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The effect of inertial loading on wrist kinetic tremor and rhythmic muscle activity in individuals with essential tremor
Clinical Neurophysiology 122 (2011) 1794–1801
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The effect of inertial loading on wrist kinetic tremor and rhythmic muscle activity in individuals with essential tremor M.E. Héroux a,⇑, G. Pari b,c, K.E. Norman d,e a
School of Human Kinetics, University of British Columbia, 210-6081 University Boulevard, Vancouver, BC, Canada V6T 1Z1 Movement Disorders Clinic, Kingston General Hospital, ON, Canada K7L 2V7 c School of Medicine, Queen’s University, 68 Barrie Street, ON, Canada K7L 3N6 d School of Rehabilitation Therapy, Queen’s University, L.D. Acton Building, ON, Canada K7L 3N6 e Centre for Neuroscience Studies, Queen’s University, Botterell Hall, ON, Canada K7L 3N6 b
a r t i c l e
i n f o
Article history: Accepted 28 October 2010 Available online 21 December 2010 Keywords: Essential tremor Kinetic tremor Electromyography Power spectral analysis Rhythmic muscle activity
a b s t r a c t Objectives: Determine the effect of concentric and eccentric movement and contraction intensity on the strength of rhythmic muscle activity in individuals with essential tremor (ET). Methods: 21 ET subjects and 22 healthy controls produced wrist flexion–extension movements while supporting sub-maximal loads (no-load, 5%, 15% and 25% 1-repetition maximum). Kinetic tremor and wrist extensor neuromuscular activity were recorded using an angular displacement sensor and electromyography (EMG). Results: Rhythmic muscle activity was twice as big during movement compared to previous results involving postural or isometric tasks. ET subjects with greater rhythmic muscle activity had (1) larger overall kinetic tremor amplitude, (2) greater tremor spectral power during eccentric compared to concentric movement and (3) a reduction in overall kinetic tremor amplitude and the percentage of EMG spectral power accounted for by the tremor spectral peak in the presence of inertial loading. Conclusions: Greater than normal kinetic tremor amplitude appears to be limited to ET subjects with higher levels of rhythmic muscle activity. Furthermore, rhythmic muscle activity is much greater during movement compared to during postural or closed-kinetic tasks. Significance: The strength of rhythmic muscle activity in ET is influenced by the type of contraction (i.e., static vs. dynamic) being performed. Clinicians and researchers should include measures of simple kinetic tremor as part of their assessments. Ó 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
1. Introduction The Consensus Statement of the Movement Disorder Society on Tremor (Deuschl et al., 1998) defines kinetic tremor as ‘‘tremor occurring during any voluntary movement’’. This movement can be visually guided or not, as well as goal-directed (e.g., finger-tonose test) or not (e.g., repetitive flexion/extension movements of the hand). The finger-to-nose maneuver and other pointing-type tasks have traditionally been used to assess intention tremor (Fahn et al., 1998; Deuschl et al., 2000; Feys et al., 2003). As highlighted by Herzog et al. (2007), however, intention tremor is a form of ataxic (i.e., disordered) movement typically associated with cerebellar dysfunction; the latter being present in cases of severe essential tremor (ET) (Vilis and Hore, 1977; Deuschl et al., 2000; Herzog et al., 2007; Kronenbuerger et al., 2007). This view of inten-
⇑ Corresponding author. Tel.: +1 604 827 3372; fax: +1 604 822 6842. E-mail address: [email protected] (M.E. Héroux).
tion tremor is reflected by the use of movement curvature to quantify intention tremor in subjects with ET (Deuschl et al., 2000; Herzog et al., 2007). Several other studies have evaluated kinetic (and intention) tremor by means of observer-based rating scales (Brennan et al., 2002; Louis et al., 2001a,b, 2005, 2009). While such measures are invaluable in quantifying ataxic movements and providing a gross measure of kinetic tremor amplitude, they do not provide direct insight into the strength of rhythmic muscle activity. This key pathological feature of ET (i.e., rhythmic muscle activity) results in a spectral peak at the tremor frequency in the power spectrum of rectified electromyography (EMG) recordings. It has previously been demonstrated that during postural (Héroux et al., 2009) and closed-kinetic chain isometric tasks (Héroux et al., 2010) the strength of rhythmic muscle activity remains relatively constant across light to moderate loads and contraction intensities. Interestingly, the percentage of overall EMG spectral power accounted for by tremor-related muscle activity was lower during the isometric task. Given that closed-kinetic chain isometric tasks minimize the influence of stretch reflexes
1388-2457/$36.00 Ó 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.clinph.2010.10.050
M.E. Héroux et al. / Clinical Neurophysiology 122 (2011) 1794–1801
on EMG activity (Burne et al., 1984; Doemges and Rack, 1992), we proposed that abnormal stretch reflex activity may have contributed to the increased tremor-related rhythmic muscle activity when the hand was free to move during the postural task (Héroux et al., 2009). In terms of what may be occurring during motion, movement control has been shown to differ considerably from postural or force control at many levels of the neuraxis (Kakuda et al., 1999; Semmler et al., 2002; Kurtzer et al., 2005; Duchateau and Enoka, 2008), all of which could potentially influence the strength of rhythmic muscle activity. For example, Bawa and Sinkjaer (1999) have previously shown in healthy subjects that during slow sinusoidal movements, short- and long-latency stretch reflex amplitudes in forearm muscles are reduced by 45% compared to an isometric task. If stretch-reflex excitability does impact ongoing tremor activity, the results of Bawa and Sinkjaer indicate that rhythmic muscle activity may be reduced during movement in subjects with ET. Alternatively, Vallbo and Wessberg (1993) have shown that slow controlled movements are comprised of motion discontinuities and EMG activity bursts occurring at 8 Hz, which was later associated with the activity of a cerebello-thalamo-premotormotor cortical loop at the same frequency (Gross et al., 2002). Importantly, Schnitzler et al. (2009) recently reported that synchronized activity of this same brain network was associated with the rhythmic muscle activity present in individuals with ET. Thus, it would appear that ET is associated with a central pathological increase of a very useful physiological oscillatory network (Schnitzler and Gross, 2005) and, given the nature of this network, raises the possibility that rhythmic muscle activity in ET will be most prominent during slow movements. The present study was designed to evaluate kinetic tremor in subjects with ET during extension–flexion movements of the wrist while supporting various light to moderate inertial loads similar to those manipulated during everyday tasks. In particular, we investigated the following questions. (1) Does the level of tremor-related rhythmic muscle activity increase in relation to the increased neuromuscular activity associated with inertial loading? (2) Given the difference in activation strategies used by the nervous system to generate concentric and eccentric contractions (see Duchateau and Enoka (2008) for a review), does the type of contraction being performed (i.e., concentric vs. eccentric) influence kinetic tremor characteristics in subjects with ET? (3) What is the effect of inertial loading on overall kinetic tremor amplitude as well as on kinetic and neuromuscular tremor spectral power? Based on our previous results and recent evidence that ET is associated with a pathological increase of a central oscillatory network involved in smooth movement production, we hypothesized that rhythmic muscle activity would remain relatively constant with increasing contraction activity and would be greater in amplitude when compared to the postural or isometric tasks. Furthermore, we hypothesized that the effect of inertial loading on mechanical resonance (Héroux et al., 2009) will result in smaller overall tremor amplitude with increasing load.
