Movement-related cortical potentials preceding repetitive and random-choice hand movements in parkinson's disease

The movement-related cortical electroencephalographic potential was recorded from scalp electrodes in 8 patients with idiopathic Parkinson's disease studied at least 12 hours after withdrawal of their normal drug therapy, and compared with the results from a group of 8 age-matched control subjects. Two types of self-paced voluntary arm movements were examined: repetitive forward movement of a joystick, and random-choice movements of the same joystick in which subjects had to choose freely the direction in which they were to move the stick (forward, backward, left, or right). In normal subjects, the movement-related cortical potential was larger prior to random-choice movements, whereas in the patients, the amplitude was the same in both tasks. The implication is that processes involved in self-selection of movement are abnormal in Parkinson's disease. This may contribute to the difficulty that patients have in initiating voluntary movement in the absence of any external cues.     

Ballistic and corrective movements on an aiming task. Intention tremor and parkinsonian movement disorders compared.

Six patients with Parkinson's disease, six patients with essential or intention tremor, and nine controls were tested on a step-tracking task using a joystick control and oscilloscope display. Tremor subjects resembled controls in making an initial ballistic movement followed by (defective) corrections, and took longer than the controls to reach the target with small amplitude jumps, but not with larger ones. The reverse was true for parkinsonian subjects, who acquired the target with slow corrective movements only. This suggests that two kinds of movement available to normal people are selectively impaired in these disorders; ballistic movements in Parkinson's disease and small amplitude corrective movements in the other disorders.     

Jaw movement dysfunction related to Parkinson's disease and partially modified by levodopa.

OBJECTIVES--To test the hypotheses that Parkinson's disease can differentially produce deficits in voluntary and rhythmic jaw movements, which involve different neuronal circuits, and that levodopa treatment improves specific components of the motor deficit. METHODS--Patients with idiopathic Parkinson's disease and control subjects were tested on a series of jaw motor tasks that included simple voluntary movement, isometric clenching, and natural and paced rhythmic movements. Jaw movements were measured by changes in electromagnetic fields and EMG activity. Patients with Parkinson's disease with fluctuations in motor responses to levodopa were tested while off and on. RESULTS--During the off state, patients with Parkinson's disease were significantly worse than the control subjects on most tasks. The deficits included a decrease in amplitude and velocity during jaw opening and closing, aberrant patterns and low amplitude of EMG activity during clenching, and low vertical amplitude and prolonged durations of occlusion during rhythmic movements. No decrements were found in the amplitude of voluntary lateral jaw movements or the frequency of rhythmic movements. During the on state, improvements occurred in the patterns and level of EMG activity during clenching and in the vertical amplitude and duration of occlusion during rhythmic movements, although a significant decrement occurred in the lateral excursion of the jaw. CONCLUSIONS--Parkinson's disease affects the central programming of functionally related muscles involved in voluntary and rhythmic jaw movements and levodopa replacement influences only certain aspects of jaw movement, most likely those requiring sensory feedback.     

Dipole source analysis suggests selective modulation of the supplementary motor area contribution to the readiness potential

The readiness potential preceding voluntary movement is modulated by the mode of movement selection, i.e. it has a higher amplitude preceding freely selected than before prescribed movements (Praamstra, P., Stegeman, D.F., Horstink, M.W.I.M., Brunia, C.H.M. and Cools, A.R. Movement-related potentials preceding voluntary movement are modulated by the mode of movement selection. Exp. Brain Res., 1995, 103: 429–439). One cortical area that is likely to be involved in this modulation is the supplementary motor area (SMA). Recent attempts to elucidate the neural generators of the readiness potential using spatiotemporal dipole source analysis, however, failed to establish a significant SMA contribution to the readiness potential. This might be explained by a failure of the proposed analyses to discriminate between SMA and motor cortex contributions to the readiness potential. We applied a dipole source analysis approach that better separates these overlapping source activities. The resulting source model includes an SMA source generating premovement activity consistent with evidence from intracranial recordings in humans. The SMA source accounts almost completely for the modulation of the readiness potential by different modes of movement selection. On the basis of these results, the relation between scalp-recorded movement-related activity, intracranially recorded potentials, and findings from functional imaging studies of voluntary movement, appears more transparent than suggested by previous dipole source analyses of premovement potentials.     

