Does the cerebellum initiate movement?

Opinion is divided on what the exact function of the cerebellum is. Experiments are summarized that support the following views: (1) the cerebellum is a combiner of multiple movement factors; (2) it contains anatomically fixed permanent focal representation of individual body parts (muscles and segments) and movement modes (e.g., vestibular driven vs. cognitive driven); (3) it contains flexible changing representations/memory of physical properties of the body parts including muscle strength, segment inertia, joint viscosity, and segmental interaction torques (dynamics); (4) it contains mechanisms for learning and storage of the properties in item no. 3 through trial-and-error practice; (5) it provides for linkage of body parts, motor modes, and motordynamics via the parallel fiber system; (6) it combines and integrates the many factors so as to initiate coordinated movements of the many body parts; (7) it is thus enabled to play the unique role of initiating coordinated movements; and (8) this unique causative role is evidenced by the fact that: (a) electrical stimulation of the cerebellum can initiate compound coordinated movements; (b) in naturally initiated compound movements, cerebellar discharge precedes that in downstream target structures such as motor cerebral cortex; and (c) cerebellar ablation abolishes the natural production of compound movements in the awake alert individuals.

Is the parvocellular red nucleus involved in cerebellar motor learning?

The anatomical connections of the parvocellular red nucleus (RNp) have led to the suggestion that it might participate along with the cerebellum in modifying old and developing new programs for the control of complex, compound, coordinated movements of multiple body parts. RNp projects to and excites the inferior olivary nuclear neurons, which send climbing fibers to excite neurons in contralateral cerebellar cortex and nuclei. RNp receives excitatory inputs from ipsilateral cerebral cortex (onto distal dendrites) and from contralateral cerebellar nuclei (onto proximal dendrites). We here further develop a hypothesis as to mechanism, and offer preliminary evidence from RNp inactivation studies in awake, trained macaques during modification of their gaze-reach calibration while wearing wedge prism spectacles.

On the mechanism of cerebellar contributions to cognition.

The cerebellum is highly stereotyped in its cellular circuitry. Output neurons in the nuclei with one exception excite their downstream targets in other parts of the nervous system. Yet the much more voluminous cerebellar cortex inhibits these output neurons. This has suggested that the desired output activity pattern is achieved by removing all unwanted activity patterns ('sculpting'). Lesions of the lateral cerebellum impair cognitive functions including speech. These lateral portions are active during imagined as well as overt movements. Imagined movements could be used to time task performances in the absence of an external clock. The intrinsic circuitry suggests that the cerebellar cortex links together and combines nuclear output activities. A linkage mechanism is consistent with the motor deficits in coordination after midline vermal section in humans and Purkinje cell recording in trained animals. The lateral cerebellum, which projects to frontal and parietal 'association' cortex, may link together cerebral 'cognitive units' as a substrate for coordinated thought.

On-beam synchrony in the cerebellum as the mechanism for the timing and coordination of movement.

In trained reaching rats, we recorded simple spikes of pairs of Purkinje cells that, with respect to each other, were either aligned on a beam of shared parallel fibers or instead were located off beam. Rates of simple spike firing in both on-beam and off-beam Purkinje cell pairs commonly showed great variety in depth of modulation during reaching behavior. But with respect to timing, on-beam Purkinje cell pairs had simple spikes that were tightly time-locked to each other (either delayed or simultaneous) and to movement, despite the variability in rate. By contrast, off-beam Purkinje cell pairs had simple spikes that were not time-locked to each other, neither delayed nor simultaneous. We discuss the implications of these observations for the cerebellar role in timing and coordinating movement.

How do strength, sensation, spasticity and joint individuation relate to the reaching deficits of people with chronic hemiparesis?

