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Tardive dyskinesia and coupling constraints in inter-limb tremor
ELSEVIER
Human Movement
Science 15 (1996) 237-251
Tardive dyskinesia and coupling constraints in inter-limb tremor Karl M. Newell a3*, Robert L. Sprague ’ a The
Pennsylcania
State Uniw-sit!.
b Unic,ersity
of Illinois
109 White Building,
at Urbana-Champaign.
Uniwrsity
Park, PA 16802. USA
Urbana-Champaign,
USA
Abstract The coupling of inter-limb tremor in finger and arm postural tasks was examined in adult tardive dyskinetic, severely/profoundly mentally retarded, tardive dyskinetic and severely/profoundly mentally retarded, and normal healthy subjects. In finger tremor, the index fingers were found to operate independently in the time and frequency domains for normal adults but there was a modest level of coupling in the time domain in both tardive dyskinetic groups. Inter-limb coupling in the time and frequency domains was enhanced in arm tremor for all groups, with the effect stronger in the time domain for the tardive dyskinetic groups and in the frequency domain for the groups of normal intelligence. There was also a persistent phase lag in the coupling of the two limbs in both postural tasks for the tardive dyskinetic subjects. These data show that prolonged intake of neuroleptic medication constrains inter-limb coupling even when the task demands do not explicitly require such a coordination strategy. The coupling effects are stronger in arm tremor which suggests that the mass of the effector system is also a factor in constraining the coupling of inter-limb coordination. PsycINFO Kepvrd.s:
classification:
2330; 2580
Tremor: Tardive dyskinesia:
Posture; Coordination
1. Introduction Tardive dyskinesia is a movement disorder syndrome that arises from prolonged use of neuroleptic medication (American Psychiatric Association, 1979,
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1992; Jeste and Wyatt, 19821, and is particularly prevalent in institutionalized mentally retarded populations (Kalachnik, 1984; Kalachnik et al., 1984; Stone et al., 1989). The symptoms of the disorder include jerky and sometimes rhythmical stereotypic movements of the peripheral effector units, particularly the toes, feet, hands, fingers, lips and tongue, but it can also include disorders in the motions of other body parts. The movement disorders of tardive dyskinesia can be so severe that they can interfere with the conduct of activities of daily living and vocational actions (Sprague and Newell, 1987). The disorder of tardive dyskinesia is sometimes identified clinically with the aid of observational rating scale techniques, such as: AIMS - Abnormal Involuntary Movements Scale (Guy, 1976); Abbreviated Simpson/Rockland Dyskinesia Scale (Simpson et al., 1979); and DISCUS - Dyskinesia Identification System Condensed User Scale (Sprague et al., 1989). However, these techniques are not particularly sensitive to detecting changes and differences in the movement dynamics (Newell and Sprague, 19901, tending to focus on the mere presence of a category of motion in some effector unit that is above a particular threshold level. Recently, there has been more emphasis given to directly recording and examining the movement dynamics of tardive dyskinesia in both nonhuman (Alpert et al., 1976) and human (Caligiuri and Lohr, 1990; Hansen et al., 1986; Rondot and Bathien, 1986; Stacy and Jankovic, 1992; Tyron and Pologe, 1987) species, particularly the tremor-like properties of the stereotypical rhythmic movements. Indeed, tremor has been advocated as a viable movement property to assess the onset and status of tardive dyskinesia (May, 1987; Sprague and Newell, 1987). A standard finding is that the variability of postural tremor is greater in a tardive dyskinetic population when contrasted with an age-matched normal healthy control group (Caligiuri and Lohr, 1990; Van Emmerik et al., 1993a, b; Ko et al., 1992). There is also evidence that the modal frequency of tremor is reduced in the tardive dyskinetic population in that a lower more broadband profile in the frequency spectrum is evident (Van Emmerik et al., 1993a, b). This different frequency profile in the tremor of individuals diagnosed with tardive dyskinesia may be reflective of a unique geometry of the attractor dynamics supporting the postural actions. An attractor is the qualitative geometry of the successive points (trajectories) in phase space of the dynamical system that emerges as the number of iterations of the points goes to infinity (Hilbom, 1994). Recently, there have been direct examinations of the structure of attractor dynamics in postural actions of normal and tardive dyskinetic subjects. In both whole-body posture (Newell et al., 1993b) and finger tremor (Newell et al.,
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1995) it has been shown that the dimensionality (correlation dimension) of the postural time-series is lower in a tardive dyskinetic group than an age-matched normal healthy control group. This finding is consistent with the proposition that the tdrdive dyskinetic system is more constrained in motor output in that fewer degrees of freedom are required to specify the dynamic of the postural time-series (Packard et al., 1980). In short, tardive dyskinesia appears to be reflective of what Glass and Mackey (1988) have called a dynamical disease - the breakdown of normal system organization and exhibition of abnormal dynamics. In this paper we report experiments that examine the influence of tardive dyskinesia on the coupling of inter-limb tremor in postural tasks. The tasks required the subjects to maintain the respective posture of the fingers or arms with minimal motion of the effector units, that is in a dual index fingers task (finger tremor) and a dual arms task (arm tremor). Previously, we have shown that the degree of motion in these postural tasks is greater in tardive dyskinetic subjects than their age-matched counter parts, although the degree of variability in the dual limb task is approximately the same as that produced in the respective single limb task (Van Emmerik et al., 1993a, b). In both the finger and arm dual limb tremor tasks there were no instructional constraints to coordinate the tremors of the two limbs. There has been no extensive study of inter-limb coordination in finger or arm tremor tasks, although Marsden et al. (1969a, b) have provided data suggesting that in normal healthy adult subjects there is no coupling between the two index fingers in a dual limb tremor task. The degree to which the effects of tardive dyskinesia generalize across the different effector units within-subject is poorly understood. Recent studies of the movement dynamics of tardive dyskinesia consistently suggest that the neuroleptic medication appears to overconstrain the motor system and that this influence on coordination is related to enhanced movement variability (Newell, in press; Newell et al., 1993a). The strength of this relation may also vary with the particular effector unit used and the mass of the predominant limb segment(s) supporting the action. In finger tremor the natural resonant frequency of the finger is about 20-25 Hz, which is considerably higher than the 2 Hz resonant frequency that is apparent in elbow tremor (Marsden, 1984). The need to coordinate the limbs in the dual limb postural task may be greater in the larger mass effector system that also has a slower natural modal frequency. Furthermore, given the previous findings on the effect of tat-dive dyskinesia on intra-limb variability, the inter-limb coupling constraint also may be enhanced with the prolonged intake of neuroleptic medication. In summary, this study examined the coupling in inter-limb tremor (time and frequency domains) in finger and arm postural tasks in adult normal healthy,
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retarded, tardive dyskinetic, mentally retarded subjects.
