Disturbances of rhythm formation in patients with Parkinson's disease: part II. a forced oscillation model

The origin of the characteristic disturbances of rhythm formation in patients with Parkinson's disease (the hastening phenomenon) was discussed, using a second-order system of the periodic response. The input signal was regarded as a pulse series of a Dirac function. The output process of the system had maximal errors of response at input frequencies of f = omega0/n (n = 1, 2, . . .), where omega0 was the intrinsic frequency of the system. Damping coefficient epsilon represented a function of an inhibitor against these maximal errors and the errors diverged to infinity when epsilon = 0. The solution of this forced oscillation system indicated that the intrinsic oscillation of the system has a possibility to be excited at these critical frequencies f = omega/n. Inferred from data on the tapping test, the frequency of an intrinsic oscillation was 5 Hz in the central nervous system, then the critical frequencies were predicted 5/n = 5, 2.5, . . . Hz. On the tapping test the errors of response become maximum around 2.5 and 5 Hz (taps per second), and their peak heights increased from the minimum in well trained normal subjects to the maximum in patients. An inhibitory mechanism against the maximal error would function well, i.e. epsilon greater than 0, in normal subjects but so insufficiently (epsilon leads to 0) in patients that the excited intrinsic oscillation would control their response directly. Thus some patients could no longer maintain a synchronous tapping response at 2.5 Hz or 5 Hz and showed a hastened tapping of 5 6 Hz independent of the signal frequency.     

Clinical assessment of motor function: a processes oriented instrument based on a speed-accuracy trade-off paradigm

In this study, we developed a digitizing tablet-based instrument for the clinical assessment of human voluntary movements targeting motor processes of planning, programming and execution. The tool was used to investigate an adaptation of Fitts' reciprocal tapping task [10], comprising four conditions, each of them modulated by three indices of difficulty related to the amplitude of movement required. Temporal, spatial and sequential constraints underlying the various conditions allowed the intricate motor processes to be dissociated. Data obtained from a group of elderly healthy subjects (N=50) were in agreement with the literature on motor control, in the temporal and spatial domains. Speed constraints generated gains in the temporal domain and costs in the spatial one, while spatial constraints generated gain in the spatial domain and costs in the temporal one; finally, sequential constraints revealed the integrative nature of the cognitive operations involved in motor production. This versatile instrument proved capable of providing quantitative, accurate and sensitive measures of the various processes sustaining voluntary movement in healthy subjects. Altogether, analyses performed in this study generated a theoretical framework and reference data which could be used in the future for the clinical assessment of patients with various movement disorders, in particular Parkinson's disease.     

The influence of playing a non-reward game on motor ability and executive function in Parkinson's disease

The aim of this study is to evaluate the acute effect of playing games on executive function and motor ability in Parkinson's disease (PD). Consecutive cases with PD were studied with the Unified Parkinson Disease Rating Scale (UPDRS), Mini-Mental State examination (MMSE), Beck Depression Inventory (BDI), Stroop test, finger tapping and 14-meter walk test. After randomization, patients performed a game of dominoes and were tested before and after experiment being further categorized as control, winners or non-winners. Forty patients, 27 male (67.5%), aged 48 to 84 years (63.2 ± 8.5), Hoehn & Yahr I to III were included. Twenty-eight (70%) presented depressive symptoms (BDI > 10). Groups (Control N = 13; Winners = 14 and Non-winners = 13) were not different regarding age, disease duration, age at onset, BMI, MMSE scores, depressive symptoms, levodopa dose, and previous practice of games. Winners presented significantly better results on executive function (Stroop test, p = 0.002) and on motor activity (Finger tapping, p = 0.01). Non-winners showed a trend of better performance in the 14-meter-walk test. This study shows that the practice of a non-reward game acutely improved memory and motor skills in PD. Our results suggest a role for the reward system in the modulation of the dopaminergic function of the basal ganglia in these patients.     

