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53 Functional Topography oftheHuman Cerebellum
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345
Fig. 53.1 Voxel-based lesion-symptom mapping of cerebellar motor
syndrome and the CCAS. Each color represents an individual patient’s
stroke. (a) Patients with cerebellar motor syndrome and no CCAS had
strokes impacting the anterior lobe of the cerebellum. (b) Patients with
functional activation patterns during motor learning tasks
reported bilateral activation in the anterior/medial cerebellum extending into lobule VI across all tasks (Hardwick
etal. 2013). When movement-related activation was controlled for, the cluster in lobule VI remained, suggesting
that this region is associated with motor learning independent of motor execution demands (Hardwick etal. 2013).
Damage to the anterior lobe and lobules VIII and IX of
the posterior lobe of the cerebellum are more often associated with the cerebellar motor syndrome (including ataxia,
dysmetria, and dysarthria; Holmes 1939), including disturbances in balance and gait (Konczak et al. 2005; Schoch
et al. 2006; Ilg et al. 2008; Schmahmann et al. 2009;
Bultmann etal. 2014; Stoodley etal. 2016). Lesion-decit
correlations in cerebellar stroke patients reveal that limb and
gait ataxia are more strongly associated with stroke in superior cerebellar artery (SCA) territory than in the posterior
inferior cerebellar artery (PICA) territory (e.g., Schmahmann
etal. 2009), and voxel-based morphometry showed correlations between ataxia scores and anterior lobe damage (lobules II-V extending into lobule VI; Schoch et al. 2006;
Maderwald etal. 2012). Dysarthria is also associated with
anterior cerebellar damage (see Ackermann 2008), including
lobule VI, and particularly rostral paravermal regions (Urban
et al. 2003). Voxel-based lesion-symptom mapping in
cerebellar stroke patients conrms these ndings, with anterior lobe damage associated with higher ataxia scores and
poorer peg-moving and nger-tapping measures (Stoodley
et al. 2016; see Fig. 53.1). Similar relationships between
intact motor performance but symptoms of CCAS had strokes that
spared the anterior lobe and impacted posterolateral cerebellar regions.
Figure adapted with permission from Stoodley etal. (2016)
motor impairment and lobular volumes in the anterior lobe
and lobule VI are evident in patients with cerebellar degeneration (Kansal et al. 2017) and spinocerebellar ataxia
(SCA6; Rentiya etal. 2017).
Damage to the deep cerebellar nuclei can also produce
predictable motor outcomes based on their connectivity patterns. Upper limb ataxia was associated with damage to the
interpositus nucleus (which receives projections from medial
cerebellar regions) and the dorsal (motor-related) part of the
dentate nucleus (Konczak et al. 2005; Maderwald et al.
2012). Poor postural control has been associated with dam-
age to the fastigial nucleus in children and adolescents following cerebellar tumor removal (Konczak et al. 2005).
These ndings indicate that disruption to the sensorimotor
cerebellum produces the cerebellar motor syndrome.
53.5 Cognitive/Aective Cerebellum
Early physiological studies revealed posterior parietal cortical interactions with the cerebellar posterior lobe (Allen and
Tsukahara 1974), and anatomical tract tracing studies in the
monkey showed corticopontine projections arising from
higher-order association areas of the cerebral cortex
(Schmahmann and Pandya 1997), providing the initial indication that cerebellum had access to cognitively relevant
information (Schmahmann 1991). Studies using viral tracers
capable of transsynaptic anterograde and retrograde transmission subsequently demonstrated that prefrontal and pari-
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C. J. Stoodley and J. D. Schmahmann
etal cortices are anatomically interconnected with lobule VII
(Kelly and Strick 2003), further conrming the cerebrocerebellar linkage underpinning the nonmotor functions of the
cerebellum.
Consistent with these anatomical studies, the posterolateral cerebellum is engaged during a range of cognitive tasks
in human participants, even when the motor demands of the
tasks are controlled for or eliminated (see below, and
Stoodley and Schmahmann 2009; Keren-Happuch et al.
