RESEARCH ARTICLE

Premovement brain activity in a bimanual load-lifting task

Tommy H. B. Ng • Paul F. Sowman •

Jon Brock • Blake W. Johnson

Received: 1 August 2010 /Accepted: 19 October 2010! Springer-Verlag 2010

Abstract Even the simplest volitional movements mustbe precisely coordinated with anticipatory postural adjust-

ments. Little is currently known about the neural networks

that coordinate these adjustments in healthy adults. Wemeasured brain activity prior to movement during a

bimanual load-lifting task, designed to elicit anticipatory

adjustments in a restricted and well-defined set of muscu-lature in the arm. Electroencephalography and magneto-

encephalography brain measurements were obtained from

eleven participants while they performed a bimanual load-lifting task that required precise inter-limb coordination.

Anticipatory biceps brachii inhibition in the loaded arm

was associated with a robust desynchronization of thebeta rhythm. Beamforming analyses localized beta band

responses to the parietal lobules, pre- and post-central gyri,

middle and medial frontal gyri, basal ganglia and thalamus.The current study shows that premovement brain activity in

a bimanual load-lifting task can be imaged with magne-

toencephalography. Future experiments will partition outbrain activity associated with anticipatory postural adjust-

ments and volitional movements. The experimental para-digm will also be useful in the study of motor function in

patients with developmental or degenerative disorders.

Keywords Anticipatory postural adjustments !Beamforming ! Bimanual load-lifting task ! Event-relateddesynchronization ! Magnetoencephalography ! Motor

coordination

Introduction

Anticipatory postural adjustments (APA) are necessary forcounteracting destabilizing forces induced by prime move-

ments. Even the simplest movements must be precisely

coordinated with anticipatory adjustments. For example,during rapid upward arm movements while standing,

activity in leg, neck and trunk muscles must precede arm

movement in order to minimize postural disturbance (Gur-finkel et al. 1988; Benvenuti et al. 1997). APA is also crucial

in more complex functional movements including locomo-

tion (Taga 1998; McFadyen et al. 2001), catching/throwing(Lacquaniti and Maioli 1989; Morton et al. 2001; Crenna

and Frigo 1991; Hirashima et al. 2002), and reach-to-grasp

movements (Mason et al. 2001; Schneiberg et al. 2002) andmay be susceptible to disruption in developmental or

degenerative brain pathologies such as autism spectrumdisorder (Schmitz et al. 2003) and Parkinson’s disease

(Viallet et al. 1987).

The bimanual load-lifting (BMLL) task involves high-level neuro-motor coordination of the upper limbs and has

been extensively used for the study of APA (Hugon et al.

1982; Viallet et al. 1987; Forget and Lamarre 1990; Ioffeet al. 1996; Schmitz et al. 2002). In this paradigm, the

participant supports a weight placed on one arm and

maintains the elbow joint at a desired angle before liftingthe weight with the other hand. The brain not only contends

with muscle activations in the lifting arm, it has to pre-

emptively modulate muscle activations in the loaded arm

This work was supported by a PhD research grant from the MacquarieCentre for Cognitive Science. THBN is supported by a MacquarieUniversity PhD scholarship. PFS is supported by National Health andMedical Research Council Training Fellowship (#543438). JB issupported by Australian Research Council Discovery Project andAustralian Research Fellowship (DP0984666).

T. H. B. Ng ! P. F. Sowman ! J. Brock ! B. W. Johnson (&)Macquarie Centre for Cognitive Science,Macquarie University, Sydney, Australiae-mail: blake.johnson@mq.edu.auURL: www.maccs.mq.edu.au

123

Exp Brain Res

DOI 10.1007/s00221-010-2470-5

(i.e. biceps brachii) with temporal precision in order to

minimize upward arm deflection during unloading. Pre-mature, late or abnormal inhibition of biceps brachii

activity would result in augmented arm deflection. A spe-

cific advantage of this paradigm is that the clear-cutcompartmentalization of the flexion musculature in the

loaded arm means that electromyography (EMG) from the

prime flexor (i.e. biceps brachii) of the elbow can be reli-ably isolated. Furthermore, it is possible to image brain

activity during performance since the task does not requirelocomotion.

Using the BMLL task, Viallet et al. (1987) reported

profound impairment of APA in patients with Parkinson’sdisease consistent with studies showing APA deficits in

patients with other types of basal ganglia pathology (Traub

et al. 1980; Johnson et al. 1998; Almeida et al. 2002). In alater study, Viallet et al. (1992) found similar impairments

of the anticipatory response in patients with supplementary

motor area (SMA) lesions, concurring with findings fromprevious studies that found bimanual coordination deficits

in humans and primates with SMA ablations (Laplane et al.

1977; Brinkman 1981, 1984). The severity of impairmentwas more pronounced when the lesions were contralateral

to the loaded arm (Viallet et al. 1992). Based on these

observations, the authors proposed that the basal gangliaand SMA contralateral to the loaded arm are crucially

involved in the central organization of APA in bimanual

load lifting.Functional neuroimaging studies that could test this

proposal in healthy subjects are surprisingly rare. Using

functional magnetic resonance imaging (fMRI), Schmitzet al. (2005) reported that bimanual load lifting was asso-

ciated with activation of SMA, consistent with Viallet

et al.’s (1992) model. However, increased activation wasalso observed in the sensorimotor areas and the cerebellum.

This latter finding conflicts with reports of preserved

anticipatory adjustments in patients with cerebellar damage(Muller and Dichgans 1994; Babin-Ratte et al. 1999).

Additionally, given that the temporal resolution of fMRI is

in the order of seconds (Ogawa et al. 1990; Kim et al.1997), it is impossible to differentiate between neural

activity occurring before or after movement onset. It is

possible, therefore, that cerebellar activation in the fMRIrelates to post-movement sensory-motor correction pro-

cesses (cf. Jueptner and Weiller 1998) rather than antici-

patory adjustments.Martineau et al. (2004) reported an electroencephalog-

raphy (EEG) study of bimanual load lifting in 5- to 11-

year-old children. Desynchronization of brain rhythms(i.e. event-related desynchronization; ERD) was observed

immediately prior to movement onset from a single elec-

trode overlying the motor cortex. However, EEG electrodetopographies do not necessarily reflect underlying cortical

sources (Nunez and Westdorp 1994), so it is impossible to

determine whether the ERD actually reflected activity inthe motor cortex or in other adjacent cortical regions.