2. Methods 2.1. Subjects Twenty-one subjects with ET for and 22 healthy control subjects of similar age participated (see Héroux et al., 2009, 2010) for detailed inclusion criteria). Similar to our two previous two studies (Héroux et al., 2009, 2010), ET subjects were divided into two groups based on the strength and consistency of rhythmic muscle activity (see Section 2.4.2 for details); two subjects with mild tremor from the previous postural tremor study had highly
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variable and at times absent rhythmic muscle activity and their data were not included. All subjects provided informed consent to the protocol, which was approved by the local Research Ethics Board. 2.2. Apparatus The subject was seated in a straight-backed chair in front of a computer monitor. The forearm of the side being tested was in full pronation and was supported and secured on a height-adjustable table positioned next to the subject. The set-up permitted full wrist flexion and extension while greatly limiting wrist pronation and supination. During one-repetition maximum (1-RM) testing, the subject’s hand was fitted with a support device that permitted the suspension of weights. During kinetic tremor testing, the subject’s hand was positioned in a similar support device connected to two shafts on either side of the wrist, which rotated within low friction bearings. A small magnetic disc fixed to the end of one of the shafts and a 360° magnetic rotary position sensor (Melexis MLX90316, Rotary Position Sensor IC) was used to measure angular displacement about the long axis of the shaft, which corresponded to angular displacement about the wrist in a flexion–extension motion. In order to add inertial loads, a plastic cylinder containing the test load was bolted to the device on the palmar side of the hand and combinations of calibrated weights (Troemner, NJ) were used to provide a resolution of 1 g for loads ranging between 1 and 3110 g. The resolution of the system was 0.11°. The computer monitor (21 inch Dell M992, 60 Hz refresh rate, set to1024 768 pixels) was positioned 50 cm from the subject. The subject viewed a triangular (i.e., sawtooth) template spanning 90% of the width and 75% of the height of the monitor. The vertical axis corresponded to the angular position in degrees and ranged from negative 35° (flexion) to positive 35° (extension). The horizontal axis corresponded to time in seconds and represented 25 s of data. The triangular template consisted of 11=4 cycles of flexion–extension and started in the middle of the vertical axis (neutral wrist position) and moved downwards into 30° of flexion at a rate of 6°/s. From this point, the template reversed direction and moved through 60° of extension, followed by another reversal of direction and then moved through 60° of flexion. Presented on the same screen was a white line corresponding to the angular position of the wrist. The initial 0–30° flexion provided time for the subject to track the template. Surface EMG measured the neuromuscular activity of the extensor carpi radialis brevis and longus. Skin abrasion, cleaning with an alcohol solution, and application of conductive electrode cream (Synapse, Med-tek Corporation) were used to prepare the electrode sites. A Delsys electrode (two 10 mm 99.9% Ag bars spaced 10 mm apart) was adhered to the skin surface 5 cm distal to the lateral epicondyle and aligned along the line of action of the underlying muscle fibers. The common reference electrode (4 cm2) was placed over the olecranon of the ulna. Electromyography data were collected using a Delsys 8-channel amplifier system (Bandpass 10 Hz to 1 kHz, CMRR > 100 dB at 60 Hz, Input impedance 1 Gohm, amplification factor 1000). A 16-bit analog-to-digital converter (National Instrument PCI-MIO-16XE-10) controlled by a Pentium Xeon 2.66 GHz personal computer sampled EMG and angular displacement signals at 1024 Hz. Angular displacement sensor and EMG data were collected using custom-built LabView 8 software and saved to the hard disk of the personal computer for subsequent analysis. 2.3. Procedures In subjects with ET, the hand reported to have the most severe tremor was measured. In the case of symmetrical tremor, the
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dominant hand was tested. The side tested in healthy controls was selected in order to obtain approximately the same ratio for dominant/non-dominant between the ET and control groups. The 1-RM of the wrist extensors was first determined, which consists of the maximal load that can be successfully lifted once through full range of motion. A rest period of 90 s was given between each increment in load. In most subjects it took 4–5 lifts to determine the 1-RM and no subject needed more than 8. Next, the subject was asked to match the triangular template while supporting four sub-maximal loads (unloaded, 5%, 15% and 25% of 1-RM). The nature of these loads was such that as load torque increased, so did load inertia and load stiffness (Chew, 2009), which is the case for most loads encountered during everyday activities. Importantly, these loads were the same as those used in a previous study investigating postural tremor in these individuals (Héroux et al., 2009) and thus facilitates interpretation of the present study. For each trial, the subject flexed and extended their wrist in order to superimpose the angular position line on the monitor (i.e., angular position of the wrist in degrees) on the triangular template line. A block of two trials was recorded for each load, with the order of load presentation being randomized. There was a 60 s rest period between trials of a given block, and a minimum of 120 s rest between each block. 2.4. Data processing The EMG data were band-passed filtered (dual-pass 20–450 Hz 4th order Butterworth filter), the offset value was removed and the resulting signals was digitally rectified. Next, the EMG and angular displacement data were digitally filtered using a dual-pass 4th order Butterworth filter with a low-pass cutoff frequency of 40 Hz. Neuromuscular data for each subject was normalized to the peak in EMG obtained during maximal voluntary contraction trials (see Héroux et al. (2010) for details). Angular displacement data were differentiated to create velocity time series (Duval and Jones, 2005) and the middle 6 s of data from the extension and flexion movements were selected and their means removed. All data processing and subsequent time and frequency analyses were performed using software written in Matlab 7 (The MathWorks Inc., Natick, MA). 2.4.1. Amplitude of overall kinetic tremor and EMG activity Overall kinetic tremor amplitude was determined by calculating the standard deviation of the extension and flexion sections of each velocity time series. For the EMG signal, the mean level of neuromuscular activity of the extension (concentric) and flexion (eccentric) sections of each trial was computed on the rectified signal. The mean of both trials for a given load and contraction type were computed and used for statistical analysis. 2.4.2. Spectral measures of kinetic tremor and neuromuscular activity Angular velocity and EMG auto-spectra were calculated for each inertial load and movement type using the method of disjoint sections (Halliday et al., 1995). The two 6 s segments within each inertial load condition were concatenated and the spectra were estimated by averaging the finite Fourier transforms calculated from six non-overlapping windows of 2048 points, resulting in a frequency resolution of 0.5 Hz. As was the case previously (Héroux et al., 2009, 2010), visual inspection of individual EMG auto-spectra revealed reduced amplitude in, or total absence of, a prominent peak indicative of pathological tremor at one or sometimes two of the higher inertial loads (i.e., 15% or 25% 1-RM) in subjects with clinically less marked ET. Thus subjects with ET were divided into two groups based on the strength and consistency of rhythmic muscle activity (Héroux et al., 2009, 2010). Subjects in group 1 had prominent spectral
peaks in EMG for all trials (relative EMG tremor spectral power >10%; see below for details). Subjects included in group 2 had less prominent EMG spectral peaks at no-load and 5% 1-RM, which either (1) reduced in amplitude at either or both of the heavier loads (relative EMG tremor spectral power 65%) or (2) were not present at one of the heavier loads and reduced at the other. Based on the reduction or absence of prominent peaks in some subjects in ET group 2 at 15% and 25% 1-RM, the four calculated spectra – one for each load condition –were visualized simultaneously and the single spectrum with the most distinct and representative tremor spectral peak in the 4–12 Hz bandwidth was selected to calculate template tremor frequency values (i.e., peak frequency and left/right half-power bandwidth frequencies; see below for details). This procedure was carried out for angular velocity and EMG spectra of each ET subject and the resulting template values were used to calculate spectral outcomes when spectral peaks were difficult to discern (Héroux et al., 2009, 2010). The power of the main spectral peak associated with the central tremor component, referred to here as kinetic tremor, was calculated for each of the four angular velocity and EMG spectra for ET subjects based on the half-power bandwidth (Héroux et al., 2009). Also, for EMG data the percent of the total power in the 0–40 Hz bandwidth accounted for by the central tremor component was computed ([tremor spectral power/total power] 100); this measure has been used as an index of tremor severity and rhythmic muscle activity (Elble et al., 1994). 2.5. Statistical analysis Given the skewed distribution of tremor amplitude measures in ET (Héroux et al., 2006, 2009, 2010), all data were examined to verify Gaussian distribution prior to performing statistical analysis. Measures which were not normally distributed were log-transformed (Bland et al., 1996) and analyzed again to ensure a Gaussian distribution. Summary statistics and plots present mean and 95% confidence interval values of back-transformed data using the antilog (Bland et al., 1996); this process results in asymmetrical 95% confidence intervals, reflecting the skewed distribution of the data. The dependent variables were each compared in a 3-way ANOVA with a between subject factor for group and repeated measures for inertial load and contraction type. Post-hoc testing was performed using Tukey’s Honestly Significant Difference test. A value of 0.05 was chosen as the level of significance for all tests. Statistical analyses were carried out using SPSS statistical package (version 15.0.1). 3. Results Subject characteristics are presented in Table 1; 13 subjects were included in ET in group 1 and the 8 others were included in group 2. There was no strength difference between subjects in the control group (1-RM mean: 6.90 kg; 95% CI: 3.00–11.25), ET group 1 (1-RM mean: 6.60 kg; 95% CI: 4.25–12.00) and ET group 2 (1-RM mean: 7.00 kg; 95% CI: 4.50–10.25) (p = 0.725). An example of four trials from a control subject is shown in Fig. 1A. As can be seen in the angular displacement time-series, the subject was able to produce smooth extension (concentric) and flexion (eccentric) movements with at all loads. Angular velocity power spectra of the trials illustrate that the majority of the spectral power was located below 5 Hz. Also, EMG spectra had evenly distributed power with a global increase in amplitude with inertial loading. Fig. 1B shows data from an ET subject from group 1 who was not the most extreme of these subjects. The most striking feature from the angular displacement time-series is the presence of a consistent low amplitude tremor at the lighter two loads
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M.E. Héroux et al. / Clinical Neurophysiology 122 (2011) 1794–1801 Table 1 Subject characteristics and kinetic tremor and neuromuscular activity spectral peak frequencies. Age (years)
Gendera Side testedb Years with tremor Peak frequencyc 0% 1-RMd
ET group 1 (n = 13) 61.2 ± 9.9 (46–74) ET group 2 (n = 8) Controls (n = 22)
6m 7f
63.5 ± 10.5 (47–78) 5 m 3f 64.3 ± 14.3 (38–84) 9 m 13 f
5% 1-RM
15% 1-RM
25% 1-RM
6D 7 ND
23.5 ± 15.8 (6–61)
6.2 ± 1.7 (4.50–9.50) 6.2 ± 1.2 (4.25–9.25) 6.4 ± 1.1 (4.25–9.00) 6.5 ± 1.4 (4.25–9.00) 6.2 ± 1.5 (4.50–9.50) 6.4 ± 1.4 (4.25–9.50) 6.5 ± 1.3 (4.50–9.00) 6.6 ± 1.5 (4.50–9.25)
3D 5 ND 12 D 10 ND
26.1 ± 18.6 (7–60)
6.5 ± 1.1 (5.00–8.00) 6.5 ± 1.1 (5.25–8.50) 6.6 ± 1.1 (5.00–8.75) 6.7 ± 1.2 (5.25–9.25) 6.5 ± 0.9 (5.00–8.25) 6.5 ± 1.0 (5.50–8.25) 6.7 ± 0.9 (5.25–8.75) 6.9 ± 0.8 (5.25–9.00)
–
–
–
–
–
Values are mean ± standard deviation (minimum–maximum). a m = male; f = female. b D = dominant; ND = non-dominant. c Upper row = kinetic tremor; lower row = EMG. d 1-MR = one-repetition maximum.
