Cerebellum

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Introduction[edit | edit source]

Cerebellum gif.gif

The cerebellum is a vital component in the human brain as it plays a role in motor movement regulation and balance control. The cerebellum [1] (see image on R, horizontal fissure marked red)

  • Coordinates gait
  • Maintains posture,
  • Controls muscle tone and voluntary muscle activity
  • Is unable to initiate muscle contraction.

Damage to this area in humans results in a loss in the ability to control fine movements, maintain posture, and motor learning

The cerebellum is neuron-rich, containing 80% of the brain’s neurones organized in a dense cellular layer, and it's surface area when unfolded is nearly 75% of the surface area of the cerebrum.[1]

Anatomical Position[edit | edit source]

The cerebellum is located at the back of the brain, immediately inferior to the occipital and temporal lobes, and within the posterior cranial fossa. It is separated from these lobes by the tentorium cerebelli, a tough layer of dura mater.

It lies at the same level of and posterior to the pons, from which it is separated by the fourth ventricle.

Structure[edit | edit source]

The cerebellum consists of two hemispheres which are connected by the vermis, a narrow midline area. The cerebellum consists of grey matter and white matter:[2]

  • Grey matter – located on the surface of the cerebellum. It is tightly folded, forming the cerebellar cortex. The gray matter of the cortex divides into three layers: an external - the molecular layer; a middle - the Purkinje cell layer; and an internal - the granular layer. The molecular layer contains two types of neurons: the outer stellate cell and the inner basket cell.[1]
  • White matter – located underneath the cerebellar cortex. Embedded in the white matter are the four cerebellar nuclei (the dentate, emboliform, globose, and fastigial nuclei).

There are three ways that the cerebellum can be subdivided – anatomical lobes, zones and functional division[2]

  1. Anatomical Lobes
    There are three anatomical lobes that can be distinguished in the cerebellum. These lobes are divided by two fissures – the primary fissure and posterolateral fissure;
    • The anterior lobe,
    • The posterior lobe
    • The flocculonodular lobe. It is the oldest part of the brain in evolutionary terms (archicerebellum) and participates mainly in balance and spatial orientation. Its primary connections are with the vestibular nuclei, although it also receives visual and other sensory input.[3]
  2. Zones
    There are three cerebellar zones. In the midline of the cerebellum is the vermis. Either side of the vermis is the intermediate zone. Lateral to the intermediate zone are the lateral hemispheres. There is no difference in gross structure between the lateral hemispheres and intermediate zones
  3. Functional Divisions
    The cerebellum can also be divided by function. There are three functional areas of the cerebellum – the cerebrocerebellum, the spinocerebellum and the vestibulocerebellum.
    • Cerebrocerebellum – the largest division, formed by the lateral hemispheres. It is involved in planning movements and motor learning. It receives inputs from the cerebral cortex and pontine nuclei and sends outputs to the thalamus and red nucleus. This area also regulates coordination of muscle activation and is important in visually guided movements.
    • Spinocerebellum – comprised of the vermis and intermediate zone of the cerebellar hemispheres. It is involved in regulating body movements by allowing for error correction. It also receives proprioceptive information.
    • Vestibulocerebellum – the functional equivalent to the flocculonodular lobe. It is involved in controlling balance and ocular reflexes, mainly fixation on a target. It receives inputs from the vestibular system, and sends outputs back to the vestibular nuclei.

Dissection[edit | edit source]

Enjoy watching this about Lab dissection of cerebellum.

Radiology[edit | edit source]

Enjoy this MRI..

Cells (gray matter) [4][edit | edit source]

Schematic representation of the cerebellar cytoarchitecture. The cerebellar cortex is organized in three layers: molecular layer, Purkinje cell (PC) layer, and granular layer (GL). Purkinje, Golgi, stellate, and basket cells are inhibitory neurons; granule and unipolar brush cells are excitatory.

This picture introduce us to the cerebellar cells, so let's deep dive into it.

As you see, cerebellum is multilayer structure with folds. Each one of these folds consists of white matter core surrounded by gray matter layer.

The cortex gray matter has three layers: [5]

  • External - the molecular layer; contains two types of neurons: the outer stellate cell and the inner basket cell.
  • Middle - the Purkinje cell layer.
  • Internal - the granular layer.