The objective of the present study was to characterise

rhythmic brain responses during a BMLL task in healthyadults, and to localise their generators in the brain. We

employed a BMLL task comparable to that used by Mar-

tineau et al. (2004). Brain rhythms were measured withconcurrent EEG and magnetoencephalography (MEG).

EEG data were used to construct a grand mean time–fre-quency spectrum of cortical rhythms during unloading.

Beamforming analyses were used to localise the anatomi-

cal sources of the MEG rhythms.

Methods

Participants

Eleven healthy right-handed adults (7 male, 4 female;

mean age 31.5, range 24–49) participated in the experi-

ment. The participants gave informed consent to the pro-cedures, in accordance with the Declaration of Helsinki.

The study was approved by the Macquarie University

Human Research Ethics Committee.

Procedures

Participants performed a modified version of the BMLL

task described by Martineau et al. (2004), adapted for the

supine rather than seated positioning of the participants inour MEG system. The participant’s left arm was positioned

adjacent to the trunk so that elbow flexion could be per-

formed comfortably. In order to minimize movements atthe left shoulder joint, the upper arm was taped to a

10 9 20 9 5 cm support placed proximal to the elbow

joint. The left hand rested on a 10 9 20 9 15 cm supportplaced near the wrist joint such that the forearm was

inclined about 15" from the horizontal plane. A photode-

tector mounted on a 12 9 12 cm platform was secured tothe left arm. The right arm rested near the abdomen.

Visual instructions were presented using E-Prime ver-

sion 1.0 (Psychology Software Tools, Inc, Pittsburgh, US)and were projected via a mirror onto a screen, which was

directly in the participant’s line of sight. Throughout the

experiment, the participant was instructed to fixate on across on the screen to minimize eye-movement artefacts

and ensure that the lifting action was obscured from their

line of sight.At the start of a trial, the participant’s arms were rested

as described earlier. A visual display ‘Ready’ cued the

participant to raise the left arm to an angle approximately20" from the horizontal plane (Fig. 1a). This ready posture

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was necessitated by the supine positioning requirements ofour MEG system. An experimenter in the magnetically

shielded room then placed a 1-kg weight over the photo-detector. Once the weight was positioned, the word ‘Vol-

untary’ or ‘Imposed’ appeared on the screen above the

fixation point. During a voluntary trial, the participant firstpositioned the right hand near the weight. Once the hand

was positioned with the appropriate grip aperture, the

weight was lifted sharply. Immediately after lifting, theexperimenter retrieved the weight from the participant.

During an imposed trial, the experimenter lifted the weight

in a similar manner. Although the participant knew that theweight would be lifted, there was no indication of when

this would occur. The participant was instructed before-hand to return the arms to the resting position immediately

after lifting. In both conditions, lifting the weight off the

photodetector triggered a transistor-to-transistor logic pulsethat was sent to the data acquisition computer. A total of 80

trials (4 blocks of 20 trials) per condition were performed

in a fixed pseudo-random order. Figure 1b, c shows thelifting procedures and timing of visual stimuli during a trial

respectively.

(a)

(c)

Elbow Support

Wrist Support

Scanner

Postural forearm ‘Ready’ position(Flexed about 20 degrees from the horizontal plane)

Postural forearm ‘Rest’ position(Flexed about 15 degrees from the horizontal plane)

About 5 degrees

Scanner bed

(b)Voluntary unloading

Start End

Imposed unloadingStart End

Rest+

Weight On+

Ready +

Voluntary / Imposed+

4 2 1-3 5 Time (sec)

Fig. 1 a Positions of thepostural forearm during a trial.b Participant’s position in themagnetically shielded roomduring the task. (Top) At thestart of a voluntary trial, theparticipant positioned the righthand near the 1 kg weight (left).Once in position, the weight waslifted sharply (right). (Bottom)During an imposed trial, anexperimenter lifted the weightin a similar manner. Althoughthe participant knew that theweight would be lifted, therewas no indication when it wouldoccur. c Timing of visualinstructions presented on thecomputer screen during a trial

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Data acquisition

EMG activity was sampled at 1 kHz using MEG-compat-ible surface electrodes (BrainProducts, Gilching, Ger-

many). The recorded signals were amplified and band-pass

filtered between 20 and 450 Hz. During the trials, EMGactivity was recorded from two muscles contributing to the

elbow joint torque of the loaded (left) arm: biceps brachii

and triceps brachii.Brain activity was recorded with simultaneous whole-

head MEG and MEG-compatible EEG. The MEG system

(Model PQ1160R-N2, KIT, Kanazawa, Japan) consisted of160 coaxial first-order gradiometers with a 50 mm baseline

(Kado et al. 1999; Uehara et al. 2003). Prior to MEG

measurements, five marker coils were placed on an elas-ticised cap on the participant’s head and their positions and

the participant’s head shape were measured with a pen

digitiser (Polhemus Fastrack, Colchester, VT). Head posi-tion was measured by energizing the marker coils in the

MEG dewar before and after recording session. Movement

tolerance was set at a threshold maximum of 5 mm for anyindividual coil. The EEG electrode cap (BrainProducts,

Herrsching, Germany) consisted of 64 Ag/AgCl pellet

electrodes. EEG and MEG were sampled at 1 kHz with abandpass of 0.03–200 Hz. Electrode impedances were

maintained below 10 kX.T1-weighted, 3-D sagittal structural scans were obtained

from all participants in a separate session using a 3T

Phillips Achieva MRI scanner at St Vincent’s Hospital,

Darlinghurst, NSW, Australia. Scans were 1-mm isotropic.

Data analysis

EMG data 1,000 ms preceding and 1,000 ms following

unloading were grouped by condition, rectified and aver-

aged across trials for each participant. Amplitude againsttime functions were plotted to show EMG modulation

during unloading. The latency of the first downward

deflection in biceps brachii EMG (i.e. onset of inhibition)was determined by a threshold-crossing algorithm similar

to that described by DiFabio (1987). A paired-samples ttest compared the onset latency of biceps brachii EMGinhibition during both conditions.

