The role of the cerebellum in reconstructing social action sequences: a pilot study.

Recent research has revealed that the cerebellum plays a critical role in social reasoning and in particular in understanding false beliefs and making trait attributions. One hypothesis is that the cerebellum is responsible for the understanding of sequences of motions and actions, which may be a prerequisite for social understanding. To investigate the role of action sequencing in mentalizing, we tested patients with generalized cerebellar degenerative lesions on tests of social understanding and compared their performance with matched healthy volunteers. The tests involved understanding violations of social norms making trait and causal attributions on the basis of short behavioral sentences and generating the correct chronological order of social actions depicted in cartoons (picture sequencing task). Cerebellar patients showed clear deficits only on the picture sequencing task when generating the correct order of cartoons depicting false belief stories and showed at or close to normal performance for mechanical stories and overlearned social scripts. In addition, they performed marginally worse on trait attributions inferred from verbal behavioral descriptions. We conclude that inferring the mental state of others through understanding the correct sequences of their actions requires the support of the cerebellum.

A Japanese Family of Spinocerebellar Ataxia Type 21: Clinical and Neuropathological Studies.

Spinocerebellar ataxia type 21 (SCA21) is a rare subtype of autosomal dominant cerebellar ataxias, which was first identified in a French family and has been reported almost exclusively in French ancestry so far. We here report the first Japanese family with SCA21, in which all affected members examined carried a heterozygous c.509C > T:p.Pro170Leu variant in TMEM240. Their clinical features were summarized as a slowly progressive ataxia of young-adult onset (5-48 years) associated with various degree of psychomotor retardation or cognitive impairment. The MR images revealed atrophy in the cerebellum, but not in the cerebrum or brainstem. These clinical findings were consistent with those in the original French families with SCA21. Neuropathological findings in one autopsied patient showed a prominent decrease of cerebellar Purkinje cells, but no specific abnormalities outside the cerebellum.

Flight simulation using a Brain-Computer Interface: A pilot, pilot study.

As Brain-Computer Interface (BCI) systems advance for uses such as robotic arm control it is postulated that the control paradigms could apply to other scenarios, such as control of video games, wheelchair movement or even flight. The purpose of this pilot study was to determine whether our BCI system, which involves decoding the signals of two 96-microelectrode arrays implanted into the motor cortex of a subject, could also be used to control an aircraft in a flight simulator environment. The study involved six sessions in which various parameters were modified in order to achieve the best flight control, including plane type, view, control paradigm, gains, and limits. Successful flight was determined qualitatively by evaluating the subject's ability to perform requested maneuvers, maintain flight paths, and avoid control losses such as dives, spins and crashes. By the end of the study, it was found that the subject could successfully control an aircraft. The subject could use both the jet and propeller plane with different views, adopting an intuitive control paradigm. From the subject's perspective, this was one of the most exciting and entertaining experiments she had performed in two years of research. In conclusion, this study provides a proof-of-concept that traditional motor cortex signals combined with a decoding paradigm can be used to control systems besides a robotic arm for which the decoder was developed. Aside from possible functional benefits, it also shows the potential for a new recreational activity for individuals with disabilities who are able to master BCI control.

Secondary orthostatic tremor in the setting of cerebellar degeneration.

Orthostatic tremor (OT) and cerebellar ataxia are uncommon and difficult to treat. We present two patients with OT and cerebellar degeneration, one of whom had spinocerebellar ataxia type 2 and a good treatment response.

Contribution of the Cerebellum in Cue-Dependent Force Changes During an Isometric Precision Grip Task.

The "raspberry task" represents a precision grip task that requires continuous adjustment of grip forces and pull forces. During this task, subjects use a specialised grip rod and have to increase the pull force linearly while the rod is locked. The positions of the fingers are unrestrained and freely selectable. From the finger positions and the geometry of the grip rod, a physical lever was derived which is a comprehensive measurement of the subject's grip behaviour. In this study, the involvement of the cerebellum in establishing cued force changes (CFC) was examined. The auditory stimulus was associated with a motor behaviour that has to be readjusted during an ongoing movement that already started. Moreover, cerebellar involvement on grip behaviour was examined. The results show that patients presenting with degenerating cerebellar disease (CBL) were able to elicit CFC and were additionally able to optimise grip behaviour by minimising the lever. Comparison of the results of CBL with a control group of healthy subjects showed, however, that the CFC incidence was significantly lower and the reduction of the lever was less in CBL. Hence, the cerebellum is involved not only in the classical conditioning of reflexes but also in the association of sensory stimuli with complex changes in motor behaviour. Furthermore, the cerebellum is involved in the optimisation of grip behaviour during ongoing movements. Recent studies lead to the assumption that the cerebello-reticulo-spinal pathway might be important for the reduced optimisation of grip behaviour in CBL.