2014; King etal. 2019). Lobule VII (VIIA at the vermis, its
hemispheric extensions Crus I and Crus II, and lobule VIIB)
is functionally connected with association areas in the prefrontal, posterior parietal, temporal and cingulate cortices,
participating in fronto-parietal, dorsal and ventral attention,
and default mode networks (e.g., Buckner etal. 2011). These
cortical networks each have multiple representations in the
cerebellum, progressing from the sensorimotor representation in the anterior lobe to the fronto-parietal network in
Crus I, inverting around the Crus I/II border and extending to
the sensorimotor representation in lobule VIII, with a tertiary
set of network representations in lobule IX (Buckner etal.
2011; Guell etal. 2018).
This pattern is evident in meta-analyses of convergent
activation patterns across studies (e.g., Stoodley and
Schmahmann 2009; Keren-Happuch et al. 2014), in
experiments investigating relative activation in multiple task
paradigms (e.g., Stoodley etal. 2012; King etal. 2019; see
Fig. 53.2), and in individual imaging studies investigating
specic cognitive tasks. Meta-analytic connectivity modeling likewise reveals co-activation of lobules V–VI and VIII
with sensorimotor regions during action/execution tasks,
while Crus I and II show task co-activation with prefrontal
and parietal association cortices during cognitive tasks
(Balsters etal. 2014). In general, spatial activations tend to
be left-lateralized, with a midline cluster and more lateral
cluster, both in lobule VI (Stoodley and Schmahmann 2009).
Language clusters are predominantly right-lateralized and
involve lobules VI and VII (Stoodley and Schmahmann
2009; Keren-Happuch etal. 2014). Bilateral activation is evi-
dent during working memory paradigms and includes regions
of Crus I and right VIIIA (Stoodley and Schmahmann 2009;
Keren-Happuch et al. 2014). For other executive function
tasks, such as the Tower of London and Random Number
Generation, data across both analyses converge on bilateral
Crus I (Stoodley and Schmahmann 2009; Keren-Happuch
etal. 2014). Emotional processing paradigms activate lateralized regions in VI and Crus I (Stoodley and Schmahmann
2009; Keren-Happuch etal. 2014).
Vermal lobule VII and lateral parts of lobules VI and Crus
I are activated by emotion processing tasks, including viewing facial expressions, emotional images, and emotional
vocal intonations, and in studies of empathy, panic, sadness,
grief, and aversion to unpleasant stimuli (Stoodley and
Schmahmann 2009). The posterolateral cerebellar hemispheres are engaged during a range of tasks involving more
complex social and emotional processing (for reviews, see
Leggio and Olivito 2018; Van Overwalle etal. 2020). Leggio
and Olivito (2018) differentiate between “limbic” and “cognitive/emotional” regions of the cerebellum, with limbic vermal/paravermal regions and cognitive/emotional regions
mapping to the lateral hemispheres, overlapping with executive function systems.
The CCAS (including decits in language, spatial processing, working memory, and affective regulation) is associated with damage to the cerebellar posterior lobe
(Schmahmann and Sherman 1998; Stoodley etal. 2016; see
Fig.53.1), and can exist in the absence of motor difculties
(Paulus et al. 2004; Stoodley et al. 2016). Voxel-based
lesion- symptom mapping studies have shown that cognitive
decits are associated with posterolateral cerebellar damage (e.g., Ilg etal. 2013; Stoodley etal. 2016) and performance on a range of cognitive measures is associated with
regional volumes in VI, VII, and IX in patients with cerebellar degeneration (Kansal etal. 2017). In patients with
SCA6, grey matter in lobules VII and VIIIA correlated with
performance on an executive function task (Rentiya etal.
2017). Decits on specic tasks (e.g., working memory,
verb generation) were associated with damage to regions
engaged during similar tasks in healthy controls (Ilg etal.
2013; Stoodley etal. 2016). The limbic connections of the
vermis and fastigial nucleus underlie alterations in emotional control from midline cerebellar injury, and damage
to the posterior vermis has been associated with decits in
social and affective processing (Schmahmann and Sherman
1998; Levisohn etal. 2000; Riva and Giorgi 2000; Tavano
etal. 2007).
