Unilateral cerebellar lesions influence arm movements bilaterally

Limb ataxia is seen as a sign of ipsilateral cerebellar dysfunction. However, imaging studies have shown a bilateral cerebellar activation during unilateral hand movements. We questioned whether unilateral cerebellar lesions affect pointing movements not only of the ipsilateral hand but also of the contralateral hand. Horizontal saccadic pointing movements of 10 patients with unilateral cerebellar infarctions (infarctions of the posterior inferior or superior cerebellar artery) were compared with those of 19 controls. The movements were recorded with an infrared video motion analysis system. The peak velocity, time lag, and dysmetria of the ipsilateral and contralateral hands were calculated. Patients with cerebellar infarctions had significantly slower movements not only for the ipsilateral but also for the contralateral arm. The time lag of these movements in patients was also significantly larger for both arms. In contrast, there was no significant difference in dysmetria at the endpoints. These findings indicate that both ipsilateral and contra-lateral movements of patients with unilateral cerebellar lesions are slightly impaired.     

Disturbances in human arm movement trajectory due to mild cerebellar dysfunction.

The temporal structure of arm movements was studied in nine cerebellar patients with mild impairment of the upper limbs and in six age-matched control subjects. The experimental paradigm consisted of visually guided, step tracking movements about the elbow. Movements ranged from 10 degrees to 70 degrees in amplitude and were made under different instructions (fast, fast/accurate, accurate). As in normal subjects, cerebellar patients were able to scale peak velocity with movement amplitude. This relationship was highly linear under all instruction conditions. Similar relationships existed between movement duration and amplitude. In contrast to normal subjects who produced movements with nearly symmetric velocity profiles, movements made by cerebellar patients were characterised by short acceleration and long deceleration durations. The degree of asymmetry was directly related to movement duration but was unaffected by movement peak velocity. Acceleration durations did not increase beyond 300 ms even in movements lasting up to 1s. These findings demonstrate that, despite little or no obvious impairment of the limb during routine examination, the temporal structure of voluntary movements in cerebellar patients is clearly disturbed. This supports the view that the production of an optimal movement trajectory is under cerebellar influence.     

Quantitative analysis of stance in late cortical cerebellar atrophy of the anterior lobe and other forms of cerebellar ataxia.

(1) Methods have been developed to measure, analyse and document postural sway. The main parameters studied were: average sway amplitude; length of the sway path per unit time; sway direction and sway position histograms; and the frequency spectra of the antero-posterior and lateral sway components. (2) Postural ataxia was quantitatively studied in three groups of patients with cerebellar lesions: (a) late atrophy of the anterior lobe, (b) tumours of the cerebellar hemisphere and (c) tumours within the vestibulo-cerebellum. Characteristic differences were found. (3) Patients with anterior lobe lesion show a specific 3 Hz postural tremor in the antero-posterior direction. The tremor can be evoked by sudden destabilization in incipient cases. Less characteristic and smaller in amplitude is a mainly lateral sway component with an average frequency of 0.5 Hz. This is also seen in cases with spinal ataxia. Visual stabilization of posture is frequently preserved. Its amount does not correlate with general instability of posture. Tremor and characteristically exaggerated intersegmental responses between head, trunk, hips and legs are interpreted as the consequence of hyper-excitability of postural reflexes in these patients. (4) Patients with lesions of the hemispheres show only slight postural instability without directional preference. Their sway parameters with eyes open are within the 2 sigma range of normals and there is no significant difference from normals in these parameters even when the eyes are closed. Therefore these patients cannot be distinguished from normals by means of their platform recordings. (5) Two patients with posterior vermal and flocculo-nodular lesions were very unstable without preferred axis or frequency of instability. In contrast to the anterior lobe group the instability was characterized by the absence of intersegmental movements.     

