This study quantified the laterality of motor unit activation properties in
females with Parkinson’s disease during force production (low to high-intensity
contraction) using high-density surface electromyography. Sixteen females with
Parkinson’s disease (age = 69.9
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by unilateral motor symptoms [1]. These symptoms are caused by asymmetric central nervous system degeneration [2]. The central nervous system regulates motor unit (MU) recruitment and firing rates that regulate force output [3]. Previous studies using intramuscular electromyography (EMG) and high-density surface EMG (HD-SEMG) have shown that people with PD exhibit higher MU firing rates than healthy subjects [4, 5]. In particular, they have reported that people with PD have higher amplitudes of MU activity during low-intensity muscle contraction [5, 6]. Although MUs are newly recruited as the force increases in accordance with the size principle [7], Nishikawa et al. [5] reported that the more-affected side of females with PD deviates from the muscle activity pattern according to the size principle and shows abnormal MU firing behavior. Furthermore, Glendinning et al. [4] reported a possible shift in the MU population to lower recruitment thresholds in people with PD compared with healthy subjects.
Clinically, people with PD often present with asymmetry of physical symptoms (such as tremor and rigidity) [8] and MU firing behavior has been reported to differ between the more- and less-affected sides [5]. However, those studies analyzed MU firing behavior only during low-intensity muscle contraction. It is not clear what activity patterns MUs exhibit during high-intensity muscle contraction. Another study reported that people with PD experience selective atrophy of fast-twitch muscle fibers in addition to degeneration of the central nervous system [9]. Therefore, there may be a limitation of MU activation properties during high-intensity force production in people with PD. Although needle EMG is used to evaluate MU activation properties, it is painful and unsuitable for measuring the activity of MUs during high-intensity muscle contraction while HD-SEMG has the advantage of collecting similar information both noninvasively and painlessly.
HD-SEMG is a recently developed noninvasive method for evaluating individual MU activation properties using multiple electrodes (e.g., 64–400 channels) and spatial activation patterns across an entire muscle (Fig. 1A) [10, 11]. Studies that use this technique have shown that the spatial distribution of HD-SEMG activation across a muscle is affected by the intensity of contractions or fatigue level [12, 13, 14]. This phenomenon has been explained by the presence of spatial heterogeneity in the locations of different types of muscle fibers [15] and the clustering of muscle fibers innervated by one MU in a defined area [16]. Accordingly. changes in the spatial distribution of HD-SEMG signals can be explained by differences in MU recruitment patterns across the muscle, suggesting that the spatial distribution of HD-SEMG signals can be used to study changes in MU recruitment [17, 18]. Another study documented higher overall amplitudes of SEMG signals and lower heterogeneity in the SEMG signal distribution on the more-affected side of people with PD during force production than in healthy subjects [6]. The lower level of heterogeneity in the spatial EMG potential distribution may be due to the smaller number of newly recruited MUs in people with PD. However, to the best of the author’s knowledge, no studies have identified the laterality of MU activation properties in people with PD during high-intensity muscle contraction or the relationship with clinical measures of function.
High-density SEMG evaluates the spatial distribution
pattern of muscle activity within a muscle. (A) Topographic map of the SEMG RMS
values at 10% MVIC of a control subject (age 67). (B) During measurement, the
hip and knee joint angles were fixed at 90
The purpose of this study was to examine the laterality of the spatial distribution pattern of MU activation properties during force production (low- to high-intensity contraction) using HD-SEMG. It was hypothesized that compared with controls, people with PD would exhibit laterality of MU activation properties.
Sixteen idiopathic females with PD and 14 age-matched female controls were
enrolled in the present study (Table 1). A previous study reported that females
with PD exhibited larger asymmetries of motor symptoms than males with PD [19].
Thus, gender is an important factor in the unilateral symptoms of PD. For this
reason only females with PD were recruited for this study. The exclusion criteria
included: Hoehn & Yahr stage
Variables (unit) | Parkinson’s disease | Control subjects |
Age (years) | 69.9 |
68.6 |
Height (cm) | 155.9 |
153.3 |
Weight (kg) | 54.1 |
54.9 |
Knee extension torque (Nm) | 53.0 |
67.3 |
More-affected side/Less-affected side or Right/Left | ||
Disease duration (years) | 4.9 |
N/A |
UPDRS part III | 9 (1–14) | |
Data are shown as mean * Significant difference between contralateral side of people with PD and control subjects. |
All participants underwent measurement of maximal voluntary isometric
contraction (MVIC) of the bilateral knee extensors. The order of the measurements
was randomized to avoid bias toward the more or the less-affected side (or toward
the right or left side). A Dynamometer (Biodex System 4; Biodex Medical Systems,
Shirley, NY, USA) was used to measure the MVIC. During measurement, the hip and
knee joint angles were fixed at 90
HD-SEMG signals were detected from both sides of the VL muscle using a two-dimensional grid of 64 electrodes (ELSCH064NM2; OT Bioelettronica, Torino, Italy) during the MVIC and submaximal ramp-up contraction in accordance with previous studies [6, 20, 22, 23]. The multi-electrode grid consisted of thirteen rows and five columns (interelectrode distance, 8 mm in each direction, Fig. 1D). The tested area was shaved and cleaned with alcohol. Multiple electrodes were attached to the skin using a biadhesive sheet (KITAD064NM2; OT Bioelettronica) after adaptation of the conductive paste (Elefix Z-181BE; Nihon Kohden, Tokyo, Japan). A multiple electrode was attached at the center of the line between the femoral greater trochanter and the lateral edge of the patella. A ground electrode was placed at the anterior superior iliac spine [6, 20, 22, 23]. All EMG measurements were performed by the same examiner.
