Finger tapping movements of Parkinson's disease patients automatically rated using nonlinear delay differential equations.

Parkinson's disease is a degenerative condition whose severity is assessed by clinical observations of motor behaviors. These are performed by a neurological specialist through subjective ratings of a variety of movements including 10-s bouts of repetitive finger-tapping movements. We present here an algorithmic rating of these movements which may be beneficial for uniformly assessing the progression of the disease. Finger-tapping movements were digitally recorded from Parkinson's patients and controls, obtaining one time series for every 10 s bout. A nonlinear delay differential equation, whose structure was selected using a genetic algorithm, was fitted to each time series and its coefficients were used as a six-dimensional numerical descriptor. The algorithm was applied to time-series from two different groups of Parkinson's patients and controls. The algorithmic scores compared favorably with the unified Parkinson's disease rating scale scores, at least when the latter adequately matched with ratings from the Hoehn and Yahr scale. Moreover, when the two sets of mean scores for all patients are compared, there is a strong (r = 0.785) and significant (p<0.0015) correlation between them.

Rhythmic movement in Parkinson's disease: effects of visual feedback and medication state.

Previous studies examining discrete movements of Parkinson's disease (PD) patients have found that in addition to performing movements that were slower than those of control participants, they exhibit specific deficits in movement coordination and in sensorimotor integration required to accurately guide movements. With medication, movement speed was normalized, but the coordinative aspects of movement were not. This led to the hypothesis that dopaminergic medication more readily compensates for intensive aspects of movement (such as speed), than for coordinative aspects (such as coordination of different limb segments) (Schettino et al., Exp Brain Res 168:186-202, 2006). We tested this hypothesis on rhythmic, continuous movements of the forearm. In our task, target peak speed and amplitude, availability of visual feedback, and medication state (on/off) were varied. We found, consistent with the discrete-movement results, that peak speed (intensive aspect) was normalized by medication, while accuracy, which required coordination of speed and amplitude modulation (coordinative aspect), was not normalized by dopaminergic treatment. However, our findings that amplitude, an intensive aspect of movement, was also not normalized by medication, suggests that a simple pathway gain increase does not act to remediate all intensive aspects of movement to the same extent. While it normalized movement peak speed, it did not normalize movement amplitude. Furthermore, we found that when visual feedback was not available, all participants (PD and controls) made faster movements. The effects of dopaminergic medication and availability of visual feedback on movement speed were additive. The finding that movement speed uniformly increased both in the PD and the control groups suggests that visual feedback may be necessary for calibration of peak speed, otherwise underestimated by the motor control system.

Non-monotonicity on a spatio-temporally defined cyclic task: evidence of two movement types?

We tested 23 healthy participants who performed rhythmic horizontal movements of the elbow. The required amplitude and frequency ranges of the movements were specified to the participants using a closed shape on a phase-plane display, showing angular velocity versus angular position, such that participants had to continuously control both the speed and the displacement of their forearm. We found that the combined accuracy in velocity and position throughout the movement was not a monotonic function of movement speed. Our findings suggest that specific combinations of required movement frequency and amplitude give rise to two distinct types of movements: one of a more rhythmic nature, and the other of a more discrete nature.

Visual and "phonetic" coding of movement: evidence from American sign language.

Hearing subjects unfamiliar with American Sign Language and deaf native signers made triadic comparisons of movements of the hands and arms isolated from American Sign Language. Clustering and scaling of subjects' judgments revealed different psychological representations of movement form for deaf and hearing observers. Linguistically relevant dimensions acquired modified salience for users of a visual-gestural language. The data indicate that the modification of natural perceptual categories after language acquisition is not bound to a particular transmission modality, but rather can be a more general consequence of acquiring a formal linguistic system.

Visual and "phonetic" coding of movement: evidence from american sign language.

