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.     

Planning dysfunction in schizophrenia: impairment of potentials preceding fixed/free and single/sequence of self-initiated finger movements

To test the hypothesis of a planning dysfunction in schizophrenia using a precise temporal definition, the readiness potential (RP), a negative cortical wave preceding self-initiated movements and reflecting motor preparation processes, was studied in patients under stable medication and in controls. The supplementary motor area (SMA), known to be involved in the generation of the RP, has also been implicated in movement selection (fixed versus free) and complexity (single versus sequence). This is the first study using RP for the assessment of the influence of these factors on motor preparation in schizophrenics. Our results show that schizophrenics' RP amplitude is significantly lower than in controls at central and contralateral electrodes. However, RP amplitude increases with task difficulty in both groups, offering important new insight into classical SMA hypoactivation in schizophrenics performing motor tasks. Topographic analysis shows that RP amplitude is, for both groups, significantly higher in sequence than in single movements at fronto-central sites and higher for free than for fixed movements at centro-parietal sites. Finally, RP onset occurs significantly later in schizophrenics than in controls. These results support the view of a motor-preparation and decision-making dysfunction in schizophrenia. They are interpreted within the framework of a fronto-striatal disorder in this disease.     

The current state of health care in the former Soviet Union: implications for health care policy and reform

OBJECTIVE: To study planning of movement in Parkinson's disease. METHODS: The spatiotemporal pattern of movement related desynchronisation (MRD) preceding a self paced voluntary wrist flexion was compared between two groups of 10 untreated right and left hemiparkinsonian patients receiving no treatment and 10 control subjects. The MRD was computed in the 9 to 11 Hz frequency band from 11 source derivations covering the frontocentral, central, and parietocentral areas, during two successive left and right experimental conditions. RESULTS: In the two patient groups the desynchronisation appeared over the primary sensorimotor area contralateral to the affected side with a shorter latency (750 ms before movement onset for the right hemiparkinsonian group and 875 ms for the left hemiparkinsonian group) than in the control group (1750 ms), only when the movements were performed with the akinetic hand. For the non-affected hand, the same latency as in the control group was noted (1750 ms). CONCLUSION: The delay of appearance of MRD in Parkinson's disease confirmed that the programming of movement is affected, thus partially explaining akinesia.     

Changing directions of forthcoming arm movements: neuronal activity in the presupplementary and supplementary motor area of monkey cerebral cortex

1. To understand roles played by two cortical motor areas, the presupplementary motor area (pre-SMA) and supplementary motor area (SMA), in changing planned movements voluntarily, cellular activity was examined in two monkeys (Macaca fuscata) trained to perform an arm-reaching task in which they were asked to press one of two target buttons (right or left) in three different task modes. 2. In the first mode (visual), monkeys were visually instructed to result and press either a right or left key in response to a forth coming trigger signal. In the second mode (stay), monkeys were required to wait for the trigger signal and press the same target key as pressed in preceding trials. In the third mode (shift), a 50 Hz auditory cue instructed the monkey to shift the target of the future reach from the previous target to the previous nontarget. 3. While the monkeys were performing this task, we recorded 399 task-related cellular activities from the SMA and the pre-SMA. Among them, we found a group of neurons that exhibited activity changes related specifically to shift trials (shift-related cells). The following properties characterized these 112 neurons. First, they exhibited activity changes after the onset of the 50-Hz auditory cue and before the movement execution when the monkeys were required to change the direction of forthcoming movement. Second, they were not active when the monkeys pressed the same key without changing the direction of the movements. Third, they were not active when the monkeys received the 50-Hz auditory cue but failed to change the direction of the movements by mistake. These observations indicate that the activity of shift-related cells is related to the redirection of the forthcoming movements, but not to the auditory instruction itself or to the location of the target key or the direction of the forthcoming movements. 4. Although infrequently, monkeys made errors in the stay trials and changed directions of the reach voluntarily. In that case, a considerably high proportion of shift-related neurons (12 of 19) exhibited significant activity changes long before initiation of the reach movement. These long-lasting activities were not observed during the preparatory period in correct stay trials, but resembled the shift-related activity observed when the target shift was made toward the same direction. Thus these activity changes were considered to be also related to the process of changing the intended movements voluntarily. 5. We found another population of neurons that showed activity modulation when the target shift was induced by the visual instruction in visual trials (visually guided shift-related neurons). These neurons were active when the light-emitting diode (LED) guided the forthcoming reach to the previous nontarget but not to the previous target. Therefore their activity was not a simple visual response to the LED per se. A majority of them also showed shift-related activity in shift trials (19 of 22 in monkey 2). 6. Neurons exhibiting the shift-related activity were distributed differentially among the two areas. In the pre-SMA, 31% of the neurons recorded showed the shift-related activity, whereas in the SMA, only 7% showed such an activity. These results suggest that pre-SMA and SMA play differential roles in updating the motor plans in accordance with current requirements.     

