cortex 46 (2010) 907–918

available at www.sciencedirect.com

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Special issue: Research report

Evidence for a link among cognition, language and emotion

in cerebellar malformations

Alessandro Tavano and Renato Borgatti*

Department of Child Neuropsychiatry and Neurorehabilitation, ‘‘Eugenio Medea’’ Scientific Institute, Bosisio Parini (LC), Italy

article info abstract

Article history: We compared the neurobehavioral profiles of children with Joubert syndrome (JS partici-
Received 12 December 2008 pants), a rare autosomal recessive condition characterized on magnetic resonance imaging
Reviewed 14 May 2009 (MRI) by hypoplasia of the cerebellar vermis and midbrain–hindbrain malformations, and
Revised 19 June 2009 children with malformations confined to the cerebellar vermis and one or both hemi-
Accepted 31 July 2009 spheres (Cerebellar malformations – CM participants). We aimed at investigating the
Published online 16 September 2009 influence of anatomo-clinical similarities (vermian malformation) and differences (intact
cerebellar hemispheres vs sparing of the pons, respectively) with respect to cognitive,
Keywords: linguistic and emotional development, assuming as a reference framework the Cerebellar
Cognition Cognitive Affective Syndrome (CCAS). Results show that severe to moderate mental
Language retardation is infrequent in JS children, while it is present in more than half the sample of
Emotion CM children. Affect development was generally preserved in JS, in high-functioning CM
Cerebellum individuals and also in some of the CM children with moderate mental retardation, which
Malformation raised questions as to the role of a cerebellar vermis lesion in determining affect disorders.
Joubert syndrome Further, cognitive and linguistic profiles on both intellectual and neuropsychological
Cerebellar Cognitive Affective evaluations provided evidence for distinct patterns of peaks and valleys in the two groups,
Syndrome with JS children being significantly more impaired in language and verbal working memory
and CM individuals showing a significant impairment of executive functions and
emotional development. The overall evidence provides support for an important role of
cerebellar structures per se in shaping emotional, cognitive and linguistic development,
when vermian lesions are associated to cerebellar hemispheric lesions. Cerebellar vermis
and brainstem lesions instead appear to have a major impact on motor-related skills,
including oro-motor abilities and verbal working memory.
ª 2009 Elsevier Srl. All rights reserved.

1. Introduction a neurobehavioral model of higher-order cognition (Ito, 1984,

1.1. The cerebellum and higher-order cognition
Since the beginning of the 1980s there has been a growing
interest in cerebellar non-motor functions and their role in
1993, 2002, 2008; Ivry and Keele, 1989; Leiner et al., 1991, 1993;
Schmahmann, 1991, 1997, 2006; Schmahmann and Sherman,
1998). At present, the precise nature of the cerebellar contri-
bution to higher-order information processing is unclear, and
experimental and clinical investigations have provided