Hearing subjects unfamiliar with American Sign Language and deaf native signers made triadic comparisons of movements of the hands and arms isolated from American Sign Language. Clustering and scaling of subjects' judgments revealed different psychological representations of movement form for deaf and hearing observerd. Linguistically relevant dimensions acquired modified salience for users ofa visual-gestural language. The data indicate that the modification of natural perceptual categories after language acquisition is not bound to a particular transmission modality, but rather can be a more general consequence of acquiring a formal linguistic system.

Deep brain stimulation of the subthalamic nucleus facilitates coordination of hand preshaping in Parkinson's disease.

Several studies have found that Parkinson's disease (PD) disrupts the organization of complex motor sequences regardless of the influence of parkinsonian medications. A clear candidate for the neural bases of such deficits, which we term "coordinative," is the failure to integrate propioceptive and visual information by cortico-striatal circuits in a timed fashion. Recent reports, however, have indicated that deep-brain stimulation of the subthalamic nucleus (STN DBS) may result in an improvement in coordinative deficits beyond the amelioration of "intensive deficits" such as bradykinesia and scaling errors. The present study examined the spatio-temporal organization underlying the shaping of the hand during reaching to grasp objects differing in shape. Six PD patients ON and OFF their STN DBS when OFF their concomitant medications and six age-matched controls participated in this study. STN DBS improved the coordination involved in preshaping the hand while grasping. We discuss these results in light of our earlier work with PD patients on and off dopamine replacement therapy.

Dopamine replacement therapy does not restore the ability of Parkinsonian patients to make rapid adjustments in motor strategies according to changing sensorimotor contexts.

The ability of dopamine replacement to restore rapid motor adjustments in Parkinson's disease (PD) was investigated. Medicated and non-medicated patients performed finger-to-nose movements while simultaneously bending the trunk forward, without vision. Trunk motion was blocked unexpectedly, necessitating rapid adjustments in arm trajectories. Patients exhibited irregular hand paths, plateaus in hand velocity, and prolonged movement times, which were significantly greater in perturbed trials. Medication improved kinematics but perturbation-induced disturbances persisted and did not approximate the levels of non-perturbed trials nor those of controls. Dopaminergic replenishment in PD may therefore have limited restorative benefits for rapid context-specific motor control.

Language, modality and the brain.

Studies of the signed languages of deaf people have shown that fully expressive languages can arise, outside of the mainstream of spoken languages, that exhibit the complexities of linguistic organization found in all spoken languages. Thus, the human capacity for language is not linked to some privileged cognitive-auditory connection. However, the formal properties of languages (spoken or signed) appear to be highly conditioned by the modalities involved in their perception and production. Multi-layering of linguistic elements and the use of space in the service of syntax appear to be modality-determined aspects of signed languages. Analyses of patterns of breakdown of signed languages provide new perspectives on the nature of cerebral organization for language. The studies reviewed in this article show that the left cerebral hemisphere in man is specialized for signed as well as spoken languages, and thus may have an innate predisposition for language, independent of language modality.

Hand dominance for signing: clues to brain lateralization of language.

Virtually all right-handed individuals are left hemisphere dominant for language. Sign languages of the deaf provide an unusual vehicle for exploring the link between handedness and hemispheric specialization for language since in sign language the hands themselves are the language articulators. Performance of the right and left hand was examined in deaf native users of American Sign Language (ASL) for speeded production of one-handed signs and for shadowing of signed discourse. Opposite patterns of asymmetries in hand performance were found in right- and left-handers. However, left-handers were more flexible than right-handers in signing with their non-preferred hand. Furthermore, unusual patterns of hand use for sign were found in a deaf signer with a left hemisphere lesion, possibly indexing increased mediation of the intact hemisphere. Implications for brain organization of language in a visual-gestural mode are discussed.

Interarticulator co-ordination in deaf signers with Parkinson's disease.