The frequency content of EEG and MEG signals within

an epoch 4,000 ms preceding and 4,000 ms followingunloading were analysed off-line using Brain Electrical

Source Analysis (BESA) version 5.3 (MEGIS Software

GMbH, Grafelfing, Germany). MEG-MRI coregistrationwas performed using BrainVoyager version 1.10 (Brain-

Innovation BV, Maastricht, The Netherlands). Artefactsincluding blinks and eye-movements were removed using

the artefact scan tool in BESA, which rejects trials based

on abnormally high amplitudes or abrupt rises or falls in

amplitudes (i.e. gradients). Rejection thresholds were set at

2.7 pT for amplitude and 2 pT for gradient. For each par-ticipant and condition, at least 90% of trials survived

artefact rejection.

MEG beamforming analyses were performed on a 400-ms time window immediately preceding the onset of biceps

brachii EMG inhibition in the voluntary unloading condi-

tion. Analyses were performed on the beta (16–30 Hz) andgamma (60–90 Hz) frequency bands, rhythms associated

with motor behaviours (e.g. Pfurtscheller and Lopes daSilva 1999; Taniguchi et al. 2000; Cheyne et al. 2008).

Estimation of source power was carried out using a linearly

constrained minimum variance beamformer implementedin BESA 5.3. This approach optimizes the weight of the

beamformer to capture the signal of interest while con-

comitantly minimizing interfering signals and noiseapproaching from other directions (Van Veen and Buckley

1988). Independent beamformers constructed for each

location in brain space resulted in a three-dimensionalestimate of source power during lifting, which was nor-

malized to a baseline, i.e. 3,000–4,000 ms post-unloading

when the arms had returned to the resting position.Beamforming analyses were computed on the premove-

ment epoch in the voluntary condition relative to the same

time period in the imposed condition (see Fig. 2).Group statistical analyses based on random effects

models were performed using SPM 8 (Welcome Institute of

Cognitive Neurology, London, UK). Peak-level inferencewith significance threshold set at P\ 0.05 (family-wise

error; FWE-corrected) determined voxels that were sig-

nificantly activated. Additionally, based on previous liter-ature, local maxima within the basal ganglia, SMA (see

Viallet et al. 1987, 1992) or cerebellum (see Schmitz et al.

2005) were subjected to small volume correction using asphere with radius 20 mm (Worsley et al. 1996; Green and

McDonald 2008). These sources were superimposed onto a

template brain, and their location in brain space wasdetermined using the Talairach Daemon (Lancaster et al.

2000). Regions of interest (ROI, 20 mm radius sphere)

were defined using WFU Pickatlas (Maldjian et al. 2004)and eigenvariates were extracted using a singular value

decomposition of the time series across all voxels within

each ROI.

Results

EMG data

Figure 2 shows biceps brachii and triceps brachii EMG

recorded from a representative participant. During volun-

tary unloading, the onset latency of biceps brachii EMGinhibition was -269 ms. In contrast, during imposed

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unloading, the onset latency of biceps brachii EMG inhi-bition was -67 ms. Across participants, the onset latency

was significantly (t(10) = -11.2, P\ 0.01) earlier during

voluntary (M = -249 ms, SD = 84 ms) compared toimposed (M = -18 ms, SD = 23 ms) unloading. Mean

biceps brachii EMG amplitude was about 12 times that of

triceps brachii from -1,000 ms to onset of biceps brachiiEMG inhibition in both conditions.

EEG data

Figure 3 shows grand mean time–frequency represen-

tation (TFR) for EEG oscillations recorded in the

proximity of the left (C1) and right sensorimotor cortex(C2). For left sensorimotor cortex, the TFR plots show

robust beta (16–30 Hz) ERD from about -4 s to about

2 s during voluntary unloading. In the imposed condition,a phasic beta ERD immediately after t = 0 occurred

between two separate even-related synchronizations

(ERS), 4–10 and 30–60 Hz at t = 0 and 1 s respectively.The TFR plots in the right sensorimotor cortex show

prominent ERD in frequency band 4–30 Hz from about

-2 s to about 2.5 s during voluntary unloading, charac-teristic of activated motor cortices. In contrast, in the

imposed condition, 4–30 Hz ERD was observed only

after movement onset.

Fig. 2 Single-participantbiceps brachii and tricepsbrachii EMG amplitude as afunction of time. T = 0represents the time when theweight was completely lifted offthe photodetector. Bicepsbrachii EMG amplitude startedto decrease at a latency of about-269 and -67 ms duringvoluntary and imposedunloading respectively (dottedcircles). From -1 s to onset ofbiceps brachii inhibition, bicepsbrachii EMG amplitude wasabout 12 times that of tricepsbrachii in both conditions.A 400-ms epoch prior to onsetof biceps brachii EMGinhibition (grey box) was usedfor subsequent MEG analyses

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MEG data

A distributed system of bilateral motor structures showedsignificant beta band ERD during the voluntary condition

relative to the imposed condition of the BMLL task.

Table 1 and Fig. 4 show statistically significant (P\ 0.05;FWE-corrected) activations were obtained in bilateral

inferior and superior parietal cortices, bilateral postcentral

gyri, bilateral middle and medial frontal gyri, bilateralglobus pallidus, and bilateral thalamus. Unilateral sources

were observed in the left precentral gyrus and right puta-

men. Brain areas with greatest differences in source power(i.e. greater ERD, reflecting more cortical activity, in the

voluntary condition) were lateralized to the left hemi-

sphere. In these areas, the amplitude of source powerdecrease was 1.3–3 times larger than homologous areas in

Fre

quen

cy (H

z)Imposed unloading

Voluntary unloading

4

20

40

60

-40(ERD)

(ERS)

40

Source power

(% change from

baseline)

t=0-4 -2 2 4

Time (sec)

4

20

40

60

t=0-4 -2 2 4

Left sensorimotor cortex (C1) Right sensorimotor cortex (C2)Fig. 3 Grand mean time–frequency representation (TFR)plots of representative EEGelectrodes over the left (C1) andright (C2) sensorimotor cortices.(Top) During voluntaryunloading, the TFR plot showsbeta band (16–30 Hz) ERDbefore movement (i.e. beforet = 0). (Bottom) In contrast,during imposed unloading, betaband ERD started aftermovement

Table 1 Talairach coordinatesof beta sources threshold atT[ 3.20 (P\ 0.05, FWE-corrected) for a contrastbetween voluntary and imposedunloading during an epoch400 ms before the onset ofbiceps brachii EMG inhibition.