Effects of focal basal ganglia lesions on timing and force control

Studies of basal ganglia dysfunction in humans have generally involved patients with degenerative disorders, notably Parkinson's disease. In many instances, the performance of these patients is compared to that of patients with focal lesions of other brain structures such as the cerebellum. In the present report, we studied the performance of patients with focal basal ganglia lesions on three fundamental motor tasks. The patients all had suffered unilateral damage in the striatum and were tested in the chronic state. The first task required the participants to tap with their index finger as fast as possible; this test provided a simple assessment of motor competence. Compared to controls, the maximum tapping rate was lower for the patients when tapping with their contralesional limb, although the deficit was not severe. The second and third tasks were designed to assess timing and force control, two functions that have been associated with basal ganglia function. The patients performed similar to controls on both tasks and showed no evidence of impairment when using their contralesional limb compared to their ipsilesional limb. The results indicate that unilateral basal ganglia lesions tend to produce minor motor problems in force control, and fail to support the hypothesized role of the basal ganglia in timing.     

Coordination of a discrete response with periodic finger tapping: additional experimental aspects for a subtle mechanism

The authors investigated the coordination of periodic right-hand tapping with single stimulus-evoked discrete lefthand taps to check for task interactions and a possible relationship between phase resetting (see tapping literature; e.g., J. Yamanishi, M. Kawato, & R. Suzuki, 1979) and phase entrainment (see tremor literature; e.g., R. J. Elble, C. Higgins, & L. Hughes, 1994). The experimental paradigm employs a dual-task condition as used by K. Yoshino, K. Takagi, T. Nomura, S. Sato, and M. Tonoike (2002), and it includes normal tapping and isometric tapping with the authors recording finger positions and ground contact forces. Four different types of coordination schemes were observed in tapping behavior: marginal tapping interaction (MTI), periodic tap retardation (PTR), periodic tap hastening (PTH), and discrete tap entrainment (DTE); MTI and PTR correspond to the phase-resetting effect for the coordination of periodic tapping with single discrete taps. The novel aspect of the study described in this article includes the impact of the periodic tapping on the discrete tap timing and the hastening of the periodic tapping due to the discrete tap behaviors resulting in a synchronized execution of the two concurrent tapping tasks. All participants showed a dominant tapping behavior, but they all used the other nondominant forms of the four reported coordination schemes in some trials too, which reflects possible constraints of the sensorimotor system in handling two competing tasks.     

Multidimensional sequence learning in patients with focal basal ganglia lesions

Parkinson's patients have been found to be impaired in learning movement sequences. In the current study, patients with unilateral basal ganglia lesions due to stroke were tested on a serial reaction time task in which responses were based on the spatial location of each stimulus. The spatial locations either followed a fixed sequence or were selected at random, with learning operationalized as the difference in reaction time between these two conditions. In addition, three response-to-stimulus intervals were used, and these either followed a fixed sequence or were randomized. Compared to control participants, the patients showed normal learning of the spatial and temporal sequences, as well as normal cross-dimensional learning. This was true for performance with either the contralesional or ipsilesional hand. Sequence learning was not correlated with maximum tapping rate, a simple measure of motor impairment. These results raise questions concerning the use of Parkinson's disease as a model for studying basal ganglia dysfunction.     

Coordination of a Discrete Response With Periodic Finger Tapping: Additional Experimental Aspects for a Subtle Mechanism

The authors investigated the coordination of periodic right-hand tapping with single stimulus-evoked discrete lefthand taps to check for task interactions and a possible relationship between phase resetting (see tapping literature; e.g., J. Yamanishi, M. Kawato, & R. Suzuki, 1979) and phase entrainment (see tremor literature; e.g., R. J. Elble, C. Higgins, & L. Hughes, 1994). The experimental paradigm employs a dual-task condition as used by K. Yoshino, K. Takagi, T. Nomura, S. Sato, and M. Tonoike (2002), and it includes normal tapping and isometric tapping with the authors recording finger positions and ground contact forces. Four different types of coordination schemes were observed in tapping behavior: marginal tapping interaction (MTI), periodic tap retardation (PTR), periodic tap hastening (PTH), and discrete tap entrainment (DTE); MTI and PTR correspond to the phase-resetting effect for the coordination of periodic tapping with single discrete taps. The novel aspect of the study described in this article includes the impact of the periodic tapping on the discrete tap timing and the hastening of the periodic tapping due to the discrete tap behaviors resulting in a synchronized execution of the two concurrent tapping tasks. All participants showed a dominant tapping behavior, but they all used the other nondominant forms of the four reported coordination schemes in some trials too, which reflects possible constraints of the sensorimotor system in handling two competing tasks.     

