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<a href=Clinical Neurophysiology 122 (2011) 153–162 Contents lists available at ScienceDirect Clinical Neurophysiology journal homepage: www.else vier.com/locate/clinph Plasticity of motor cortex induced by coordination and training F. Tycˇ * , A. Boyadjian Laboratoire Plasticité et Physio-Pathologie de la Motricité, UMR 6196, CNRS, 31 Chemin J. Aiguier, 13402 Marseille Cedex 20, France article info Article history: Accepted 24 May 2010 Available online 17 June 2010 Keywords: TMS Motor cortex Training Coordination Plasticity Mapping abstract Objective: To study the modifications induced by training of a coordinated movement on the primary motor cortex (M1) maps of one proximal muscle and one distal muscle activated alone and during their co-contraction. Methods: Six healthy female sport students performed a 6-week training program during which they were trained in darts 3–4 times a week. At the end each subject had made more than 1200 throws. Trans- cranial magnetic stimulation (TMS) was used to map the proximal medial deltoid (MD) and the distal brachio-radialis (BR) muscle representations on M1. Motor evoked potentials (MEPs) amplitude and excitability curves were used to test corticomotor excitability. Results: The cortical representation areas of each muscle separately increased after training. The cortical representation and the excitability curve of the BR muscle increased during co-activation with the MD. Combining co-contraction and training produced a further enlargement of the M1 representation of the BR muscle. Conclusions: The enlargement of the BR representation in M1 suggests the development of overlapping zones specifying functional synergies between distal and proximal muscles. Significance: Our findings support the idea that training of a coordinated movement involving several muscles and joints requires an activity-dependent coupling of cortical networks. 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. 1. Introduction In healthy humans, the ability to learn novel motor skills through practice is accompanied by functional reorganization of the motor system including the primary motor cortex (M1) ( Pascual-Leone et al., 1994; Karni et al., 1995; Nudo et al., 1996; Classen et al., 1998 ). Motor practice induces changes in cortical motor representa- tion that can be measured with transcranial magnetic stimulation (TMS). The changes are principally an enlargement of the cortical representation of the muscle used in the task and a facilitation of the motor evoked potentials (MEPs), indicating an increase in corti- cal excitability. In short-term motor learning studies, cortical changes can be observed for a few minutes ( Garry et al., 2004 ), whereas learning a piano sequence produces more pronounced changes ( Pascual-Leone et al., 1994, 1995 ). Classen et al. (1998) used TMS to evoke isolated and directional thumb movements and showed that training modified the thumb cortical networks, which encoded movement kinetics. This suggests a short-term memory for movement that is the first step in skill acquisition ( Classen et al., 1998; Karni et al., 1995 ). Most of the cited studies were focused on distal hand muscles known to have larger cortical * Corresponding author. Tel./fax: +33 3 20 74 85 66. E-mail address: tycfr@free.fr (F. Tycˇ ). representations and explored the effects of short-term plasticity on their cortical representations. TMS has been used to map cortical representations of different muscles at rest ( Wassermann et al., 1992 ) and during low level activity ( Wilson et al., 1995 ). Motor cortex representations in hu- mans have shown discrete amplitude peaks included within a dif- fuse representation. Maps of different upper extremity muscles overlapped on the motor cortex in spite of a lateral shift ( Penfield and Rasmussen, 1950 ). The threshold for the activation of proximal muscles by transcranial electrical stimulation (TES, Rothwell et al., 1987 ) or TMS ( Wassermann et al., 1992 ) was higher than for distal muscles. A low level voluntary contraction permitted the observa- tion of MEPs at a lower rate of stimulation ( Wilson et al., 1995 ), especially for proximal muscles of the upper extremities that were difficult to map at rest ( Levy et al., 1991 ; see Amassian et al., 1995 ). Since Penfield and Boldrey (1937) and Penfield (1950) , the large representation of distal muscles has been generally associated with a fine level of control. Cortical maps revealed some size differences depending on handedness and the muscle location (proximal versus distal). Wassermann et al. (1992) showed that distal muscle representations were larger than proximal ones, and that they were larger for the dominant side, contrary to proximal muscles. A few studies have investigated the changes of proximal muscle representation induced by motor practice (see Tycˇ and Boyadjian, 1388-2457/$36.00 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. doi: 10.1016/j.clinph.2010.05.022 " id="pdf-obj-0-5" src="pdf-obj-0-5.jpg">