and the low frequency angular fluctuations when heavier inertial loads were being supported. This is clearly reflected in the angular velocity power spectra, whereas the EMG power spectra are all dominated by large spectral peaks at the tremor frequency. 3.1. Kinetic tremor amplitude and spectral content Even after the application of a log-transformation, the distribution of overall kinetic tremor amplitudes for the ET group was not Gaussian. Visual inspection of the data revealed that this was the result of two ET subjects in group 1 having extremely large overall kinetic tremor. Data from these two subjects were therefore not included in the ANOVA; it is, however, presented in an inset for comparison with the overall group results shown in Fig. 2. The analysis of variance revealed a significant main effect for group (p < 0.001) and load (p < 0.001), as well as a significant load by group interaction (p < 0.001). Post-hoc testing revealed that inertial loading did not influence overall kinetic tremor amplitude of control subjects (p > 0.691) or of subjects in ET group 2 (p > 0.08). In subjects in ET group 1, inertial loading resulted in a reduction in overall kinetic tremor amplitude. Specifically, there were significant differences between the no-load and 5% 1-RM condition (p = 0.019) as well as between the 15% and 25% 1-RM load conditions (p = 0.003); the difference between the 5% and 15% 1-RM load conditions did not reach statistical significance (p = 0.093). Furthermore, subjects in ET group 1 had significantly greater overall kinetic tremor amplitude than ET group 2 (p < 0.013) and the control group (p < 0.001) for all loads, whereas the control group and ET group 2 were not significantly different from one another after correcting for multiple comparisons (p > 0.043). Finally, there was a tendency for subjects in ET group 1 to have greater kinetic tremor during the concentric portion of the movement compared to the eccentric portion (group by contraction type interaction: p = 0.054). 3.2. Neuromuscular activity amplitude and spectral content The frequency of the spectral peak associated with tremor activity remained relatively constant across inertial loads for all ET subjects (1). In terms of tremor-specific spectral power, inclusion of two subjects with large tremor spectral power once again resulted in a non-Gaussian distribution even after log-transformation. Their data were not included in the ANOVA, but are once again plotted in an inset for comparison (Fig. 2B). The analysis revealed a significant main effect for group (p = 0.001) and load (p = 0.001) as well as a significant group by contraction type interaction (p = 0.039). Post-hoc testing revealed that all load conditions were significantly different from one another (p = 0.001) whereas the group by contraction type interaction was due to
subjects in ET group 1 having greater tremor power during the concentric portion of the movement compared to the eccentric portion (p = 0.008) and subjects in ET group 2 having the opposite pattern (p = 0.021). As expected, neuromuscular activity increased with inertial loading in all three groups (p < 0.001) and was always greater during the concentric portion of the movement (main effect for contraction type: p < 0.001) with the difference between the two contraction types increasing at higher inertial loads (load by contraction type interaction: p = 0.001). The ANOVA confirmed there was no main effect for group (p = 0.752), thus Fig. 3A shows only pooled results. The rhythmic muscle activity characteristic of ET resulted in EMG spectral peaks at the tremor frequency (Table 1). Given that the ET groups were largely selected based on the amplitude and consistency of EMG tremor spectral peaks, it was not surprising to find a significant main effect for group (p < 0.001) (see Fig. 3B). There was also a significant main effect for load (p = 0.02) with post-hoc analysis revealing that EMG tremor power was significantly greater at 15% and 25% 1-RM compared to no-load and 5% 1-RM (p < 0.001). While the amplitude of the EMG tremor spectral peak increased with inertial loading, this increase was not as great as the overall increase in neuromuscular activity with inertial loading. As can be seen in Fig. 3C, relative EMG tremor power was greater in subjects in ET group 1 (p < 0.001) and it decreased with inertial loading in both ET groups (p < 0.023). Post-hoc analysis revealed that relative EMG spectral power was significantly lower at 25% 1-RM when compared to both the no-load (p = 0.005) and 5% 1-RM (p = 0.005) condition. 4. Discussion Tremor during movement can have severe functional consequences (Héroux et al., 2006; Bain et al., 1994), thus it is not surprising that recent reports have emphasized the importance of kinetic tremor in the clinical presentation of ET (Pahwa and Lyons, 2003; Sethi, 2003; Elble and Deuschl, 2009). To date, however, the extent of rhythmic muscle activity during movement and its impact on overall kinetic tremor amplitude were not known. The key finding from the present study was that relative EMG kinetic tremor power was very large (>30% total power) during both concentric and eccentric contractions at the two lightest loads tested for subjects in ET group 1. Thus, rhythmic muscle activity in subjects with moderate to severe ET appears to be accentuated when these individuals attempt to produce slow controlled movements. In addition, it was also found that: (1) overall kinetic tremor amplitude was greater in ET subjects with greater levels of rhythmic muscle activity compared to control and ET subjects with less pronounced entrainment, the latter two groups not being different from one another; (2) inertial loading resulted in smaller overall
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Fig. 1. Kinetic tremor data from a control subject (A) and a subject with low to moderate tremor from ET group 1(B). The upper graph shows one trial for each of the inertial loads tested. The kinetic tremor and neuromuscular activity power spectra for each inertial load are shown below the corresponding portions of the trials.
kinetic tremor amplitude in ET group 1 whereas it did not affect the other two groups; (3) subjects in ET group 1 had greater kinetic tremor and tremor spectral power when wrist extensors were contracting concentrically compared to eccentrically.
4.1. The effect of movement and inertial loading on kinetic tremor A consistent finding from previous studies investigating postural tremor in ET is that inertial loading results in a reduction in
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Fig. 2. Group results for kinetic tremor (A) overall amplitude and (B) tremor spectral power during wrist extension (concentric) and flexion (eccentric). Overall kinetic tremor amplitude (A) corresponds to the standard deviation of the angular velocity (degrees/s) time-series, whereas tremor spectral power (B) corresponds to the spectral power associated with the tremor peak of this same data. The inset in both figures shows the data from two subjects in ET group 1 who had very large amplitude kinetic tremor; their data follow the same pattern as their counterparts in ET group 1 although with much higher values. (A) Overall kinetic tremor amplitude was significantly greater in ET group 1 when compared to the two other groups, which were not different from one another. Inertial loading resulted in a significant reduction in overall kinetic tremor amplitude only in ET group 1. (B) Kinetic tremor power was significantly greater in subjects in ET group 1, while inertial loading resulted in a significant reduction in both groups of tremor subjects. Tremor spectral power was also greater during the extension portion of the movement (concentric contraction) compared to the flexion portion (eccentric contraction). con = concentric; ecc = eccentric.
