Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_24_библиотеки_им_акад_М_И_Перельмана
.pdf
378
https://t.me/medicina_free
P. Mariën and K. van Dun
experimental neuroimaging studies consistently show a lateralized involvement of the right lateral cerebellar regions in
nonmotor linguistic processes. The exact underlying pathophysiological mechanisms, however, remain to be
elucidated.
References
Baillieux H, Vandervliet EJM, Manto M, Parizel PM, De Deyn PP,
Mariën P (2009) Developmental dyslexia and widespread activation
across the cerebellar hemispheres. Brain Lang 108:122–132
Baillieux H, De Smet HJ, Dobbeleir A, Paquier PF, De Deyn PP, Mariën
P (2010) Cognitive and affective disturbances following focal cerebellar damage in adults: a neuropsychological and SPECT study.
Cortex 46:869–879
Brown WE, Eliez S, Menon V, Rumsey JM, White CD, Reiss AL (2001)
Preliminary evidence of widespread morphological variations of the
brain in dyslexia. Neurology 56:781–783
De Smet HJ, Engelborghs S, Paquier PF, De Deyn PP, Mariën P (2011)
Cerebellar-induced apraxic agraphia: a review and three new cases.
Brain Cogn 76:424–434
Frank B, Schoch B, Hein-Kropp C, Dimitrova A, Hövel M, Ziegler
W, Gizewski ER, Timmann D (2007) Verb generation in children
and adolescents with acute cerebellar lesions. Neuropsychologia
45:977–988
Leggio MG, Solida A, Silveri MC, Gainotti G, Molinari M (1995)
Verbal uency impairments in patients with cerebellar lesions. Soc
Neurosci Abstracts 21:917
Leggio MG, Silveri MC, Petrosini L, Molinari M (2000) Phonological
grouping is specically affected in cerebellar patients: a verbal uency study. J Neurol Neurosurg Psychiatry 69:102–106
Manto M, Bower JM, Conforto AB, Delgado-García JM, da Guarda
SN, Gerwig M, Habas C, Hagura N, Ivry RB, Mariën P, Molinari
M, Naito E, Nowak DA, Oulad Ben Taib N, Pelisson D, Tesche
CD, Tilikete C, Timmann D (2012) Consensus paper: roles of the
cerebellum in motor control– the diversity of ideas on cerebellar
involvement in movement. Cerebellum 11:457–487
Mariën P, Saerens J, Nanhoe R, Moens E, Nagels G, Pickut B, Dierckx
RA, De Deyn PP (1996) Cerebellar induced aphasia: case report
of cerebellar induced prefrontal aphasic language phenomena supported by SPECT ndings. J Neurol Sci 144:34–43
Mariën P, Engelborghs S, Fabbro F, De Deyn PP (2001) The lateralized
linguistic cerebellum: a review and a new hypothesis. Brain Lang
79:580–600
Mariën P, Verhoeven J, Engelborghs S, Rooker S, Pickut BA, De Deyn
PP (2006) A role for the cerebellum in motor speech planning:
evidence from foreign accent syndrome. Clin Neurol Neurosurg
108:518–522
Mariën P, Verhoeven J, Brouns R, De Witte L, Dobbeleir A, De Deyn
PP (2007) Apraxic agraphia following a right cerebellar hemor-
rhage. Neurology 69:926–929
Mariën P, Baillieux H, De Smet HJ, Engelborghs S, Wilssens I, Paquier
P, De Deyn PP (2009) Cognitive, linguistic and affective distur-
bances following a right superior cerebellar artery infarction: a case
study. Cortex 45:527–536
Mariën P, De Smet HJ, Wijgerde E, Verhoeven J, Crols R, De Deyn PP
(2013) Posterior fossa syndrome in adults: a new case and compre-
hensive survey of the literature. Cortex 49:284–300
Mariën P, Ackermann H, Adamaszek M, Barwood CHS, Beaton A,
Desmond J, De Witte E, Fawcett AJ, Hertrich I, Küper M, Leggio
M, Marvel C, Molinari M, Murdoch BE, Nicolson RI, Schmahmann
JD, Stoodley CJ, Thürling M, Timmann D, Wouters E, Ziegler W
(2014) Consensus paper: language and the cerebellum: an ongoing
enigma. Cerebellum 13:386–410
Moretti R, Bava A, Torre P, Antonello RM, Cazzato G (2002)
Reading errors in patients with cerebellar vermis lesions. J Neurol
249:461–468
Nicolson RI, Fawcett AJ, Dean P (1995) Time estimation decits in
developmental dyslexia: evidence of cerebellar involvement. Proc R
Soc Lond Ser B Biol Sci 259:43–47
Nicolson RI, Fawcett AJ, Berry EL, Jenkins IH, Dean P, Brooks DJ
(1999) Association of abnormal cerebellar activation with motor
learning difculties in dyslexic adults. Lancet 353:1662–1667
Nicolson RI, Fawcett AJ, Dean P (2001) Developmental dyslexia: the
cerebellar decit hypothesis. Trends Neurosci 24:508–511
Papathanassiou D, Etard O, Mellet E, Zago L, Mazoyer B, Tzourio-
Mazoyer N (2000) A common language network for comprehension
and production: a contribution to the denition of language epicen-
ters with PET.NeuroImage 11:347–357
Rae C, Harasty JA, Dzendrowskyj TE, Talcott JB, Simpson JM, Blamire
AM etal (2002) Cerebellar morphology in developmental dyslexia.
Neuropsychologia 40:1285–1292
Schmahmann JD, Pandya DN (1997) The cerebrocerebellar system. In:
Schmahmann JD (ed) The cerebellum and cognition, international
review of neurobiology. Academic Press, San Diego, CA, pp31–60
Schweizer TA, Alexander MP, Gillingham S, Cusimano M, Stuss DT
(2010) Lateralized cerebellar contributions to word generation: a
phonemic and semantic uency study. Behav Neurol 23:31–37
Silveri MC, Leggio MG, Molinari M (1994) The cerebellum contrib-
utes to linguistic production: a case of agrammatic speech following
a right cerebellar lesion. Neurology 44:2047–2050
Silveri MC, Misciagna S, Leggio MG, Molinari M (1997) Spatial dys-
graphia and cerebellar lesion: a case report. Neurology 48:1529–1532
Silveri MC, Di Betta AM, Filippini V, Leggio MG, Molinari M
(1998) Verbal short-term store-rehearsal system and the cerebel-
lum. Evidence from a patient with a right cerebellar lesion. Brain
121:2175–2187
Spencer KA, Slocomb DL (2007) The neural basis of ataxic dysarthria.
