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.     

Fast complex arm movements in Parkinson''s disease.

Fast arm movements involving the shoulder and elbow joints have been analysed in normal controls and in patients with Parkinson's disease. The subjects were requested to draw on a graphic tablet triangles and squares of different size and shape. The patients produced a larger number of EMG burst compared with controls. The movements were accurate, and each segment of the geometric figures was performed with a roughly straight trajectory, but the time necessary to trace the geometric figures and the pauses at the vertices were prolonged. We conclude that in Parkinson's disease the disability in generating two joint ballistic movements depends on a difficulty in running motor programmes for complex trajectories.     

The execution of bimanual movements in patients with Parkinson''s, Huntington''s and cerebellar disease.

Patients with Parkinson's disease have difficulty in performing two different tasks simultaneously. The present study tested whether this deficit was specific to the disease or was found in other patient groups. An identical pattern of performance was shown by a group of patients with cerebellar disease and, to a lesser extent, by a group of patients with Huntington's disease. Further research should focus on clarifying the nature of the deficits and the reasons for the similar performances in the various patient groups.     

Coherence of sequential movements and motor learning.

The analysis of oscillatory EEG phenomena such as interregional coherence (task-related coherence [TRCoh] or event-related coherence) has advanced our knowledge of neurophysiological processes underlying the performance and learning of skilled finger movements. It has become clear that various types of higher task demands are reflected by changes in the functional coupling of different cortical areas and not only by changes in regional activation. Neuroscientists are merely starting to understand how coherent oscillations might encode information in the human motor system ("sensorimotor binding") and how well this can be measured from the surface EEG. However, interregional coherence is a potentially independent mechanism that can, up to now, only be investigated with electrophysiological techniques such as EEG and MEG. The studies reviewed below focus on coherence of finger movements and motor learning: increasing complexity of a movement sequence, internal rhythm generation, visuomotor integration, deficits in interhemispheric coupling, and bimanual coordination. Evidence is presented for a special functional significance of TRCoh in the beta frequency range (13 to 21 Hz) for information processing in large-scale sensorimotor networks during motor tasks.     

Cerebellar continuous theta‐burst stimulation affects motor learning of voluntary arm movements in humans

In this study we investigated in healthy subjects whether continuous theta‐burst stimulation (cTBS) over the lateral cerebellum alters motor practice and retention phases during ipsilateral index finger and arm reaching movements. In 12 healthy subjects we delivered cTBS before repeated index finger abductions or arm reaching movements differing in complexity (reaching‐to‐grasp and reaching‐to‐point). We evaluated kinematic variables for index finger and arm reaching movements and changes in primary motor cortex (M1) activity tested with transcranial magnetic stimulation. Peak acceleration increased during motor practice for index finger abductions and reaching‐to‐grasp movements and persisted during motor retention. Peak acceleration decreased during motor practice for reaching‐to‐point movements and the decrease remained during motor retention. Cerebellar cTBS left the changes in peak acceleration during motor practice for index finger abductions and reaching‐to‐grasp arm movements unchanged but reduced peak acceleration at motor retention. Cerebellar cTBS prevented the decrease in peak acceleration for reaching‐to‐point movements during motor practice and at motor retention. Index finger abductions and arm reaching movements increased M1 excitability. Cerebellar cTBS decreased the motor evoked potential (MEP) facilitation induced by index finger movements, but increased the MEP facilitation after reaching‐to‐grasp and reaching‐to‐point movements. Cerebellar stimulation prevents motor retention for index finger abductions, reaching‐to‐grasp and reaching‐to‐point movements and degrades motor practice only for reaching‐to‐point movements. Cerebellar cTBS alters practice‐related changes in M1 excitability depending on how intensely the cerebellum contributes to the task. Changes in M1 excitability reflect mechanisms of homeostatic plasticity elicited by the interaction of an ‘exogenous’ (cTBS‐induced) and an ‘endogenous’ (motor practice‐induced) plasticity‐inducing protocol.     

Central motor pathways in patients with mirror movements.