tremor amplitude (Elble, 1986; Homberg et al., 1987). It has recently been shown that this reduction in tremor amplitude is likely due to the effect inertial loading has on the interaction between mechanical reflex and central oscillatory tremor components (Héroux et al., 2009). Briefly, the reduction in wrist mechanical resonant frequency incurred by inertial loading results in damping of the frequency-invariant tremor component associated with rhythmic muscle activity. Although spectral separation of mechanical reflex and central tremor components was not always obvious in the present study, a similar pattern to that observed during postural tremor was evident in a majority of subjects in ET group 1. As can be seen in the results presented in Fig. 3B, rhythmic muscle activity increased slightly with inertial loading. However, the damping effect associated with the difference in frequency between mechanical reflex and central tremor components resulted in a reduction in the amplitude of tremor spectral power during inertial loading. In the present study, ET subjects with more prominent and consistent rhythmic muscle activity (i.e., ET group 1) had greater tremor spectral power when the wrist extensors were contracting concentrically, opposite to the pattern observed in ET group 2. The overall reduction in neuromuscular activity associated with eccentric contractions may have resulted in a greater reduction in EMG tremor power in subjects in ET group 1. Although the group by type interaction was not significant, the pattern just described is evident in Fig. 3B. Specifically, the reduction in overall neuromuscular activity during the eccentric contraction had little impact on the amplitude of EMG tremor power in ET group 2, whereas it was associated with a relatively large reduction in EMG tremor power in ET group 1. 4.2. The effect of movement and inertial loading on rhythmic muscle activity In the present study, inertial loading resulted in a significant increase in tremor related EMG spectral power in all subjects with ET. This is in contrast to our two previous studies where increased contraction intensity during postural and closed-kinetic isometric
tasks was not associated with an increase in the level of EMG tremor power. Thus, it appears that when contraction intensity increases while executing a movement, a significant number of newly recruited motor units are being entrained by abnormal oscillatory neural drive. Another important difference with our two previous studies was that the extent of rhythmic muscle activity was much greater during movement compared to postural or isometric tasks. In subjects in ET group 1, for example, relative EMG spectral power was approximately 50% during the no-load condition. This means that 50% of the EMG spectral power in the 0–40 Hz bandwidth was accounted for by EMG tremor power. The corresponding values were 26% and 20% for the smallest load (postural) and lowest contraction intensity (closed-kinetic chain), respectively, in our previous studies (Héroux et al., 2009, 2010). It should also be noted, however, that contrary to what has previously been suggested by Gillies (1994) but in line with our previous findings, rhythmic muscle activity does not affect a constant proportion of the motorneuron pool. This is reflected by the significant reduction in relative EMG spectral power with inertial loading, which for subjects in ET group 1 went from approximately 50% during the no-load condition down to 12–15% for the heaviest inertial load. This finding has important implications in terms of the pathophysiology of ET as well as its clinical manifestation. In terms of physiological processes that may have contributed to increased rhythmic muscle activity during movement, it remains unclear whether stretch-reflex excitability is normal in ET (Elble et al., 1992, 1987). However, there is mounting evidence that mechanical resonance and its influence on stretch-reflex excitability interacts with descending oscillatory drive in ET (Elble et al., 1992; Britton et al., 1992; Heroux et al., 2009). Thus, even if stretch-reflex excitability was normal in ET, the large amplitude oscillatory motion resulting from rhythmic muscle activity could induce stretch reflex activity that would interact and, based on our current results, possibly increase ongoing rhythmic muscle activity. In terms of a possible increase in descending oscillatory drive during motion, Schnitzler et al. (2009) have demonstrated the presence of synchronized activity at the tremor frequency in the cerebello-thalamo-premotor-motor cortical loop in individuals
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the need for research to confirm whether the increase in rhythmic muscle activity we observed during movement is in fact accompanied by an increase in activity in the involved oscillatory brain networks in people with ET. 4.3. Study limitations The present study did not measure stretch-reflex excitability during the slow wrist flexion–extension movements, thus it is not possible to determine whether abnormal reflex excitability contributed to the greater levels of rhythmic muscle activity observed in this study. In future experiments it would of interest to measure stretch reflex amplitude in subjects with ET while they are maintaining a steady posture as well as when they are performing slow controlled movements in order to determine whether differences in stretch-reflex excitability contribute to the differences in rhythmic muscle activity levels. The loads used in the present study were selected to resemble the types of loads encountered by individuals with ET during activities of daily living. Thus, results from the present study can be generalized, cautiously, to activities of daily living involving movement of light to moderate loads and compared to our previous study on postural tremor involving these same subjects and loads (Héroux et al., 2009). It has previously been shown, however, that load torque and stiffness (and likely inertia) can independently influence postural tremor characteristics (amplitude, spectral profile, force-angle relationship) (Chew et al., 2008).Our previous study provided some insight regarding the independent influence of increasing contraction intensity, and thus torque, on the strength of rhythmic muscle activity during closed-kinetic chain isometric contractions(Héroux et al., 2010), but the current study did not independently manipulate torque, stiffness and inertia. It would thus be of considerable interest to investigate how load torque, stiffness and inertia independently influence tremor characteristics during both posture and movement. Given the considerable influence of mechanical resonance on how rhythmic muscle activity manifests as tremor (Elble, 1986; Elble et al., 2005; Héroux et al., 2009), it would be important to also consider how these load properties influence mechanical resonance in order to discern if there are distinct effects of these load manipulations in subjects with ET. 5. Conclusion Fig. 3. Neuromuscular activity results. (A) There was a significantly greater neuromuscular activity (EMG) amplitude with increased inertial loading. Given that this increase was similar in all groups, the groups were pooled. There was also a significant main effect for contraction type, with EMG amplitude being significantly smaller during eccentric contractions. (B) EMG tremor power was significantly greater in subjects in ET group 1 compared to those in ET group 2. EMG tremor power was significantly greater at 15% and 25% 1-RM load conditions compared to the no-load and 5% 1-RM load conditions. There was also a group by contraction type interaction due to subjects in ET group 1 having greater EMG tremor power during concentric contractions whereas subjects in ET group 2 had greater EMG tremor power during eccentric contractions. (C) EMG relative tremor power, which corresponds to the percent of total EMG power in the 0–40 Hz bandwidth that is accounted for by the EMG tremor peak, was significantly greater in subjects in ET group 1 compared to subjects in ET group 2. There was a significant reduction in EMG relative tremor power in both ET groups with increasing contraction intensities. con = concentric; ecc = eccentric.
The current study found that rhythmic muscle activity was present during simple movements of the wrist in subjects with ET, and that this activity was almost twice at great during movement compared to what was previously observed during postural and closedkinetic isometric tasks (Héroux et al., 2009, 2010). Functionally, the large amplitude kinetic tremor occurring when moving light loads is consistent with the types of tasks that most affect subjects with ET. Furthermore, given the greater correlation of kinetic tremor amplitude with measures of disability (D’Amboise et al., 2010), clinicians and researchers should continue to include measures of simple kinetic tremor (e.g., slow flexion–extension of the supported wrist) as part of their assessments. References
with ET performing a postural task. This brain network is associated with 8 Hz movement discontinuities and muscle bursts during smooth movement production in healthy subjects (Gross et al., 2002; Schnitzler and Gross, 2005). Thus, it would not be unreasonable to expect tremor-related rhythmic muscle activity to be greater during slow controlled movements in people with ET. This hypothesis was confirmed by the present study, and highlights
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M.E. Héroux et al. / Clinical Neurophysiology 122 (2011) 1794–1801 disease, essential tremor, and normal subjects mimicking tremor. Ann Neurol 1992;31:507–14. Burne JA, Lippold OC, Pryor M. Proprioceptors and normal tremor. J Physiol 1984;348:559–72. Brennan KC, Jurewicz EC, Ford B, Pullman SL, Louis ED. Is essential tremor predominantly a kinetic or a postural tremor? A clinical and electrophysiological study. Mov Disord 2002;17:313–6. Chew JZ, Gandevia SC, Fitzpatrick RC. Postural control at the human wrist. J Physiol 2008;586:1265–75. Chew J. External load and the neural control of posture. Doctoral Thesis, University of New South Wales, Australia; 2009. D’Amboise SN, Héroux ME, Pari G, Norman KE. Tremor during movement correlates well with disability in people who have essential tremor. In: Annual congress of the canadian physiotherapy association, St. John’s, NL, Canada; 2010. p. A94. Doemges F, Rack PM. Changes in the stretch reflex of the human first dorsal interosseous muscle during different tasks. J Physiol 1992;447:563–73. Deuschl G, Bain P, Brin M. Consensus statement of the movement disorder society on tremor. Ad hoc scientific committee. Mov Disord 1998;13(Suppl. 3):2–23. Deuschl G, Wenzelburger R, Löffler K, Raethjen J, Stolze H. Essential tremor and cerebellar dysfunction clinical and kinematic analysis of intention tremor. Brain 2000;123:1568–80. Duchateau J, Enoka RM. Neural control of shortening and lengthening contractions: influence of task constraints. J Physiol 2008;586:5853–64. Duval C, Jones J. Assessment of the amplitude of oscillations associated with highfrequency components of physiological tremor: impact of loading and signal differentiation. Exp Brain Res 2005;163:261–6. Elble RJ. Physiologic and essential tremor. Neurology 1986;36:225–31. Elble RJ, Higgins C, Moody CJ. Stretch reflex oscillations and essential tremor. J Neurol Neurosurg Psychiat 1987;50:691–8. Elble RJ, Higgins C, Hughes L. Phase resetting and frequency entrainment of essential tremor. Exp Neurol 1992;116:355–61. Elble RJ, Higgins C, Leffler K, Hughes L. Factors influencing the amplitude and frequency of essential tremor. Mov Disord 1994;9:589–96. Elble RJ, Higgins C, Elble S. Electrophysiologic transition from physiologic tremor to essential tremor. Mov Disord 2005;20:1038–42. Elble RJ, Deuschl G. An update on essential tremor. Curr Neurol Neurosci Rep 2009;9:273–7. Fahn S, Tolosa E, Marin C. Clinical rating scale for tremor. In: Jankovic J, Tolosa E, editors. Parkinson’s disease and movement disorders. Baltimore: Urban and Schwarzenberg; 1998. p. 225–34. Feys PG, Davies-Smith A, Jones R, Romberg A, Ruutiainen J, Helsen WF, et al. Intention tremor rated according to different finger-to-nose test protocols: a survey. Arch Phys Med Rehab 2003;84:79–82. Gillies JD. Measurement of physiological and essential tremor. In: Gandevia SC, Burke D, Anthony S, editors. Science and practice in clinical neurology. Cambridge, UniversityPress; 1994. p. 191–201. Gross J, Timmermann L, Kujala J, Dirks M, Schmitz F, Salmelin R, et al. The neural basis of intermittent motor control in humans. Proc Natl Acad Sci USA 2002;99:2299–302.