Practice as an intervention to improve speeded motor performance and motor learning in Parkinson's disease

Individuals with Parkinson's disease have difficulty initiating and performing complex, sequential movements. Practice generally leads to faster initiation and execution of movements in healthy adults, however, whether practice similarly improves motor performance in patients with Parkinson's disease remains controversial. To assess the effects of practice on motor performance, patients with Parkinson's disease and control subjects practiced two, rapid arm-reaching tasks with different levels of movement complexity for 120 trials each over 2 days. Response programming was studied by analyzing the overall reaction time latency of each movement and its fractionated sub-components, premotor and motor time. Practice effects were investigated by comparing pretest performance to immediate and delayed retention test performances (10-min and 48-h rest intervals, respectively). Both patients with Parkinson's disease and control subjects improved speeded performance of sequential targeting tasks by practice and retained the improvement across both retention test intervals. Finding a learning effect for persons with Parkinson's disease supports practice as an effective rehabilitation strategy to improve motor performance of specific tasks for patients with Parkinson's disease.     

Impaired mesial frontal and putamen activation in Parkinson's disease: a positron emission tomography study.

Selection of movement in normal subjects has been shown to involve the premotor, supplementary motor, anterior cingulate, posterior parietal, and dorsolateral prefrontal areas. In Parkinson's disease (PD), the primary pathological change is degeneration of the nigrostriatal dopaminergic projections, and this is associated with difficulty in initiating actions. We wished to investigate the effect of the nigral abnormality in PD on cortical activation during movement. Using C15O2 and positron emission tomography (PET), we studied regional cerebral blood flow in 6 patients with PD and 6 control subjects while they performed motor tasks. Subjects were scanned while at rest, while repeatedly moving a joystick forward, and while freely choosing which of four possible directions to move the joystick. Significant increases in regional cerebral blood flow were determined with covariance analysis. In normal subjects, compared to the rest condition, the free-choice task activated the left primary sensorimotor cortex, left premotor cortex, left putamen, right dorsolateral prefrontal cortex and supplementary motor area, anterior cingulate area, and parietal association areas bilaterally. In the patients with PD, for the free-choice task, compared with the rest condition, there was significant activation in the left sensorimotor and premotor cortices but there was impaired activation of the contralateral putamen, the anterior cingulate, supplementary motor area, and dorsolateral prefrontal cortex. Impaired activation of the medial frontal areas may account for the difficulties PD patients have in initiating movements.     

The preparation and execution of saccadic eye and goal-directed hand movements in patients with Parkinson's disease

The oculomotor and manual motor systems were studied in a two-segment movement task in a group of patients with Parkinson's disease and in age matched normal controls. In order to avoid reflexive motor movements the selection of the correct motor sequence was derived from the interpretation of symbolic (coloured) cues. The latencies and dynamics of eye and hand (pointing) movements performed during the first (fixed) movement segment were measured and the planning and execution processes were manipulated by varying the complexity of the second movement segment relative to the first (with regard to direction and amplitude). The results showed that the eye and hand movements made by patients with Parkinson's disease were not impaired in the initiation of the first movement segment. Interestingly, both Parkinson's patients and controls showed increased eye and hand reaction time latencies for the first movement when the second movement was in the direction opposite to the first. This indicates that the complexity of the second movement influences the execution of the first movement, and importantly that complexity affects motor initiation and execution processes in both normal subjects and in patients with Parkinson's disease. The execution of hand movements was found to be impaired in patients with Parkinson's disease as indicated by a reduced peak velocity of manual pointing responses when compared to age matched controls. By contrast, no differences were found in the dynamics of saccadic eye movements. This dissociation is consistent with the notion that the skeletomotor loop passes through the functionally corresponding portions of the basal ganglia independently of the oculomotor loop. Together, these results demonstrate that Parkinson's patients are able to generate multiple non-reflexive eye and hand movements and that the observed (manual) motor deficits are specific to the processes of motor execution.     

Readiness potential of cortical area 6 preceding self paced movement in Parkinson''s disease.

The vertex Readiness Potential (RP) (Bereitschaftspotential) preceding self paced voluntary movements is reduced in duration and amplitude in patients with Parkinsonism. It cannot be used as an index for delayed initiation of movement. The negative potential is commonly replaced by a positive slow wave. In hemi-Parkinsonism, the abnormal RP is more apparent on moving the affected limb. The abnormal RP is related to the severity but not to the duration of Parkinsonism. Short-term fluctuations of akinesia and rigidity, spontaneous or caused by levodopa are associated with changes of RP duration and amplitude. The abnormality does not correlate with reaction or movement times. It is suggested that the Readiness Potential is a diffuse response of area 6 cortex (especially Supplementary Motor Area) evoked by pallido-thalamo-cortical afferents under dopaminergic control. It is not obligatory for pre-programming of voluntary movement. The authors postulate a dendritic potential of basket cells associated with a pallidal activated gate control of postural set.     