Motor control deficits in signers with Parkinson's disease (PD) were examined through analysis of their production of American Sign Language (ASL) fingerspelling, which is sequential and rapid motor behavior that has theoretical models of its underlying structure. Free conversation of two Deaf signers with PD and two Deaf control signers was analysed. In addition, scripted productions of one control signer were also analysed and directly compared to the same productions by the signers with PD. A featural analysis of ASL fingerspelling and a frame-by-frame analysis of multiple articulator movements were used to examine the fingerspelled productions. On the basis of the featural analysis, the signers with PD showed a variety of error patterns, all of which reflected attempts to reduce the motoric demands of coarticulation and thereby facilitate ease of articulation. Signers with PD either held individual segments in a fingerspelling sequence for a long time (segmentation), blended adjacent segments into a single segment (sequential blending), or broke handshapes down sequentially into their component features (featural unraveling). The results of both the featural analysis and the frame-by-frame analysis show that the PD signers have difficulty co-ordinating the movements of independent articulators in complex sequences. For example, the movements of independent articulators for fingerspelling (the thumb, fingers, and wrist) were markedly farther apart in time and more variable for the signers with PD. In addition, the signers with PD used fewer wrist movements while fingerspelling. Such deficits are consistent with claims that patients with PD are impaired in their ability to use ongoing sensorimotor information to program multi-articulator movements.

Automatic orienting of visuospatial attention in Parkinson's disease.

The basal ganglia are involved in not only motor behavior, but also other more cognitive processes, such as attention. We tested Parkinson's disease (PD) patients in a task that measures reflexive orienting of spatial attention. Seven patients with idiopathic PD and eight control subjects performed a covert orienting task where spatial attention was directed by means of exogenous cues (luminance increments) with no predictive validity for target position. The subjects' task was to make a speeded saccade to a visual target, which appeared a variable time after onset of the cue either in the cued or an uncued spatial position. There was no overall difference between PD patients and control subjects in terms of the initial facilitation following reflexive cues, and later inhibition of return (IOR). However, PD patients differed from control subjects in two important respects. First, they were significantly faster than were control subjects on this reflexive visual-orienting task. Second, disease severity correlated with attentional performance; more advanced patients showed less initial facilitation but greater IOR. Thus PD patients show better performance on a reflexive saccade task and, for more advanced patients, greater IOR than control subjects. These findings are consistent with the possibility that reflexive attentional processes in PD patients may be more active.

Visual-imitative dissociation apraxia.

Liepmann posited that, in right handers, the left parietal lobe contains movement formulas or representations. Therefore, performance failures may be induced by degraded representations, a failure of these representations to influence motor systems or a failure of stimuli to fully access these representations. Imitation may help the performance of subjects with degraded representations. However, patients who have impaired visual access to movement representations may perform more poorly with imitation than to verbal command. Trajectories of repetitive 'slicing' gestures made by a previously reported subject (Raymer et al.) with an infarction in the left visual association cortex (left occipital and inferior temporal lobe) that spared the parietal lobe were contrasted with those of three apraxic subjects with lesions that included the left parietal lobe and four non-brain-damaged control subjects. All subjects were asked to produce the gesture to verbal command and to imitation. Movements of the left hand, wrist, elbow and shoulder were digitized from neighboring views, reconstructed in three dimensions, and analysed graphically and numerically. The apraxic subjects with left parietal damage were unable to maintain the proper linearity and spatiotemporal attributes of their wrist motions and showed interjoint coordination deficits. Their deficits were most pronounced to verbal command, with their movements improving though remaining poorly performed when they imitated. The subject with the left occipital and inferior temporal lesion that spared parietal cortex, however, showed an opposite pattern. This subject exhibited close to normal performance when producing the movement to verbal command, but significant deficits when imitating.

The interaction of visual and proprioceptive inputs in pointing to actual and remembered targets in Parkinson's disease.