Purkinje, Golgi, stellate, and basket cells are inhibitory neurons; granule and unipolar brush cells are excitatory.

Granule cells project their axons into the molecular layer, giving rise to the parallel fibers, which synapse with the dendrites of all inhibitory neurons of the molecular layer and with those of Golgi cells.

Afferents are of two main types: mossy and climbing fibers. Both are excitatory.

Mossy fibers originate from brainstem nuclei and the spinal cord, whereas climbing fibers come from the contralateral inferior olive.

Most mossy fibers synapse directly on the dendrites of four to five granule cells in specialized synaptic glomeruli (blue-gray circle), which also receive inhibitory feedback from Golgi cell axons. A small mossy fiber subset, first synapses on unipolar brush cells that then relay amplified excitatory signals to granule cells.

Each purkinje cell receives a connection from a single climbing fiber. Purkinje cell axons carry inhibitory signals to the cerebellar nuclei, whereas mossy and climbing fiber collaterals provide the cerebellar nuclei with excitatory afferents. The large glutamatergic neurons of the cerebellar nuclei project their axons to nuclei located in the brainstem and diencephalon.

Deep nuclei (white matter)[edit | edit source]

From lateral to medial, the four deep cerebellar nuclei are;

  • Dentate nucleus.
  • Emboliform nucleus.
  • Globose nucleus.
  • Fastigial nucleus.
Cross-section of human cerebellum shows cerebellar deep nuclei.

Pathways [6][edit | edit source]

Afferent Pathways

From Cerebral Cortex, there are three pathways sent to the Cerebellum;

  • Corticopontocerebellar pathway
  • Cerebro-olivocerebellar pathway
  • Cerebroreticulocerebellar pathway

From Spinal Cord (somatosensory receptors), there are also three pathways;

  • Anterior spinocerebellar pathway
  • Posterior spinocerebellar pathway
  • cuneocerebellar pathway

From Vestibular Nerve

Cerebellum also receives small bundles of afferent fibers from tectum and the red nucleus.

Efferent Pathways
  • Globose-emboliform-rubral pathway
  • Dentatothalamic pathway
  • Fastigial vestibular pathway
  • Fastigial reticular pathway

Cerebellar Peduncles[edit | edit source]

The cerebellum attaches to the brainstem by three groups of nerve fibers called the superior, middle and inferior cerebellar peduncles, through which efferent and afferent fibers pass to connect with the rest of the nervous system.

Function[edit | edit source]

Function by regions

  • The cortex of the vermis coordinates the movements of the trunk, including the neck, shoulders, thorax, abdomen, and hips.
  • Control of the distal extremity muscles is by the intermediate zone of cerebellar hemispheres, located adjacent to the vermis.
  • The remaining lateral area of each cerebellar hemisphere provides the planning of sequential movements of the entire body along with involvement in the conscious assessment of movement errors


Main Functions overall[3]

  • The cerebellum is essential for making fine adjustments to motor actions. Cerebellar dysfunction primarily results in problems with motor control.
  • Four principles are important to cerebellar processing: feedforward processing, divergence and convergence, modularity, and plasticity.
  • Signal processing in the cerebellum is almost entirely feedforward. Signals move through the system from input to output with very little internal transmission.
  • The cerebellum both receives input and transmits output via a limited number of cells.
  • The cerebellar system is divided into thousands of independent modules with similar structure.

Blood Supply[edit | edit source]

Circle of Willis en.svg.png

The cerebellum receives its blood supply from three paired arteries of vertebrobasilar system[2]

  • Superior cerebellar artery (SCA)
  • Anterior inferior cerebellar artery (AICA)
  • Posterior inferior cerebellar artery (PICA)

The SCA and AICA are branches of the basilar artery, which wraps around the anterior aspect of the pons before reaching the cerebellum. The PICA is a branch of the vertebral artery.

Venous drainage of the cerebellum is by the superior and inferior cerebellar veins. They drain into the superior petrosal, transverse and straight dural venous sinuses.

You can check this amazing Ninja Nerd video about cerebellum.