* Corresponding author. Department of Child Neuropsychiatry and Neurorehabilitation, ‘‘Eugenio Medea’’ Scientific Institute, Bosisio
Parini (LC), Italy.
E-mail address: renato.borgatti@bp.lnf.it (R. Borgatti).
0010-9452/$ – see front matter ª 2009 Elsevier Srl. All rights reserved.
doi:10.1016/j.cortex.2009.07.017
908 cortex 46 (2010) 907–918
evidence for different theoretical stances that see the cere-
bellum as an event timing device (Ivry and Keele, 1989; Ivry
et al., 2002; Ivry and Spencer, 2004); an active sensory
mismatch detection mechanism (Devor, 2000; Bower, 2002);
an internal prearticulatory verbal code enhancer (Ackermann
et al., 2004); a homeostatic supervisor of on-going perfor-
mance (Schmahmann, 1996); an internal model encoder (Ito,
2008). However, all these theories share the assumption that
the cerebellar function is based on the computational power
of the cerebellar unit learning machines, constituted by highly
modular and serially repeated complexes of parallel fiber-
Purkinje cell synapses, modulated by error-signaling, long-
term depression inducing climbing fibers (Ito, 2006). Moreover,
the purported cerebellar function should be domain-general
and cut across information levels, sensorimotor as well as
cognitive, autonomic as well as emotional (Bower, 2002;
Schmahmann, 2000, 2004; Ackermann, 2008; Ito, 2008).
Cerebro-cerebellar connection pathways constitute
a prerequisite neuroanatomical basis for cerebellar non-
motor functions (Ito, 2008). Important findings to this end
have been collected in anatomical studies on non-human
primates. Particularly relevant for higher-order cognition and
language in humans, in monkeys reciprocal connections have
been described between the prefrontal cortex and the cere-
bellar hemispheres through the dentate nucleus (Middleton
and Strick, 1994; Kelly and Strick, 2003), between the anterior
cingulate gyrus and both the prefrontal cortex and cerebellar
hemispheres (through the pons basalis) (Schmahmann and
Pandya, 1989, 1997; Fang et al., 2005), and connections from
both the prefrontal cortex and the cerebellar hemispheres to
the temporo-parietal association areas (Fang et al., 2005).
Further, the cerebellar vermis and flocculonodular lobe
appear to be tightly connected to structures involved in
different aspects of affect modulation, and specifically basic
autonomic functions (Haines and Dietrichs, 1984), emotion
(Heath, 1973), and mood (Schmahmann, 2000).
1.2. The Cerebellar Cognitive Affective Syndrome (CCAS)
The concept of a ‘‘CCAS’’ has been introduced as a likely
candidate for a multidomain nosological picture of cognition
and affect deficits in patients with acquired or congenital
malformative lesions confined to the cerebellum (Schmah-
mann and Sherman, 1998; Steinlin et al., 1998, 1999; Levisohn
et al., 2000; Riva and Giorgi, 2000; Schmahmann, 2004; Paulus
et al., 2004; Tavano et al., 2007a, 2007b, 2007c). In particular,
acquired cerebellar lesions may induce disorders of executive
functions, and specifically error-detecting, planning, set-
shifting, abstract reasoning, verbal fluency and working
memory (Fiez et al., 1992; Grafman et al., 1992; Courchesne
et al., 1994a; Fiez, 1996; Desmond et al., 1997; Molinari et al.,
1997a; Tanaka et al., 2003; Justus et al., 2005; Ravizza et al.,
2006); impaired spatial cognition often associated to distract-
ibility, perseveration and inattention, lack of visuospatial
organization and procedural memory deficits, sequencing
disorders (Molinari et al., 1997b; Schmahmann and Sherman,
1998; Fabbro et al., 2004; Leggio et al., 2008); speech and
language disorders such as dysprosodia, mild agrammatism
and mild anomia (Silveri et al., 1993; Molinari et al., 1997a,
1997b; Fabbro et al., 2004; Justus, 2004; Mariën et al., 2009);
personality change with blunting of affect and disinhibited or
inappropriate behavior (Courchesne, 1991; Courchesne et al.,
1994b; Schmahmann, 2000, 2004). Overall, a more marked
expression of the CCAS was found for posterior lobe lesions.
Furthermore, while lesions confined to the cerebellar hemi-
spheres and related output nuclei induced more severe
cognitive disorders, vermian lesions were more likely to lead
to emotional disorders (Kim et al., 1994; Schmahmann and
Sherman, 1998; Mariën et al., 2001; Jansen et al., 2005).
The onset of a CCAS following cerebellar tumor surgery has
been described in children (Levisohn et al., 2000; Riva and
Giorgi, 2000; Scott et al., 2001; Steinlin et al., 2003), where
a consistent pattern of deficits of executive functions, visuo-
spatial abilities, expressive language abilities and verbal
memory as well as communicative modulation of emotions
has been described. These findings suggest the relevance of
a life-span contribution of the cerebellum to the processing of
cognition, language and emotions (Steinlin, 2007; Tavano
et al., 2007a, 2007c). In this light, malformative lesions of the
cerebellum can be especially informative, since they are likely
to cause a major impairment of the cerebellar contribution to
cognition, language, affect and their relationships from the
earliest developmental stages (Tavano et al., 2007b, 2007c).
Such a developmental perspective highlights the relevance
of three major axes in the study of children with malformative
cerebellar lesions: 1) Evolution: how do cognitive, linguistic
and emotional behavioral characteristics, considered sepa-
rately and in their interrelationships, change with time?
2) Affective primitive: are all forms of mental retardation and/
or verbal impairment associated with affect disruption? 3)
Profile specificity: do cognitive and linguistic deficits, and
psychiatric features present with association patterns of
peaks and valleys proper to different types of syndromes?
1.3. Cerebellar malformations (CM)
Steinlin et al. (1999) studied 11 adult patients with pure non-
progressive congenital ataxia with or without cerebellar
hypoplasia. Seven displayed a full intelligence quotient (IQ)
from 60 to 92, the remaining four patients obtained
a harmonic full IQ between 30 and 49. Thus a first distinction
can be made between cerebellar patients who exhibit
a generalized severe impairment of higher-order functions
and those who may present with mild mental retardation or
an average intellectual profile. In the group amenable to
testing the authors described marked difficulties in visuo-
spatial and visuoconstructive abilities, and sustained atten-
tion, while language abilities and selective attention were
within normal limits. Chedda et al. (2002) studied 8 patients
(6 children and 2 adults) with cerebellar agenesis and found
that the severity of motor, neropsychological and affective
deficits correlated with the extension of agenesis. Cognitive
deficits affected executive functions (perseveration, disinhi-
bition, and difficulty in abstract reasoning, working memory
and verbal fluency) and visuospatial abilities, with disorders
of perceptual organization, visuospatial copying and recall. All
cases displayed marked prosodic difficulties but expressive
language difficulties were limited to two cases. Behavioral
disorders included obsessive rituals, failure in understanding
 cortex 46 (2010) 907–918
social cues, and episodes of psychotic depression in the two
adults.
In a recent retrospective study we were able to show that
cognitive and affective deficits in patients with cerebellar
malformations confined to the cerebellum (CM), both children
and adults, are also to be ascribed to the nosological picture of
the CCAS (Tavano et al., 2007c), with three important
differences:
I) Although the initial delay may be marked and general-
ized, it does not preclude the development of higher-
order abilities, even at an advanced age (Tavano et al.,
2007a), which does not confirm the general stance that
the earlier the influence, the more pronounced the
problem (Steinlin, 2007). In such a case, a dysexecutive
syndrome with lack of visuospatial organization and
memory deficits characterizes the ensuing neuro-
cognitive profile.
II) Severe verbal and non-verbal communication deficits,
likely to result from affective and behavioral dysregu-
lation following extensive vermian damage, are associ-
ated with moderate to severe mental retardation and in
some cases lie within the diagnostic limits of the autism
spectrum disorder. However, this was true for only
a subset of patients, while others displayed a neuro-
cognitive profile consistent with the nosological picture
of the CCAS, and among these, we were able to find
evidence for a dissociation of language and affect in
a patient with vermal malformation who did not present
with affect disturbances (Tavano et al., 2007b).
III) Specific linguistic impairments characterize both
receptive and expressive skills in patients with a positive
outcome.
The descriptive flexibility of the CCAS can integrate find-
ings from different types of cerebellar deficits. It also provides
a framework of reference that can be used to distinguish
between mental retardation as a generalized failure in neu-
rocognitive development, and specific deficits within the
neurocognitive profile of the CCAS (Mariën et al., 2008).
1.4. Joubert syndrome (JS)
In our former study we specifically excluded JS, among others,
as we were interested in studying malformations confined to
the cerebellum only (Tavano et al., 2007c). JS is an autosomal
recessive condition clinically characterized by hypotonia,
psychomotor delay, ataxia, and oculomotor apraxia (OMA)
(Valente et al., 2008). As a structural pathognomonic sign, JS
presents with a set of midbrain–hindbrain abnormalities
consisting of deepened interpeduncular fossa with narrow
isthmus and upper pons, thickened, elongated and mal-
oriented superior cerebellar peduncles, and vermian hypo-
plasia/aplasia/dysplasia of varying degree, which overall take
the appearance of a ‘‘molar tooth’’ sign on axial brain
magnetic resonance imaging (MRI) (Maria et al., 1997). It was
first described by Joubert and collaborators (Joubert et al.,
1968), and mental retardation was defined as a hallmark
characteristic. However, recently a combination of molecular
genetics and enhanced structural neuroimaging allowed
909
researchers to identify a set of Joubert syndrome related
disorders (JSRD), of which classical or pure JS represents but
a subtype (Gleeson et al., 2004; Millen and Gleeson, 2008;
Valente et al., 2005, 2008). At the same time, neurobehavioral
investigations in JS documented the existence of a spectral
distribution in cognition, with full IQ ranging from <30 to 85
(Steinlin et al., 1997). Fennell’s et al. (1999) brief neuro-
psychological investigation showed that the majority of
patients were not amenable to testing, in some cases due to
their very young age, but those who were, displayed impaired
verbal working and narrative memory, verbal fluency, visuo-
motor integration, and fine motor control. Besides, evidence
from parents’ reports suggested the presence of problems in
temperament, hyperactivity, aggressiveness and dependency.
Severe motor and oculomotor difficulties can make it hard to
assess children with JS aged younger than 5 and may thus lead
to an overgeneralization of severe learning disability as
a characterizing feature (Hodgkins et al., 2004). Similarly,
children with a diagnosis of JS do not appear to present with
a specific association to classical autism (Takahashi et al.,
2005). However, as has been reported for children with CM
(Tavano et al., 2007c), a disordered neurodevelopment of
cerebellar vermis may induce dysregulation of affect and an
invalidating impairment in speech intelligibility (Harris et al.,
1998), which in turn may give rise to severe temper tantrums
in children who have otherwise good receptive skills (Hodg-
kins et al., 2004). Such a change in clinical perspective on JS
has provided evidence for impairments in cognition, expres-
sive but not receptive language, and emotion, as well as
a developmental trajectory that may present with unexpected
capabilities at follow-up after age 5 years.
In this work we compared the neurobehavioral profiles of
children with malformations confined to the cerebellum (CM)
and children with JS. Specifically, for the CM group we selected
children exhibiting hypoplasia affecting the vermis and one or
both cerebellar hemispheres. Vermian hypoplastic malfor-
mation is a shared feature with JS, which however addition-
ally presents with malformation of pontine and medullary
structures, including pons basalis, reticular formation and
inferior olivary nuclei (Poretti et al., 2007). Conversely,
involvement of the cerebellar hemispheres has not been
documented in JS; however, an association of ‘‘molar tooth’’
sign and neocortical polymicrogyria over the sylvian fissure
has been observed in some cases (Gleeson et al., 2004). We
aimed at verifying the effects of such neuroanatomic differ-
ences on neurodevelopment along the three main axes of
evolution, affective primitive and cognitive profile specificity.
2. Materials and methods
2.1. Participants
2.1.1. CM group
A sample of 16 subjects was extracted from the pool of 27
presented in Tavano et al. (2007c) (12 children, 4 young adults
aged 19–25 years; 11 males, 5 females; mean chronological age
143  84 months; range 42–300; mean mental age 59  47
months; range 10–151). We selected all patients with a Type III
malformation according to Altman et al. (1992), i.e., with
910 cortex 46 (2010) 907–918