and tardive dyski-
2. Method 2. I. Subjects There were four groups of adult subjects. One group contained 32 individuals (18 men and 14 women> who were diagnosed as developmentally disabled (profoundly and severely mentally retarded) and screened as having tat-dive dyskinesia. The mean age of this group was 34 years, with an age range from 23 to 60 years. In a second group, data from 26 normal healthy adults were collected and matched in age (k six months for each subject matched) and gender with the developmentally disabled and tardive dyskinetic group. The mean age of this normal control group was 33 years, with a range in age from 24 to 59 years. None of the control group subjects had any history of neuroleptic medication and at the time of testing the subjects were not on any other form of medication. The third group consisted of 1 I individuals described as a nondevelopmentally disabled tardive dyskinetic group. The mean age of this group was 53 years, and the individuals ranged in age from 38 to 72 years. The fourth group contained 40 developmentally disabled (severely and profoundly mentally retarded) adults who had no history of neuroleptic medication regimes. The mean age of this group was 39 years, with an age range from 16 to 73 years. The exact medication history of the two tardive dyskinesia groups was not available, which is often the case with individuals in these populations. All subjects in both groups, however, had been on neuroleptic medication for a number of years, and all were diagnosed by their consulting physician as having tardive dyskinesia. The severity of tardive dyskinesia was also examined by rating scale methods. The tardive dyskinesia of the developmentally disabled group had been evaluated through the use of the DISCUS tardive dyskinesia rating scale test (Sprague et al.. 1989). The mean DISCUS score of the developmentally disabled with tardive dyskinesia group was 7.7, with a range of 3.0 to 16.0. Most of the subjects in the group were assessed as falling above the cutoff score of 5 (cf. Sprague et al., 1989) for determining the presence of tardive dyskinesia. The tardive dyskinesia of normal intelligence subjects was also determined both by clinical judgment and the DISCUS rating scale. The mean DISCUS score of the group was 8.4, with a range of 2.0 to 12.0. All but one subject were judged by
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the rating scale test as falling within the tardive dyskinesia range. Thus, the range and mean DISCUS scores of the tardive dyskinesia group of average or above average intelligence were consistent with that of the developmentally disabled with tardive dyskinesia group. 2.2. Apparatus The acceleration of each finger and arm effector unit was measured with a Coulboum T45-10 accelerometer. The T45-10 is a one-axial miniature solid state piezoresistive accelerometer with a full scale direct current (DC) frequency response up to 500 Hz. Each accelerometer was factory calibrated and provided with an individual sensitivity level. To calibrate the voltage output the accelerometer was zero balanced in DC mode with the accelerometer fixed in a horizontal position on a level surface. The amplified accelerometer data were collected on a PC through a 12-bit analog to digital converter. Given that the spectral bandwidth of interest in finger tremor does not exceed 30 Hz, and that the frequency of arm tremor is even slower than that of finger tremor (Van Emmerik et al., 1993a; Marsden, 19841, a digital Butterworth low-pass filter with a cutoff of 30 Hz was used to filter the data for both the finger and arm tremor tasks. All acceleration data was collected at a sample rate of 200 Hz. 2.3. Procedures The procedures for testing the different groups of subjects were identical. The testing for all subjects took place in an isolated testing room with similar environmental testing conditions. The finger and arm tremor were recorded in the same experimental session for each subject. Preliminary analysis of the variability of the finger (Van Emmerik et al., 1993a) and arm tremor (Van Emmerik et al., 1993b) data have been reported, but these papers did not examine the coupling between limbs in these tasks or the within-subject coupling relations across the postural tasks. For the finger tremor task each person was seated in a chair of normal height and rested both forearms on a table of normal desk top height. Accelerometers were taped to the nail of the index finger of both the left and right hand. Subjects were asked and shown to make a fist with each hand, to rest each hand on the table, and to outstretch each index finger so that it was still and parallel to the table with the nail of the index finger facing upward. In the arm tremor task the accelerometers were fixed on the third metacarpal of the dorsal surface of the wrist of both the right and left hands. The subjects task was to stand still on
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a force platform with both arms outstretched in front of them, with the arms, wrist and fingers still and parallel to the ground. In both tasks subjects performed two 10 s trials in each condition. Each subject had previously produced, in both the finger and arm tasks, two trials on each limb measured in a single limb tremor protocol the data of which are not presented here (see Van Emmerik et al., 1993a, b). Not all subjects completed each postural tremor task but the number of subjects or trials dropped from analysis in each group (the non-normal groups) was very small as shown by the degrees of freedom reported for each analysis in the subsequent results section.
3. Results The analyses of the coupling between limbs was separated by task into finger and arm tremor. The coordination between the limbs in each task was examined in both the time and frequency domains. The final section of the results examines the within-subject relation between coupling across the finger and the arm tremor data. 3.1. Finger tremor The variability (standard deviation) of the finger acceleration values as a function of group have been reported previously in Van Emmerik et al. (1993a). In brief, the variability of acceleration was significantly higher in the two groups with tardive dyskinesia than the two nontardive dyskinetic groups. There was no difference in degree of variability between the two tardive dyskinetic groups or between the two nontardive dyskinetic groups. 3. I. I. Time domain The relation in the time domain between the fingers was assessed though correlating (using Pearson Product correlation coefficient) the acceleration values of each index finger over the time span of each trial. The mean group correlations of the acceleration signals were considered with respect to their absolute and algebraic values. Fig. 1 shows the mean absolute correlation values for finger tremor as a function of population group. The group effect on the absolute correlation was significant, F(3,93) = 4.67, p < 0.01. Post hoc tests revealed that the tardive dyskinetic group of normal intelligence had a significantly higher absolute correlation than all the other groups and that the control group had a significantly lower correlation than both
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TD
hlR
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TDtMR
Group Fig. 1. Mean correlation for finger and arm tremor as a function of population group. (C = control group; MR = group with mental retardation; TD = group with tardive dyskinesia; TDfMR = group with tardive dyskinesia and mental retardation.)
the severely/profoundly mentally retarded tardive dyskinetic group and the severely/profoundly mentally retarded group without tardive dyskinesia. These latter two groups were not significantly different from each other. The main effect of trial and the trial by group interaction for the absolute correlations were both nonsignificant ( p’s > 0.05). The group effect on the algebraic value of the correlations was nonsignificant, F(3,93) = 1.07, p > 0.05. The trial main effect and the trial by group interaction effect for the algebraic correlations were also both nonsignificant ( p’s > 0.05). The pattern of the relative group algebraic values was similar to the pattern of the group absolute values shown in Fig. 1. 3.1.2. Frequency domain The finger tremor frequency domain was assessed in the range of 30 Hz and below as this accommodated the majority of the frequency range of the signal. Table 1 shows the mean coherence value (expressed as a proportion) and the mean phase difference at maximum coherence as a function of group. The coherence quantity measures the linear correlation between the two components of the bivariate process at frequency w and is analogous to the square of a usual correlation coefficient (Chatfield, 1984). The coherence values are generally low (0.22 to 0.25) and the group effect on the mean coherence values was nonsignif-
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Table I Mean coherence (proportion). phase lag (degrees) at maximum coherence and continuous relative phase measures (algebraic, absolute and standard deviation values in degrees) of finger and arm tremor as a function of population group. Standard deviation values are in parentheses Control Finger Coherence Phase lag Cont. tel.
ph.(ak)
Cont. rel. ph. tabs) AU!? Coherence Phase lag Cont. rel. ph. (alg) Cont. ret. ph. cabs)
0.25 (0.09) -5.01 (66.46) - 1.89 (79.68) 63.64
0.790 (0.25) - 0.239 (4.09) - 1.98 t- 17.16) 14.13
TD
0.22 (0.07) 38.18 (95.55) -0.87 (84.65) 70.8 I
0.555 (0.28) - 5.05 (22.58) 0.46 (- 34.07) 21.48
MR
TD+MR
0.24 (0.14) -5.34 (100.55) - 2.23 (90.62) 17.43
0.23 (0.11) 34.18 (105.31) - 1.53 (89.92) 75.62
0.30 I (0.15) -11.114 (70.53) 2.9 I (73.77) 61.54
0.314 (0.19) 4.4 (90.84) 0.12 (85.38) 73.83
Note: Control = normal healthy group; TD = tardive dyskinesia group: MR = severely/profoundly retarded group; TDf MR = tardive dyskinesia and severely/profoundly mentally retarded group.
mentally
icant, F(3,93) < 1. The trial main effect and the trial by group interaction were both nonsignificant on the mean coherence values ( p’s > 0.05). The phase difference or phase lag at maximum coherence was also calculated. The main effect of population group was nonsignificant on the phase difference at maximum coherence, F(3,93) = 1.33, p > 0.05, although there was a trend for the tardive dyskinesia groups to have a larger phase lag between the fingers. The trial main effect and the trial by group interaction were also nonsignificant (p’s > 0.05). The values for phase lag variability at maximum coherence were high across all groups, but there was no significant group effect (p’s > 0.05). A further assessment of the frequency relations between the fingers as a function of group was made through the calculation of continuous relative phase. The acceleration signal for each finger was differentiated and the phase angle for each finger calculated so that a phase difference between fingers could be determined for each time point in the trial. The mean absolute, mean algebraic, and standard deviation values of continuous relative phase were determined and these are shown in Table 1 as a function of group. The algebraic mean of continuous relative phase tends to zero in all groups while the variability of this relative phase measure is high (SDS 80 to 901, although similar
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across all groups. ANOVA showed that there were no group differences of these values of continuous relative phase ( p’s > 0.05).
