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Vol 83, No 3 (2024): Folia Morphologica
Review article
Published online: 2024-07-02

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The cerebellum: the ‘little’ brain and its big role

Natalia Melka1, Adriana Pszczolinska1, Ilona Klejbor23, Janusz Moryś24
DOI: 10.5603/fm.93251
Pubmed: 38963083
Folia Morphol 2024;83(3):497-508.

Abstract

Reports from recent years provide compelling evidence about the structure and the existence of functional topography in the cerebellum. However, most of them focused on the motor functions of the cerebellum. Recent studies suggest the involvement of the posterior lobe of the cerebellum in the context of neurodegenerative and cognitive disorders. The pathophysiology of these diseases is not sufficiently understood, and recent studies indicate that it could also affect additional subregions of the cerebellum. Anatomical and clinical studies, combined with neuroimaging, provide new ways of thinking about the organisation and functioning of the cerebellum. This review summarises knowledge about the topography and functions of the cerebellum, and focuses on its anatomical and functional contributions to the development of neurological diseases.

Keywords: cerebellumanatomical organizationlimbic system

REVIEW ARTICLE

Folia Morphol.

Vol. 83, No. 3, pp. 497–508

DOI: 10.5603/fm.93251

Copyright © 2024 Via Medica

ISSN 0015–5659

eISSN 1644–3284

journals.viamedica.pl

The cerebellum: the ‘little’ brain and its big role

Natalia Melka1Adriana Pszczolinska1Ilona Klejbor23Janusz Moryś24
1Department of Anatomy and Neurobiology, Medical University of Gdańsk, Gdańsk, Poland
2Department of Human Anatomy and Physiology, Pomeranian University in Słupsk, Słupsk, Poland
3Department of Anatomy, Jan Kochanowski, University of Kielce, Kielce, Poland
4Department of Normal Anatomy, Pomeranian Medical University in Szczecin, Szczecin, Poland

[Received: 16 December 2022; Accepted: 1 July 2024; Early publication date: 2 July 2024]

Address for correspondence: Janusz Moryś, Department of Human Anatomy and Physiology, Pomeranian University in Słupsk, 64 Bohaterów Westerplatte St, 76–200 Słupsk, Poland; e-mail: janusz.morys@pum.edu.pl

This article is available in open access under Creative Common Attribution-Non-Commercial-No Derivatives 4.0 International (CC BY-NC-ND 4.0) license, allowing to download articles and share them with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially.

Reports from recent years provide compelling evidence about the structure and the existence of functional topography in the cerebellum. However, most of them focused on the motor functions of the cerebellum. Recent studies suggest the involvement of the posterior lobe of the cerebellum in the context of neurodegenerative and cognitive disorders. The pathophysiology of these diseases is not sufficiently understood, and recent studies indicate that it could also affect additional subregions of the cerebellum. Anatomical and clinical studies, combined with neuroimaging, provide new ways of thinking about the organisation and functioning of the cerebellum. This review summarises knowledge about the topography and functions of the cerebellum, and focuses on its anatomical and functional contributions to the development of neurological diseases. (Folia Morphol 2024; 83, 3: 497–508)
Keywords: cerebellum, anatomical organisation, limbic system

INTRODUCTION

One of the first reports linking the cerebellum to cognitive functions was the work of Vincenzo Malacarne in a book entirely devoted to the cerebellum [63], in which the author correlated an individual’s intelligence level with the number and degree of development of cerebellar lamellae. Since then, more and more research has focused on non-motor functions, including cognitive and emotional processes; however, interpretation and reference to the results were hindered by a strongly entrenched view regarding the purely motor role of the cerebellum. A breakthrough occurred after 1997 when patients with damage to the posterior lobe of the cerebellum were observed to have a series of emotional-cognitive symptoms that went beyond the realm of motor dysfunction previously attributed to the cerebellum. Since then, interest in the topic has been rapidly increasing. The results obtained also help in understanding why the cerebellum, accounting for only 10% of the total brain volume, has over 50% of the total number of neurons in the central nervous system [48, 102, 108]. Currently, we know that the cerebellum occupies an important place in the neural circuits underlying cognitive processes, and its numerous connections with the limbic system indicate a strong involvement in emotions [1, 11, 91]. This hypothesis is confirmed by clinical observations conducted in individuals with cerebellar hemisphere injuries, where a characteristic cognitive-emotional syndrome has been identified based on the clinical symptoms observed, also known as Schmahmann syndrome [91]. Concurrent research has shown strong connections between non-motor areas of the cerebral cortex and the cerebellum [15], demonstrating that over half of the cerebellum may be associated with non-motor functions, and the efferent and afferent connections with the limbic system and cerebral cortex are the basis for explaining the cerebellum’s involvement in emotional processes and its contribution to motivation [11]. Considering the complex function of the cerebellum, we should treat this structure as a collection of more or less independent centres, distinguishing within it, for example, motor centres if they are connected to the motor system or the limbic one if the connections of these areas of the cerebellum are related to the limbic system. In this approach, within the cerebellum, we can distinguish characteristic regions responsible for processing motor and non-motor information, including those related to emotions. The latter are often called the limbic cerebellum, emphasising its role in higher-order behavioural functions.

Cerebellar anatomy

Over the years, several proposals for dividing the cerebellum have emerged. The most anatomical division of this structure is based on the existence of 2 classic fissures present in all organisms possessing this structure (Fig. 1). It includes the anterior lobe, separated from the posterior lobe by the primary fissure, and the cerebellar vermis, separated from the posterior lobe by the posterolateral fissure. The second most popular division is based on functional zones localised parallel to the midline, including the vermis zone located medially, the intermediate or paravermal zone, and the lateral (hemispheral) zone located laterally. Additionally, within the cerebellar vermis, 10 lobules have been identified, which can be grouped into transverse zones [4, 5, 72] (Tab. 1). A unique combination of Purkinje cell phenotypes characterises each transverse zone, and different zones have distinct developmental timelines. A simple explanation for the evolutionary development of cerebellar lobules is that it was a way to increase surface area and thus adapt to the increased number of cells, which in turn facilitated the acquisition of more complex functional circuits [72, 112].

Figure 1. Depending on the chosen division, the surface of the cerebellum can be divided into lobes (based on constant fissures) or based on zones parallel to the median line. The latter division is more functional than anatomical. Considering the phylogenetic aspects due to the time of origin, we can distinguish 3 characteristic parts within the cerebellum, also reflecting the functional division of this structure. The division of the cerebellum based on the midline includes the vermis, paravermis, and hemispheres. The division of the vermis includes 10 lobules, which combine into functional transverse zones: anterior (AZ), central (CZ), posterior (PZ), and nodular zone (NZ). The anterior zone forms the anterior lobe (AL). The central and posterior zones form the posterior lobe (PL). The nodular zone forms the flocculonodular lobes. The division between the anterior and posterior lobes is demarcated by the primary fissure (pf). The phylogenetic division of the cerebellum includes: archicerebellum (nodule — X), paleocerebellum (anterior lobe — I–V), and neocerebellum (posterior lobe — VI–IX).
Table 1. Comparison of current cerebellar divisions with a division into lobules.