Movement sequence-related activity reflecting numerical order of components in supplementary and presupplementary motor areas

The supplementary motor area (SMA) and presupplementary motor areas (pre-SMA) have been implicated in movement sequencing, and neurons in SMA have been shown to encode what might be termed the relational order among sequence components (e.g., movement X followed by movement Y). To determine whether other aspects of movement sequencing might also be encoded by SMA or pre-SMA neurons, we analyzed task-related activity recorded from both areas in conjunction with a sequencing task that dissociated the numerical order of components (e.g., movement X as the 2nd component, irrespective of which movements precede or follow X). Sequences were constructed from eight component movements, each characterized by three spatial variables (origin, direction, and endpoint). Task-related activity recorded from 56 SMA and 63 pre-SMA neurons was categorized according to both the epoch (delay, reaction time, and movement time) and the spatial variable or component movement with which it was associated. All but one instance of task-related activity was selective for one of the spatial variables (SV-selective) rather than for any of the component movements themselves. Of 110 instances of SV-selective activity in SMA, 43 (39%) showed significant effects of numerical order. The corresponding incidence in pre-SMA, 82 (71%) of 116, was substantially higher (P < 0.00001). No effects of numerical order were evident among the hand paths, movement times, or electromyographic activity associated with task performance. We concluded that neurons in SMA and pre-SMA may encode the numerical order of components, at least for sequences that are distinguished mainly by that aspect of component ordering.     

Increased dependence on visual information for movement control in patients with Parkinson's disease

Studies were made of visually and non-visually guided movements by patients with Parkinson's disease. The subjects moved a light, horizontal handle using rotation primarily about the elbow. During visually guided trials both handle and target positions were displayed to the subject; during non-visually guided trials only the handle position was displayed. During non-visually guided trials all patients showed a tendency for an overall flexion drift, although there was no change in average movement amplitude. The overall error in position by the end of the non-visually guided trials was greatly in excess of the reported values for passive displacement thresholds in normal subjects. It is suggested that the data indicate an increased dependence on visual information for control of motor activity in Parkinson's patients.     

Retinal arterial occlusions in young adults

Stereotactic posteroventral pallidotomy can improve motor performance in Parkinson's disease. Interruption of inhibitory pallidal projections to ventrolateral thalamus, components of a cortical-basal ganglia motor loop allows for this clinical benefit. We hypothesized that pallidotomy would lead to increased movement related activity in motor cortical areas receiving projections from ventrolateral thalamus. This was tested in 6 Parkinson's disease patients who underwent stereotactic posteroventral pallidotomy. Each patient was imaged with positron emission tomography (PET) measures of regional cerebral blood flow (rCBF) during performance of a simple prehension task and at rest. Scans were acquired before and 17 weeks after surgery. After pallidotomy, movement-related changes of rCBF increased significantly in both the supplementary motor area (SMA) and premotor cortex but not in primary motor cortex. The results demonstrate the importance of pallidothalamic circuitry for regulating volitional movements and confirm that disruption of inhibitory input to the ventrolateral thalamus can augment movement-related activity in motor association areas.     