Central motor pathways were investigated in three patients with congenital mirror movements using magnetic motor cortex stimulation. Response thresholds, amplitudes and latencies were normal. The projection of the corticomotoneuronal pathways was assessed by placing the coil over the vertex and comparing the size of responses in the first dorsal interosseous (FDI) muscles evoked by anticlockwise and clockwise [corrected] coil currents. In normal subjects, right FDI responses are larger with anticlockwise currents than with clockwise [corrected] currents at the same stimulation strength and vice versa. In two out of three patients with congenital mirror movements, this sensitivity of response amplitude to coil current direction was reversed. The third patient with congenital mirror movements and a fourth patient with acquired mirror movements had responses which were normally sensitive to current direction. These findings support the hypothesis that some cases of congenital mirror movements may be due to abnormal projection of corticomotoneuronal pathways.     

Physiological analysis of simple rapid movements in patients with cerebellar deficits.

Patients with cerebellar deficits made elbow flexion movements as rapidly as possible for three different angular distances. Electromyographic activity of biceps and triceps and the kinematics of the movements were analysed. Results were compared with those of normal subjects making both rapid and slow movements. In the patients, the first agonist burst of the biceps was frequently prolonged regardless of the distance or speed of the movement. The most striking kinematic abnormality was prolonged acceleration time. The pattern of acceleration time exceeding deceleration time was common in patients but uncommon in normal subjects. The best kinematic correlate of the duration of the first agonist burst was acceleration time. Altered production of appropriate acceleration may therefore be an important abnormality in cerebellar dysfunction for attempted rapid voluntary movements.     

Timing of rhythmic movements in patients with cerebellar degeneration

A distinction in temporal performance has been identified between two classes of rhythmic movements: those requiring explicit timing of salient events marking successive cycles, i.e., event timing, and continuous movements in which timing is hypothesized to be emergent. Converging evidence in support of this distinction is reviewed, including neuropsychological studies showing that individuals with cerebellar damage are selectively impaired on tasks requiring event timing (e.g., tapping). Recent behavioral evidence in neurologically healthy individuals suggests that for continuous movements (e.g., circle drawing), the initial cycle is marked by a transformation from event to emergent timing, allowing the participant to match their movement rate to an externally defined cycle duration. We report a new experiment in which individuals with cerebellar ataxia produced rhythmic tapping or circle drawing movements. Participants were either paced by a metronome or unpaced. Ataxics showed a disproportionate increase in temporal variability during tapping compared to circle drawing, although they were more variable than controls on both tasks. However, two predictions of the transformation hypothesis were not confirmed. First, the ataxics did not show a selective impairment on circle drawing during the initial cycles, a phase when we hypothesized event timing would be required to establish the movement rate. Second, the metronome did not increase variability of the performance of the ataxics. Taken together, these results provide further evidence that the integrity of the cerebellum is especially important for event timing, although our attempt to specify the relationship between event and emergent timing was not successful.     

Stimulus-response properties of motor system in patients with cerebellar ataxia.

OBJECTIVE: The aim of the study was to examine the stimulus-response properties of the excitatory and inhibitory components of corticospinal projections at rest and during voluntary contraction in cerebellar patients. METHODS: We investigated motor evoked potential (MEP) and cortical silent period recruitment curves in response to increasing intensities of transcranial magnetic stimulation in 8 patients with 'pure' cerebellar syndromes and in 14 age-matched controls. The transcranial magnetic stimulation intensity was increased from 90 to 180% of the resting motor threshold. MEP recruitment curves were recorded at rest and during voluntary contraction in the right abductor pollicis brevis muscle. RESULTS: No statistical differences were found between patients and controls in MEP recruitment curves in either the resting or active condition. A significant difference was found between patients and controls in the cortical silent period threshold (patients: 33.2+/-3.4% of maximal stimulator output; controls 39.4+/-3.2%; P=0.01) and recruitment curve, the duration of the cortical silent period being longer in patients at transcranial magnetic stimulation intensities ranging from 90 to 130% of the resting motor threshold (patients: 135-191 ms; controls: 53-158 ms). No changes were found in the silent period evoked by peripheral nerve stimulation. CONCLUSIONS: Inhibitory components of corticospinal projections were recruited with a lower threshold in patients. No abnormalities were found in the recruitment of the excitatory networks. Our data show a prevalence of inhibitory phenomena in the motor cortex of cerebellar patients. These findings would appear to be specific to cerebellar diseases and are the opposite of those previously documented in movement disorders such as dystonia and Parkinson's disease. Our results suggest that the cerebellum and the basal ganglia may counteract each other in modulating the level of motor system excitability.     