Contents lists available at ScienceDirect

Clinical Neurophysiology

<a href=Clinical Neurophysiology 122 (2011) 153–162 Contents lists available at ScienceDirect Clinical Neurophysiology journal homepage: www.else vier.com/locate/clinph Plasticity of motor cortex induced by coordination and training F. Tycˇ * , A. Boyadjian Laboratoire Plasticité et Physio-Pathologie de la Motricité, UMR 6196, CNRS, 31 Chemin J. Aiguier, 13402 Marseille Cedex 20, France article info Article history: Accepted 24 May 2010 Available online 17 June 2010 Keywords: TMS Motor cortex Training Coordination Plasticity Mapping abstract Objective: To study the modifications induced by training of a coordinated movement on the primary motor cortex (M1) maps of one proximal muscle and one distal muscle activated alone and during their co-contraction. Methods: Six healthy female sport students performed a 6-week training program during which they were trained in darts 3–4 times a week. At the end each subject had made more than 1200 throws. Trans- cranial magnetic stimulation (TMS) was used to map the proximal medial deltoid (MD) and the distal brachio-radialis (BR) muscle representations on M1. Motor evoked potentials (MEPs) amplitude and excitability curves were used to test corticomotor excitability. Results: The cortical representation areas of each muscle separately increased after training. The cortical representation and the excitability curve of the BR muscle increased during co-activation with the MD. Combining co-contraction and training produced a further enlargement of the M1 representation of the BR muscle. Conclusions: The enlargement of the BR representation in M1 suggests the development of overlapping zones specifying functional synergies between distal and proximal muscles. Significance: Our findings support the idea that training of a coordinated movement involving several muscles and joints requires an activity-dependent coupling of cortical networks. 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. 1. Introduction In healthy humans, the ability to learn novel motor skills through practice is accompanied by functional reorganization of the motor system including the primary motor cortex (M1) ( Pascual-Leone et al., 1994; Karni et al., 1995; Nudo et al., 1996; Classen et al., 1998 ). Motor practice induces changes in cortical motor representa- tion that can be measured with transcranial magnetic stimulation (TMS). The changes are principally an enlargement of the cortical representation of the muscle used in the task and a facilitation of the motor evoked potentials (MEPs), indicating an increase in corti- cal excitability. In short-term motor learning studies, cortical changes can be observed for a few minutes ( Garry et al., 2004 ), whereas learning a piano sequence produces more pronounced changes ( Pascual-Leone et al., 1994, 1995 ). Classen et al. (1998) used TMS to evoke isolated and directional thumb movements and showed that training modified the thumb cortical networks, which encoded movement kinetics. This suggests a short-term memory for movement that is the first step in skill acquisition ( Classen et al., 1998; Karni et al., 1995 ). Most of the cited studies were focused on distal hand muscles known to have larger cortical * Corresponding author. Tel./fax: +33 3 20 74 85 66. E-mail address: tycfr@free.fr (F. Tycˇ ). representations and explored the effects of short-term plasticity on their cortical representations. TMS has been used to map cortical representations of different muscles at rest ( Wassermann et al., 1992 ) and during low level activity ( Wilson et al., 1995 ). Motor cortex representations in hu- mans have shown discrete amplitude peaks included within a dif- fuse representation. Maps of different upper extremity muscles overlapped on the motor cortex in spite of a lateral shift ( Penfield and Rasmussen, 1950 ). The threshold for the activation of proximal muscles by transcranial electrical stimulation (TES, Rothwell et al., 1987 ) or TMS ( Wassermann et al., 1992 ) was higher than for distal muscles. A low level voluntary contraction permitted the observa- tion of MEPs at a lower rate of stimulation ( Wilson et al., 1995 ), especially for proximal muscles of the upper extremities that were difficult to map at rest ( Levy et al., 1991 ; see Amassian et al., 1995 ). Since Penfield and Boldrey (1937) and Penfield (1950) , the large representation of distal muscles has been generally associated with a fine level of control. Cortical maps revealed some size differences depending on handedness and the muscle location (proximal versus distal). Wassermann et al. (1992) showed that distal muscle representations were larger than proximal ones, and that they were larger for the dominant side, contrary to proximal muscles. A few studies have investigated the changes of proximal muscle representation induced by motor practice (see Tycˇ and Boyadjian, 1388-2457/$36.00 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. doi: 10.1016/j.clinph.2010.05.022 " id="pdf-obj-0-16" src="pdf-obj-0-16.jpg">

Plasticity of motor cortex induced by coordination and training

F. Tycˇ * , A. Boyadjian

Laboratoire Plasticité et Physio-Pathologie de la Motricité, UMR 6196, CNRS, 31 Chemin J. Aiguier, 13402 Marseille Cedex 20, France

article info

Article history:

Accepted 24 May 2010 Available online 17 June 2010

Keywords:

TMS

Motor cortex

Training

Coordination

Plasticity

Mapping

abstract

Objective: To study the modifications induced by training of a coordinated movement on the primary motor cortex (M1) maps of one proximal muscle and one distal muscle activated alone and during their co-contraction.

Methods: Six healthy female sport students performed a 6-week training program during which they were trained in darts 3–4 times a week. At the end each subject had made more than 1200 throws. Trans- cranial magnetic stimulation (TMS) was used to map the proximal medial deltoid (MD) and the distal brachio-radialis (BR) muscle representations on M1. Motor evoked potentials (MEPs) amplitude and excitability curves were used to test corticomotor excitability. Results: The cortical representation areas of each muscle separately increased after training. The cortical representation and the excitability curve of the BR muscle increased during co-activation with the MD. Combining co-contraction and training produced a further enlargement of the M1 representation of the BR muscle. Conclusions: The enlargement of the BR representation in M1 suggests the development of overlapping zones specifying functional synergies between distal and proximal muscles. Significance: Our findings support the idea that training of a coordinated movement involving several muscles and joints requires an activity-dependent coupling of cortical networks. 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

