaging Observations in Humans
The Cerebellar Motor Syndrome: Clinical Features and Structure-Function Correlations in Stroke
The Cerebellar Cognitive Affective Syndrome: The Initial Description
The Cerebellar Cognitive Affective Syndrome: Subsequent Reports
Selected Case Series
Selected Case Reports
The Cerebellar Cognitive Affective Syndrome in Children
Postoperative Pediatric Cerebellar Mutism and CCAS
Neuropsychiatry of the Cerebellum: The Affective Component of the CCAS
The Cerebellum in Psychiatric Disease: Focus on the Vermis
Cognition in Ataxic Disorders
Cerebellar Lesions Impair Cognition in the Developing Brain: Developmental CCAS
Mechanisms of the Cerebellar Contribution to Cognition and Emotion
An Approach to Testing Cerebellar Cognition at the Bedside
Implications for Diagnosis and Management of Patients with Cerebellar Disease
References
87 Cerebellar Mutism Syndrome in Children and Adults
Introduction
Semiological Characteristics of Cerebellar Mutism Syndrome
Cerebellar Mutism Syndrome in Children
Cerebellar Mutism Syndrome in Adults
Preoperative Neurocognitive Assessments
Risk Factors for POPCMS
Pathophysiological Explanations and Hypotheses
Functional Lateralization of the Cerebellum: Evidence from CMS
Treatment and Rehabilitation
Concluding Remarks
Cross-References
References
88 Human Cerebellum in Motivation and Emotion
Introduction
Argument 1
Argument 2
Argument 3
Argument 4
Argument 5
Argument 6
Discussion
Conclusions and Future Directions
References
Part VII: Cerebellar Disorders
89 Clinical Scales of Cerebellar Ataxias
Introduction
International Cooperative Ataxia Rating Scale (ICARS)
Validation
Clinical Application
Friedreich Ataxia Rating Scale (FARS)
Validation
Clinical Application
Scale for the Assessment and Rating of Ataxia (SARA)
Validation
Clinical Application
Brief Ataxia Rating Scale (BARS)
Validation
Clinical Application
Scales for the Clinical Evaluation of Cerebellar Disorders: From Pediatric Perspective
ICARS, SARA, and BARS in Pediatric Patients
Clinical Implications
In Conclusion
References
90 Approach to the Differential Diagnosis of Cerebellar Ataxias
Introduction
The Natural History and Pathophysiological Approaches of Ataxia
Autosomal Recessive Cerebellar Ataxias (ARCAs)
Autosomal Dominant Cerebellar Ataxias (ADCAs)
Episodic Ataxias
X-Linked Cerebellar Ataxias
Mitochondrial Cerebellar Ataxias
Idiopathic Late-Onset Cerebellar Ataxias
Spastic Ataxias
Molecular Genetics of Ataxias
Genetic Testing
Conclusions and Future Directions
Cross-References
References
91 Cerebellar Malformations
Introduction
Cerebellar Malformations
Rhombencephalosynapsis
Congenital Muscular Dystrophies
Molar Tooth Malformations
Cystic Posterior Fossa Malformations
Dandy Walker Malformation
Mega Cisterna Magna
Blake Pouch Cyst
Isolated Inferior Vermian Hypoplasia
Posterior Fossa Arachnoid Cysts
Cerebellar Hypoplasia
Cerebellar Agenesis
Global Cerebellar Hypoplasia
Unilateral Cerebellar Hypoplasia
Pontocerebellar Hypoplasia
Cerebellar Cortical Dysplasias
Lhermitte-Duclos Disease
Conclusions and Future Directions
References
92 Consequences for Cerebellar Development of Very Premature Birth
Introduction
Preterm Birth: Background
Classification of Prematurity
Brain Injury in the Perinatal Period
Injury to the Developing Cerebellum
Cerebellar Hemorrhage
IVH
Neonatal Adversity
Iatrogenic Steroids
Effect of Damage Elsewhere in the Brain