Modulation of error-sensitivity during a prism adaptation task in people with cerebellar degeneration.

Cerebellar damage can profoundly impair human motor adaptation. For example, if reaching movements are perturbed abruptly, cerebellar damage impairs the ability to learn from the perturbation-induced errors. Interestingly, if the perturbation is imposed gradually over many trials, people with cerebellar damage may exhibit improved adaptation. However, this result is controversial, since the differential effects of gradual vs. abrupt protocols have not been observed in all studies. To examine this question, we recruited patients with pure cerebellar ataxia due to cerebellar cortical atrophy (n = 13) and asked them to reach to a target while viewing the scene through wedge prisms. The prisms were computer controlled, making it possible to impose the full perturbation abruptly in one trial, or build up the perturbation gradually over many trials. To control visual feedback, we employed shutter glasses that removed visual feedback during the reach, allowing us to measure trial-by-trial learning from error (termed error-sensitivity), and trial-by-trial decay of motor memory (termed forgetting). We found that the patients benefited significantly from the gradual protocol, improving their performance with respect to the abrupt protocol by exhibiting smaller errors during the exposure block, and producing larger aftereffects during the postexposure block. Trial-by-trial analysis suggested that this improvement was due to increased error-sensitivity in the gradual protocol. Therefore, cerebellar patients exhibited an improved ability to learn from error if they experienced those errors gradually. This improvement coincided with increased error-sensitivity and was present in both groups of subjects, suggesting that control of error-sensitivity may be spared despite cerebellar damage.

TMEM240 mutations cause spinocerebellar ataxia 21 with mental retardation and severe cognitive impairment.

Autosomal dominant cerebellar ataxia corresponds to a clinically and genetically heterogeneous group of neurodegenerative disorders that primarily affect the cerebellum. Here, we report the identification of the causative gene in spinocerebellar ataxia 21, an autosomal-dominant disorder previously mapped to chromosome 7p21.3-p15.1. This ataxia was firstly characterized in a large French family with slowly progressive cerebellar ataxia, accompanied by severe cognitive impairment and mental retardation in two young children. Following the recruitment of 12 additional young family members, linkage analysis enabled us to definitively map the disease locus to chromosome 1p36.33-p36.32. The causative mutation, (c.509C>T/p.P170L) in the transmembrane protein gene TMEM240, was identified by whole exome sequencing and then was confirmed by Sanger sequencing and co-segregation analyses. Index cases from 368 French families with autosomal-dominant cerebellar ataxia were also screened for mutations. In seven cases, we identified a range of missense mutations (c.509C>T/p.P170L, c.239C>T/p.T80M, c.346C>T/p.R116C, c.445G>A/p.E149K, c.511C>T/p.R171W), and a stop mutation (c.489C>G/p.Y163*) in the same gene. TMEM240 is a small, strongly conserved transmembrane protein of unknown function present in cerebellum and brain. Spinocerebellar ataxia 21 may be a particular early-onset disease associated with severe cognitive impairment.

[Neurorehabilitation for spinocerebellar degeneration].

It remains to be elucidated whether there is a use- or dose-dependent effect of rehabilitative intervention on impairment and disability of spinocerebellar degeneration since the disease progressively damages cerebellar structure that plays a crucial role in motor learning. Moreover there is a trade-off between functional improvement after rehabilitation and functional deterioration due to disease progression. Recent clinical trials from Germany and Japan have demonstrated that comprehensive intensive rehabilitation focusing on balance function have immediate and lasting effect up to 1 year on ataxia and gait disorder in patients with spinocerebellar degeneration. For sustained gain after the intensive rehabilitation, customized attempts to boost patients' daily activities according to their ability appears to be important.

Physiotherapy in degenerative cerebellar ataxias: utilisation, patient satisfaction, and professional expertise.