Lobes (based on fissures)

Lobules (based on folia)

Transverse zone

Anterior

(Paleocerebellum)

I

II

III

IV

V

AZ (anterior zone)

Posterior

(Neocerebellum)

VI

VII

CZ (central zone)

VIII

IX

PZ (posteriori zone)

Flocculonodular

(Archicerebellum)

X

NZ (nodular zone)

Considering the phylogenetic development of the cerebellum, we distinguish 3 characteristic parts within this structure: archicerebellum, paleocerebellum, and neocerebellum. The phylogenetic division of the cerebellum largely corresponds to the traditional functional division of this structure. The oldest part of the cerebellum, the cerebellar vermis, is connected to the vestibular system and the reticular formation of the brainstem. This system participates in the control of balance, posture, and eye movements. The slightly younger paleocerebellum, also called the spinocerebellum, includes the anterior lobe, the vermis, and the paravermis. Until recently, this part was considered the main region responsible for controlling postural movements of the body; however, modern research has shown that the vermis has many connections with subcortical areas of the brain directly involved in motivation and emotions, and the term “limbic cerebellum” emphasises these connections. The posterior lobes, considered the youngest evolutionary structures, include the third and last system and are called the neocerebellum.

Methods of cerebellar segmentation

Due to the complex division of the cerebellum, which is also subject to classification changes, manual division and description of the cerebellum is an extremely time-consuming process. To shorten this time, various semi-automatic or automatic methods supporting researchers in describing and identifying individual cerebellar lobules have been developed. One of the first semi-automatic algorithms is the spatially unbiased infra-tentorial template (SUIT) [31]. However, this method does not allow for the detection of anatomical differences. More recent and accurate methods are fully automatic, such as the automatic classification of cerebellar lobules algorithm using implicit multi-boundary evolution (ACCLAIM) [13], the method based on multi-atlas segmentation called MAGeT brain (multiple automatically generated templates of different brains) [17], and the rapid automatic segmentation of the human cerebellum and its lobules (RASCAL) [111], or the innovative method of cerebellar lobule segmentation called CERES (cerebellum segmentation) [83, 84]. Undoubtedly, the implementation of a technique that allows for automatic segmentation in a maximally shortened time offers tremendous potential for working with a large number of patients and helps better understand the anatomy of the cerebellum and the consequences of its disorders.

Cellular structure

The cerebellum consists of an outer grey matter area, an inner white matter area, and 3 pairs of deep cerebellar nuclei [26]. The cerebellar cortex has 3 layers [102] (Fig. 2). The outermost layer is the molecular layer containing inhibitory interneurons, the intermediate layer contains Purkinje cells, and the innermost layer is the granular cell layer. Purkinje cells are a unique type of neuron with a specific structure. Due to their massive and highly branched dendritic tree, they can integrate large amounts of information and learn through dendritic remodeling. The Purkinje cell layer integrates excitatory signals from the granular layer with inhibitory information from the molecular layer. Purkinje cells are the only cells that project out of the cerebellum and are essential for motor coordination [7], as well as for other important cognitive functions such as emotions. The ability to characterise each type of cerebellar neuron is crucial for understanding cerebellar pathology [102]. Various cerebellar defects, including developmental dysfunctions, can manifest as motor disorders and be associated with non-motor states such as depression and cognitive deficits [29, 40, 98]. Changes in cerebellar volume and molecular alterations in Purkinje cells have been noted in patients with affective disorders, depression, as well as neurotic traits [1, 67, 92]. Purkinje cell involvement in disorders such as autism is also indicated. Postmortem studies in patients with autism spectrum disorders have shown loss of cerebellar Purkinje cells [104], and it is also suggested that dysregulated GABA production in Purkinje cells may contribute to the clinical features of autism [116]. The availability of cell-specific markers is essential for understanding the role of each type of neuron in the cerebellum. Numerous molecular markers, such as the calcium-binding protein calbindin D28K (CB), can be used for labelling and quantitatively assessing Purkinje cells. Purkinje cells are the only cerebellar cells that express CB. Staining of the cerebellum for calbindin expression reveals regular transverse divisions, with distinct transition regions that divide the vermis into the aforementioned 4 transverse zones [7]. It is also important to note that CB in Purkinje cells plays a significant role in coordinating motor behaviours [7]. Studies indicate that the selective genetic deletion of calbindin from cerebellar Purkinje cells results in a new mouse phenotype with marked deficits in the precision of motor coordination and the processing of visual information important for coordination.

Figure 2. Cytoarchitecture and neuronal circuitry of the cerebellar cortex: Purkinje cells make synaptic connections with granule cells. Purkinje cells transfer the signals from granule cells and other interneurons and send the final output to the deep cerebellar nuclei. Climbing fibres and mossy fibres are the main afferents from outside the cerebellum [76] the activity of inhibitory interneurons proved the key to endow networks with complex computational and dynamic properties. In the last 50 years, the prevailing view on the functional role of cerebellar cortical inhibitory circuits was that excitatory and inhibitory inputs sum spatially and temporally in order to determine the motor output through Purkinje cells (PCs).
Where do emotions reside in the cerebellum?
Anatomical evidence

It has long been known that the cerebellum has direct connections with motor centres (Fig. 3). However, contemporary research has also shown bidirectional connections of the cerebellum with brain regions involved in emotion regulation. Understanding the physiological significance of these connections has a fundamental impact on explaining the role of the cerebellum in higher cognitive functions [78] because it explains the mechanisms through which these areas mutually influence each other [11, 52, 76]. Extensive connections have also been identified and described between the cerebellum and prefrontal cortical and posterior parietal regions [79, 110]. The posterior lobe, known as the limbic cerebellum, plays a crucial role in these loops, as it has connections with the prefrontal, temporal, cingulate, and posterior parietal cortices. Additionally, connections with the brainstem have been demonstrated, which through neurotransmitters such as norepinephrine, serotonin, and dopamine, influence mood regulation in humans [37, 56, 87].

Figure 3. The image depicts a macroscopic diagram of the cerebellum and indicates the regions and type of function with which they are mainly associated.
The cerebello-amygdala circuit — a missing link?

In light of current research findings, the cerebellum is described as an essential structure for affective, cognitive, and memory processing. Functional connections between the cerebellum and the amygdala, a key structure in the limbic system responsible for emotional processes, were identified over 4 decades ago [47]. Recent anatomical evidence has ruled out the existence of a monosynaptic connection between these structures [52]. Using transneuronal tracing techniques, researchers described a new polysynaptic network of connections between the deep cerebellar nuclei and the basolateral part of the amygdala, passing through the thalamus [52]. Additionally, the latest reports indicate that there is a functional connectivity between the cerebellum and the amygdala, which is correlated with anxiety [119]. This discovery marks the beginning of a path towards new knowledge regarding the role of the cerebellum in influencing the emotion-controlling structure in humans.

“HippoBellum”

Years of research yielding convergent results report on the role of the cerebellum in spatial cognition. There is evidence of anatomical and functional connections between the cerebellum and the hippocampus [85, 117]. Evidence of communication between these structures provides the opportunity to delineate new therapeutic pathways for pathologies related to the hippocampus. The therapeutic potential in an increasing number of diverse neuropsychiatric and neurological diseases is provided by experimental cerebellar neurostimulation [66]. Studies report on the potential use of the cerebellum in treating temporal lobe epilepsy [99]. There is growing interest in the clinical aspect of the cerebellum due to its involvement in cognitive functions, including episodic memory. The role of the cerebellum in cognitive deficits is also indicated [51]. Influencing the hippocampus through cerebellar stimulation opens up possibilities in the therapy of hippocampal-dependent memory disorders occurring in neurodegenerative diseases such as Alzheimer’s.