1. Introduction

In healthy humans, the ability to learn novel motor skills through practice is accompanied by functional reorganization of the motor system including the primary motor cortex (M1) (Pascual-Leone et al., 1994; Karni et al., 1995; Nudo et al., 1996; Classen et al., 1998). Motor practice induces changes in cortical motor representa- tion that can be measured with transcranial magnetic stimulation (TMS). The changes are principally an enlargement of the cortical representation of the muscle used in the task and a facilitation of the motor evoked potentials (MEPs), indicating an increase in corti- cal excitability. In short-term motor learning studies, cortical changes can be observed for a few minutes (Garry et al., 2004), whereas learning a piano sequence produces more pronounced changes (Pascual-Leone et al., 1994, 1995). Classen et al. (1998) used TMS to evoke isolated and directional thumb movements and showed that training modified the thumb cortical networks, which encoded movement kinetics. This suggests a short-term memory for movement that is the first step in skill acquisition (Classen et al., 1998; Karni et al., 1995). Most of the cited studies were focused on distal hand muscles known to have larger cortical

* Corresponding author. Tel./fax: +33 3 20 74 85 66. E-mail address: tycfr@free.fr (F. Tycˇ ).

representations and explored the effects of short-term plasticity on their cortical representations. TMS has been used to map cortical representations of different muscles at rest (Wassermann et al., 1992) and during low level activity (Wilson et al., 1995). Motor cortex representations in hu- mans have shown discrete amplitude peaks included within a dif- fuse representation. Maps of different upper extremity muscles overlapped on the motor cortex in spite of a lateral shift (Penfield and Rasmussen, 1950). The threshold for the activation of proximal muscles by transcranial electrical stimulation (TES, Rothwell et al., 1987) or TMS (Wassermann et al., 1992) was higher than for distal muscles. A low level voluntary contraction permitted the observa- tion of MEPs at a lower rate of stimulation (Wilson et al., 1995), especially for proximal muscles of the upper extremities that were difficult to map at rest (Levy et al., 1991; see Amassian et al., 1995). Since Penfield and Boldrey (1937) and Penfield (1950), the large representation of distal muscles has been generally associated with a fine level of control. Cortical maps revealed some size differences depending on handedness and the muscle location (proximal versus distal). Wassermann et al. (1992) showed that distal muscle representations were larger than proximal ones, and that they were larger for the dominant side, contrary to proximal muscles. A few studies have investigated the changes of proximal muscle representation induced by motor practice (see Tycˇ and Boyadjian,

1388-2457/$36.00 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  • 154 F. Tycˇ , A. Boyadjian / Clinical Neurophysiology 122 (2011) 153–162

2006). Liepert et al. (1999) have shown that short-term training of synchronous thumb and foot movements modified motor output

written consent for the study. All subjects were right-handed according to the Edinburgh Handedness Inventory (Oldfield, 1971).

maps due to interactions between hand and foot representation areas in M1. This result indicated a shift of the thumb motor output

  • 2.2. Training protocol

map towards the leg map. Changes in hand muscle corticomotor excitability in relation to static shoulder positions have been inter- preted as a proximal–distal synergism operating through reaching movements (Ginanneschi et al., 2005). More recently, comparison of the effects of short-term training at proximal and distal upper limb joints, revealed a greater effect on the pathways controlling the index finger and a smaller effect on pathways controlling more proximal joints (Krutky and Perreault, 2007). These findings sug- gested a difference in the motor cortical contributions to short- term motor plasticity in the pathways controlling proximal and distal joints in the upper limb. Ackerley et al. (2007) used TMS to explore whether training in different coordination patterns affects the development of motor plasticity. A simple repetitive thumb movement made in synchrony, or in syncopation, with respect to an auditory metronome, shifted both synchronized and syncopated motor practice modified thumb movements in the trained direc- tion. These studies have raised questions about the role of the mo- tor cortex in coordinating multi-joint movements and the impact of training. To date, it has not been established whether long-term training of a complex coordinated movement affects the cortical representation of muscles during their co-activation. In a previous study, we examined the effect of highly-skilled

The subjects participated in a six-week training program during which they trained at throwing darts 3–4 times a week. Each sub- ject received a complete dart game set including a dartboard and three darts. The dartboard was used on the side showing 10 con- centric circles worth one point for the external circle and 10 points for the centre. The throwing distance was indicated by a black line on the floor set at 2.4 m from the dartboard. The subject had her right hip facing the target, with her right foot on the black line and threw the dart with her right arm. In this specific position MD and BR muscles are co-contracted as shown by EMG recordings (Fig. 1). During each training session the subject had to maintain the same position at the same distance from the dartboard and place darts as close as possible to the centre of the target in order to obtain a maximum number of points. Each session lasted 15– 20 min and consisted of 60–80 throws. At the end of the six weeks, each subject had made more than 1200 throws. Before starting the six-week training program and at the end of the six-week training program, each subject performed a test with 15 throws. The mean point obtained per dart was calculated by summing the number of points of the 15 throws and then dividing by 15. Comparison of the two scores provided an evaluation of the effect of training.

behaviour on motor cortex representations of upper extremity muscles in volleyball players. We showed an expansion of proximal

  • 2.3. Electromyographic recordings (EMG)

muscle representation in the contralateral M1 with an increase in overlap between proximal and distal muscle representations (Tycˇ et al., 2005). This overlap was suggested to play a role in muscle control during coordinated multi-joint movements. It was consis- tent with other findings that generated the hypothesis that M1 could control the different limb segments as a whole rather than individually (Scott 2000). For example, shoulder, elbow and wrist muscle activation during pointing movements appeared to involve common motor cortical circuits (Devanne et al., 2002). As Schieber

The skin was prepared for EMG recordings obtained from paired surface electrodes placed over the belly of the MD and BR muscles of the right arm (see Fig. 1). A large reference electrode was placed around the wrist. EMGs were recorded over a 250 ms time window including 50 ms prior to the stimulus. EMG signals were amplified ( 1000) with high pass filtering at 10 Hz and low pass filtering at 1 kHz before being sampled at 2 kHz by an A/D converter and stored on a computer for off-line analysis.

