The cerebellum: its role in language and related cognitive and affective functions.

The traditional view on the cerebellum as the sole coordinator of motor function has been substantially redefined during the past decades. Neuroanatomical, neuroimaging and clinical studies have extended the role of the cerebellum to the modulation of cognitive and affective processing. Neuroanatomical studies have demonstrated cerebellar connectivity with the supratentorial association areas involved in higher cognitive and affective functioning, while functional neuroimaging and clinical studies have provided evidence of cerebellar involvement in a variety of cognitive and affective tasks. This paper reviews the recently acknowledged role of the cerebellum in linguistic and related cognitive and behavioral-affective functions. In addition, typical cerebellar syndromes such as the cerebellar cognitive affective syndrome (CCAS) and the posterior fossa syndrome (PFS) will be briefly discussed and the current hypotheses dealing with the presumed neurobiological mechanisms underlying the linguistic, cognitive and affective modulatory role of the cerebellum will be reviewed.

"Apraxic dysgraphia" in a 15-year-old left-handed patient: disruption of the cerebello-cerebral network involved in the planning and execution of graphomotor movements.

Apraxic agraphia is a peripheral writing disorder caused by neurological damage. It induces a lack or loss of access to the motor engrams that plan and programme the graphomotor movements necessary to produce written output. The neural network subserving handwriting includes the superior parietal region, the dorsolateral and medial premotor cortex and the thalamus of the dominant hemisphere. Recent studies indicate that the cerebellum may be involved as well. To the best of our knowledge, apraxic agraphia has not been described on a developmental basis. This paper reports the clinical, neurocognitive and (functional) neuroimaging findings of a 15-year-old left-handed patient with an isolated, non-progressive developmental handwriting disorder consistent with a diagnosis of "apraxic dysgraphia". Gross motor coordination problems were objectified as well but no signs of cerebellar, sensorimotor or extrapyramidal dysfunction of the writing limb were found to explain the apraxic phenomena. Brain MRI revealed no supra- and infratentorial damage but quantified Tc-99m-ECD SPECT disclosed decreased perfusion in the anatomoclinically suspected prefrontal and cerebellar brain regions crucially involved in the planning and execution of skilled motor actions. This pattern of functional depression seems to support the hypothesis that "apraxic dysgraphia" might reflect incomplete maturation of the cerebello-cerebral network involved in handwriting. In addition, it is hypothesized that "apraxic dysgraphia" may have to be considered to represent a distinct nosological category within the group of the developmental dyspraxias following dysfunction of the cerebello-cerebral network involved in planned actions.

Posterior fossa syndrome in adults: a new case and comprehensive survey of the literature.

Although the posterior fossa syndrome (PFS) can be considered as an aetiologically heterogeneous condition affecting children and adults, it most often occurs in paediatric patients after cerebellar tumour surgery. In patients with a tumoural aetiology, the syndrome is typically characterised by a short symptom-free postoperative period followed by mutism of variable duration and behavioural and affective changes. More than 200 paediatric cases have been described but reports of adult patients are extremely rare. This paper discusses PFS in adults on the basis of a comprehensive literature survey and describes the pre- and postoperative findings in a new adult patient. In the preoperative phase, cognitive, behavioural and affective abnormalities were identified, matching a diagnosis of cerebellar cognitive affective syndrome (CCAS) (Schmahmann and Sherman, 1998; Schmahmann, 2004). The immediate postoperative course was characterised by prefrontal-like behavioural and affective abnormalities, peduncular hallucinations and confusion evolving to psychosis. Akinetic mutism subsequently developed, lasted for 12 days and then alternated with episodes of diminished responsiveness in which pathological laughing and crying (PLC) occurred. Akinetic mutism resolved after treatment with a non-ergoline dopamine-agonist but CCAS persisted during longitudinal follow-up. From a semiological point of view "relapsing-remitting akinetic mutism" and PLC in our patient might add relevant information to current insights in the clinical expression of the PFS. As evidenced by a close parallelism between single photon emission computed tomography (SPECT) and clinical findings, CCAS as well as PFS seem to reflect functional disruption of the cerebello-cerebral network involved in cognitive, behavioural and affective functions. These findings may indicate that both syndromes share overt semiological resemblances and a common pathophysiological substrate. Consequently, CCAS and PFS may both be regarded as cerebellar-induced clinical conditions showing different aspects of a spectrum that range in degree of severity and symptom duration.

Auditory-perceptual speech analysis in children with cerebellar tumours: a long-term follow-up study.