Cerebellar Development in the Neonatal Period
The Long-Term Consequences of VPT Birth
The Ongoing Contribution of the Cerebellum
Risk and Resilience
Conclusion and Future Directions
References
93 Cerebellar Agenesis
Introduction
Cerebellar Development, Pathological Mechanisms of Cerebellar Anomalies, and Classifications
Cerebellar Development
Pathological Mechanisms of Cerebellar Anomalies
Classification Systems
Cases Report
Literature Review
Recent Neuroradiological Studies
Personal Case
Clonclusion and Future Directions
References
94 Chiari Malformations
Introduction
Historical Aspects
Classification and Description of Chiari Malformations
Chiari Type I
Chiari Type II
Chiari Type III
Chiari Type IV
Roles of Imaging Techniques
Pathogenesis of Chiari Malformations
Management
Surgery
Tracheostomy
Medications
Rehabilitation
Incidental Discovery
Prognosis
References
95 Dandy-Walker Malformations
Introduction
Etiology
Diagnosis
Symptomatology
Central Nervous System Abnormalities
Non-CNS Abnormalities
Management
Prognosis
Conclusions and Future Directions
References
96 Autism Spectrum Disorders and Ataxia
Introduction
The Cerebellum Has a Role in Multiple Domains Impaired in Autism
Structural Pathology of the Cerebellum in Autism
Deficits in Specific Proteins in Autistic Cerebellum
Ataxia
Conclusions and Future Directions
Cross-References
References
97 Cerebellum and Schizophrenia: The Cerebellum Volume Reduction Theory of Schizophrenia
Introduction
Schizophrenia Overview
Classifications
Studies of Risk Factors
Prevalence and Mortality
Pharmacological Treatment
Typical Antipsychotics
Atypical Antipsychotics
Pharmacological Mechanism of Neuroleptic Therapy
Nonpharmacological Therapy
Psychotherapies
Electroconvulsive Therapy (ECT)
Cognitive Behavioral Therapy (CBT)
Social Skill Training (SST)
Studies of Cerebellum Volume and Schizophrenia
Neuroimaging Studies
Structural Magnetic Resonance Imaging (MRI) Studies
Cerebellum Volume Reduction and Schizophrenia
Evidence for Progressive Volume Reduction in Schizophrenia
Diffusion Tensor Imaging (DTI) Studies
Susceptibility Genes and Neuronal Disconnectivity in Schizophrenia
Conclusion and Future Directions
Volume Reduction Theory of Schizophrenia
References
98 Progressive Myoclonic Epilepsies
Introduction
Unverricht-Lundborg Disease (ULD; Baltic Myoclonus)
Introduction
Epidemiology
Genetics
Pathology
Clinical Manifestations
EEG Characteristics
Diagnosis
Myoclonic Epilepsy and Ragged Red Fibers (MERRF)
Introduction
Epidemiology
Genetics
Pathology
Clinical Manifestations
EEG Characteristics
Diagnosis
Neuronal Ceroid Lipofuscinosis
Introduction
Epidemiology
Genetics
Clinical-Pathological Manifestations-EEG Findings
Diagnosis
Dentatorubropallidoluysian Atrophy (DRPLA)
Introduction
Epidemiology
Genetics
Pathology
Clinical Manifestations
Diagnosis
EEG Characteristics
Gaucher Disease
Introduction
Epidemiology
Genetics
Pathology
Clinical Manifestations
Diagnosis
EEG Characteristics
Lafora Disease (LD)
Introduction
Epidemiology
Genetics
Pathology
Clinical Manifestations
Diagnosis
EEG Characteristics
Cherry-Red Spot Myoclonus Syndrome (Type 1 Sialidosis)
Introduction
Epidemiology
Genetics
Pathology
Clinical Manifestations
Diagnosis
EEG Characteristics
Other Rare Forms of PME
Treatment of PME
Cross-References
References
99 Cerebellar Stroke
Introduction
General Clinical Features
Headache
Dizziness
Ataxia
Dysarthria
Ocular Motor Dysfunction
