Inter- and intralimb oscillator coupling in parkinsonian tremor.

This study reports the findings of an analysis of temporal correlation between tremor of different muscles of the same and different limbs in four patients with Parkinson's disease. Spectral coherence methods were used for determining whether simultaneously occurring oscillations in the electromyograms of different muscles are statistically coupled. The incidence of significant coherence was considerably higher for muscle pairs in the same limb than for pairs in different limbs; Parkinson's disease tremor is coupled within but not between limbs. Because the characteristics of tremor are known to vary under different behavioral situations, the intralimb coupling was examined for different tasks. A mental arithmetic task resulted in an increase in the coherence between muscles of the same limb, whereas the finger-to-nose task decreased the coherence. No significant change in coherence was found for a postural task. The amplitude and regularity of tremor electromyography showed changes analogous to those in coherence. These results support the hypothesis that tremor in different limbs results from the activity of several neural circuits oscillating independently. The results also emphasize the value of these methods for rigorously characterizing tremor, in relation to disease state, behavioral conditions, and the selection of treatment strategies.

Are automatic postural responses in patients with Parkinson's disease abnormal due to their stooped posture?

Abnormal automatic postural responses are thought to contribute to balance impairment in Parkinson's disease. However, because postural responses are modifiable by stance, we have speculated that some postural abnormalities in patients with Parkinson's disease are secondary to their stooped stance. We have studied this assumption by assessing automatic postural responses in 30 healthy subjects who were instructed either to stand upright or to assume a typical parkinsonian posture. During both conditions, subjects received 20 serial 4 degrees 'toe-up' rotational perturbations from a supporting forceplate. We recorded short-latency (SL) and medium-latency (ML) responses from stretched gastrocnemius muscles and long-latency (LL) responses from shortened tibialis anterior muscles. We also assessed changes in the center of foot pressure (CFP) and the center of gravity (COG). The results were qualitatively compared to a previously described group of patients with Parkinson's disease who, under these circumstances, typically have large ML responses, small LL responses and insufficient voluntary postural corrections, accompanied by a slow rate of backward CFP displacement and an increased posterior COG displacement. The stooped posture resulted in unloading of medial gastrocnemius muscles and loading of tibialis anterior muscles. Onset latencies of stretch responses in gastrocnemius muscles were delayed in stooped subjects, but the onset of LL responses was markedly reduced. Amplitudes of both ML and LL responses were reduced in stooped subjects. Prestimulus COG and, to a lesser extent, CFP were shifted forwards in stooped subjects. Posterior COG displacement and the rate of backward CFP displacement were diminished in stooped subjects. Voluntary postural corrections were unchanged while standing stooped. These results indicate that some postural abnormalities of patients with Parkinson's disease (most notably the reduced LL responses) can be reproduced in healthy subjects mimicking a stooped parkinsonian posture. Other postural abnormalities (most notably the increased ML responses and insufficient voluntary responses) did not appear in stooped controls and may contribute to balance impairment in Parkinson's disease.

Postural reflexes in patients with HIV-1 infection.

OBJECTIVE: We studied whether medium latency (ML) and long latency (LL) postural reflexes, which are abnormal in a number of neurological conditions including basal ganglia disorders, provide an early marker of CNS involvement in HIV-positive patients. METHODS: Leg reflexes were elicited in 9 neurologically normal HIV-positive patients and 10 healthy controls who were standing upright, using toe-up forceplate rotations of varying amplitude (4 degrees and 10 degrees) and predictability (serial and random). RESULTS: For predictable amplitude perturbations, posturally destabilizing ML and stabilizing LL responses in HIV-seropositives did not differ from controls. However, for unpredictable amplitude perturbations, HIV-positive patients inappropriately manifested a mid-size default LL response, in contrast to healthy subjects who showed a maximum size default response. CONCLUSIONS: These results suggest that impaired modulation of LL reflex processing occurs in early stages of HIV infection, prior to the onset of clinical postural instability, and this dysregulation may be influenced by cognitive factors.

Clinimetrics of postural instability in Parkinson's disease.

Judgement of the ability to recover balance after a sudden shoulder pull is used as a clinical measure of postural instability in Parkinson's disease. To further evaluate its merits, we compared this 'retropulsion test' with dynamic posturography in 23 Parkinson patients. Dynamic posturography involved 20 serial 'toe-up' support surface rotations, which induced backward body sway. We found a moderate correlation (Spearman's p = 0.54; P < 0.05) between the retropulsion test and body sway after platform rotations during the 'off' phase, but no correlation during the 'on' phase (Spearman's p = 0.43; P = 0.11). These results cast doubt on the use of the retropulsion test as a measure of postural instability in Parkinson's disease.