Cerebellum 6:58–65
Theory ofMind andCerebellum
https://t.me/medicina_free
GiusyOlivito, LiberaSiciliano, andMariaLeggio
59
Abstract
In recent decades, the consensus has been reached about
the role of the cerebellum in social cognition. In addition
to its well-known role in emotional processing, the specic involvement of the cerebellum in modulating theory
of mind (ToM) abilities has been documented. With a
focus on this topic, we open the current chapter with a
general introduction of the denition of ToM and the
importance of considering the cerebellum as a crucial hub
in the brain network involved in predicting mental states
and related behaviors, function needed to adaptively
engage in social interactions. We then report the recent
advances on cerebro-cerebellar circuits related to ToM
functions as studied on healthy subjects, and we emphasize the cerebellar sequential and predictive coding as
responsible for cerebellar modulation on ToM-related
cortical areas. Afterward, we highlight the effects of cerebellar damages on ToM impairments focusing on clinical populations, starting from patients with primary
cerebellar damages and then broadening this issue to further pathological populations. Specically, we take into
account other neurological conditions, together with psychiatric and neurodevelopmental disorders, whose ToM
and resulting social struggles have also been linked to
cerebellar structural or functional alterations.
Conclusively, we briey outline the signicance of the
collected ndings on cerebellar functioning related to
clinical practice and to the implementation of therapeutic
interventions aiming at improving ToM and social skills.
G. Olivito · L. Siciliano · M. Leggio (*)
Department of Psychology, Sapienza University of Rome,
Rome, Italy
Ataxia Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy
e-mail: g.olivito@hsantalucia.com; libera.siciliano@uniroma1.it;
maria.leggio@uniroma1.it
Keywords
Theory of mind · Cerebellum · Functional connectivity
Mentalizing network · Prediction
59.1 Introduction
Social environments constantly challenge human behaviors.
The ability to interpret surrounding social cues and others’
intentions is fundamental to making optimal and adaptive
decisions to perform successful social interactions (Brothers
and Ring 1990). To move properly in ambiguous interactive
realities, people are naturally disposed to engage sophisticated mental processes to perceive and understand their own
and others’ states of mind. These mental processes encompass the abilities to detect and decode beliefs, desires, and
purposes of the self and of others and are grouped in the
notion of “theory of mind” (ToM) or “mentalizing” (Brothers
and Ring 1990). The ability to create internal models of these
mental processes and of correspondent behaviors allows
humans to make predictions about social outcomes. Indeed,
in ever-changing social contexts, the brain is due to regularly
predicting future events to avoid repeating errors and to netune behaviors. To this aim, a constant comparison between
the stored internal models and the ongoing social result is
required. As the cerebellum acts as a feedforward controller,
it is suggested to be a critical node in the brain circuits that
support such predictive coding in social functioning (Leggio
and Molinari 2015). Indeed, in line with the “sequence detection theory” according to which the cerebellar supramodal
operational mode consists of the detection of sequences of
events (Leggio etal. 2011), the cerebellum may allow us to
deal with social environmental stimuli by constructing internal models of social interactions and of related ToM processes based on the prediction of sequential events (Leggio
and Molinari 2015). However, social mentalizing requires
the cooperation of highly specialized neural networks.
Within the extensive brain circuits in charge when humans
© 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_59
379
380
https://t.me/medicina_free
G. Olivito et al.
are required to join ToM processes, the cerebellum operates
as a coprocessor whose effect depends on the cerebral centers to which different cerebellar modules are connected.
Accordingly, the notion of a “social cerebellum” is supported
by observations of specic cerebellar and cerebral coactivation in many functional imaging studies involving mental
state inference tasks (Van Overwalle et al. 2014; Van
Overwalle and Mariën 2016). Additionally, accumulating
ndings show that the performance of patients with cerebellar damage is impaired in a range of mentalizing tasks
(Sokolov 2018; Clausi etal. 2019) and cerebellar structural
and functional alterations occur in pathological conditions
that present behavioral issues consistent with a compromised
ToM (D’Mello et al. 2015; Andreasen and Pierson 2008).
Advances in these topics enrich the current knowledge of
cerebellar functioning and will be highlighted in the following paragraphs.
59.2 Cerebro-Cerebellar Circuits Related
toToM Functions
The functional topography within the cerebellum has been
demonstrated as an essential feature of cerebellar information processing. The understanding of anatomical connectivity with the cerebral cortex has provided substantial support
for dening the functions of each cerebellar subregion
(Stoodley and Schmahmann 2010), and it is now clear that
the cerebellum plays a crucial role in emotional and social
processing through functional interactions with cerebral
regions. Beyond the sensorimotor and cognitive domains,
cerebellar functional topography for emotional (Stoodley
and Schmahmann 2010) and social processing (Van
Overwalle etal. 2014, 2015) has been well-established. The
cerebellar vermis, which is the principal target of limbic connections, has been implicated in the modulation of more
“primitive” emotions (Stoodley and Schmahmann 2010),
while phylogenetically newer lobules, such as lobules VI and
VII (crus I–II) (Andreasen and Pierson 2008; Stoodley and
Schmahmann 2010) in the posterolateral cerebellar hemisphere, have been implicated in social cognition that involves
more complex cognitive processes, i.e., considering another’s mental state (empathy) (Decety and Ickes 2009). Strong
support for this evidence has been derived from an activation
likelihood estimation meta-analysis by Van Overwalle etal.
(2014). This study revealed that the cerebellum, and in particular its posterior portion encompassing Crus I–II, is
strongly involved during abstract mentalizing, suggesting
that the increased difculty or cognitive load involved in
abstraction causes increased cerebellar activity.