Cognitive Functions
Cerebellar Infarction
PICA Infarction
AICA Infarction
SCA Infarction
Nonterritorial Small Infarcts
Bilateral Cerebellar Infarction
Complications
Cerebellar Hemorrhage
Cerebellar Venous Infarction or Hemorrhage
Diagnosis
Treatment
Conclusion and Future Directions
Cross-References
References
100 Immune Diseases
Introduction
Gluten Ataxia
Anti-GAD Ataxia
Primary Autoimmune Cerebellar Ataxia (PACA)
Opsoclonus Myoclonus Ataxia Syndrome (OMAS)
Post-infectious Cerebellitis
Less Common Immune-Mediated Ataxias
Miller Fisher Syndrome
Anti-DPPX Ataxia
Anti-MAG Ataxia
CLIPPERS
HIV-Associated Cerebellar Ataxia
Conclusions and Future Directions
References
101 Endocrine Disorders
Thyroid Disorders
Hypothyroidism
Hyperthyroidism
Hashimoto Ataxia
Drug-Induced Dysfunction
Parathyroid Disorders
Hypoparathyroidism
Pseudohypoparathyroidism and Pseudopseudohypoparathyroidism
Hyperparathyroidism
Cerebellar Ataxia and Diabetes
Friedreich Ataxia
Mitochondrial Diseases
Anti-GAD Antibodies
APS Syndromes (Autoimmune Polyglandular Syndromes)
Aceruloplasminemia
Von Hippel-Lindau Disease
Langerhans Histiocytosis
Wolfram Disease (DIDMOAD Syndrome)
Cerebellar and Pancreatic Agenesis
Cerebellar Ataxia and Hypogonadism
Most Common Causes: Holmes Ataxia and Boucher-Neuhäuser Syndrome
Marinesco-Sjögren Syndrome
Septo-Optic Dysplasia
Kallman Syndrome
Congenital Disorders of Glycosylation
4H Syndrome
Conclusion and Future Directions
References
102 Infectious Diseases of the Posterior Fossa
Introduction
Bacterial Infections
Epidemiology
Clinical Presentation
Investigations
Pathogenesis
Treatment
Cerebellitis
Epidemiology
Clinical Presentation
Investigations
Pathogenesis
Treatment
Human Prion Diseases
Epidemiology
Clinical Presentation
Investigations
Pathogenesis
Treatment
Conclusion and Future Directions
Cross-References
References
103 Diagnosis of Neoplastic and Paraneoplastic Cerebellar Ataxia
Introduction
Cerebellar Tumors
Clinical Presentation
Neuroimaging
Biological Evaluation
Different Cerebellar Tumor
Medulloblastoma
Pilocytic Astrocytomas
Cerebellar Metastasis
Hemangioblastoma
Other Cerebellar Tumors
Paraneoplastic Cerebellar Ataxia (PCA)
Clinical and Biological Features of Patients with PCA
Clinical Specificities According to the Type of Onconeuronal Antibody
PCA with Anti-Yo
Anti-Hu Patients with Cerebellar Ataxia
PCA with Anti-Tr Antibodies
Anti-CV2/CRMP5 and Cerebellar Ataxia
PCA Associated with Anti-Channel Blockers
PCA Associated with Anti-Ri
Treatment
Conclusion
References
104 Posterior Fossa Trauma
Introduction
Epidemiology
Types of Posterior Fossa Trauma
Intra-Axial Lesions
Concussion
Contusion
Diffuse Axonal Injury
Secondary Traumatic Lesions
Extra-Axial Lesions
Epidural Hematoma
Subdural Hematoma
Subarachnoid Hemorrhage
Traumatic Vascular Lesions
Clinical Presentation
General Presentation
Traumatic Brainstem Lesions
Traumatic Cerebellar Lesions
Hematoma Within the Posterior Fossa
Vertebral Artery Dissection
Imaging
Computed Tomography (CT) and Magnetic Resonance (MR) Imaging
Intra-axial Lesion
Cerebellar Injuries: CT Findings
Cerebellar Injuries: MRI Findings
Brainstem Injuries
Diffuse Axonal Injury
Extra-Axial Lesions
Epidural Hematoma (EDH)
Subdural Hematoma
Subarachnoid Hemorrhage
Traumatic Vascular Lesions
Other Techniques: Diffusion Tensor Imaging (DTI), MR Spectroscopy, Voxel-Based Morphometry (VBM), Positron Emission Tomography...