Physiotherapy plays an important role in the management of patients with degenerative cerebellar ataxias. However, our insight in the quantity and quality of physiotherapy prescription in this group of patients is incomplete. The purposes of this study were to investigate the utilization of physiotherapy and patient satisfaction in patients with degenerative ataxias in The Netherlands and to examine the level of expertise and needs of physiotherapists treating ataxia patients. Questionnaires were sent to members of the Dutch association for patients with degenerative cerebellar ataxias (n = 532). In addition, 181 questionnaires were sent to the physiotherapists who had recently treated the patients who responded. Eventually, 317 questionnaires from patients (60 %) and 114 questionnaires from physiotherapists (63 %) could be used for further analysis. Sixty-four percent of the patients were currently treated by a physiotherapist. Their median treatment duration was 5 years. Nineteen percent of the patients had never been referred, often despite the presence of limitations in daily activities. On the other hand, some participants without reported limitations had received physiotherapy. In general, participants were satisfied with their physiotherapist. The most reported treatment goals were improvement or maintenance of balance, general physical condition, and mobility. Physiotherapists reported lack of ataxia-specific expertise and expressed the need for education and evidence-based guidelines. Referral to and use of physiotherapy in patients with degenerative cerebellar ataxia in The Netherlands are currently inconsistent and not in agreement with the little scientific evidence available. Referral rates are high, but referrals and actual necessity are discrepant; treatment duration is long; and ataxia-specific expertise among physiotherapists is insufficient. Evidence-based recommendations and specific training of physiotherapists are needed.

Oculomotor deficits affect neuropsychological performance in oculomotor apraxia type 2.

INTRODUCTION: Ataxia with oculomotor apraxia type 2 is a rare and early-disabling neurodegenerative disease, part of a subgroup of autosomal recessive cerebellar ataxia, in which oculomotor symptoms (e.g., increased saccade latency and hypometria) and executive function deficits have been described. The aim of this study was to evaluate the impact of oculomotor symptoms on cognitive performance and, in particular, over reading in 2 Italian siblings affected by ataxia with oculomotor apraxia type 2. METHODS: The neuropsychological profiles and the oculomotor patterns during nonverbal and verbal tasks were recorded and analyzed. RESULTS: Saccadic intrusions and/or nystagmus were observed in all eye movement tasks. The neuropsychological profiles were substantially preserved, with only subtle deficits that affected visuomotor integration and attention. Reading ability decreased and became impaired. The reading scan was disturbed by saccadic intrusions and/or nystagmus. However, an ad hoc reading task demonstrated that deficits appeared only when the items that were displayed enhanced oculomotor requests. The preservation of lexical-semantic processes confirmed that the reading disability was caused by oculomotor deficits, not cognitive problems. CONCLUSION: Present findings indicate that in patients who are affected by ataxia with oculomotor apraxia type 2, performance on neuropsychological tests, especially those that require rapid performance and eye or hand-eye control, must be analyzed with respect to oculomotor components.

Deficient use of visual information in estimating hand position in cerebellar patients.

We tested cerebellar degeneration in human patients in a task designed to isolate different aspects of motor planning and found a specific relationship between their ability to do inverse kinematic transformation and sparing of Crus I. Our approach was based on an experimental design introduced by Sober and Sabes (2003, 2005). Their paradigm allows behavioral deficits in planning of movement direction to be dissociated from deficits in generation of motor commands and also allows for the relative role played by visual and proprioceptive information to be quantified. Perturbation of visual information about hand position affected cerebellar degeneration patients (N = 12) and age-matched controls equally in determining movement direction, but had less of an effect in both groups in the transformation of movement direction to motor command. However, when provided with vision of the joints, control participants were more affected in generating the motor command in perturbed trials, and cerebellar degeneration participants were not. Thus, cerebellar patients were less able to use visual information about the joints in generating motor commands. Voxel-based morphometric analysis showed that this inability was primarily correlated with degeneration of Crus I. These results show that the cerebellum plays a role in motor planning, and specifically in the generation of inverse kinematic models for sensorimotor processing. The involvement of Crus I is consistent with an emerging picture in which increasingly posterior lobules of the anterior cerebellar cortex are associated with increasingly complex and abstract aspects of motor behavior.

The functional role of the cerebellum in visually guided tracking movement.