Postural responses to multidirectional stance perturbations in cerebellar ataxia

Previous studies of patients with focal cerebellar damage underscored the importance of the cerebellum for balance control. These studies were restricted to postural control in the pitch plane, and focused mainly on leg muscle responses. Here, we examined the effect of degenerative cerebellar lesions on postural control in multiple directions, and studied how such lesions affect intersegmental coordination of the legs, trunk and arms. We formulated two main questions. (a) Do patients with cerebellar ataxia predominantly have balance problems in the sagittal or frontal planes? (b) Is instability in cerebellar ataxia associated with increased joint motion or with reduced joint motion? We selected nine patients with autosomal dominant spinocerebellar ataxia (SCA)--three with pure ataxia and six with mild extra-cerebellar features--and 12 matched controls. Upright standing subjects received support surface rotations (7.5 degrees at 60 degrees /s) that were randomly delivered in eight different directions of pitch or roll. We used full body kinematics to determine displacements of the center of mass (COM) and of individual body segments. We also collected surface EMG from 10 leg, trunk and arm muscles. Primary variables of interest were COM displacement and trunk control (angles and muscle responses). Secondary analyses focused on angles and muscle responses of the legs and arms. COM analysis demonstrated that SCA patients had greatest instability following backward and laterally directed perturbations. Major factors in causing this instability were, first, a marked reduction of stimulus-induced knee flexion and, second, excessive "hypermetric" motion of the pelvis (in roll) and trunk (in pitch). Muscle responses of SCA patients were characterized by increased late balance correcting activity. Responses of patients with pure ataxia were comparable to those of patients with mild extra-cerebellar features. A main underlying cause of postural instability in SCA patients appears to be "locking" of the knees, which may reflect compensation (by reducing interaction between body links) or reduced vestibulocerebellar control over leg muscles. The observed pathophysiology is very different from that seen in other patient populations.     

Quantitative evaluation of functional limitation of upper limb movements in subjects affected by ataxia

Background and purpose:  The design of useful and effective treatment strategies for movement disorders largely depends on the ability to objectively quantify changes in performances, providing reliable outcome measures. Evaluation of ataxia remains mainly assigned to different clinical scales, providing a semi-quantitative assessment. The aim of this study was to quantitatively characterize functional changes in upper limb movements in ataxic patients, using an optoelectronic system for objective measurements.
Methods:  Fourteen patients with cerebellar ataxia and 27 healthy subjects were analyzed using an optoelectronic system with passive markers during pointing task and hand-to-mouth movement. Quantitative parameters capable of characterizing ataxic movements were defined using recorded kinematics.
Results:  In both the considered functional movements, ataxic patients showed increased adjustment during the last phase of movement. The movement was less smooth than that in controls, with a fragmented trajectory presenting more direction changes than controls.
Conclusions:  The proposed protocol allows the quantitative characterization of the motion pattern of ataxic subjects in a non-invasive way. We believe that this analysis could represent a good tool for ataxia evaluation in a clinical context such as neurorehabilitation.     

Impairment of the accuracy of tracking movements in lesions of the cerebellum and pyramidal system in man

Kinematic and electromyographic characteristics of step-tracking movements performed with and without visual guidance have been studied in 3 groups of patients suffering from hereditary lesions of intermedial and lateral systems of the cerebellum and pyramidal tract. Lesions of the intermedial cerebellum not changing parameters of the first preprogrammed component altered deeply the maintenance phase that was performed as large oscillations around a required level. Lesions of the lateral cerebellum, on the contrary, were followed by inability to control accurately the amplitude of steps which were performed with a constant hypermetric error; the maintenance phase of movement was not disturbed in this group. In patients suffering from pyramidal lesions the initial rapid limb position adjustment was replaced by slow approximating tracking; the maintenance component of the movement was performed with fluctuations and constant drift towards the ground. It is concluded that whereas the lateral cerebellar system is involved in central motor program mechanisms, the intermedial cerebellum is essential for accurate postural maintenance.     

Influence of sensory manipulation on postural control in Parkinson''s disease.

Postural control was assessed on a tilting platform system in 20 patients with idiopathic Parkinson's disease and 20 age-matched controls. The amount of information provided by vision and lower limb proprioception was varied during the experiment to investigate the influence of changes in sensory cues on postural control. The patient group with clinical evidence of impaired postural control (Hoehn and Yahr III) had significantly higher sway scores over all sensory conditions than either the Hoehn and Yahr II group or controls. The pattern of sway scores indicated that no obvious deficit in the quality, or processing, of sensory information was responsible for the postural instability observed in this group. The patients in both Hoehn and Yahr groups were also able to respond appropriately to potentially destabilising sensory conflict situations and significantly improved their sway scores when provided with visual feedback of body sway. The results indicate that in Parkinson's disease, the main site of dysfunction in postural control is likely to be at a central motor level.     

Pathophysiology of cerebellar ataxia.