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Halliday DM, Rosenberg JR, Amjad AM, Breeze P, Conway BA, Farmer SF. A framework for the analysis of mixed time series/point process data – theory and application to the study of physiological tremor, single motor unit discharges and electromyograms. Prog Biophys Mol Biol 1995;64:237–78. Herzog J, Hamel W, Wenzelburger R, Potter M, Pinsker MO, Bartussek J, et al. Kinematic analysis of thalamic versus subthalamic neurostimulation in postural and intention tremor. Brain 2007;130:1608–25. Homberg V, Hefter H, Reiners K, Freund HJ. Differential effects of changes in mechanical limb properties on physiological and pathological tremor. J Neurol Neurosurg Psychiatry 1987;50:568–79. Héroux ME, Parisi SL, Larocerie-Salgado J, Norman KE. Upper-extremity disability in essential tremor. Arch Phys Med Rehab 2006;87:661–70. Héroux M, Pari G, Norman KE. The effect of inertial loading on postural tremor in essential tremor. Clin Neurophysiol 2009;120:1020–9. Héroux ME, Pari G, Norman KE. The effect of contraction intensity on force fluctuations and motor unit entrainment in individuals with essential tremor. Clin Neurophysiol 2010;121:233–9. Kakuda N, Nagaoka M, Wessberg J. Common modulation of motor unit pairs during slow wrist movement in man. J Physiol 1999;520(Pt 3):929–40. Kronenbuerger M, Gerwig M, Brol B, Block F, Timmann D. Eyeblink conditioning is impaired in subjects with essential tremor. Brain 2007;130:1538–51. Kurtzer I, Herter TM, Scott SH. Random change in cortical load representation suggests distinct control of posture and movement. Nat Neurosci 2005;8:498–504. Louis ED, Applegate LM, Borden S, Moskowitz C, Jin Z. Feasibility and validity of a modified finger-nose-finger test. Mov Disord 2005;20:636–9. Louis ED, Barnes L, Albert SM, Cote L, Schneier FR, Pullman SL, et al. Correlates of functional disability in essential tremor. Mov Disord 2001a;16:914–20. Louis ED, Barnes L, Wendt KJ, Ford B, Sangiorgio M, Tabbal S, et al. A teaching videotape for the assessment of essential tremor. Mov Disord 2001b;16:89–93. Louis ED, Frucht SJ, Rios E. Intention tremor in essential tremor: prevalence and association with disease duration. Mov Disord 2009;24:626–7. Pahwa R, Lyons KE. Essential tremor: differential diagnosis and current therapy. Am J Med 2003;115:134–42. Semmler JG, Kornatz KW, Dinenno DV, Zhou S, Enoka RM. Motor unit synchronisation is enhanced during slow lengthening contractions of a hand muscle. J Physiol 2002;545:681–95. Sethi KD. Tremor. Curr Opin Neurol 2003;16:481–5. Schnitzler A, Gross J. Normal and pathological oscillatory communication in the brain. Nat Rev Neurosci 2005;6:285–96. Schnitzler A, Munks C, Butz M, Timmermann L, Gross J. Synchronized brain network associated with essential tremor as revealed by magnetoencephalography. Mov Disord 2009;24:1629–45. Vallbo AB, Wessberg J. Organization of motor output in slow finger movements in man. J Physiol 1993;469:673–91. Vilis T, Hore J. Effects of changes in mechanical state of limb on cerebellar intention tremor. J Neurohysiol 1977;40:1214–24.
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Clinical Neurophysiology journal homepage: www.elsevier.com/locate/clinph
The effect of inertial loading on wrist kinetic tremor and rhythmic muscle activity in individuals with essential tremor M.E. Héroux a,⇑, G. Pari b,c, K.E. Norman d,e a
School of Human Kinetics, University of British Columbia, 210-6081 University Boulevard, Vancouver, BC, Canada V6T 1Z1 Movement Disorders Clinic, Kingston General Hospital, ON, Canada K7L 2V7 c School of Medicine, Queen’s University, 68 Barrie Street, ON, Canada K7L 3N6 d School of Rehabilitation Therapy, Queen’s University, L.D. Acton Building, ON, Canada K7L 3N6 e Centre for Neuroscience Studies, Queen’s University, Botterell Hall, ON, Canada K7L 3N6 b
a r t i c l e
i n f o
Article history: Accepted 28 October 2010 Available online 21 December 2010 Keywords: Essential tremor Kinetic tremor Electromyography Power spectral analysis Rhythmic muscle activity
a b s t r a c t Objectives: Determine the effect of concentric and eccentric movement and contraction intensity on the strength of rhythmic muscle activity in individuals with essential tremor (ET). Methods: 21 ET subjects and 22 healthy controls produced wrist flexion–extension movements while supporting sub-maximal loads (no-load, 5%, 15% and 25% 1-repetition maximum). Kinetic tremor and wrist extensor neuromuscular activity were recorded using an angular displacement sensor and electromyography (EMG). Results: Rhythmic muscle activity was twice as big during movement compared to previous results involving postural or isometric tasks. ET subjects with greater rhythmic muscle activity had (1) larger overall kinetic tremor amplitude, (2) greater tremor spectral power during eccentric compared to concentric movement and (3) a reduction in overall kinetic tremor amplitude and the percentage of EMG spectral power accounted for by the tremor spectral peak in the presence of inertial loading. Conclusions: Greater than normal kinetic tremor amplitude appears to be limited to ET subjects with higher levels of rhythmic muscle activity. Furthermore, rhythmic muscle activity is much greater during movement compared to during postural or closed-kinetic tasks. Significance: The strength of rhythmic muscle activity in ET is influenced by the type of contraction (i.e., static vs. dynamic) being performed. Clinicians and researchers should include measures of simple kinetic tremor as part of their assessments. Ó 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
1. Introduction The Consensus Statement of the Movement Disorder Society on Tremor (Deuschl et al., 1998) defines kinetic tremor as ‘‘tremor occurring during any voluntary movement’’. This movement can be visually guided or not, as well as goal-directed (e.g., finger-tonose test) or not (e.g., repetitive flexion/extension movements of the hand). The finger-to-nose maneuver and other pointing-type tasks have traditionally been used to assess intention tremor (Fahn et al., 1998; Deuschl et al., 2000; Feys et al., 2003). As highlighted by Herzog et al. (2007), however, intention tremor is a form of ataxic (i.e., disordered) movement typically associated with cerebellar dysfunction; the latter being present in cases of severe essential tremor (ET) (Vilis and Hore, 1977; Deuschl et al., 2000; Herzog et al., 2007; Kronenbuerger et al., 2007). This view of inten-
⇑ Corresponding author. Tel.: +1 604 827 3372; fax: +1 604 822 6842. E-mail address: [email protected] (M.E. Héroux).
tion tremor is reflected by the use of movement curvature to quantify intention tremor in subjects with ET (Deuschl et al., 2000; Herzog et al., 2007). Several other studies have evaluated kinetic (and intention) tremor by means of observer-based rating scales (Brennan et al., 2002; Louis et al., 2001a,b, 2005, 2009). While such measures are invaluable in quantifying ataxic movements and providing a gross measure of kinetic tremor amplitude, they do not provide direct insight into the strength of rhythmic muscle activity. This key pathological feature of ET (i.e., rhythmic muscle activity) results in a spectral peak at the tremor frequency in the power spectrum of rectified electromyography (EMG) recordings. It has previously been demonstrated that during postural (Héroux et al., 2009) and closed-kinetic chain isometric tasks (Héroux et al., 2010) the strength of rhythmic muscle activity remains relatively constant across light to moderate loads and contraction intensities. Interestingly, the percentage of overall EMG spectral power accounted for by tremor-related muscle activity was lower during the isometric task. Given that closed-kinetic chain isometric tasks minimize the influence of stretch reflexes
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on EMG activity (Burne et al., 1984; Doemges and Rack, 1992), we proposed that abnormal stretch reflex activity may have contributed to the increased tremor-related rhythmic muscle activity when the hand was free to move during the postural task (Héroux et al., 2009). In terms of what may be occurring during motion, movement control has been shown to differ considerably from postural or force control at many levels of the neuraxis (Kakuda et al., 1999; Semmler et al., 2002; Kurtzer et al., 2005; Duchateau and Enoka, 2008), all of which could potentially influence the strength of rhythmic muscle activity. For example, Bawa and Sinkjaer (1999) have previously shown in healthy subjects that during slow sinusoidal movements, short- and long-latency stretch reflex amplitudes in forearm muscles are reduced by 45% compared to an isometric task. If stretch-reflex excitability does impact ongoing tremor activity, the results of Bawa and Sinkjaer indicate that rhythmic muscle activity may be reduced during movement in subjects with ET. Alternatively, Vallbo and Wessberg (1993) have shown that slow controlled movements are comprised of motion discontinuities and EMG activity bursts occurring at 8 Hz, which was later associated with the activity of a cerebello-thalamo-premotormotor cortical loop at the same frequency (Gross et al., 2002). Importantly, Schnitzler et al. (2009) recently reported that synchronized activity of this same brain network was associated with the rhythmic muscle activity present in individuals with ET. Thus, it would appear that ET is associated with a central pathological increase of a very useful physiological oscillatory network (Schnitzler and Gross, 2005) and, given the nature of this network, raises the possibility that rhythmic muscle activity in ET will be most prominent during slow movements. The present study was designed to evaluate kinetic tremor in subjects with ET during extension–flexion movements of the wrist while supporting various light to moderate inertial loads similar to those manipulated during everyday tasks. In particular, we investigated the following questions. (1) Does the level of tremor-related rhythmic muscle activity increase in relation to the increased neuromuscular activity associated with inertial loading? (2) Given the difference in activation strategies used by the nervous system to generate concentric and eccentric contractions (see Duchateau and Enoka (2008) for a review), does the type of contraction being performed (i.e., concentric vs. eccentric) influence kinetic tremor characteristics in subjects with ET? (3) What is the effect of inertial loading on overall kinetic tremor amplitude as well as on kinetic and neuromuscular tremor spectral power? Based on our previous results and recent evidence that ET is associated with a pathological increase of a central oscillatory network involved in smooth movement production, we hypothesized that rhythmic muscle activity would remain relatively constant with increasing contraction activity and would be greater in amplitude when compared to the postural or isometric tasks. Furthermore, we hypothesized that the effect of inertial loading on mechanical resonance (Héroux et al., 2009) will result in smaller overall tremor amplitude with increasing load.