Pathophysiology
Management
Control of Vital Functions
Control of Intracranial Pressure
Relief of Space-Occupying Lesions
Vertebral Artery Dissection
Long-Term Complications
``Delayed-Onset Cerebellar Syndrome,´´ ``Delayed-Onset Intention Tremor´´ and ``Rubral Tremor``
Crossed Cerebellar Atrophy
Olivary Hypertrophy
Superficial Siderosis
Conclusion and Future Directions
References
105 Cerebellotoxic Agents
Cerebellar Toxicity of Alcohol
Clinical Findings
Cerebellar Atrophy
Posture and Gait Studies
Blood Studies
Neuropathological Findings
Pathogenesis
Risk Factors
Treatment
Prognosis
Drugs
Anticonvulsants
Phenytoin
Carbamazepine
Other Anticonvulsants
Antineoplastics
5-FU and Capecitabine
Ara-C (Cytarabine)
Methotrexate
Cisplatin, Oxaliplatin, Taxol
Epothilone D
Other Drugs
Lithium Salts
Amiodarone
Procainamide
Cyclosporin and Other Calcineurin Inhibitors (Tacrolimus, Sirolimus)
Bismuth
Mefloquine
Isoniazid
Lindane
Statins
Metronidazole
Nicotine
Diphenoxylate-Atropine
Drug Abuse and Addiction
Cocaine
Heroin
Phencyclidine
Herbs
Methadone
Environment
Metals
Mercury
Lead
Manganese
Copper
Gadolinium
Aluminum
Thallium
Germanium
Uranium
Vanadium
Toluene/Benzene Derivatives
Hyperthermia
Carbon Monoxide
Chemical Weapons
Insecticides/Herbicides/Pesticides
Others
Dimethylamine Borane
Eucalytpus Oil
Saxitoxin (Shellfish Poisoning)
Edible Morels
Seasonal Ataxia
Cyanide
Baptisia Poisoning
Animal-Related Cerebellar Toxicity
Scorpions
Conclusions and Future Directions
References
106 Multiple System Atrophy (MSA)
Introduction
Epidemiology
Clinical Features and Diagnostic Criteria
Diagnostic Criteria
Investigations
Disease Progression
Neuropathology
Pathogenesis
Therapies
Disease-Modifying Strategies
Symptomatic Treatment
Motor Symptoms
Parkinsonism
Dopaminergic Agents
NMDA Receptor Antagonists
Selective Serotonin Receptor Inhibitors
Anticholinergic Agents
Cerebellar Ataxia
Dystonia
Sialorrhea
Autonomic Symptoms
Urinary Dysfunction
Orthostatic Hypotension
Constipation
Erectile Dysfunction
Non-medical Therapy and Palliative Care
Conclusions
References
107 Idiopathic Late Onset Cerebellar Ataxia (ILOCA), and Cerebellar Plus Syndrome
Introduction
Idiopathic Late-Onset Cerebellar Ataxia (ILOCA)
ILCOA with Cerebellar-Plus Syndrome
Multiple System Atrophy (MSA)
Epidemiology of SCAs in Japan
References
108 Essential Tremor
Introduction
Epidemiology
Clinical Features
Tremors
Accessory Motor Features
Cognitive Features
Psychiatric Features
Electrophysiological Studies
Neuroimaging Studies
Pathological Features and Pathophysiology
ET as a Cerebellar Disorder: Conclusions and Future Directions
References
109 Autosomal Recessive Cerebellar Ataxias
Introduction
Friedreich´s Ataxia
Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS)
Autosomal Recessive Cerebellar Ataxia Type 1 (ARCA-1)
Autosomal Recessive Cerebellar Ataxia Type 2 (ARCA-2)
Ataxia with Oculomotor Apraxia Type 1 (AOA-1)
Ataxia with Oculomotor Apraxia Type 2 (AOA-2)
Ataxia with Vitamin E Deficiency (AVED)
Conclusion and Future Directions
References
110 Autosomal Dominant Spinocerebellar Ataxias and Episodic Ataxias
History, Nomenclature, and Classification
Epidemiology and Frequency
Spinocerebellar Ataxias (SCAs and DRPLA)
Genetic Bases
Anticipation
Neuropathology
Pathogenesis
Polyglutamine SCAs
Other SCAs
General Clinical Presentation
Neuroimaging
Clinical Description of Subforms
SCA1
SCA2
SCA3 (Machado-Joseph Disease)
SCA4
SCA5
SCA6
SCA7
SCA8
SCA10
SCA11
SCA12
SCA13
SCA14
SCA15/SCA16
SCA17
SCA18
SCA19 and SCA22
SCA20
SCA21
SCA23
SCA25
SCA26
SCA27
SCA28
SCA29
SCA30
SCA31
SCA32
SCA35
SCA36
DRPLA
Episodic Ataxias
EA1
EA2
EA3
EA4
EA5
EA6
EA7
Conclusions
Diagnosis
Treatment
Future Perspectives
References
111 Mitochondrial Disorders