Hemiparetic subjects present with movement deficits including weakness, spasticity and an inability to isolate movement to one or a few joints. Voluntary attempts to move a single joint often result in excessive motion at adjacent joints. We investigated whether the inability to individuate joint movements is associated with deficits in functional reaching. Controls and hemiparetic subjects performed two different reaching movements and three individuated arm movements, all in the parasagittal plane. The reaching movements were a sagittal 'reach up' (shoulder flexion and elbow flexion) and 'reach out' (shoulder flexion and elbow extension). Joint individuation was assessed by getting each subject to perform an isolated flexion-extension movement at each of the shoulder, elbow and wrist joints. In addition, we measured strength, muscle tone and sensation using standard clinical instruments. Hemiparetic subjects showed varying degrees of impairment when performing reaching movements and individuated joint movements. Reaching impairments (hand path curvature, velocity) were worse in the reach out versus the reach up condition. Typical joint individuation abnormalities were excessive flexion of joints that should have been held fixed during movement of the instructed joint. Hemiparetic subjects tended to produce concurrent flexion motions of shoulder and elbow joints when attempting any movement, one explanation for why they were better at the 'reach up' than the 'reach out' task. Hierarchical regression analysis showed that impaired joint individuation explained most of the variance in the reach path curvature and end point error; strength explained most of the variance in reaching velocity. Sensation also contributed significantly, but spasticity and strength were not significant in the model. We conclude that the deficit in joint individuation reflects a fundamental motor control problem that largely explains some aspects of voluntary reaching deficits of hemiparetic subjects.

Cerebellar control of constrained and unconstrained movements. I. Nuclear inactivation.

The aim of this study was to determine in monkeys if inactivation of dentate and lateral interposed deep cerebellar nuclei preferentially impairs certain movements relative to others. Constrained movements of the digits were trained with digits, hand, and elbow constrained in a cast. Simple movements were flexion of Thumb or Index. A compound movement was simultaneous flexion of Thumb+Index. An unconstrained movement consisted of a reach to, pinch of, and retrieval of a small food reward (Reach+Pinch). In two monkeys we mapped the dentate and interpositus with 66 injections of muscimol (3 microl of 5 microg/microl). Thirty-two percent of the injections resulted in increased reaction times of Thumb, Index, and Thumb+Index (mean = 24, 24, 28 + 26, respectively). Fifty percent of the injections impaired Reach+Pinch, producing target overshoot, curved reach trajectory, missed target (X and Y errors), and clumsy pinch with dropped fruit bits. Inactivation impaired each and all of Thumb, Index, Thumb+Index, and Reach+Pinch in 27%, only Reach+Pinch in 23%, and only Thumb, Index, Thumb+Index in 5% of injections. In sum, all types of movement were impaired. Thumb+Index was no more impaired than Thumb or Index alone, suggesting that the lateral cerebellar nuclei are not specifically required for combining movements of the two digits when constrained. Reach+Pinch appeared so greatly impaired and Thumb, Index, Thumb+Index so little as to be consistent with the hypothesis that a principal role of the cerebellum is to control those interactions that occur between body segments in natural unconstrained movements. However, the fact that all movements were impaired shows that the cerebellum contributes to the control of all movements.

Cerebellar control of constrained and unconstrained movements. II. EMG and nuclear activity.

The aim of this study was to see in monkeys if neurons in dentate and lateral interposed deep cerebellar nuclei are preferentially active in relation to certain movements relative to others. Simple and compound digit movements were trained with digits, hand, and elbow constrained in a cast. The constrained simple movement was flexion of Thumb or Index; the constrained compound movement, flexion of Thumb+Index. An unconstrained compound movement consisted of a reach to, pinch of, and retrieval of a small food reward (Reach+Pinch). Electromyographic (EMG) recording showed that many muscles in the upper extremity, shoulder girdle, and trunk were active in all movements. EMG/muscle stimulation during the constrained digit movements showed that the digit prime movers were active during, sufficient for, and necessary for performance of these digit tasks. By contrast, EMG/muscle stimulation showed that the proximal muscles (though co-active during the tasks) were neither sufficient nor necessary for performance of the digit tasks. A fraction of those neurons that were active during both the constrained and the unconstrained movements fired at a higher frequency during the unconstrained task. Some neurons were active during Reach+Pinch only; a few others were active during one or more of Thumb, Index, Thumb+Index only. There was no distinct preferential discharge relationship to the compound Thumb+Index as compared with the simple Thumb or Index. These correlational data are consistent with an interpretation that the cerebellar discharge influenced all of these movements-simple and compound, constrained, and unconstrained-no one type seemingly more than any other.

Cerebellar subjects show impaired coupling of reach and grasp movements.

