Impaired and preserved aspects of independent finger control in patients with cerebellar damage.

The influence of the cerebellum on independent finger control has rarely been investigated. We examined multidigit control in 22 patients with cerebellar degeneration, 20 patients with cerebellar stroke, and 21 patients with surgical lesions after cerebellar tumor removal. In the first task, either the index finger or the middle finger was actively lifted from an object during static holding. Both controls and cerebellar patients increased the forces of the nearby digits in synchrony with lift-off to maintain the total finger force. Patients used increased finger forces but showed no significant deficits in the pattern and timing of rearrangement of finger forces. In the second task, subjects had to press and release one finger against a force-sensitive keypad with the other fingers being inactive. All patient groups showed increased force production of the noninstructed (enslaved) fingers compared with controls. Lesion-symptom mapping in the focal patients revealed that lesions of the superior hand area were related to abnormal levels of enslaving. Increased finger forces in the finger-lifting task likely reflect an unspecific safety strategy. Increased effects of enslaving in the individuated key-press task, however, may be explained by a deterioration of cerebellar contribution to feedforward commands necessary to suppress activity in noninstructed fingers or by increased spread of the motor command intended for the instructed finger. Despite the large and diverse patient sample, surprisingly few abnormalities were observed. Both holding an object and finger typing are overlearned, automatized motor tasks, which may not or little depend on the integrity of the cerebellum.

Influences of load characteristics on impaired control of grip forces in patients with cerebellar damage.

Various studies showed a clear impairment of cerebellar patients to modulate grip force in anticipation of the loads resulting from movements with a grasped object. This failure corroborated the theory of internal feedforward models in the cerebellum. Cerebellar damage also impairs the coordination of multiple-joint movements and this has been related to deficient prediction and compensation of movement-induced torques. To study the effects of disturbed torque control on feedforward grip-force control, two self-generated load conditions with different demands on torque control-one with movement-induced and the other with isometrically generated load changes-were directly compared in patients with cerebellar degeneration. Furthermore the cerebellum is thought to be more involved in grip-force adjustment to self-generated loads than to externally generated loads. Consequently, an additional condition with externally generated loads was introduced to further test this hypothesis. Analysis of 23 patients with degenerative cerebellar damage revealed clear impairments in predictive feedforward mechanisms in the control of both self-generated load types. Besides feedforward control, the cerebellar damage also affected more reactive responses when the externally generated load destabilized the grip, although this impairment may vary with the type of load as suggested by control experiments. The present findings provide further support that the cerebellum plays a major role in predictive control mechanisms. However, this impact of the cerebellum does not strongly depend on the nature of the load and the specific internal forward model. Contributions to reactive (grip force) control are not negligible, but seem to be dependent on the physical characteristics of an externally generated load.

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.

Impairments of prehension kinematics and grasping forces in patients with cerebellar degeneration and the relationship to cerebellar atrophy.

OBJECTIVE: This study established the relationship between kinematic and grip force parameters in prehension tasks, disease severity and cerebellar atrophy in patients with cerebellar degeneration. METHODS: Prehension was tested in a condition during which the hand reached out, grasped, and lifted an object. Task complexity was modified by limiting the transport component to a single-joint movement, and introducing a bimanual condition. RESULTS: Compared to controls the cerebellar patients showed disturbances in hand transport, in hand shaping and the most pronounced in time to peak grip force and the grip/load force coupling. Task-dependent changes did not differ between groups. Ataxia scores revealed significant correlations with hand transport and shaping measures only. Ataxia subscores correlated with volume reduction of appropriate longitudinal cerebellar zones. Volume reduction of the intermediate zone was associated with grip force coordination deficits. CONCLUSIONS: Results indicate that the cerebellum may have a more general role in motor control of grasping independent of task complexity. Temporal and coordinative measures of grip force appear to be most useful to assess the severity of grasping deficits in patients with cerebellar degeneration not detectable by clinical ataxia scales. SIGNIFICANCE: To assess the severity and course of cerebellar disease grip force control in a standard prehension task is a sensitive quantitative measure.

Lesions of the dentate and interposed nuclei are associated with impaired prehension in cerebellar patients.

In a recent study using voxel based lesion symptom mapping (VLSM) in cerebellar patients following stroke we found associations of prehensile deficits to lesions of the cerebellar cortex and dentate nucleus (DN). Associations to lesions of the interposed nucleus (IN), which has been shown to contribute to prehension in monkeys, could not be established. One possible reason was that the IN was largely unaffected in the stroke patients. To further address the question of IN involvement in prehension we performed VLSM in patients with surgical cerebellar lesions (n=20), exhibiting high lesion overlap in the medial and intermediate cerebellum including the IN. Prehensile deficits were quantified by analyses of movement kinematics and finger forces. In the patient population prehensile deficits comprised lower movement velocity in reaching and increased lift-off time in grasping. These were associated with lesions of the intermediate and lateral cerebellar cortex together with their output nuclei. Specifically, IN lesions were linked to increased lift-off time in grasping and not to slower reaching movements. Thus, our data support IN contribution particularly for the fluent production of grip forces during dexterous prehension in humans.

Size-weight illusion, anticipation, and adaptation of fingertip forces in patients with cerebellar degeneration.

The smaller of two equally weighted objects is judged to be heavier when lifted (size-weight illusion [SWI]). In contrast, fingertip forces show an initial size effect but adapt to the true object weights within a few trials. The aim of this study was to investigate possible contributions of the cerebellum to SWI, force anticipation, and adaptation based on object size and weight. Eighteen participants with isolated cerebellar degeneration and 18 age- and gender-matched controls alternately lifted objects of equal weight but different size in 40 trials. All participants perceived the small object to be heavier after lifting (perceptive SWI). Fingertip forces were significantly higher during the first lift of the large object compared with the small object in the control and cerebellar groups. For the load-force rate and lifting acceleration, effects of anticipation were significantly less in the cerebellar compared with the control group. Grip and load forces were adapted to object weight during repeated lifts in both groups. Preserved perceptive SWI in cerebellar patients supports the hypothesis that perceptive SWI depends on the function of the ventral visual path that receives no or few efferents from the cerebellum. The findings of preserved anticipation and adaptation of grip forces in cerebellar patients, however, were unexpected. Reduced anticipation of load forces suggests that the neural presentation of predictive grip- and load-force control may be different. Findings show that representation and adaptation of internal models of object characteristics are not exclusively located in the cerebellum.