The monopolar signals were amplified (off-line bandpass filtered 10–500 Hz) by a factor of 1000, sampled at 2048 Hz, digitized by a 12-bit A/D converter (EMG-USB2+, OTBioelettronica) and processed using MATLAB software (MATLAB 2019b, Math Works GK, MA, USA). The root mean square (RMS) of EMG signals was calculated for a section of 500 ms centered at each 10% increase in MVIC force up to 70% MVIC during the submaximal ramp-up contraction task [6]. The RMS values of each electrode during the submaximal ramp-up contraction task were normalized by the RMS values of the MVIC.
The modified entropy and coefficient of variation (CoV) of the RMS were used to analyze the measurement of the heterogeneity of the spatial distribution pattern of the HD-SEMG amplitudes in each section. The modified entropy was calculated from the RMS values of each specific torque during submaximal ramp-up contraction (i.e., 10% to 70% MVIC) in accordance with a previous study [24]. The RMS coefficient of variation (CoV) was calculated from the mean and standard deviation of the 59 RMS measurements at each specific torque level (i.e., 10% to 70% MVIC) [6]. The changes in these variables indicate changes in the spatial distribution pattern of the MU activation properties within a muscle. A lower modified entropy and a higher CoV of the RMS indicate more heterogeneity in the spatial EMG distribution pattern within the multiple electrodes [25, 26]. Correlation coefficients were calculated from the RMS value of each channel between 10% MVIC and the other torque levels (i.e., 20% to 70% MVIC) to compare the temporal changes in the spatial distribution pattern of MU activation. The modified entropy and CoV of the RMS provide insight into the regulation of the nervous system for muscle activation patterns within a muscle, irrespective of the magnitude of activation [27]. The correlation coefficients provide information about temporal changes in the activation properties of MUs [21].
TResults are presented as the mean
The knee extension torque on the more-affected side of people with PD was
significantly smaller than on the contralateral sides of people with PD and
control subjects (p
A topographic map of HD-SEMG amplitude on both sides of people with PD and
control subjects is shown in Fig. 2A–D. Marked differences were evident in the
spatial distribution of the HD-SEMG signals at each torque level. In this example
and across the dataset in general, the normalized RMS magnitude of the
more-affected side of a person with PD was larger than the contralateral side of
people with PD and control subjects. The normalized RMS significantly differed
between the two groups (p
Topographic map of HD-SEMG amplitudes during the submaximal ramp-up contraction task. The RMS was normalized to the maximal voluntary contraction value.(A) The less-affected side in PD subjects. (B) The more-affected side in PD subjects. (C) The right side of control subjects. (D) The left side of control subjects.
Comparison of the normalized RMS between the two sides of
control subjects and PD subjects. The more-affected side in PD subjects showed a
significantly higher normalized RMS value than the contralateral side in PD
subjects or either side in control subjects. * p
Moderate correlations were observed between the scores of UPDRS part III and
Association between the UPDRS part III and EMG variables during
the submaximal ramp-up contraction task. Correlations between UPDRS part III
scores and
The CoV of the RMS and modified entropy differed significantly between the
groups (p
Comparison of EMG variables during the submaximal ramp-up
contraction task. The CoV of the RMS (A) and modified entropy (B) between the
two sides of control subjects and people with PD. The more-affected side in the
people with PD showed a significantly lower CoV of the RMS and a significantly
higher modified entropy than the contralateral side in people with PD or either
side in control subjects. * p
The
Comparison of the
The present study compared the laterality of MU activation properties between
people with PD and control subjects. The primary results were that the
more-affected side in people with PD exhibited (1) higher normalized RMS values
and (2) less heterogeneity than the contralateral side in people with PD or
either side in control subjects. (3) Furthermore, people with PD exhibited
moderate correlations between UPDRS part III scores and the laterality of EMG
variables (
These findings support the hypothesis that the more-affected side of people with PD shows higher amplitude and lower heterogeneity than the contralateral side of people with PD and control subjects during the force production (low to high-intensity contraction).
The knee extension torque of the more-affected side of people with PD was significantly lower than that of the contralateral side in people with PD and control subjects in the present study. This finding is consistent with the findings of previous studies that showed asymmetries in lower limb muscle strength [29, 30]. The muscle weakness and asymmetrical motor symptoms of people with PD may be related to the asymmetry of dopamine in the SNPc, resulting in extrapyramidal dysfunction and impaired motor output [31, 32, 33]. Consequently, the results of the present study may reflect asymmetry in neurodegeneration. Although people with PD who take oral medications that compensate for the reduced level of dopamine neurons exhibit improved motor function [28, 34], here, it is shown that asymmetric motor patterns persist.
