In the 1820s, Gall and Spurzheim tried to analyse and localise cerebral functions physiologically. They developed new ideas of brain function. To test Gall’s assertions of cerebral localisation, Marie-Jean-Pierre Flourens (1794–1867) working on pigeons developed crude ablation as a procedure to explore the workings of the brain. Flourens’ general conclusion was that the brain functioned as a whole, the mistaken concept of ‘cerebral equipotentiality’ [1]. However, when he removed the cerebellum, the animals could no longer coordinate movements. He therefore stated that the cerebellum regulates and coordinates motor activity [2].

Charles Sherrington in 1906 referred to the cerebellum as the “head ganglion of the proprioceptive system.” When Gordon Holmes analysed cerebellar injuries sustained during the First World War, he recalled Weir Mitchell’s animal experiments reported in Researches on the physiology of the cerebellum (1869) that showed the cerebellum as a “great motor reinforcing organ of the cerebrospinal motor system [3].” Holmes noted:

It sets or tunes, or regulates the activity of certain motor mechanisms …effective and proportional to the intensity of the cerebral impulse.

This notion that the cerebellum was a structure that modified movement was soundly established. Cerebellar lesions caused ataxia, loss of balance, hypotonia, slurred speech and nystagmus. Motor impairments are ipsilateral to cerebellar lesions. Injuries, multiple sclerosis, tumours, vascular and various genetic and degenerative lesions were the common causes.

The clinical spectrum more recently has widened to include non–motor disorders.

Phylogenetically, the cerebellum has three subdivisions: the archicerebellum (vestibular cerebellum) is the oldest part, comprising the flocculonodular lobe and lingula with mainly vestibular connections. The paleocerebellum (spinal cerebellum) includes the anterior lobe except the lingual, pyramid and uvula. It subserves spinocerebellar connections. The neocerebellum (cerebral cerebellum) the most recent, includes the posterior lobe except the pyramid and uvula. It subserves cortico-ponto-cerebellar connections. Based both on experimental evidence and information processing theory it is suggested that the phylogenetically newest neocerebellum contributes to mental skills in a way similar to the phylogenetically older structures’ contribution to motor activity [4].

Non–motor functions

As recently as 1998, based on twenty patients, Schmahmann and Sherman described a cerebellar cognitive affective (Schmahmann’s) syndrome and coined the term “dysmetria of cognitive function.” They surmised:

It may also transpire that in the same way as the cerebellum regulates the rate, force, rhythm, and accuracy of movements, so may it regulate the speed, capacity, consistency, and appropriateness of mental or cognitive processes [5].

The idea is that the cerebellum forms part of a network of cerebro-cerebellar and cerebello-cerebral connections that mediate cognitive functions. They are primarily distributed in the neocerebellum which includes part of the dentate nuclei. These areas were massively increased in size during hominid evolutionary development, at the same time as similar increases in prefrontal and association cortices.

Clinical observations

A litany of psychiatric disorders are now claimed to relate to cerebellar disorders: bipolar disorder, posttraumatic stress disorder, attention deficit and autistic disorders, and schizophrenia.

In MS cerebral cortical and cerebellar lesions in gray and white matter are common, but cerebellar damage and functional connectivity changes are prominent mainly in secondary progressive MS and related to cognitive impairment [6].

Cerebellar atrophy is found in neurodegenerative Alzheimer’s disease, frontotemporal dementia, amyotrophic lateral sclerosis, multiple system atrophy, and progressive supranuclear palsy, but not in Parkinson’s or Huntington’s diseases [7]; the patterns of atrophy are disease specific rather than relating to specific cognitive disorders. Likewise, reports of focal lesions in the cerebellum accurately correlated with resulting cognitive disorders are sparse. Some respected physicians remain sceptical.