53 Functional Topography oftheHuman Cerebellum
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347
Fig. 53.2 Cerebellar functional topography is evident in task-based
fMRI studies. Top left, A direct comparison between sensorimotor and
cognitive task activation patterns reveals co-activation between sensorimotor cortical regions and cerebellar sensorimotor representations
(red) and cerebellar posterolateral hemispheres and frontal and parietal
association cortices (blue); top right, activation patterns during individual sensorimotor and cognitive tasks mapped within the same participants; adapted from Stoodley etal. (2012). Bottom, a at map of the
cerebellum revealing activation patterns associated with a large battery
of sensorimotor and cognitive tasks adapted from King etal. (2019)
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C. J. Stoodley and J. D. Schmahmann
53.6 Summary
Cerebellar functions are topographically arranged, enabling
cerebellar modulation of vestibular, sensorimotor, and cognitive/affective domains via cerebrocerebellar circuits. The
primary sensorimotor cerebellum is in the anterior lobe—
lobules II through V, and adjacent parts of lobule VI; the
secondary sensorimotor representation is in lobule VIII.The
cognitive cerebellum in the posterior lobe is interconnected
with association and paralimbic cerebral cortices, and
includes lobules VI, VIIA at the vermis and Crus I and II in
the hemispheres, and lobule VIIB.The limbic cerebellum in
the posterior vermis regulates affective/emotional processing and autonomic functions. Consistent with this topography, the cerebellar motor syndrome follows damage to
cerebellar sensorimotor regions; the CCAS/Schmahmann
syndrome (Manto and Mariën 2015) from damage to the
cognitive- limbic cerebellum; and vestibular symptoms from
damage to the vestibulocerebellum. These syndromes may
coexist or occur in isolation following circumscribed
lesions.
Acknowledgements Supported in part by the National Institutes of
Health (R15R15MH106957 and U54HD090257 C1; CJS), the US
Department of Defense (W81XWH-19-1-0249 to CJS), the National
Ataxia Foundation (JDS), and the MINDLINK Foundation (JDS).
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fMRI-Based Anatomy: Mapping
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theCerebellum
XavierGuell andJeremyD.Schmahmann
54
Abstract
The cerebellum contributes to virtually all aspects of behavior in health and disease. Cerebellar ndings are common
across different types of neuroimaging studies of brain function and dysfunction. A large and expanding body of literature mapping motor and non-motor functions in the healthy
human cerebellar cortex using fMRI has served as a tool for
interpreting these observations. For example, cerebellar
atrophy in Alzheimer’s disease in some areas of Crus I/II
and lobule IX can be interpreted by consulting a large number of task, resting-state, and gradient- based reports that
describe the functional characteristics of these focal regions
of the cerebellar cortex. Here, we summarize the organizational principles observed consistently across these imaging
studies of the cerebellum. This basic framework may be
useful for investigators performing or reading experiments
that require a functional interpretation of human cerebellar
topography. Text in this chapter is adapted, updated, and
expanded based on a prior publication by the same authors
(Guell and Schmahmann, Cerebellum. 19:1–5, 2020).
Keywords
Neuroimaging · fMRI · Resting state functional
connectivity · Task activation · Functional gradients
Cerebellum
X. Guell (*)
Ataxia Center, Cognitive Behavioral Neurology Unit, Laboratory
for Neuroanatomy and Cerebellar Neurobiology, Department of
Neurology, Massachusetts General Hospital, Harvard Medical
School, Boston, MA, USA
Department of Brain and Cognitive Sciences, McGovern Institute
for Brain Research at MIT, Massachusetts Institute of Technology,
Boston, MA, USA
e-mail: xaviergp@mgh.harvard.edu
J. D. Schmahmann
Ataxia Center, Cognitive Behavioral Neurology Unit, Laboratory
for Neuroanatomy and Cerebellar Neurobiology, Department of
Neurology, Massachusetts General Hospital, Harvard Medical
School, Boston, MA, USA
e-mail: jschmahmann@mgh.harvard.edu
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023
D. L. Gruol et al. (eds.), Essentials of Cerebellum and Cerebellar Disorders, https://doi.org/10.1007/978-3-031-15070-8_54
54.1 Introduction
Numerous studies have mapped motor and non-motor task
processes and resting-state networks in the human cerebellar
cortex using fMRI (Buckner etal. 2011; Guell etal. 2018a,b;
King etal. 2019; Brissenden etal. 2016; Stoodley etal. 2010,
2012; Keren-Happuch etal. 2014; Stoodley and Schmahmann
2009; Habas etal. 2009; O’Reilly etal. 2010; Marek etal.