Not only motor support — important collaboration between basal ganglia and cerebellum

Just like the cerebellum, the basal ganglia were until recently overlooked in the context of emotional functions [74]. Their connections with the cerebellum were not considered at all, and it was thought that these structures modulate cortical activity independently of each other, through separate pathways passing through the thalamus. Similar to the cerebellum, the basal ganglia were attributed only a motor function. Recent reports describe the involvement of these structures not only in motor but also in cognitive functions. Today, it is known that there are direct connections between the cerebellum and the basal ganglia, meaning that they jointly shape and adapt both motor and emotional functions [24, 45, 54, 75, 114]. Their functions are not separate but overlap. The cerebellum precisely adjusts the response to improve the final outcome according to the current physiological state [74]. Such a mechanism of cooperation, consistent with the context of a given situation, allows for the generation of a proportional and situationally appropriate response. Understanding the importance of this collaboration between the cerebellum and basal ganglia is important from the perspective of neurodegenerative diseases associated with aging and the decline in both motor and cognitive functions. References in the literature regarding brain aging have so far mainly referred to the cerebral cortex. Establishing the role of connections between structures that play a crucial role in motor behaviours and affect higher-order mental functions [45, 96, 97], as well as the connections of these structures with motor, prefrontal, and associative cortex [43, 45, 79, 109], is important for a better understanding of the pathomechanisms of diseases such as Parkinson’s disease [81, 120] or Huntington’s disease [38, 86]. In the case of these diseases, both structural and functional changes in the cerebellum have been noted.

Functional neuroimaging studies — what about the cerebellum and its topography?

The lack of direct monosynaptic connections between the cerebral cortex and the cerebellum poses a significant challenge in studying the organisation of the brain-cerebellar network [100]. Centripetal connections pass through the pons, and centrifugal connections lead from the deep cerebellar nuclei through the thalamus [90]. Brain-cerebellar connections cannot be studied using monosynaptic retrograde tracing. A breakthrough was the use of polysynaptic tracing in nonhuman primates, which revealed the fundamental nature of brain-cerebellar connections [53]. The authors described separate brain-cerebellar connections for motor and non-motor functions.

We now know that the spatial organisation of motor and nonmotor function representations within the cerebellum is based on polysynaptic connections between the cerebellum and other brain areas. Radiological studies based on functional magnetic resonance imaging (fMRI) techniques indicate the existence of a functional division of the cerebellum. MRI provides a comprehensive view of brain structures, including the entire brain, and importantly, its sensitivity and specificity allow for the study of polysynaptic connections, making them the basis of today’s cerebellar functional research. fMRI studies in healthy individuals indicate cerebellar activation during a wide range of activities, from simple motor tasks to higher-order cognitive tasks. Patterns of this activation vary for sensorimotor, affective, and cognitive tasks. These findings are confirmed by electrophysiological experiments and pathway analysis in animal models [53]. Understanding the functional topography is crucial for understanding and interpreting clinical data in the case of cerebellar diseases or injuries. This allows for an understanding of the role of the cerebellum in both motor and higher-order mental functions [96].

Available research findings in healthy individuals indicate that half of the cerebellar cortex is involved in cognitive processes. Non-motor functions have their representation in the posterior lobe of the cerebellum, which includes lobules VI–IX. There is evidence of functionally diverse regions within each lobule, which are associated with distinct functional networks, in various ways supporting affective or cognitive processing [93]. A hypothesis has been put forward about the involvement of the posterior lobe of the cerebellum in intrinsic connectivity networks involved in higher-order mental functions [43]. According to the results of these studies, the neocerebellum participates in 1) executive control networks, 2) the salience network, and 3) the default-mode network [43]. Imaging studies also describe the existence of a functional network between lobules VIIB, VIII, and IX of the cerebellum and the amygdala [12, 42, 57, 88, 96]. Activation of the neocerebellum in healthy adults depends on the nature of the task being performed [96]: emotional processing activated lobules VI, VIIA, and crus I, executive functions activated VI, VII crus I, and crus II, and working memory was associated with the activation of lobules CI, VII, and VIIIA. Social cognitive tasks activated lobules IX and crus I [107]. Interestingly, in the case of motor tasks that required action planning, lobules VI and VII were sometimes activated in addition to anterior lobe activation [89].

The cerebellum and depression

A better and more precise understanding of the cerebellum’s involvement in non-motor functions develops our knowledge of the neurobiology of emotions. Cerebellar damage has caused patients to experience impairments in higher mental and executive functions [100], as well as emotional disorders [1]. Conversely, any cerebellar dysfunction is directly associated with emotional impairment, as observed in anxiety [69], post-traumatic stress disorder [68], schizophrenia [19, 35, 70], autism [63], as well as with emotional and cognitive disorders collectively referred to as cerebellar cognitive-affective syndrome [49, 58, 91]. Increasingly, data indicate the involvement of the cerebellum in depression [6, 12, 23]. Many clinical studies point to the coexistence of depression with cerebellar diseases [23, 24, 62].

Cerebellar structural and functional abnormalities in depression

Depression is defined as “cortico-limbic dysregulation”: a disruption of connections between the dorsal cognitive control system and the ventral emotional system [65]. Altered responses have also been noted in the cerebellum [36]. Studies in patients with depression indicate abnormal cerebellar-brain couplings in affective-limbic and cognitive networks. Cerebellar areas including crus I, crus II, and lobule VIIa showed significantly decreased connectivity with the ventromedial prefrontal cortex [2, 61], as well as with the dorsolateral prefrontal cortex [2, 61], areas implicated in cognitive functions. A strong correlation between connections and symptom severity indicates the significant role of the cerebellum in both affective and cognitive dysfunction in depression. Habas [43] points to the involvement of the cerebellum in 2 major neuronal networks involved in depression: the salience network and the default mode network. He also suggests a modulating role of lobule VI in the salience network. In support of the affective role of the cerebellum, the network connecting the amygdala and neocerebellum is mentioned here as well. Abnormalities in posterior cerebellar activity, such as significantly reduced cerebello-cerebral functional connectivity, have been observed in patients with severe depressive disorders [2, 41, 61]. Structural studies of non-motor cerebellar areas in patients with depression [12, 27, 28, 67, 71] have shown significant differences in the volume of these areas compared to the volume in patients in remission and healthy individuals. Cerebellar volume was strongly associated with the severity and duration of the disease. The relationship between the volume of lobule VI and symptom severity is particularly emphasised [12]. Interestingly, in cerebellar areas involved in higher mental functions, increased blood flow has been noted in cases of depressive disorders [30].

What about stress?

Stress and depression may rely on similar mechanisms of neuronal plasticity disruption. Stress leads to physical and behavioural impairment, and stress-related diseases and mental disorders can be disabling and life-threatening. The consequences of stress include not only cardiovascular, autoimmune, or metabolic diseases but also anxiety disorders, mood disorders, depression, or post-traumatic stress disorder. The contribution of the cerebellum to higher mental functions is no longer subject to debate; it is known to have connections with brain structures also associated with stress. Studies indicate changes in the cerebellum, both morphological and functional, due to stress. Individuals who experienced events such as maltreatment and sexual abuse in childhood showed volumetric changes in the cerebellum [3, 60, 108, 115]. Here, as in the case of depression, studies have shown increased blood flow [3]. In individuals who developed obsessive-compulsive disorder as a result of stressful events, significant differences were observed in the cerebellum, with an increase in volume compared to a control group of healthy individuals. [14, 80]. Patients with post-traumatic stress disorder showed reduced volume of the posterior cerebellar lobe [8, 16, 20, 101]. Neuroimaging studies conducted on individuals who experienced episodes of major depression showed reduced functional connectivity [32, 34, 59, 73, 105]. In individuals with post-traumatic stress disorder, numerous reports describe reduced functional connectivity of the posterior cerebellar lobe [18, 21, 33, 44, 46, 50, 69]. Interestingly, in individuals who experienced chronic work-related stress leading to burnout, changes in functional connectivity between the cerebellum and the amygdala were observed [39].