For a better denition of segregated cerebellar functional
organization in emotional and social-cognitive domains,
advanced techniques assessing functional connectivity (FC)
have proven very useful and greatly contributed to cerebellar
research in the social domain. FC refers to the mechanism
reecting synchronous activation of spatially separated brain
regions (Damoiseaux etal. 2006) and can be measured by
detecting spontaneous uctuations in brain activity during
resting-state functional magnetic resonance imaging (rsfMRI) (Biswal etal. 1997). This technique has the potential
to capture the full distribution and functional networking of
regions belonging to a functional network (Raichle 2011).
The FC ndings accumulated within the past decade have
consistently indicated cerebellar functional zones that are
also engaged in emotional and social processes, playing specic roles through functional interactions with emotional
and social brain regions in the cerebral cortex. The FC study
of Buckner etal. (2011) mapped the functional topography
of the human cerebellum based on functional connectivity to
seven major networks in the cerebrum (Yeo etal. 2011), thus
showing that the cerebellum also mapped to the default/mentalizing network. In the context of mentalizing functions, the
default mode network (DMN) is of particular interest
(Raichle etal. 2001) since it is indispensable for functions
that are integral to the social understanding of others
(Schilbach et al. 2008). It includes a set of brain regions,
such as the posterior cingulate cortex (PCC), the precuneus,
the lateral parietal/angular gyrus, the medial prefrontal cortex (mPFC), the superior frontal gyrus (SFG), and the temporoparietal junction (TPJ) (Raichle et al. 2001). Van
Overwalle etal. (2015) detected a function-specic connectivity between the cerebellar clusters of social mentalizing
(Van Overwalle etal. 2014) and the default/mentalizing network, as well as between cerebellar areas involved in social
mirroring or behavior understanding (i.e., “body” reading)
and the somatomotor networks described by Buckner etal.
(2011). The cerebellar clusters mainly recruited during mentalizing tasks (Van Overwalle etal. 2015a) are connected to
default/mentalizing regions in the cerebrum, including major
areas of the mPFC, TPJ, and PCC.The participation of the
cerebellum in the DMN (Habas et al. 2009; Krienen and
Buckner 2009) has been evidenced by several resting-state
FC studies in healthy subjects, thus suggesting that the cerebellum modulates the activity of default regions. In particular, the main region coupled with the DMN (Krienen and
Buckner 2009; Buckner et al. 2011) is Crus I–II, with an
additional indication for lobule XI (Habas et al. 2009;
Krienen and Buckner 2009; Buckner etal. 2011), thus supporting the hypothesis that cerebellar coupling to the DMN
is selective. The functional coupling between the DMN and
the specic mentalizing regions of the cerebellum identied
by Buckner et al. (2011) has been supported by Van
Overwalle and Mariën (2016). In their meta-analysis of FC
studies, Van Overwalle and Mariën (2016) showed that complex social cognition tasks strongly recruit the Crus I/
II.Furthermore, their psychophysiological interaction (PPI)
59 Theory ofMind andCerebellum
https://t.me/medicina_free
381
analysis identied a network in which connectivity from the
mPFC and right TPJ converged on the right posterior cerebellum (i.e., Crus II) and then back to the left TPJ junction,
which in turn received connectivity from the dorsal mPFC
and the right TPJ (see Fig.2 in Van Overwalle and Mariën
2016). This connectivity pattern indicates that social pro-
cesses in the cerebrum trigger activity in a domain-specic
mentalizing network in the cerebellum that is connected
back to a domain-specic network in the cerebrum serving
the same mentalizing function. Overall, FC observations are
consistent in indicating cerebellar functional segregation for
social processing, showing in particular that the cerebellum
plays a domain-specic regulatory role and is strongly
recruited when abstraction increases and complex cognitive
processes are in demand.
59.3 Cerebrocerebellar Circuits
Underpinning Social Sequencing
andPrediction
With regard to the cerebellar role in social sequencing and
prediction, the effective connectivity (EC) between the
posterior cerebellum and mentalizing areas in the cerebral
cortex has been demonstrated to play a critical role in the
understanding and construction of the correct order of
social and nonsocial action sequences (Van Overwalle
etal. 2019). The application of dynamic causal modelling
(DCM) to resting- state fMRI data overcomes the main
limitation of other FC techniques, such as PPI analysis
and seed-based analysis, which do not allow for inferences about the direction of connectivity abnormalities.
The application of DCM allows us to make inferences on
the EC, i.e., the two directions of connectivity (from one
brain region to the other and vice versa), making it possible to drive causal interpretations of neural processing
loops (Van Overwalle etal. 2019). By applying DCM to
the results of previous task-related fMRI studies, Van
Overwalle etal. (2019) showed closed loops between the
bilateral posterior cerebellar lobes and the bilateral TPJ, a
key area of the mentalizing network, together with a unidirectional connection from the cerebellum to the precuneus (see Fig. 1a in Van Overwalle et al. 2019). This
pattern of connectivity suggested that cerebrocerebellar
connections play a crucial role in generating internal cerebellar “forward” models, potentially serving the automatic understanding, prediction, and error correction of
behavioral sequences. Accordingly, constructing social
sequences of actions that require understanding the mental state of the protagonist (e.g., involving false or true
beliefs) strongly activates the posterior cerebellum,
mainly Crus I–II (Heleven etal. 2019). In contrast, nonsocial pictorial sequencing tasks activate closed loops
between the bilateral posterior cerebellar lobes and the
bilateral TPJ, while no closed loops are detected with
other mentalizing areas in the cortex, such as the precuneus and the mPFC (Van Overwalle etal. 2020). In addition, only a unidirectional connection from the cerebellum
to the precuneus was found, and no cerebral connections
with the dmPFC were found. The characteristics of
cerbello- cerebral connectivity indicate that the cerebellum emits a kind of error signal acting as a forward controller that matches internal cerebellar models of event
sequences against external sources and contexts in the
cerebrum (Van Overwalle etal. 2020). In particular, in
comparison with nonsocial sequencing, functional specialization for social sequencing has been specically
related to a selected Crus II region (MNI±25, − 75, − 40)
(Van Overwalle etal. 2020), thus suggesting its crucial
role in processing sequences of actions that allow us to
infer the state of mind of another person both in terms of
his or her beliefs (Heleven etal. 2019) and personality
traits (Pu etal. 2021).