2018). This eld of research has contributed to the develop-
ment of modern cerebellar systems neuroscience—the cerebellum is now appreciated as a structure relevant to virtually
all aspects of behavior in health and disease (Schmahmann
etal. 2019). This large body of human cerebellar neuroimaging literature has also served as a tool for interpreting the
functional signicance of cerebellar neuroimaging ndings
in studies of brain disorders. For example, a study of a neurological condition reporting decreased volume in the intersection between left cerebellar Crus I and Crus II is now
informed by a large number of task, resting-state, and
gradient- based reports that describe the functional characteristics of this specic region of the cerebellar cortex. The
objective of this chapter is to provide a concise summary that
outlines organizational principles observed consistently in
functional imaging studies of the human cerebellum. This
basic framework may help guide the interpretation of human
cerebellar topography in functional and morphometric imaging studies. Text in this chapter is adapted, updated, and
expanded based on a prior publication by the same authors
(Guell and Schmahmann 2020).
54.2 Three Functional Subdivisions: Motor,
Attentional/Executive (Task-Positive),
andDefault-Mode (Task-Negative)
Data-driven analyses of cerebellar fMRI data indicate that (i)
motor, (ii) attentional/executive (task-positive), and (iii)
default-mode (task-negative) processing are three fundamen-
351
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cd
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X. Guell and J. D. Schmahmann
tal poles of cerebellar functional neuroanatomy (Guell etal.
2018b). Our didactic summary will be based on this division
(Fig. 54.1a). Processes that cannot be clearly classied
according to these categories (e.g., emotion processing, or
the property of language lateralization) will be discussed
separately.
DIDACTIC SUMMARY
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EVIDENCE FOR MULTIPLE REPRESENTATIONS AND ANATOMICAL ORDER EVIDENCE FOR FUNCTIONAL ORDER
Three functional
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Motor processing refers to regions in cerebellar cortex
that exhibit activation in fMRI task contrasts such as moving
a nger following a visual cue minus observing the same cue
without performing any movement, or regions in cerebellar
cortex that exhibit functional connectivity to cerebral motor
areas such as M1. Attentional/executive processing refers to
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Fig. 54.1 Didactic summary of cerebellar functional anatomy based
on human fMRI evidence. Top row: (a) Data-driven analyses of cere-
bellar fMRI indicate that motor, attentional/executive (task-positive),
and default-mode (task-negative) processing constitute three fundamental poles of cerebellar functional neuroanatomy (Guell et al.
2018b). Our didactic summary is based on this division. (b, c) Motor
processing is represented twice in each cerebellar cortical hemisphere
(lobules I–VI; lobule VIII). Non-motor processes (attentional/executive
and default-mode) are represented three times in each cerebellar cortical hemisphere (lobules VI-Crus I; lobules Crus II-VIIB; lobules IX–X).
A specic anatomical order from motor (blue), to attentional/executive
(yellow), to default-mode territories (red) is conserved throughout the
cerebellar cortex. This specic functional ordering (motor, attentional/
executive, default-mode) propagates from rst motor towards rst nonmotor representation (i.e., from lobules I–VI to Crus I), from second
motor towards second non-motor representation (i.e., from lobule VIII
to Crus II), and from second motor toward third non-motor representation (i.e., from lobule VIII to IX/X). Of note, rst and second non-motor
representations can be contiguous (as in the case of default-mode pro-
cessing shown in red, see overlapping red arrows in Crus I/II) or separate (as in the case of attentional/executive processing shown in yellow).
(d) The principal axis of macroscale functional organization in cerebellar cortex progresses from motor, to attentional/executive, to defaultmode processing. This progression is captured in the anatomical order
of cerebellar functional territories as shown in (b, c), and also revealed
by a data-driven analysis of functional gradients in cerebellar cortex
based on resting-state functional connectivity between cerebellar cortical areas (functional gradient 1 shown in the y axis progresses from
motor, to attentional/executive, to default-mode processing) (Guell
etal. 2018b). Functional gradient 2 captures a smaller portion of data
variability, and reveals that a secondary axis in cerebellar macroscale
functional neuroanatomy isolates attentional/executive processing.
