Cerebellar deep nuclei involvement in cognitive adaptation and automaticity.

To determine the role of the interpositus nuclei of cerebellum in rule-based learning and optimization processes, we studied (1) successive transfers of an initially acquired response rule in a cross maze and (2) behavioral strategies in learning a simple response rule in a T maze in interpositus lesioned rats (neurotoxic or electrolytic lesions). Even though lesioned animals showed no impairment in learning the initial stimulus-response association, they had difficulties in transferring the acquired adapted response rule, and in optimizing their response strategy. These results add information on the role of interpositus nuclei in adaptation to environmental changes.

Teachers' report of learning and behavioural difficulties in children treated for cerebellar tumours.

PRIMARY OBJECTIVE: The aim of the study was the validation of the Deasy-Spinetta Questionnaire (DSQ) in 6-11 year olds with attention to the verification of three factors (learning difficulties, socialization and emotionality) and its application in children treated for cerebellar tumour. METHODS AND PROCEDURES: Twenty-nine children aged between 6-11 years were compared with 609 classmates. Teachers completed the DSQ. Patients were evaluated according to Wechsler Scales, the Purdue Pegboard and the International Cooperative Ataxia Rating scale. MAIN OUTCOMES AND RESULTS: In classmates, the DSQ factorial analysis showed three factors: learning, socialization difficulties and disturbing behaviour. Teachers reported more learning difficulties in patients than in classmates. Learning difficulties in patients were greater for mathematics and reasoning than for reading. Patients were described as less active, without evidence of autistic-like behaviour or irritability. The teachers' report of learning difficulties was significantly correlated with IQ scores, but not with neurological deficits. CONCLUSIONS: The proposed DSQ scores are interesting for the assessment of learning and behavioural difficulties in children treated for cerebellar tumours, as they provide complementary ecological information to that given by clinical and neuropsychological testing.

The neural cell adhesion molecule-derived peptide FGL facilitates long-term plasticity in the dentate gyrus in vivo.

The neural cell adhesion molecule (NCAM) is known to play a role in developmental and structural processes but also in synaptic plasticity and memory of the adult animal. Recently, FGL, a NCAM mimetic peptide that binds to the Fibroblast Growth Factor Receptor 1 (FGFR-1), has been shown to have a beneficial impact on normal memory functioning, as well as to rescue some pathological cognitive impairments. Whether its facilitating impact may be mediated through promoting neuronal plasticity is not known. The present study was therefore designed to test whether FGL modulates the induction and maintenance of synaptic plasticity in the dentate gyrus (DG) in vivo. For this, we first assessed the effect of the FGL peptide on synaptic functions at perforant path-dentate gyrus synapses in the anesthetized rat. FGL, or its control inactive peptide, was injected locally 60 min before applying high-frequency stimulation (HFS) to the medial perforant path. The results suggest that although FGL did not alter basal synaptic transmission, it facilitated both the induction and maintenance of LTP. Interestingly, FGL also modified the heterosynaptic plasticity observed at the neighboring lateral perforant path synapses. The second series of experiments, using FGL intracerebroventricular infusion in the awake animal, confirmed its facilitating effect on LTP for up to 24 h. Our data also suggest that FGL could alter neurogenesis associated with LTP. In sum, these results show for the first time that enhancing NCAM functions by mimicking its heterophilic interaction with FGFR facilitates hippocampal synaptic plasticity in the awake, freely moving animal.

Cognitive processing impairments in a supra-second temporal discrimination task in rats with cerebellar lesion.

The role of interpositus nuclei (IN) in timing in the sub-second range is well supported in eyeblink conditioning studies. Timing impairments shown in the seconds range in patients with intermediate cerebellar lesion, and known intermediate cerebellar cortex projection to IN raise the question of a possible involvement of IN in timing in the supra-second range as well. To address this question, we tested rats (Sprague-Dawley) given bilateral lesions of IN with Colchicine in a 2- vs. 8-s temporal discrimination task, followed by three daily sessions of a temporal bisection tests with five added intermediate non-reinforced durations. IN lesioned rats showed normal acquisition of the temporal discrimination, but a transient impairment of temporal sensitivity during the bisection tests. In addition, their response latencies suggested a different behavioral strategy from that of control animals. Our results indicate that the IN of the cerebellum may not be critically involved in temporal processing in the 2-8 s range, but may play a role in the cognitive processes that access temporal information in the mediation of choice behavior.

Cognitive and academic outcome after benign or malignant cerebellar tumor in children.