59.4 Theory ofMind Impairment Driven by
Cerebellar Structural andFunctional
Alterations: AFocus ontheClinic
59.4.1 Cerebellar Diseases
According to the abovementioned evidence, the study of
connectivity within cerebello-cerebral mentalizing networks
has gained increased attention in the context of pathological
conditions that differentially affect the cerebellum.
Consistent with the idea that cerebellar modulatory function
underlies social cognition, cerebellar structural alterations
would impair cerebellar checking, interfering with the modulatory function of the cerebellum on the cortical projection
areas involved in the social process so that social behavior is
not always appropriately adjusted to specic social environmental requirements (Van Overwalle et al. 2019a, 2020).
This interference could account for specic impaired social
outcomes, particularly when stimuli processing requires
complex ToM abilities and a high level of prediction.
Accordingly, clinical evidence on impaired ability to attribute beliefs and intentions to others in patients with primary
cerebellar damage has been collected in recent decades
(Hoche etal. 2016; Clausi etal. 2019).
A severe impairment in ToM tasks and empathetic reasoning was described in a patient who suffered from a cerebellar bilateral infarction involving the vermis and the medial
and posterior regions of both cerebellar hemispheres
(Gerschovich etal. 2011).
Hypoconnectivity between the cerebellum and specic
frontal regions has been described in a 43-year-old female
382
https://t.me/medicina_free
G. Olivito et al.
who presented signicant impairment in social interaction
following left-side cerebellar lesion (Lupo etal. 2018).
In addition, impaired social skills related to altered performance in ToM tasks were reported in patients with Chiari
malformation type I, a neurological disorder that involves
the cerebellar tonsils (García etal. 2020).
Altered performances in social cognition tasks, both concerning emotion recognition and mentalizing abilities, were
also reported in patients with complex cerebello-cerebral
degeneration, such as spinocerebellar ataxia (SCA) type 1,
SCA type 2, and SCA type 7, as well as in patients with isolated cerebellar degeneration, such as SCA type 6, SCA type
8, and episodic ataxia type 2 (Sokolovsky et al. 2010;
D’Agata etal. 2011; Hoche etal. 2016).
Focusing on social cognition impairments and the underlying neuroanatomical alterations in a homogenous cohort of
SCA2 patients, Clausi etal. (2021) proved that structural and
microstructural alterations in the cerebellum are responsible
for social functioning impairments in this pathological population. Focusing on ToM impairments, the authors evidenced
a correlation between patients’ altered performances in complex mentalizing tasks and a specic pattern of atrophy in the
right Crus II.Regarding microstructural alterations, correlations were found between altered performances in a ToM
task that requires the attribution of mental states based on
eye expression and damage occurring in both the middle and
the superior cerebellar peduncles. These peduncles are
known to represent the anatomical cerebellar-cortical connections and the feedback and feedforward systems that
allow the cerebellum to collect information from and send
information back to cerebral regions. The study by Clausi
et al. (2021) proved that the degeneration of cerebellar
peduncle bers may affect mentalizing processes by impacting proper communication between the cerebellum and coupled cortical regions. This proposal is also supported by
evidence of disrupted FC in cerebellar-cerebral loops.
Indeed, in SCA2 patients, functional disconnections between
the posterior Crus II and cerebral regions of the mentalizing
network (Van Overwalle and Mariën 2016) have been linked
to social impairment in domain-specic complex and abstract
forms of social functioning (Olivito etal. 2020).
Validations of such assumptions have been obtained
based on heterogeneous cohorts of patients with different
kinds of cerebellar degenerative pathologies. In an integrated
behavioral and neuroimaging study, patients with primary
degenerative cerebellar atrophy showed altered performances in both automatic processes and more complex
aspects of ToM, as assessed by tasks whose stimuli required
different levels of predictive coding (Clausi et al. 2019).
Additionally, patients showed patterns of atrophy in cerebellar regions known to modulate social functioning at different
levels, such as Crus I–II, which regulates mentalization, and
lobule IX and lobule VIIIa, which control for more automatic
ToM processes. As expected, the areas of decreased gray
matter (GM) revealed decreased FC with the dmPFC, the
superior frontal gyrus and the orbitofrontal cortex, cortical
areas involved in specic aspects of social mentalizing
(Clausi et al. 2019). In line with the “sequence detection
theory,” the authors suggest that the alteration in specic cerebellar lobules may interfere with the modulatory function
that the cerebellum exerts on the cortical projection areas,
having an impact on the creation and detection of internal
models of social events at different levels (Clausi etal. 2019).
Specically, at a lower level, disrupted cerebellar modulation may impede the implicit matching of external information with the internal model of eye expression, affecting
immediate judgement about others’ mental state. At a more
complex level, a disrupted cerebellar modulation may result
in an impaired ability to predict the social consequences of
ours and others’ intentions, impeding the continuous checking between stored mentalizing processes and current behaviors. Currently, the sequencing hypothesis related to ToM is
being investigated (Van Overwalle et al. 2019a, 2020). By
using a sequential task in which participants are required to
generate the correct order of cartoon-like drawings depicting
mechanical cause effects, overlearned social routines or
social false-belief events, the authors found that a heterogeneous group of patients with cerebellar pathologies had a
selective poor performance in the task evaluating the
sequences of false-belief events (Van Overwalle etal. 2019a).
False belief is known to mirror complex ToM abilities since
it implies the capacity to understand that others may have
mental states that differ from ours and are denied by reality
(Van Overwalle etal. 2019a).
Overall, these previous studies are consistent in terms of
the presence of ToM impairments in patients with different
types of cerebellar pathologies as driven by damage in specic cerebellar regions and by impaired cerebellar operational mode. These ndings constitute new viewpoints that
highlight the impact of social problems on the quality of life
of patients with cerebellar diseases and thus on clinical
practice.
59.4.2 Insight fromNeurodegenerative,
Psychiatric, andNeurodevelopmental
Conditions
Based on cerebellar connections with supramodal association cortices and the limbic system, structural and functional
cerebellar alterations have also been reported to be relevant
in the onset of behavioral and mentalizing impairments in
several pathological conditions (Stoodley 2014; Lupo etal.
2019; Siciliano and Clausi 2020).