Mutism and Subsequent Dysarthria (MSD) and the Posterior Fossa Syndrome (PFS) have become well-recognized clinical entities which may develop after resection of cerebellar tumours. However, speech characteristics following a period of mutism have not been documented in much detail. This study carried out a perceptual speech analysis in 24 children and adolescents (of whom 12 became mute in the immediate postoperative phase) 1-12.2 years after cerebellar tumour resection. The most prominent speech deficits in this study were distorted vowels, slow rate, voice tremor, and monopitch. Factors influencing long-term speech disturbances are presence or absence of postoperative PFS, the localisation of the surgical lesion and the type of adjuvant treatment. Long-term speech deficits may be present up to 12 years post-surgery. The speech deficits found in children and adolescents with cerebellar lesions following cerebellar tumour surgery do not necessarily resemble adult speech characteristics of ataxic dysarthria.

Posterior fossa syndrome in an adult patient following surgical evacuation of an intracerebellar haematoma.

The posterior fossa syndrome (PFS) consists of transient cerebellar mutism, cognitive symptoms and neurobehavioural abnormalities that typically develop in children following posterior fossa tumour resection. Although PFS has been documented in more than 350 paediatric cases, reports of adult patients with a vascular aetiology are extremely rare. In addition, the pathophysiological substrate of the syndrome remains unclear. We report an adult patient with PFS after surgical evacuation of a cerebellar bleeding. After 45 days of (akinetic) mutism, the patient's cognitive and behavioural profile closely resembled the "cerebellar cognitive-affective syndrome". A quantified SPECT study showed perfusional deficits in the anatomoclinically suspected supratentorial areas, subserving language dynamics, executive functioning, spatial cognition and affective regulation. We hypothesize that cerebello-cerebral diaschisis might be an important pathophysiological mechanism underlying akinetic mutism, cognitive deficits and behavioural-affective changes in adult patients with PFS.

Cerebellar-induced apraxic agraphia: a review and three new cases.

Apraxic agraphia is a writing disorder due to a loss or lack of access to motor engrams that program the movements necessary to produce letters. Clinical and functional neuroimaging studies have demonstrated that the neural network responsible for writing includes the superior parietal region and the dorsolateral and medial premotor cortex. Recent studies of two cases with atypical lesion localisations in the left thalamus and the right cerebellum support the hypothesis that the written language network is larger than previously assumed. The aim of this study is twofold: (1) to provide a survey of cases of apraxic agraphia published between 1973 and June 2010, and (2) to provide further evidence for a role of the cerebellum in writing via three additional cases who presented with apraxic agraphia after ischemic damage in the cerebellum. Functional neuroimaging studies by means of brain perfusion SPECT showed perfusional deficits in the anatomoclinically suspected supratentorial areas, subserving language dynamics, syntax, naming, writing and executive functioning.

Cognitive and affective disturbances following focal cerebellar damage in adults: a neuropsychological and SPECT study.

The traditional view on cerebellar functioning has recently been challenged by results from neuroanatomical, neuroimaging and clinical studies. In this contribution, eighteen patients with primary cerebellar lesions (vascular: n=13; neoplastic: n=5) were systematically investigated by means of an extensive neuropsychological test battery. Fifteen patients (83%) presented with a broad variety of cognitive and linguistic deficits following cerebellar damage. Disturbances of attention (72%), executive functioning (50%) and memory (50%) were most commonly found. Analyses of our results tend to support the hypothesis of a lateralization of cognitive modulation within the cerebellum, the right cerebellar hemisphere being associated with logical reasoning and language processing and the left cerebellum mediating right-hemispheric functions including attentional and visuo-spatial skills. In addition, nine patients (50%) presented with frontal-like behavioural and affective alterations. In an attempt to determine the working-mechanism underlying cerebellar-induced cognitive and affective disturbances, all patients were investigated by means of quantified Tc-99m-ethylenecysteine dimer (ECD) single photon emission computerized tomography (SPECT) studies. From a semiological point of view, damage to the cerebellum can cause a broad spectrum of clinically significant cognitive and affective disturbances. From a pathophysiological point of view, quantified SPECT data, reflecting the phenomenon of cerebello-cerebral diaschisis, support the functional impact of the cerebellar lesion on cortical functioning through disruption of cerebello-cerebral connections.

Long-term cognitive deficits following posterior fossa tumor resection: a neuropsychological and functional neuroimaging follow-up study.