hypoplasia of varying degree affecting the vermis and one or
both cerebellar hemispheres. The remaining subjects from
that study presented with near total cerebellar agenesis (Type
I malformation), vermal agenesis (complete or partial, Type II),
or malformations involving only the cerebellar hemispheres
(one or both, Type IV), and were therefore excluded, since
their neuroanatomical lesion did not match the requirements
for comparison with the JS group (i.e., vermian hypoplasia).
To better isolate the specific contribution of a malformative
cerebellar lesion to the development of cognitive and affective
functions, the following exclusion criteria were also applied:
1) radiological picture or medical history consistent with
a diagnosis of acquired lesions due to pre-perinatal suffering;
2) progressive cerebellar pathology; 3) metabolic diseases
associated with congenital malformation of the cerebellum; 4)
malformation affecting other cerebral structures besides the
cerebellum; 5) syndromic patterns involving the cerebellum
which can be associated to secondary cortical suffering (e.g.,
JS, Arnold Chiari Syndrome); 6) epileptic seizures or febrile
convulsions or even focal or generalized paroxysmal EEG
abnormalities (spikes or spike-wave complexes) in the
patient’s clinical history.
2.1.2. JS group
A sample of 8 subjects with a JS related clinical phenotype was
recruited from a residential program for genetic syndromes at
our Institute in Bosisio Parini (Lecco, Italy) (3 males, 5 females;
mean chronological age 90  63 months; range 17–179; mean
mental age 51  47 months; range 10–137). For each patient,
a specific diagnosis within the JSRD spectrum was formulated
based on the nosological classification in Valente et al. (2008).
We found five children with pure JS (JS1, JS2, JS3, JS6, JS7), one
child with COACH (Cerebellar hypoplasia, oligophrenia, ataxia,
coloboma, and hepatic fibrosis) (JS4), one child with oro-facial-
digital VI syndrome (JS5), and one child with CORS (cerebello-
oculo-renal syndrome, i.e., JS þ retinopathy) (JS8). See Table 1
for classification details.
For both experimental groups, a written informed consent,
approved by the Ethics Committee of our Institute, was
obtained from each child participant’s parents or guardians,
and from young adult participants.
2.2. Method
2.2.1. Neuroradiological investigation
For all participants, the neuroradiological study was per-
formed with .5 or 1.5 Tesla MRI equipment, proton density
and T1-, T2-weighted spin-echo sequences, through axial
and coronal sections, 4 or 5 mm thick. For the CM sample, all
the MRI scans were reviewed according to the Atlas of
Schmahmann et al. (1999) by a neuroradiologist blind to the
patients’ identity and clinical data. The CM participants
showed hypoplasia involving the vermis and one or both
hemispheres (see Fig. 1a, b). For the JS sample, based on the
same procedure all the MRI scans were reviewed for the
‘‘molar tooth’’ sign on axial MRI: deep interpeduncular fossa;
thickening of superior cerebellar peduncles; hypoplasia of
vermis characterized by incomplete lobulation and enlarged
fourth ventricle (see Fig. 2a, b). No patient presented with
Dandy–Walker syndrome. One patient (JS2) presented with
corpus callosum hypoplasia.
2.2.2. Neuropsychological, neurolinguistic and
neuropsychiatric assessments
All tests were tailored to each participant’s chronological age
(Intellectual profile), cognitive and cooperation levels (neuro-
psychological and neurolinguistic tests). All the tests were
used in their Italian version. Mental age scores for high-func-
tioning CM and JS participants were calculated from their full
IQ score [Mental Age (MA)_months ¼ (IQ  Chronological
Age_months)/100] to allow comparison with low-functioning
individuals. For patient JS8, only the performance subscale
(and relative mental age) from the Griffiths’ scale was
available.