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3.2. Arm tremor The variability in the arm acceleration values has been reported previously in Van Emmerik et al. (1993b). Briefly, the data revealed that the two tardive dyskinetic groups had higher arm variability than the two nontardive dyskinetic groups. Again, as with finger tremor, there was no significant difference in the degree of variability of the two tardive dyskinetic groups and between the two nontardive dyskinetic groups. 3.2.1. Time domain The mean absolute values of the correlation of the arm acceleration time-series as a function of population group are shown in Fig. 1. These correlation values are generally larger than the respective group finger tremor correlations that are also shown in Fig. 1. The main effect of group on the absolute correlation value was significant, F(3,88) = 9.21, p < 0.01. Post hoc analysis revealed that the tardive dyskinetic group of normal intelligence had a higher correlation between arms than all the other groups. Furthermore, the control group had a lower correlation between arms than all other groups, while the profoundly/severely mentally retarded group and the tardive dyskinetic group with profound/severe mental retardation were not different from each other. There was a trial main effect, F(1,88) = 5.44, p < 0.05, with the first trial having a consistently higher correlation than the second trial. The group by trial interaction was nonsignificant ( p > 0.05). The group effect on the algebraic value of the correlation was nonsignificant, F(3,88) = 1.22, p > 0.05. The trial main effect and the trial by group interaction effect were both nonsignificant ( p’s > 0.05). As with the finger tremor data, the mean correlation values were slightly lower in the algebraic than the absolute correlation values. The similarity of the pattern of the algebraic and absolute group mean correlation values suggests, however, that the predominant mode of coupling in the arm tremor task was in-phase rather than anti-phase. 3.2.2. Frequency domain The dominant frequency spectrum of arm tremor is significantly lower than finger tremor (Marsden, 1984). Accordingly, we analyzed the frequency properties within the range of less than 15 Hz as that accommodates most of the frequency range of the arm acceleration signal (Van Emmerik et al., 1993b).
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Coherence and phase difference at maximum coherence of the arm signals were determined. Table 1 shows the mean coherence of the acceleration time-series as a function of group and the mean phase lag between the acceleration signals as a function of group. The coherence data on the arm tremor produced much larger values (0.30 to 0.79) than those reported for finger tremor. The main effect of population group for mean coherence was significant, F(3,89) = 35.75, p < 0.01. Post hoc analysis of the coherence data revealed that the two normal intelligence groups had a higher degree of coherence in the frequency profile than the two severely/profoundly mentally retarded groups. There was no difference in mean coherence between the two nonretarded groups or between the two groups with mental retardation. The trial effect and the trial by group interaction were both nonsignificant for mean coherence ( p’s > 0.05). The analysis of the phase lag at the maximum coherence determined that the group, trial, and trial by group interaction were all nonsignificant (p’s > 0.05). The means shown in Table 1 reveal that the phase lags for arm tremor varied little from zero and were generally lower than that reported for finger tremor. There was, however, a significant difference in the variability of phase lag, F(3,89) = 23.18, p < 0.01, with the tardive dyskinesia and mental retardation group having a significantly higher phase lag variability than the other groups. The mental retardation group also had a significantly higher phase lag variability than the two groups without mental retardation. The assessment of continuous relative phase between the two arms produced data that was compatible with the other frequency analyses. The algebraic value of continuous relative phase showed that on average subjects relative phase was small and tended to zero across all groups. The mean within-trial variability of the continuous relative phase was different over groups, however, as shown in the standard deviation, F(3,81) = 18.35, p < 0.05, and the absolute value, F(3,81) = 15.38, p < 0.05, for continuous relative phase. Post hoc analyses showed that the normal intelligence groups had a lower variability of continuous relative phase than the mentally retarded groups. The variability in continuous relative phase was lower in the arm than the fingers for the normal intelligence groups, but the level of variability was similar across effector units for the mentally retarded groups. 3.3. Within-subject
correlations
between indices offinger
and arm coordination
The relation between the individual pattern of the degree of constraint on coupling of the fingers and the arms was assessed by considering the within
K.M. Newell, R.L. Sprague/Human Table 2 Correlations
between the mean correlations
Absolute Algebraic
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of arm and finger tremor as a function of group
Control
TJ3
MR
TD+MR
0.03 0.04
0.14 0.19
- 0.06 -0.19
-0.17 0.14
group correlations of the respective indices of coordination in the finger and arm tasks. In normal subjects the generality of individual differences in variability across tasks has been shown previously to be essentially nonexistent (Beggs et al., 1974). The generality of trends in the variability of individuals across tasks may be higher in tardive dyskinetic subjects if there is a coupling constraint on the motor system brought about by the prolonged regimen of neuroleptic medication. There has been no examination of this question in rating scale approaches to the characterization of tardive dyskinesia. Table 2 shows the correlations (absolute and algebraic) between the mean arm and finger absolute correlations as a function of population group. It is useful to assess the degree of relation with and without a consideration of the direction of the relation. Overall, the correlations are uniformly low and all nonsignificant (p’s > 0.05). These findings suggest that there is no relation within-subject in any group between the inter-limb coupling in the time domain in the finger and arm tremor tasks.
4. Discussion This study examined the inter-limb coupling in finger and arm tremor during arm postural tasks as a function of population conditions. The population groups consisted of an adult tardive dyskinetic group, an adult group with severe/profound mental retardation, an adult group with tardive dyskinesia and severe/profound mental retardation, and a normal healthy age-matched control group. It is well established that there is more movement variability produced by tardive dyskinetic than normal subjects in postural tasks (Caligiuri and Lohr, 1990; Van Emmerik et al., 1993a, b), but there is little evidence as to if and how tardive dyskinesia constrains the inter-limb coupling organization of the motor system over and above that exhibited by normal subjects. In examining this question in the current arm posture experiments, it is important to reemphasize that neither the finger nor the arm tasks used in this study had explicit task instructions or other constraints that required subjects to couple the limbs with any particular strategy in the pursuit of minimizing motion variability of the
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respective effector units. The findings show some population group effects that are consistent over the time and frequency domains, but there are also a few inconsistencies within population groups in the degree and nature of the coupling between limbs. In the time domain, the tardive dyskinesia without mental retardation group exhibited the greatest degree of correlation in the level of acceleration between fingers and between the arms. This tardive dyskinesia group had a higher mean age than the other tardive dyskinesia group and, therefore, this finding is consistent with the established notion that advanced age magnifies the effects of tardive dyskinesia (Kane and Smith, 1982; Sprague and Kalachnik, 1991). The normal group had the lowest correlation in acceleration between the limbs in both the finger tremor and arm tremor tasks. Indeed, in the finger task, there was essentially no common variance between the acceleration values of the two limbs, a finding that is consistent with the earlier work of Marsden et al. (1969a, b). The time domain relations between limbs were enhanced for all groups in the arm tremor task when compared to the finger tremor task. This suggests that the mass of the limb adds additional coupling constraints to the postural tasks over and above those provided by the population group effects of mental retardation and tardive dyskinesia. The influence of limb mass on inter-limb coupling in postural tasks deserves a more systematic investigation than that provided here through the finger and arm task manipulations, which naturally confound mass differences with other changes in structural and functional organization. There were significant differences in the population group effects in inter-limb coupling when considered in the frequency domain. In all groups the degree of mean coherence was greater in the arm tremor task than the finger tremor task. This effect parallels the time domain correlations for the groups and provides further evidence that enhanced mass increases the coupling of the limbs in postural tasks. The mean coherence in the arm tremor was particularly high in the groups of normal intelligence with the control group having the highest mean coherence. These group trends for coherence in the frequency domain are inversely related to phase lag variability. It appears the two groups with mental retardation have particular difficulty minimizing phase lag variability in the arm task and that this is related to lower mean coherence. This effect is magnified in the group with mental retardation and tardive dyskinesia which confirms earlier findings that mental retardation interacts with tardive dyskinesia in the control of posture (Van Emmerik et al., 1993a, b). The evidence of a relation in inter-limb postural motion in the tardive dyskinesia groups is consistent with the general proposition that prolonged
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intake of neuroleptic medication constrains the output of the motor system (Newell, in press; Newell et al., 1993a). Previous analyses had shown this effect in tardive dyskinesia within the output of a single limb (Newell et al., 19951, but here the neural coupling constraint in tardive dyskinesia is shown in inter-limb coordination. The data also reveal in the arm tremor task, where the correlations between the limbs were higher than in finger tremor, that practice is a factor in reducing the degree of coupling constraint between limbs in that there was an higher correlation on the first than the second trial. This practice effect although over a very short time period is consistent with the general proposition that the coordination solution can change with practice to accommodate the independent regulation of more degrees of freedom (Arutyunyan et al., 1968, 1969; Bernstein, 1967; Newell and McDonald, 1994). In all groups there was essentially no relation between the degree of coupling in the fingers and the degree of coupling in the arms. This suggests that the effect of prolonged intake of neuroleptic medication has a selective effect on the disturbance to the organization of movement. In rating scale analyses of tardive dyskinesia a pattern between the overall level of the movement disorder and the contributions to that assessment from specific effector units (e.g., lips, tongue, toes, fingers, etc.) has not been established to date (cf. Sprague et al., 1989). The data reported here suggest that this relation is weak or nonexistent in tardive dyskinesia but this is clearly an area in need of additional research. The finding of no relation in the degree of coupling across effector units in the normal subjects is consistent with previous research that suggests there are no general individual difference effects in variability considered across tasks (Beggs et al., 1974) and that no common source is driving the tremor in the two limbs (Marsden et al., 1969a, b). In summary, the findings of this study are consistent with the proposition that prolonged intake of neuroleptic medication constrains the coupling organization of motor output in inter-limb tasks (Newell, in press). This constraint reduces the potential adaptive control of the limbs and is related to enhanced variability in performance on the task criterion (Van Emmerik et al., 1993a, b). Our findings suggest that these effects are selective to particular effector units rather than general to the motor system, and that the enhanced mass of the limb significantly influences the degree of constraint on inter-limb postural tremor. Acknowledgements The preparation of this article was supported by National Institutes of Health Grant PHS ROl HD21212. Richard van Emmerik assisted with data collection
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and Tim Benner with data analysis. We would like to thank Steven Morrison and the reviewers for helpful comments on earlier versions of the manuscript.