Neuronal populations in primary motor cortex encode bimanual arm movements

Previous studies have shown that activity of neuronal populations in the primary motor cortex (MI), processed by the population vector method, faithfully predicts upcoming movements. In our previous studies we found that single neurons responded differently during movements of one arm vs. combined movements of the two arms. It was, therefore, not clear whether the population vector approach could produce reliable movement predictions also for bimanual movements. This study tests this question by comparing the predictive quality of population vectors for unimanual and bimanual arm movements. We designed a bimanual motor task that requires coordinated movements of the two arms, in which each arm may move in eight directions, and recorded single unit activity in the MI of two rhesus (Macaca mulatta) monkeys during the performance of unimanual and bimanual arm movements. We analysed the activity of 212 MI cells from both hemispheres and found that, despite bimanual related activity, the directional tuning and preferred directions of most cells were preserved in unimanual and bimanual movements. We demonstrate that population vectors, constructed from the activity of MI cells, predict accurately the direction of movement both for unimanual and for bimanual movements even when the two arms move simultaneously in different directions.     

Three-dimensional tuning profile of motor cortical activity during arm movements

The neural firing activity in the primary motor cortex was modulated to the direction of hand movement. In contradiction to previous reports, a recent study found a non-uniform distribution of preferred directions of neurons while monkeys made center-out reaching movements in a horizontal plane. To re-examine the distribution of preferred directions in three-dimensional space, we recorded the activity of 117 arm-related neurons in the primary motor cortex and electromyographic signals of shoulder and upper arm muscles of a monkey while it performed center-out reaching movements towards 26 target points placed on a sphere-shaped workspace. We found that the distribution of preferred directions of neurons was non-uniform and that it was correlated to muscle activity and arm joint rotations.     

Periodic arm movements in patients with the restless legs syndrome

A high proportion of patients with restless legs syndrome (RLS) also complain of arm paresthesia but the presence of periodic arm movements (PAM) has never been documented in a sleep laboratory in these patients. We investigated the prevalence of PAM during nocturnal sleep and awakenings in 22 RLS patients. Fifteen patients had a PAM index >5 movements per hour during wakefulness and among them only 3 had a PAM index >5 during sleep. Twenty patients had a periodic leg movement (PLM) index >5 during wakefulness and 17 had a PLM index >5 during sleep. In 42.8% of cases, PAM showed temporal relationship with PLM during wakefulness. These results show that PAM is frequent in RLS and suggest that the basic neurological dysfunction responsible for RLS is probably not located exclusively at the level of the lumbar spinal cord but involves neuronal systems located at upper levels.     

Spatial and temporal sequence learning in patients with Parkinson's disease or cerebellar lesions

The functional role of different subcortical areas in sequence learning is not clear. In the current study, Parkinson's patients, patients with cerebellar damage, and age-matched control participants performed a serial reaction time task in which a spatial sequence and a temporal sequence were presented simultaneously. The responses were based on the spatial sequence, and the temporal sequence was incidental to the task. The two sequences were of the same length, and the phase relationship between them was held constant throughout training. Sequence learning was assessed comparing performance when both sequences were present versus when the dimension of interest was randomized. In addition, sequence integration was assessed by introducing phase-shift blocks. A functional dissociation was found between the two patient groups. Whereas the Parkinson's patients learned the spatial and temporal sequences individually, they did not learn the relationship between the two sequences, suggesting the basal ganglia play a functional role in sequence integration. In contrast, the cerebellar patients did not show any evidence of sequence learning at all, suggesting the cerebellum might play a general role in forming sequential associations.     

Intact artificial grammar learning in patients with cerebellar degeneration and advanced Parkinson's disease

In an artificial grammar learning task, subjects were asked to memorise short lists of letter strings formed according to complex rules for letter order. After an interval they were unexpectedly asked to discriminate new grammatical strings from strings which used the same letters but violated the sequential constraints of the grammar. Artificial grammar learning can be mastered successfully by amnesic patients and is considered to be an implicit learning task independent of declarative learning and memory mechanisms. In this study, 10 patients with cerebellar degeneration (CD), 21 Parkinson's disease (PD) and 15 control subjects were tested on artificial grammar learning. Additionally PD patients with advanced disease were examined under adequate medication and dopaminergic withdrawal. All patient groups showed intact artificial grammar learning. Neither cerebellar damage nor basal ganglia dysfunction nor dopaminergic medication impairs or affects artificial grammar learning. Although the patients showed significant executive dysfunction, implicit learning remains intact. The conclusion is that cerebellar and basal ganglia circuits play no essential part in this kind of implicit learning. The results suggest that artificial grammar learning is a cortically mediated function comparable to the mechanism of visual priming.     