We examined how cerebellar deficits in isolated reaching or grasping movements contribute to abnormalities in a combined reach and grasp movement, and whether people with cerebellar damage show abnormalities in the spatiotemporal relationships of reach and grasp movements. We studied subjects with cerebellar damage and matched controls as they performed a combined reach and grasp, an isolated reach, and an isolated grasp. These movements were performed under slow-accurate and fast speed conditions. Subjects were also tested for their ability to correctly estimate the target size based on visual information. We measured the three-dimensional position of the index finger, thumb and wrist joint during all tasks. Results showed that cerebellar subjects overestimated the target size to a greater extent than did controls. During movement testing, cerebellar subjects were impaired on isolated reach and isolated grasp. However, they did not worsen parameters of reach or grasp movements during the combined reach and grasp. Instead there were distinct deficits in the coupling of the reach and grasp movement. Compared with controls, cerebellar subjects showed abnormalities in the sequence of the reach and grasp movement and highly variable timing of peak grip aperture. In the slow-accurate condition, cerebellar subjects decomposed the reach and grasp movement into separate reach then grasp components, and produced multiple peaks in grip aperture. In the fast condition, cerebellar subjects did not decompose, produced a single peak grip aperture, and dropped the target more often. These results indicate that cerebellar damage can cause a specific breakdown in the coupling of reach and grasp movements. The cerebellum may be involved in combining reach and grasp movements into a single motor program.

Thalamic stimulation reduces essential tremor but not the delayed antagonist muscle timing.

BACKGROUND: Electrical stimulation of the thalamus dramatically reduces essential tremor (ET). It has been hypothesized that the cerebellum and inferior olive are involved in the generation of ET, and thalamic stimulation is presumed to dampen ET through interactions with cerebellar output to the thalamus. Evidence suggests that abnormal timing of agonist and antagonist muscle responses contribute to cerebellar tremor (CbT); however, this relationship has not been investigated for ET. The mechanisms of the tremor and improvement are unknown. OBJECTIVE: To measure the effect of ventral intermediate thalamic stimulation in controlling the ET response to sudden stretch of an agonist muscle and to determine whether, in ET, the timing relationships between the initial agonist and antagonist electromyography (EMG) responses show abnormalities similar to those seen in CbT. METHODS: The authors studied ET subjects (with implanted thalamic stimulators turned off and on) and normal controls as they responded to mechanical torque pulses given at the wrist joint. The wrist joint angle, wrist agonist, and antagonist EMG were recorded. RESULTS: Like CbT, patients with ET showed delayed onsets of antagonist EMG and excessive rebound. Thalamic stimulation reduced the tremor but did not alter the antagonist delay or the rebound. CONCLUSIONS: In ET, antagonist muscle responses to a torque pulse are similar to that in CbT. However, benefit from thalamic stimulation did not alter these EMG responses; therefore, suppression of tremor must be caused by mechanisms other than the re-establishment of normal agonist-antagonist timing.

Role of the posterolateral cerebellum in language.

Historically, scientists have believed that the cerebellum controls only movement. However, recent evidence from neuroimaging and human lesion studies suggests that the right posterolateral cerebellar hemisphere is involved, independently of movement, in helping an individual to generate verbs for given nouns. We sought to elucidate the key factors contributing to the verb generation deficits of subjects with right posterolateral cerebellar damage and thus to better understand the specific contributions of the postero-lateral cerebellum to language. We compared the performance of subjects with focal left-sided posterolateral cerebellar lesions, those with focal right-sided posterolateral cerebellar lesions, and neurologically normal pilot control subjects on an antonym generation task, noun (category member) generation task, verb selection task, and lexical decision task. Preliminary results show that subjects with right cerebellar lesions are impaired relative to other subjects only on the antonym generation task. The results provide evidence that the right cerebellar language deficit is not due solely to deficits in "mental movement" coupled to a verb and that internal generation of a word seems to be a key factor in eliciting a deficit. In addition, a semantic processing demand may be necessary but insufficient to elicit a right cerebellar language deficit. The results support the theory that the right posterolateral cerebellar hemisphere assists the left cerebral hemisphere in helping an individual learn to generate specific types of spoken, two-word associations. The full nature of this process awaits further investigation.

Prism adaptation of reaching is dependent on the type of visual feedback of hand and target position.