References Alpert, M., F. Diamond and A.J. Friedhoff, 1976. Tremorgraphic studies in tardive dyskinesia. Psychopharmacology Bulletin 12. 5-7. American Psychiatric Association, 1979. Tardive dyskinesia. Washington DC: American Psychiatric Association. American Psychiatric Association, 1992. Tardive dyskinesia: A task force report of the American Psychiatric Association. Washington DC: American Psychiatric Association Task Force on Tardive Dyskinesia. Arutyunyan, G.H., V.S. Gurlinkel, and M.L. Mirskii, 1968. Investigation of aiming at a target. Biophysics 13, 536-538. Arutyunyan. G.H., V.S. Gurfinkel and M.L. Mirskii, 1969. Organization of movements on execution by man of an exact postural task. Biophysics 14, 1162-I 167. Beggs, W.D.A., R. Sakstein and C.I. Howarth, 1974. The generality of a theory of the intermittent control of accurate movements. Ergonomics 17. 757-768. Bernstein. N.. 1967. The co-ordination and regulation of movements. New York: Pergamon Press. Caligiuri, M. and J.B. Lohr, 1990. Fine force instability: A quantitative measure of neuroleptic-induced dyskinesia in the hand. Journal of Neuropsychiatry 2, 395-398. Chatfield, C., 1984. The analysis of time series (3rd Ed.). London: Chapman and Hall. Glass, L. and M.C. Mackey. 1988. From clocks to chaos: The rhythms of life. Princeton, NJ: Princeton University Press. Guy, W. (Ed.), 1976. ECDEU assessment manual for psychopharmacology. Washington DC: US Government Printing Office. Hansen. T.E.. W.M. Glazer and D.C. Moore, 1986. Tremor and tardive dyskinesia. Journal of Clinical Psychiatry 47, 461-464. Hilborn, R.C., 1994. Chaos and nonlinear dynamics. Oxford: Oxford University Press. Jeste, D.V. and R.J. Wyatt, 1982. Understanding and treating tardive dyskinesia. New York: Guildford Press. Kalachnik. J.E., 1984. ‘Tardive dyskinesia and the mentally retarded: A review’. In: S.E. Bruening (Ed.), Advances in mental retardation and developmental disabilities (Vol. 2, pp. 329-356). Greenwich, CT: JAI Press. Kalachnik. J.E.. S.R. Harder, P. Kidd-Nielson. E. Errickson, M. Doebler and R.L. Sprague, 1984. Persistent tardive dyskinesia in randomly assigned neuroleptic medication, neuroleptic nonreduction, and no-neuroleptic history groups: Preliminary results. Psychopharmacology Bulletin 20, 27-32. Kane, J.M. and J.M. Smith. 1982. Tardive dyskinesia: Prevalence and risk factors, 1959-1979. Archives of General Psychiatry 39. 473-48 1. Ko, Y.G., R.E.A. van Emmerik, R.L. Sprague and K.M. Newell, 1992. Postural stability, tardive dyskinesia and developmental disability. Journal of Intellectual Disability 36, 309-323. Marsden, C.D., 1984. ‘Origins of normal and pathological tremor’. In: L.J. Findley and R. Capildeo (Eds.), Movement disorders: Tremor (pp. 37-84). New York: Oxford University Press. Marsden. C.D., J.C. Meadows, G.W. Lange and R.S. Watson, 1969a. The role of the ballistocardiac impulse in the genesis of physiological tremor. Brain 92, 647-662. Marsden, C.D., J.C. Meadows, G.W. Lange and R.S. Watson. 1969b. The relation between physiological tremor of the two hands in healthy subjects. Electroencephalography and Clinical Nemophysiology 27, 179-185. May, P.R.A.. 1987. Measurement of extrapyramidal symptoms and involuntary movement by electronic instruments. Psychopharmacology Bulletin 23, I87- 188.
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Newell, K.M. (in press). ‘The dynamics of tardive dyskinesia’. In: R.L. Sprague and K.M. Newell (Eds.). Stereotypes: Brain-behavior relationships. Washington DC: American Psychological Association. Newell. K.M. and P.V. McDonald, 1994. ‘Learning to coordinate redundant biomechanical degrees of freedom’. In: S. Swinnen, H. Heuer, J. Massion and P. Casaer (Eds.), Interlimb coordination: Neural, dynamical, and cognitive constraints (pp. 515-536). New York: Academic Press. Newell. K.M. and R.L. Sprague, 1990. ‘Early diagnosis of tardive dyskinesia’. In: A. Vermeer (Ed.), Motor development. adapted physical activity and mental retardation (pp. 30-46). Amsterdam: North-Holland. Newell, K.M., F. Gao and R.L. Sprague, 1995. The dynamical structure of tremor in tardive dyskinesia. Chaos 5. 43-47. Newell, K.M.. R.E.A. van Emmerik and R.L. Sprague, 1993a. ‘Stereotypy and variability’. In: K.M. Newell and D.M. Corcos (Eds.), Variability and motor control (pp. 475-496). Champaign, IL: Human Kinetics. Newell, K.M., R.E.A. van Emmerik, D. Lee and R.L. Sprague, 1993b. On postural stability and variability. Gait and Posture 4, 225-230. Packard. N.H., J.P. Crutchfield, J.D. Farmer and R.S. Shaw. 1980. Geometry from a time series. Physical Review Letters 45, 712-715. Rondot, P. and N. Bathien, 1986. ‘Movement disorders in patients with coexistent neuroleptic-induced tremor and tardive dyskinesia: EMG and pharmacological study’. In: M.D. Yahr and K.J. Bergmann (Eds.). Advances in neurology (Vol. 45, pp. 361-366). New York: Raven Press. Simpson, G.M., J.H. Lee and B. Zoubok, 1979. A rating scale for tardive dyskinesia. Psychopharmacology Bulletin 19, 266-276. Sprague, R.L.. J.E. Kalachnik and K.M. Slaw, 1989. Psychometric properties of the Dyskinesia Identification System: Condensed User Scale (DISCUS). Mental Retardation, 27-14 I - 148. New York: Raven Press. Sprague, R.L. and K.M. Newell, 1987. ‘Toward a movement control perspective of tardive dyskinesia’. In: H.Y. Metzler (Ed.), Psychopharmacology: The third generation of progress (pp. 1233- 1238). New York: Raven Press. Sprague. R.L. and J.E. Kalachnik, 1991. Reliability, validity, and a total score cutoff for the Dyskinesia Identification System: Condensed User Scale (DISCUS) with mentally retarded populations. Psychopharmacology Bulletin 27, 5 l-58. Stacy. M. and J. Jankovic, 1992. Tardive tremor. Movement Disorders 7, 53-57. Stone. R.K.. J.E. May, W.F. Alvarez and G. Ellman, 1989. Prevalence of dyskinesia and related movement disorders in a developmentally disabled population. Journal of Mental Deficiency Research 33, 41-53. Tyron. W.W. and B. Pologe, 1987. Accelerometric assessment of tardive dyskinesia. American Journal of Psychiatry 144, 1584-1587. Van Emmerik, R.E.A., R.L. Sprague and K.M. Newell, 1993a. Finger tremor and tardive dyskinesia. Experimental and Clinical Psychopharmacology 1, 259-268. Van Emmerik. R.E.A., R.L. Sprague and K.M. Newell, 1993b. Arm tremor, tardive dyskinesia and developmental disability. American Journal on Mental Retardation 98, 74-93.