Insights into the role of the cerebellum in ToM come from
studies on neurodegenerative disorders presenting with cer-
59 Theory ofMind andCerebellum
https://t.me/medicina_free
383
ebellar alterations. In patients with Parkinson’s disease, cognitive, behavioral and mentalizing impairments occur as
structural and functional changes in the cerebellum and cortical areas involved in higher-order functions increase
(Camicioli et al. 2009; Nishio et al. 2010). Similarly, in
Alzheimer’s disease, social-affective behavioral changes
have been found to evolve with the augmented decrease in
cerebellar volumes. Specically, decreased GM has been
found to rst involve the cerebellar vermis and to evolve to
the posterior cerebellar lobe in more advanced stages of the
disease (Toniolo etal. 2018). In addition, in patients affected
by behavioral variants of frontotemporal dementia, correlations have been found between performances in mentalizing
tasks and the pattern of atrophy in the posterior cerebellar
lobules Crus I–II (Van den Stock etal. 2019).
Furthermore, cerebellar abnormalities and cerebellarcortical network dysfunctions have been described in psychiatric disorders characterized by affective dysregulation and
compromised social interactions (Andreasen and Pierson
2008). Schizophrenic individuals, who often show difcul-
ties in mentalizing processes, exhibit microstructural disruptions in cerebellar-cerebral loops and in intracerebellar white
matter (Kanaan etal. 2009; Kim etal. 2014). The failure to
discriminate between internal states and external events that
cause their hallucinations has been ascribed to the impaired
cerebellar forward control normally exerted on cortical areas
(Ford and Mathalon 2012). A recent systematic review (Lupo
et al. 2019) identied several studies demonstrating disrupted functional connectivity between the posterior cerebellum and mentalizing regions (i.e., TPJ, mPFC, and PCC) in
individuals experiencing a depressive state and in patients
with a diagnosis of bipolar disorder (Liu etal. 2012; Wang
etal. 2015). Interestingly, in a recent review that focused on
the “antisocial” cerebellum, Moreno-Rius (2019) found a
specic pattern of cerebellar alterations consistent across
social anxiety disorder, antisocial personality disorder, and
pedophilic disorder and showed that in 81% of the reviewed
neuroimaging studies, changes in the posterior cerebellar
hemispheres were reported. Studies and advances on the cerebellar role in the abovementioned psychiatric conditions
have been encouraged by the large number of studies
conducted on individuals with autism spectrum disorders
(ASD), whose main symptoms relate to social functioning
and whose changes in the cerebellum were rst reported
many years ago (Bauman and Kemper 1985; Ritvo et al.
1986). The current literature points to a role for the cerebel-
lum in the onset of emotional and mentalizing difculties
described in ASD. As reported in an anatomic likelihood
estimate meta-analysis, reduced GM in the right Crus I and
left VIIIb were found to be ASD-specic across developmental stages (Stoodley 2014). In addition, reduced volumes
in the right Crus I/II were more marked as symptom severity
increased in children with autism (D’Mello etal. 2015), in
accordance with postmortem ndings of reduced Purkinje
cell density in lobules Crus I and II (Skefos etal. 2014). In
support of impaired cerebellar-cerebral loops as the basis of
social dysfunctions, both structural and functional connectivity abnormalities within the cerebellum and in the projection areas carrying information to and from the cerebellum
have been frequently reported in ASD (Olivito etal. 2017,
2018). For example, hypoactivation of the right Crus I/II and
decreased connectivity between the right Crus I/II and
regions of the default mode network, such as the STS, TPJ,
and mPFC, are evidenced in individuals with ASD (D’Mello
and Stoodley 2015; Olivito etal. 2018). Changes in these circuits have been associated with ASD mentalizing and poor
ToM performance (Jack and Morris 2014). The general
hypothesis posits that when developmental damage occurs
early in the cerebellum, it may cause long-term effects in
ASD due to decient modulation of the cerebral cortex,
impacting the optimization of both structure and functions
(D’Mello and Stoodley 2015). Further support for this notion
was obtained from a recent study that aimed to compare ToM
abilities and the underlying structural and functional cerebellar changes in ASD and in degenerative cerebellar pathologies (Clausi et al. 2021). The results revealed that both
groups were impaired in the rst stage of mental state attribution based on eyes’ expression and in advanced concepts
of ToM that require further contextual processing. In line
with overlapping ToM proles, areas of overlapping cerebellar GM reduction were found in a specic portion of the right
Crus II, recurrently reported as being part of the mentalizing
brain network. These results support that impaired modulation of the cerebellum to cerebral activity interrupts the optimized feedforward control required to turn social interactions
into uid and automatic behaviors and to rapidly adapt to
novel social contexts.
In summary, this evidence suggests the importance of
investigating cerebellar functioning in various pathological
conditions to better address the specic cerebellar operational role in relation to ToM.
59.5 Conclusion
In the current chapter, we aimed to describe the current evidence that points to a role of the cerebellum in specic
aspects of ToM and address both clinical and neuroimaging
studies in patients with cerebellar alterations and in other
pathological conditions. The empirical data collected thus
far are consistent on the role of cerebellar–cerebral networks
in mentalizing decits driven by cerebellar damage.
In terms of future perspectives, the existing ndings may
provide an innovative framework for further experimental
studies that may prove crucial for clinical practice. Indeed,
behavioral alterations due to ToM impairments may impact
384
https://t.me/medicina_free
G. Olivito et al.
the quality of life and treatment compliance in individuals
who present with cerebellar damage. In addition, the cerebellum may be considered a potential target for novel therapeutic interventions and neuromodulation implementation used
to improve social skills across several pathological
conditions.
References
Andreasen NC, Pierson R (2008) The role of the cerebellum in schizo-
phrenia. Biol Psychiatry 64:81–88. https://doi.org/10.1016/j.
biopsych.2008.01.003
Bauman M, Kemper TL (1985) Histoanatomic observation of the brain
in early infantile autism. Neurology 35:866–874
Biswal BB, Van Kylen J, Hyde JS (1997) Simultaneous assessment
of ow and BOLD signals in resting-state functional connectivity
maps. NMR Biomed 10:165–170
Brothers L, Ring B (1990) A neuroethological framework for the
representation of mind. J Cogn Neurosci 4:107–118. https://doi.
org/10.1162/jocn.1992.4.2.107
Buckner R, Krienen F, Castellanos A, Diaz JC, Yeo BT (2011) The
organization of the human cerebellum estimated by intrinsic functional connectivity. J Neurophysiol 106:2322–2345
Camicioli R, Gee M, Bouchard TP (2009) Voxel-based morphom-
etry reveals extra-nigral atrophy patterns associated with dopamine refractory cognitive and motor impairment in parkinsonism.