The cerebellum and neurodegenerative diseases

In addition to its involvement in many physiological brain functions, the cerebellum is also implicated in pathological processes, including disorders of higher nervous functions. A detailed delineation of the cerebellum’s functions as a whole, as well as further divisions, can be used to better understand its structural changes and to diagnose and monitor the development of many diseases. For example, patients with Alzheimer’s disease showed decreased volumes of posterior cerebellar lobes [94, 103]. Differences were also noted in patients with multiple sclerosis [55], Huntington’s disease [82, 86], and Parkinson’s disease [10, 113]. However, many publications provide ambiguous results regarding the role of the cerebellum in various neurodegenerative disorders regarding cognitive functions. This can be explained by the fact that accurate segmentation of the cerebellum is quite difficult due to its complex structure [84].

At the end — chemical messengers

The cerebellum plays a significant role in both motor and non-motor functions through a complex interaction of neurotransmitters. Dopamine, serotonin, norepinephrine, and acetylcholine act as neuromodulators influencing cerebellar functions such as motor coordination, cognition, and emotion. Studies indicate that serotonin levels in the cerebellum affect mood regulation, memory, and learning [106]. Dopaminergic projections to the cerebellum are involved in decision-making and reward-based learning [25]. Dopamine receptors located in the cerebellum influence cognitive flexibility and executive functions, with receptor-level changes affecting social behaviours [25]. Norepinephrine impacts focus and the effective processing of sensory information, influencing the cerebellum’s role in cognitive functions under stress, emotion regulation, and decision-making [9, 95]. Similarly, acetylcholine affects cerebellar functions related to learning and attention maintenance. Cholinergic signals in the cerebellum influence the accuracy and efficiency of cognitive tasks requiring sustained attention and play a role in encoding new information and memory consolidation processes [118]. Dysregulation of these chemical messengers has been implicated in various neurological and psychiatric disorders, including depression and stress-related conditions. Understanding the roles of these chemical messengers in cerebellar function and dysfunction is critical for developing targeted therapeutic interventions for such disorders.

CONCLUSIONS

The cerebellum, previously considered solely a motor structure, plays a key role in non-motor functions such as cognitive and emotional processes. Because the cerebellum has extensive connections with the cerebral cortex, limbic system, and basal ganglia, it can directly influence emotions, motivation, and cognitive functions. Neuroimaging studies provide evidence of the functional organisation of the cerebellum. Activation of the cerebellum has been observed during both simple motor tasks and complex cognitive tasks. Today, it is known that the symptoms of many neurological diseases have unique associations with different areas of the cerebellum. The posterior lobe of the cerebellum is particularly significant in the context of cognitive and neurodegenerative disorders. Damage to the cerebellum can lead to emotional and cognitive disturbances, such as Schmahmann’s syndrome. Changes in the volume and functionality of the cerebellum are observed in cases of depression, autism, PTSD, and other mental disorders. Neurotransmitters also play an important role in regulating cerebellar functions, affecting cognitive processes, motor coordination, and emotional regulation. Better understanding the role of the cerebellum in non-motor functions opens new therapeutic possibilities, especially in treating neurodegenerative diseases, emotional disorders, and cognitive impairments.

Conflict of interest

The authors declare that they have no conflict of interest.