Quantitative measurement of handwriting in the assessment of drug-induced parkinsonism

Monitoring drug-induced side effects is especially important for patients who undergo treatment with antipsychotic medications, as these drugs often produce extrapyramidal side effects (EPS) resulting in movement abnormalities similar to parkinsonism. Scientists have developed several objective laboratory tests to measure and research drug-induced movement disorders, but equipment and tests are complex and costly and have not become accepted in large-scale, multi-site clinical trials. The goals of this study were to test whether a simple handwriting measure can discriminate between individuals with psychotropic-induced parkinsonism, Parkinson's disease, and healthy individuals, and to examine some of the psychometric properties of the measure. We examined pen movement kinematics during cursive writing of a standard word in 13 patients with idiopathic Parkinson's disease (PD), 10 schizophrenia patients with drug-induced parkinsonism (SZ), and 12 normal healthy control participants (NC). Participants were instructed to write the word "hello" in cursive twice, at three vertical height scales. Software was used for data acquisition and analysis of vertical stroke velocities, velocity scaling, and smoothness. There were four important results from this study: (1) both SZ patients with drug-induced EPS and PD participants exhibited impaired movement velocities and velocity scaling; (2) performance on the velocity scaling measure distinguished drug-induced EPS from normal with 90% accuracy; (3) SZ, but not PD participants displayed abnormalities in movement smoothness; and (4) there was a positive correlation between age and magnitude of the velocity scaling deficit in PD participants. This study demonstrates that kinematic analyses of pen movements during handwriting may be useful in detecting and monitoring subtle changes in motor control related to the adverse effects of psychotropic medications.     

Motor variability in elicited repeated bout rate enhancement is associated with higher sample entropy

In this study we investigated motor variability in individuals who showed (responders) and who did not show (non-responders) a behavioural phenomenon termed repeated bout rate enhancement. The phenomenon is characterized by an increase of the freely chosen index finger tapping rate during the second of two consecutive tapping bouts. It was hypothesized that responders would perform (i) tapping with a lower magnitude, but more complex structure of variability than non-responders and (ii) bout 2 with a lower magnitude and increased complexity of variability than bout 1, as opposed to non-responders. Individuals (n = 102) performed two 3-min tapping bouts separated by 10 min rest. Kinetic and kinematic recordings were performed. Standard deviation (SD), coefficient of variation (CV), and sample entropy (SaEn), representing magnitude and complexity of variability, were computed. For responders, SaEn of vertical displacement of the index finger was higher than for non-responders (p = .046). Further, SaEn of vertical force and vertical displacement was higher in bout 2 than in bout 1 for responders (p < .001 and p = .006, respectively). In general, SD of vertical displacement was lower in bout 2 than in bout 1 (p < .001). SaEn of vertical force was higher in bout 2 than in bout 1 (p = .009). The present lower SD and higher SaEn values of vertical force and displacement time series in bout 2 as compared to bout 1 suggest differences in the dynamics of finger tapping. Further, it is possible that the increases in SaEn of vertical displacement reflected a greater adaptability in the dynamics of motor control among responders compared with non-responders.     

