Juergen Konczak

Proprioception and Motor Control in Parkinson's Disease

ABSTRACT Parkinsons disease (PD) is a neurodegenerative disorder that leads to a progressive decline in motor function. Growing evidence indicates that PD patients also experience an array of sensory problems that negatively impact motor function. This is especially true for proprioceptive deficits, which profoundly degrade motor performance. This review specifically address the relation between proprioception and motor impairments in PD. It is structured around 4 themes: (a) It examines whether the sensitivity of kinaesthetic perception, which is based on proprioceptive inputs, is actually altered in PD. (b) It discusses whether failed processes of proprioceptive-motor integration are central to the motor problems in PD. (c) It presents recent findings focusing on the link between the proprioception and the balance problems in PD. And (d) it discusses the current state of knowledge of how levodopa medication and deep brain stimulation affect proprioceptive and motor function in PD. The authors conclude that a failure to evaluate and to map proprioceptive information onto voluntary and reflexive motor commands is an integral part of the observed motor symptoms in PD.

Postural and gait performance in children with attention deficit/hyperactivity disorder

Up to 50% of children and adolescents with attention deficit/hyperactivity disorder (ADHD) exhibit motor abnormalities including altered balance. Results from brain imaging studies indicate that these balance deficits could be of cerebellar origin as ADHD children may show atrophy in those regions of the cerebellum associated with gait and balance control. To address this question, this study investigated postural and gait abilities in ADHD children and compared their static and dynamic balance with children with known lesions in the cerebellum. Children diagnosed with ADHD according to DSM IV-TR diagnostic criteria were compared with children with chronic surgical cerebellar lesions and age-matched controls. A movement coordination test was used to assess differences in motor development. Postural and gait abilities were assessed using posturography, treadmill walking and a paced stepping task. Volumes of the cerebellum and the cerebrum were assessed on the basis of 3D magnetic resonance images (MRI). Children with cerebellar lesions showed significant performance decrements in all tasks compared with the controls, particularly in the movement coordination test and paced stepping task. During dynamic posturography ADHD-participants showed mild balance problems which correlated with findings in cerebellar children. ADHD children showed abnormalities in a backward walking task and minor abnormalities in the paced stepping test. They did not differ in treadmill walking from the controls. These findings support the notion that cerebellar dysfunction may contribute to the postural deficits seen in ADHD children. However, the observed abnormalities were minor. It needs to be examined whether balance problems become more pronounced in ADHD children exhibiting more prominent signs of clumsiness.

Balance and motor speech impairment in essential tremor

The pathogenesis of essential tremor (ET) is still under debate. Several lines of evidence indicate that ET is associated with cerebellar dysfunction. The aim of the present study was to find corroborating evidence for this claim by investigating balance and speech impairments in patients with ET. In addition, the effect of deep brain stimulation (DBS) on balance and speech function was studied. A group of 25 ET patients including 18 with postural and/or simple kinetic tremor (ETpt) and seven ET patients with additional clinical signs of cerebellar dysfunction (ETc) was compared to 25 healthy controls. In addition, 12 ET patients with thalamic DBS participated in the study. Balance control was assessed during gait and stance including tandem gait performed on a treadmill as well as static and dynamic posturography. Motor speech control was analyzed through syllable repetition tasks. Signs of balance impairment were found in early stages and advanced stages of ET. During locomotion, ET patients exhibited an increased number of missteps and shortened stride length with tandem gait. ETc patients and, to a lesser extent, ETpt patients had increased postural instability in dynamic posturography conditions that are sensitive to vestibular or vestibulocerebellar dysfunction. ETc but not ETpt patients exhibited significantly increased syllable durations. DBS had no discernable effect on speech performance or balance control. We conclude that the deficits in balance as well as the subclinical signs of dysarthria in a subset of patients confirm and extend previous findings that ET is associated with an impairment of the cerebellum.