(2001) has suggested, an organization of the motor cortex with lar- ger representations of the proximal muscles overlapping those of

  • 2.4. Transcranial magnetic stimulation

the distal muscles might facilitate coordination and motor learning. The purpose of the present study was to use TMS to further ana- lyze the changes in cortical representations of a shoulder muscle and of a forearm muscle used to execute a complex coordinated movement. The key parameters in our protocol were the learning of a coordinated complex movement, the co-contraction of a prox- imal and a distal muscle, and long-term motor training. We chose the traditional game of darts, in which all joints in an upper limb are involved in a specific coordination pattern and timing of proximal and distal muscles (Temprado et al., 1997). We report the changes in the cortical representations of the proximal medial deltoid (MD) and the distal brachio-radialis (BR) muscles following a six-week training period together with an enlargement of the scalp-evoked motor maps when the two muscles are co-contracted.

A snugly fitting cap was positioned over the subject’s head and a grid was drawn with stimulus sites spaced 1.5 cm from the ver- tex using the nasion-inion line and the inter-aural line as refer- ences. TMS was delivered using a figure-of-eight coil with external loop diameter of 9 cm connected to a MagStim 200 elec- tromagnetic stimulator (maximum output intensity 2.0 T, Mag- stim, Dyfed, UK). The coil was held tangentially to the skull positioned at 45 in relation to the nasion-inion line with the han- dle to the rear so that the induced monophasic current flow was in a posterior to anterior direction. This is the most favorable orienta- tion for activating the corticospinal tract transynaptically (Kaneko et al., 1996). The junction of the coil was placed over the site to be stimulated on the left hemisphere that elicited MEPs in the right contralateral target muscles.

Part of this work has been presented in abstract form (Tycˇ and Boyadjian, 2008).

  • 2.5. Experimental protocol

2. Methods

Two sessions of identical measurements were carried out. The first one was carried out before the training period (control) and

2.1. Subjects

the second one at the end of the training period (six weeks later). To record EMG activity, subjects were comfortably seated and

Studies conforming to the standards set by the declaration of Helsinki were carried out on six healthy female sport students (mean age 21 ± 0.26) who did not regularly participate in a sport involving specific arm activity. All subjects gave their free informed

adopted a static position in order to produce constant low level activity in each muscle. EMG activity was displayed on line on a computer screen to allow the subject to maintain a constant and stable low EMG activity set at 5% of the maximal EMG activity. Two sets of 2 s recordings were made to measure EMG activity,

F. Tycˇ , A. Boyadjian / Clinical Neurophysiology 122 (2011) 153–162

155

F. Tycˇ , A. Boyadjian / Clinical Neurophysiology 122 (2011) 153–162 155 Fig. 1. Photo showing

Fig. 1. Photo showing the position of the throwing arm and the place of the electrodes on MD and BR muscles. Right, rectified EMG obtained during the three phases of throwing. Note the co-activation of MD and BR muscles during throwing.

the first during low level activity produced during mapping and the second during maximum voluntary contraction. The value of the rectified EMG during low activity was divided by the values ob- tained during maximal EMG activity to quantify the activity during mapping. The mean values of the rectified EMG during low level activity were stable at 5% of the maximal EMG activity in both ses- sions. For MD recordings, the subject placed their arm in a stable position aiming at a target to throw a dart. For BR, recordings were obtained under two conditions. (1) Alone condition: the subject maintained the 5% low activity in the BR muscle in a static position with the forearm on an arm-rest. Particular care was taken to en- sure that only the BR muscle was contracted and no EMG activity could be recorded in the MD muscle as verified online at high mag- nification on the screen. Mapping only started when the MD mus- cle was silent. (2) Co-active condition: the subject maintained 5% low EMG activity in both muscles (BR and MD).

  • 2.6. Motor output mapping

Prior to mapping, the hot spot and the active motor threshold (aMT) were determined for each muscle. The hot spot was the site at which the largest MEP could be induced with suprathreshold single stimuli applied with TMS. The aMT was defined as the low- est stimulation intensity that induced a peak-to-peak MEP ampli- tude of more than 200 lV in 5 out of 10 trials in the target muscle. The TMS intensity was then adjusted to 1.2 times the aMT of each muscle for mapping. Three TMS response maps were established on the left hemisphere: one for MD muscle and two for BR muscle (Alone and Co-active condition). Four stimuli were delivered at each grid site with intervals randomly ranging be- tween 3 and 5 s. The four recordings were averaged and stored on a computer for further off-line analysis.

  • 2.7. Excitability curves

Excitability curves (Ridding and Rothwell, 1997) were obtained by stimulating the BR hot spot with ten increasing TMS intensities (from 1.2 to 1.65 aMT) under two conditions. Alone condition, with only the BR muscle contracted and Co-active condition with the two muscles (BR and MD) contracted. At each intensity, three stimuli were applied and MEPs stored for further analysis.