We previously reported that Parkinson's disease patients could point with their eyes closed as accurately as normal subjects to targets in three-dimensional space that were initially presented with full vision. We have now further restricted visual information in order to more closely examine the individual and combined influences of visual information, proprioceptive feedback, and spatial working memory on the accuracy of Parkinson's disease patients. All trials were performed in the dark. A robot arm presented a target illuminated by a light-emitting diode at one of five randomly selected points composing a pyramidal array. Subjects attempted to "touch" the target location with their right finger in one smooth movement in three conditions: dark, no illumination of arm or target during movement; movement was to the remembered target location after the robot arm retracted; finger, a light-emitting diode on the pointing fingertip was visible during the movement but the target was extinguished; again, movement was to the remembered target location; and target, the target light-emitting diode remained in place and visible throughout the trial but there was no vision of the arm. In the finger condition, there is no need to use visual-proprioceptive integration, since the continuously visualized fingertip position can be compared to the remembered location of the visual target. In the target condition, the subject must integrate the current visible target with arm proprioception, while in the dark condition, the subject must integrate current proprioception from the arm with the remembered visual target. Parkinson's disease patients were significantly less accurate than controls in both the dark and target conditions, but as accurate as controls in the finger condition. Parkinson's disease patients, therefore, were selectively impaired in those conditions (target and dark) which required integration of visual and proprioceptive information in order to achieve accurate movements. In contrast, the patients' normal accuracy in the finger condition indicates that they had no substantial deficits in their relevant spatial working memory. Final arm configurations were significantly different in the two subject groups in all three conditions, even in the finger condition where mean movement endpoints were not significantly different. Variability of the movement endpoints was uniformly increased in Parkinson's disease patients across all three conditions. The current study supports an important role for the basal ganglia in the integration of proprioceptive signals with concurrent or remembered visual information that is needed to guide movements. This role can explain much of the patients' dependence on visual information for accuracy in targeted movements. It also underlines what may be an essential contribution of the basal ganglia to movement, the integration of afferent information that is initially processed through multiple, discrete modality-specific pathways, but which must be combined into a unified and continuously updated spatial model for effective, accurate movement.

Azimuth errors in pointing to remembered targets under extreme head rotations.

Errors in pointing to remembered target locations in 3-D space were studied when subjects were free to move their heads, and when they rotated their heads to the extreme right or left. Relative to pointing when the head was free to move, head rotations to the right shifted the final position of the responding arm to the left, whereas head rotations to the left shifted the final position of arm to the right. Horizontal rotation of the head had no systematic influence on elevation and radial distance errors. The influence of head rotations on pointing errors may be mediated by small shifts in the internal representation of external space, shifting the presentation of space in the opposite direction of the head rotation.

Computergraphic modeling and analysis II: three-dimensional reconstruction and interactive analysis.

The analysis of human motion can be advanced by analyzing motion not only numerically, but also graphically. A new system is presented for the computergraphic analysis of human motion in three-dimensional space. The system allows the three-dimensional reconstruction, visualization, manipulation, and graphic editing of digitized movement trajectories. An entire sequence of the positions of the arm in three-dimensional space can be displayed simultaneously, or the actual motion can be recreated in real time. Along with the reconstruction of the spatial path, the temporal characteristics of the movement can be concurrently displayed. Graphic procedures for interactively examining couplings between spatial and temporal aspects of trajectories were developed. Finally, based on digitized trajectories, stimuli can be generated and sequenced in real time for studies of the perception of motion. In conjunction with new methods of three-dimensional movement tracking, the computergraphic methods presented here offer new approaches to the analysis of human movement and its underlying neural control.

A novel quantitative method for 3D measurement of Parkinsonian tremor.

OBJECTIVE: To demonstrate the usefulness of a three dimensional (3D) motion analysis system for the quantitative measurement of tremor in patients with Parkinson's disease (PD). METHODS: Six PD patients with hand tremors were studied using a system that employed 3D electromagnetic position sensors to measure the actual, cumulative displacement of the tremoring finger. Patients were studied in different hand positions and activating conditions before and 30, 60, 90 and 120 min after intake of Pramipexole, a dopamine agonist known to reduce tremor. Tremor amplitude and frequency, before and after drug intake, were compared using Mann-Whitney U test and Wilcoxon rank test, respectively. RESULTS: The motion analysis system allowed discrimination of tremor related events from movement artifact and allowed the calculation of real world movement of the finger tremor despite altered hand positions and orientation. Average 3D tremor frequency ranged from 3.71 to 4.34 Hz. Median tremor amplitude (total distance traveled per 5 s interval) decreased with drug from 4.9 to 1.6 cm for resting tremor, 4.5 to 3.7 cm for postural tremor, 3.4 to 3.3 cm for precision tremor, 10.2 to 3.3 cm for tapping activation and 108.6 to 5.7 cm for counting activation. CONCLUSIONS: Our method of 3D analysis provides a robust, single quantitative measure of tremor amplitude that is intuitive and likely to reflect the functional impact of tremor. This methodology should be useful in comparing tremor across patients and in measuring the efficacy of therapeutic interventions.