We propose a new method to provide a functional interpretation of motor commands (i.e., muscle activities) and their relationship to movement kinematics. We evaluated our method by analyzing the motor commands of normal controls and patients with cerebellar disorders for visually guided tracking movement of the wrist joint. Six control subjects and six patients with cerebellar disorders participated in this study. We asked the subjects to perform visually guided smooth tracking movement of the wrist joint with a manipulandum, and recorded the movements of the wrist joint and activities of the four wrist prime movers with surface electrodes. We found a symmetric relationship between the second-order linear equation of motion for the wrist joint and the linear sum of activities of the four wrist prime movers. The symmetric relationship determined a set of parameters to characterize the muscle activities and their similarity to the components of movement kinematics of the wrist joint. We found that muscle activities of the normal controls encoded both the velocity and the position of the moving target, resulting in precise tracking of the target. In contrast, muscle activities of the cerebellar patients were characterized by a severer impairment for velocity control and more dependence on position control, resulting in poor tracking of the smoothly moving target with many step-like awkward movements. Our results suggest that the cerebellum plays an important role in the generation of motor commands for smooth velocity and position control.

Humor and laughter in patients with cerebellar degeneration.

Humor is a complex behavior which includes cognitive, affective and motor responses. Based on observations of affective changes in patients with cerebellar lesions, the cerebellum may support cerebral and brainstem areas involved in understanding and appreciation of humorous stimuli and expression of laughter. The aim of the present study was to examine if humor appreciation, perception of humorous stimuli, and the succeeding facial reaction differ between patients with cerebellar degeneration and healthy controls. Twenty-three adults with pure cerebellar degeneration were compared with 23 age-, gender-, and education-matched healthy control subjects. No significant difference in humor appreciation and perception of humorous stimuli could be found between groups using the 3 Witz-Dimensionen Test, a validated test asking for funniness and aversiveness of jokes and cartoons. Furthermore, while observing jokes, humorous cartoons, and video sketches, facial expressions of subjects were videotaped and afterwards analysed using the Facial Action Coding System. Using depression as a covariate, the number, and to a lesser degree, the duration of facial expressions during laughter were reduced in cerebellar patients compared to healthy controls. In sum, appreciation of humor appears to be largely preserved in patients with chronic cerebellar degeneration. Cerebellar circuits may contribute to the expression of laughter. Findings add to the literature that non-motor disorders in patients with chronic cerebellar disease are generally mild, but do not exclude that more marked disorders may show up in acute cerebellar disease and/or in more specific tests of humor appreciation.

Health-related quality of life among community-dwelling patients with intractable neurological diseases and their caregivers in Japan.

AIMS: The aims of this study were: (i) to clarify the general quality of life (QOL) of patients with intractable neurological disease; (ii) to clarify the general QOL of the caregivers of these patients; and (iii) to explore the association of QOL in patient-caregiver pairs. METHODS: A cross-sectional survey was conducted between November 2003 and May 2004 among community-dwelling patients diagnosed with Parkinson's disease (PD), spinocerebellar degeneration (SCD), multiple system atrophy (MSA), and amyotrophic lateral sclerosis (ALS) and their caregivers using a mailed, self-administered questionnaire. To measure QOL, we used the Medical Outcome Study 36-Item Short Form (SF-36) for patients and the short form of the health-related QOL scale SF-36 (SF-8) for caregivers. RESULTS: A total of 418 questionnaires were analyzed. For the patients, all of the general QOL domains of the SF-36 were significantly lower than the national standard value for all of the diagnoses. Physical function, role physical, and role emotional domains were also low. For caregivers, all of the QOL summary scores of the SF-8 for all diagnoses were significantly lower than the national standard value. Although there were several significant correlations of QOL between patients and caregivers, overall the correlations were low. CONCLUSIONS: Support for patients with neurological diseases and their caregivers is needed in order to maintain physical and mental QOL.

Behavioral characteristics, associative learning capabilities, and dynamic association mapping in an animal model of cerebellar degeneration.