OBJECTIVE: To examine the impact of malignancy and location of the cerebellar tumor on motor, cognitive, and psychologic outcome. BACKGROUND: Although many studies focus on long-term outcome after cerebellar tumor treatment in childhood, the impact of its precise location remains unclear. PATIENTS AND METHODS: Children, aged from 6 to 13 years, with a cerebellar malignant tumor (MT; MT group, n=20) or a cerebellar benign tumor (BT; BT group, n=19) were examined at least 6 months after the end of treatment using the international cooperative ataxia rating scale, the Purdue pegboard for manual skill assessment and the age-adapted Weschler scale. Structural changes in brain anatomy were evaluated and parents and teachers answered 2 independent questionnaires. RESULTS: Parents and teachers reported high rate of learning and academic difficulties, but without any difference with respect to the type of tumor. However, children with cerebellar MT showed increased cognitive and motor difficulties compared with children with cerebellar BT. Cerebellar signs at clinical examination and manual skill impairment were strongly associated with cognitive difficulties. Both motor and cognitive impairments were found to be associated with extension of the lesion to the dentate nuclei. CONCLUSIONS: Dentate nuclei lesions are major risk factors of motor and cognitive impairments in both cerebellar BT and MT.

Injuries to inferior vermis and dentate nuclei predict poor neurological and neuropsychological outcome in children with malignant posterior fossa tumors.

BACKGROUND: Children treated for a malignant posterior fossa tumor (PFT) are at risk of intellectual impairment. Its severity is not explained by age and radiotherapy alone. The current study was designed to define the correlations between the anatomical damage and the neurological/neuropsychological deficits in children with a malignant PFT. METHODS: Sixty-one consecutive children (mean age, 6.0 years) treated for a malignant PFT with surgery, chemotherapy, and radiotherapy underwent a detailed neuropsychological evaluation, including a full-scale intelligence quotient (FSIQ), on average 5.6 years after the diagnosis. The neurological examination was recorded 1 month after surgery and at the time of the neuropsychological evaluation. Cerebellar and brain injuries were scored based on the magnetic resonance imaging (MRI). Correlation of these injuries with neurological and cognitive outcome were performed after adjustment for other potential risk factors (radiotherapy schedule, age, hydrocephalus, duration of symptoms, socioeconomic status, and surgical complications). RESULTS: Neurological deficits were strong predictors of low cognitive performances irrespective of the other risk factors. The extent of cerebellar deficits and fine motor dexterity impairment were correlated with the degree of damage to the dentate nuclei and inferior vermis. The IQ scores were inversely correlated with the severity of the damage to the dentate nuclei; mean FSIQ was 83 if they were both intact and 65 in the case of bilateral damage (P=.009). CONCLUSIONS: Damage to the dentate nuclei and to the inferior vermis, observed on MRI, predict the degree of impairment of neurological and neuropsychological functions in children treated for a malignant PFT.

Parental report of cognitive difficulties, quality of life and rehabilitation in children with epilepsy or treated for brain tumour.

PURPOSE: Paediatric neurological chronic conditions are often associated with physical, cognitive, psychological and behavioural difficulties that may affect quality of life (QOL) of children and their families. In this study, we compare parental report of difficulties and rehabilitation in children with various epileptic syndromes or treated for a benign or malignant brain tumour. METHOD: One hundred fifty-three children aged between 6 and 12 years were included, 119 with epilepsy (non-idiopathic generalized 31, non-idiopathic partial 62, idiopathic 26) and 34 treated for a brain tumour. Parents answered a multidimensional questionnaire on child's autonomy and cognitive or behavioural difficulties, impact of the illness on their own everyday life, and rehabilitation. RESULTS: Learning difficulties were reported by a majority of parents in all groups. Behavioural and autonomy problems were more often reported in the non-idiopathic generalized epilepsy group. Report of tiredness was more frequent and of disrupting behaviour less frequent in the tumour group than in epilepsy. Impact of the child's illness on parents' QOL was strong in all groups, and stronger in case of severe forms of epilepsy. CONCLUSIONS: Parental concerns are important to consider for rehabilitation programmes adapted to each child with these neurological conditions.

Remediation of learning difficulties in children after treatment for a cerebellar medulloblastoma: a single-case study.

In the process of establishing a methodology for individualized remediation programmes in children treated for cerebellar tumour, this study followed prospectively over 11 years a young child treated for a medulloblastoma at 18 months of age throughout the rehabilitation process. Repeated neuropsychological and academic evaluations evidenced temporary disruptive behaviour, deficient manual and visual abilities, attention and working memory difficulties, but preserved language abilities, in relation with vermian and left cerebellar damage. However, the described remediation programmes and interventions allowed the child to have fluent progression in school. Limits and benefits of rehabilitation are discussed.

Habit learning dissociation in rats with lesions to the vermis and the interpositus of the cerebellum.

After cerebellar tumors resection, patients show motor skill learning impairments but also cognitive deficits. However, their exact origins remain controversial. Using a rat model of cerebellar injury, we assessed the involvement of two structures often damaged during resection (vermis and interpositus nuclei) on habits development. During extended training of an instrumental task, rats develop response routines that are no longer voluntary or goal-directed but habit-based, evidenced by their insensitivity to changes in the value of the reward. Here we showed that, in contrast to sham or vermis lesioned rats, discrete lesions to interpositus nuclei prevented rats from developing habits with overtraining, without motor difficulties, nor alteration of the instrumental task acquisition. Our results suggest that the role of the cerebellum can be extended from motor skill learning to cognitive routines learning. Similar habit impairment could possibly account for some of the long-term outcome difficulties observed in cerebellar-damaged patients.