L left, R right

* Indicates adjusted T valuesafter small volume correction

Brain region Hemisphere T value Coordinates (mm)

x y z

Parietal lobe

Inferior parietal lobule L 9.20 -34 -36 44

Inferior parietal lobule R 3.49 44 -38 54

Superior parietal lobule L 6.75 -18 -64 62

Superior parietal lobule R 3.91 18 -54 62

Postcentral gyrus L 7.45 -42 -32 60

Postcentral gyrus R 3.61 32 -30 46

Frontal lobe

Precentral gyrus L 6.86 -38 -26 62

Middle frontal gyrus L 4.48* -24 6 50

Middle frontal gyrus R 3.23* 24 12 62

Medial frontal gyrus/SMA L 3.80* -8 -12 66

Medial frontal gyrus/SMA R 3.25* 8 -17 72

Basal ganglia

Lentiform nucleus/globus pallidus L 4.79* -18 -4 -4

Lentiform nucleus/globus pallidus R 4.77* 18 -2 2

Lentiform nucleus/putamen R 4.52* 24 4 4

Thalamus L 6.01* -18 -18 10

Thalamus R 3.95* 14 -22 14

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the right hemisphere. The hemispheric asymmetry in

source power modulation was not observed in the SMA andglobus pallidus. In these areas, the amplitude of source

power decrease was approximately the same.

Table 2 shows brain regions with gamma source powermodulation during pre- and post-movement phases of the

BMLL task. Statistically significant (P\ 0.05; FWE-cor-

rected) activations were obtained in the left superior pari-etal lobule and left precentral gyrus after unloading. In

contrast, brain sources corresponding to premovement

gamma ERD were statistically non-significant, consistent

with previous observation of gamma frequency band steady

state during premovement period of self-initiated move-ments (cf. Cheyne et al. 2008).

Figure 5a shows the time course of premovement

activity in the ROIs including the right SMA, putamen,globus pallidus and thalamus. At -250 ms, decrease in

beta source power was mainly observed in the subcorti-

cal structures, whereas at -50 ms, it was prominentlyobserved in the SMA. The effect size of beta source power

modulation within these ROIs for the contrast between

voluntary and imposed unloading is shown in Fig. 5b.

0

10

Thalamus

T = 3.95

Globus pallidus

T = 4.77

Putamen

T = 4.52

SMA

T = 3.25

X = 8 Z = 72

X = 24

X = 18

X = 14 Z = 14

Left Right

Y = 4

Y = -2

Fig. 4 Loci of brain sourcesconstituting the basal ganglia-thalamo-cortical motor circuit inthe hemisphere contralateral tothe loaded arm. SMAsupplementary motor area.Source power decrease in betafrequency band (i.e. 16–30 Hz)was significantly (P\ 0.05,FWE-corrected) greater involuntary than imposedunloading during a time window400 ms before to actual onset ofbiceps brachii EMG inhibition.The colour bar refers to sourcepower modulation expressed inT values. Lighter map coloursrepresent enhanced sourcepower decrease. Coordinates arein Talairach reference space.Note there is no source powerincrease in beta frequency bandduring the same time window

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Discussion

In the current study, we used beamforming analysis of MEG

data to show that a distributed system of bilateral motor

structures is activated immediately prior to execution of aBMLL task. Since the present experiment was not explicitly

designed to isolate the anticipatory (i.e. associated with

preparing the loaded arm for unloading) and volitional (i.e.associated with preparing the voluntary movement of the

contralateral arm) motor systems, these activations repre-

sent both aspects of the motor task. However, on the basisthat distal musculature is controlled primarily by contra-

lateral brain structures (Colebatch et al. 1991; Wexler et al.

1997) and that anticipatory adjustments are elicited only in

volitional movements (Taga 1998; McFadyen et al. 2001;Hirashima et al. 2002), we can reasonably assume that

activations contralateral to the loaded arm (right hemi-

sphere) revealed by the contrast between voluntary andimposed unloading reflect important aspects of anticipatory

motor control, whereas activations contralateral to the lift-ing arm (left hemisphere) reflect aspects of volitional motor

control. The finding of severely impaired APA in patients

with SMA lesion in the hemisphere contralateral to theloaded arm but not in patients with SMA lesion in the

hemisphere ipsilateral to the loaded arm further supports

this assumption (Viallet et al. 1992).

Table 2 Talairach coordinatesof gamma sources during pre-and post-movement phases ofthe BMLL task.

L left

* Indicates FWE-correctedP values

Brain region Hemisphere T value P value Coordinates (mm)

x y z

Postmovement

Superior parietal lobule L 8.19 \0.05* -16 -64 58

Precentral gyrus L 5.86 \0.05* -36 -14 46

Premovement

Postcentral gyrus L 5.49 P = 0.10 -50 -16 58

Superior parietal lobule L 4.52 P = 0.21 -30 -56 60

Fig. 5 a Time course ofpremovement activity in theright supplementary motor area(SMA), putamen (Put), globuspallidus (GP) and thalamus(Tha). Immediately beforeunloading, a robust beta sourcepower decrease was observed inthe SMA. b The effect size ofbeta source power decreasewithin the SMA wassignificantly (P\ 0.005, falsediscovery rate-corrected)greater compared to thesubcortical ROIs

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The volitional movement (i.e. unloading) performed by

the right hand elicited robust beta ERD that was observedover the contralateral (left) sensorimotor cortex. The tim-

ing of the current ERD agrees well with the onset latency

of premovement ERD in self-initiated movements(Pfurtscheller and Berghold 1989; Derambure et al. 1993;

Stancak and Pfurtscheller 1996b). In these studies, a

homologous ERD starting immediately before movementwas also observed over the ipsilateral sensorimotor cortex.