Bottom row: evidence supporting the organizational principles presented in the top row: task activation (Guell etal. 2018a), seed-based
resting-state connectivity (Guell etal. 2018a), cerebellar mapping of
cerebral cortical resting-state networks (Buckner etal. 2011), and functional gradients (Guell et al. 2018b). These organizational principles
have been conrmed at the single-subject level (Xue etal. 2021)
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cerebellar cortical areas that exhibit functional connectivity
to cerebral systems relevant for stimulus-driven attention
(ventral attention network, salience network), goal- oriented
attention (dorsal attention network), and related executive
functions (frontoparietal network). Tasks engaging these
systems include contrasts such as working memory 2-back
minus 0-back conditions. Default-mode processing refers to
cerebellar cortical areas that exhibit functional connectivity
to cerebral default network (Buckner etal. 2008), engagement in inattentive states such as mind wandering, and deactivation during highly attention-demanding processes. Task
contrasts engaging this system include listening to a story
minus doing math, where attentional demands are subtracted
in the control condition.
A division of cognition based on default-mode versus
attentional/executive processing is supported across multiple
human and animal studies of brain physiology. Default-mode
and attentional/executive territories are anti-correlated at rest
(Fox et al. 2005), dissociated in inattentive as opposed to
vigilant brain state activity (Hayden etal. 2009; Barch etal.
2013), and causally interfere with the activation of each other
(Chen etal. 2013).
54.3 Anatomical Order inCerebellar
Cortex
These three functional domains are organized anatomically
in cerebellar cortex obeying the following four principles.
1. Motor processing is represented twice in each cerebellar
cortical hemisphere (rst motor representation = lobules
I–VI; second motor representation=lobule VIII). Nonmotor processes (attentional/executive and default-mode)
are represented three times in each cerebellar cortical
hemisphere (rst non-motor representation = lobules VICrus I; second non-motor representation = lobules Crus
II-VIIB; third non-motor representation = lobules IX-X).
There are thus two motor (Snider and Eldred 1952) and
three non-motor (Buckner etal. 2011; Guell etal. 2018a)
representations in cerebellar cortex (Fig.54.1b, c).
2. A specic anatomical order from (a) motor, to (b) atten-
tional/executive, to (c) default-mode territories is conserved throughout the cerebellar cortex (Fig. 54.1b, c)
(e.g., see (Buckner etal. 2011; Guell etal. 2018b; Xue
etal. 2021)). This organization is similar to what previous
studies have reported in cerebral cortex (in the case of the
cerebral cortex, a basic conserved organization throughout many cortical regions progresses from primary motor/
auditory/visual, to attentional/executive, to default-mode
territories; see (Braga and Buckner 2017; Margulies etal.
2016; Yeo etal. 2011)).
3. The two principles stated so far result in the propagation
of a specic functional ordering (motor, attentional/executive, default-mode) from rst motor toward rst nonmotor representation (i.e., from lobules I-VI to Crus I),
from second motor towards second non-motor representation (i.e., from lobule VIII to Crus II), and from second
motor towards third non-motor representation (i.e., from
lobule VIII to IX/X) (see three arrows in Fig.54.1c).
4. This organization results in the anatomical peculiarity
that Crus I—Crus II intersection is the intersection of rst
default-mode representation and second default-mode
representation. In this way, rst and second non-motor
representations can be contiguous (as in the case of
default-mode processing) or separate (as in the case of
attentional/executive processing) (see overlapping arrows
in Crus I/II in Fig.54.1c).