Human Movement
Science 15 (1996) 237-251
Tardive dyskinesia and coupling constraints in inter-limb tremor Karl M. Newell a3*, Robert L. Sprague ’ a The
Pennsylcania
State Uniw-sit!.
b Unic,ersity
of Illinois
109 White Building,
at Urbana-Champaign.
Uniwrsity
Park, PA 16802. USA
Urbana-Champaign,
USA
Abstract The coupling of inter-limb tremor in finger and arm postural tasks was examined in adult tardive dyskinetic, severely/profoundly mentally retarded, tardive dyskinetic and severely/profoundly mentally retarded, and normal healthy subjects. In finger tremor, the index fingers were found to operate independently in the time and frequency domains for normal adults but there was a modest level of coupling in the time domain in both tardive dyskinetic groups. Inter-limb coupling in the time and frequency domains was enhanced in arm tremor for all groups, with the effect stronger in the time domain for the tardive dyskinetic groups and in the frequency domain for the groups of normal intelligence. There was also a persistent phase lag in the coupling of the two limbs in both postural tasks for the tardive dyskinetic subjects. These data show that prolonged intake of neuroleptic medication constrains inter-limb coupling even when the task demands do not explicitly require such a coordination strategy. The coupling effects are stronger in arm tremor which suggests that the mass of the effector system is also a factor in constraining the coupling of inter-limb coordination. PsycINFO Kepvrd.s:
classification:
2330; 2580
Tremor: Tardive dyskinesia:
Posture; Coordination
1. Introduction Tardive dyskinesia is a movement disorder syndrome that arises from prolonged use of neuroleptic medication (American Psychiatric Association, 1979,
* Corresponding
author. E-mail: [email protected],
Tel.: +
1 814 863-1163, Fax: + I 814 863-7360.
0167-9457/96/$1.5.00 0 1996 Elsevier Science B.V. All rights reserved SSDI 0167.9457(95)00045-3
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1992; Jeste and Wyatt, 19821, and is particularly prevalent in institutionalized mentally retarded populations (Kalachnik, 1984; Kalachnik et al., 1984; Stone et al., 1989). The symptoms of the disorder include jerky and sometimes rhythmical stereotypic movements of the peripheral effector units, particularly the toes, feet, hands, fingers, lips and tongue, but it can also include disorders in the motions of other body parts. The movement disorders of tardive dyskinesia can be so severe that they can interfere with the conduct of activities of daily living and vocational actions (Sprague and Newell, 1987). The disorder of tardive dyskinesia is sometimes identified clinically with the aid of observational rating scale techniques, such as: AIMS - Abnormal Involuntary Movements Scale (Guy, 1976); Abbreviated Simpson/Rockland Dyskinesia Scale (Simpson et al., 1979); and DISCUS - Dyskinesia Identification System Condensed User Scale (Sprague et al., 1989). However, these techniques are not particularly sensitive to detecting changes and differences in the movement dynamics (Newell and Sprague, 19901, tending to focus on the mere presence of a category of motion in some effector unit that is above a particular threshold level. Recently, there has been more emphasis given to directly recording and examining the movement dynamics of tardive dyskinesia in both nonhuman (Alpert et al., 1976) and human (Caligiuri and Lohr, 1990; Hansen et al., 1986; Rondot and Bathien, 1986; Stacy and Jankovic, 1992; Tyron and Pologe, 1987) species, particularly the tremor-like properties of the stereotypical rhythmic movements. Indeed, tremor has been advocated as a viable movement property to assess the onset and status of tardive dyskinesia (May, 1987; Sprague and Newell, 1987). A standard finding is that the variability of postural tremor is greater in a tardive dyskinetic population when contrasted with an age-matched normal healthy control group (Caligiuri and Lohr, 1990; Van Emmerik et al., 1993a, b; Ko et al., 1992). There is also evidence that the modal frequency of tremor is reduced in the tardive dyskinetic population in that a lower more broadband profile in the frequency spectrum is evident (Van Emmerik et al., 1993a, b). This different frequency profile in the tremor of individuals diagnosed with tardive dyskinesia may be reflective of a unique geometry of the attractor dynamics supporting the postural actions. An attractor is the qualitative geometry of the successive points (trajectories) in phase space of the dynamical system that emerges as the number of iterations of the points goes to infinity (Hilbom, 1994). Recently, there have been direct examinations of the structure of attractor dynamics in postural actions of normal and tardive dyskinetic subjects. In both whole-body posture (Newell et al., 1993b) and finger tremor (Newell et al.,
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1995) it has been shown that the dimensionality (correlation dimension) of the postural time-series is lower in a tardive dyskinetic group than an age-matched normal healthy control group. This finding is consistent with the proposition that the tdrdive dyskinetic system is more constrained in motor output in that fewer degrees of freedom are required to specify the dynamic of the postural time-series (Packard et al., 1980). In short, tardive dyskinesia appears to be reflective of what Glass and Mackey (1988) have called a dynamical disease - the breakdown of normal system organization and exhibition of abnormal dynamics. In this paper we report experiments that examine the influence of tardive dyskinesia on the coupling of inter-limb tremor in postural tasks. The tasks required the subjects to maintain the respective posture of the fingers or arms with minimal motion of the effector units, that is in a dual index fingers task (finger tremor) and a dual arms task (arm tremor). Previously, we have shown that the degree of motion in these postural tasks is greater in tardive dyskinetic subjects than their age-matched counter parts, although the degree of variability in the dual limb task is approximately the same as that produced in the respective single limb task (Van Emmerik et al., 1993a, b). In both the finger and arm dual limb tremor tasks there were no instructional constraints to coordinate the tremors of the two limbs. There has been no extensive study of inter-limb coordination in finger or arm tremor tasks, although Marsden et al. (1969a, b) have provided data suggesting that in normal healthy adult subjects there is no coupling between the two index fingers in a dual limb tremor task. The degree to which the effects of tardive dyskinesia generalize across the different effector units within-subject is poorly understood. Recent studies of the movement dynamics of tardive dyskinesia consistently suggest that the neuroleptic medication appears to overconstrain the motor system and that this influence on coordination is related to enhanced movement variability (Newell, in press; Newell et al., 1993a). The strength of this relation may also vary with the particular effector unit used and the mass of the predominant limb segment(s) supporting the action. In finger tremor the natural resonant frequency of the finger is about 20-25 Hz, which is considerably higher than the 2 Hz resonant frequency that is apparent in elbow tremor (Marsden, 1984). The need to coordinate the limbs in the dual limb postural task may be greater in the larger mass effector system that also has a slower natural modal frequency. Furthermore, given the previous findings on the effect of tat-dive dyskinesia on intra-limb variability, the inter-limb coupling constraint also may be enhanced with the prolonged intake of neuroleptic medication. In summary, this study examined the coupling in inter-limb tremor (time and frequency domains) in finger and arm postural tasks in adult normal healthy,
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retarded, tardive dyskinetic, mentally retarded subjects.