REFERENCES

  1. Adamaszek M, D’Agata F, Ferrucci R, et al. Consensus paper: cerebellum and emotion. Cerebellum. 2017; 16(2): 552–576, doi: 10.1007/s12311-016-0815-8, indexed in Pubmed: 27485952.
  2. Alalade E, Denny K, Potter G, et al. Altered cerebellar-cerebral functional connectivity in geriatric depression. PLoS One. 2011; 6(5): e20035, doi: 10.1371/journal.pone.0020035, indexed in Pubmed: 21637831.
  3. Anderson CM, Teicher MH, Polcari A, et al. Abnormal T2 relaxation time in the cerebellar vermis of adults sexually abused in childhood: potential role of the vermis in stress-enhanced risk for drug abuse. Psychoneuroendocrinology. 2002; 27(1-2): 231–244, doi: 10.1016/s0306-4530(01)00047-6, indexed in Pubmed: 11750781.
  4. Apps R, Hawkes R. Cerebellar cortical organization: a one-map hypothesis. Nat Rev Neurosci. 2009; 10(9): 670–681, doi: 10.1038/nrn2698, indexed in Pubmed: 19693030.
  5. Ashida R, Cerminara NL, Brooks J, et al. Principles of organization of the human cerebellum: macro- and microanatomy. Handb Clin Neurol. 2018; 154: 45–58, doi: 10.1016/B978-0-444-63956-1.00003-5, indexed in Pubmed: 29903451.
  6. Baek SJi, Park JS, Kim J, et al. VTA-projecting cerebellar neurons mediate stress-dependent depression-like behaviors. Elife. 2022; 11, doi: 10.7554/eLife.72981, indexed in Pubmed: 35156922.
  7. Barski JJ, Hartmann J, Rose CR, et al. Calbindin in cerebellar Purkinje cells is a critical determinant of the precision of motor coordination. J Neurosci. 2003; 23(8): 3469–3477, doi: 10.1523/JNEUROSCI.23-08-03469.2003, indexed in Pubmed: 12716955.
  8. De Bellis MD, Hooper SR, Chen SD, et al. Posterior structural brain volumes differ in maltreated youth with and without chronic posttraumatic stress disorder. Dev Psychopathol. 2015; 27(4 Pt 2): 1555–1576, doi: 10.1017/S0954579415000942, indexed in Pubmed: 26535944.
  9. Benarroch E. What is the role of norepinephrine in cerebellar modulation and stress-induced episodic ataxia? Neurology. 2023; 100(8): 383–386, doi: 10.1212/WNL.0000000000206882, indexed in Pub­med: 36806456.
  10. Bhattacharya K, Saadia D, Eisenkraft B, et al. Brain magnetic resonance imaging in multiple-system atrophy and Parkinson disease: a diagnostic algorithm. Arch Neurol. 2002; 59(5): 835–842, doi: 10.1001/archneur.59.5.835, indexed in Pubmed: 12020268.
  11. Blatt GJ, Oblak AL, Schmahmann JD. Cerebellar connections with limbic circuits: Anatomy and functional implications. In: Manto MJ, Schmahmann JD, Rossi F. ed. Handbook of the Cerebellum and Cerebellar Disorders. Springer, Dordrecht 2013: 479–496.
  12. Bogoian HR, King TZ, Turner JA, et al. Linking depressive symptom dimensions to cerebellar subregion volumes in later life. Transl Psychiatry. 2020; 10(1): 201, doi: 10.1038/s41398-020-00883-6, indexed in Pubmed: 32561707.
  13. Bogovic JA, Bazin PL, Ying SH, et al. Automated segmentation of the cerebellar lobules using boundary specific classification and evolution. Inf Process Med Imaging. 2013; 23: 62–73, doi: 10.1007/978-3-642-38868-2_6, indexed in Pubmed: 24683958.
  14. Brooks SJ, Naidoo V, Roos A, et al. Early-life adversity and orbitofrontal and cerebellar volumes in adults with obsessive-compulsive disorder: voxel-based morphometry study. Br J Psychiatry. 2016; 208(1): 34–41, doi: 10.1192/bjp.bp.114.162610, indexed in Pubmed: 26338992.
  15. Buckner RL. The cerebellum and cognitive function: 25 years of insight from anatomy and neuroimaging. Neuron. 2013; 80(3): 807–815, doi: 10.1016/j.neuron.2013.10.044, indexed in Pubmed: 24183029.
  16. Carrion VG, Weems CF, Watson C, et al. Converging evidence for abnormalities of the prefrontal cortex and evaluation of midsagittal structures in pediatric posttraumatic stress disorder: an MRI study. Psychiatry Res. 2009; 172(3): 226–234, doi: 10.1016/j.pscychresns.2008.07.008, indexed in Pubmed: 19349151.
  17. Chakravarty MM, Steadman P, van Eede MC, et al. Performing label-fusion-based segmentation using multiple automatically generated templates. Hum Brain Mapp. 2013; 34(10): 2635–2654, doi: 10.1002/hbm.22092, indexed in Pubmed: 22611030.
  18. Chen HJ, Zhang Li, Ke J, et al. Altered resting-state dorsal anterior cingulate cortex functional connectivity in patients with post-traumatic stress disorder. Aust N Z J Psychiatry. 2019; 53(1): 68–79, doi: 10.1177/0004867418812674, indexed in Pubmed: 30453750.
  19. Chen YL, Tu PC, Lee YC, et al. Resting-state fMRI mapping of cerebellar functional dysconnections involving multiple large-scale networks in patients with schizophrenia. Schizophr Res. 2013; 149(1-3): 26–34, doi: 10.1016/j.schres.2013.05.029, indexed in Pubmed: 23810119.
  20. Cheng B, Huang X, Li S, et al. Gray matter alterations in post-traumatic stress disorder, obsessive-compulsive disorder, and social anxiety disorder. Front Behav Neurosci. 2015; 9: 219, doi: 10.3389/fnbeh.2015.00219, indexed in Pubmed: 26347628.
  21. Clausen AN, Francisco AJ, Thelen J, et al. PTSD and cognitive symptoms relate to inhibition-related prefrontal activation and functional connectivity. Depress Anxiety. 2017; 34(5): 427–436, doi: 10.1002/da.22613, indexed in Pubmed: 28370684.
  22. Clausi S, Coricelli G, Pisotta I, et al. Cerebellar damage impairs the self-rating of regret feeling in a gambling task. Front Behav Neurosci. 2015; 9: 113, doi: 10.3389/fnbeh.2015.00113, indexed in Pubmed: 25999829.
  23. Clausi S, Lupo M, Olivito G, et al. Depression disorder in patients with cerebellar damage: awareness of the mood state. J Affect Disord. 2019; 245: 386–393, doi: 10.1016/j.jad.2018.11.029, indexed in Pubmed: 30423466.
  24. Cox J, Witten IB. Striatal circuits for reward learning and decision-making. Nat Rev Neurosci. 2019; 20(8): 482–494, doi: 10.1038/s41583-019-0189-2, indexed in Pubmed: 31171839.
  25. Cutando L, Puighermanal E, Castell L, et al. Cerebellar dopamine D2 receptors regulate social behaviors. Nat Neurosci. 2022; 25(7): 900–911, doi: 10.1038/s41593-022-01092-8, indexed in Pubmed: 35710984.
  26. Dekeyzer S, Vanden Bossche S, De Cocker L. Anything but little: a Pictorial review on anatomy and pathology of the cerebellum. Clin Neuroradiol. 2023; 33(4): 907–929, doi: 10.1007/s00062-023-01326-7, indexed in Pubmed: 37410171.
  27. Depping MS, Nolte HM, Hirjak D, et al. Cerebellar volume change in response to electroconvulsive therapy in patients with major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2017; 73: 31–35, doi: 10.1016/j.pnpbp.2016.09.007, indexed in Pubmed: 27665684.
  28. Depping MS, Schmitgen MM, Bach C, et al. Abnormal cerebellar volume in patients with remitted major depression with persistent cognitive deficits. Cerebellum. 2020; 19(6): 762–770, doi: 10.1007/s12311-020-01157-z, indexed in Pubmed: 32642931.
  29. Depping MS, Schmitgen MM, Kubera KM, et al. Cerebellar contributions to major depression. Front Psychiatry. 2018; 9: 634, doi: 10.3389/fpsyt.2018.00634, indexed in Pubmed: 30555360.