2. Methods 2.1. Subjects Twenty-one subjects with ET for and 22 healthy control subjects of similar age participated (see Héroux et al., 2009, 2010) for detailed inclusion criteria). Similar to our two previous two studies (Héroux et al., 2009, 2010), ET subjects were divided into two groups based on the strength and consistency of rhythmic muscle activity (see Section 2.4.2 for details); two subjects with mild tremor from the previous postural tremor study had highly
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variable and at times absent rhythmic muscle activity and their data were not included. All subjects provided informed consent to the protocol, which was approved by the local Research Ethics Board. 2.2. Apparatus The subject was seated in a straight-backed chair in front of a computer monitor. The forearm of the side being tested was in full pronation and was supported and secured on a height-adjustable table positioned next to the subject. The set-up permitted full wrist flexion and extension while greatly limiting wrist pronation and supination. During one-repetition maximum (1-RM) testing, the subject’s hand was fitted with a support device that permitted the suspension of weights. During kinetic tremor testing, the subject’s hand was positioned in a similar support device connected to two shafts on either side of the wrist, which rotated within low friction bearings. A small magnetic disc fixed to the end of one of the shafts and a 360° magnetic rotary position sensor (Melexis MLX90316, Rotary Position Sensor IC) was used to measure angular displacement about the long axis of the shaft, which corresponded to angular displacement about the wrist in a flexion–extension motion. In order to add inertial loads, a plastic cylinder containing the test load was bolted to the device on the palmar side of the hand and combinations of calibrated weights (Troemner, NJ) were used to provide a resolution of 1 g for loads ranging between 1 and 3110 g. The resolution of the system was 0.11°. The computer monitor (21 inch Dell M992, 60 Hz refresh rate, set to1024 768 pixels) was positioned 50 cm from the subject. The subject viewed a triangular (i.e., sawtooth) template spanning 90% of the width and 75% of the height of the monitor. The vertical axis corresponded to the angular position in degrees and ranged from negative 35° (flexion) to positive 35° (extension). The horizontal axis corresponded to time in seconds and represented 25 s of data. The triangular template consisted of 11=4 cycles of flexion–extension and started in the middle of the vertical axis (neutral wrist position) and moved downwards into 30° of flexion at a rate of 6°/s. From this point, the template reversed direction and moved through 60° of extension, followed by another reversal of direction and then moved through 60° of flexion. Presented on the same screen was a white line corresponding to the angular position of the wrist. The initial 0–30° flexion provided time for the subject to track the template. Surface EMG measured the neuromuscular activity of the extensor carpi radialis brevis and longus. Skin abrasion, cleaning with an alcohol solution, and application of conductive electrode cream (Synapse, Med-tek Corporation) were used to prepare the electrode sites. A Delsys electrode (two 10 mm 99.9% Ag bars spaced 10 mm apart) was adhered to the skin surface 5 cm distal to the lateral epicondyle and aligned along the line of action of the underlying muscle fibers. The common reference electrode (4 cm2) was placed over the olecranon of the ulna. Electromyography data were collected using a Delsys 8-channel amplifier system (Bandpass 10 Hz to 1 kHz, CMRR > 100 dB at 60 Hz, Input impedance 1 Gohm, amplification factor 1000). A 16-bit analog-to-digital converter (National Instrument PCI-MIO-16XE-10) controlled by a Pentium Xeon 2.66 GHz personal computer sampled EMG and angular displacement signals at 1024 Hz. Angular displacement sensor and EMG data were collected using custom-built LabView 8 software and saved to the hard disk of the personal computer for subsequent analysis. 2.3. Procedures In subjects with ET, the hand reported to have the most severe tremor was measured. In the case of symmetrical tremor, the
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dominant hand was tested. The side tested in healthy controls was selected in order to obtain approximately the same ratio for dominant/non-dominant between the ET and control groups. The 1-RM of the wrist extensors was first determined, which consists of the maximal load that can be successfully lifted once through full range of motion. A rest period of 90 s was given between each increment in load. In most subjects it took 4–5 lifts to determine the 1-RM and no subject needed more than 8. Next, the subject was asked to match the triangular template while supporting four sub-maximal loads (unloaded, 5%, 15% and 25% of 1-RM). The nature of these loads was such that as load torque increased, so did load inertia and load stiffness (Chew, 2009), which is the case for most loads encountered during everyday activities. Importantly, these loads were the same as those used in a previous study investigating postural tremor in these individuals (Héroux et al., 2009) and thus facilitates interpretation of the present study. For each trial, the subject flexed and extended their wrist in order to superimpose the angular position line on the monitor (i.e., angular position of the wrist in degrees) on the triangular template line. A block of two trials was recorded for each load, with the order of load presentation being randomized. There was a 60 s rest period between trials of a given block, and a minimum of 120 s rest between each block. 2.4. Data processing The EMG data were band-passed filtered (dual-pass 20–450 Hz 4th order Butterworth filter), the offset value was removed and the resulting signals was digitally rectified. Next, the EMG and angular displacement data were digitally filtered using a dual-pass 4th order Butterworth filter with a low-pass cutoff frequency of 40 Hz. Neuromuscular data for each subject was normalized to the peak in EMG obtained during maximal voluntary contraction trials (see Héroux et al. (2010) for details). Angular displacement data were differentiated to create velocity time series (Duval and Jones, 2005) and the middle 6 s of data from the extension and flexion movements were selected and their means removed. All data processing and subsequent time and frequency analyses were performed using software written in Matlab 7 (The MathWorks Inc., Natick, MA). 2.4.1. Amplitude of overall kinetic tremor and EMG activity Overall kinetic tremor amplitude was determined by calculating the standard deviation of the extension and flexion sections of each velocity time series. For the EMG signal, the mean level of neuromuscular activity of the extension (concentric) and flexion (eccentric) sections of each trial was computed on the rectified signal. The mean of both trials for a given load and contraction type were computed and used for statistical analysis. 2.4.2. Spectral measures of kinetic tremor and neuromuscular activity Angular velocity and EMG auto-spectra were calculated for each inertial load and movement type using the method of disjoint sections (Halliday et al., 1995). The two 6 s segments within each inertial load condition were concatenated and the spectra were estimated by averaging the finite Fourier transforms calculated from six non-overlapping windows of 2048 points, resulting in a frequency resolution of 0.5 Hz. As was the case previously (Héroux et al., 2009, 2010), visual inspection of individual EMG auto-spectra revealed reduced amplitude in, or total absence of, a prominent peak indicative of pathological tremor at one or sometimes two of the higher inertial loads (i.e., 15% or 25% 1-RM) in subjects with clinically less marked ET. Thus subjects with ET were divided into two groups based on the strength and consistency of rhythmic muscle activity (Héroux et al., 2009, 2010). Subjects in group 1 had prominent spectral
peaks in EMG for all trials (relative EMG tremor spectral power >10%; see below for details). Subjects included in group 2 had less prominent EMG spectral peaks at no-load and 5% 1-RM, which either (1) reduced in amplitude at either or both of the heavier loads (relative EMG tremor spectral power 65%) or (2) were not present at one of the heavier loads and reduced at the other. Based on the reduction or absence of prominent peaks in some subjects in ET group 2 at 15% and 25% 1-RM, the four calculated spectra – one for each load condition –were visualized simultaneously and the single spectrum with the most distinct and representative tremor spectral peak in the 4–12 Hz bandwidth was selected to calculate template tremor frequency values (i.e., peak frequency and left/right half-power bandwidth frequencies; see below for details). This procedure was carried out for angular velocity and EMG spectra of each ET subject and the resulting template values were used to calculate spectral outcomes when spectral peaks were difficult to discern (Héroux et al., 2009, 2010). The power of the main spectral peak associated with the central tremor component, referred to here as kinetic tremor, was calculated for each of the four angular velocity and EMG spectra for ET subjects based on the half-power bandwidth (Héroux et al., 2009). Also, for EMG data the percent of the total power in the 0–40 Hz bandwidth accounted for by the central tremor component was computed ([tremor spectral power/total power] 100); this measure has been used as an index of tremor severity and rhythmic muscle activity (Elble et al., 1994). 