The present study demonstrated that the magnitude of after-effect due to wedge prisms depends on the form of the visual feedback used to represent hand and target position in fast, targeted, transverse reaches. Trained human subjects made reaches with and without prisms in three visuomotor representations (VR): (1) the subject's actual hand and targets (Direct), (2) a real-time video broadcast of hand and targets (Video), or (3) abstract, computer-generated targets and a cursor representing hand position (Cursor). A significant after-effect occurred in each VR. However, the magnitude of the after-effect was significantly different among VRs: the magnitude was greatest in Direct, smaller in Video and smallest in Cursor. A significant after-effect (carryover) also occurred when a subject prism-adapted reaches in one VR and then removed the prisms and made initial reaches in another VR. Our data showed that when reaches were prism-adapted in Direct and then prisms were removed, there was a large carryover to initial reaches in Video or Cursor (D-->V and D-->C). In contrast, when prisms were worn in Video and removed for reaches in Direct (V-->D), there was a significantly smaller carryover than from both D-->V and D-->C. Finally, when prisms were worn in Cursor and removed for reaches in Direct (C-->D), there was very little detectable carryover. Our results suggest that adaptation is context-dependent and that the magnitude of carryover is dependent on the VR in which adaptation occurred. Interpretations of adaptations made in abstract training and experimental conditions may be greatly affected by this finding.

Throwing accuracy in the vertical direction during prism adaptation: not simply timing of ball release.

In a previous study, others have hypothesized that the variance in vertical errors that occurs while throwing at visual targets is caused by changes in any of three throw parameters: hand location in space, hand translational velocity, and hand orientation. From an analysis of skilled throwers, those authors concluded that vertical error is best correlated with variance in hand orientation, which in turn is related to the timing of ball release. We used a vertical prism adaptation paradigm to investigate which of these throwing parameters subjects use when adapting to external perturbation. Our subjects showed no correlation between hand position or hand translational velocity and ball impact height in normal, over-practiced throwing. However, video-based motion analysis showed that modifications both of position and speed of the hand play an important role when subjects are forced to compensate for a vertically shifting prism perturbation during a dart-like throw (these factors contribute approximately 30% of the adaptation). We concluded that, during adaptation, more degrees of freedom and more sources of potential error are modified to achieve the gaze-throw recalibration required to hit the target than are employed in this type of throw during normal conditions.

Cerebellar ataxia: torque deficiency or torque mismatch between joints?

Prior work has shown that cerebellar subjects have difficulty adjusting for interaction torques that occur during multi-jointed movements. The purpose of this study was to determine whether this deficit is due to a general inability to generate sufficient levels of phasic torque inability or due to an inability to generate muscle torques that predict and compensate for interaction torques. A second purpose was to determine whether reducing the number of moving joints by external mechanical fixation could improve cerebellar subjects' targeted limb movements. We studied control and cerebellar subjects making elbow flexion movements to touch a target under two conditions: 1) a shoulder free condition, which required only elbow flexion, although the shoulder joint was unconstrained and 2) a shoulder fixed condition, where the shoulder joint was mechanically stabilized so it could not move. We measured joint positions of the arm in the sagittal plane and electromyograms (EMGs) of shoulder and elbow muscles. Elbow and shoulder torques were estimated using inverse dynamics equations. In the shoulder free condition, cerebellar subjects made greater endpoint errors (primarily overshoots) than did controls. Cerebellar subjects' overshoot errors were largely due to unwanted flexion at the shoulder. The excessive shoulder flexion resulted from a torque mismatch, where larger shoulder muscle torques were produced at higher rates than would be appropriate for a given elbow movement. In the shoulder fixed condition, endpoint errors of cerebellar subjects and controls were comparable. The improved accuracy of cerebellar subjects was accompanied by reduced shoulder flexor muscle activity. Most of the correct cerebellar trials in the shoulder fixed condition were movements made using only muscles that flex the elbow. Our findings suggest that cerebellar subjects' poor shoulder control is due to an inability to generate muscle torques that predict and compensate for interaction torques, and not due to a general inability to generate sufficient levels of phasic torque. In addition, reducing the number of muscles to be controlled improved cerebellar ataxia.

Mirror movements complicate interpretation of cerebral activation changes during recovery from subcortical infarction.