  30. Depping MS, Wolf ND, Vasic N, et al. Aberrant resting-state cerebellar blood flow in major depression. J Affect Disord. 2018; 226: 227–231, doi: 10.1016/j.jad.2017.09.028, indexed in Pubmed: 28992587.
  31. Diedrichsen J. A spatially unbiased atlas template of the human cerebellum. Neuroimage. 2006; 33(1): 127–138, doi: 10.1016/j.neuroimage.2006.05.056, indexed in Pubmed: 16904911.
  32. Du L, Wang J, Meng B, et al. Early life stress affects limited regional brain activity in depression. Sci Rep. 2016; 6: 25338, doi: 10.1038/srep25338, indexed in Pubmed: 27138376.
  33. Elman I, Upadhyay J, Langleben DD, et al. Reward and aversion processing in patients with post-traumatic stress disorder: functional neuroimaging with visual and thermal stimuli. Transl Psychiatry. 2018; 8(1): 240, doi: 10.1038/s41398-018-0292-6, indexed in Pubmed: 30389908.
  34. Elsey J, Coates A, Lacadie CM, et al. Childhood trauma and neural responses to personalized stress, favorite-food and neutral-relaxing cues in adolescents. Neuropsychopharmacology. 2015; 40(7): 1580–1589, doi: 10.1038/npp.2015.6, indexed in Pubmed: 25567424.
  35. Fatemi SH, Folsom TD, Rooney RJ, et al. Expression of GABAA α2-, β1- and ε-receptors are altered significantly in the lateral cerebellum of subjects with schizophrenia, major depression and bipolar disorder. Transl Psychiatry. 2013; 3(9): e303, doi: 10.1038/tp.2013.64, indexed in Pubmed: 24022508.
  36. Fitzgerald PB, Laird AR, Maller J, et al. A meta-analytic study of changes in brain activation in depression. Hum Brain Mapp. 2008; 29(6): 683–695, doi: 10.1002/hbm.20426, indexed in Pubmed: 17598168.
  37. Flace P, Livrea P, Basile GA, et al. The cerebellar dopaminergic system. Front Syst Neurosci. 2021; 15: 650614, doi: 10.3389/fnsys.2021.650614, indexed in Pubmed: 34421548.
  38. Franklin GL, Camargo CH, Meira AT, et al. The role of the cerebellum in Huntington’s disease: a systematic review. Cerebellum. 2021; 20(2): 254–265, doi: 10.1007/s12311-020-01198-4, indexed in Pubmed: 33029762.
  39. Golkar A, Johansson E, Kasahara M, et al. The influence of work-related chronic stress on the regulation of emotion and on functional connectivity in the brain. PLoS One. 2014; 9(9): e104550, doi: 10.1371/journal.pone.0104550, indexed in Pubmed: 25184294.
  40. Guell X, Schmahmann J. Cerebellar functional anatomy: a didactic summary based on human fMRI evidence. Cerebellum. 2020; 19(1): 1–5, doi: 10.1007/s12311-019-01083-9, indexed in Pubmed: 31707620.
  41. Guo W, Liu F, Xue Z, et al. Abnormal resting-state cerebellar-cerebral functional connectivity in treatment-resistant depression and treatment sensitive depression. Prog Neuropsychopharmacol Biol Psychiatry. 2013; 44: 51–57, doi: 10.1016/j.pnpbp.2013.01.010, indexed in Pubmed: 23352887.
  42. Habas C. Research note: a resting-state, cerebello-amygdaloid intrinsically connected network. Cerebellum Ataxias. 2018; 5: 4, doi: 10.1186/s40673-018-0083-0, indexed in Pubmed: 29468083.
  43. Habas C, Kamdar N, Nguyen D, et al. Distinct cerebellar contributions to intrinsic connectivity networks. J Neurosci. 2009; 29(26): 8586–8594, doi: 10.1523/JNEUROSCI.1868-09.2009, indexed in Pubmed: 19571149.
  44. Hall SA, Brodar KE, LaBar KS, et al. Neural responses to emotional involuntary memories in posttraumatic stress disorder: differences in timing and activity. Neuroimage Clin. 2018; 19: 793–804, doi: 10.1016/j.nicl.2018.05.009, indexed in Pubmed: 30013923.
  45. Hausman HK, Jackson TB, Goen JRM, et al. From synchrony to asynchrony: cerebellar-basal ganglia functional circuits in young and older adults. Cereb Cortex. 2020; 30(2): 718–729, doi: 10.1093/cercor/bhz121, indexed in Pubmed: 31219563.
  46. He Y, Wang Y, Chang TT, et al. Abnormal intrinsic cerebro-cerebellar functional connectivity in un-medicated patients with bipolar disorder and major depressive disorder. Psychopharmacology (Berl). 2018; 235(11): 3187–3200, doi: 10.1007/s00213-018-5021-6, indexed in Pubmed: 30206663.
  47. Heath RG, Harper JW. Ascending projections of the cerebellar fastigial nucleus to the hippocampus, amygdala, and other temporal lobe sites: evoked potential and histological studies in monkeys and cats. Exp Neurol. 1974; 45(2): 268–287, doi: 10.1016/0014-4886(74)90118-6, indexed in Pubmed: 4422320.
  48. Herculano-Houzel S. The human brain in numbers: a linearly scaled-up primate brain. Front Hum Neurosci. 2009; 3: 31, doi: 10.3389/neuro.09.031.2009, indexed in Pubmed: 19915731.
  49. Hoche F, Guell X, Vangel MG, et al. The cerebellar cognitive affective/Schmahmann syndrome scale. Brain. 2018; 141(1): 248–270, doi: 10.1093/brain/awx317, indexed in Pubmed: 29206893.
  50. Holmes SE, Scheinost D, DellaGioia N, et al. Cerebellar and prefrontal cortical alterations in PTSD: structural and functional evidence. Chronic Stress (Thousand Oaks). 2018; 2, doi: 10.1177/2470547018786390, indexed in Pubmed: 30035247.
  51. Jacobs HIL, Hedden T, Schultz AP, et al. Structural tract alterations predict downstream tau accumulation in amyloid-positive older individuals. Nat Neurosci. 2018; 21(3): 424–431, doi: 10.1038/s41593-018-0070-z, indexed in Pubmed: 29403032.
  52. Jung SeJ, Vlasov K, D’Ambra AF, et al. Novel cerebello-amygdala connections provide missing link between cerebellum and limbic system. Front Syst Neurosci. 2022; 16: 879634, doi: 10.3389/fnsys.2022.879634, indexed in Pubmed: 35645738.
  53. Kelly RM, Strick PL. Cerebellar loops with motor cortex and prefrontal cortex of a nonhuman primate. J Neurosci. 2003; 23(23): 8432–8444, doi: 10.1523/JNEUROSCI.23-23-08432.2003, indexed in Pubmed: 12968006.
  54. Kostadinov D, Beau M, Blanco-Pozo M, et al. Predictive and reactive reward signals conveyed by climbing fiber inputs to cerebellar Purkinje cells. Nat Neurosci. 2019; 22(6): 950–962, doi: 10.1038/s41593-019-0381-8, indexed in Pubmed: 31036947.
  55. Kutzelnigg A, Faber-Rod JC, Bauer J, et al. Widespread demyelination in the cerebellar cortex in multiple sclerosis. Brain Pathol. 2007; 17(1): 38–44, doi: 10.1111/j.1750-3639.2006.00041.x, indexed in Pubmed: 17493036.
  56. Lanore F, Rothman J, Coyle D, et al. Norepinephrine controls the gain of the inhibitory circuit in the cerebellar input layer. bioRxiv. 2019; [preprint], doi: 10.1101/567172.
  57. Leggio M, Olivito G. Topography of the cerebellum in relation to social brain regions and emotions. Handb Clin Neurol. 2018; 154: 71–84, doi: 10.1016/B978-0-444-63956-1.00005-9, indexed in Pubmed: 29903453.
  58. Levisohn L, Cronin-Golomb A, Schmahmann JD. Neuropsychological consequences of cerebellar tumour resection in children: cerebellar cognitive affective syndrome in a paediatric population. Brain. 2000; 123 (Pt 5): 1041–1050, doi: 10.1093/brain/123.5.1041, indexed in Pubmed: 10775548.