The posterior fossa syndrome (PFS) consists of transient cerebellar mutism, cognitive symptoms, and neurobehavioral abnormalities that typically develop in children following posterior fossa (PF) tumor resection. The pathophysiological substrate of the syndrome remains unclear. We investigated eight children of whom five presented with a variety of clinically relevant non-motor language symptoms associated with cognitive and behavioral disturbances after PF tumor resection. Four children developed transient cerebellar mutism followed by dysarthric speech. Non-motor language symptoms consisted of agrammatism, anomia, impaired verbal fluency, comprehension deficits, and a spontaneous speech. Neurocognitive deficits included executive dysfunctions, concentration deficits, and visuo-spatial disorders. In addition, all children presented with behavioral and affective disturbances. Functional neuroimaging studies during the phase of mutism by means of SPECT showed perfusional deficits in the anatomo-clinically suspected supratentorial areas subserving language dynamics, syntax, naming, executive functioning, affective regulation, and behavior. A significant improvement of frontal perfusional deficits paralleled the clinical remission of mutism. These results add to the view that the PFS might represent a cerebello-cerebral diaschisis phenomenon, reflecting the metabolic impact of the cerebellar lesion on supratentorial cognitive and affective functions.

Cognitive, linguistic and affective disturbances following a right superior cerebellar artery infarction: a case study.

The cerebellar cognitive affective syndrome (CCAS) is a neurobehavioral syndrome that may develop after congenital and acquired cerebellar lesions. The syndrome consists of deficits in executive functioning, spatial cognition, visual-spatial memory and language and also involves personality and behavioral changes. We describe a 58-year-old right-handed man who in addition to affective disturbances presented with a unique combination of cognitive and linguistic deficits following an ischemic infarction in the vascular territory of the right superior cerebellar artery (SCA). Neurocognitive and neurolinguistic examinations were performed in the acute phase (10 days post-onset) and lesion phase (four weeks post-onset) of the stroke. A Tc-99m-ECD SPECT study was performed five weeks after the stroke. Acute phase data revealed a generalized cognitive decline and mild transcortical sensory aphasia. In the lesion phase, the neurobehavioral tableau was dominated by executive dysfunctions, disrupted divided attention, disturbed visual-spatial organization and behavioral abnormalities. Neurolinguistic investigations disclosed visual dyslexia and surface dysgraphia. Reading of words and visual lexical decision tasks of words and nonwords were severely defective and predominantly characterized by visual errors. In addition, writing irregular and ambiguous words resulted in regularization errors (phonologically plausible errors based on phoneme-grapheme correspondence rules). In the absence of any structural damage in the supratentorial brain regions, a quantified SPECT study showed a relative hypoperfusion in the right cerebellar hemisphere and the left medial frontal lobe. CCAS is for the first time reported in association with visual dyslexia and surface dysgraphia. We hypothesize that the cognitive and linguistic deficits might result from functional disruption of the cerebellar-encephalic pathways, connecting the cerebellum to the frontal supratentorial areas which subserve attentional and planning processes. This phenomenon of crossed cerebellar-cerebral diaschisis is supported by SPECT findings revealing a hypoperfusion in the anatomoclinically suspected brain regions. The constellation of cognitive, linguistic and behavioral symptoms adds new evidence to the multifaceted area of cerebellar neurocognition and demonstrates that the cerebellum might play a crucial role in cognitive, linguistic, and affective processing.

Cerebellar neurocognition: insights into the bottom of the brain.

The traditional view on the core functions of the cerebellum consists of the regulation of motor coordination, balance and motor speech. However, during the past decades results from neuroanatomical, neuroimaging and clinical studies have substantially extended the functional role of the cerebellum to cognitive and affective regulation. Neuroanatomical studies convincingly showed cerebellar connectivity with associative areas of the cerebral cortex involved in higher cognitive functioning, while functional neuroimaging provided evidence of cerebellar activation during a variety of cognitive tasks. In addition, more systematic neuropsychological research performed in patients with cerebellar lesions and the development of more sensitive neuropsychological tests allowed clinicians to identify significant cognitive and affective disturbances following cerebellar damage. In this review, an overview is presented of the cerebellar role in a variety of cognitive processes, such as executive functioning, memory, learning, attention, visuo-spatial regulation, language and behavioral-affective modulation. In addition, recent evidence with regard to cerebellar induced clinical entities such as the cerebellar cognitive affective syndrome (CCAS) and the posterior fossa syndrome (PFS), will be discussed. Although extensive research has substantially broadened the insights in the cognitive and affective role of the cerebellum, the precise nature of the cerebellar contribution to cognitive and affective regulation is not yet clear. In this review experimental and clinical data will be discussed that substantiate the presumed neurobiological mechanisms underlying the cognitive and affective modulatory role of the cerebellum.

The cerebellum and language: the story so far.