Lesion-Symptom Mapping of the Human Cerebellum

High-resolution structural magnetic resonance imaging (MRI) has become a powerful tool in human cerebellar lesion studies. Structural MRI is helpful to analyse the localisation and extent of cerebellar lesions and to determine possible extracerebellar involvement. Functionally meaningful correlations between a cerebellar lesion site and behavioural data can be obtained both in subjects with degenerative as well as focal cerebellar disorders. In this review, examples are presented which demonstrate that MRI-based lesion-symptom mapping is helpful to study the function of cerebellar cortex and cerebellar nuclei. Behavioural measures were used which represent two main areas of cerebellar function, that is, motor coordination and motor learning. One example are correlations with clinical data which are in good accordance with the known functional compartmentalisation of the cerebellum in three sagittal zones: In patients with cerebellar cortical degeneration ataxia of stance and gait was correlated with atrophy of the medial (and intermediate) cerebellum, oculomotor disorders with the medial, dysarthria with the intermediate and limb ataxia with atrophy of the intermediate and lateral cerebellum. Similar findings were obtained in patients with focal lesions. In addition, in patients with acute focal lesions, a somatotopy in the superior cerebellar cortex was found which is in close relationship to animal data and functional MRI data in healthy control subjects. Finally, comparison of data in patients with acute and chronic focal lesions revealed that lesion site appears to be critical for motor recovery. Recovery after lesions to the nuclei of the cerebellum was less complete. Another example which extended knowledge about functional localisation within the cerebellum is classical conditioning of the eyeblink response, a simple form of motor learning. In healthy subjects, learning rate was related to the volume of the cortex of the posterior cerebellar lobe. In patients with focal cerebellar lesions, acquisition of eyeblink conditioning was significantly reduced in lesions including the cortex of the superior posterior lobe, but not the inferior posterior lobe. Disordered timing of conditioned eyeblink responses correlated with lesions of the anterior lobe. Findings are in good agreement with the animal literature. Different parts of the cerebellar cortex may be involved in acquisition and timing of conditioned eyeblink responses in humans. These examples demonstrate that MRI-based lesion-symptom mapping is helpful to study the contribution of functionally relevant cerebellar compartments in motor control and recovery in patients with cerebellar disease. In addition, information about the function of cerebellar cortex and nuclei can be gained.

Current advances in lesion-symptom mapping of the human cerebellum

While high-resolution structural magnetic resonance imaging (MRI) combined with newer analysis methods has become a powerful tool in human cerebral lesion studies, comparatively few studies have used these advanced imaging techniques to study lesions of the human cerebellum and their associated symptoms. This review will summarize the methodology of MRI-based lesion-symptom mapping of the human cerebellum and discuss its potential for gaining insights into cerebellar function. The investigation of patients with defined focal lesions yields the greatest potential for obtaining meaningful correlations between lesion site and behavioral deficits. In smaller groups of patients overlay plots and subtraction analysis are good options. If larger groups of patients are available, different statistical techniques have been introduced to compare behavior and lesion site on a voxel-by-voxel basis. Although localization in degenerative cerebellar disorders is less accurate because of the diffuse nature of the disease, certain information about the supposed function of larger subdivisions of the cerebellum can be gained. Examples are given which show that lesion-symptom mapping allows to investigate the function of the intermediate zone and cerebellar nuclei. We conclude that meaningful correlations between lesion site and behavioral data can be obtained in patients with degenerative as well as focal cerebellar disorders.

Kinesthesia is impaired in focal dystonia.

Parkinsons disease (PD) and focal dystonia (FD) are both predominantly characterized by motor symptoms. Also, recent research has shown that sensory processing is impaired in both movement disorders. FD is characterized by involuntary movements and abnormal limb postures; thus, abnormal kinesthesia could be involved in the pathogenesis. We examined passive index finger movements in patients with FD (n = 12) and PD (n = 11) and in age‐matched healthy controls (n = 13). Compared to healthy controls, patients with PD and FD were significantly impaired in the correct detection of the movement direction. The perceptual thresholds for 75% correct responses of movement direction were 0.21 degrees for FD and 0.28 degrees for PD patients compared to 0.13 degrees in control subjects. Subjects with PD and FD were also significantly impaired when they had to judge consecutive amplitudes. Results of the present study point to impaired kinesthesia in FD. Defective sensory processing could be involved in the pathophysiology of the disease and may influence dystonic contractions.