Common pathways in mental imagery and pain perception: an fMRI study of a subject with an amputated arm

The present paper reviews data from two previous studies in our laboratory, as well as some additional new data, on the neuronal representation of movement and pain imagery in a subject with an amputated right arm. The subject imagined painful and non-painful finger movements in the amputated stump while being in a MRI scanner, acquiring EPI-images for fMRI analysis. In Study I (Ersland et al., 1996) the Subject alternated tapping with his intact left hand fingers and imagining "tapping" with the fingers of his amputated right arm. The results showed increased neuronal activation in the right motor cortex (precentral gyrus) when tapping with the fingers of the left hand, and a corresponding activation in the left motor cortex when imagining tapping with the fingers of the amputated right arm. Finger tappings of the intact left hand fingers also resulted in a larger activated precentral area than imagery "finger tapping" of the amputated right arm fingers. In Study II (Rosen et al., 2001 in press) the same subject imagining painful and pleasurable finger movements, and still positions of the fingers of the amputated arm. The results showed larger activations over the motor cortex for movement imagining versus imagining the hand being in a still position, and larger activations over the sensory cortex when imagining painful experiences. It can therefore be concluded that not only does imagery activate the same motor areas as real finger movements, but also that adding instructions of pain together with imaging moving the fingers intensified the activation compared with adding instructions about non-painful experiences. From these studies, it is clear that areas activated during actual motor execution to a large extent also are activated during mental imagery of the same motor commands. In this respect the present studies add to studies of visual imagery that have shown a similar correspondence in activation between actual object perception and imagery of the same object.     

What effect can rhythmic finger tapping have on the phonological similarity effect?

The effects of rhythmic finger tapping on the phonological similarity effect were investigated in two experiments. In both, subjects were tested for serial recall of visually presented letter sequences that were either phonologically similar or dissimilar. The letter sequences had to be remembered under three tapping conditions: right-hand tapping, left-hand tapping, and a no-tapping control. Experiment 1 showed clear phonological similarity effects in both the control and the left-hand tapping conditions, but not in the right-hand tapping condition, when recall responses were written with the right hand. When the number of tapping practice trials was fixed at two and recall was vocal in Experiment 2, the phonological similarity effect was eliminated in both the right-hand and the left-hand tapping conditions. These results suggest that some form of speech motor programs played an important role in serial recall.     

Relationship between extremities in motor performance

The purpose of the study was to examine the relationship between the extremities in different aspects of motor performance, including simple reaction time, choice reaction time, speed of movement, tapping speed, and coordination, i.e., speed of movement/accuracy. 186 healthy randomly selected right-handed subjects (93 men, 93 women; aged 21-70 years) were measured on a test battery of five tests for both hands and feet. Correlations between the extremities in motor performance were highest between hands (r=.71-.80, p<.001) or between feet (r=.57-.88, p<.001) depending on the complexity of response for all subjects. These relations remained at almost the same magnitude even when age was eliminated. Correlations between the upper and lower extremities were lower (r = .40-.62). Correlations between extremities were lower for one age group (21-30 years) than for all subjects (21-70 years). These results showed that the motor performance for the hands is not a very good indicator of the motor performance of the lower extremities, especially in a homogeneous age group, and it seems that the lower extremities should be studied with specific motor performance tests.     

Altered CSF 5-HIAA Disposition in Pathologic Male Gamblers

Previous reports concerning the cerebrospinal fluid (CSF) of pathologic gamblers have described disturbed norepinephrine and dopamine (but not serotonin) functioning in the central nervous system. We analyzed neurotransmitter metabolites in two consecutive 6-mL samples of CSF obtained from 10 pathologic male gamblers punctured at the L4-5 level following 8 hours of fasting along with strict bed rest. Data were compared with those for healthy male controls. In conformity with findings in healthy male controls, we found gradients in CSF 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA), but not 4-hydroxy-3-methoxyphenyl glycol (HMPG). Expressing the CSF concentrations as nmol x L-1 x min-1 of tapping time (an estimate of the mass flow through the needle), the levels of 5-HIAA and HMPG (but not HVA) were found to be significantly lower in gamblers. Levels of 5-HIAA and HVA showed a significant correlation in gamblers but not in healthy controls. Taking tapping time into account, the CSF levels of HMPG and 5-HIAA were significantly lower in gamblers. We concluded that, in light of previous CSF findings of disturbed norepinephrine and dopamine function, altered indolamine function cannot be fully ruled out.     