  59. Li G, Ma X, Bian H, et al. A pilot fMRI study of the effect of stressful factors on the onset of depression in female patients. Brain Imaging Behav. 2016; 10(1): 195–202, doi: 10.1007/s11682-015-9382-8, indexed in Pubmed: 25864196.
  60. Lim L, Hart H, Mehta M, et al. Grey matter volume and thickness abnormalities in young people with a history of childhood abuse. Psychol Med. 2018; 48(6): 1034–1046, doi: 10.1017/S0033291717002392, indexed in Pubmed: 29122037.
  61. Lo RY, Figueroa KP, Pulst SM, et al. Depression and clinical progression in spinocerebellar ataxias. Parkinsonism Relat Disord. 2016; 22: 87–92, doi: 10.1016/j.parkreldis.2015.11.021, indexed in Pubmed: 26644294.
  62. Ma Q, Zeng LL, Shen H, et al. Altered cerebellar-cerebral resting-state functional connectivity reliably identifies major depressive disorder. Brain Res. 2013; 1495: 86–94, doi: 10.1016/j.brainres.2012.12.002, indexed in Pub­med: 23228724.
  63. Malacarne V. Nuova esposizione della struttura del cerveletto umano. G. Briolo, Torino 1776.
  64. Mapelli L, Soda T, D’Angelo E, et al. The cerebellar involvement in autism spectrum disorders: from the social brain to mouse models. Int J Mol Sci. 2022; 23(7), doi: 10.3390/ijms23073894, indexed in Pubmed: 35409253.
  65. Mayberg HS. Limbic-cortical dysregulation: a proposed model of depression. J Neuropsychiatry Clin Neurosci. 1997; 9(3): 471–481, doi: 10.1176/jnp.9.3.471, indexed in Pubmed: 9276848.
  66. Miterko LN, Baker KB, Beckinghausen J, et al. Consensus paper: experimental neurostimulation of the cerebellum. Cerebellum. 2019; 18(6): 1064–1097, doi: 10.1007/s12311-019-01041-5, indexed in Pubmed: 31165428.
  67. Moorhead TW, McKirdy J, Sussmann JED, et al. Progressive gray matter loss in patients with bipolar disorder. Biol Psychiatry. 2007; 62(8): 894–900, doi: 10.1016/j.biopsych.2007.03.005, indexed in Pubmed: 17617385.
  68. Moreno-Rius J. The cerebellum under stress. Front Neuroendocrinol. 2019; 54: 100774, doi: 10.1016/j.yfrne.2019.100774, indexed in Pubmed: 31348932.
  69. Naegeli C, Zeffiro T, Piccirelli M, et al. Locus coeruleus activity mediates hyperresponsiveness in posttraumatic stress disorder. Biol Psychiatry. 2018; 83(3): 254–262, doi: 10.1016/j.biopsych.2017.08.021, indexed in Pubmed: 29100627.
  70. Okugawa G, Sedvall GC, Agartz I. Smaller cerebellar vermis but not hemisphere volumes in patients with chronic schizophrenia. Am J Psychiatry. 2003; 160(9): 1614–1617, doi: 10.1176/appi.ajp.160.9.1614, indexed in Pubmed: 12944335.
  71. Okumuş B, Besenek M, Sönmez D, et al. Cerebellum and nucleus caudatus asymmetry in major depressive disorder. J Surg Med. 2022; 6(4): 470–475, doi: 10.28982/josam.939233.
  72. Ozol K, Hayden J, Oberdick J, et al. Transverse zones in the vermis of the mouse cerebellum. J Comp Neurol. 1999; 412(1): 95–111, doi: 10.1002/(sici)1096-9861(19990913)412:1<95::aid-cne7>3.3.co;2-p.
  73. Philip NS, Kuras YI, Valentine TR, et al. Regional homogeneity and resting state functional connectivity: associations with exposure to early life stress. Psychiatry Res. 2013; 214(3): 247–253, doi: 10.1016/j.pscychresns.2013.07.013, indexed in Pubmed: 24090510.
  74. Pierce JE, Péron J. The basal ganglia and the cerebellum in human emotion. Soc Cogn Affect Neurosci. 2020; 15(5): 599–613, doi: 10.1093/scan/nsaa076, indexed in Pubmed: 32507876.
  75. Pine A, Sadeh N, Ben-Yakov A, et al. Knowledge acquisition is governed by striatal prediction errors. Nat Commun. 2018; 9(1): 1673, doi: 10.1038/s41467-018-03992-5, indexed in Pubmed: 29700377.
  76. Prestori F, Mapelli L, D’Angelo E. Diverse neuron properties and complex network dynamics in the cerebellar cortical inhibitory circuit. Front Mol Neurosci. 2019; 12: 267, doi: 10.3389/fnmol.2019.00267, indexed in Pubmed: 31787879.
  77. Qi Z, An Y, Zhang Mo, et al. Altered cerebro-cerebellar limbic network in AD spectrum: a resting-state fMRI study. Front Neural Circuits. 2019; 13: 72, doi: 10.3389/fncir.2019.00072, indexed in Pubmed: 31780903.
  78. Rajmohan V, Mohandas E. The limbic system. Indian J Psychiatry. 2007; 49(2): 132–139, doi: 10.4103/0019-5545.33264, indexed in Pubmed: 20711399.
  79. Ramnani N. Frontal lobe and posterior parietal contributions to the cortico-cerebellar system. Cerebellum. 2012; 11(2): 366–383, doi: 10.1007/s12311-011-0272-3, indexed in Pubmed: 21671065.
  80. Real E, Subirà M, Alonso P, et al. Brain structural correlates of obsessive-compulsive disorder with and without preceding stressful life events. World J Biol Psychiatry. 2016; 17(5): 366–377, doi: 10.3109/15622975.2016.1142606, indexed in Pubmed: 26784523.
  81. Riou A, Houvenaghel JF, Dondaine T, et al. Functional role of the cerebellum in Parkinson disease: a PET study. Neurology. 2021; 96(23): e2874–e2884, doi: 10.1212/WNL.0000000000012036, indexed in Pub­med: 33910940.
  82. Rodda RA. Cerebellar atrophy in Huntington’s disease. J Neurol Sci. 1981; 50(1): 147–157, doi: 10.1016/0022-510x(81)90049-6, indexed in Pubmed: 6453209.
  83. Romero JE, Coupé P, Giraud R, et al. CERES: A new cerebellum lobule segmentation method. Neuroimage. 2017; 147: 916–924, doi: 10.1016/j.neuroimage.2016.11.003, indexed in Pubmed: 27833012.
  84. Romero JE, Coupe P, Lanuza E, et al. Alzheimer’s Disease Neuroimaging Initiative. Toward a unified analysis of cerebellum maturation and aging across the entire lifespan: A MRI analysis. Hum Brain Mapp. 2021; 42(5): 1287–1303, doi: 10.1002/hbm.25293, indexed in Pubmed: 33385303.
  85. Rondi-Reig L, Paradis AL, Fallahnezhad M. A Liaison brought to light: cerebellum-hippocampus, partners for spatial cognition. Cerebellum. 2022; 21(5): 826–837, doi: 10.1007/s12311-022-01422-3, indexed in Pubmed: 35752720.
  86. Rüb U, Hoche F, Brunt ER, et al. Degeneration of the cerebellum in Huntington’s disease (HD): possible relevance for the clinical picture and potential gateway to pathological mechanisms of the disease process. Brain Pathol. 2013; 23(2): 165–177, doi: 10.1111/j.1750-3639.2012.00629.x, indexed in Pubmed: 22925167.
  87. Saitow F, Hirono M, Suzuki H. Serotonin and synaptic transmission in the cerebellum. In: Manto M, Schmahmann JD, Rossi F. et al. ed. Handbook of the cerebellum and cerebellar disorders. Springer, Dordrecht 2013: 915–926.
  88. Sang Li, Qin W, Liu Y, et al. Resting-state functional connectivity of the vermal and hemispheric subregions of the cerebellum with both the cerebral cortical networks and subcortical structures. Neuroimage. 2012; 61(4): 1213–1225, doi: 10.1016/j.neuroimage.2012.04.011, indexed in Pubmed: 22525876.
  89. Schlerf JE, Verstynen TD, Ivry RB, et al. Evidence of a novel somatopic map in the human neocerebellum during complex actions. J Neurophysiol. 2010; 103(6): 3330–3336, doi: 10.1152/jn.01117.2009, indexed in Pubmed: 20393055.