Movement amplitude choice reaction time performance in Parkinson''s disease may be independent of dopaminergic status.

The effect of circulating levels of plasma levodopa on reaction time performance was studied in patients with Parkinson's disease and untreated normal controls when instructed to move either a shorter or longer distance. On half the movements, subjects were pre-cued on the direction and amplitude of an impending movement. On the remaining movements, only the direction was pre-specified, and the amplitude was determined only when the cue to move was presented. Reaction time performance of patients was evaluated at three infusion levels of levodopa so that the patients were optimally, moderately, or minimally medicated. Parkinsonian patients were always slower to react and move than normal subjects. Clinical state correlated with movement time, but not with reaction time. These results contrast with those in which reaction time was related to plasma levodopa levels when movement direction and initiation were processed concomitantly, but the movement amplitude was pre-cued. It is possible that specification of the amount of muscle activity is partially independent of dopaminergic transmission.     

Bereitschaftspotential in patients with unilateral lesions of the supplementary motor area.

In the present study, an attempt was made to examine the sensitivity of the Bereitschaftspotential (BP) preceding simple finger movement in revealing pathophysiological patterns of premovement cortical activity in patients with chronic unilateral lesions of the supplementary motor area (SMA). Usually, in healthy subjects, BP has a clear maximum in Cz with larger amplitudes than in Ccon (located over the motor cortex, contralateral to the performing hand). In the patients, amplitudes did not differ between Cz and Ccon. This effect of the lesion on BP topography, was found in movements of either side. However, intraindividual comparisons revealed that the reduction of the BP in Cz (relative to Ccon) was larger for movements contralateral to the SMA lesion than for those ipsilateral of it.     

Impairments in the learning and performance of a new manual skill in patients with Parkinson''s disease.

Twelve patients with Parkinson's disease learned two novel skills in which they had to track a target by moving a joystick. In task 1 they had to learn to anticipate the movements of a semi predictable target. In task 2 they had to learn a novel control system in which the movements of the joystick were mirror reversed in relation to the computer screen. On each task they performed two sessions of three minutes continuous practice separated by a 10 minute rest. In both tasks the patients performed much worse than the controls, but showed clear evidence of learning, particularly after the ten minute rest. Detailed examination of their performance suggested that the skill was becoming automatic, releasing attention for aspects of the task that could not be learned. The major difference from the controls appeared during the first minute of each practice session when the controls showed a marked improvement in performance while the patients did not. We suggest that this rapid but temporary improvement in performance reflects the acquisition of a motor "set" whereby existing motor programs or skills are modified to suit the task currently in hand. We concluded that patients with Parkinson's disease have difficulty in maintaining such sets.     

Oculomotor abnormalities in Parkinson's disease.

Ocular movement was studied in 19 patients with Parkinson's disease and in ten normal controls. Common abnormalities included "hypometric saccade" on the eye-tracking test and on command, "saccadic pursuit," and convergence paresis. Reaction time was longer in patients with Parkinson's disease than in controls for horizontal saccadic gaze, finger movements, and body movements. Maximal saccadic velocity of horizontal gaze was slower in patients with Parkinson's disease than in controls. Slowing of the horizontal saccadic movement correlated significantly with an increased reaction time of finger and body movements. Correlation of decreased saccadic velocity with increased reaction time of finger movement was found for the finger ipsilateral to the direction of horizontal gaze, but not for the contralateral finger. It is postulated from these facts that bradykinesia also exists in eye movements in Parkinson's disease.     

Functional changes in the activity of cerebellum and frontostriatal regions during externally and internally timed movement in Parkinson's disease

We used fMRI to investigate the neurofunctional basis of externally and internally timed movements in Parkinson's disease (PD) patients. Ten PD patients whose medication had been withheld for at least 18h and 11 age- and sex-matched healthy controls were scanned while performing continuation paradigm with a visual metronome. Compared with the controls, PD patients displayed an intact capability to store and reproduce movement frequencies but with a significantly increased movement latencies. No differences in BOLD response were found in both groups when comparing the continuation with the preceding synchronization phase and viceversa, except for activity in visually related regions. Relative to healthy controls during the synchronization phase, PD patients exhibited an overall signal increase in the cerebellum and frontostriatal circuit (putamen, SMA and thalamus) activity together with specific brain areas (right inferior frontal gyrus and insula cortex) that are also implicated in primary timekeeper processes. By contrast, in the continuation phase the only neural network involved to a greater extent by the PD group was the cerebello-thalamic pathway. The lack of neurofunctional differences between the two timing phases suggests that rhythmic externally and internally guided movements engage similar neural networks in PD and matched healthy controls. Moreover, between-group comparison indicates that PD patients OFF medication may compensate for their basal ganglia-cortical loop's dysfunction using different motor pathways involving cerebellum and basal ganglia relays during the two phases of rhythmic movement.     