2.5. Statistical analysis Given the skewed distribution of tremor amplitude measures in ET (Héroux et al., 2006, 2009, 2010), all data were examined to verify Gaussian distribution prior to performing statistical analysis. Measures which were not normally distributed were log-transformed (Bland et al., 1996) and analyzed again to ensure a Gaussian distribution. Summary statistics and plots present mean and 95% confidence interval values of back-transformed data using the antilog (Bland et al., 1996); this process results in asymmetrical 95% confidence intervals, reflecting the skewed distribution of the data. The dependent variables were each compared in a 3-way ANOVA with a between subject factor for group and repeated measures for inertial load and contraction type. Post-hoc testing was performed using Tukey’s Honestly Significant Difference test. A value of 0.05 was chosen as the level of significance for all tests. Statistical analyses were carried out using SPSS statistical package (version 15.0.1). 3. Results Subject characteristics are presented in Table 1; 13 subjects were included in ET in group 1 and the 8 others were included in group 2. There was no strength difference between subjects in the control group (1-RM mean: 6.90 kg; 95% CI: 3.00–11.25), ET group 1 (1-RM mean: 6.60 kg; 95% CI: 4.25–12.00) and ET group 2 (1-RM mean: 7.00 kg; 95% CI: 4.50–10.25) (p = 0.725). An example of four trials from a control subject is shown in Fig. 1A. As can be seen in the angular displacement time-series, the subject was able to produce smooth extension (concentric) and flexion (eccentric) movements with at all loads. Angular velocity power spectra of the trials illustrate that the majority of the spectral power was located below 5 Hz. Also, EMG spectra had evenly distributed power with a global increase in amplitude with inertial loading. Fig. 1B shows data from an ET subject from group 1 who was not the most extreme of these subjects. The most striking feature from the angular displacement time-series is the presence of a consistent low amplitude tremor at the lighter two loads
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M.E. Héroux et al. / Clinical Neurophysiology 122 (2011) 1794–1801 Table 1 Subject characteristics and kinetic tremor and neuromuscular activity spectral peak frequencies. Age (years)
Gendera Side testedb Years with tremor Peak frequencyc 0% 1-RMd
ET group 1 (n = 13) 61.2 ± 9.9 (46–74) ET group 2 (n = 8) Controls (n = 22)
6m 7f
63.5 ± 10.5 (47–78) 5 m 3f 64.3 ± 14.3 (38–84) 9 m 13 f
5% 1-RM
15% 1-RM
25% 1-RM
6D 7 ND
23.5 ± 15.8 (6–61)
6.2 ± 1.7 (4.50–9.50) 6.2 ± 1.2 (4.25–9.25) 6.4 ± 1.1 (4.25–9.00) 6.5 ± 1.4 (4.25–9.00) 6.2 ± 1.5 (4.50–9.50) 6.4 ± 1.4 (4.25–9.50) 6.5 ± 1.3 (4.50–9.00) 6.6 ± 1.5 (4.50–9.25)
3D 5 ND 12 D 10 ND
26.1 ± 18.6 (7–60)
6.5 ± 1.1 (5.00–8.00) 6.5 ± 1.1 (5.25–8.50) 6.6 ± 1.1 (5.00–8.75) 6.7 ± 1.2 (5.25–9.25) 6.5 ± 0.9 (5.00–8.25) 6.5 ± 1.0 (5.50–8.25) 6.7 ± 0.9 (5.25–8.75) 6.9 ± 0.8 (5.25–9.00)
–
–
–
–
–
Values are mean ± standard deviation (minimum–maximum). a m = male; f = female. b D = dominant; ND = non-dominant. c Upper row = kinetic tremor; lower row = EMG. d 1-MR = one-repetition maximum.
and the low frequency angular fluctuations when heavier inertial loads were being supported. This is clearly reflected in the angular velocity power spectra, whereas the EMG power spectra are all dominated by large spectral peaks at the tremor frequency. 3.1. Kinetic tremor amplitude and spectral content Even after the application of a log-transformation, the distribution of overall kinetic tremor amplitudes for the ET group was not Gaussian. Visual inspection of the data revealed that this was the result of two ET subjects in group 1 having extremely large overall kinetic tremor. Data from these two subjects were therefore not included in the ANOVA; it is, however, presented in an inset for comparison with the overall group results shown in Fig. 2. The analysis of variance revealed a significant main effect for group (p < 0.001) and load (p < 0.001), as well as a significant load by group interaction (p < 0.001). Post-hoc testing revealed that inertial loading did not influence overall kinetic tremor amplitude of control subjects (p > 0.691) or of subjects in ET group 2 (p > 0.08). In subjects in ET group 1, inertial loading resulted in a reduction in overall kinetic tremor amplitude. Specifically, there were significant differences between the no-load and 5% 1-RM condition (p = 0.019) as well as between the 15% and 25% 1-RM load conditions (p = 0.003); the difference between the 5% and 15% 1-RM load conditions did not reach statistical significance (p = 0.093). Furthermore, subjects in ET group 1 had significantly greater overall kinetic tremor amplitude than ET group 2 (p < 0.013) and the control group (p < 0.001) for all loads, whereas the control group and ET group 2 were not significantly different from one another after correcting for multiple comparisons (p > 0.043). Finally, there was a tendency for subjects in ET group 1 to have greater kinetic tremor during the concentric portion of the movement compared to the eccentric portion (group by contraction type interaction: p = 0.054). 3.2. Neuromuscular activity amplitude and spectral content The frequency of the spectral peak associated with tremor activity remained relatively constant across inertial loads for all ET subjects (1). In terms of tremor-specific spectral power, inclusion of two subjects with large tremor spectral power once again resulted in a non-Gaussian distribution even after log-transformation. Their data were not included in the ANOVA, but are once again plotted in an inset for comparison (Fig. 2B). The analysis revealed a significant main effect for group (p = 0.001) and load (p = 0.001) as well as a significant group by contraction type interaction (p = 0.039). Post-hoc testing revealed that all load conditions were significantly different from one another (p = 0.001) whereas the group by contraction type interaction was due to
subjects in ET group 1 having greater tremor power during the concentric portion of the movement compared to the eccentric portion (p = 0.008) and subjects in ET group 2 having the opposite pattern (p = 0.021). As expected, neuromuscular activity increased with inertial loading in all three groups (p < 0.001) and was always greater during the concentric portion of the movement (main effect for contraction type: p < 0.001) with the difference between the two contraction types increasing at higher inertial loads (load by contraction type interaction: p = 0.001). The ANOVA confirmed there was no main effect for group (p = 0.752), thus Fig. 3A shows only pooled results. The rhythmic muscle activity characteristic of ET resulted in EMG spectral peaks at the tremor frequency (Table 1). Given that the ET groups were largely selected based on the amplitude and consistency of EMG tremor spectral peaks, it was not surprising to find a significant main effect for group (p < 0.001) (see Fig. 3B). There was also a significant main effect for load (p = 0.02) with post-hoc analysis revealing that EMG tremor power was significantly greater at 15% and 25% 1-RM compared to no-load and 5% 1-RM (p < 0.001). While the amplitude of the EMG tremor spectral peak increased with inertial loading, this increase was not as great as the overall increase in neuromuscular activity with inertial loading. As can be seen in Fig. 3C, relative EMG tremor power was greater in subjects in ET group 1 (p < 0.001) and it decreased with inertial loading in both ET groups (p < 0.023). Post-hoc analysis revealed that relative EMG spectral power was significantly lower at 25% 1-RM when compared to both the no-load (p = 0.005) and 5% 1-RM (p = 0.005) condition. 4. Discussion Tremor during movement can have severe functional consequences (Héroux et al., 2006; Bain et al., 1994), thus it is not surprising that recent reports have emphasized the importance of kinetic tremor in the clinical presentation of ET (Pahwa and Lyons, 2003; Sethi, 2003; Elble and Deuschl, 2009). To date, however, the extent of rhythmic muscle activity during movement and its impact on overall kinetic tremor amplitude were not known. The key finding from the present study was that relative EMG kinetic tremor power was very large (>30% total power) during both concentric and eccentric contractions at the two lightest loads tested for subjects in ET group 1. Thus, rhythmic muscle activity in subjects with moderate to severe ET appears to be accentuated when these individuals attempt to produce slow controlled movements. In addition, it was also found that: (1) overall kinetic tremor amplitude was greater in ET subjects with greater levels of rhythmic muscle activity compared to control and ET subjects with less pronounced entrainment, the latter two groups not being different from one another; (2) inertial loading resulted in smaller overall
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Fig. 1. Kinetic tremor data from a control subject (A) and a subject with low to moderate tremor from ET group 1(B). The upper graph shows one trial for each of the inertial loads tested. The kinetic tremor and neuromuscular activity power spectra for each inertial load are shown below the corresponding portions of the trials.
kinetic tremor amplitude in ET group 1 whereas it did not affect the other two groups; (3) subjects in ET group 1 had greater kinetic tremor and tremor spectral power when wrist extensors were contracting concentrically compared to eccentrically.