Human and animal experiments performed recently have resulted in a more detailed understanding of limb movement and body posture disorders associated with cerebellar dysfunction. The delay in movement initiation can be explained by a delay in onset of phasic motor cortex neural discharge owing to decreased input from the cerebellar hemispheres. Disorders of movement termination (dysmetria), which can occur for movements at proximal and distal joints, result from disturbances of the timing and intensity of antagonist electromyographic (EMG) activity necessary to break the movement. Disorders in velocity and acceleration of limb movements result from muscular activity that is smaller in amplitude and more prolonged. The cerebellum is important for control of constant force but not for generation of maximal force. Dysdiadochokinesia is explained by a combination of the above mentioned mechanisms. During complex movements in three-dimensional space, the cerebellum contributes to timing between single components of a movement, scales the size of muscular action, and coordinates the sequence of agonists and antagonists. The basic structure of motor programs is not generated in the cerebellum. Hypotonia can be observed only in acute cerebellar lesions. Cerebellar tremor appears to result from a central mechanism, but is modulated or provoked through increased long-loop EMG responses. The common assumption that cerebellar ataxia of stance does not improve with visual feedback is true only of vestibulocerebellar lesions, not for ataxia resulting from atrophy of the anterior lobe of the cerebellum.     

Quantification of postural sway in normals and patients with cerebellar diseases

Posturography was performed in 41 patients with cerebellar diseases by means of a force measuring platform using an on-line computer program which calculated sway path, sway area, antero-posterior and lateral sway components and the amount of visual stabilization. Postural ataxia was quantitatively studied in 8 patients with spinal ataxia (Friedreich's), 6 patients with vestibulocerebellar lesions, 11 patients with anterior lobe atrophy, 7 patients with hemispheral cerebellar lesions, and 9 patients with a disease affecting all parts of the cerebellum. Patients with lesions of the cerebellar hemispheres could not be separated from normals by means of posturography. Lesions of the spino-cerebellar afferents (Friedreich' ataxia) caused an omnidirectional low frequency sway with preserved visual stabilization. Patients with anterior lobe atrophy showed a predominant antero-posterior sway, often with a spontaneous high frequency body tremor around 3 Hz. Vestibulo-cerebellar lesions exhibited omnidirectional low frequency sway poorly stabilized by vision. Quantitative posturography helps to localize cerebellar lesions and allows for quantitative follow-up studies of cerebellar diseases.     

Disturbed vestibular-neck interaction in cerebellar disease

Cerebellar dysfunction results in ataxia including postural deficits. Evidence from animal experiments suggests convergence of vestibular and neck-position related inputs in cerebellar midline structures. We investigated 20 ambulatory patients with cerebellar disease for disturbed postural control using posturography during static lateral head turns. Binaural bipolar sine-wave galvanic vestibular stimulation (GVS) was used to evoke specific body movements. The Klockgether clinical score was used to assess the severity of cerebellar dysfunction (4–17 of maximal 35 points). In 12 healthy controls and seven lightly affected patients (score <8), GVS elicited physiologic alternating body sway in the head-frontal plane in seven head-on-trunk positions (0°; 30°, 45° and 60° left and right). Body sway turning with head excursion was progressively attenuated or abolished in more severely affected patients (scores 9–17; r = 0.57, p = 0.008). With most severe impairment, body sway was always in the body-frontal plane irrespective of head turn. A simple clinical test with walking under maximal head turn and closed eyes correlated with posturography data (r = 0.87, p < 0.001) and with Klockgether scores (r = 0.71, p < 0.001). Thus in cerebellar disease, head on trunk position can have a pronounced effect on postural control.     

A loss of a velocity‐duration trade‐off impairs movement precision in patients with cerebellar degeneration

Current theories discussing the role of the cerebellum have been consistently pointing towards the concept of motor learning. The unavailability of a structure for motor learning able to use information on past errors to change future movements should cause consistent metrical deviations and an inability to correct them; however, it should not boost “motor noise.” However, dysmetria, a loss of endpoint precision and an increase in endpoint variability (“motor noise”) of goal‐directed movements is the central aspect of cerebellar ataxia. Does the prevention of dysmetria or “motor noise” by the healthy cerebellum tell us anything about its normal function? We hypothesize that the healthy cerebellum is able to prevent dysmetria by adjusting movement duration such as to compensate changes in movement velocity. To address this question, we studied fast goal‐directed index finger movements in patients with global cerebellar degeneration and in healthy subjects. We demonstrate that healthy subjects are able to maintain endpoint precision despite continuous fluctuations in movement velocity because they are able to adjust the overall movement duration in a fully compensatory manner (“velocity‐duration trade‐off”). We furthermore provide evidence that this velocity‐duration trade‐off accommodated by the healthy cerebellum is based on a priori information on the future movement velocity. This ability is lost in cerebellar disease. We suggest that the dysmetria observed in cerebellar patients is a direct consequence of the loss of a cerebellum‐based velocity‐duration trade‐off mechanism that continuously fine‐tunes movement durations using information on the expected velocity of the upcoming movement.     