  • 2.8. Data analysis

To determine the cortical representation of each muscle the four non-rectified EMG recordings were averaged for each stimula- tion site. The peak-to-peak amplitude of the MEPs was measured and plotted on medio-lateral and antero-posterior coordinates. For each subject and for each muscle, a contour plot was drawn with its external borderline corresponding to the amplitude of

the minimal MEP (2D representation). The area of the contour plot, i.e. the muscle map representation on the scalp in cm 2 was then calculated. For 3D representation, the Lorentzian 3D function was used to fit data by the Levenberg–Marquard nonlinear least-mean-square algorithm (Press et al., 1986; Tycˇ et al., 2005; Devanne et al., 2006). This algorithm determines the function parameters that minimize the sum of the squared differences between the observed and the predicted values of the dependent variable using a gradient descent-based optimization procedure. Before fitting, the baseline was adjusted to the mean rectified EMG activity recorded during the 2 s low level activity. The Lorentzian equation relating the peak-to-peak amplitude of the MEP and the antero-posterior (y) and medio-lateral (x) coordinates was given by the following equation:

Z max

Z ¼

1 þ

ðx x0Þ a

2

1 þ

ðy y0Þ b

2

Zmax is the estimated amplitude of the maximal MEP that is located at coordinates x0 and y0. The parameters a and b reflect the straightness of the peak in the medio-lateral and antero-posterior directions, respectively. It has been shown that the estimated coor- dinates of the theoretical hot spot (x0 and y0) of each muscle’s rep- resentation were within the area from which MEPs were evoked and very close to the site at which the largest response was ob- tained experimentally (Devanne et al. 2006). For excitability curve fitting, we used the Boltzmann sigmoidal function where MEPmax represents the plateau level, S 50 the stim- ulus intensity required to obtain the 50% plateau value, and k re- flects the slope of the curve:

MEP ¼

MEP max

1 e ðs s 50 =kÞ

For statistics a two-way ANOVA for repeated measurements was calculated. Muscle representation variables (2D and 3D) and the excitability curves were compared between sessions for both muscles and between both conditions for BR muscle (Alone and Co-active) using a paired t-test as appropriate. To test the effect of independent variables on excitability curves, we used a t-test based on the standard error of estimate associated with each best-fit parameter in each subject. The level of significance was set at 5%.

3. Results

The six-week training period induced an increase in the performance in the throwing test for each subject. Before training, the 15 throws test resulted in a score between 47 and 89 points

  • 156 F. Tycˇ , A. Boyadjian / Clinical Neurophysiology 122 (2011) 153–162

156 F. Tycˇ , A. Boyadjian / Clinical Neurophysiology 122 (2011) 153–162 Fig. 2. Mean of

Fig. 2. Mean of 4 MEPs produced by TMS in MD and BR muscles at each scalp position in one subject before and after the 6 weeks training session. The location of the MEP traces on the grid corresponds to the scalp sites from where they were evoked. V, vertex position.

with a mean of 70 points for the six subjects (4.7 points per dart). The score after training was 77 to 112 points with a mean of 94 points (6.3 points per dart). The aMT were stable and no statistical difference was observed throughout the training session for each subject and for both mus- cles. The aMT of the BR muscle expressed as a percentage of the maximal stimulator output were 34.8 ± 1.72% (mean ± SEM) before the training program and 34 ± 2.08% after training. For the MD

muscle the aMT were 37.7 ± 2.69% and 37 ± 2.21% before and after the training program. By stimulating M1 and recording the MEPs from the target mus- cles, an estimate of the representation of each muscle was obtained on the scalp. Fig. 2 is an example of the MEPs obtained for the MD and BR muscle representations before and after six-weeks training in one subject. The location of MEP traces on the grid corresponds to the scalp position from which they were evoked. The same

F. Tycˇ , A. Boyadjian / Clinical Neurophysiology 122 (2011) 153–162

157

Table 1

Map areas and number of MEPs for MD muscle for six subjects before and after the

6 weeks training. Means are shown ± SEM.

 

MD map area (cm2)

 

Number of MEP

 

Before

After

%

Before

After

%

  • 1 37.1

47

127

15

22

147

  • 2 21.2

34.9

165

12

16

133

  • 3 32.3

35.9

111

17

17

100

  • 4 22.4

26.4

118

11

14

127

  • 5 22.6

30.7

136

12

16

133

  • 6 27.4

32.1

117

13

17

131

Mean

27 ± 2.6

35 ± 2.9

129 ± 8.0

13 ± 0.9

17 ± 1.1

128 ± 6.3

protocol was applied to each subject. The data obtained for the six subjects before and after training on MD muscle are provided in Table 1. The mean number of sites from which a MEP could be in- duced in the MD muscle increased from 13 to 17. The mean surface area of the MD muscle representation containing the sites in- creased significantly (p < 0.006) from 27 to 35 cm 2 after training. This modification is illustrated by the contour plots obtained in one subject in Fig. 3A. After the training session the mean motor area for the MD muscle represented 129% of the mean motor area obtained before training. For the BR muscle cortical map area, the interaction between ses- sion (before and after training) and condition (Alone and Co-active) was tested with two way repeated ANOVA. No statistically signifi-

cant interaction was found (F = 0.0546, P = 0.824). The BR muscle representation was determined before and after training, as was the representation of the MD muscle (Fig. 2). Training induced sim-

ilar increases in the number of MEPs and map area for the BR muscle

as was observed for the MD muscle representation (Fig. 3B). The size of the surface area of the cortical representation of the BR after training was significantly different from before training (p < 0.02). The results are given in Table 2 for the six subjects (BR alone).