Table 1 – Classification of JS related disorders.

JSRD features JS1 JS2 JS3 JS4 JS5 JS6 JS7 JS8

JSRD subgroup Pure Pure Pure COACH OFDVI Pure Pure CORS
OMA  þ þ þ þ þ þ Nystagmus
Mental retardation Borderline Mild Borderline Mild Borderline Severe Severe Mild
Respiratory abnormalities        
Dysmorphic features  þ  þ Cleft lip, tongue cyst   
Postaxial polydactyly     a   
‘‘Molar tooth’’ sign þ þ þ þ þ þ þ þ
Other CNS malformations  Corpus callosum      
hypoplasia
Situs inversus        
Congenital heart defects     Bicuspid aortic valve   
Gastroenteric    Increased    
malformations GOT & GPT
Recurrent pulmonary        
infections

OFDVI ¼ oro-facio-digital syndrome VI; CNS ¼ central nervous system; GOT ¼ glutamic oxalacetic transaminase; GPT ¼ glutamyl pyruvic
transaminase.
a ¼ mesaxial polydactyly, preaxial esadactily.
 cortex 46 (2010) 907–918 911

Fig. 1 – Sagittal and coronal brain MRI sections (case GD) showing mild cerebellar hypoplasia involving the vermis and both
hemispheres.