Interestingly, the current beta ERD over the same brainregion did not start immediately but about 2 s before

movement (Fig. 3, top right plot), suggesting that the

premovement ERD in the present study was not an epi-phenomenon of volitional movement, nor reflected brain

activations for supporting the weight as the same ERD was

not observed during imposed unloading (Fig. 3, bottomright plot). We postulate that the premovement ERD over

the right sensorimotor cortex was associated with antici-

patory motor control.On this view, the significant activation of the right SMA,

putamen, globus pallidus and thalamus prior to lifting

indicates that these regions are all involved in the media-tion of APA. These findings agree well with Viallet et al.’s

(1992) account of the central organization of movement-

APA coordination in bimanual load lifting. These authorssuggested that during unloading, a timing signal is sent

from the hemisphere contralateral to the lifting arm (voli-tional motor system) to activate the SMA and basal gangliain the other hemisphere (anticipatory motor system), after

which the two motor systems independently control

movement and APA. The pathway of the timing signal isunlikely to be through the corpus callosum as patients with

complete resection of the commissure exhibited normal

APA (Viallet et al. 1992; Diedrichsen et al. 2005). Thepresent results confirm the activation of the SMA and basal

ganglia in the hemisphere contralateral to the loaded arm.

Indeed, we were able to localize activity more specificallyto the putamen and globus pallidus.

Together with the thalamus, the SMA, putamen and

globus pallidus make up a basal ganglia-thalamo-cortical‘motor’ circuit (Alexander and Crutcher 1990; Alexander

et al. 1990; Beiser et al. 1997). The putamen receives input

from the SMA and motor cortex (Brooks 1995) and con-nects to the thalamus (Devito and Anderson 1982; Illinsky

et al. 1985) via the globus pallidus (Szabo 1967; Johnson

and Rosvold 1971; Parent et al. 1984). In turn, the thalamusprojects to the SMA (Strick 1976; Schell and Strick 1984;

Wiesendanger and Wiesendanger 1985). This circuit is

implicated in the selection and preparation of motor pro-grammes and the suppression of inappropriate actions

before movement implementation (Kropotov and Etlinger

1999). The present results indicate that the motor circuitmay also be involved in APA.

In addition to these activations, which were predicted on

the basis of Viallet et al.’s (1992) model, we also observedrobust beta ERDs of bilateral inferior and superior parietal

lobules. In the left hemisphere, the peak ERD lay in the

inferior parietal lobule (IPL). Previous studies haveimplicated beta ERD in this area of the cortex in neural

processes related to volitional movements during simple

motor tasks (Ball et al. 1999; Cheyne et al. 2006;Pfurtscheller and Aranibar 1979; Pfurtscheller et al. 2003).

This suggests that in the current study, anticipatory ERD inthe left IPL is related to the preparation of self-initiated

movements (Andersen et al. 1997; Ball et al. 1999) rather

than being associated with APA specifically. AnticipatoryERDs in the right parietal lobule may relate to the fact that

participants had to rely on proprioceptive information to

coordinate the movement of the right arm with respect tothe weight placed on the left arm. Primate studies have

shown that bilateral IPL and SPL function in tandem to

coordinate arm movements in relation to proprioceptiveinformation (Rushworth et al. 1997).

ERDs were also observed in the middle frontal gyri. The

ventral premotor area of the left middle frontal gyrus is acomponent of a fronto-parietal network that has been

implicated in object manipulation (Binkofski et al. 1999a,

b). This is consistent with the fact that all participants wereright-handed and the lifting was performed with the right

hand. A homologous network in the hemisphere contra-

lateral to the loaded arm could be related to tactile prop-erties of the weight resting on the arm (Janke et al. 2001;

Stoeckel et al. 2003).

In contrast to the robust ERDs observed elsewhere, wedid not find any evidence for anticipatory involvement of

the primary motor cortex (i.e. in the hemisphere contra-

lateral to the loaded arm) in the BMLL task. As notedearlier, Martineau et al. (2004) reported anticipatory ERD

from an electrode placed over the primary motor cortex

during a similar study using EEG. However, this mayreflect volume conduction from other cortical sources

(Nunez and Westdorp 1994). Martineau et al.’s subjects

were children and their analyses focused on the theta fre-quency range, which corresponds to the mu rhythm in

adults (Cochin et al. 2001). EEG (Pfurtscheller et al. 1994)

and MEG (Salmelin et al. 1995) studies have shown thatthe mu rhythm originates mainly from the somatosensory

region and is broadly associated with afferent signal pro-

cessing. We suspect, therefore, that the theta ERD observedby Martineau and colleagues may not have originated in

the primary motor cortex.

We also failed to find any evidence of cerebellarinvolvement during APA. This is in line with previous

studies that showed preservation of the anticipatory

response in patients with cerebellar damage (Diener et al.1989; Serrien and Wiesendanger 1999; Nowak et al. 2002;

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Diedrichsen et al. 2005) but contradicts the recent fMRI

study of bimanual load lifting by Schmitz et al. (2005). Onepossibility is that cerebellar activation reflects post-move-

ment sensory feedback (Jueptner and Weiller 1998) rather

than any pre-movement activity. Alternatively, it could beargued that the MEG system is simply incapable of picking

up cerebellar activity, although we note that other recent

MEG studies have demonstrated significant cerebellaractivation during motor tasks (e.g. Fujioka et al. 2010).

The role of the cerebellum in bimanual coordination isnot well understood. Findings of poorly timed APA in

cerebellar patients suggests that the subcortical structure

may be involved in the temporal organization of theanticipatory response (Diedrichsen et al. 2005). A number

of other studies have also associated cerebellar function

with timing of self-initiated movements (Ivry et al. 1988;Sakai et al. 1999). The cerebellum has also been impli-

cated in motor learning as a module for computing sen-

sory errors that result from a mismatch between anintended motor plan and the actual motor outcome

(Wolpert et al. 1998; Kawato 1999; Imamizu et al. 2000).

On this view, lesion to this region would severely impairsensorimotor integration and subsequently motor learning.

Indeed, Diedrichsen et al. (2005) found that patients with

cerebellar damage failed to acquire APA, even afterextended practice, when participants triggered unloading

artificially via a button press.

Conclusions

The current data support and extend Viallet et al.’s (1992)

model of APA, implicating the canonical basal ganglia-

thalamo-cortical ‘motor’ circuit in the selection or prepa-ration of the motor programme for APA implementation.