  • 3.1. The effects of co-contraction

Mapping was performed to evaluate the effect of co-contraction on the representation of the BR muscle (Fig. 2, BR Co-active). The surface area of the BR representation increased during co-contrac- tion as shown in Fig. 3C. Table 2 provides the results for the six subjects (BR Co-active). The mean number of cortical sites from which a MEP could be obtained on the BR muscle in the Co-active condition was 19 compared to 16 in the Alone condition. The mean BR muscle representation area was 39 cm 2 in the Co-Active Condi- tion and was significantly larger (p < 0.02) than the 31 cm 2 when the BR muscle was tested alone.

  • 3.2. Dual effects of co-contraction and training

The effect of co-contraction of both muscles was measured on the BR muscle representation before and after the training session.

F. Tycˇ , A. Boyadjian / Clinical Neurophysiology 122 (2011) 153–162 157 Table 1 Map areas

Fig. 3. Cortical representations obtained in one subject for MD (A) and BR (B) muscles before (straight line) and after (dotted line) training. C and D, cortical representations of BR muscle obtained in the Alone (arrows) and the Co-Active (dashed line) Conditions before training (C) and after training (D).

  • 158 F. Tycˇ , A. Boyadjian / Clinical Neurophysiology 122 (2011) 153–162

Table 2

Map areas and number of MEPs for BR muscles of six subjects before and after the 6 weeks training in the two conditions: Alone (only BR muscle contracted) and Co-Active (BR and MD muscles co-contracted). Means are shown ± SEM.

 

BR Alone

BR Co-Active

% Co-Active/Alone

Before

After

%

Before

After

%

Before

After

Map area (cm 2 )

1

38.4

58.8

153

54.5

60.1

110

142

102

2

31.7

39.3

124

34.5

42.6

123

109

109

3

39.1

42.8

110

41.2

50.3

122

105

118

4

28.6

40.3

141

39.9

54.5

137

140

135

5

24.8

29.8

120

31.3

34.6

111

126

116

6

25.3

32.6

129

34.1

44.9

132

135

138

Mean

31 ± 2.6

41 ± 4.2

129 ± 6.3

39 ± 3.4

48 ± 3.7

122 ± 4.4

126 ± 6.4

120 ± 5.8

Number of MEP

1

17

25

147

22

26

118

129

104

2

17

20

118

17

23

135

100

115

3

19

20

105

20

21

105

105

105

4

16

19

119

19

24

126

119

126

5

13

15

115

15

18

120

115

120

6

14

18

129

18

20

111

129

111

Mean

16 ± 0.9

20 ± 1.3

122 ± 5.8

19 ± 1.0

22 ± 1.2

119 ± 4.4

116 ± 4.9

113 ± 3.5

One example obtained in one subject is shown in Fig. 3C and D where an increase in the surface area of the BR muscle was ob- served. Data for the six subjects are given in Table 2, confirming the effect of co-contraction and the effect of training on the mean surface area of BR muscle representation. The mean number of cor- tical sites from which a MEP could be obtained on the BR in the Co- Active Condition was 19 before training against 22 after training. The 48 cm 2 of the mean surface area of the BR muscle reached after training must be compared to the 39 cm 2 measured before train- ing. The increase was significant (p < 0.02) and represented 122% of the map area before training.

3.3. 3D representation of the MD and BR muscles

To estimate the coordinates (x 0 , y 0 ) of the theoretical hot spots, a 3D representation of the muscles was calculated in order to fol- low the modification of the location of the hot spots in the three experimental situations. Fig. 4A illustrates the modification ob- tained on 3D representations after training for both muscles. It indicates an increase in the cortical excitability associated with an increase of the cortical surface from which the muscle could be activated. The mean R 2 values were between 0.71 and 0.84 for the six subjects. The distances between the theoretical hot spots of the MD and the BR (Table 3) were significantly different (p < 0.03) in the Alone Condition but not in the Co-Active Condition (p < 0.06). For one subject fig. 4B (left) shows that the co-contrac- tion induced a reduction of the inter-spot distance from 18 to 7.5 mm before training. After training, the inter-spot distance was 4.1 mm for the BR alone while the location of the hot-spots nearly coincided (0.5 mm) in the Co-Active Condition. The histo- grams in Fig. 4B (right) show the differences in inter-spot distances between before and after training. In the Alone Condition a reduc- tion of the inter-spot distances was observed in five out of six sub- jects and in all subjects in the Co-Active Condition. The reduction emphasizes the dual effect of training and co-contraction.

3.4. Excitability curves

The excitability curves measured on the BR muscle showed an increased MEP area when the stimulation intensity was increased before and after the training session under the Alone and Co-Active Condition (Fig. 5, left). During co-activation, the plateau levels of the curves reached higher values in each subject and for each

session compared to the levels reached when the BR muscle was activated alone. The histograms of Fig. 5 (right) confirm that the values of the plateau levels obtained from the excitability curves before and after training for the six subjects were systematically and significantly higher during co-contraction (142% and 159% be- fore and after training). The increase in cortical excitability re- sulted from the combined effects of training and co-contraction.