4.1. The effect of movement and inertial loading on kinetic tremor A consistent finding from previous studies investigating postural tremor in ET is that inertial loading results in a reduction in
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Fig. 2. Group results for kinetic tremor (A) overall amplitude and (B) tremor spectral power during wrist extension (concentric) and flexion (eccentric). Overall kinetic tremor amplitude (A) corresponds to the standard deviation of the angular velocity (degrees/s) time-series, whereas tremor spectral power (B) corresponds to the spectral power associated with the tremor peak of this same data. The inset in both figures shows the data from two subjects in ET group 1 who had very large amplitude kinetic tremor; their data follow the same pattern as their counterparts in ET group 1 although with much higher values. (A) Overall kinetic tremor amplitude was significantly greater in ET group 1 when compared to the two other groups, which were not different from one another. Inertial loading resulted in a significant reduction in overall kinetic tremor amplitude only in ET group 1. (B) Kinetic tremor power was significantly greater in subjects in ET group 1, while inertial loading resulted in a significant reduction in both groups of tremor subjects. Tremor spectral power was also greater during the extension portion of the movement (concentric contraction) compared to the flexion portion (eccentric contraction). con = concentric; ecc = eccentric.
tremor amplitude (Elble, 1986; Homberg et al., 1987). It has recently been shown that this reduction in tremor amplitude is likely due to the effect inertial loading has on the interaction between mechanical reflex and central oscillatory tremor components (Héroux et al., 2009). Briefly, the reduction in wrist mechanical resonant frequency incurred by inertial loading results in damping of the frequency-invariant tremor component associated with rhythmic muscle activity. Although spectral separation of mechanical reflex and central tremor components was not always obvious in the present study, a similar pattern to that observed during postural tremor was evident in a majority of subjects in ET group 1. As can be seen in the results presented in Fig. 3B, rhythmic muscle activity increased slightly with inertial loading. However, the damping effect associated with the difference in frequency between mechanical reflex and central tremor components resulted in a reduction in the amplitude of tremor spectral power during inertial loading. In the present study, ET subjects with more prominent and consistent rhythmic muscle activity (i.e., ET group 1) had greater tremor spectral power when the wrist extensors were contracting concentrically, opposite to the pattern observed in ET group 2. The overall reduction in neuromuscular activity associated with eccentric contractions may have resulted in a greater reduction in EMG tremor power in subjects in ET group 1. Although the group by type interaction was not significant, the pattern just described is evident in Fig. 3B. Specifically, the reduction in overall neuromuscular activity during the eccentric contraction had little impact on the amplitude of EMG tremor power in ET group 2, whereas it was associated with a relatively large reduction in EMG tremor power in ET group 1. 4.2. The effect of movement and inertial loading on rhythmic muscle activity In the present study, inertial loading resulted in a significant increase in tremor related EMG spectral power in all subjects with ET. This is in contrast to our two previous studies where increased contraction intensity during postural and closed-kinetic isometric
tasks was not associated with an increase in the level of EMG tremor power. Thus, it appears that when contraction intensity increases while executing a movement, a significant number of newly recruited motor units are being entrained by abnormal oscillatory neural drive. Another important difference with our two previous studies was that the extent of rhythmic muscle activity was much greater during movement compared to postural or isometric tasks. In subjects in ET group 1, for example, relative EMG spectral power was approximately 50% during the no-load condition. This means that 50% of the EMG spectral power in the 0–40 Hz bandwidth was accounted for by EMG tremor power. The corresponding values were 26% and 20% for the smallest load (postural) and lowest contraction intensity (closed-kinetic chain), respectively, in our previous studies (Héroux et al., 2009, 2010). It should also be noted, however, that contrary to what has previously been suggested by Gillies (1994) but in line with our previous findings, rhythmic muscle activity does not affect a constant proportion of the motorneuron pool. This is reflected by the significant reduction in relative EMG spectral power with inertial loading, which for subjects in ET group 1 went from approximately 50% during the no-load condition down to 12–15% for the heaviest inertial load. This finding has important implications in terms of the pathophysiology of ET as well as its clinical manifestation. In terms of physiological processes that may have contributed to increased rhythmic muscle activity during movement, it remains unclear whether stretch-reflex excitability is normal in ET (Elble et al., 1992, 1987). However, there is mounting evidence that mechanical resonance and its influence on stretch-reflex excitability interacts with descending oscillatory drive in ET (Elble et al., 1992; Britton et al., 1992; Heroux et al., 2009). Thus, even if stretch-reflex excitability was normal in ET, the large amplitude oscillatory motion resulting from rhythmic muscle activity could induce stretch reflex activity that would interact and, based on our current results, possibly increase ongoing rhythmic muscle activity. In terms of a possible increase in descending oscillatory drive during motion, Schnitzler et al. (2009) have demonstrated the presence of synchronized activity at the tremor frequency in the cerebello-thalamo-premotor-motor cortical loop in individuals
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the need for research to confirm whether the increase in rhythmic muscle activity we observed during movement is in fact accompanied by an increase in activity in the involved oscillatory brain networks in people with ET. 4.3. Study limitations The present study did not measure stretch-reflex excitability during the slow wrist flexion–extension movements, thus it is not possible to determine whether abnormal reflex excitability contributed to the greater levels of rhythmic muscle activity observed in this study. In future experiments it would of interest to measure stretch reflex amplitude in subjects with ET while they are maintaining a steady posture as well as when they are performing slow controlled movements in order to determine whether differences in stretch-reflex excitability contribute to the differences in rhythmic muscle activity levels. The loads used in the present study were selected to resemble the types of loads encountered by individuals with ET during activities of daily living. Thus, results from the present study can be generalized, cautiously, to activities of daily living involving movement of light to moderate loads and compared to our previous study on postural tremor involving these same subjects and loads (Héroux et al., 2009). It has previously been shown, however, that load torque and stiffness (and likely inertia) can independently influence postural tremor characteristics (amplitude, spectral profile, force-angle relationship) (Chew et al., 2008).Our previous study provided some insight regarding the independent influence of increasing contraction intensity, and thus torque, on the strength of rhythmic muscle activity during closed-kinetic chain isometric contractions(Héroux et al., 2010), but the current study did not independently manipulate torque, stiffness and inertia. It would thus be of considerable interest to investigate how load torque, stiffness and inertia independently influence tremor characteristics during both posture and movement. Given the considerable influence of mechanical resonance on how rhythmic muscle activity manifests as tremor (Elble, 1986; Elble et al., 2005; Héroux et al., 2009), it would be important to also consider how these load properties influence mechanical resonance in order to discern if there are distinct effects of these load manipulations in subjects with ET. 5. Conclusion Fig. 3. Neuromuscular activity results. (A) There was a significantly greater neuromuscular activity (EMG) amplitude with increased inertial loading. Given that this increase was similar in all groups, the groups were pooled. There was also a significant main effect for contraction type, with EMG amplitude being significantly smaller during eccentric contractions. (B) EMG tremor power was significantly greater in subjects in ET group 1 compared to those in ET group 2. EMG tremor power was significantly greater at 15% and 25% 1-RM load conditions compared to the no-load and 5% 1-RM load conditions. There was also a group by contraction type interaction due to subjects in ET group 1 having greater EMG tremor power during concentric contractions whereas subjects in ET group 2 had greater EMG tremor power during eccentric contractions. (C) EMG relative tremor power, which corresponds to the percent of total EMG power in the 0–40 Hz bandwidth that is accounted for by the EMG tremor peak, was significantly greater in subjects in ET group 1 compared to subjects in ET group 2. There was a significant reduction in EMG relative tremor power in both ET groups with increasing contraction intensities. con = concentric; ecc = eccentric.
The current study found that rhythmic muscle activity was present during simple movements of the wrist in subjects with ET, and that this activity was almost twice at great during movement compared to what was previously observed during postural and closedkinetic isometric tasks (Héroux et al., 2009, 2010). Functionally, the large amplitude kinetic tremor occurring when moving light loads is consistent with the types of tasks that most affect subjects with ET. Furthermore, given the greater correlation of kinetic tremor amplitude with measures of disability (D’Amboise et al., 2010), clinicians and researchers should continue to include measures of simple kinetic tremor (e.g., slow flexion–extension of the supported wrist) as part of their assessments. References
with ET performing a postural task. This brain network is associated with 8 Hz movement discontinuities and muscle bursts during smooth movement production in healthy subjects (Gross et al., 2002; Schnitzler and Gross, 2005). Thus, it would not be unreasonable to expect tremor-related rhythmic muscle activity to be greater during slow controlled movements in people with ET. This hypothesis was confirmed by the present study, and highlights
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