Additionally, on the bases that the primary motor cortex

was not activated in the hemisphere contralateral to theloaded arm and that the decrease in SMA beta source

power was most robust immediately before unloading, we

postulate that the control of APA likely results from acorticospinal pathway that originates in the SMA. Several

studies have shown that movement execution can occur in

SMA regions with high proportion of pyramidal cells(Macpherson et al. 1982; Dum and Strick 1991; He et al.

1995; Lee et al. 1999). Figure 6 shows a schematic rep-

resentation of our updated model.Further work is required to adequately test this model, to

tease apart the anticipatory and volitional components of

bimanual load lifting, and ultimately, to determine thetiming and interaction of neural activity across the dis-

tributed cortical and subcortical network. Nonetheless, the

current study represents an important step, showing for thefirst time that brain areas involved in the mediation of APA

can be reliably imaged using MEG. This has important

implications, not only for research on motor coordinationin healthy adults but also our understanding of the acqui-

sition of motor coordination and the neurological bases of

motor dysfunction in developmental and degenerativedisorders such as autism spectrum disorders and Parkin-

son’s disease.

Acknowledgments The authors gratefully acknowledge the col-laboration of Kanazawa Institute of Technology and YokogawaElectric Corporation in establishing the KIT-Macquarie MEG labo-ratory. We thank Dr. Graciela Tesan and Ms. Melanie Reid fortechnical assistance and Dr. Thomas Nichols, Dr. Mark Williams, andDr. Vladimir Litvak for helpful advice regarding SPM analysis.

Conflict of interest The authors report no conflict of interest.

Cortex

PutGP

Tha

Cortical level

Subcortical level

Medulla level

APA in loaded arm Lifting arm

Cortex

SMA

Spinal level

Fig. 6 Schematic representation of the central organization ofanticipatory adjustments in bimanual load lifting (adapted fromViallet et al. 1992). SMA supplementary motor area, Put putamen, GPglobus pallidus, Tha thalamus. The connection between these brainareas constitutes the basal ganglia-thalamo-cortical motor circuit(red). This neural circuit, which lies contralateral to the loaded arm, isactivated prior to unloading to bring about anticipatory adjustments inthe loaded arm. The corticospinal pathway mediating these adjust-ments originates from the SMA (bold). Unloading movement iscontrolled by the cerebral cortex (i.e. presumably the primary motorarea) contralateral to the lifting arm

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123

References

Alexander GE, Crutcher MD (1990) Functional architecture of basalganglia circuits: neural substrates of parallel processing. TrendsNeurosci 13:266–271

Alexander GE, Crutcher MD, Delong MR (1990) Basal gangliathalamo-cortical circuits: parallel substrates for motor, oculo-motor, ‘‘prefrontal’’ and ‘‘limbic’’ functions. Prog Brain Res85:119–146

Almeida QJ, Wishart LR, Lee TD (2002) Bimanual coordinationdeficits with Parkinson’s disease: the influence of movementspeed and external cueing. Mov Disord 17:30–37

Andersen RA, Snyder LH, Bradley DC, Xing J (1997) Multimodalrepresentation of space in the posterior parietal cortex and its usein planning movement. Annu Rev Neurosci 20:303–330

Babin-Ratte S, Sirigu A, Gilles M, Wing A (1999) Impairedanticipatory finger grip-force adjustments in a case of cerebellardegeneration. Exp Brain Res 128:81–85

Ball T, Schreiber A, Feige B, Wagner M, Lucking CH, Kristeva-FeigeR (1999) The role of higher-order motor areas in voluntarymovement as revealed by high-resolution EEG and fMRI.Neuroimage 10:682–694

Beiser DG, Hua SE, Houk JC (1997) Network models of the basalganglia. Curr Opin Neurobiol 7:185–190

Benvenuti F, Stanhope SJ, Thomas SL, Panzer VP, Hallet M (1997)Flexibility of anticipatory postural adjustments revealed by self-paced and reaction-time arm movements. Brain Res 7:59–70

Binkofski F, Buccino G, Posse S, Seitz RJ, Rizzolatti G, Freund HJ(1999a) A fronto-parietal circuit for object manipulationin man: evidence from an fMRI study. Eur J Neurosci 11:3276–3286

Binkofski F, Buccino G, Stephan KM, Rizzolatti G, Seitz RJ, FreundHJ (1999b) A parieto-premotor network for object manipulation:evidence from neuroimaging. Exp Brain Res 128:210–213

Brinkman C (1981) Lesions in supplementary motor area interferewith a monkey’s performance of a bimanual coordination task.Neurosci Lett 27:267–270

Brinkman C (1984) Supplementary motor area of the monkey’scerebral cortex: short- and long term deficits after unilateralablation and the effects of subsequent callosal section. J Neurosci4:918–929

Brooks DJ (1995) The role of basal ganglia in motor control:contributions from PET. J Neurol Sci 128:1–13

Cheyne D, Bakhtazad L, Gaetz W (2006) Spatiotemporal mapping ofcortical activity accompanying voluntary movements using anevent-related beamforming approach. Hum Brain Mapp 27:213–229

Cheyne D, Bells S, Ferrari P, Gaetz W, Bostan AC (2008) Self-pacedmovements induce high-frequency gamma oscillations inprimary motor cortex. Neuroimage 42:332–342

Cochin S, Barthelemy C, Roux S, Martineau J (2001) Electroen-cephalographic activity during perception of motion in child-hood. Eur J Neurosci 13:1791–1796

Colebatch JG, Deiber MP, Passingham RE, Friston KJ, FrackowiakRS (1991) Regional cerebral blood flow during voluntary armand hand movements in human subjects. J Neurophysiol65:1392–1401

Crenna P, Frigo C (1991) A motor programme for the initiation offorward-oriented movements in humans. J Physiol (Lond)437:635–653

Derambure P, Defebvre L, Dujardin K, Bourriez JL, Jacquesson JM,Destee A, Guieu JD (1993) Effect of aging on the spatio-temporal pattern of event-related desynchronization duringvoluntary movement. Electroencephalogr Clin Neurophysiol89:197–203

DeVito JL, Anderson ME (1982) An autoradiographic study ofefferent connections of the globus in Macaca mulatta. Exp BrainRes 46:107–117