Clinical Significance[edit | edit source]

The cerebellum receives afferent information about voluntary muscle movements from the cerebral cortex and from the muscles, tendons, and joints. It also receives information concerning balance from the vestibular nuclei. Each cerebellar hemisphere controls the same side of the body, thus if damaged the symptoms will occur ipsilaterally.[1]

Dysfunction of the cerebellum can produce a wide range of symptoms and signs. 

The most common cause of cerebellar dysfunction is alcohol poisoning, but also trauma, multiple sclerosis, tumors, thrombosis of the cerebellar arteries and stroke.[1]

The clinical picture depends on the functional area of the cerebellum that is affected[3].

  • Damage to the flocculonodular lobe (vestibulocerebellum): loss of equilibrium causing an altered walking gait
  • Lateral zone damage: problems with skilled voluntary and planned movements leading to errors in intended movements (eg., dysdiadochokinesia, the inability to perform rapid alternating movements).
  • Damage to the midline portion: disruption of whole-body movements
  • Damage to the upper part of the cerebellum: gait impairments and other problems with leg coordination (ie, ataxia).

A wide variety of manifestations are possible (remembered by acronym ‘DANISH‘)[2]

  • Dysdiadochokinesia - the lack of ability to perform rapidly alternating movements. Ask the patient to quickly supinate and pronate both forearms simultaneously. Movements will be slow and incomplete on the side of the cerebellar lesion.[1]
  • Ataxia - voluntary movement disturbance involves tremor with fine movements eg writing or buttoning the clothes. Finger to nose test is performed to examine the coordination of the muscle movements, testing tip of the nose with the index finger test the movements are not properly coordinated, and tremor is observed at the end of the movement, called intention tremor. A similar test can be performed on the lower limbs ask patient to place the heel of one foot against the shin of the opposite leg.[1]
  • Nystagmus (coarse) - Ataxia of ocular muscles, a rhythmical oscillation of the eyes. To provoke nystagmus, the patient should rotate eyes horizontally
  • Intention tremor
  • Dysarthria/Scanning speech -  ataxia of the larynx muscles, speech is slurred and syllables are separated from one another.
  • Hypotonia - the muscles lose resistance to palpation due to diminished influence of the cerebellum on gamma motor neurons. The patient walks with a broad-based gait and leans toward the affected side.[1]

Occlusion of PICA cause Wallenberg syndrome

The short video below gives a good picture of the manifestations of cerebellum damage

[7]

The cerebellum appears to play a role in many types of behaviours. Cerebellar damage not only affects movement coordination but also disrupts some perceptual abilities such as visual motion discrimination. The cerebellum acts to make predictions for different cerebral areas of the brain to optimize their abilities-- helping to predict optimal motor commands for movement control and upcoming sensory events for sensory perception possibly explaining how cerebellar damage affects other behaviours.[8]

Physiotherapy[edit | edit source]

Physiotherapy management focuses on Compensatory or Restorative approach. Compensatory approach includes the used of assistive devices, reducing the degree of freedom and environment modifications. On the other hand, Restorative approach targets in improving the function by improving the impairment, Neuroplastic changes are seen to occur with practice[9].

Dynamic task practice by challenging the stability, exploring the stability limits and aiming to reduce upper limb weight bearing has been found to be more effective in improving the gait and balance[10]. Some evidence suggests that better outcomes are seen with less severe ataxia and patient’s ability in learning[11].

Physical therapy treatment includes,

Video-game based coordinative training

Although Intensive co-ordination training has shown to be effective in adults, children due to lack of interest and motivation does not show a great result. Instead, Intensive co-ordination training using Whole body-controlled video game was effective in children with progressive ataxia, but this intervention was no seen its effectiveness in adults and non-ambulant Childs[12].