Visual "closed-loop" and "open-loop" characteristics of voluntary movement in patients with Parkinsonism and intention tremor

Normal voluntary movements are considered to be of two kinds, or to involve two components, (i) a ballistic or "open-loop" type, which are preprogrammed and executed without reference to current sensory information and (ii) a corrective or "closed-loop" type, whose course or termination are regulated by such information. In a previous paper it was suggested that Parkinsonism disrupted the first kind of movement, but intention tremor did not. In the present paper three experiments designed to test this hypothesis are described. Subjects were tested on an acquisition-tracking task using an oscilloscope display and joystick control, and measurements were made of the duration, velocity and error of their initial movements to acquire the target. Parkinsonian movements were found to be considerably different from normal in that (a) most movements by this group lasted longer than the reaction time for their initiation, as if including some secondary correction in their execution, (b) the rate of movement was not varied for different amplitudes (so keeping the duration fairly constant) as in normal subjects, but rather movements of all amplitudes were made at a constant slow rate, so that duration increased markedly with the larger steps, (c) error increased disproportionately as the velocity of movement increased; in particular any movements completed in one reaction time or less tended to be wildly inaccurate, (d) removing either the target or the response marker from the screen at the beginning of a movement had a significant effect, making it shorter in duration and smaller in amplitude than those usually produced with both markers visible all the time. Parkinsonian subjects showed no improvement in performance with repeated attempts at one movement over a whole sequence, so their deficit appears to be stable even after practice on a known fixed task. These results are interpreted as supporting the hypothesis that Parkinsonism interferes with the generation of accurate ballistic action which are characteristic of normal skilled movement. Tremor subjects in general resembled normal control subjects in their initial acquistion movements, but their accuracy was less with the larger steps.     

Step-tracking movements of the wrist. IV. Muscle activity associated with movements in different directions

We examined the patterns of muscle activity associated with multiple directions of step-tracking movements of the wrist in humans and monkeys. Human subjects made wrist movements to 12 different targets that required varying amounts of flexion-extension and radial-ulnar deviation. Wrist muscles displayed two patterns of electromyographic (EMG) modulation as movement direction changed: amplitude graded and temporally shifted. The amplitude-graded pattern was characterized by modulation of the quantity of muscle activity that occurred during two distinct time periods, an agonist burst interval that began before movement onset and an antagonist burst interval that began just after movement onset. The timing of muscle activity over the two intervals showed little variation with changes in movement direction. For some directions of movement, EMG activity was present over both time intervals, resulting in "double bursts." Modulation of activity during the agonist burst interval was particularly systematic and was well fit by a cosine function. In contrast, the temporally shifted pattern was characterized by a gradual change in the timing of a single burst of muscle activity. The burst occurred at a time intermediate between the agonist and antagonist burst intervals. The temporally shifted pattern was seen less frequently than the amplitude-graded pattern and was present only in selected wrist muscles for specific directions of movement. Monkeys made wrist movements to 8-16 different targets that required varying amounts of flexion-extension and radial-ulnar deviation. These movements were performed more slowly than those of human subjects. The wrist muscles of the monkeys we examined displayed the amplitude-graded pattern of activity but not the temporally shifted pattern. Stimulation of individual wrist muscles in monkeys resulted in wrist movements that were markedly curved, particularly for the wrist extensors. These results indicate that step-tracking movements of the wrist are generated mainly by using the amplitude-graded pattern to modulate muscle activity. We propose that this pattern reflects a central process that decomposes an intended movement into an agonist, "propulsive" component and an antagonist, "braking" component. Separate bursts of muscle activity then are generated to control each component. On the other hand, we argue that the temporally shifted pattern may function to reduce the amount of movement curvature associated with the activation of wrist muscles.     