4. Discussion

The principal finding of the present study is that co-activation of the proximal MD muscle with the distal BR muscle enlarges the cortical representation of the BR muscle and that a six-weeks training period produces an enlargement of the cortical motor rep- resentations of the co-contracted muscle.

4.1. Condition of recordings

At rest, proximal muscles are difficult to map (Levy et al., 1991; Amassian et al., 1995). Stimulus intensity can reach 80% of the max- imal intensity of the stimulator that is approximately twice the intensity used during low level activity (Tycˇ and Boyadjian, 2006). In contrast, when a muscle is slightly activated, the MEP threshold is decreased and TMS mapping is facilitated (Wilson et al., 1995). Our experimental protocol relies on these observations.

4.2. Location of training-dependent plasticity

The increase of MEP size induced by co-activation and training reflects a modification of the excitability of the cortico-spinal sys- tem as a whole without providing evidence that plasticity occurs at cortical levels. However, it can be argued that the observed effects on corticomotor excitability cannot exclusively operate at the spinal level even though the spinal neuronal circuitry has been shown to exhibit adaptive plasticity in experimental animals (Wolpaw and Carp, 1993) and in humans (Baylor and Benjuya, 1989). Because TES produces a greater proportion of direct activa- tion of corticospinal neurons than TMS (Day et al., 1987a, b; Rothwell, 1997) and because training induces an increase in MEPs evoked by TMS but not by TES brain stem or cervical stimulation (Classen et al., 1998; Muellbacher et al., 2001; Perez et al., 2004; Garry et al., 2004), this form of plasticity is more likely to occur at the level of the cortical networks than at subcortical levels.

F. Tycˇ , A. Boyadjian / Clinical Neurophysiology 122 (2011) 153–162

159

F. Tycˇ , A. Boyadjian / Clinical Neurophysiology 122 (2011) 153–162 159 Fig. 4. (A) Three-dimensional

Fig. 4. (A) Three-dimensional reconstructions of MD and BR muscles based on MEP recordings before and after training. The total variance accounted for by fitting the Lorentzian function to the data points is given by the R 2 value. (B) Left, the diagrams illustrate the measure of the distance between MD and BR hot spots in one subject chosen to illustrate the maximal reduction of the inter-spot distances. Right, the histograms represent the differences between inter-spot distances before and after training in the two conditions for the six subjects.

4.3. Reproducibility of cortical M1 maps

Although there can be no doubt that the brain displays plastic- ity, stability of cortical networks is also needed, as discussed in a recent review by Wandell and Smirnakis (2009). That motor cortical map representations are reproducible in subjects over a long period of time is well documented. The

TMS-mapped representations of two intrinsic hand muscles were found to be very reproducible when mapping was repeated after intervals of up to 181 days (Wilson et al., 1993). A method for mapping the motor cortex by TMS was tested statistically for its reproducibility and found to be reliable for mapping the human motor cortex (Mortifee et al., 1994). Maeda et al. (2002) investi- gated the reproducibility of mapping techniques on six normal

  • 160 F. Tycˇ , A. Boyadjian / Clinical Neurophysiology 122 (2011) 153–162

Table 3

Distances (mm) between estimated hot spot of MD and BR muscles before and after training in the two conditions (Alone and Co-active) for the six subjects. These data

were used to measure the differences between inter-spot distances represented in Fig. 4B right.

 

Distance between MD and BR hot spot

 

Alone Condition

Co-Active Condition

Before

After

Before

After

  • 1 20.0

18.1

22.7

14.2

  • 2 18.0

4.1

7.5

0.5

  • 3 10.4

11.5

11.7

11.3

  • 4 15.3

9.8

14.2

11.3

  • 5 15.5

7.2

15.3

10.4

  • 6 15.3

13

13.2

8.8

Mean

15.7

10.6

14.1

9.4

volunteers, each studied on two occasions several weeks apart (ranging from 21 to 132 days) and showed a low degree of variabil- ity of repetitive TMS (rTMS) effects in the human brain. The areas of the scalp from which responses were evoked from corticospinal cells projecting to three intrinsic hand muscles were systematically mapped using TMS on eight normal subjects at different intervals (24 h, one week and two weeks). The area, ‘‘volume”, and centre of gravity of these maps did not change significantly over that per- iod. It was concluded that TMS mapping is suitable for studies that aim to examine the effect of various interventions on the cortical representation of individual muscles in human subjects (Miranda et al., 1997; Uy et al., 2002.; Pitcher et al., 2003; Monfils et al., 2005). Variation in the response to TMS in the general population allowed Wassermann (2002) to state with confidence that the MEP to single and paired TMS is a sensitive measurement of the cortico- spinal function. Taken together, and even though some differences in aMT and cortical excitability exist between subjects, these find- ings demonstrate that cortical maps are reproducible in a given subject over long periods of time and are similar in both hemi- spheres, and are similar in left- and right-handed subjects. The sta- bility of aMT observed in our experiments between the two sessions validates our choice to consider the first session of mea- surements before training as the control condition, as well as our use of map parameters for investigation of long-term effects of training.