BACKGROUND: The cerebellum was traditionally considered to be exclusively involved in the coordination of voluntary movement, gait, posture, balance and motor speech. However, this view was challenged by recent neuroanatomical, neuroimaging and clinical findings, providing preliminary evidence of a cerebellar contribution to linguistic functioning. AIM: To discuss the role of the cerebellum in a variety of linguistic functions and to explore the underlying mechanisms. METHODS: A literature search was conducted via electronic databases. Exclusion criteria were: disorders following congenital cerebellar lesions, motor speech disorders, cognitive deficits outside the language sphere, neuropsychiatric disorders and insufficient information on the cerebellar role in language. Abstracts were not included. In addition, only adult subjects were taken into consideration. RESULTS: A variety of linguistic disorders were found to occur following acquired cerebellar lesions: (1) impaired phonological and semantic fluency; (2) agrammatism (at morphological and sentence level); (3) naming and word finding difficulties; (4) cerebellar-induced aphasia; (5) reading difficulties; (6) writing problems, and (7) higher-level language deficits, including disturbed listening comprehension, impaired language proficiency and metalinguistic ability. Several hypotheses have been suggested to explain the nature of the cerebellar contribution to language. However, findings are not univocal. CONCLUSION: The cerebellum appears to be involved in a variety of linguistic functions. However, the precise nature of this contribution is not clear yet. Linguistic, neuroimaging, neuroanatomical and neuropsychological studies should be combined in order to disentangle the specific contribution of the cerebellum to linguistic processing.

Postoperative motor speech production in children with the syndrome of 'cerebellar' mutism and subsequent dysarthria: a critical review of the literature.

Transient cerebellar mutism is a well-known clinical entity which may develop after surgery to the cerebellum. As the period of mutism is followed by motor speech deficits, the condition has also been termed the syndrome of (cerebellar) Mutism and Subsequent Dysarthria (MSD). In children, its incidence is estimated between 8% and 31%. Unfortunately, the literature provides contradictory information regarding motor speech production post-mutism. We therefore critically reviewed data on 283 childhood cases to chart the mode of recovery of motor speech production after the mute period. After applying stringent exclusion criteria, we found that 98.8% of the children displayed motor speech deficits. This percentage is much higher than commonly reported in the literature. In addition, recovery of speech appeared to be less favourable than previously ascertained. Future studies should investigate more carefully the patients' speech characteristics in order to be able to offer children an adequate and complete rehabilitation program.

Neurobehavioral alterations in an adolescent following posterior fossa tumor resection.

The posterior fossa syndrome (PFS) consists of a variety of symptoms, including cerebellar mutism, behavioral disturbances and personality changes. We report longitudinal clinical, neuroradiological and neurobehavioral findings in a 19-year-old left-handed patient, diagnosed with attentional deficit hyperactivity disorder (ADHD) at the age of 12, who underwent posterior fossa tumor resection. Although the patient did not develop cerebellar mutism after surgery, marked apathy and emotional indifference, urinary retention, eye-lid apraxia and visual hallucinosis became apparent after a brief interval of normal functioning. Based on these findings it is argued that the PFS might be considered a semiological heterogeneous condition with variable clinical expressions. Long-term follow-up investigations revealed subtle, but significant cognitive and affective deficits, resembling the cerebellar cognitive affective syndrome in adults. As demonstrated by functional neuroimaging studies with SPECT, symptoms were associated with perfusional deficits in the anatomoclinically suspected supratentorial regions, reflecting the distant impact of the cerebellum on cognitive and affective functions.

Acquired alexia with agraphia syndrome in childhood.

The acquired alexia with agraphia syndrome is a conspicuous disorder of reading and writing in the absence of significant other language impairments that has mainly been recorded in adults. Pure cases are rare, with most patients displaying mild aphasic deficits. In children, acquired reading and writing disorders are generally reported as part of more encompassing aphasic syndromes affecting oral and written language equally, for example, Broca or Wernicke aphasia. Documented instances of predominant acquired reading and writing disorders in childhood are exceptional. We report an 11-year-old, right-handed boy who sustained a left temporoparieto-occipital hematoma following rupture of an arteriovenous malformation and who consecutively presented with the acquired alexia with agraphia syndrome associated with word-finding difficulties. Neuropsychologic and neurolinguistic data showed that there was no concomitant Gerstmann and/or angular gyrus syndrome. Th e recoveryfrom the anomia was quite favorable, but recovery of written language was more protracted and acted on the patient's further scholastic achievement. This case is reminiscent of a historical childhood case reported in 1939 and is consonant with adult cases in terms of lesion location and semiologic picture.