The control of bimanual aiming movements in Parkinson''s disease.

The control of unimanual and bimanual aiming movements by Parkinson's disease and control subjects was examined. Despite greater bimanual movement initiation asynchrony and overall bradykinesia, the Parkinson's disease subjects were affected by the experimental manipulations in the same way as controls. Symmetrical and, more especially, asymmetrical bimanual movements required more preparation time and were executed more slowly by both groups than were unimanual movements. Both groups also showed temporal linkage of movements to targets of different extents--movements which have different movement times when performed unimanually, as well as of the faster and slower limbs. A majority in both groups over-compensated for asynchrony in bimanual movement initiation by modulation of movement times, but there was no group difference in this tendency. The results are discussed in terms of underlying motor control processes and with regard to previous evidence for impaired control of simultaneous movements in Parkinson's disease.     

Control of movement distance in Parkinson's disease.

Studies of electromyographic (EMG) patterns during movements in Parkinson's disease (PD) have often yielded contradictory results, making it impossible to derive a set of rules to explain how muscles are activated to perform different movement tasks. We sought to clarify the changes in modulation of EMG parameters associated with control of movement distance during fast movements in patients with PD. Specifically, we studied surface EMG activity during rapid elbow flexion movements over a wide range of distances (5-72 degrees) in 14 patients with relatively mild symptoms of PD and 14 control subjects of similar age, sex, height, and weight. The PD group exhibited several changes in EMG modulation including impaired modulation of agonist burst duration; increased number of agonist bursts; reduced scaling of agonist EMG magnitude in the more severely impaired subjects; and increased temporal overlap of the antagonist and agonist signals in the most severely impaired subjects. These findings suggest that progressive motor dysfunction in PD is accompanied by increasing deficits in modulating muscle activation. These results help clarify previous disparate and sometimes contradictory results of EMG patterns in subjects with PD.     

Bimanual coordination dysfunction in early, untreated Parkinson's disease

Bimanual coordination involves the simultaneous performance of either symmetrical (in-phase) or asymmetrical (anti-phase) movements with both hands and is known to be impaired in Parkinson's disease (PD). At present, it is unclear whether this aspect of motor function is already impaired in early stage, untreated PD patients. Therefore, we investigated the accuracy of bimanual coordination in 13 early stage, untreated PD patients and 13 age- and sex-matched healthy controls. Each subject performed bimanual coordination tasks at two different movement frequencies (1 and 1.75 Hz) and with two different phase relationships (in-phase and anti-phase). The percentage of unsuccessful trials (as a measure of overall task performance) in PD patients was significantly higher than in healthy subjects. PD patients performed high frequency in-phase and anti-phase bimanual coordination tasks less accurately with their non-dominant hand than healthy subjects. Furthermore, PD patients had more difficulty than healthy subjects in maintaining a constant phase relationship between the hands in the anti-phase condition at low movement frequency. This study demonstrates that bimanual coordination dysfunction is a very early sign of PD. Bimanual coordination tasks, in particular those involving high frequency anti-phase movements, might prove useful in the early diagnosis of PD.     

What is the Bereitschaftspotential?

Since discovery of the slow negative electroencephalographic (EEG) activity preceding self-initiated movement by Kornhuber and Deecke [Kornhuber HH, Deecke L. Hirnpotential?nderungen bei Willkurbewegungen und passiven Bewegungen des Menschen: Bereitschaftspotential und reafferente Potentiale. Pflugers Archiv 1965;284:1-17], various source localization techniques in normal subjects and epicortical recording in epilepsy patients have disclosed the generator mechanisms of each identifiable component of movement-related cortical potentials (MRCPs) to some extent. The initial slow segment of BP, called 'early BP' in this article, begins about 2 s before the movement onset in the pre-supplementary motor area (pre-SMA) with no site-specificity and in the SMA proper according to the somatotopic organization, and shortly thereafter in the lateral premotor cortex bilaterally with relatively clear somatotopy. About 400 ms before the movement onset, the steeper negative slope, called 'late BP' in this article (also referred to as NS'), occurs in the contralateral primary motor cortex (M1) and lateral premotor cortex with precise somatotopy. These two phases of BP are differentially influenced by various factors, especially by complexity of the movement which enhances only the late BP. Event-related desynchronization (ERD) of beta frequency EEG band before self-initiated movements shows a different temporospatial pattern from that of the BP, suggesting different neuronal mechanisms for the two. BP has been applied for investigating pathophysiology of various movement disorders. Volitional motor inhibition or muscle relaxation is preceded by BP quite similar to that preceding voluntary muscle contraction. Since BP of typical waveforms and temporospatial pattern does not occur before organic involuntary movements, BP is used for detecting the participation of the 'voluntary motor system' in the generation of apparently involuntary movements in patients with psychogenic movement disorders. In view of Libet et al.'s report [Libet B, Gleason CA, Wright EW, Pearl DK. Time of conscious intention to act in relation to onset of cerebral activity (readiness-potential). The unconscious initiation of a freely voluntary act. Brain 1983;106:623-642] that the awareness of intention to move occurred much later than the onset of BP, the early BP might reflect, physiologically, slowly increasing cortical excitability and, behaviorally, subconscious readiness for the forthcoming movement. Whether the late BP reflects conscious preparation for intended movement or not remains to be clarified.     