Diedrichsen J, Verstynen T, Lehman SL, Ivry RB (2005) Cerebellarinvolvement in anticipating the consequences of self-producedactions during bimanual movements. J Neurophysiol 93:801–812

Diener HC, Dichgans J, Guschlbauer B, Bacher M, Langenbach P(1989) Disturbances of motor preparation in basal ganglia andcerebellar disorders. Prog Brain Res 80:481–488

DiFabio RP (1987) Reliability of computerized surface electromyog-raphy for determining the onset of muscle activity. Phys Ther67:43–48

Dum RP, Strick PL (1991) The origin of corticospinal projectionsfrom the premotor areas in the frontal lobe. J Neurosci11:667–689

Forget R, Lamarre Y (1990) Anticipatory postural adjustment in theabsence of normal peripheral feedback. Brain Res 508:176–179

Fujioka T, Zendel BR, Ross B (2010) Endogenous neuromagneticactivity for mental hierarchy of timing. J Neurosci 30:3458–3466

Green JJ, McDonald JJ (2008) Electrical neuroimaging reveals timingof attentional control activity in human brain. PLoS Biol6:730–738

Gurfinkel VS, Lipshits MI, Lestienne FG (1988) Anticipatory neckmuscle activity associated with rapid arm muscles. Neurosci Lett94:104–108

He SQ, Dum RP, Strick PL (1995) Topographic organization ofcortico-spinal projections from the frontal lobe: motor areas onthe medial surface of the hemisphere. J Neurosci 15:3284–3306

Hirashima M, Kadota H, Sakurai S, Kudo K, Ohtsuki T (2002)Sequential muscle activity and its functional role in the upperextremity and trunk during overarm throwing. J Sports Sci20:301–310

Hugon M, Massion J, Wiesendanger M (1982) Anticipatory posturalchanges induced by active unloading and comparison withpassive unloading in man. Eur J Physiol 393:292–296

Illinsky IA, Jouandet ML, Goldman-Rakic PS (1985) Organization ofthe nigrothalamocortical system in the rhesus monkey. J CompNeurol 236:315–330

Imamizu H, Miyauchi S, Tamada T, Sasaki Y, Takino R, Puetz B,Yoshoka T, Kawato M (2000) Human cerebellar activityreflecting an acquired internal model of a new tool. Nature403:192–195

Ioffe M, Massion J, Gantchev N, Dufosse M, Kulikov MA (1996)Coordination between posture and movement in a bimanualload-lifting task: is there a transfer? Exp Brain Res 109:450–456

Ivry RB, Keele SW, Diener HC (1988) Dissociation of the lateral andmedial cerebellum in movement timing and movement execu-tion. Exp Brain Res 73:167–180

Janke L, Kleinschmidt A, Mirazazade S, Shah NJ, Freund HJ (2001)The role of the inferior parietal cortex in linking the tactileperception and manual construction of object shapes. CerebCortex 11:114–121

Johnson TN, Rosvold HE (1971) Topographic projections on theglobus pallidus and the substantia nigra of selectively placedlesions in the precommissural caudate nucleus and putamen inthe monkey. Exp Neurol 33:584–596

Johnson KA, Cunnington R, Bradshaw JL, Phillips JG, Iansek R,Rogers MA (1998) Bimanual coordination in Parkinson’sdisease. Brain 121:743–753

Jueptner M, Weiller C (1998) A review of differences between basalganglia and cerebellar control of movements as revealed byfunctional imaging studies. Brain 121:1437–1449

Kado H, Higuchi M, Shimogawara M, Haruta Y, Adachi Y, Kawai J,Ogata H, Uehara G (1999) Magnetoencephalogram systemdeveloped at KIT. IEEE T Appl Supercon 9:4057–4062

Exp Brain Res

123

Kawato M (1999) Internal models for motor control and trajectoryplanning. Curr Opin Neurobiol 9:718–727

Kim SG, Richter W, Ugurbil K (1997) Limitations of temporalresolution in functional MRI. Magnet Reson Med 37:631–636

Kropotov JD, Etlinger SC (1999) Selection of actions in the basalganglia-thalamocortical circuits: review and model. Int JPsychophysiol 31:197–217

Lacquaniti F, Maioli C (1989) The role of preparation in tuninganticipatory and reflex responses during catching. J Neurosci9:134–148

Lancaster JL, Woldorff MG, Parsons LM, Liotti M, Freitas CS,Rainey L, Kochunov PV, Nickerson D, Mikiten SA, Fox PT(2000) Automated Talairach atlas labels for functional brainmapping. Hum Brain Mapp 10:120–131

Laplane D, Talairach J, Meininger V, Bancaud J, Orgogozo JM(1977) Clinical consequences of corticectomies involving sup-plementary motor area in man. J Neurol Sci 43:301–314

Lee KM, Chang KH, Roh JK (1999) Subregions within thesupplementary motor area activated at different stages ofmovement preparation and execution. Neuroimage 9:117–123

Macpherson J, Wiesendanger M, Marangoz C, Miles TS (1982)Corticospinal neurones of the supplementary motor area ofmonkeys. Exp Brain Res 48:81–88

Maldjian JA, Laurienti PJ, Burdette JH (2004) Precentral gyrusdiscrepancy in electronic versions of the Talairach atlas.Neuroimage 21:450–455

Martineau J, Schmitz C, Assaiante C, Blanc R, Barthelemy C (2004)Impairment of a cortical related desynchronisation during abimanual load-lifting task in children with autistic disorder.Neurosci Lett 367:298–303

Mason CR, Gomez JE, Ebner TJ (2001) Hand synergies during reach-to-grasp. J Neurophysiol 86:2896–2910

McFadyen B, Malouin F, Dumas F (2001) Anticipatory locomotorcontrol for obstacle avoidance in mid-childhood aged children.Gait Posture 13:7–16

Morton SM, Lang CE, Bastian AJ (2001) Inter- and intra-limbgeneralization of adaptation during catching. Exp Brain Res141:438–445

Muller F, Dichgans J (1994) Dyscoordination of pinch and lift forcesduring grasp in patients with cerebellar lesions. Exp Brain Res101:485–492

Nowak DA, Hermsdorfer J, Marquardt C, Fuchs HH (2002) Grip andload force coupling during discrete vertical arm movements witha grasped object in cerebellar atrophy. Exp Brain Res 145:28–39