The un-expected waist pull perturbation with A-TPAD (Active Tethered Pelvic Assisted Device) on a treadmill assisted gait training has shown its effectiveness on balance control during steady walking[13]

Lokomat-Pro-Robotic-Gait-Training.jpg

Treadmill training with or without partial body weight support, functional electrical stimulation of voluntary muscles and exergames that use computer technologies to provide an interactive environment which requires limb movement to react to on-screen gameplay (e.g. Wii, X Box).[14]

Exercise interventions includes,

  • Task-specific training with the aim of (re)acquiring a motor skill (with or without using robotic exoskeletons)[15]
  • Exercises that focus on regaining or sustaining control of the proximal muscles of the trunk, shoulder and pelvic girdle[16]
  • Exercises that aim to improve static and dynamic balance and proprioception as a component of postural control
  • Stretching exercises that aim to improve range of movement

An important finding of a recent study[17] was that the level of challenge to balance was more important than the duration of exercise in producing Neurorehabilitation and neural repair. Cerebellar patients with ataxia can benefit from a home exercise program focused on balance training (with significant improvements after just six weeks). Highlighted was the importance of the level of challenge to balance being of upmost importance and also individualizing the program and offering continued training and progression if necessary to see effect retention.

A systematic review seeing the effectiveness of exercise and physiotherapy intervention for children with ataxia concluded that the existing “studies reported promising results but were of low methodological quality (no RCTs), used small sample sizes and were heterogeneous in terms of interventions, participants and outcomes”. It emphasized the necessity of further of high quality child centered research[18].

Regeneration ?[edit | edit source]

Current research is going on into the search for neurogenesis of the central nervous system. An exciting prospect. Some of the news is reported below.

  • A current project is exploring the degree to which the brain can be repaired after neuron loss and identify factors that can stimulate stem cells to regenerate neurons.[19]
  • A 2019 [20]) report shows compelling evidence that the mature central nervous system (CNS) harbours stem cell populations outside conventional neurogenic regions. It has been demonstrated that brain pericytes (PCs) in both mouse and human exhibit multipotency to differentiate into various neural lineages following cerebral ischemia. Importantly putative ischemia-induced multipotent stem cells are present in poststroke cerebellum and possess region-specific traits, suggesting a potential capacity to regenerate functional cerebellar neurons following ischemic stroke[20].
  • Another 2019 study reported "Nerves in the central nervous system of adult mammals do not usually regenerate when injured. The granule cell, a nerve cell located in the cerebellum, is different. When its fibres, called parallel fibres, are cut, rapid regeneration ensues and junctions with other neurons called "synapses" are rebuilt. The precise mechanism for this was unclear"

Further Viewing[edit | edit source]

The below 4-minute video gives a great 3D view of the cerebellum and highlights it's similar structure to that of the cerebrum.

[21]

References[edit | edit source]