Impaired activation of the supplementary motor area in Parkinson's disease is reversed when akinesia is treated with apomorphine.

Using positron emission tomography (PET) we previously showed that activation of the putamen, supplementary motor area, and cingulate cortex is impaired in patients with Parkinson's disease (PD) when they are off treatment and perform volitional motor tasks. Evidence suggests that these areas are involved in the generation of internally cued movements in normal subjects. We have now studied the effect of the dopamine agonist apomorphine on cerebral activation when used to treat the akinesia of PD. Regional cerebral blood flow was measured using C15O2 PET in PD patients at rest and when performing paced joystick movements with the right hand in one of four freely chosen directions. All patients used apomorphine regularly, and were studied before treatment, while still "off" but receiving a subcutaneous apomorphine infusion, and when switched "on" with apomorphine. Significant increases in regional cerebral blood flow were determined using statistical parametric mapping. Under resting conditions apomorphine had no effect on focal or global cerebral blood flow. Seven patients with PD performed the motor task adequately in the "off" and "on" states. This group of subjects demonstrated impaired activation of the supplementary motor area and contralateral putamen in the "off" state. Activation of the supplementary motor area significantly improved when the akinesia was reversed with apomorphine. We conclude that the concomitant improvement of supplementary motor area activation and motor function in apomorphine-treated patients with PD provides further evidence for the role of this structure in generating motor programs.     

Scaling of the size of the first agonist EMG burst during rapid wrist movements in patients with Parkinson''s disease.

Rapid wrist flexion movements were studied in a group of 10 patients with Parkinson's disease both on and off their normal drug therapy, and were compared with the same movements made by a group of eight normal individuals. When normal subjects made movements through 60 degrees, the first agonist burst of EMG activity in the wrist flexor muscles was longer and larger than that seen in movements of 15 degrees. If a large opposing load of 2.2 Nm was added, this also increased the size and duration of the first agonist EMG burst. Although the movements made by the patients were slower than those of normals, the size and duration of the first agonist EMG burst changed with movement size and added load in the normal way. This shows that patients can produce large, long bursts of EMG activity, but that there is a failure to match these parameters appropriately to the size of movement required. The effect of levodopa therapy on the movements was not dramatic. Although patients produced faster wrist movements when on medication than when off, the change was relatively small compared with the change seen in their overall clinical rating. Changes in the velocity of movements at a single joint are not a good reflection of the overall clinical state of patients with Parkinson's disease.     

Nigrostriatal dopamine system and motor lateralization

The mechanism by which most people favor use of the right hand remains unknown. It has been proposed that asymmetries in the nigrostriatal dopamine system may be related to motor lateralization in humans. We explored this hypothesis in vivo by using [18F]fluorodopa positron emission tomography. Whereas the degree of right hand preference was found to correlate with left putamen dominance as assessed by asymmetry in fluorodopa uptake (K(i)), right caudate dominance was positively correlated with the level of performance during simultaneous bimanual movements in right-handed normal subjects. In addition, right-handed patients with Parkinson's disease with higher right than left caudate K(i) performed much better in bimanual movement tests than those in whom the K(i) value of the left caudate was higher than that of the right. These findings support the notion that the nigrostriatal dopaminergic system may play a role in motor lateralization, and suggest a functional model for bimanual movements. We propose that the skill for performing simultaneous bilateral hand movements in right-handed subjects might depend upon both the activation (through the dominant left putamen circuitry) of the left supplementary motor area (SMA), and the inhibition (through the right caudate circuitry) of motor programs stored in the right SMA.