Young adult heterozygous Lurcher mice constitute an excellent model for studying the role of the cerebellar cortex in motor performance-including the acquisition of new motor abilities-because of the early postnatal degeneration of almost all of their Purkinje and granular cells. Wild-type and Lurcher mice were classically conditioned for eyelid responses using a delay paradigm with or without an electrolytic lesion in the interpositus nucleus. Although the late component of electrically evoked blink reflexes was smaller in amplitude and had a longer latency in Lurcher mice than that in controls, the two groups of animals presented similar acquisition curves for eyeblink conditioning. The lesion of the interpositus nucleus affected both groups of animals equally for the generation of reflex and conditioned eyelid responses. Furthermore, we recorded the multiunitary activity at the red and interpositus nuclei during the same type of associative learning. In both nuclei, the neural firing activity lagged the beginning of the conditioned response (determined by orbicularis oculi muscle response). Although red nucleus neurons and muscle activities presented a clear functional coupling (strong correlation and low asymmetry) across conditioning, the coupling between interpositus neurons and either red nucleus neurons or muscle activities was slightly significant (weak correlation and high asymmetry). Lurcher mice presented a nonlinear coupling (high asymmetry) between red nucleus neurons and muscle activities, with an evident compensatory adjustment in the correlation of firing between interpositus and red nuclei neurons (a coupling with low asymmetry), aimed probably at compensating the absence of cerebellar cortical neurons.

Analysis of subjective evaluations of the functions of tele-coaching intervention in patients with spinocerebellar degeneration.

Few studies have revealed the impact of tele-coaching on patients with intractable diseases, including intractable neurological diseases. This study aimed to analyze and describe subjective evaluations of coaches and intervention subjects on the functions of tele-coaching intervention for patients with spinocerebellar degeneration. This qualitative descriptive study was conducted between December 2005 to July 2006. Immediately prior to data collection three experienced coaches had delivered individual 10 session semi-structured tele-coaching interventions to 24 subjects. Data from the 24 logs kept by coaches and individual interviews with the three coaches and nine patients were analyzed using a content analysis technique. Although patients' subjective evaluations varied, the themes that emerged from the data analysis were generally positive: that the tele-coaching enabled patients to tell their own stories in a daily-life setting, encouraged them to experience and adopt fresh points of view, and helped them to start working towards attainable goals without giving up. Our results indicate that it is especially important to encourage patients with intractable diseases to become aware of their latent desires and goals. For patients such as those with spinocerebellar degeneration the time frame for coaching interventions might be extended when required to accommodate treatment of their changing medical and mental condition.

Characteristics of depression in Parkinson's disease: evaluating with Zung's Self-Rating Depression Scale.

The purpose of the study was to elucidate characteristics of depression in Parkinson's disease (PD). Fifty-eight PD patients were evaluated with Zung's Self-Rating Depression Scale (SDS) and the Unified Parkinson's Disease Rating Scale (UPDRS). Scores for "suicidal ideation" on the SDS correlated with posture and gait disturbances on the UPDRS. Twenty-six patients with spinocerebellar degeneration (SCD) were also evaluated with the SDS. SDS scores for "indecisiveness" and "constipation" were significantly higher in PD patients than SCD patients. Our results suggest that depression is common in disabled persons but PD patients might have a characteristic clinical presentation.

Effect of coaching on psychological adjustment in patients with spinocerebellar degeneration: a pilot study.

OBJECTIVE: To examine effect of coaching intervention on psychological adjustment to illness and health-related QOL (HRQOL) in patients with spinocerebellar degeneration. DESIGN: Randomized controlled trial. SUBJECTS: Twelve independently living patients with spinocerebellar degeneration aged 20-65 years old, without cognitive impairment or psychiatric disorder received coaching intervention, which was postponed in another 12 (control). INTERVENTIONS: Three physician coaches telephoned assigned patients for 15-30 minutes in each of 10 weekly coaching sessions over three months. MAIN OUTCOME MEASURES: Primary endpoints were HRQOL (SF-36) and psychological adjustment to illness (Nottingham Adjustment Scale, Japanese version; NAS-J). RESULTS: Two-way analysis of variance (group x time) showed statistically significant main effects of time for vitality (F = 5.00; P = 0.036), anxiety/depression (F = 5.15; P = 0.033), and locus of control (F = 5.58; P = 0.027), indicating improvement of scores over time in both coaching and control groups. No main effect of group or interaction was seen. However analysis of covariance with baseline scores as the covariate showed the coaching group to have better self-efficacy scores than controls at follow-up (least-square mean, experimental group, 65.1; control group, 52.7; P = 0.037). CONCLUSION: Carefully structured telephone coaching can improve self-efficacy in patients with spinocerebellar degeneration.