Postural and resting tremor in the upper limb.

OBJECTIVE: Tremor from multiple segments of the upper limb was recorded under postural and resting conditions. The aims of this study were to examine the nature of tremor within a single limb segment, intra- and inter-limb co-ordination of tremor, and the influence of cardiac mechanical events on physiological tremor. METHODS: Tremor was recorded from eight healthy adult subjects during a postural pointing task where the level of support for the upper limb segments was successively increased. The dynamics of tremor within a single segment were examined using power spectral, ApEn and amplitude analyses. Inter-segment tremor relations were determined using coherence and Cross-correlation analyses.RESULTS: Single segment analysis demonstrated that each (unsupported) limb segment contained two major frequency peaks (at 1-4 Hz and 8-12 Hz). Both peaks were still evident in the distal segments when the proximal segments were supported. External support of the more proximal limb segments also resulted in decreased finger tremor, but these changes were not simply additive over segments within a limb or equal across fingers. There were significant relations between adjacent proximal and distal limb segment pairs but no correlations between contralateral limb segments or between heart rate and limb tremor.CONCLUSIONS: These findings imply that: the low frequency component (1-4 Hz) of physiological tremor in the hand and finger could not be attributed to passive transmission of oscillations from the upper arm and forearm; and the contribution of proximal segments on tremor in the index finger tremor could not be predicted from mechanical principles alone. The minimization of finger tremor involved compensatory coupling of segments of the upper arm with particular emphasis upon active control of the wrist joint.     

Influence of pitch tilts on the perception of gravity-referenced eye level in labyrinthine defective subjects

We investigate the role of vestibular information in judging the gravity-referenced eye level (i.e., earth-referenced horizon or GREL) during sagittal body tilt whilst seated. Ten bilateral labyrinthine-defective subjects (LDS) and 10 age-matched controls set a luminous dot to their perception of GREL in darkness, with and without arm pointing. Although judgements were linearly influenced by the magnitude of whole-body tilt, results showed no significant difference between LDS and age-matched controls in the subjective GREL accuracy or in the intra-subject variability of judgement. However, LDS performance without arm pointing was related to the degree of vestibular compensation inferred from another postural study performed with the same patients. LDS did not utilize upper limb input during arm pointing movements as a source of graviceptive information to compensate for the vestibular loss. The data suggest that vestibular cues are not of prime importance in GREL estimates in static conditions. The absence of difference between controls and LDS GREL performance, and the correlation between the postural task and GREL accuracy, indicate that somatosensory input may convey as much graviceptive information required for GREL judgements as the vestibular system.     

How the eyes move the body

The increased postural sway of patients with disorders of the vestibular system improves with vision. The suppression of pathologic nystagmus also reduces sway. Because the latter effect cannot be attributed to retinal slip as a relevant feedback for postural control, the authors investigated how eye movements rather than retinal slip affect balance. They found that slow eye movements increase sway, possibly by an efference copy, which explains why spontaneous nystagmus causes postural imbalance.     

Eye-head co-ordination in patients with Parkinsonism and cerebellar ataxia.

Eye-head co-ordination of patients with Parkinsonism and cerebellar ataxia was investigated and compared with that of normal subjects. In Parkinsonian patients eye-head co-ordination was of the same pattern as normals, with an accurate and stable gaze. Reaction times for both eyes and head, however, were prolonged. It was also noted that the contribution of head movements to gaze shift was abnormally large and that the gaze accuracy was decreased when the head was immobilised. In patients with cerebellar ataxia, gaze was dysmetric, often hypermetric, and was unstable during head movements. The contribution of head movements to gaze was also large. It is concluded that Parkinsonism and cerebellar diseases influence eye-head co-ordination differently.     

Ataxia induced by small amounts of alcohol

A patient is described who exhibited cerebellar ataxia afterdrinking small amounts of alcohol. Intake of 5 g alcohol induced a gazeevoked nystagmus, a scanning speech, a body sway after eye closure, andbilateral postural leg tremor. Kinematic and EMG analysis of fast wristmovements showed normal movements before and marked hypermetria afteralcohol intake. Dysmetria was due to abnormal programming of antagonistmuscle activity.