and tardive dyski-
2. Method 2. I. Subjects There were four groups of adult subjects. One group contained 32 individuals (18 men and 14 women> who were diagnosed as developmentally disabled (profoundly and severely mentally retarded) and screened as having tat-dive dyskinesia. The mean age of this group was 34 years, with an age range from 23 to 60 years. In a second group, data from 26 normal healthy adults were collected and matched in age (k six months for each subject matched) and gender with the developmentally disabled and tardive dyskinetic group. The mean age of this normal control group was 33 years, with a range in age from 24 to 59 years. None of the control group subjects had any history of neuroleptic medication and at the time of testing the subjects were not on any other form of medication. The third group consisted of 1 I individuals described as a nondevelopmentally disabled tardive dyskinetic group. The mean age of this group was 53 years, and the individuals ranged in age from 38 to 72 years. The fourth group contained 40 developmentally disabled (severely and profoundly mentally retarded) adults who had no history of neuroleptic medication regimes. The mean age of this group was 39 years, with an age range from 16 to 73 years. The exact medication history of the two tardive dyskinesia groups was not available, which is often the case with individuals in these populations. All subjects in both groups, however, had been on neuroleptic medication for a number of years, and all were diagnosed by their consulting physician as having tardive dyskinesia. The severity of tardive dyskinesia was also examined by rating scale methods. The tardive dyskinesia of the developmentally disabled group had been evaluated through the use of the DISCUS tardive dyskinesia rating scale test (Sprague et al.. 1989). The mean DISCUS score of the developmentally disabled with tardive dyskinesia group was 7.7, with a range of 3.0 to 16.0. Most of the subjects in the group were assessed as falling above the cutoff score of 5 (cf. Sprague et al., 1989) for determining the presence of tardive dyskinesia. The tardive dyskinesia of normal intelligence subjects was also determined both by clinical judgment and the DISCUS rating scale. The mean DISCUS score of the group was 8.4, with a range of 2.0 to 12.0. All but one subject were judged by
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the rating scale test as falling within the tardive dyskinesia range. Thus, the range and mean DISCUS scores of the tardive dyskinesia group of average or above average intelligence were consistent with that of the developmentally disabled with tardive dyskinesia group. 2.2. Apparatus The acceleration of each finger and arm effector unit was measured with a Coulboum T45-10 accelerometer. The T45-10 is a one-axial miniature solid state piezoresistive accelerometer with a full scale direct current (DC) frequency response up to 500 Hz. Each accelerometer was factory calibrated and provided with an individual sensitivity level. To calibrate the voltage output the accelerometer was zero balanced in DC mode with the accelerometer fixed in a horizontal position on a level surface. The amplified accelerometer data were collected on a PC through a 12-bit analog to digital converter. Given that the spectral bandwidth of interest in finger tremor does not exceed 30 Hz, and that the frequency of arm tremor is even slower than that of finger tremor (Van Emmerik et al., 1993a; Marsden, 19841, a digital Butterworth low-pass filter with a cutoff of 30 Hz was used to filter the data for both the finger and arm tremor tasks. All acceleration data was collected at a sample rate of 200 Hz. 2.3. Procedures The procedures for testing the different groups of subjects were identical. The testing for all subjects took place in an isolated testing room with similar environmental testing conditions. The finger and arm tremor were recorded in the same experimental session for each subject. Preliminary analysis of the variability of the finger (Van Emmerik et al., 1993a) and arm tremor (Van Emmerik et al., 1993b) data have been reported, but these papers did not examine the coupling between limbs in these tasks or the within-subject coupling relations across the postural tasks. For the finger tremor task each person was seated in a chair of normal height and rested both forearms on a table of normal desk top height. Accelerometers were taped to the nail of the index finger of both the left and right hand. Subjects were asked and shown to make a fist with each hand, to rest each hand on the table, and to outstretch each index finger so that it was still and parallel to the table with the nail of the index finger facing upward. In the arm tremor task the accelerometers were fixed on the third metacarpal of the dorsal surface of the wrist of both the right and left hands. The subjects task was to stand still on
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a force platform with both arms outstretched in front of them, with the arms, wrist and fingers still and parallel to the ground. In both tasks subjects performed two 10 s trials in each condition. Each subject had previously produced, in both the finger and arm tasks, two trials on each limb measured in a single limb tremor protocol the data of which are not presented here (see Van Emmerik et al., 1993a, b). Not all subjects completed each postural tremor task but the number of subjects or trials dropped from analysis in each group (the non-normal groups) was very small as shown by the degrees of freedom reported for each analysis in the subsequent results section.
3. Results The analyses of the coupling between limbs was separated by task into finger and arm tremor. The coordination between the limbs in each task was examined in both the time and frequency domains. The final section of the results examines the within-subject relation between coupling across the finger and the arm tremor data. 3.1. Finger tremor The variability (standard deviation) of the finger acceleration values as a function of group have been reported previously in Van Emmerik et al. (1993a). In brief, the variability of acceleration was significantly higher in the two groups with tardive dyskinesia than the two nontardive dyskinetic groups. There was no difference in degree of variability between the two tardive dyskinetic groups or between the two nontardive dyskinetic groups. 3. I. I. Time domain The relation in the time domain between the fingers was assessed though correlating (using Pearson Product correlation coefficient) the acceleration values of each index finger over the time span of each trial. The mean group correlations of the acceleration signals were considered with respect to their absolute and algebraic values. Fig. 1 shows the mean absolute correlation values for finger tremor as a function of population group. The group effect on the absolute correlation was significant, F(3,93) = 4.67, p < 0.01. Post hoc tests revealed that the tardive dyskinetic group of normal intelligence had a significantly higher absolute correlation than all the other groups and that the control group had a significantly lower correlation than both
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C
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TD
hlR
243
TDtMR
Group Fig. 1. Mean correlation for finger and arm tremor as a function of population group. (C = control group; MR = group with mental retardation; TD = group with tardive dyskinesia; TDfMR = group with tardive dyskinesia and mental retardation.)
the severely/profoundly mentally retarded tardive dyskinetic group and the severely/profoundly mentally retarded group without tardive dyskinesia. These latter two groups were not significantly different from each other. The main effect of trial and the trial by group interaction for the absolute correlations were both nonsignificant ( p’s > 0.05). The group effect on the algebraic value of the correlations was nonsignificant, F(3,93) = 1.07, p > 0.05. The trial main effect and the trial by group interaction effect for the algebraic correlations were also both nonsignificant ( p’s > 0.05). The pattern of the relative group algebraic values was similar to the pattern of the group absolute values shown in Fig. 1. 3.1.2. Frequency domain The finger tremor frequency domain was assessed in the range of 30 Hz and below as this accommodated the majority of the frequency range of the signal. Table 1 shows the mean coherence value (expressed as a proportion) and the mean phase difference at maximum coherence as a function of group. The coherence quantity measures the linear correlation between the two components of the bivariate process at frequency w and is analogous to the square of a usual correlation coefficient (Chatfield, 1984). The coherence values are generally low (0.22 to 0.25) and the group effect on the mean coherence values was nonsignif-
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Table I Mean coherence (proportion). phase lag (degrees) at maximum coherence and continuous relative phase measures (algebraic, absolute and standard deviation values in degrees) of finger and arm tremor as a function of population group. Standard deviation values are in parentheses Control Finger Coherence Phase lag Cont. tel.
ph.(ak)
Cont. rel. ph. tabs) AU!? Coherence Phase lag Cont. rel. ph. (alg) Cont. ret. ph. cabs)
0.25 (0.09) -5.01 (66.46) - 1.89 (79.68) 63.64
0.790 (0.25) - 0.239 (4.09) - 1.98 t- 17.16) 14.13
TD
0.22 (0.07) 38.18 (95.55) -0.87 (84.65) 70.8 I
0.555 (0.28) - 5.05 (22.58) 0.46 (- 34.07) 21.48
MR
TD+MR
0.24 (0.14) -5.34 (100.55) - 2.23 (90.62) 17.43
0.23 (0.11) 34.18 (105.31) - 1.53 (89.92) 75.62
0.30 I (0.15) -11.114 (70.53) 2.9 I (73.77) 61.54
0.314 (0.19) 4.4 (90.84) 0.12 (85.38) 73.83
Note: Control = normal healthy group; TD = tardive dyskinesia group: MR = severely/profoundly retarded group; TDf MR = tardive dyskinesia and severely/profoundly mentally retarded group.
mentally
icant, F(3,93) < 1. The trial main effect and the trial by group interaction were both nonsignificant on the mean coherence values ( p’s > 0.05). The phase difference or phase lag at maximum coherence was also calculated. The main effect of population group was nonsignificant on the phase difference at maximum coherence, F(3,93) = 1.33, p > 0.05, although there was a trend for the tardive dyskinesia groups to have a larger phase lag between the fingers. The trial main effect and the trial by group interaction were also nonsignificant (p’s > 0.05). The values for phase lag variability at maximum coherence were high across all groups, but there was no significant group effect (p’s > 0.05). A further assessment of the frequency relations between the fingers as a function of group was made through the calculation of continuous relative phase. The acceleration signal for each finger was differentiated and the phase angle for each finger calculated so that a phase difference between fingers could be determined for each time point in the trial. The mean absolute, mean algebraic, and standard deviation values of continuous relative phase were determined and these are shown in Table 1 as a function of group. The algebraic mean of continuous relative phase tends to zero in all groups while the variability of this relative phase measure is high (SDS 80 to 901, although similar
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across all groups. ANOVA showed that there were no group differences of these values of continuous relative phase ( p’s > 0.05).