In an eighteen-year-old patient whose right cerebellar hemisphere was removed for a tumour, transient short-term memory deficit but no other cognitive deficits were noted [8]. In a 49-yr-old male with right cerebellar damage standard tests of memory, intelligence, ‘frontal function’ and language skills were excellent, but practice-related learning and detection of errors were impaired [9]. A study of patients with left cerebellar infarcts noted they were slow in a visuospatial task, whereas those with right–sided lesions had verbal memory difficulties. Yet, such laterality of function has also been disputed [10].

Evidence suggests that the cerebellum modulates four main ‘cognitive domains’: executive functions, language and verbal memory, spatial tasks and emotions. Posterior lobe lesions result in the cerebellar cognitive affective syndrome, characterised by deficits in executive function, visual spatial processing, linguistic skills and regulation of affect [11,12].

Figure 1. Simplified diagram of the Cerebro–cerebellar circuit [12]
Figure 1. Simplified diagram of the Cerebro–cerebellar circuit [12]

Anatomy

There is clinical and physiological evidence to support this association, consistent with anatomical connections between the cerebellum, basal nuclei and the neocortex, which may be involved in cognitive sequencing, executive, visuo–spatial, and language functions and mood changes [11].

The posterolateral lobules of the cerebellum are richly populated with neurons interconnected through polysynaptic circuits with the contralateral cerebral hemispheres [12]. The afferent channels from the neocortex to the cerebellum synapse in the pons then cross to the cerebellum; an efferent channel projects via the dentate nucleus of the cerebellum to the basal ganglia, thalamus, and finally to newly discovered cerebral association areas of the neocortex and basal ganglia [5]. (Figure 1)

A suggested mechanism is that the cerebellum modulates cerebral functions by a process that predicts then prepares for a planned operation (motor, verbal or mental). It is tentatively suggested that this operates by altering blood flow or by enhancing neural responsiveness in different areas [13]. This complements Schmahmann’s “dysmetria of cognitive function theory” that the cerebellum modulates behaviour, maintaining it around a homeostatic baseline appropriate to context [5].

Both positron emission tomography and task-based fMRI studies show cerebellar activation during a variety of cognitive, emotional, and sensory paradigms such as the completion of a puzzle [14]. Using highly sophisticated technology it appears these cerebellar activations are topographically arranged [15]. The anterior lobe is mainly related to sensorimotor activities; the posterior lobe in particular Lobules VI and VII mainly involved in higher-level cognitive tasks [16]. During neuropsychological investigations the human cerebellum responds to verbal and cognitive tasks. They may have been overlooked because defects are less severe than the more obvious motor disturbances [9,17] and are shown only by refined psychometric testing.

The cerebello-parietal component of grey matter structural networks and the frontal component have been significantly associated with intelligence [18]. Intelligence and cognitive functions are often confused, and intelligence still defies accurate definition. In most relevant papers Trail Making Tests (TMT), and the Wechsler Adult Intelligence Scale (WAIS) consisting of vocabulary, arithmetic, block design, arbitrarily assess it and picture arrangement subtests.

Conclusion

In Holmes’ seminal paper he said:

[the cerebellum] receives and integrates proprioceptive impulses from all parts of the body, and by virtue of these it keeps the motor mechanisms in such a state of “tone” that they can react promptly and efficiently to voluntary impulses, and it thus assures the correct co-operation of the separate motor centres that are concerned in individual acts [3].

Although uncertainties remain, a similar concept is now applied to various types of cognition, language, affect, and behaviour— based on dysfunction of the massive network of cerebello–cerebral association areas. However, clinicopathological reports of cerebellar lesions (focal or diffuse) accurately correlated with resulting cognitive disorders are few. Precisely how the cerebellum works in synergy with basal ganglia and cerebral cortex in affecting thought, behaviour and emotions has yet to be clarified.