Habituation of lower leg stretch responses in Parkinson's disease.

In young healthy subjects, initially large stretch responses in leg muscles are progressively attenuated following a series of identical postural perturbations. We have studied whether this habituation of stretch responses is impaired in Parkinson's disease. Ten patients and 10 elderly controls received 10 serial 'toe-up' rotational perturbations (amplitude 10 degrees) while standing on a supporting forceplate. We recorded posturally destabilizing medium latency (ML) stretch responses from the medial gastrocnemius muscle. Functional habituation across the first few trials occurred in patients, but not in elderly controls. The rate of habituation was influenced by the size of the response to the first perturbation. This observation explained the absence of habituation in elderly subjects because their responses during the first few trials were much smaller compared to patients. These results suggest that habituation of lower leg stretch responses is unimpaired in Parkinson's disease. The presence of initially large and 'unpracticed' responses may partially explain why Parkinson patients fall in response to unexpected postural disturbances that commonly occur in daily life.

Influence of dopaminergic medication on automatic postural responses and balance impairment in Parkinson's disease.

It is still unclear why balance impairment in Parkinson's disease (PD) often responds insufficiently to dopaminergic medication. We have studied this issue in 23 patients with idiopathic PD and 24 healthy controls. Our specific purposes were (a) to investigate the contribution of abnormal automatic postural responses to balance impairment in PD and (b) to assess the influence of dopaminergic medication on abnormal automatic postural responses and balance impairment. Standing subjects received 4 degrees "toe-up" rotational perturbations of a supporting forceplate. We bilaterally recorded posturally destabilizing medium latency (ML) responses from the stretched gastrocnemius muscles and functionally corrective long latency (LL) responses from the shortened tibialis anterior (TA) muscles. We also assessed changes in the center of foot pressure (CFP) and the center of gravity (COG). All patients were tested in the "off" and "on" phases. All controls were tested and retested after 1 h. During the off phase, we found enlarged ML amplitudes and diminished LL amplitudes in patients, together with a markedly increased posterior displacement of the COG. The abnormal ML and LL responses were partially responsible for the increased body sway in patients because the initial forward (destabilizing) displacement of the CFP was increased, while the subsequent backward displacement of the CFP (a measure of the corrective braking action of LL responses) was delayed. Abnormal late automatic or possibly more voluntary postural corrections also contributed substantially to the increased body sway. During the on phase, ML amplitudes were reduced in patients but remained increased compared with controls. LL amplitudes no longer differed between both groups due to a modest, possibly dopamine-related increase in patients and a simultaneous decrease in controls. The abnormal CFP displacement was only partially improved by dopaminergic medication. The later postural corrections were not improved at all. Consequently, the increased posterior COG displacement was not ameliorated during the on phase. We conclude that (a) a combination of abnormal automatic and perhaps more voluntary postural corrections contributes to increased body sway in PD and (b) dopaminergic medication fails to improve balance impairment in PD because early automatic postural responses are only partially corrected, while later occurring postural corrections are not improved at all. These electrophysiological results support clinical observations and suggest that nondopaminergic lesions play a significant role in the pathophysiology of postural abnormalities in PD.

Clinical correlates of motor performance during paced postural tasks in Parkinson's disease.

Bradykinesia and hypokinesia may both play a significant role in postural instability commonly seen in patients with Parkinson's disease. We investigated which factor--movement time or movement amplitude--is the more significant limiting variable in patients with Parkinson's disease during a paced postural task. We also assessed the effect of antiparkinson medication upon these movement factors and the degree of correlation with changes in clinical performance. Subjects performed paced left-right (L-R) and forward-backward (F-B) continuous weight-shifting tasks at slow, medium and fast paces. Ten Parkinson patients were studied both OFF and ON their usual antiparkinson medication. Ten age-matched healthy controls were also tested and subsequently retested on the same schedule as the patients. Movement times and amplitudes were measured and correlated with clinical changes in UPDRS motor subscores. Parkinson patients performed similar to controls with respect to movement time, but significantly displayed underscaled (reduced) movement amplitude. Movement amplitude improved after antiparkinson medication, but remained significantly less than that of controls. Improvements in L-R movement amplitude correlated with clinical improvements in bradykinesia and postural instability, while improved F-B movement amplitude correlated only with reduced postural instability. We conclude that hypometric movement amplitude, and not abnormal movement time, is the primary abnormality observed in Parkinson patients during a paced postural task. Amplitude underscaling seems antiparkinson medication-dependent and improvement correlates with favorable clinical changes in bradykinesia and postural instability scores.