In recovered stroke patients, performance of motor tasks with the affected limb has been reported to activate cortical areas ipsilateral to the affected side. The better to determine the causal role these areas play in recovery of motor function, we assessed cerebral activation during motor activity longitudinally after hemiparesis due to cerebral infarction. A secondary goal was to ascertain the relation between mirror movements and activation ipsilateral to motor activity. Positron emission tomography with oxygen-15 water measured regional cerebral blood flow during wrist movement early and late in the course of recovery from hemiparesis. Surface electromyography recorded muscular activity, and computer-assisted video analysis quantified movement during the scans. Mirror movements, movements contralateral to the instructed movement of the hemiparetic arm, were often seen. Activation of motor areas in the hemisphere ipsilateral to the affected limb roughly correlated with presence of mirror movements. Other changes in cerebral activation were small, when the task was controlled for rate, but high-rate-specific recruitment of ipsilateral cortical areas occurred in one case. However, the common occurrence of mirror movements, particularly with effortful tasks, complicates interpretation of data regarding the role of the ipsilateral hemisphere in recovery.

Posterior vermal split syndrome.

We have studied a battery of movements in 5 children (age, 6-15 years) after transection of the posterior inferior cerebellar vermis. In each case, the surgery destroyed the midline vermis only (ranging from lobules VI-X). Tandem gait was badly impaired in all subjects. No subjects had impairments of kicking, reaching, pinching, or speech. Regular gait, standing, and hopping on one leg were relatively unimpaired. Cutting the parallel fibers that cross the midline may be the critical variable causing incoordination in tandem gait.

A role for the cerebellum in learning movement coordination.

We have examined several different paradigms of adaptation and of "acquisition of skill"-skill defined as a movement specialized to meet a certain goal and gained through practice. In each paradigm, change occurs through trial-and-error performance. In some of the tasks, damage of cerebellar cortex impairs adaptation and not performance. The deficits in performance cannot explain the deficits in adaptation. In some of the tasks, the discharge of Purkinje cells and, by inference, the discharge of inferior olive cells and mossy fibers have occurred in a manner consistent with the Marr-Albus theory of motor learning. We extend the theory to show how parallel fibers could implement both the coordination of complex movements and the learning of new movements. The size of the response combinations would be proportionate to the length of parallel fibers. The mechanism proposed here would permit optimized complex movement behaviors to respond to specific behavioral contexts rapidly, stereotypically, and automatically. The mechanism would permit storage of many context-response couplings and many complex responses. The mechanism would permit privacy, individuality, and a large number of behavioral responses.

Combination, complementarity and automatic control: a role for the cerebellum in learning movement coordination.

We have examined several different paradigms of adaptation and of 'acquisition of skill'--skill defined as a movement specialized to meet a certain goal and gained through practice. In each paradigm, change occurs through trial-and-error performance. In some of the tasks, damage of cerebellar cortex impairs adaptation and not performance. The deficits in performance cannot explain the deficits in adaptation. In some of the tasks, the discharge of Purkinje cells and, by inference, the discharge of inferior olive cells and mossy fibres has behaved in a manner consistent with the Marr-Albus theory of motor learning. We extend the theory to show how parallel fibres could implement both the coordination of complex movements and the learning of new movements. The size of the response combinations would be proportionate to the length of parallel fibres. The mechanism proposed here would permit optimized complex movement behaviours to respond to specific behavioural contexts rapidly, stereotypically and automatically. The mechanism would permit storage of many context-response couplings, and many complex responses. The mechanism would permit privacy, individuality and a large number of behavioural responses.

What is the role of the cerebellum in motor learning and cognition?

The exact role of the cerebellum in motor learning and cognition is controversial. Nonetheless, recent ideas and facts have prompted an attempt at building and testing a more unified and coherent conceptualization. This article will suggest that the cerebellum might indeed participate in both motor control and cognition, and in motor adaptation, motor learning, and procedural learning. The proposed process would entail stimulus-response linkage through trial and error learning, and would consist of groupings of single-response elements-motor and cognitive-into large combinations. After practice, the occurrence of a sensory or experiential `context' would automatically trigger the combined response. The parallel fiber is the proposed agent of stimulus-response linkage and of combining the response elements. The attempt here is to focus on the role of the parallel fiber as a possible combiner of downstream motor and cognitive elements.