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on any
3.2. Arm tremor The variability in the arm acceleration values has been reported previously in Van Emmerik et al. (1993b). Briefly, the data revealed that the two tardive dyskinetic groups had higher arm variability than the two nontardive dyskinetic groups. Again, as with finger tremor, there was no significant difference in the degree of variability of the two tardive dyskinetic groups and between the two nontardive dyskinetic groups. 3.2.1. Time domain The mean absolute values of the correlation of the arm acceleration time-series as a function of population group are shown in Fig. 1. These correlation values are generally larger than the respective group finger tremor correlations that are also shown in Fig. 1. The main effect of group on the absolute correlation value was significant, F(3,88) = 9.21, p < 0.01. Post hoc analysis revealed that the tardive dyskinetic group of normal intelligence had a higher correlation between arms than all the other groups. Furthermore, the control group had a lower correlation between arms than all other groups, while the profoundly/severely mentally retarded group and the tardive dyskinetic group with profound/severe mental retardation were not different from each other. There was a trial main effect, F(1,88) = 5.44, p < 0.05, with the first trial having a consistently higher correlation than the second trial. The group by trial interaction was nonsignificant ( p > 0.05). The group effect on the algebraic value of the correlation was nonsignificant, F(3,88) = 1.22, p > 0.05. The trial main effect and the trial by group interaction effect were both nonsignificant ( p’s > 0.05). As with the finger tremor data, the mean correlation values were slightly lower in the algebraic than the absolute correlation values. The similarity of the pattern of the algebraic and absolute group mean correlation values suggests, however, that the predominant mode of coupling in the arm tremor task was in-phase rather than anti-phase. 3.2.2. Frequency domain The dominant frequency spectrum of arm tremor is significantly lower than finger tremor (Marsden, 1984). Accordingly, we analyzed the frequency properties within the range of less than 15 Hz as that accommodates most of the frequency range of the arm acceleration signal (Van Emmerik et al., 1993b).
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Coherence and phase difference at maximum coherence of the arm signals were determined. Table 1 shows the mean coherence of the acceleration time-series as a function of group and the mean phase lag between the acceleration signals as a function of group. The coherence data on the arm tremor produced much larger values (0.30 to 0.79) than those reported for finger tremor. The main effect of population group for mean coherence was significant, F(3,89) = 35.75, p < 0.01. Post hoc analysis of the coherence data revealed that the two normal intelligence groups had a higher degree of coherence in the frequency profile than the two severely/profoundly mentally retarded groups. There was no difference in mean coherence between the two nonretarded groups or between the two groups with mental retardation. The trial effect and the trial by group interaction were both nonsignificant for mean coherence ( p’s > 0.05). The analysis of the phase lag at the maximum coherence determined that the group, trial, and trial by group interaction were all nonsignificant (p’s > 0.05). The means shown in Table 1 reveal that the phase lags for arm tremor varied little from zero and were generally lower than that reported for finger tremor. There was, however, a significant difference in the variability of phase lag, F(3,89) = 23.18, p < 0.01, with the tardive dyskinesia and mental retardation group having a significantly higher phase lag variability than the other groups. The mental retardation group also had a significantly higher phase lag variability than the two groups without mental retardation. The assessment of continuous relative phase between the two arms produced data that was compatible with the other frequency analyses. The algebraic value of continuous relative phase showed that on average subjects relative phase was small and tended to zero across all groups. The mean within-trial variability of the continuous relative phase was different over groups, however, as shown in the standard deviation, F(3,81) = 18.35, p < 0.05, and the absolute value, F(3,81) = 15.38, p < 0.05, for continuous relative phase. Post hoc analyses showed that the normal intelligence groups had a lower variability of continuous relative phase than the mentally retarded groups. The variability in continuous relative phase was lower in the arm than the fingers for the normal intelligence groups, but the level of variability was similar across effector units for the mentally retarded groups. 3.3. Within-subject
correlations
between indices offinger
and arm coordination
The relation between the individual pattern of the degree of constraint on coupling of the fingers and the arms was assessed by considering the within
K.M. Newell, R.L. Sprague/Human Table 2 Correlations
between the mean correlations
Absolute Algebraic
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of arm and finger tremor as a function of group
Control
TJ3
MR
TD+MR
0.03 0.04
0.14 0.19
- 0.06 -0.19
-0.17 0.14
group correlations of the respective indices of coordination in the finger and arm tasks. In normal subjects the generality of individual differences in variability across tasks has been shown previously to be essentially nonexistent (Beggs et al., 1974). The generality of trends in the variability of individuals across tasks may be higher in tardive dyskinetic subjects if there is a coupling constraint on the motor system brought about by the prolonged regimen of neuroleptic medication. There has been no examination of this question in rating scale approaches to the characterization of tardive dyskinesia. Table 2 shows the correlations (absolute and algebraic) between the mean arm and finger absolute correlations as a function of population group. It is useful to assess the degree of relation with and without a consideration of the direction of the relation. Overall, the correlations are uniformly low and all nonsignificant (p’s > 0.05). These findings suggest that there is no relation within-subject in any group between the inter-limb coupling in the time domain in the finger and arm tremor tasks.
4. Discussion This study examined the inter-limb coupling in finger and arm tremor during arm postural tasks as a function of population conditions. The population groups consisted of an adult tardive dyskinetic group, an adult group with severe/profound mental retardation, an adult group with tardive dyskinesia and severe/profound mental retardation, and a normal healthy age-matched control group. It is well established that there is more movement variability produced by tardive dyskinetic than normal subjects in postural tasks (Caligiuri and Lohr, 1990; Van Emmerik et al., 1993a, b), but there is little evidence as to if and how tardive dyskinesia constrains the inter-limb coupling organization of the motor system over and above that exhibited by normal subjects. In examining this question in the current arm posture experiments, it is important to reemphasize that neither the finger nor the arm tasks used in this study had explicit task instructions or other constraints that required subjects to couple the limbs with any particular strategy in the pursuit of minimizing motion variability of the
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respective effector units. The findings show some population group effects that are consistent over the time and frequency domains, but there are also a few inconsistencies within population groups in the degree and nature of the coupling between limbs. In the time domain, the tardive dyskinesia without mental retardation group exhibited the greatest degree of correlation in the level of acceleration between fingers and between the arms. This tardive dyskinesia group had a higher mean age than the other tardive dyskinesia group and, therefore, this finding is consistent with the established notion that advanced age magnifies the effects of tardive dyskinesia (Kane and Smith, 1982; Sprague and Kalachnik, 1991). The normal group had the lowest correlation in acceleration between the limbs in both the finger tremor and arm tremor tasks. Indeed, in the finger task, there was essentially no common variance between the acceleration values of the two limbs, a finding that is consistent with the earlier work of Marsden et al. (1969a, b). The time domain relations between limbs were enhanced for all groups in the arm tremor task when compared to the finger tremor task. This suggests that the mass of the limb adds additional coupling constraints to the postural tasks over and above those provided by the population group effects of mental retardation and tardive dyskinesia. The influence of limb mass on inter-limb coupling in postural tasks deserves a more systematic investigation than that provided here through the finger and arm task manipulations, which naturally confound mass differences with other changes in structural and functional organization. There were significant differences in the population group effects in inter-limb coupling when considered in the frequency domain. In all groups the degree of mean coherence was greater in the arm tremor task than the finger tremor task. This effect parallels the time domain correlations for the groups and provides further evidence that enhanced mass increases the coupling of the limbs in postural tasks. The mean coherence in the arm tremor was particularly high in the groups of normal intelligence with the control group having the highest mean coherence. These group trends for coherence in the frequency domain are inversely related to phase lag variability. It appears the two groups with mental retardation have particular difficulty minimizing phase lag variability in the arm task and that this is related to lower mean coherence. This effect is magnified in the group with mental retardation and tardive dyskinesia which confirms earlier findings that mental retardation interacts with tardive dyskinesia in the control of posture (Van Emmerik et al., 1993a, b). The evidence of a relation in inter-limb postural motion in the tardive dyskinesia groups is consistent with the general proposition that prolonged
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intake of neuroleptic medication constrains the output of the motor system (Newell, in press; Newell et al., 1993a). Previous analyses had shown this effect in tardive dyskinesia within the output of a single limb (Newell et al., 19951, but here the neural coupling constraint in tardive dyskinesia is shown in inter-limb coordination. The data also reveal in the arm tremor task, where the correlations between the limbs were higher than in finger tremor, that practice is a factor in reducing the degree of coupling constraint between limbs in that there was an higher correlation on the first than the second trial. This practice effect although over a very short time period is consistent with the general proposition that the coordination solution can change with practice to accommodate the independent regulation of more degrees of freedom (Arutyunyan et al., 1968, 1969; Bernstein, 1967; Newell and McDonald, 1994). In all groups there was essentially no relation between the degree of coupling in the fingers and the degree of coupling in the arms. This suggests that the effect of prolonged intake of neuroleptic medication has a selective effect on the disturbance to the organization of movement. In rating scale analyses of tardive dyskinesia a pattern between the overall level of the movement disorder and the contributions to that assessment from specific effector units (e.g., lips, tongue, toes, fingers, etc.) has not been established to date (cf. Sprague et al., 1989). The data reported here suggest that this relation is weak or nonexistent in tardive dyskinesia but this is clearly an area in need of additional research. The finding of no relation in the degree of coupling across effector units in the normal subjects is consistent with previous research that suggests there are no general individual difference effects in variability considered across tasks (Beggs et al., 1974) and that no common source is driving the tremor in the two limbs (Marsden et al., 1969a, b). In summary, the findings of this study are consistent with the proposition that prolonged intake of neuroleptic medication constrains the coupling organization of motor output in inter-limb tasks (Newell, in press). This constraint reduces the potential adaptive control of the limbs and is related to enhanced variability in performance on the task criterion (Van Emmerik et al., 1993a, b). Our findings suggest that these effects are selective to particular effector units rather than general to the motor system, and that the enhanced mass of the limb significantly influences the degree of constraint on inter-limb postural tremor. Acknowledgements The preparation of this article was supported by National Institutes of Health Grant PHS ROl HD21212. Richard van Emmerik assisted with data collection
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and Tim Benner with data analysis. We would like to thank Steven Morrison and the reviewers for helpful comments on earlier versions of the manuscript.