Long latency postural reflexes are under supraspinal dopaminergic control.

Scaling of posturally stabilizing long latency (LL) reflexes in tibialis anterior muscles induced by "toe-up" rotational perturbations is abnormal in standing patients with Parkinson's disease. To investigate the contribution of dopaminergic pathways to abnormal scaling, we studied LL reflexes in 22 patients with selective hypodopaminergic syndromes: 10 psychiatric patients taking chronic neuroleptic medication (7 with mild parkinsonism), 8 patients with young-onset Parkinson's disease, and 4 patients with MPTP-induced parkinsonism. Results were compared with those of 10 healthy controls. Stimuli consisted of (a) 10 serial (predictable) perturbations of 4 degrees amplitude, (b) 10 serial (predictable) perturbations of 10 degrees amplitude, and (c) 20 randomly mixed (unpredictable) perturbations of either 4 or 10 degrees amplitude. In normal subjects, LL reflex amplitudes were adapted to match predictable variations in stimulus size, whereas under unpredictable conditions a "default" response emerged that anticipated the 10 degrees perturbation. LL reflex scaling under predictable conditions was intact in patients with neuroleptic-induced parkinsonism and young-onset Parkinson's disease, but the large default LL response under unpredictable conditions was absent. In patients with MPTP-induced parkinsonism, LL reflex scaling was absent during both predictable and unpredictable conditions. We conclude that abnormal scaling of posturally stabilizing LL reflexes is related to decreased supraspinal dopaminergic influence.

Postural reflexes in Parkinson's disease during 'resist' and 'yield' tasks.

Postural reflexes in leg muscles appear to be set at a fixed gain in Parkinson's disease. To further investigate gain adaptation, we instructed 16 patients with idiopathic Parkinson's disease (studied during the 'off' phase) and 21 healthy controls to either 'resist' or 'yield' in response to 20 serial 4 degrees toe-up perturbations of a supporting platform on which they were standing. We bilaterally recorded destabilizing medium latency (ML) reflexes from stretched gastrocnemius muscles and corrective long latency (LL) reflexes from shortened tibialis anterior muscles. We also assessed changes in center of foot pressure (CFP) and center of gravity (COG). During the 'resist' condition, patients had increased destabilizing ML reflexes, decreased corrective LL reflexes, increased backward displacement of the COG and increased forward (destabilizing) displacement of the CFP. In addition, the backward (corrective) displacement of CFP between 150 and 250 ms was delayed. During the 'yield' condition, reflex gains were modified in controls: LL reflexes were markedly attenuated, whereas ML reflexes were markedly increased. Although this reflex pattern resembled the 'resist' condition in patients, it was not associated with an increased forward displacement of the CFP, but only with a strongly delayed backward displacement of CFP which started after 150 ms. In patients, ML reflex amplitudes remained unchanged during the 'yield' condition, suggesting a fixed reflex gain. LL reflex amplitudes were reduced in patients but significantly less compared to controls, which again suggests a fixed reflex gain. This 'inflexibility' of postural reflexes was reflected by the CFP which showed much smaller changes between 0 and 250 ms in patients than controls. These results could not be ascribed to a different ability to yield because posterior displacement of the COG was identical in patients and controls during the 'yield' condition. We conclude that (1) patients with Parkinson's disease have abnormal and 'inflexible' postural reflexes, associated with delayed corrective movements about the ankle joint and increased body sway; and (2) the increased forward displacement of the CFP in patients likely reflects high stiffness in ankle muscles because reflex changes in controls only affected the CFP more than 150 ms after the perturbation. The increased muscle stiffness and inflexibility of postural reflexes in Parkinson's disease may contribute to balance impairment in daily life.

Medium latency stretch reflexes in young-onset Parkinson's disease and MPTP-induced parkinsonism.