54.4 Functional Order inCerebellar Cortex
The principal axis of macroscale functional organization in
cerebellar cortex progresses from motor, to attentional/executive, to default-mode processing (Fig.54.1d). This progression is captured in the anatomical order of cerebellar
functional territories as discussed in the previous section
(principle ii, Fig.54.1b, c), and also revealed by a data-driven
analysis of functional gradients in cerebellar cortex based on
resting-state functional connectivity between cerebellar cortical areas (functional gradient 1 shown in the y axis progresses from motor, to attentional/executive, to default-mode
processing) (Guell etal. 2018b). Functional gradient 1 captures the highest portion of variability in cerebellar cortical
resting-state functional connectivity patterns. Functional
gradient 2 captures a smaller portion of data variability, and
reveals that a secondary axis in cerebellar macroscale functional neuroanatomy isolates attentional/executive processing. These two dimensions (functional gradients 1 and 2)
provide an alternative functional rather than anatomical
space for the visualization of the results of cerebellar neuroimaging (Guell etal. 2019a).
54.5 Special Cases: Emotion, Vestibular,
Language, andSocial Processing
Some functional domains require special consideration
because of peculiarities of their anatomical or functional distribution in cerebellar cortex that are not captured by the
summary provided in the previous sections.
Emotion processing follows the principle of a triple representation in cerebellar cortex (Guell etal. 2018a), but it is
located centrally along functional gradients 1 and 2. It is
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X. Guell and J. D. Schmahmann
therefore not possible to classify emotion processing wholly
within default-mode (high gradient 1 values), motor (low
gradient 1 values), and attentional/executive (high gradient 2
values) divisions (Guell etal. 2018b). Emotion processing
also shows a tendency to engage cerebellar vermis, consistent with the theory of a vermal location of emotion processing in the cerebellum (Guell et al. 2018a; Schmahmann
1991; Schmahmann and Sherman 1998). Within the frame-
work presented here, Crus I/II vermal engagement in emotion processing is viewed as a rst and contiguous second
representation, and lobule IX/X emotion processing activation corresponds to the third representation (Guell et al.
2018a).
Vestibular functions are in many cases difcult to investigate within the constraints of fMRI experimental designs.
Physiology and anatomy investigations in animals, and clinical studies in humans, underscore the engagement of cerebellar vermis (predominantly vermal lobules V-VII, named
oculomotor vermis) as well as lobules IX and X in vestibular
control (Goldberg et al. 2012; Manto and Mariën 2015).
Human fMRI experiments map ocular movements to these
regions (King etal. 2019; Voogd etal. 2012). It is possible
that there is an overlap between oculomotor control and
visual attention in the cerebellum (King etal. 2019; van Es
etal. 2019), as well as links between vestibular and emotion
processing that both engage vermal aspects of the cerebellar
cortex (Levinson 1989; Schmahmann etal. 2007).
Language processing in the cerebellar cortex has a wellestablished predominant right lateralization that mirrors the
predominant left lateralization of language processing in
cerebral cortex. This distribution follows the logic of anatomical connections that link the majority of cerebellar cortex to the contralateral cerebral hemisphere (Gelinas etal.
2014; Marien etal. 2001).
Social cognition processing in cerebellum overlaps with
default-mode processing territories (Guell etal. 2018a; Van
Overwalle etal. 2015), reecting an engagement of defaultmode network in processes that are relevant for social cognition (Buckner etal. 2008; Mars etal. 2012). Social cognition
also extends diffusely along functional gradient 1, resonating
with the understanding that this multimodal function engages
multiple levels of information processing along the principal
dimensions of cerebellar functional neuroanatomy, without
exclusive localization at any of its poles (default-mode,
attentional/executive, or motor) (Guell etal. 2018b).
54.6 Recent Trends andFuture Directions
The organizational principles described here remain observable at the single-subject level, as evidenced by recent neuroimaging studies examining functional anatomy in highly
sampled individuals (Marek etal. 2018; Xue et al. 2021).
This discovery highlights the possibility to transform these
organizational principles into practical, clinically relevant
applications. These applications may include cerebellar
stimulation or modulation therapies guided by functional
imaging mapping (Brady etal. 2019; Benussi etal. 2021),
neuroimaging-guided diagnosis and prognosis, and discovery of natural history of cerebellar and cerebellar-linked
disorders.