References Alpert, M., F. Diamond and A.J. Friedhoff, 1976. Tremorgraphic studies in tardive dyskinesia. Psychopharmacology Bulletin 12. 5-7. American Psychiatric Association, 1979. Tardive dyskinesia. Washington DC: American Psychiatric Association. American Psychiatric Association, 1992. Tardive dyskinesia: A task force report of the American Psychiatric Association. Washington DC: American Psychiatric Association Task Force on Tardive Dyskinesia. Arutyunyan, G.H., V.S. Gurlinkel, and M.L. Mirskii, 1968. Investigation of aiming at a target. Biophysics 13, 536-538. Arutyunyan. G.H., V.S. Gurfinkel and M.L. Mirskii, 1969. Organization of movements on execution by man of an exact postural task. Biophysics 14, 1162-I 167. Beggs, W.D.A., R. Sakstein and C.I. Howarth, 1974. The generality of a theory of the intermittent control of accurate movements. Ergonomics 17. 757-768. Bernstein. N.. 1967. The co-ordination and regulation of movements. New York: Pergamon Press. Caligiuri, M. and J.B. Lohr, 1990. Fine force instability: A quantitative measure of neuroleptic-induced dyskinesia in the hand. Journal of Neuropsychiatry 2, 395-398. Chatfield, C., 1984. The analysis of time series (3rd Ed.). London: Chapman and Hall. Glass, L. and M.C. Mackey. 1988. From clocks to chaos: The rhythms of life. Princeton, NJ: Princeton University Press. Guy, W. (Ed.), 1976. ECDEU assessment manual for psychopharmacology. Washington DC: US Government Printing Office. Hansen. T.E.. W.M. Glazer and D.C. Moore, 1986. Tremor and tardive dyskinesia. Journal of Clinical Psychiatry 47, 461-464. Hilborn, R.C., 1994. Chaos and nonlinear dynamics. Oxford: Oxford University Press. Jeste, D.V. and R.J. Wyatt, 1982. Understanding and treating tardive dyskinesia. New York: Guildford Press. Kalachnik. J.E., 1984. ‘Tardive dyskinesia and the mentally retarded: A review’. In: S.E. Bruening (Ed.), Advances in mental retardation and developmental disabilities (Vol. 2, pp. 329-356). Greenwich, CT: JAI Press. Kalachnik. J.E.. S.R. Harder, P. Kidd-Nielson. E. Errickson, M. Doebler and R.L. Sprague, 1984. Persistent tardive dyskinesia in randomly assigned neuroleptic medication, neuroleptic nonreduction, and no-neuroleptic history groups: Preliminary results. Psychopharmacology Bulletin 20, 27-32. Kane, J.M. and J.M. Smith. 1982. Tardive dyskinesia: Prevalence and risk factors, 1959-1979. Archives of General Psychiatry 39. 473-48 1. Ko, Y.G., R.E.A. van Emmerik, R.L. Sprague and K.M. Newell, 1992. Postural stability, tardive dyskinesia and developmental disability. Journal of Intellectual Disability 36, 309-323. Marsden, C.D., 1984. ‘Origins of normal and pathological tremor’. In: L.J. Findley and R. Capildeo (Eds.), Movement disorders: Tremor (pp. 37-84). New York: Oxford University Press. Marsden. C.D., J.C. Meadows, G.W. Lange and R.S. Watson, 1969a. The role of the ballistocardiac impulse in the genesis of physiological tremor. Brain 92, 647-662. Marsden, C.D., J.C. Meadows, G.W. Lange and R.S. Watson. 1969b. The relation between physiological tremor of the two hands in healthy subjects. Electroencephalography and Clinical Nemophysiology 27, 179-185. May, P.R.A.. 1987. Measurement of extrapyramidal symptoms and involuntary movement by electronic instruments. Psychopharmacology Bulletin 23, I87- 188.
K.M. Newell. R.L. Sprague/Human
Movement Science 15 f15961237-251
251
Newell, K.M. (in press). ‘The dynamics of tardive dyskinesia’. In: R.L. Sprague and K.M. Newell (Eds.). Stereotypes: Brain-behavior relationships. Washington DC: American Psychological Association. Newell. K.M. and P.V. McDonald, 1994. ‘Learning to coordinate redundant biomechanical degrees of freedom’. In: S. Swinnen, H. Heuer, J. Massion and P. Casaer (Eds.), Interlimb coordination: Neural, dynamical, and cognitive constraints (pp. 515-536). New York: Academic Press. Newell. K.M. and R.L. Sprague, 1990. ‘Early diagnosis of tardive dyskinesia’. In: A. Vermeer (Ed.), Motor development. adapted physical activity and mental retardation (pp. 30-46). Amsterdam: North-Holland. Newell, K.M., F. Gao and R.L. Sprague, 1995. The dynamical structure of tremor in tardive dyskinesia. Chaos 5. 43-47. Newell, K.M.. R.E.A. van Emmerik and R.L. Sprague, 1993a. ‘Stereotypy and variability’. In: K.M. Newell and D.M. Corcos (Eds.), Variability and motor control (pp. 475-496). Champaign, IL: Human Kinetics. Newell, K.M., R.E.A. van Emmerik, D. Lee and R.L. Sprague, 1993b. On postural stability and variability. Gait and Posture 4, 225-230. Packard. N.H., J.P. Crutchfield, J.D. Farmer and R.S. Shaw. 1980. Geometry from a time series. Physical Review Letters 45, 712-715. Rondot, P. and N. Bathien, 1986. ‘Movement disorders in patients with coexistent neuroleptic-induced tremor and tardive dyskinesia: EMG and pharmacological study’. In: M.D. Yahr and K.J. Bergmann (Eds.). Advances in neurology (Vol. 45, pp. 361-366). New York: Raven Press. Simpson, G.M., J.H. Lee and B. Zoubok, 1979. A rating scale for tardive dyskinesia. Psychopharmacology Bulletin 19, 266-276. Sprague, R.L.. J.E. Kalachnik and K.M. Slaw, 1989. Psychometric properties of the Dyskinesia Identification System: Condensed User Scale (DISCUS). Mental Retardation, 27-14 I - 148. New York: Raven Press. Sprague, R.L. and K.M. Newell, 1987. ‘Toward a movement control perspective of tardive dyskinesia’. In: H.Y. Metzler (Ed.), Psychopharmacology: The third generation of progress (pp. 1233- 1238). New York: Raven Press. Sprague. R.L. and J.E. Kalachnik, 1991. Reliability, validity, and a total score cutoff for the Dyskinesia Identification System: Condensed User Scale (DISCUS) with mentally retarded populations. Psychopharmacology Bulletin 27, 5 l-58. Stacy. M. and J. Jankovic, 1992. Tardive tremor. Movement Disorders 7, 53-57. Stone. R.K.. J.E. May, W.F. Alvarez and G. Ellman, 1989. Prevalence of dyskinesia and related movement disorders in a developmentally disabled population. Journal of Mental Deficiency Research 33, 41-53. Tyron. W.W. and B. Pologe, 1987. Accelerometric assessment of tardive dyskinesia. American Journal of Psychiatry 144, 1584-1587. Van Emmerik, R.E.A., R.L. Sprague and K.M. Newell, 1993a. Finger tremor and tardive dyskinesia. Experimental and Clinical Psychopharmacology 1, 259-268. Van Emmerik. R.E.A., R.L. Sprague and K.M. Newell, 1993b. Arm tremor, tardive dyskinesia and developmental disability. American Journal on Mental Retardation 98, 74-93.