  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 Jimsheleishvili S, Dididze M. Neuroanatomy, Cerebellum. InStatPearls [Internet] 2019 Mar 2. StatPearls Publishing.Available from:https://www.ncbi.nlm.nih.gov/books/NBK538167/ (last accessed 19.1.2020)
  2. 2.0 2.1 2.2 2.3 Teach me anatomy. The Cerebellum Available from: https://teachmeanatomy.info/neuroanatomy/structures/cerebellum/ (last accessed 20.1.2020)
  3. 3.0 3.1 3.2 Lumenlearning. Cerebellum Available from:https://courses.lumenlearning.com/boundless-ap/chapter/the-cerebellum/ (last accessed 20.1.2020)
  4. Consalez GG, Goldowitz D, Casoni F, Hawkes R. Origins, development, and compartmentation of the granule cells of the cerebellum. Frontiers in neural circuits. 2021:88.
  5. Jimsheleishvili S, Dididze M. Neuroanatomy, cerebellum. July 24, 2023.
  6. Ryan Splittgerber. Cerebellum and Its Connections. Snell's Clinical Neuroanatomy. 2018
  7. Soton brain hub Cerebellar disease symptoms Available from:https://www.youtube.com/watch?v=fMMcMPI68V0&app=desktop (last accessed 20.1.2020)
  8. Bastian AJ. Moving, sensing and learning with cerebellar damage. Current opinion in neurobiology. 2011 Aug 1;21(4):596-601.Available from:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3177958/ (last accessed 20.1.2020)
  9. Armutlu K, Karabudak R, Nurlu G. Physiotherapy Approaches in the Treatment of Ataxic Multiple Sclerosis: A Pilot Study. Neurorehabilitation and Neural Repair (Internet). 2001 Sep (cited 2023 Apr 17);15(3):203–11. Available from: https://pubmed.ncbi.nlm.nih.gov/11944742/%0A%0A‌
  10. Balliet R, Harbst KB, Kim D, Stewart RV. Retraining of functional gait through the reduction of upper extremity weight-bearing in chronic cerebellar ataxia. International Rehabilitation Medicine (Internet). 1986 Jan (cited 2023 Apr 17);8(4):148–53. Available from: https://pubmed.ncbi.nlm.nih.gov/3610487/%0A%0A‌
  11. Hatakenaka M, Miyai I, Mihara M, Yagura H, Hattori N. Impaired Motor Learning by a Pursuit Rotor Test Reduces Functional Outcomes During Rehabilitation of Poststroke Ataxia. Neurorehabilitation and Neural Repair [Internet]. 2011 Sep 29 (cited 2023 Apr 17);26(3):293–300. Available from: https://pubmed.ncbi.nlm.nih.gov/21959676/%0A%0A‌
  12. Ilg W, Schatton C, Schicks J, Giese MA, Schols L, Synofzik M. Video game-based coordinative training improves ataxia in children with degenerative ataxia. Neurology (Internet). 2012 Oct 31 (cited 2023 Apr 17);79(20):2056–60. Available from: https://pubmed.ncbi.nlm.nih.gov/23115212/%0A%0A‌
  13. Aprigliano F, Martelli D, Kang J, Kuo SH, Kang UJ, Monaco V, et al. Effects of repeated waist-pull perturbations on gait stability in subjects with cerebellar ataxia. Journal of NeuroEngineering and Rehabilitation (Internet). 2019 Apr 11 (cited 2023 Apr 17);16(1). Available from: https://pubmed.ncbi.nlm.nih.gov/30975168/%0A%0A‌
  14. Hartley H, Cassidy E, Bunn L, Kumar R, Pizer B, Lane S, Carter B. Exercise and Physical Therapy Interventions for Children with Ataxia: a systematic review. The Cerebellum. 2019 Aug 7:1-8.Available from:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6761087/ (last accessed 20.1.2020)
  15. Kim SH, Han JY, Song MK, Choi IS, Park HK. Effectiveness of Robotic Exoskeleton-Assisted Gait Training in Spinocerebellar Ataxia: A Case Report. Sensors (Internet). 2021 Jul 17 (cited 2023 Apr 17);21(14):4874. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8309925/
  16. Elshafey MA, Abdrabo MS, Elnaggar RK. Effects of a core stability exercise program on balance and coordination in children with cerebellar ataxic cerebral palsy. Journal of musculoskeletal & neuronal interactions (Internet). 2022 (cited 2023 Apr 17);22(2):172–8. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9186458/
  17. Keller JL, Bastian AJ. A home balance exercise program improves walking in people with cerebellar ataxia. Neurorehabilitation and neural repair. 2014 Oct;28(8):770-8. Available from:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4133325/ (last accessed 20.1.2020)
  18. Hartley H, Cassidy E, Bunn L, Kumar R, Pizer B, Lane S, et al. Exercise and Physical Therapy Interventions for Children with Ataxia: A Systematic Review. The Cerebellum (Internet). 2019 Aug 7 (cited 2023 Apr 17);18(5):951–68. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6761087/%0A%0A‌
  19. Sloan Kettering Inst. Cerebellum development and regeneration Available from: https://www.mskcc.org/research/ski/labs/alexandra-joyner/cerebellum-development-and-regeneration (last accessed 21.1.2020)
  20. 20.0 20.1 Beppu M, Nakagomi T, Takagi T, Nakano-Doi A, Sakuma R, Kuramoto Y, Tatebayashi K, Matsuyama T, Yoshimura S. Isolation and Characterization of Cerebellum-Derived Stem Cells in Poststroke Human Brain. Stem cells and development. 2019 Apr 15;28(8):528-42. Available from:https://www.liebertpub.com/doi/abs/10.1089/scd.2018.0232?journalCode=scd (last accessed 21.1.2020)
  21. Neuromatic The Cerebellum AVAILABLE FROM:https://www.youtube.com/watch?v=gqwCIXD0218&app=desktop (last accessed 21.1.2020)