Influence of movement speed on accuracy of pointing to memorized targets in 3D space.

Subjects performed three-dimensional (3D) pointing movements as accurately as possible with their eyes closed under four different speed conditions: 'slow', 'normal', 'fast' and 'maximal' (peak velocities of 0.62, 1.61, 2.51 and 4.68 m/s, respectively). Movement speed did not significantly affect the magnitude of constant pointing errors, nor that of variable errors, except for movements in the 'maximal' condition when peak velocity values larger than 4.5 m/s were reached. The findings are consistent with the hypothesis that final arm position may be specified regardless of movement dynamics.

Left hemispheric specialization for learned, skilled, and purposeful action.

Three-dimensional motion analyses were performed on trajectories of repetitive "slicing" gestures by 4 participants with left-hemisphere lesions and limb apraxia, 6 participants with right-hemisphere lesions, and 7 neurologically intact participants. Left hemispheric lesioned participants with apraxia, but not right hemispheric lesioned participants showed impaired coupling of spatial and temporal aspects of wrist trajectories and deficits in interjoint coordination. Both groups of brain-lesioned participants differed from control participants in the 3-D plane of the wrist motion. The deficits of some right hemispheric lesioned participants in controlling the plane of wrist motion may be a consequence of left hemispatial neglect with rightward deviations. In contrast, the deficits of apraxic participants in controlling wrist trajectories and coordinating joint motions seem to reflect a deficit in these participants for the movement plan.

Crossed apraxia: implications for handedness.

Liepmann posited that right hand preference relates to left hemisphere dominance for learned skilled movements. Limb apraxia, impairment of skilled movement, typically occurs in individuals with left hemisphere (LH) lesions. The occurrence of apraxia in right-handed individuals following right-hemisphere lesions appears to refute Liepmann's hypothesis. We studied the apraxia of a right-handed man, RF, following a right frontal lesion to determine whether his apraxia paralleled the apraxia seen following LH lesions. Results of behavioral testing indicated that, like individuals with apraxia following left frontal lesions, RF was better at gesture recognition than gesture production which was significantly impaired across tasks. Kinematic motion analyses of movement linearity, planarity, and the coupling of temporospatial aspects of movements substantiated the parallel impairments in RF and patients with LH apraxia. The impairment seen in our patient with crossed apraxia provides evidence for the fractionation of systems underlying hand preference and skilled movement.

Virtual reality-enhanced stroke rehabilitation.

A personal computer (PC)-based desktop virtual reality (VR) system was developed for rehabilitating hand function in stroke patients. The system uses two input devices, a CyberGlove and a Rutgers Master II-ND (RMII) force feedback glove, allowing user interaction with a virtual environment. This consists of four rehabilitation routines, each designed to exercise one specific parameter of hand movement: range, speed, fractionation or strength. The use of performance-based target levels is designed to increase patient motivation and individualize exercise difficulty to a patient's current state. Pilot clinical trials have been performed using the above system combined with noncomputer tasks, such as pegboard insertion or tracing of two-dimensional (2-D) patterns. Three chronic stroke patients used this rehabilitation protocol daily for two weeks. Objective measurements showed that each patient showed improvement on most of the hand parameters over the course of the training. Subjective evaluation by the patients was also positive. This technical report focuses on this newly developed technology for VR rehabilitation.