It is still unclear why components of the phasic stretch reflex are increased in Parkinson's disease (PD). To study the role of aging, we assessed medium latency (ML) stretch reflexes in 19 Parkinson patients (8 with young-onset PD, 11 with late-onset PD) and 23 normal subjects (10 young, 13 old). To assess the contribution of supraspinal dopaminergic influences, we also studied 5 young parkinsonian patients with a selective central dopamine deficiency induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). ML responses were recorded from the medial gastrocnemius muscle which was stretched by 4 degrees toe-up rotations of a platform upon which subjects were standing. ML responses were significantly enhanced in late-onset patients compared with older controls. In contrast, ML responses did not differ between young-onset patients and young controls. This observation could be attributed to the significantly different influence of age on ML-amplitudes in patients and controls. Thus, ML-amplitudes declined with age in controls, whereas they increased with age in PD possibly because older patients were more severely affected than younger patients. Thus, the difference between young-onset and late-onset PD seems to be related to the opposite effects of increasing age and disease severity in patients and controls. ML-amplitudes did not differ between patients with MPTP-induced parkinsonism, patients with young-onset PD and controls, suggesting that supraspinal dopaminergic systems are not critically involved in control of ML responses. This result also indicates that the severity effect in PD may be related to disruption of non-dopaminergic pathways which occurs in late-onset, but not young-onset patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Disinhibition of automatic word reading in Parkinson's disease.

The Stroop phenomenon was studied in patients with early and late onset Parkinson's disease (PD) and in normal controls to examine the effect of this disease on generating and controlling automatic mental processes. In the Stroop task subjects are presented with color or neutral words in various colors and asked to ignore the word and name its color as fast as possible. We examined the facilitory and interference effects of the irrelevant word upon naming the color by using computerized version of the Stroop test. Vocal reaction times of both early and late onset PD patients presented an augmented facilitory effect. In addition, error data of the late onset PD patients showed an enlarged interference effect. These effects are related to an impairment in the ability to control automatic-reflexive processes. The augmented facilitory effect is manifest early in the course of PD suggesting that the basal ganglia act to inhibit some automatic cognitive processes. The origin of the interference effect in late onset PD patients is less clear. It may reflect more severe basal ganglia dysfunction; or a decline in cortical inhibitory processes.

Correction for the influence of background muscle activity on stretch reflex amplitudes.

Background muscle activity (BGR) exerts a strong influence on stretch reflex amplitudes. While it is considered important to correct for this influence, which method best able to eliminate the effects of BGR remains unknown. We have therefore compared one previously described and one novel correction method which respectively consisted of calculating (1) the difference between reflex amplitude and BGR, and (2) the ratio of reflex amplitude to BGR. These correction methods were evaluated in a group of 23 healthy individuals. BGR and stretch reflexes were recorded from the gastrocnemius muscle of standing subjects who received sudden toe-up perturbations of a supporting platform upon which they were standing. Calculation of differences markedly reduced the influence of BGR on stretch reflex amplitudes in most, although not all, subjects. Calculation of ratios failed to correct for BGR in most subjects and caused a net increase in the influence of BGR on stretch reflex amplitudes. Because both correction methods insufficiently corrected for BGR in normal subjects, we introduce the use of analysis of covariance (ANCOVA) to reliably remove the influence of BGR on stretch reflex amplitudes. The use of ANCOVA is exemplified by showing that stretch reflex amplitudes are enhanced in patients with Parkinson's disease even if the influence of high BGR is completely taken into account.

Impaired scaling of long latency postural reflexes in patients with Parkinson's disease.

Young normal subjects adapt the size of posturally stabilizing reflexes in the lower extremity to predictable and unpredictable perturbations through shifts in cognitive set. It is unknown whether limitations in this ability to shift cognitive set may contribute to impaired scaling of postural reflexes in patients with Parkinson's disease. In this study, we have addressed this issue in 12 posturally unstable Parkinson patients and 13 age- and sex-matched controls. Postural stability was disturbed by sudden toe-up rotations of a supporting platform upon which subjects were standing. Subjects' cognitive set was altered by varying the perturbation amplitude either predictably (serial 4 degrees versus serial 10 degrees) or unpredictably (random mixture of 4 degrees and 10 degrees). Posturally stabilizing long latency (LL) reflexes were recorded from the shortened tibialis anterior muscle of both legs. We found that Parkinson patients, unlike some control subjects, were unable to scale the size of their LL reflex in response to variations in perturbation amplitude during predictable conditions. In addition, we observed that Parkinson patients could not modify the amplitude of the LL reflex through alterations in cognitive set during random conditions. We conclude that Parkinson patients have a fundamental difficulty in modifying the size of posturally stabilizing LL reflexes, as reflected by both problems with amplitude scaling and difficulties with changes in cognitive set. It is possible that this inability to modify LL reflexes may be a factor contributing to postural instability in Parkinson's disease.

Altered postural reflexes in Parkinson's disease: a reverse hypothesis.