 Neuropsychiatric evaluation:
All the patients received a standard clinical psychiatric
assessment. Psychopathological diagnoses were formulated
in line with the DSM IV (APA, 1994).
 Intellectual profile:
Griffiths Mental Developmental Scale – Revised (Griffiths,
1996); Stanford-Binet Scale – Revised (Bozzo and Mansueto,
1993); Wechsler Preschool and Primary Scale of Intelligence
(WPPSI, Wechsler, 1973); Wechsler Intelligence Scale for
Children-Revised (WISC-R, Wechsler, 1986); Wechsler Adult
Intelligence Scale-Revised (WAIS-R, Wechsler, 1997).
 Executive functions and memory:
Wisconsin Card Sorting Test (Heaton et al., 1993); Tower of
London Test (Shallice, 1982); Continuous Performance Test
(Cornoldi et al., 1996); Wide Range Assessment of Memory and
Learning (WRAML, Sheslow and Adams, 1990); Rey Complex
Figure Test, B (Rey, 1959); Corsi Span (Corsi, 1972); Digit span
(Wechsler Memory Scale, Wechsler, 1963). Word span,
forward (Spinnler and Tognoni, 1987); Verbal Long-Term
Memory Test (Spinnler and Tognoni, 1987); Mirror Star Tracing
Task (Sanes et al., 1990).
 Perceptual, visuospatial and graphic abilities:
Test of Visual–Perceptual Skills (non-motor) – Revised (TVPS,
Gardner, 1996); Judgment of Line Orientation (Benton, 1983),
Rey Complex Figure Test, A (Rey, 1959); Draw-a-Bicycle Test
(Kolb and Whishaw, 1985); Test for Constructive Apraxia
(Arrigoni and De Renzi, 1964); Visual motor integration Test
(VMI, Beery, 2000).

Fig. 2 – Brain MRI of a Joubert patient (case SM) showing the typical constellation of cerebellar and brainstem abnormalities:
(a) axial sections at the pontine level showing the ‘‘molar tooth’’ sign (circle); (b) median sagittal section illustrating
deepened interpeduncular fossa (arrow) and cerebellar vermis hypoplasia (arrow).
912 cortex 46 (2010) 907–918

 Speech and Language:

Mental age 1.06–3.00 (years, months): First Language Test
(Axia, 1995).
Mental age 3.00–6.00: Language Assessment Test (Cianchetti
and Fancello, 1997).
Mental age 4.00–15.00: Language Assessment Battery (see
Tavano et al., 2007b for a detailed summary of the relevant
norm-referenced tests).

All neuropsychological and neurolinguistic test results

were transformed into a set of ordinal qualitative evaluations
ranging from 0 (no impairment) to 3 (severe impairment).
Three main domains were considered: emotion, cognition and
language. Within cognition, three further subdomains were
identified: executive functions, visuospatial skills, and
memory skills (verbal and visuospatial). Language compre-
hension and expression were distinguished.
Fig. 3 – Crossed distribution of chronological and mental
2.2.3. Statistics age in the CM group.
Pearson Chi-square and Mann–Whitney Test were run on
demographic data to ascertain the sample characteristics.
Further, a Spearman correlation analysis was run between
results (Fig. 3). As for the JS group, a closer pacing of mental
chronological age and mental age separately for the CM and JS
and chronological age is evident on graphical inspection of the
groups.
data (Fig. 4).
As for the intellectual profile, a Mann–Whitney Test was
Table 2 reports the overall profile of both groups of
run on the Wechsler subtest scores for the two subsets of
patients with respect to psychopathological signs and the
patients for whom data were available. A Kolmogorov–
determination of clinically relevant neuropsychiatric
Smirnov Test was run on verbal IQ (VIQ) and performance
syndromes. It appears that, while CM participants may
IQ (PIQ).
present with severe psychopathological disorders such as
Finally, ordinal data from the available qualitative evalu-
Pervasive Developmental Disorder (PDD) or Atypical Autism
ations of the cognitive, linguistic and emotional domains were
(AA) with a frequency of 5 out of 16 (31.25%), JS participants
compared again using a Mann–Whitney Test to verify the
have a lower incidence of autistic-like traits (1 out of 8,
presence of significant differences between the two groups.
12.5%).
Association patterns were investigated using Spearman
The Wechsler subtest scores were converted into Z scores
correlation analysis. Values of p  .05 were declared signifi-
for a better comparison of weaknesses and strengths (in bold
cant. SPSS 13.0 software was used (SPSS, Chicago, IL).
in Table 3). Regarding the overall full scale IQs, values below 50
were reported as equal to 50. A significant difference was
found in the Arithmetic subtest (Mann–Whitney U ¼ 4.00,
3. Results

With regard to demographic characteristics, no significant

differences in numerosity (Spearman c2 ¼ 2.667, p ¼ .10) and
gender (Spearman c2 ¼ .667, p ¼ .41) were found. No differ-
ences were found between the two experimental groups in
chronological age (Mann–Whitney U ¼ 46.00, p ¼ .14; mean
CM ¼ 143  84 months; mean JS ¼ 90  63) and mental age
(Mann–Whitney U ¼ 58.00, p ¼ .37; mean CM ¼ 59  47 months;
mean JS ¼ 51  47). Therefore, the two groups were well
balanced in all relevant characteristics. The correlation anal-
ysis between mental and chronological age yielded a signifi-
cant positive correlation coefficient for both CM (Spearman
r ¼ .51, p < .05) and JS (Spearman r ¼ .86, p < .01). However, in
the CM group variance was higher for chronological age than
for mental age, due to the presence of two different groups:
patients 1–9 displayed a severe generalized psychomotor
delay (severe mental retardation in cases 1–5, moderate
mental retardation in cases 6–9) which did not change as
a function of age; patients 10–16 were within the range of mild
retardation – normal cognitive profile, and therefore their Fig. 4 – Crossed distribution of chronological and mental
mental age results were closer to their chronological age age in the JS group.
 cortex 46 (2010) 907–918 913