  90. Schmahmann JD, Pandya DN. The cerebrocerebellar system. Int Rev Neurobiol. 1997; 41: 31–60, doi: 10.1016/s0074-7742(08)60346-3, indexed in Pubmed: 9378595.
  91. Schmahmann JD, Sherman JC. Cerebellar cognitive affective syndrome. Int Rev Neurobiol. 1997; 41: 433–440, doi: 10.1016/s0074-7742(08)60363-3, indexed in Pubmed: 9378601.
  92. Schutter DJ, Koolschijn PC, Peper JS, et al. The cerebellum link to neuroticism: a volumetric MRI association study in healthy volunteers. PLoS One. 2012; 7(5): e37252, doi: 10.1371/journal.pone.0037252, indexed in Pub­med: 22615955.
  93. Seeley WW, Menon V, Schatzberg AF, et al. Dissociable intrinsic connectivity networks for salience processing and executive control. J Neurosci. 2007; 27(9): 2349–2356, doi: 10.1523/JNEUROSCI.5587-06.2007, indexed in Pub­med: 17329432.
  94. Sjöbeck M, Englund E. Alzheimer’s disease and the cerebellum: a morphologic study on neuronal and glial changes. Dement Geriatr Cogn Disord. 2001; 12(3): 211–218, doi: 10.1159/000051260, indexed in Pubmed: 11244215.
  95. Stanley AT, Post MR, Lacefield C, et al. Norepinephrine release in the cerebellum contributes to aversive learning. Nat Commun. 2023; 14(1): 4852, doi: 10.1038/s41467-023-40548-8, indexed in Pubmed: 37563141.
  96. Stoodley CJ, Schmahmann JD. Functional topography in the human cerebellum: a meta-analysis of neuroimaging studies. Neuroimage. 2009; 44(2): 489–501, doi: 10.1016/j.neuroimage.2008.08.039, indexed in Pubmed: 18835452.
  97. Stoodley CJ, Schmahmann JD. Evidence for topographic organization in the cerebellum of motor control versus cognitive and affective processing. Cortex. 2010; 46(7): 831–844, doi: 10.1016/j.cortex.2009.11.008, indexed in Pubmed: 20152963.
  98. Strata P. The emotional cerebellum. Cerebellum. 2015; 14(5): 570–577, doi: 10.1007/s12311-015-0649-9, indexed in Pubmed: 25626523.
  99. Streng ML, Tetzlaff MR, Krook-Magnuson E. Distinct fastigial output channels and their impact on temporal lobe seizures. J Neurosci. 2021; 41(49): 10091–10107, doi: 10.1523/JNEUROSCI.0683-21.2021, indexed in Pubmed: 34716233.
  100. Strick PL, Dum RP, Fiez JA. Cerebellum and nonmotor function. Annu Rev Neurosci. 2009; 32: 413–434, doi: 10.1146/annurev.neuro.31.060407.125606, indexed in Pubmed: 19555291.
  101. Sussman D, Pang EW, Jetly R, et al. Neuroanatomical features in soldiers with post-traumatic stress disorder. BMC Neurosci. 2016; 17: 13, doi: 10.1186/s12868-016-0247-x, indexed in Pubmed: 27029195.
  102. Tam WY, Wang X, Cheng ASK, et al. In search of molecular markers for cerebellar neurons. Int J Mol Sci. 2021; 22(4), doi: 10.3390/ijms22041850, indexed in Pubmed: 33673348.
  103. Thomann PA, Schläfer C, Seidl U, et al. The cerebellum in mild cognitive impairment and Alzheimer’s disease — a structural MRI study. J Psychiatr Res. 2008; 42(14): 1198–1202, doi: 10.1016/j.jpsychires.2007.12.002, indexed in Pubmed: 18215400.
  104. Tsai PT, Hull C, Chu Y, et al. Autistic-like behaviour and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice. Nature. 2012; 488(7413): 647–651, doi: 10.1038/nature11310, indexed in Pubmed: 22763451.
  105. Vai B, Riberto M, Ghiglino D, et al. Mild adverse childhood experiences increase neural efficacy during affective theory of mind. Stress. 2018; 21(1): 84–89, doi: 10.1080/10253890.2017.1398231, indexed in Pubmed: 29105572.
  106. van Hoft JA, Oostland M. Serotonin in the cerebellum. In: Gruol DL, Koibuchi N, Manto M. et al. ed. Essentials of cerebellum and cerebellar disorders. Springer, Berlin 2013: 209–213.
  107. Van Overwalle F, D’aes T, Mariën P. Social cognition and the cerebellum: a meta-analytic connectivity analysis. Hum Brain Mapp. 2015; 36(12): 5137–5154, doi: 10.1002/hbm.23002, indexed in Pubmed: 26419890.
  108. Walsh ND, Dalgleish T, Lombardo MV, et al. General and specific effects of early-life psychosocial adversities on adolescent grey matter volume. Neuroimage Clin. 2014; 4: 308–318, doi: 10.1016/j.nicl.2014.01.001, indexed in Pubmed: 25061568.
  109. Wang VY, Zoghbi HY. Genetic regulation of cerebellar development. Nat Rev Neurosci. 2001; 2(7): 484–491, doi: 10.1038/35081558, indexed in Pubmed: 11433373.
  110. Watson TC, Becker N, Apps R, et al. Back to front: cerebellar connections and interactions with the prefrontal cortex. Front Syst Neurosci. 2014; 8: 4, doi: 10.3389/fnsys.2014.00004, indexed in Pubmed: 24550789.
  111. Weier K, Fonov V, Lavoie K, et al. Rapid automatic segmentation of the human cerebellum and its lobules (RASCAL)--implementation and application of the patch-based label-fusion technique with a template library to segment the human cerebellum. Hum Brain Mapp. 2014; 35(10): 5026–5039, doi: 10.1002/hbm.22529, indexed in Pubmed: 24777876.
  112. Welker WI. The significance of foliation and fissuration of cerebellar cortex. The cerebellar folium as a fundamental unit of sensorimotor integration. Arch Ital Biol. 1990; 128(2-4): 87–109, indexed in Pubmed: 2268185.
  113. Wu T, Hallett M. Reply: The cerebellum in Parkinson’s disease and parkinsonism in cerebellar disorders. Brain. 2013; 136(Pt 9): e249, doi: 10.1093/brain/awt100, indexed in Pubmed: 23739172.
  114. Xiao Le, Bornmann C, Hatstatt-Burklé L, et al. Regulation of striatal cells and goal-directed behavior by cerebellar outputs. Nat Commun. 2018; 9(1): 3133, doi: 10.1038/s41467-018-05565-y, indexed in Pubmed: 30087345.
  115. Yang S, Cheng Y, Mo Y, et al. Childhood maltreatment is associated with gray matter volume abnormalities in patients with first-episode depression. Psychiatry Res Neuroimaging. 2017; 268: 27–34, doi: 10.1016/j.pscychresns.2017.07.005, indexed in Pubmed: 28843886.
  116. Yip J, Soghomonian JJ, Blatt GJ. Increased GAD67 mRNA expression in cerebellar interneurons in autism: implications for Purkinje cell dysfunction. J Neurosci Res. 2008; 86(3): 525–530, doi: 10.1002/jnr.21520, indexed in Pubmed: 17918742.
  117. Zeidler Z, Hoffmann K, Krook-Magnuson E. HippoBellum: acute cerebellar modulation alters hippocampal dynamics and function. J Neurosci. 2020; 40(36): 6910–6926, doi: 10.1523/JNEUROSCI.0763-20.2020, indexed in Pubmed: 32769107.
  118. Zhang C, Zhou P, Yuan T. The cholinergic system in the cerebellum: from structure to function. Rev Neurosci. 2016; 27(8): 769–776, doi: 10.1515/revneuro-2016-0008, indexed in Pubmed: 27559688.
  119. Zhang XY, Wu WX, Shen LP, et al. A role for the cerebellum in motor-triggered alleviation of anxiety. Neuron. 2024; 112(7): 1165–1181.e8, doi: 10.1016/j.neuron.2024.01.007, indexed in Pubmed: 38301648.
  120. Zhong Y, Liu H, Liu G, et al. A review on pathology, mechanism, and therapy for cerebellum and tremor in Parkinson’s disease. NPJ Parkinsons Dis. 2022; 8(1): 82, doi: 10.1038/s41531-022-00347-2, indexed in Pubmed: 35750692.

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