References

  1. Pearce JMS. Marie-Jean-Pierre Flourens (1794-1867) and Cortical Localization. Eur Neurol 1 April 2009;61(5):311-314. https://doi.org/10.1159/000206858
  2. Flourens MJP. Recherches expérimentales sur les propriétés et les fonctions du système nerveux, dans les animaux vertébrés (ed 1). Paris, Chez Crevot, 1824;26:20.
  3. Holmes GM. The symptoms of acute cerebellar injuries due to gunshot injuries. Brain. 1917;40:461-535. https://doi.org/10.1093/brain/40.4.461
  4. Leiner HC, Leiner AL, Dow RS. Does the cerebellum contribute to mental skills? Behav. Neurosci 1986;100:443-454. https://doi.org/10.1037/0735-7044.100.4.443
  5. Schmahmann JD, Sherman JC. The cerebellar cognitive affective syndrome. Brain 1998;121:561-579. https://doi.org/10.1093/brain/121.4.561
  6. Schoonheim MM, Douw L, Broeders TA, Eijlers AJ, Meijer KA, Geurts JJ. The cerebellum and its network: Disrupted static and dynamic functional connectivity patterns and cognitive impairment in multiple sclerosis. Mult Scler. 2021;27(13):2031-39. https://doi.org/10.1177/1352458521999274
  7. Gellersen HM, Guo CC, O’Callaghan C, et al Cerebellar atrophy in neurodegeneration-a meta-analysis Journal of Neurology, Neurosurgery & Psychiatry 2017;88:780-788. https://doi.org/10.1136/jnnp-2017-315607
  8. Silveri M C, Di Betta A M, Filippini V, Leggio M G, Molinari M. Verbal short-term store-rehearsal system and the cerebellum. Evidence from a patient with a right cerebellar lesion. Brain 1998;121(11):2175-2187. https://doi.org/10.1093/brain/121.11.2175
  9. Fiez JA et al. Impaired non-motor learning and error detection associated with cerebellar damage: a single case study. Brain. 1992;115:155-178. https://doi.org/10.1093/brain/115.1.155
  10. Tedesco AM, Chiricozzi FR, Clausi S, Lupo M, Molinari M,. Leggio MG. The cerebellar cognitive profile. Brain. 2011;134(12):3672-3686. https://doi.org/10.1093/brain/awr266
  11. Schmahmann JD. The cerebellum and cognition. Neurosci Lett. 2019:Jan1;688:62-75. https://doi.org/10.1016/j.neulet.2018.07.005
  12. Buckner R. L., The cerebellum and cognitive function: 25 years of insight from anatomy and neuroimaging. Neuron. 2013;80:807-815. https://doi.org/10.1016/j.neuron.2013.10.044
  13. Courchesne E , Allen G. Prediction and preparation, fundamental functions of the cerebellum. Learn Mem 1997;4:1-35 https://doi.org/10.1101/lm.4.1.1
  14. Klein AP, Ulmer JL, Quinet SA, Mathews V, Mark LP. Nonmotor Functions of the Cerebellum: An Introduction. Am J Neuroradiol. 2016;Jun 37(6):1005-9. https://doi.org/10.3174/ajnr.A4720
  15. Guell X, Gabrieli JDE, Schmahmann JD. Triple representation of language, working memory, social and emotion processing in the cerebellum: convergent evidence from task and seed-based resting-state fMRI analyses in a single large cohort. Neuroimage. 2018;May15;172:437-449. https://doi.org/10.1016/j.neuroimage.2018.01.082
  16. Grimaldi G, Manto M. Topography of cerebellar deficits in humans. Cerebellum 2012;11:336-51. https://doi.org/10.1007/s12311-011-0247-4
  17. Gottwald B, Wilde B, Mihajlovic Z, et al Evidence for distinct cognitive deficits after focal cerebellar lesions Journal of Neurology, Neurosurgery & Psychiatry 2004;75:1524-1531. https://doi.org/10.1136/jnnp.2003.018093
  18. Yoon, Y.B., Shin, WG., Lee, T.Y. et al. Brain Structural Networks Associated with Intelligence and Visuomotor Ability. Scientific Reports 2017;7:2177. https://doi.org/10.1038/s41598-017-02304-z