4.4. A cortical representation of coordination?

The capacity of M1 to undergo plastic reorganization following skill acquisition and training is well established in humans and animals (Pascual-Leone et al., 1994, 1995; Classen et al., 1998; Kar-

ni et al., 1998; Kleim et al., 1998; Liepert et al., 2000; Plautz et al.,

2000; Yahagi and Kasai, 1998; Muellbacher et al., 2001; Tycˇ and

Boyadjian, 2006.). Many studies have investigated the effect of short-term training on the cortical representation of distal muscles executing repetitive sequences of finger movements (Tycˇ and Boy- adjian, 2006). For example, in normal human subjects instructed to practice a repetitive sequence of finger movements, the amplitude and extent of finger muscle representation assessed by TMS in- creased in M1 contralateral to the performing hand as the speed of performance increased over a single day of training (Pascual- Leone et al., 1994). In contrast, we focus our experiments on the ef- fects of a six-week training period on the cortical representation of a complex coordinated movement namely the movement executed by a subject playing darts, in which all the joints in an upper limb are involved in a specific coordination pattern and timing of prox- imal and distal muscles (Temprado et al., 1997; Scott, 2000). Motor patterns at each joint must be carefully coordinated to smoothly move the joints and the hand through space. Many stud- ies have described the trajectories of hand and arm movements un- der normal conditions as straight hand paths called stereotyped movements (Bernstein, 1967; Flash and Hogan, 1985; Wolpert et al., 1995). These were defined as simple basic motor elements (‘‘primitives”). The notion that skilled movements might reflect a process for the concatenation of consecutive movement elements into complex movements was suggested by Sosnik et al. (2004). On this assumption, a new primitive movement could be generated by training which would be different from the sum of the elements that comprised the sequence of initial movements (Engel et al., 1997). By studying the acquisition of skilled motor performance, Karni et al. (1995, 1998) showed that performance was paralleled by the emergence of a more extensive representation of a trained sequence of movements in M1. It has been suggested that a specific representation of the sequence might be implemented at the M1 level as a new functional unit, differentially from the component movements (Karni et al., 1998). In monkeys, practice-dependent changes in the functional topography of M1 were reported by Nudo

160 F. Tycˇ , A. Boyadjian / Clinical Neurophysiology 122 (2011) 153–162 Table 3 Distances (mm)

Fig. 5. (A) Excitability curves obtained on the BR muscle hot spot for one subject before and after training in the two conditions Alone (straight line) and Co-Active (dotted line). (B) Histograms representing the values of the plateau obtained on the excitability curves before and after training in the two conditions for the six subjects. Note the different scale for subject number 3 on the right (ordinates). * indicates a significant difference (p < 0.05) in the plateaus reached in the Alone and Co-Active conditions; ** indicate a significant difference (p < 0.05) in the plateaus reached before training and after training.

F. Tycˇ , A. Boyadjian / Clinical Neurophysiology 122 (2011) 153–162 161

et al. (1996, 2001). After a few weeks of training on a task that re- quired skilled manipulation, a new movement representation was observed in M1 that was not found in untrained brains. These find- ings support the idea of a cortical representation of the learned motor sequence in M1 and underpinned our experimental protocol. Our finding that the co-activation of the proximal and the distal muscles enhanced the TMS-evoked motor output in the distal BR muscle showed that some functional networks were triggered dur- ing coordinated movements. We interpreted the enlargement of the motor cortical output maps to the muscles involved in the task and their overlap indicative of a functional link between the two target muscles carrying out the coordination. Our observation that the proximal muscle modified the excitability curves of the distal muscle confirmed that the sharing of networks is necessary for coordination, as observed in other studies (Devanne et al., 2002; Ginnaneschi et al., 2006). TMS studies have shown that the cortical representations of dif- ferent muscles overlap on M1 (Wilson et al., 1993; Wassermann et al., 1993; Liepert et al., 1999; Tycˇ et al., 2005; Devanne et al., 2006). In animals, studies involving the superposition of M1 topo- graphical maps obtained by micro-stimulation, have shown that motor cortical zones controlling different forelimb segments are interconnected by intrinsic horizontal collaterals (Capaday et al., 1998; Huntley and Jones, 1991; Keller, 1993; Rioult-Pedotti and Donoghue, 2003; Tokuno and Tanji, 1993). In Rhesus monkeys, Park et al. (2001) found regions combining both distal and proxi- mal muscles following electrical stimulation of the cortical surface. In the cat, simultaneous stimulations of two cortical points were additive and resulted in a new movement that was a combination of the movements elicited by stimulation of each point on its own (Ethier et al., 2006). Brain imaging or TMS have shown that arm or hand movements were triggered by large areas of the motor cortex (Amassian et al., 1995; Devanne et al., 2002; Hallet, 2000; Kobay- ashi and Pascual-Leone, 2003; Sanes et al., 1995; Schieber and Hib- bard, 1993; Walsh and Cowey, 2000 Schieber, 2001). These findings suggest that widely distributed motor cortical territories are functionally linked during coordinated movements. Whether the expansion of the muscle representations in M1 observed in the darts players can be related to the development of a ‘‘functional unit” remains a matter of speculation. However, the highly distrib- uted organization of M1, convergence, divergence and horizontal connections with wide overlapping territories of different muscles, makes the hypothesis of a cortical representation of movement coordination plausible.

Acknowledgements

We thank our students for giving their time to participate in this study. We thank Professor A.R. Lieberman for editing our man- uscript and correcting the English language. We are grateful to Pro- fessor John C. Rothwell for his advice.

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