Adaptation of aimed arm movements to sensorimotor discordance: evidence for direction-independent gain control.

Human subjects pointed, without sight of their arm, at visual targets presented on a mirror-viewed monitor screen. During the adaptation period of each experiment, the position of the pointing fingertip was continuously recorded and displayed on the screen along with the targets. This visual feedback was not always veridical; rather, it was manipulated to require a gradual modification of the pointing response gain throughout the adaptation period. No visual feedback at all was available during the pre- and postadaptation periods of each experiment. The adaptive effect was determined as difference between pre- and postadaptation gains. In Expt. A, visual feedback during the adaptation period prescribed a gradual reduction of the horizontal response gain without specifying the gain for other directions; the adaptive effect was found to generalize uniformly to all movement directions. Expt. B1 prescribed a reduction of the horizontal, and an unchanged vertical gain component: in spite of this differential requirement, the adaptive effect was again uniform for all directions. Expt. B2 prescribed a reduction of the horizontal, and an increase of the vertical gain component: we found a reduced gain for all directions, with a mild direction-dependence in the magnitude of the adaptive effect. In a modified version of Expt. B2, no intermanual transfer of the adaptive effect was found. Expt. C1-3 prescribed gain reduction for target directions within 15, 30, or 45 degrees around the horizontal, and gain increase for all other directions: we found little or no adaptive effects under such conditions. From the above findings, we concluded that the adapted system controls movement gain largely independent of movement direction. This mechanism responds readily to requirements for gain reduction, but not gain increase. No evidence for an organization of the arm motor system in direction-selective channels was found, in contrast to findings on the saccadic control system in a paradigm similar to our Expt. A8. This discrepancy supports the view that arm and eye movements are controlled by distinct mechanisms.     

Rule-based category learning is impaired in patients with Parkinson's disease but not in patients with cerebellar disorders

The basal ganglia and cerebellum have both been implicated in motor skill acquisition. Recent hypotheses concerning cognitive functions of the basal ganglia and cerebellum have emphasized that these subcortical structures may also contribute to nonmotor learning. To explore this issue, patients with Parkinson's disease (PD) and patients with cerebellar lesions (CB) were tested on two category-learning tasks. Identical stimulus displays were used for the two tasks, consisting of a reference line and target line. In the length task, the two categories were defined based on the length of the target line. In the distance task, the two categories were defined by the distance between the target and reference lines. Thus, both categories could be defined by a simple rule in which attention must be restricted to a single relevant dimension. Consistent with previous results, the patients with PD were impaired on both tasks compared with neurologically healthy controls. In contrast, the CB patients performed similar to the control participants. Model-based analyses indicate that the patients with PD were able to select the appropriate categorization rule, but that they adopted suboptimal category boundaries in both conditions and were more variable in the application of the selected rule. These results provide an important neuropsychological dissociation on a non-motor-learning task between the effects of basal ganglia and cerebellar lesions. Moreover, the modeling work suggests that at least part of the Parkinson patients' impairment on these tasks reflect a tendency to exhibit strong response biases.     

Kinematic properties of slow arm movements in Parkinson's disease

Present pathophysiological concepts of bradykinesia stress an impairment of fast movements in Parkinson's disease. It is, however, unknown whether bradykinetic movements are different from slow movements of normal subjects. We recorded trajectories of unrestrained natural arm movements from normal subjects and patients with Parkinson's disease. The experiment required the execution of pointing movements for different movement distances and velocities. The shape of trajectories was found to be changed in Parkinson's disease. The steepness of the initial segment and the relation between steepness of the initial segment and final segment both exceeded corresponding values in normal subjects. An analysis of velocity profiles showed an impaired synchrony of vertical and horizontal velocity components. The difference from normal subjects increased with movement velocity. Parkinsonian patients suffered from a fundamental defect in the composition of complex sequences of motor programs required to perform natural arm movements.     

Involuntary movements with cerebellar tumour

We describe a child with a cerebellar astrocytoma who presented with paroxysmal segmental rhythmic myoclonus. The movement disorder was characterized by focal onset in the left eyelid followed by a sequential march of clinical events. There were no clinical or laboratory findings to suggest brainstem infiltration or cerebral involvement. Marked clinical improvement followed tumour resection. We suggest that the cerebellar lesion was primarily responsible for the movement disorder.