Age-associated modulation of apoptosis and activation in murine B lymphocytes

We examined neuronal activity in three motor cortical areas while a rhesus monkey adapted to novel visuomotor transforms. The monkey moved a joystick that controlled a cursor on a video screen. Each trial began with the joystick centered. Next, the cursor appeared in one of eight positions, arranged in a circle around a target stimulus at the center of the screen. To receive reinforcement, the monkey moved the joystick so that the cursor contacted the target continuously for Is. The video monitor provided continuous visual feedback of both cursor and target position. With those elements of the task constant, we modified the transform between joystick movement and that of the cursor at the beginning of a block of trials. Neuronal activity was studied as the monkey adapted to these novel joystick-cursor transforms. Some novel tasks included spatial transforms such as single-axis inversions, asymmetric double-axis inversions and angular deviations (also known as rotations). Other tasks involved changes in the spatiotemporal pattern and magnitude of joystick movement. As the monkey adapted to various visuomotor tasks, 209 task-related neurons (selected for stable background activity) showed significant changes in their task-related activity: 88 neurons in the primary motor cortex (M1), 32 in the supplementary motor cortex (M2), and 89 in the caudal part of the dorsal premotor cortex (PMdc). Slightly more than half of the sample in each area showed significant changes in the magnitude of activity modulation during adaptation, with the number of increases approximately equaling the number of decreases. These data support the prediction that changes in task-related neuronal activity can be observed in M1 during motor adaptation, but fail to support the hypothesis that M1 and PMdc differ in this regard. When viewed in population averages, motor cortex continued to change its activity for at least dozens of trials after performance reached a plateau. This slow, apparently continuing change in the pattern and magnitude of task-related activity may reflect the initial phases of consolidating the motor memory for preparing and executing visuomotor skills.     

Pointing errors reflect biases in the perception of the initial hand position

By comparing the visuomotor performance of 10 adult, normal subjects in three tasks, we investigated whether errors in pointing movements reflect biased estimations of the hand starting position. In a manual pointing task with no visual feedback, subjects aimed at 48 targets spaced regularly around two starting positions. Nine subjects exhibited a similar pattern of systematic errors across targets, i.e., a parallel shift of the end points that accounted, on average, for 49% of the total variability. The direction of the shift depended on the starting location. Systematic errors decreased dramatically in the second condition where subjects were allowed to see their hand before movement onset. The third task was to use a joystick held by the left hand to estimate the location of their (unseen) right hand. The systematic perceptual errors in this condition were found to be highly correlated with the motor errors in the first condition. The results support the following conclusions. 1) Kinesthetic estimation of hand position may be consistently biased. Some of the mechanisms responsible for these biases are always active, irrespective of whether position is estimated overtly (e.g., with a matching paradigm), or covertly as part of the motor planning for aimed movements. 2) Pointing errors reflect to a significant extent the erroneous estimation of initial hand position. This suggests that aimed hand movements are planned vectorially, i.e., in terms of distance and direction, rather than in terms of absolute position in space.     

Functional anatomy of pointing and grasping in humans

The functional anatomy of reaching and grasping simple objects was determined in nine healthy subjects with positron emission tomography imaging of regional cerebral blood flow (rCBF). In a prehension (grasping) task, subjects reached and grasped illuminated cylindrical objects with their right hand. In a pointing task, subjects reached and pointed over the same targets. In a control condition subjects looked at the targets. Both movement tasks increased activity in a distributed set of cortical and subcortical sites: contralateral motor, premotor, ventral supplementary motor area (SMA), cingulate, superior parietal, and dorsal occipital cortex. Cortical areas including cuneate and dorsal occipital cortex were more extensively activated than ventral occipital or temporal pathways. The left parietal operculum (putative SII) was recruited during grasping but not pointing. Blood flow changes were individually localized with respect to local cortical anatomy using sulcal landmarks. Consistent anatomic landmarks from MRI scans could be identified to locate sensorimotor, ventral SMA, and SII blood flow increases. The time required to complete individual movements and the amount of movement made during imaging correlated positively with the magnitude of rCBF increases during grasping in the contralateral inferior sensorimotor, cingulate, and ipsilateral inferior temporal cortex, and bilateral anterior cerebellum. This functional-anatomic study defines a cortical system for "pragmatic' manipulation of simple neutral objects.     