Parkinsonism Relat Disord 15:187–195
Clausi S, Olivito G, Lupo M, Siciliano L, Bozzali M, Leggio M (2019)
The cerebellar predictions for social interactions: theory of mind
abilities in patients with degenerative cerebellar atrophy. Front Cell
Neurosci 12:510
Clausi S, Olivito G, Siciliano L, Lupo M, Bozzali M, Masciullo M,
Molinari M, Romano S, Leggio M (2021) The neurobiological
underpinning of the social cognition impairments in patients with
spinocerebellar ataxia type 2. Cortex 138:101–112
D’Agata F, Caroppo P, Baudino B, Caglio M, Croce M, Bergui M
etal (2011) The recognition of facial emotions in spinocerebellar
ataxia patients. Cerebellum 10:600–610. https://doi.org/10.1007/
s12311- 011- 0276- z
D’Mello AM, Crocetti D, Mostofsky SH, Stoodley CJ (2015) Cerebellar
gray matter and lobular volumes correlate with core autism symptoms. NeuroImage Clin 7:631–639
Damoiseaux JS, Rombouts SARB, Barkhof F, Scheltens P, Stam CJ,
Smith SM et al (2006) Consistent resting-state networks across
healthy subjects. Proc Natl Acad Sci U S A 103(37):13848–13853
Decety J, Ickes W (2009) The social neuroscience of empathy. MIT
Press, Cambridge, MA
D’Mello AM, Stoodley CJ (2015) Cerebro-cerebellar circuits in autism
spectrum disorder. Front Neurosci 9:408
Ford JM, Mathalon DH (2012) Anticipating the future: automatic pre-
diction failures in schizophrenia. Int J Psychophysiol 83(2):232–239
García M, Amayra I, López-Paz JF, Martínez O, Lázaro E, Pérez M,
Berrocoso S, Al-Rashaida M, Infante J (2020) Social cognition
in Chiari malformation type I: a preliminary characterization.
Cerebellum 19(3):392–400
Gerschovich ER, Cerquetti D, Tenca E etal (2011) The impact of bilat-
eral cerebellar damage on theory of mind, empathy and decision
making. Neurocase 17(3):270–275
Habas C, Kamdar N, Nguyen D, Prater K, Beckmann CF, Menon V
etal (2009) Distinct cerebellar contributions to intrinsic connectivity networks. J Neurosci 29(26):8586–8594
Heleven E, van Dun K, Van Overwalle F (2019) The posterior cerebel-
lum is involved in constructing social action sequences: an fMRI
study. Sci Rep 9(1):11110
Hoche F, Guell X, Sherman JC, Vangel MG, Schmahmann JD (2016)
Cerebellar contribution to social cognition. Cerebellum 15:732–
743. https://doi.org/10.1007/s12311- 015- 0746- 9
Jack A, Morris JP (2014) Neocerebellar contributions to social per-
ception in adolescents with autism spectrum disorder. Dev Cogn
Neurosci 10:77–92
Kanaan RAA, Borgwardt S, McGuire PK etal (2009) Microstructural
organization of cerebellar tracts in schizophrenia. Biol Psychiatry
66(11):1067–1069
Kim D-J, Kent JS, Bolbecker AR etal (2014) Disrupted modular archi-
tecture of cerebellum in schizophrenia: a graph theoretic analysis.
Schizophr Bull 40(6):1216–1226
Krienen FM, Buckner RL (2009) Segregated fronto-cerebellar cir-
cuits revealed by intrinsic functional connectivity. Cereb Cortex
19(10):2485–2497
Leggio M, Molinari M (2015) Cerebellar sequencing: a trick for pre-
dicting the future. Cerebellum 14:35–38. https://doi.org/10.1007/
s12311- 014- 0616- x
Leggio MG, Chiricozzi FR, Clausi S, Tedesco AM, Molinari M (2011)
The neuropsychological prole of cerebellar damage: the sequenc-
ing hypothesis. Cortex 47:137–144. https://doi.org/10.1016/j.
cortex.2009.08.011
Liu C-H, Li F, Li S-F, Wang Y-J, Tie C-L, Wu H-Y et al (2012)
Abnormal baseline brain activity in bipolar depression: a resting
state functional magnetic resonance imaging study. Psychiatry Res
203(2–3):175–179
Lupo M, Olivito G, Siciliano L, Masciullo M, Molinari M, Cercignani
M etal (2018) Evidence of cerebellar involvement in the onset of a
manic state. Front Neurol 9:774
Lupo M, Siciliano L, Leggio M (2019) From cerebellar alterations
to mood disorders: a systematic review. Neurosci Biobehav Rev
103:21–28. https://doi.org/10.1016/j.neubiorev.2019.06.008
Moreno-Rius J (2019) Is there an "antisocial" cerebellum? Evidence
from disorders other than autism characterized by abnormal social
behaviours. Prog Neuro-Psychopharmacol Biol Psychiatry 89:1–8
Nishio Y, Hirayama K, Takeda A etal (2010) Corticolimbic gray mat-
ter loss in Parkinson’s disease without dementia. Eur J Neurol
17:1090–1097
Olivito G, Clausi S, Laghi F, Tedesco AM, Baiocco R, Mastropasqua C
etal (2017) Resting-state functional connectivity changes between
dentate nucleus and cortical social brain regions in autism spectrum
disorders. Cerebellum 16(2):283–292
Olivito G, Lupo M, Laghi F, Clausi S, Baiocco R, Cercignani M etal
(2018) Lobular patterns of cerebellar resting-state connectivity in
adults with autism spectrum disorder. Eur J Neurosci 47(6):729–735
Olivito G, Siciliano L, Clausi S, Lupo M, Romano S, Masciullo M,
Molinari M, Cercignani M, Bozzali M, Leggio M (2020) Functional
changes of mentalizing network in SCA2 patients: novel insights into
understanding the social cerebellum. Cerebellum 19(2):235–242
Pu M, Ma Q, Heleven E, Haihambo NP, Van Overwalle F (2021)
The posterior cerebellum and inconsistent trait implications when
learning the sequence of actions. Soc Cogn Affect Neurosci
16(7):696–706
Raichle ME (2011) The restless brain. Brain Connect 1(1):3–12
Raichle ME, MacLeod AM, Snyder AZ, Powers WJ, Gusnard DA,
Shulman GL (2001) A default mode of brain function. Proc Natl
Acad Sci 98(2):676–682
Ritvo ER, Freeman BJ, Scheibel AB, Duong T, Robinson H, Guthrie D,
Ritvo A (1986) Lower Purkinje cell counts in the cerebella of four autis-
tic subjects: initial ndings of the UCLA-NSAC Autopsy Research
Report 143(7):862–866. https://doi.org/10.1176/ajp.143.7.862
59 Theory ofMind andCerebellum
https://t.me/medicina_free
385
Schilbach L, Eickhoff SB, Rotarska-Jagiela A, Fink GR, Vogeley K
(2008) Minds at rest? Social cognition as the default mode of cognizing and its putative relationship to the ‘default system’ of the
brain. Conscious Cogn 17(2):457–467
Siciliano L, Clausi S (2020) Implicit vs. explicit emotion processing in
autism spectrum disorders: an opinion on the role of the cerebellum.