In subjects standing on a movable platform, sudden dorsiflexion of the ankle joint elicits a set of reflexes in leg muscles. These responses include a short latency (SL) and medium latency (ML) stretch reflex in the gastrocnemius muscle and a distal to proximal innervation sequence of long latency (LL) reflexes in the shortened tibialis anterior and vastus lateralis muscles. Because of their role in maintaining upright stance these responses have been termed postural reflexes. In patients with Parkinson's disease (PD), the following abnormalities have been described: 1) enhanced ML-amplitudes; 2) a reversed LL innervation sequence; and 3) delayed onset latencies. These abnormalities are thought to be due to defective motor programming and disturbed control of spinal and supraspinal reflex centers by basal ganglia circuits. The altered reflexes have been held responsible for some of the clinical features of PD, including balance impairment and rigidity. In this paper, we argue the reverse hypothesis that postural reflexes are essentially normal in PD, and that the observed alterations are at least in part consequence rather than cause of balance impairment, the stooped parkinsonian posture and rigidity of PD patients.

Are medium and long latency reflexes a screening tool for early Parkinson's disease?

We have studied whether assessment of medium latency (ML) and long latency (LL) reflex amplitudes may serve as a marker for early Parkinson's disease. Twenty-three patients with idiopathic Parkinson's disease (Hoehn and Yahr stage 1 to 4) and 24 controls received 20 4 degrees toe-up rotations of a platform upon which they were standing. All antiparkinsonian medication was withheld for at least 12 h before the study. ML reflexes in the stretched gastrocnemius muscle and LL reflexes in the shortened tibialis anterior muscle were recorded from both legs. ML responses were significantly enhanced in patients compared to controls. In contrast to previous studies which studied patients who continued their usual treatment, we observed that LL responses were significantly reduced in patients compared to controls. For the purpose of individual analysis, we subsequently determined the optimal specificity and sensitivity using various criteria for abnormality. The presence of either enhanced ML responses or reduced LL responses (or both) in at least one leg yielded a maximum sensitivity of 65.2% with a specificity of 75.0% (positive likelihood ratio 2.6; negative likelihood ratio 0.5). Abnormal reflexes were almost exclusively present in patients with advanced and long-standing Parkinson's disease. These results show abnormalities of ML and LL responses in advanced Parkinson's disease, but render it unlikely that these abnormalities are a suitable screening tool for early stages of the disease. The fact that LL responses were reduced in patients taken off antiparkinsonian medication raises the possibility that this reflex is under supraspinal dopaminergic control.

Abnormal premovement brain potentials in schizophrenia.

We assessed scalp-recorded movement related potentials (MRPs) generated prior to voluntary movements in chronic, medicated schizophrenics (n = 9) and age matched normal controls (n = 9). MRPs were recorded in a self-paced button press task in which subjects pressed a button with either their right, left or both thumbs (experimental condition I, II and III respectively). Controls generated a slowly rising readiness potential (RP) at about 1000 ms, a negative shift (NS') at about 450 ms and a motor potential (MP) at about 100 ms prior to movement. The initial MRP components (RP and NS') were reduced in schizophrenics indicating an impairment of the voluntary preparatory process in schizophrenia. Results of the present study indicate a similarity of MRP findings in schizophrenics and reported MRPs (Singh and Knight, 1990) in patients with unilateral lesions of the dorsolateral prefrontal cortex. These findings provide further support for frontal lobe dysfunction in schizophrenia.

Long latency postural responses are functionally modified by cognitive set.

We examined how cognitive set influences the long latency components of normal postural responses in the legs. We disturbed the postural stability of standing human subjects with sudden toe-up ankle rotations. To influence the subjects' cognitive set, we varied the rotation amplitude either predictably (serial 4 degrees versus serial 10 degrees) or unpredictably (random mixture of 4 degrees and 10 degrees). The subjects' responses to these ankle rotations were assessed from the EMG activity of the tibialis anterior, the medial gastrocnemius, and the vastus lateralis muscles of the left leg. The results indicate that, when the rotation amplitude is predictable, only the amplitude of the long latency (LL) response in tibialis anterior and vastus lateralis varied directly with perturbation size. Furthermore, when the rotation amplitude is unpredictable, the central nervous system selects a default amplitude for the LL response in the tibialis anterior. When normal subjects are exposed to 2 perturbation amplitudes which include the potential risk of falling, the default LL response in tibialis anterior appropriately anticipates the larger amplitude perturbation rather than the smaller or an intermediate one.