Movement-related potentials accompanying unilateral finger movements with special reference to rate of force development

The aim of this study was to examine the relationship between force and rate of force development with electroencephalogram correlates. The primary question was whether the different components of movement related potentials (MRPs) were related to specific properties of force output while subjects performed index finger force production tasks. The peak force and rate of force development (e.g., a product of peak force over time-to-peak force) were manipulated, and the effects of these manipulations on components of MRPs preceding and accompanying force production tasks were examined. The hypothesis was that the rate of force development, rather than level of force itself, would directly influence the later component of MRPs. Consistent with this hypothesis was the finding that the amplitudes of MRP components preceding (MP) and accompanying (MMP, MTP) finger force production movements were significantly correlated with force development rate.     

Sequence heterogeneity in Parkinsonian speech

Parkinson's disease (PD) is a neurodegenerative movement disorder primarily due to basal ganglia dysfunction. While much research has been conducted on Parkinsonian deficits in the traditional arena of musculoskeletal limb movement, research in other functional motor tasks is lacking. The present study examined articulation in PD with increasingly complex sequences of articulatory movement. Of interest was whether dysfunction would affect articulation in the same manner as in limb-movement impairment. In particular, since very similar (homogeneous) articulatory sequences (the tongue twister effect) are more difficult for healthy individuals to achieve than dissimilar (heterogeneous) gestures, while the reverse may apply for skeletal movements in PD, we asked which factor would dominate when PD patients articulated various grades of artificial tongue twisters: the influence of disease or a possible difference between the two motor systems. Execution was especially impaired when articulation involved a sequence of motor program heterogeneous in terms of place of articulation. The results are suggestive of a hypokinesic tendency in complex sequential articulatory movement as in limb movement. It appears that PD patients do show abnormalities in articulatory movement which are similar to those of the musculoskeletal system. The present study suggests that an underlying disease effect modulates movement impairment across different functional motor systems.     

Sustained activity in the medial wall during working memory delays

We have taken advantage of the temporal resolution afforded by functional magnetic resonance imaging (fMRI) to investigate the role played by medial wall areas in humans during working memory tasks. We demarcated the medial motor areas activated during simple manual movement, namely the supplementary motor area (SMA) and the cingulate motor area (CMA), and those activated during visually guided saccadic eye movements, namely the supplementary eye field (SEF). We determined the location of sustained activity over working memory delays in the medial wall in relation to these functional landmarks during both spatial and face working memory tasks. We identified two distinct areas, namely the pre-SMA and the caudal part of the anterior cingulate cortex (caudal-AC), that showed similar sustained activity during both spatial and face working memory delays. These areas were distinct from and anterior to the SMA, CMA, and SEF. Both the pre-SMA and caudal-AC activation were identified by a contrast between sustained activity during working memory delays as compared with sustained activity during control delays in which subjects were waiting for a cue to make a simple manual motor response. Thus, the present findings suggest that sustained activity during working memory delays in both the pre-SMA and caudal-AC does not reflect simple motor preparation but rather a state of preparedness for selecting a motor response based on the information held on-line.     

Integration of auditory and kinesthetic information in motion: Alterations in Parkinson's disease.

The main aim in this work was to study the interaction between auditory and kinesthetic stimuli and its influence on motion control. The study was performed on healthy subjects and patients with Parkinson's disease (PD). Thirty-five right-handed volunteers (young, PD, and age-matched healthy participants, and PD-patients) were studied with three different motor tasks (slow cyclic movements, fast cyclic movements, and slow continuous movements) and under the action of kinesthetic stimuli and sounds at different beat rates. The action of kinesthesia was evaluated by comparing real movements with virtual movements (movements imaged but not executed). The fast cyclic task was accelerated by kinesthetic but not by auditory stimuli. The slow cyclic task changed with the beat rate of sounds but not with kinesthetic stimuli. The slow continuous task showed an integrated response to both sensorial modalities. These data show that the influence of the multisensory integration on motion changes with the motor task and that some motor patterns are modulated by the simultaneous action of auditory and kinesthetic information, a cross-modal integration that was different in PD-patients. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Primary motor cortex is involved in bimanual coordination