Effects of age, task, and frequency on variability of finger tapping

The goal was to assess whether prior studies might have overestimated performance variability in older adults in dual task conditions by relying on primary motor tasks that are not constant with aging. 30 younger and 31 older adults performed a bimanual tapping task at four different frequencies in isolation or concurrently with a secondary task. Results showed that performance of younger and older adults was not significantly different in performing the tapping task at all frequencies and with either secondary task, as indicated by mean tapping performance and low number of errors in the secondary tasks. Both groups showed increased variability as tapping frequency increased and with the presence of a secondary task. Tapping concurrently while reading words increased tapping variability more than tapping concurrently while naming colours. Although older participants' performances were overall more variable, no interaction effects with age were found and at the highest frequencies of tapping, younger and older participants did not differ in performance.     

The effect of Parkinson's disease on the control of multi-segmental coordination

An experiment was designed to test whether or not Parkinson's disease (PD) patients were able to maintain endpoint kinematic patterns in a prehension task involving movement of the torso. Nine PD patients and nine healthy controls were asked to reach for and grasp a full cup of water that was either covered or uncovered and placed beyond the reach of the outstretched arm. An OPTOTRAK (Northern Digital) 3-dimensional motion analysis system was used to capture the movement of four markers placed on the arm, hand, and torso. The results indicated the Parkinson's patients had a decreased ability to maintain the kinematics of the end effector. The PD patients were also found to be impaired in terms of their ability to synchronize the arm, hand, and torso. More specifically, although the elderly controls seemed to employ a strategy of increasing the involvement of the torso when reaching to grasp the uncovered cup, no such strategy was observed in the PD patients. Collectively, the results suggest that the multi-joint synergies observed in the elderly controls, which help preserve relatively consistent endpoint trajectories, are disrupted in Parkinson's patients.     

Short and long-term motor skill learning in an accelerated rotarod training paradigm

Rodent models of motor skill learning include skilled forelimb reaching and acrobatic locomotor paradigms. This study characterizes motor skill learning in the accelerated rotarod task. Thirty Long-Evans rats (300-400 g) were trained on an accelerated rotarod (1cm/s(2)) over eight consecutive sessions (=days, 20 trials each). Improvement in rotarod velocities mastered before falling off the rod was observed within and between sessions (plateau after five sessions). Intrasession improvement was incompletely retained at the beginning of the next day's session. Over several training sessions, intrasession improvement diminished, suggesting a ceiling effect. After 1 week of pause, the rotarod skill was retained. Locomotor exercise in a running wheel for 30 min before the first rotarod session did not affect intrasession improvement. Running-wheel exposure for 6 days did not diminish the rate of rotarod skill learning (steepness of the learning curve) but improved overall performance (upward shift of curve). Video analysis of gait on the rotarod showed that rats developed a motor strategy by modifying their gait patterns during training. The data demonstrate that rotarod improvement is not the result of enhanced general locomotor ability or fitness, which are trained in the running wheel, but requires a change in the motor strategy to master the task. Accelerated rotarod training can be regarded a valid paradigm for motor skill learning over short (intrasession, minutes) and long time frames (intersession, days).     

What catatonia can tell us about "top-down modulation": a neuropsychiatric hypothesis

Differential diagnosis of motor symptoms, for example, akinesia, may be difficult in clinical neuropsychiatry. Symptoms may be either of neurologic origin, for example, Parkinson's disease, or of psychiatric origin, for example, catatonia, leading to a so-called "conflict of paradigms." Despite their different origins, symptoms may appear more or less clinically similar. Possibility of dissociation between origin and clinical appearance may reflect functional brain organisation in general, and cortical-cortical/subcortical relations in particular. It is therefore hypothesized that similarities and differences between Parkinson's disease and catatonia may be accounted for by distinct kinds of modulation between cortico-cortical and cortico-subcortical relations. Catatonia can be characterized by concurrent motor, emotional, and behavioural symptoms. The different symptoms may be accounted for by dysfunction in orbitofrontal-prefrontal/parietal cortical connectivity reflecting "horizontal modulation" of cortico-cortical relation. Furthermore, alteration in "top-down modulation" reflecting "vertical modulation" of caudate and other basal ganglia by GABA-ergic mediated orbitofrontal cortical deficits may account for motor symptoms in catatonia. Parkinson's disease, in contrast, can be characterized by predominant motor symptoms. Motor symptoms may be accounted for by altered "bottom-up modulation" between dopaminergic mediated deficits in striatum and premotor/motor cortex. Clinical similarities between Parkinson's disease and catatonia with respect to akinesia may be related with involvement of the basal ganglia in both disorders. Clinical differences with respect to emotional and behavioural symptoms may be related with involvement of different cortical areas, that is, orbitofrontal/parietal and premotor/motor cortex implying distinct kinds of modulation--"vertical" and "horizontal" modulation, respectively.     