Front Psychol 11:96
Skefos J, Cummings C, Enzer K, Holiday J, Weed K, Levy E etal
(2014) Regional alterations in purkinje cell density in patients with
autism. PLoS One 9(2):e81255. https://doi.org/10.1371/journal.
pone.0081255
Sokolov AA (2018) The cerebellum in social cognition. Front Cell
Neurosci 12:145. https://doi.org/10.3389/fncel.2018.00145
Sokolovsky N, Cook A, Hunt H, Giunti P, Cipolotti L (2010) A prelimi-
nary characterisation of cognition and social cognition in spinocerebellar ataxia types 2, 1, and 7. Behav Neurol 23:17–29
Stoodley CJ (2014) Distinct regions of the cerebellum show gray mat-
ter decreases in autism, ADHD, and developmental dyslexia. Front
Syst Neurosci 8:1–17
Stoodley CJ, Schmahmann JD (2010) Evidence for topographic orga-
nization in the cerebellum of motor control versus cognitive and
affective processing. Cortex 46(7):831–844
Toniolo S, Serra L, Olivito G etal (2018) Patterns of cerebellar gray
matter atrophy across alzheimer’s disease progression. Front Cell
Neurosci 12:430
Van den Stock J, De Winter FL, Stam D etal (2019) Reduced tendency
to attribute mental states to abstract shapes in behavioral variant
frontotemporal dementia links with cerebellar structural integrity.
Neuroimage Clin 22:101770
Van Overwalle F, Mariën P (2016) Functional connectivity between the
cerebrum and cerebellum in social cognition: a multi-study analysis. NeuroImage 124(A):248–255
Van Overwalle F, Baetens K, Mariën P, Vandekerckhove M (2014)
Social cognition and the cerebellum: a meta-analysis of over 350
fMRI studies. NeuroImage 1:554–572. https://doi.org/10.1016/j.
neuroimage.2013.09.033
Van Overwalle F, D’aes T, Mariën P (2015) Social cognition and the
cerebellum: a meta analytic connectivity analysis. Hum Brain Mapp
36:5137–5154
Van Overwalle F, Baetens K, Mariën P, Vandekerckhove M (2015a)
Cerebellar areas dedicated to social cognition? A comparison of
meta-analytic and connectivity results. Soc Neurosci 10(4):337–344
Van Overwalle F, Van de Steen F, Mariën P (2019) Dynamic causal
modeling of the effective connectivity between the cerebrum and
cerebellum in social mentalizing across ve studies. Cogn Affect
Behav Neurosci 19(1):211–223
Van Overwalle F, De Coninck S, Heleven E, Perrotta G, Taib NOB,
Manto M etal (2019a) The role of the cerebellum in reconstructing
social action sequences: a pilot study. Soc Cogn Affect Neurosci
14(5):549–558
Van Overwalle F, Van de Steen F, van Dun K, Heleven E (2020)
Connectivity between the cerebrum and cerebellum during social
and non-social sequencing using dynamic causal modelling.
NeuroImage 206:116326
Wang Y, Zhong S, Jia Y, Zhou Z, Wang B, Pan J et al (2015)
Interhemispheric resting state functional connectivity abnormali-
ties in unipolar depression and bipolar depression. Bipolar Disord
17(5):486–495
Yeo BT, Krienen FM, Sepulcre J, Sabuncu MR, Lashkari D, Hollinshead
M etal (2011) The organization of the human cerebral cortex esti-
mated by intrinsic functional connectivity. J Neurophysiol Sep
106(3):1125–1165
Cerebellum andDecision-Making
https://t.me/medicina_free
BenDeverett andMarliesOostland
60
Abstract
In everyday life, our behavior is guided continuously by
decisions we make based on a combination of past experiences as well as information currently available to us.
Decision-making is a complex executive function that
involves many subprocesses, including detection and integration of cues, evidence accumulation, preparation and
execution of the decision, retaining information from current and past events in working memory, and reward processing to update the internal model. The decision-making
process requires involvement from many brain areas,
including the cerebellum. Here, we argue that the cerebellum is involved in every step of the decision-making process. This makes the complex process of decision-making
a tting example to highlight the variety of motor and
nonmotor aspects, including higher cognitive functions,
in which a balanced output of the cerebellum can guide
forebrain areas.
Keywords
Cerebellum · Decision-making · Preparatory movement
Evidence accumulation · Cognition
60.1 Decision-Making
Decision-making processes occur in many different situations and multiple times per day. Sometimes you have made
similar decisions so many times before that you can execute
them almost automatically, such as deciding what standard
items to get from the grocery store. At other times, your spurof- the-moment observations and decision-making process
can make a big difference for yourself and others. For
instance, imagine you are a soccer player during an important match for your team. Over the course of the game, you
notice that the goalkeeper almost always chooses a side
before the player has actually kicked the ball. So when your
teammates have created an opportunity for you to attempt a
shot at the goal, you deliberately give off the wrong impression on which side you are going to score, see the goalkeeper
respond to that prematurely, after which you change your
movement and score the goal with a simple yet effective
shot. Thus, throughout the game you rst detected the visual
cues of how the ball is kicked and where the ball lands at
each attempt, you accumulated the evidence of the goalkeeper’s behavior, you remembered their behavior for when you
get an opportunity to score, you prepared and executed the
movement of hitting the ball correctly, and you processed the
emotional reward of helping your team win this important
game. And all this is partly thanks to the cerebellum.