The results of this study showed significantly higher relative RMS values on the
more-affected side of people with PD than on the contralateral side of people
with PD and control subjects. Furthermore, the more affected side showed moderate
correlations between the scores of UPDRS part III and
Less heterogeneity (lower CoV of the RMS and higher modified entropy) is reported for the more-affected side of people with PD than the contralateral side of people with PD and control subjects during the submaximal ramp-up contraction task. A higher level of heterogeneity in the EMG signal is consistent with a more coordinated and consistent activation of the lower limb muscle [21]. Based on this finding, the more-affected side of people with PD exhibited more inefficient muscle activity than the contralateral side of people with PD and control subjects. People with PD presenting without tremor show a lower amplitude of variance in mechanical muscle oscillations and acceleration than control subjects [36]. Motor symptoms occur after a marked loss of nigral neurons, resulting in the depletion of striatal dopamine, especially on the side of disease onset [37]. A previous study using positron emission tomography showed a correlation between biochemical asymmetry in the caudate and putamen and motor symptoms in people with early PD [38]. Furthermore, the activity of the putamen and supplementary motor area during unilateral movement is significantly reduced in these individuals and the authors suggested that the asymmetrical brain activity pattern may be an underlying reason for some motor deficits [39]. The central nervous system (e.g., nigral neurons and putamen) indirectly regulates force output by modulating the cortical recruitment of MUs and their firing rates [3]. At the level of the MU, a previous study reported that the more-affected side of people with PD exhibited more MU activity at lower force thresholds and inconsistent discharge rates of MUs than participants without PD in a submaximal task [4]. Dengler et al. [40] also reported that people with PD exhibit irregular firing patterns of MUs in the early stage of the disease. Thus, the loss of neurons in the SNPc not only increases muscle tone but also increases the irregular firing patterns of MUs. Furthermore, people with PD exhibited temporal changes in spatial MU activation properties and showed significant laterality when compared to healthy controls in both low and high-intensity contractions. In addition to degeneration of the central nervous system, people with PD display selective atrophy of fast-twitch muscle fibers [9]. This finding suggests that people with PD are impaired in the recruitment of MUs during high-intensity muscle contraction. In this study, there was clear muscle weakness on the more-affected side of the people with PD, which supports the idea that their MU activation properties are impaired during high-intensity muscle contraction. Although aerobic exercise is often implemented as physical therapy for people with PD, high-intensity muscle strength training is also expected to be useful, considering the specifics of the disability caused by PD.
This study has several limitations. First, only females were recruited. As shown in a previous study, compared with healthy young males, heathy females exhibited larger differences in the spatial distribution patterns of a sustained isometric contraction [22]. However, no studies have compared muscle activation patterns between females and males with PD. Second, only people with PD presenting mild motor symptoms were recruited for this study. Patients with different severities of PD must be compared to determine whether the laterality of EMG variables is affected by the disease stage or disease progression.
In this study, the laterality of spatial distributions of HD-SEMG signal amplitudes between bilateral sides of people with PD and control subjects was compared during force production (low- to high-intensity contraction). Based on the results of this study, the more-affected side in people with PD exhibits a higher RMS value and lower heterogeneity than the contralateral side in people with PD or either side in controls. In particular, the temporal changes in spatial MU activation properties showed significant laterality in people with PD compared to healthy control subjects, not only for low-intensity contractions but also for high-intensity contractions. These findings suggest that people with PD have asymmetrical MU activation properties, independent of the magnitude of force production.
CoV, coefficient of variation; EMG, electromyography; HD-SEMG, High-density surface electromyography; MU, motor unit; MVIC, maximal voluntary isometric contraction; PD, Parkinson’s disease; RMS, root mean square; SEMG, surface electromyography; SNPc, substantia nigra parts compacta; UPDRD, Unified Parkinson’s disease rating scale; VL, vastus lateralis.
YN and KW conceived and designed the study; YN performed experiments; YN and KW analyzed data; YN, KW, TT, NM, HM, ST, and AH interpreted the results of experiments; YN, KW and AH prepared figures; YN, KW, TT, and AH drafted the manuscript; and YN, KW, TT, NM, HM, ST, and AH edited and revised the manuscript. YN, KW, TT, NM, HM, ST, and AH approved the final version of the manuscript.
All experimental procedures were performed in accordance with the Declaration of Helsinki. This research protocol was approved by the Hiroshima University Committee on Ethics in Research (approval number, E-53-2). All participants received verbal and written explanations about their participation in this study and publication of this article and signed a consent form.
We thank Naoya Orita and Masashi Shimada for technical assistance.
This study was supported in part by research grants from JSPS KAKENHI, Grants-in-Aid for Young Scientists (17K179080 and 20K19448).
The authors declare no conflict of interest.