Nunez PL, Westdorp AF (1994) The surface laplacian, high resolutionEEG and controversies. Brain Topogr 6:221–226

Ogawa S, Lee TM, Kay AR, Tank DW (1990) Brain magneticresonance imaging with contrast dependent on blood oxygena-tion. Proc Natl Acad Sci USA 87:9868–9872

Parent A, Bouchard C, Smith Y (1984) The striatopallidal andstriatonigral projections: two distinct fiber systems in primate.Brain Res 303:385–390

Pfurtscheller G, Aranibar A (1979) Evaluation of event-relateddesynchronization (ERD) preceding and following voluntaryself-paced movement. Electroencephalogr Clin Neurophysiol46:138–146

Pfurtscheller G, Berghold A (1989) Patterns of cortical activationduring planning of voluntary movement. ElectroencephalogrClin Neurophysiol 72:250–258

Pfurtscheller G, Lopes da Silva FH (1999) Event-related EEG/MEGsynchronisation and desynchronisation: basic principles. ClinNeurophysiol 110:1842–1857

Pfurtscheller G, Pregenzer M, Neuper C (1994) Visualization of thesensorimotor areas involved in preparation for hand movementbased on classification of mu and beta rhythms in single EEGtrials in man. Neurosci Lett 181:43–46

Pfurtscheller G, Graimann B, Huggins JE, Levine SP, Schuh LA(2003) Spatiotemporal patterns of beta desynchronisation andgamma synchronisation in corticographic data during self-pacedmovement. Clin Neurophysiol 114:1226–1236

Rushworth MF, Nixon PD, Passingham RE (1997) Parietal cortex andmovement. I. Movement selection and reaching. Exp Brain Res117:292–310

Sakai K, Hikosaka O, Miyauchi S, Takino R, Tamada T, Iwata NK,Nielsen M (1999) Neural representation of a rhythm depends onits interval ratio. J Neurosci 19:10074–10081

Salmelin R, Hamalainen M, Kajola M, Hari R (1995) Functionalsegregation of movement-related rhythmic activity in the humanbrain. Neuroimage 2:237–243

Schell GR, Strick PL (1984) The origin of thalamic inputs to thearcuate premotor and supplementary motor areas. J Neurosci4:539–560

Schmitz C, Martin N, Assaiante C (2002) Building anticipatorypostural adjustments during childhood: a kinematic and electro-myographic analysis of unloading in children from 4 to 8 yearsof age. Exp Brain Res 142:354–364

Schmitz C, Martineau J, Barthelemy C, Assaiante C (2003) Motorcontrol and children with autism: deficit of anticipatoryfunction? Neurosci Lett 348:17–20

Schmitz C, Jenmalm P, Westling G, Ehrsson H, Forssberg H (2005)Anticipatory postural adjustments in a bimanual load-liftingtask: central aspects. Gait Posture 21:S50

Schneiberg S, Sveistrup H, McFadyen B, McKinley P, Levin MF(2002) The development of coordination for reach-to-graspmovements in children. Exp Brain Res 146:142–154

Serrien DJ, Wiesendanger M (1999) Grip-load force coordination incerebellar patients. Exp Brain Res 128:76–80

Stancak JA, Pfurtscheller G (1996) Event-related desynchronizationof central beta rhythms in brisk and slow self-paced fingermovements of dominant and nondominant hand. Cognitive BrainRes 4:171–184

Stoeckel MC, Weder B, Binkofski F, Buccino G, Shah NJ, Seitz RJ(2003) A fronto-parietal circuit for tactile object discrimination:an event-related fMRI study. Neuroimage 9:1103–1114

Strick PL (1976) Anatomical analysis of ventrolateral thalamic inputto primate motor cortex. J Neurophysiol 39:1020–1031

Szabo J (1967) Projections from the body of the caudate nucleus inthe rhesus monkey. Exp Neurol 27:1–15

Taga G (1998) A model of the neuro-musculo-skeletal system foranticipatory adjustment of human locomotion during obstacleavoidance. Biol Cybern 78:9–17

Taniguchi M, Kato A, Fujita N, Hirata M, Tanaka H, Kihara T,Ninomiya H, Hirabuki N, Nakamura H, Robinson SE, Cheyne D,Yoshimine T (2000) Movement-related desynchronization of thecerebral cortex studied with spatially filtered magnetoencepha-lography. Neuroimage 12:298–306

Traub MM, Rothwell JC, Marsden CD (1980) Anticipatory posturalreflexes in Parkinson’s disease and other akinetic-rigid syn-dromes and in cerebellar ataxia. Brain 103:393–412

Uehara G, Adachi Y, Kawai J, Shimogawara M, Higuchi M,Haruta Y, Ogata H, Kado H (2003) Multi-channel SQUIDsystems for biomagnetic measurement. IEICE T Electron E86-C(1):43–54

Van Veen BD, Buckley KM (1988) Beamforming: a versatileapproach to spatial filtering. IEEE T Acoust Speech 5:4–24

Viallet F, Massion J, Massarino R, Khalil R (1987) Performance of abimanual load-lifting task by Parkinsonian patients. J NeurolNeurosurg Psychiatry 50:1274–1283

Viallet F, Massion J, Massarino R, Khalil R (1992) Coordinationbetween posture and movement in a bimanual load-lifting task:putative role of medial frontal region including the supplemen-tary motor area. Exp Brain Res 88:674–684

Exp Brain Res

123

Wexler BE, Fulbright RK, Lacadie CM, Skudlarski P, Kelz MB,Constable T, Gore JC (1997) An fMRI study of the humancortical motor system response to increasing functionaldemands. Magn Reson Imaging 15:385–396

Wiesendanger R, Wiesendanger M (1985) The thalamic connectionswith medial area 6 (supplementary motor cortex) in the monkey(macaca fascicularis). Exp Brain Res 59:91–104

Wolpert DM, Miall RC, Kawato M (1998) Internal models in thecerebellum. Trends Cogn Sci 2:313–321

Worsley KJ, Marret S, Neelin P, Vandal AC, Friston KJ, Evans AC(1996) A unified statistical approach for determining significantsignals in images of cerebral activation. Hum Brain Mapp4:58–73

Exp Brain Res

123