The correlation analysis, independently run for each

Table 2 – Distribution of psychopathological signs and
psychiatric diagnoses across samples. group, showed a perfect positive correlation between verbal
memory and language expression in the CM group (Spearman
Subjects Psychopathological Psychiatric
r ¼ 1.00, p < .01), and similarly for the JS group (Spearman
signs disorders
r ¼ .94, p < .05). However, the JS participants displayed
CM1 Withdrawal, stereotyped PDD a perfect positive correlation also between language compre-
behavior and activities
hension and visuospatial skills (Spearman r ¼ 1.00, p < .01),
CM2 Symbiotic dimension, autistic traits PDD
which was not present in the CM group. No other significant
CM3 Self-injury and aggressiveness, PDD
withdrawal, anxiety difference was found.
CM4 Withdrawal PDD
CM5 Minimal withdrawal N
CM6 – N 4. Discussion
CM7 Liability, rigidity, purposelessness N
CM8 Impairment in reciprocal AA
We have taken a neurodevelopmental perspective in
social interaction with
excessive anxiety and worry
analyzing the behavioral profiles of children with malforma-
CM9 Rigidity of thought and compulsion OCDa tions confined to the cerebellum and children with JS. We
with excessive aimed at verifying the effects of neuroanatomic similarities
anxiety and aggressiveness (vermian hypoplasia) and differences (involvement of the
CM10 Minimal depressive traits N cerebellar hemispheres in CM; of the brainstem in JS) on
CM11 – N
neurodevelopment along the three main axes of evolution,
CM12 Anxiety, mild depressive N
affective primitive and cognitive profile specificity.
symptoms
CM13 Minimal withdrawal N Our findings confirm the relevance of a life-span contri-
CM14 Hyperactivity, excessive anxiety ADHDa bution of the cerebellum to the processing of cognition,
CM15 Anxiety, compulsive traits N language, and emotions by showing the effects of age, the role
CM16 Anxiety, aggressiveness N of affect as compared to cognition and language, and finally by
JS1 – N providing initial evidence for the existence of a specific profile
JS2 – N of peaks and valleys in both syndrome groups.
JS3 – N
JS4 – N 4.1. Evolution
JS5 – N
JS6 Impairment in social interaction AA
CM patients 10–16 (43.75%) present with an overall positive
JS7 – N
JS8 – N
evolution, with case CM14 displaying a normal intellectual
profile (See Table 3). It appears that a principle along the lines
OCD ¼ Obsessive-Compulsive Disorder; ADHD ¼ Attention Deficit of ‘‘the earlier – the worse’’ would be too simplistic to account
Hyperactivity Disorder; N ¼ no psychiatric disorder.
for the data overall. A similar principle has been discussed in
a ¼ Syndrome-like.
the literature on supratentorial acquired brain lesions, but it
has ultimately been refined to take into account the specific
contribution of the compensatory mechanisms of the
p < .05), with JS subjects scoring lower than CM participants. subcortical structures which, together with the lesioned
No other significant differences were found. A large amount of cortical one, form a unified neurofunctional system (Tavano
within-group variance for each subtest was evident at subtest et al., 2009). Future investigations with Diffusion Tensor
mean plotting (Figs. 5 and 6). However, the performance Imaging (DTI) will allow a better understanding of the neural
profile presented with less overall variability in JS, with the pathway dynamics that underlie such differences, which may
exception of the Picture Completion subtest. A Kolmogorov– originate from compensatory plasticity processes.
Smirnov Test showed no significant differences between the As for JS, our data clearly show that including a severe
PIQ and VIQ within each group. No other significant differ- psychomotor delay as a pathognomonic feature for the clin-
ences were found. ical diagnosis of JS would be unwarranted and ultimately
The comparison of emotional, cognitive and linguistic wrong (Hodgkins et al., 2004) (see Fig. 4 and Table 3). Four out
profiles between the two groups (see Table 4) showed signifi- of eight subjects (50% of the sample) were amenable to formal
cant differences on four out of eight subdomains, and testing, and amongst the remaining four, two were too young
specifically on emotional skills (Mann–Whitney U ¼ 2.00, to be extensively evaluated (JS4 and JS7), and two (JS6 and JS8)
p < .05), executive functions (Mann–Whitney U ¼ 3.00, p < .05), were within the testable range for chronological age but
verbal memory (Mann–Whitney U ¼ 4.50, p < .05), and showed moderate to severe mental retardation and disorders
language expression (Mann–Whitney U ¼ .00, p < .01). of interpersonal relationship (JS6) or severe visual problems
However, while the mean rank for CM participants was and social disadvantage (JS8). The impact of corpus callosum
superior to that of JS participants on emotional skills (7.71 vs hypoplasia, a consistent finding within the spectrum of JS
3.00) and executive functions (7.57 vs 3.25), which were more related disorders (Valente et al., 2008), on the neurocognitive
impaired, the opposite pattern was seen for verbal memory development of JS2 remains at present unknown. Therefore,
(CM ¼ 4.64 vs JS ¼ 8.38) and expressive language skills with regard to the development of phenotypical features,
(CM ¼ 4.00 vs JS ¼ 9.50). children with JS display a spectrum of possible outcomes from
914 cortex 46 (2010) 907–918

Table 3 – Intellectual profile (Z scores).