Many voluntary movements involve coordination between the limbs. However, there have been very few attempts to study the neuronal mechanisms that mediate this coordination. Here we have studied the activity of cortical neurons while monkeys performed tasks that required coordination between the two arms. We found that most neurons in the primary motor cortex (MI) show activity specific to bimanual movements (bimanual-related activity), which is strikingly different from the activity of the same neurons during unimanual movements. Moreover, units in the supplementary motor area (SMA; the area of cortex most often associated with bimanual coordination) showed no more bimanual-related activity than units in MI. Our results challenge the classic view that MI controls the contralateral (opposite) side of the body and that SMA is responsible for the coordination of the arms. Rather, our data suggest that both cortical areas share the control of bilateral coordination.     

Passover and plague

Patients with unilateral neglect following right hemisphere damage may have difficulty in moving towards contralesional targets. To test the hypothesis that this impairment arises from competing motor programs triggered by irrelevant ipsilesional stimuli, we examined 16 right hemisphere patients, eight with left visual neglect and eight without, in addition to eight healthy control subjects. In experiment 1 subjects performed sequences of movements using their right hand to targets on the contralesional or ipsilesional side of the responding limb. The locations of successive targets in each sequence were either predictable or unpredictable. In separate blocks of trials, targets appeared either alone or with a simultaneous distractor located at the immediately preceding target location. Neglect patients were significantly slower to execute movements to contralesional targets, but only for unpredictable movements and in the presence of a concurrent ipsilesional distractor. In contrast, healthy controls and right hemisphere patients without neglect showed no directional asymmetries of movement execution. In experiment 2 subjects were required to interrupt a predictable, reciprocating sequence of leftward and rightward movements in order to move to an occasional, unpredictable target that occurred either in the direction opposite to that expected, or in the same direction but twice the extent. Neglect patients were significantly slower in reprogramming the direction and extent of movements towards contralesional versus ipsilesional targets, and they also made significantly more errors when executing such movements. Right hemisphere patients without neglect showed a similar bias in reprogramming direction (but not extent) for contralesional targets, whereas healthy controls showed no directional asymmetry in either condition. On the basis of these findings we propose that neglect involves a competitive bias in favour of motor programs for actions directed towards ipsilesional versus contralesional events. We suggest that programming errors and increased latencies for contralesional movements arise because the damaged right hemisphere can no longer effectively inhibit the release of inappropriate motor programs towards ipsilesional events.     

Development of a scoring system to assess disability in an Italian elderly population. Evaluation of a disability questionnaire

Patients with idiopathic and symptomatic restless legs syndrome (RLS) suffer from "dyskinesia while awake" or "daytime myoclonus" when at rest preceded by sensory symptoms. In order to characterise the RLS either as reflex movement or as voluntary movement we measured movement-related cortical potentials in 5 idiopathic and 8 uraemic RLS patients. Movements from both legs were polygraphically recorded concomitantly with cortical activity 2000 msec before to 500 msec after onset of EMG activity. These data were compared with a voluntary simulation of each patient's movement pattern and with 5 age-matched controls performing dorsiflexion of the right, left and both feet. Cortical activity preceding daytime myoclonus was absent in RLS patients whereas self-initiated leg movements in patients elicited onset times (1180-1380 msec) and amplitudes of Bereitschaftspotential (readiness potential) not significantly different from readiness potentials in control subjects (P > 0.05). Lack of movement-related potentials in myoclonus and/or dyskinesias during daytime in RLS patients is compatible with an involuntary mechanism of induction and points towards a subcortical or spinal origin of RLS.     

beta-endorphin1-31 in the rat pituitary

The behavioral and neural correlates of processing of motor directional information are described for two visuomotor tasks: mental rotation and context-recall. Psychological studies with human subjects suggested that these two tasks involve different time-consuming processes of directional information. Analyses of the activity of single cells and neuronal populations in the motor cortex of behaving monkeys performing in the same tasks provided direct insight into the neural mechanisms involved and confirmed their different nature. In the mental rotation task the patterns of neuronal activity revealed a rotation of the intended direction of movement. In contrast, in the context-recall task the patterns of neural activity identified a switching process of the intended direction of movement.