Neuromotor profiles: what are they and what can we learn from them?

Eye movements, alternating movements, rapid pointing movements, and various tremors were measured on patients with Parkinson's disease (n = 21), on Cree subjects exposed to methylmercury (n = 36), and on healthy control subjects (n = 30). Neuromotor profiles were created according to thirty characteristics extracted from test results of four subgroups matched for age and composed of six subjects each. Z scores were calculated with respect to the mean and standard deviation of the control group for each of the 30 characteristics. The subgroup with the lower methylmercury blood level had larger z scores than the control subgroup and with a few positive values above one standard deviation. The subgroup with the higher methylmercury blood level had several z scores above two standard deviations. Interestingly, the abnormal values for the subgroup with Parkinson's disease were mostly limited to static tremor recorded with no visual feedback and reached up to 5 standard deviations. These results indicate that neuromotor profiles can be used to summarize information extracted from different neuromotor tests and to differentiate neurological conditions.     

The Timing Effects of Accent Production in Periodic Finger-Tapping Sequences

When subjects are required to produce short sequences of equally paced finger taps and to accentuate one of the taps, the interval preceding the forceful tap is shortened and the one that immediately follows the accent is lengthened. Assuming that the tapping movements are triggered by an internal clock, one explanation attributes the rnistiming of the taps to central factors: The momentary rate of the clock is accelerated or decelerated as a function of motor preparation to, respectively, increase or decrease the movement force. This hypothesis predicts that the interresponse intervals measured between either tap movement onsets or movement terminations (taps) will show the same timing pattern. A second explanation for the observed interval effects is that the tapping movements are triggered by a regular internal clock but the timing of the successive taps is altered because the forceful movement is completed in less time than the other tap movements are. This "peripheral" hypothesis predicts regular timing of movement onsets but distorted timing of movement terminations. In the present study, the trajectories of the movements performed by subjects were recorded and the interresponse intervals were measured at the beginning and the end of the tapping movements. The results of Experiment 1 showed that neither model can fully explain the interval effects: The fast forceful movements were initiated with an additional delay that took into account the small execution time of these movements. Experiment 2 reproduced this finding and showed that the timing of the onset and contact intervals did not evolve with the repetition of trial blocks. Therefore, the assumption of an internal clock that would trigger the successive movements must be rejected. The results are discussed in the framework of a modified two-stage model in which the internal clock, instead of triggering the tapping movements, provides target time points at which the movements have to produce their meaningful effects, that is, contacts with the response key. The timing distortions are likely to reflect both peripheral and central components.     

Force Increase in a Repetitive Motor Task Inducing Motor Fatigue

To evaluate task induced motor fatigue in a well-established finger tapping task, we analyzed tapping parameters and included the time course of measures of force. We hypothesized that a decline in tapping force would reflect task induced motor fatigue, defined by a lengthening of inter-tap intervals (ITI). A secondary aim was to investigate the reliability of tapping data acquisition with the force sensor. Results show that, as expected, tapping speed decreased linearly over time, due to both an increase of ITI and tap duration. In contrast, tapping force increased non-linearly over time and was uncorrelated to changes in tapping speed. Force data could serve as a measure to characterize task induced motor fatigue. Force sensors can assess a decline in tapping speed as well as an independent increase of tapping force. We argue that the increase of force reflects central compensation, i.e. perception of fatigue, due to an increase in task effort and difficulty.