W1* IN VO AR SI CO SE PC AP BD – GD MA
W2 IN VO AR SI CO DP PC CD BD PA OA MA
W3 IN VO AR SI CO DP PC DS BD PA OA –
FIQ VIQ PIQ

CM10 60 63 L2.66 1.33 2 2 2 .66 68 1.33 1 L1.66 1 L2.33 –
CM11* 64 86 þ.66 0 L1.66 L1.66 .66 – 50 L2.66 L1.66 L2.66 – L2.33 –
CM12 56 62 3 L2.33 2 1.33 1.33 L2.33 58 L1.66 3 L2.66 1.33 L2.33 –
CM13 78 78 0 1 L1.66 1 L2.33 – 81 1.33 – 0 1.33 1.33 .66
CM14 91 102 D1.66 þ1.33 1.33 þ.33 1 .33 82 1.33 L2.33 þ.33 .33 .66 –
CM15 81 96 .33 1 .66 þ.33 þ.66 .33 69 1 1.33 3 0 2 L2.66
CM16* 74 81 .33 1 1.33 0 L1.66 – 73 L1.66 .33 .66 – L2.66 .66

Mean 72 81.14 .57 .76 L1.52 .76 1.18 .91 68.71 L1.56 L1.6 1.47 .99 L1.94 1.49
SD 12.55 15.19 1.69 1.14 .46 .97 .99 .95 11.62 .53 .95 1.37 .73 .7 1

JS1 70 68 1.33 L2.33 L2.33 .66 L2 L2.66 73 1.33 L1.66 1 1 1.33 .66
JS2* 63 80 .66 .66 3 þ.33 1.33 – 52 2 3 L2.66 – L1.66 L2.33
JS3* 76 74 L2 L1.66 L1.66 .33 1.33 – 84 þ.33 1.33 1 – 1.33 .66
JS5 77 82 0 1.33 2 .33 .66 1 76 0 L2.33 .33 1.33 L1.66 1

Mean 71.5 76 .99 1.49 L2.24 .24 1.33 L1.83 71.25 .75 L2.08 1.24 1.16 1.49 1.16
SD 6.45 6.32 .86 .69 .57 .41 .54 1.17 13.64 1.09 .74 .99 .23 .19 .79

W1 ¼ WPPSI; W2 ¼ WISC-R; W3 ¼ WAIS-R; FIQ ¼ full scale intelligence quotient; IN ¼ Information; VO ¼ Vocabulary; AR ¼ Arithmetic;
SI ¼ Similarities; CO ¼ Comprehension; SE ¼ Sentences; DP ¼ Digit span; PC ¼ Picture Completion; AP ¼ Animal Pegs; CD ¼ Coding; DS ¼ Digit
Symbol; BD ¼ Block Design; PA ¼ Picture Arrangement; GD ¼ Geometric Design; OA ¼ Object Assembly; MA ¼ Mazes; – ¼ subtest not performed;
SD ¼ standard deviation; * ¼ W1;  ¼ W3. Scores in bold character ¼ </> 1.5 SDs below/above the mean.

autistic-like behavior to borderline intelligence and normal
affect. They fare similarly to children with CM, but with an
overall better profile. Overall, it appears then that mental
retardation is not a necessary, or even frequent, outcome of
vermal hypoplasia (Mariën et al., 2008).
A recent DTI study has evidenced the absence of decus-
sation of superior cerebellar peduncles in JS (Poretti et al.,
2007). This interesting finding may underlie a difference in
the neural basis of skill acquisition in JS versus CM. Specifi-
cally, it could provide evidence for an ipsilateral arrange-
ment of cerebello-cortical connections for lateralized
cerebral functions, and thus be causal in explaining the
relatively better preserved intellectual profile in JS as
compared to CM.
Although of different sizes, our experimental groups were
well balanced on all the main demographic characteristics,
thereby excluding a group composition bias in interpreting
results. However, the CM group showed a greater variance in
the relationship between chronological and mental ages as
compared to the JS group (see Figs. 3 and 4). This fact is likely
to be due to class membership definition for CM participants,
resulting in substantial differences in the extent of the mal-
formative lesion involvement of the vermis and cerebellar
hemispheres.

Fig. 5 – Verbal and Performance intellectual profile of CM Fig. 6 – Verbal and Performance intellectual profile of JS
participants (Scaled scores). participants (Scaled scores).
 cortex 46 (2010) 907–918 915

Table 4 – Emotional, cognitive and linguistic profiles.

Subjects Emotion Executive Visuoperceptual Visuospatial Verbal Language Language
functions and visuospatial skills memory memory comprehension expression

CM10 þ þ þ þ  þ 
CM11  þþþ þþ þ  þ 
CM12 þ þ þ þ  þ 
CM13 þþ þþ þ þþ þ þ þ
CM14 þþ þþþ þþ þ þ þ þ
CM15 þþ þþ þ þ   
CM16 þþ þþþ þ þ  þ 

JS1   þ þþ þþ þ þþ
JS2  þþ þþ þþ þþþ þþþ þþþ
JS3    þ þþþ  þþþ
JS5    þþþ   þþ

þþþ ¼ severe deficit (3); þþ ¼ moderate deficit (2); þ ¼ mild deficit (1);  ¼ normal (0).