B. Deverett
Department of Anesthesiology, Palo Alto, CA, USA
M. Oostland (*)
Wolfson Institute for Biomedical Research, University College
London, London, UK
Swammerdam Institute for Life Sciences, University of
Amsterdam, Amsterdam, The Netherlands
e-mail: marlies.oostland@uva.nl
© 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_60
60.2 The Cerebellum Is Part ofaLarge
Network Involved inDecision-Making
The cerebellum controls the timing and execution of motor
as well as nonmotor functions. The cerebellum has networks
with diverse forebrain regions, with the largest connections
with somatosensory regions, while the densest connections
are with associative areas (Pisano etal. 2021), highlighting
the involvement of the cerebello-cortical network in nonmotor functions. Nonmotor functions to which the cerebellum
387
388
https://t.me/medicina_free
B. Deverett and M. Oostland
contributes include emotion, language processing, executive
functions, and working memory (Stoodley and Schmahmann
2009). This also includes decision-making. Decision-making
is a multidisciplinary executive function that involves many
subprocesses, including detection and integration of cues,
evidence accumulation, retaining recent information in
working memory, and integrating this with previous experiences. Then, that knowledge is used to guide risk calculation,
taking into account proprioceptive features such as emotions, preparation, and execution of the goal-directed movement to commit to a decision. Finally, following the decision
comes the processing of the specic outcome to update the
internal model and improve the decision-making process for
the next opportunity (Gold and Shadlen 2007).
Here, we argue that the cerebellum is involved in all steps
of this decision-making process. It is important to note that
the cerebellum is only one of many brain areas involved in
the complex behavior of decision-making. Regions such as
the orbitofrontal, anterior cingulate, and dorsolateral prefrontal cortices are critical to decision-making (Rosenbloom
etal. 2012). These prefrontal regions connect with the neocortex, limbic system, basal ganglia, and cerebellum to form
an integrated network involved in decision-making
(Rosenbloom etal. 2012). In one study, parts of the dorsal
cortex were systematically inactivated during the complex
version of a virtual reality evidence-accumulation task for
mice (Pinto etal. 2019). Inactivation of any of the individual
regions in the dorsal cortex on its own was enough to impair
performance (Pinto et al. 2019). In a similarly complex
evidence- accumulation task, inactivation of the cerebellum
also impaired performance (Deverett etal. 2018). Together,
this indicates the widespread involvement of multiple brain
areas, including the cerebellum, in decision-making in
rodents, similar to observations in humans.
60.3 Human Data Indicates aRole
fortheCerebellum
inDecision-Making
Data from healthy human subjects as well as patients with
cerebellum-specic lesions provide an indication for the role
of the cerebellum in decision-making. Meta-analyses of
human data concluded that executive function tasks, including but not limited to decision-making, activate regions
across the cerebellum, including crus I bilaterally, left crus
II, right lobule VI, and midline lobule VII (Keren‐Happuch
et al. 2014; Stoodley and Schmahmann 2009). In healthy
adults, informed decision-making was found to activate
brain areas involved in working memory and motor control,
including the cerebellum (Ernst etal. 2002). Neuroimaging
in humans has demonstrated recruitment of cerebellar activity in contexts that specically demand cognitive resources.
Cerebellar activity, and particularly activity in the lateral
posterior cerebellum, increases with decision-making under
uncertainty (Blackwood etal. 2004). In human patients with
cerebellar damage, their decision-making ability was worse
than that of the healthy control group, while still more preserved than that of individuals with frontal lobe strokes
(Cardoso et al. 2014). In patients with behavioral variant
frontotemporal dementia, cerebellar atrophy was associated
with performance in a gambling decision-making task
(Kloeters etal. 2013).
60.4 Neuronal Mechanisms ofCerebellar
Involvement inDecision-Making
Data from subjects other than humans can provide a more
detailed insight into how the cerebellum can guide decisionmaking. In mice, during the information gathering stage of
making a decision, Purkinje cell simple spike activity
increases throughout the cue period with ramp-like activity
(Deverett etal. 2018), similar to ramping other brain regions
including the dorsal cortex (Orsolic etal. 2021; Allen etal.
2017), ventral tegmental area (VTA) (Engelhard etal. 2019),
and striatum (Yartsev et al. 2018). Ramp-like activity in
Purkinje cells could be an indication of movement (Musall
etal. 2019), precise temporal processing (Ivry and Spencer
2004; Ohmae etal. 2017), or increasing condence about the
upcoming decision (Balsdon etal. 2020). Purkinje cell complex spikes may signal sensory saliency, thereby affecting
the evidence accumulation process (Oostland etal. 2021). In
addition, granule cells provide a predictive signal about
upcoming movements (Giovannucci et al. 2017). During
motor planning, there is persistent representation of information in the frontal cortex which is dependent on the cerebellum (Gao etal. 2018).
In mice, optogenetic manipulation of Purkinje cells suggests a role for the cerebellum in retaining past evidence in
working memory. In an evidence-accumulation decisionmaking task, optogenetic inactivation of Purkinje cells in
crus I during the delay period only, thus not manipulating
any time during which new evidence was presented, impaired
performance (Deverett etal. 2019). Furthermore, manipulation of the cerebellum throughout learning of an evidenceaccumulation decision-making task caused mice to stay
more focused on current evidence and less on past information (Oostland etal. 2021), suggesting neuronal representations of stimulus history in a normally functioning
cerebellum. This neural representation of stimulus history
also occurs in other brain areas, such as the posterior parietal
cortex (Akrami etal. 2018). Thus, neuronal networks including the cerebellum are able to keep track of past information,
which in complex environments can help to make informed
decisions.
Соседние файлы в папке Библиотека им академика М.И. Перельмана