Introduction to Mitochondrial Functions
Transport Systems
Degradative Metabolic Pathways
Mitochondrial Dynamics
Oxidative Phosphorylation and the Respiratory Chain
RC Function
Cerebellar Disorders Due to Defects of Nuclearly Encoded Mitochondrial Proteins
Friedreich Ataxia (FRDA)
POLG-Related Ataxias
Myoclonic Epilepsy Myopathy Sensory Ataxia (MEMSA)
Ataxia Neuropathy Spectrum (ANS)
Infantile-Onset Spinocerebellar Ataxia (IOSCA)
Ataxia with Coenzyme Q10 Deficiency
X-Linked Sideroblastic Anemia with Ataxia (XLSA/A)
Autosomal Dominant Spinocerebellar Ataxia Type 28 (SCA28)
Cerebellar Disorders Due to Defects of MtDNA
Heteroplasmic Point Mutations
Myoclonic Epilepsy with Ragged-Red Fibers (MERRF)
Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-Like Episodes (MELAS)
MELAS/MEERF Overlapping Syndrome
Neuropathy, Ataxia, and Retinitis Pigmentosa (NARP)
Maternally Inherited Leigh Syndrome (MILS)
Hearing Loss-Ataxia-Myoclonus (HAM)
Other Mitochondrial Disorders with Ataxia
Large-Scale Rearrangements of Mitochondrial DNA
Kearns-Sayre Syndrome (KSS)
References
112 X-Linked Ataxias
Introduction
Fragile X-Associated Tremor Ataxia Syndrome (FXTAS)
X-Linked Sideroblastic Anemia with Ataxia (XLSA)
X-Linked Ataxia Due to GJB1 Mutations
Spinocerebellar Ataxia Due to PMCA3 Mutations
X-Linked Adrenoleukodystrophy
X-Linked Pyruvate-Dehydrogenase (PDH) Deficiency
X-Linked Ataxias with Ataxia as a Nondominant Feature
Management
Conclusion
References
113 Neuropathology of Ataxias
Introduction
Spinocerebellar Degeneration
Sporadic Disorders
Multiple System Atrophy
Late Cortical Cerebellar Atrophy
Hereditary Disorders
Spinocerebellar Ataxia Type 1
Spinocerebellar Ataxia Type 2
Machado-Joseph Disease/Spinocerebellar Ataxia Type 3
Spinocerebellar Ataxia Type 6
Spinocerebellar Ataxia Type 7
Spinocerebellar Ataxia Type 8
Spinocerebellar Ataxia Type 31
Dentatorubral-Pallidoluysian Atrophy
Friedreich´s Ataxia
Early-Onset Ataxia with Ocular Motor Apraxia and Hypoalbuminemia/Ataxia-Oculomotor Apraxia Type 1
Marinesco-Sjögren Syndrome
Conclusions and Future Directions
References
114 General Management of Cerebellar Disorders: An Overview
Introduction
General Predictions of Functional Recovery
Medical Intervention
Idebenone in Friedreich´s Ataxia
Riluzole
Acetylleucine
Aminopyridines
Cognitive Rehabilitation
Motor Rehabilitation
Impairments in Motor Performance and the Adaptation of Movements
Animal Cerebellar Lesion Models Indicate Long-Term Adaptation and Effects of Motor Training
Motor Rehabilitation in Human Cerebellar Disease
Discussion
Current Praxis of Motor Rehabilitation
Open Questions in Cerebellar Motor Rehabilitation
Motor Rehabilitation for Upper Extremities
Further Clinical Studies in Different Disease Stages
Long-Term Studies and Quality of Life
Prediction of Intervention Benefits
Future Studies on Mechanisms of Motor Adaptation and Motor Rehabilitation
Modern Brain Imaging Techniques
The Relationship Between Short-Term Motor Adaptation Alternative Learning Methods and Motor Rehabilitation
Noninvasive Brain Stimulation Techniques
Conclusions and Future Directions
References
115 Novel Therapeutic Challenges in Cerebellar Diseases
Introduction
Treatments for Autosomal Recessive Spinocerebellar Ataxias
Friedreich´s Ataxia (FRDA)
Ataxias with Vitamin E and Coenzyme Q10 Deficiencies
Abetalipoproteinemia
Cerebrotendinous Xanthomatosis (CTX)
Refsum´s Disease
Ataxia-Telangiectasia (AT)
Treatments for Autosomal Dominant Spinocerebellar Ataxias
Treatments for Episodic Ataxias
Emerging Therapeutic Strategies
Physical Therapy in Cerebellar Diseases
Physical Therapy Examination
Physical Therapy Interventions
Concluding Remarks and Future Directions
Cross-References
References
Index