4.2. Affective primitive 4.3. Profile specificity

The basic question pertaining to affect/emotion in CM and JS is
whether the distribution of emotional disturbances within
a psychopathological range is scattered over different pheno-
types or is proper of those with associated mental retardation.
This issue is of the greatest relevance in the perspective of an
embodied acquisition of cognitive skills, mediated by first-
person emotional adherence to what we see as well as to what
we do (Wicker et al., 2003; Iacoboni, 2005; Hurley, 2008).
Our data suggest that the most severe forms of mental
retardation for CM participants are associated to affect
disruption (Cases 1–4). However, as already pointed out, the
reverse does not hold, since cases CM 5–9 show a uniform
state of moderate mental retardation which does not change
with age but is associated to emotional/behavioral distur-
bances in only 2 cases (8 and 9). Among the subjects with JS,
the only one with atypical features of autism also has
moderate mental retardation. Overall, then, CM participants
present with severe psychopathological disorders such as PDD
or AA with a frequency of 5 out of 16 (31.25%), while JS displays
a far lower incidence of such problems (1 out of 8, 12.5%).
These results confirm that JS and classical autism are not
likely to share genotype/phenotype relation traits (Takahashi
et al., 2005). However, differences within the CM patients
leave such an option open to investigation.
The qualitative results reported in Table 4 suggest that
emotional as well as cognitive functions are areas of relevant
differences between the two experimental groups. CM
subjects are less competent than JS participants in emotional
and executive skills. The two subdomains appear to be inde-
pendently affected since no correlation was detected. These
data concern only testable subjects, and therefore they are not
biased by the presence of severely impaired individuals in the
whole CM group. Following from this, it can be preliminarily
suggested that localizing moderate to severe affect distur-
bances to vermian lesions does not constitute a sufficient
causal condition. As for JS, while verbal expressive abilities as
well as verbal working memory are severely and specifically
affected in JS (Braddock et al., 2006), they are not associated
with emotional disturbances, contrary to the general stance in
the literature (Harris et al., 1998; Hodgkins et al., 2004).
Cognitive, linguistic and affective patterns of peaks and
valleys have been highlighted for both groups, with associated
between-group differences. A significant difference in the
Arithmetic subtest was observed, with JS participants scoring
lower than CM participants. A similar finding was present in
our retrospective study on CM patients (Tavano et al., 2007c).
In view of the significantly lower verbal scores for JS children,
we can envisage two likely explanations: a) a generalized
deficit in abstract reasoning; b) weak phonological represen-
tations impacting on arithmetical development, as has been
independently argued for dyslexia (Simmons and Singleton,
2007). With regard to this issue, follow-up studies of reading,
writing and arithmetic skill learning are mandatory for JS.
A visual inspection of the plots from Table 3 (Figs. 5 and 6)
shows that, on the one hand, the JS participants’ verbal profile is
overall worse than the CM participants’ (with the exception of
Information and Similarities subtests), although no statistical
differences in global VIQ scores were found. On the other hand,
the visual inspection of the performance profile appears to
disclose more differences, with CM subjects performing worse on
Block Design and Mazes tasks, and JS on the Digit Symbol task.
The comparison of emotional, cognitive and linguistic
profiles between the two groups showed significant differences
on four out of eight subdomains, and specifically on emotional
skills, executive functions, verbal memory, and language
expression. However, while the mean rank for CM subjects was
superior to that of JS participants on emotional skills (7.71 vs
3.00) and executive functions (7.57 vs 3.25), the opposite pattern
was evident for verbal memory (CM ¼ 4.64 vs JS ¼ 8.38) and
expressive language (CM ¼ 4.00 vs JS ¼ 9.50), thereby confirm-
ing the selective difficulty in on-line use of language by chil-
dren with JS. It is highly likely that a marked deficit in oro-
motor functions, a frequent finding in JS, may be one of the
underlying common causes since it would impact not only
overt verbal behavior intelligibility but also subvocal rehearsal
skills (Silveri et al., 1993; Braddock et al., 2006). Interestingly,
while perfect or almost perfect positive correlations between
verbal memory and language expression were expected in both
groups, the perfect positive correlation in JS children that was
found only between language comprehension and visuospatial
916 cortex 46 (2010) 907–918
skills suggests a new reason for the preserved comprehension
skills in JS: namely, they might heavily rely on contextual
visuospatial analysis to embody language understanding
strategies as spatial strategies (Small and Nusbaum, 2004).
5. Conclusions
Our findings enable us to confirm the presence of cognitive,
language and affective disturbances in patients with malfor-
mations confined to the cerebellum and patients with JS,
although with important differences. It can be stated that
different types of congenital malformative lesions of the
cerebellum lead to a complex picture that can be subsumed
under the CCAS, both with regard to the peaks and valleys of
the general profile (Schmahmann and Sherman, 1998; Riva
and Giorgi, 2000; Tavano et al., 2007c).
The comparison between participants with hypoplasia of
the cerebellar vermis and hemispheres and participants with
JS showed some areas of overlapping disturbances but also
intriguing differences. In particular, participants with JS seem
to be less exposed to severe affective and relational disorders.
Furthermore, severe mental retardation is more frequently
found in participants with CM and generally it is unwarranted
to consider the presence of moderate or severe psychomotor
retardation as a pathognomonic trait of JS. Participants with
CM show a greater impairment of affective and executive
functions, while participants with JS show a greater impair-
ment of verbal performances. As a wide variability was
observed in both groups, it would be advisable to carry on the
study, in particular for JS, in order to distinguish different
subtypes by means of genetic and clinical–instrumental tests
and establish a close relationship between the genotype and
the behavioral and neuropsychological phenotypes.
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