     

Visual and mechanical control of postural and kinetic tremor in cerebellar system disorders.

The influence of alterations in visual guidance and somaesthetic sensory inputs was studied in five patients with kinetic and postural tremor characteristic of cerebellar impairment. The patients performed wrist flexion-extension movements or movements about the shoulder with or without visual guidance. Different types of mechanical loads were applied to oppose the wrist movements. The tremor was greatest when the patients used visual cues to guide movements. Kinetic tremor was substantially suppressed during performance of similar movements that were not guided directly by vision. Viscous loads suppressed the tremor nearly linearly, whereas constant loads opposing extension enhanced the tremor. The postural tremor was not observed during isometric contractions. These results support the view that processing of visual information contributes to the impairment of movement in disorders with cerebellar-type tremor and that certain somaesthetic inputs can selectively influence the generation of postural tremor.     

Deficits in ocular and manual tracking due to episodic ataxia type 2.

Four patients with a novel mutation leading to episodic ataxia type 2 were studied in a task that required them to track target motion either with the eyes or with the index finger of the right hand. The target initially moved in a straight line and then changed direction at an unpredictable time by an unpredictable amount. On the day of testing, 3 of the patients were evaluated as normal on a neurological exam, whereas the fourth was severely ataxic. Nevertheless, all 4 showed deficits in tracking behavior with common features. Ocular tracking tended to result in hypermetric saccades at longer than normal latencies. Smooth pursuit tracking was absent in 1 patient and had lower than normal gain in the others. Deficits in manual tracking showed similarities to the deficits in ocular tracking, with hypermetric compensations for changes in target direction. The similarities in the deficits in manual and ocular tracking suggest that they are subject to similar control by the cerebellar structures.     

The dependence of ipsilesional aiming deficits on task demands,lesioned hemisphere,and apraxia

Neuroimaging studies as well as neurophysiological and lesion data indicate that the ipsilateral hemisphere plays a role in controlling the active limb. However, the nature and the conditions of this ipsilateral control are not well understood. We measured aiming movements with the ipsilesional limb toward targets with different characteristics which were made by patients with unilateral left brain damage (LBD) or right brain damage (RBD). The movement kinematics were analysed. Performance measures of the pointing movements were impaired in LBD patients, whereas RBD patients performed normally. LBD patients had obvious deficits during all tasks; however, they were exacerbated when high accuracy was required, and when an exocentric target had to be reached without visual feedback. Thus, the motor-dominant hemisphere plays a specific role in the programming and execution of ipsilateral aiming movements, and the importance of ipsilateral control increases with increasing task demands. To assess the relationship between pointing deficits and apraxia in LBD patients, the imitation of meaning gestures was tested. We replicated a recent study, showing that deviations of the final hand position from the demonstration were not correlated with abnormal kinematics of the corresponding arm movement when LBD patients performed this test. However, there were correlations between related kinematic measures during pointing and gesture imitation. These findings suggest a deficit of motor programming and execution after damage to the motor-dominant brain which is unrelated to the spatial errors characteristic of apraxia. This deficit affects different types of goal-directed aiming movements and its severity depends on task demands.     

Targeted tDCS selectively improves motor adaptation with the proximal and distal upper limb

BackgroundThe cerebellum and primary motor cortex (M1) are crucial to coordinated and accurate movements of the upper limbs. There is also appreciable evidence that these two structures exert somewhat divergent influences upon proximal versus distal upper limb control. Here, we aimed to differentially regulate the contribution of the cerebellum and M1 to proximal and distal effectors during motor adaptation, with transcranial direct current stimulation (tDCS). For this, we employed tasks that promote similar motor demands, but isolate whole arm from hand/finger movements, in order to functionally segregate the hierarchy of upper limb control.MethodsBoth young and older adults took part in a visuomotor rotation task; where they adapted to a 60° visuomotor rotation using either a hand-held joystick (requiring finger/hand movements) or a 2D robotic manipulandum (requiring whole-arm reaching movements), while M1, cerebellar or sham tDCS was applied.ResultsWe found that cerebellar stimulation improved adaptation performance when arm movements were required to complete the task, while in contrast stimulation of M1 enhanced adaptation during hand and finger movements only. This double-dissociation was replicated in an independent group of older adults, demonstrating that the behaviour remains intact in ageing.ConclusionsThese results suggest that stimulation of distinct motor areas can selectively improve motor adaptation in the proximal and distal upper limb. This also highlights new ways in which tDCS might be best applied to achieve reliable rehabilitation of upper limb motor deficits.