Neuroimaging methods beyond traditional resting-state
or task-based analyses are becoming increasingly relevant in
the eld of cerebellar systems neuroscience. Functional gradients based on resting-state activation (Guell etal. 2018b)
have been described here in detail. Other gradient-based
experiments including mediation analyses of task activation
data have conrmed that the main axis of macroscale organization in the cerebellum progresses from motor to increasingly abstract cognitive processing, and shown additional
properties such as interactions between cerebellar territories
along this gradient and their relationship to cerebral cortical
areas (D’Mello etal. 2020). Task-based analyses of cerebellar organization may also expand beyond classical condition
contrast testing, where activation of an experimental condition (e.g., two-back working memory task) is subtracted
from a control condition (e.g., one-back working memory
task) to isolate one specic aspect of neural processing (in
this example, working memory). A data-driven experiment
to delineate cerebellar functional boundaries used general
linear model testing on a large number of task paradigms
with no assignment of control conditions (King etal. 2019).
The results of this analysis were in agreement with the principles of organization described here, and highlighted that
cerebellar organization—from motor to increasingly abstract
cognitive functions, superimposed on the existence of two
motor and three nonmotor representations—includes signicantly sharp boundaries between these distinct functional
territories. Analyses that combine task-based and gradientbased analyses indicate that smaller, mesoscale gradients are
likely to exist within these discrete functional territories. For
example, gradients of attentional task organization are
detectable within the areas of dorsal attention representation
in the cerebellar cortex (Brissenden etal. 2018). Other methods of functional mapping such as neuroimaging following
non-invasive cerebellar stimulation (Halko et al. 2014;
Farzan etal. 2016) or lesion symptom mapping (Stoodley
etal. 2016) may become central in the future of cerebellar
systems neuroscience, as these are the only methodologies
that can establish denitive causal proof of human cerebellar
functional anatomy.
While the basic macroscale organizational principles
of the cerebellar cortex are described and replicated in an
expanding body of converging literature, other cerebellar
and cerebellar-linked structures remain understudied. It is
likely that a similar division into primary, attentional, and
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inattentive (default-mode) territories exists in the dentate
nuclei, with some minor variations (Guell etal. 2019b).
Multiple representations of these functions may also be
present in the dentate nuclei (Guell etal. 2019b), but the
relationship between multiple representations in dentate
nuclei and multiple representations in cerebellar cortex
remains unexplored. Anatomy studies in animals indicate
that distinct functional territories for specic motor, cognitive and affective functions also exist in the fastigial
nuclei and inferior olive (Fujita etal. 2020), but this anatomical reality has not yet been demonstrated in humans.
The discovery of an organization in the human dentate
nuclei similar to cerebellar cortex is supported by the anatomical knowledge that cerebellar output bers synapse in
the dentate nuclei before reaching extra-cerebellar structures. Other structures that send or receive bers to and
from the majority of the cerebellar cortex such as the pontine nuclei and the inferior olive may also follow a similar
pattern of organization; this prediction remains untested.
54.7 Conclusion
Here we have outlined general principles that remain
broadly observable across a large and growing body of literature describing the functional organization of human
cerebellar cortex (Buckner etal. 2011; Guell etal. 2018a,b;
King et al. 2019; Stoodley et al. 2010, 2012; KerenHappuch et al. 2014; Stoodley and Schmahmann 2009;
Habas etal. 2009; O’Reilly etal. 2010; Marek etal. 2018;
Xue etal. 2021; D’Mello etal. 2020; Van Overwalle etal.
2014). These principles are based on the notion of multiple
areas of motor and nonmotor representation, and a specic
ordering of functional domains (motor, attentional/executive, and default- mode) that together dene the position of,
and relationship between, each functional territory in cerebellar macroscale functional anatomy. Structural and functional neuroimaging experiments often reveal ndings in
the cerebellum that are relevant for many aspects of clinical
and fundamental neuroscience beyond the eld of imaging.
The summary presented here may be useful for investigators performing or reading experiments that require a functional interpretation of human cerebellar topography.
Notable recent trends and future directions include the
description of single-subject organization, clinical translation, testing of cerebellar organization using increasingly
diverse methods of neuroimaging analysis, and exploration
of cerebellar and cerebellar-linked structures beyond the
cerebellar cortex.
Conict of Interest The authors declare that they have no conict of
interest.
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