Learning to Play the Violin: Motor Control by Freezing, Not Freeing Degrees of Freedom

Playing a violin requires precise patterns of limb coordination that are acquired over years of practice. In the present study, the authors investigated how motion at proximal arm joints influenced the precision of bow movements in novice learners and experts. The authors evaluated the performances of 11 children (4-12 years old), 3 beginning-to-advanced level adult players, and 2 adult concert violinists, using a musical work that all had mastered as their first violin piece. The authors found that learning to play the violin was not associated with a release or freeing of joint degrees of freedom. Instead, learning was characterized by an experience-dependent suppression of sagittal shoulder motion, as documented by an observed reduction in joint angular amplitude. This reduction in the amplitude of shoulder flexion-extension correlated highly with a decrease of bow-movement variability. The remaining mechanical degrees of freedom at the elbow and shoulder showed patterns of neither suppression nor freeing. Only violinists with more than 700 practice hr achieved sagittal shoulder range of motion comparable to experts. The findings imply that restricting joint amplitude at selected joint degrees of freedom, while leaving other degrees of freedom unconstrained, constitutes an appropriate strategy for learning complex, high-precision motor patterns in children and adults. The findings also highlight that mastering even seemingly simple bowing movements constitutes a prolonged learning process.

The effect of subthalamic nucleus stimulation on kinaesthesia in Parkinson’s disease

Background: Parkinson’s disease is accompanied by deficits in passive motion and limb position sense. Objective: To investigate whether deep brain stimulation of the subthalamic nucleus (STN-DBS) reverses these proprioceptive deficits. Methods and results: A passive movement task was applied to nine patients with Parkinson’s disease and bilateral chronic STN-DBS and to seven controls. Thresholds for 75% correct responses were 0.9° for controls, 2.5° for Parkinson’s disease patients when stimulation was OFF, and 2.0° when stimulation was ON. Conclusions: STN-DBS improves kinaesthesic deficits in Parkinson’s disease, but does not lead to a full recovery of proprioceptive function.

The effect of damage to the cerebellum on sensorimotor and cognitive function in children and adolescents

This review provides a developmental perspective on our current understanding of the role of the cerebellum for sensorimotor and cognitive function. A synopsis on the contribution of the cerebellum on motor control, learning and cognition based on experiments in human adults and animals is presented. This knowledge is contrasted to the relevant literature on children and adolescents. Special attention is given to findings derived from lesion studies and clinical reports that examined the effect of cerebellar damage during development. In general, it is established that children may show the same sensorimotor deficits as adults as a result of cerebellar damage, while the findings of cognitive dysfunction in children are less clear and remain controversial. Younger children do not necessarily recover better than older children or adolescents. The sparing of the deep cerebellar nuclei and the extent of adjuvant chemo- or radiation therapy are better predictors of later motor and cognitive function in children and adolescents.

Brain changes associated with postural training in patients with cerebellar degeneration: a voxel-based morphometry study.

Recent research indicates that physiotherapy can improve motor performance of patients with cerebellar degeneration. Given the known contributions of the cerebellum to motor learning, it remains unclear whether such observable changes in performance are mediated by the cerebellum or cerebral brain areas involved in motor control and learning. The current study addressed this question by assessing the increase in gray matter volume due to sensorimotor training in cerebellar patients using voxel-based morphometry. Nineteen human subjects with pure cerebellar degeneration and matched healthy controls were trained for 2 weeks on a balance task. Postural and clinical assessments along with structural magnetic resonance imaging were performed pretraining and post-training. The main findings were as follows. First, training enhanced balance performance in cerebellar patients. Second, in contrast to controls patients revealed significantly more post-training gray matter volume in the dorsal premotor cortex. Third, training-related increase in gray matter volume was observed within the cerebellum and was more pronounced in controls than in patients. However, statistically cerebellar changes were at the trend level and thus require additional, independent confirmation. We conclude that sensorimotor training of patients with cerebellar neurodegeneration induces gray matter changes primarily within nonaffected neocortical regions of the cerebellar-cortical loop. Residual function of the cerebellum appears to be exploited suggesting either a recovery from degeneration or intact processes of cerebellar plasticity in the remaining healthy tissue.