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Neural inhibition 1 1

Neural inhibition and interhemispheric connections in two-choice reaction

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time: A Laplacian ERP study

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Chloé Meyniera,b, Boris Burlea, Camille-Aimé Possamaïb,

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Franck Vidala, and Thierry Hasbroucqa

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a

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France

Laboratoire de Neurobiologie de la Cognition, Aix-Marseille Université, CNRS, Marseille,

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b

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Poitiers, France

Centre de Recherches sur la Cognition et l'Apprentissage, Université de Poitiers, CNRS,

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Running head: Neural inhibition and interhemispheric connections

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Corresponding Author at:

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Thierry Hasbroucq

17

CNRS et Université de Provence

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Laboratoire de Neurobiologie de la Cognition, UMR 6155 Case C

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3 place Victor Hugo

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13331 Marseille cedex 3, FRANCE

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Tel: (+33) 488 57 68 67

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Fax: (+33) 488 57 68 72

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Email: [email protected]

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Abstract

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In between-hand choice reaction time tasks, the motor cortex involved in the required

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response is activated while the motor cortex involved in the non-required response is

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inhibited. Such an inhibition could be implemented actively between the responses defined as

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possible alternatives by the task instructions or, alternatively, could passively result from

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some kind of “reciprocal inhibition” between the two motor cortices. The present study

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addressed this issue. To this end, we compared the surface Laplacian transforms of

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electroencephalographic (EEG) waves recorded over the contralateral and ipsilateral motor

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cortices in between-hand and within-hand choice conditions. The dynamics of the recorded

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EEG activities suggest that inhibition is implemented in a feed-forward manner between the

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cortical zones controlling the different response alternatives rather than between homologous

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motor cortical structures.

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Neural inhibition, interhemispheric connections and formal models of reaction time: A

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Laplacian ERP study

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Recent results have shown that in between-hand two-choice RT tasks, the required

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response is activated while the non-required response is inhibited. This pattern has been

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observed at the level of the motor cortex with transcranial magnetic stimulation (Burle,

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Bonnet, Vidal, Possamaï, & Hasbroucq, 2002) and can further be evidenced from EEG

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recordings by estimating the surface Laplacian (Vidal, Grapperon, Bonnet, & Hasbroucq,

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2003): Before the response, a negative wave develops over the involved motor cortex and,

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symmetrically a positive wave develops over the non-involved cortex. Evidence indicates that

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the negative wave reflects the activation of the involved motor cortex, while the positive wave

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reflects the inhibition of the non-involved motor cortex (see Burle, Vidal, Tandonnet, &

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Hasbroucq, 2004). Such an inhibition could be “lateral”, in which case it would originate

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from the opposite motor cortex or “feedforward”, in which case it would originate from

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structures located upstream in information processing, like the anterior cingulate cortex

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(Gemba & Sasaki, 1990) or the supplementary motor area (Babiloni et al. 2003; Goldberg,

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1985; Tanji & Kurata, 1985). Whether it be lateral or feedforward, inhibition is likely to be

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implemented through interhemispheric connections (Ferbert, Priori, Rothwell, Day,

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Colebatch, & Marsden, 1992)

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While we argued that the observed inhibition was actively implemented because left-

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and right-hand responses are defined as possible alternatives by the task instructions (Vidal et

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al., 2003), it remains to be ascertained that the interhemispheric connections mediating this

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component are recruited actively because of such task demands. Indeed, between-hand

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choices entail a confounding between the involvement of the motor cortices in the responses

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and the lateral organization of the neuroaxis. In such tasks, the involved motor cortex is

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inevitably contralateral to the required response while the non-involved motor cortex is

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Neural inhibition 4 1

ipsilateral to this response. The neural inhibition observed so far in between-hand choices

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could thus be actively implemented or, alternatively, be a passive by product of

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interhemispheric connections (Asanuma & Okuda, 1962, Ferbert et al., 1992). The aim of the

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present study was to shed light on this issue. To this end, we compared the surface Laplacian

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transforms of EEG waves recorded over the contralateral and ipsilateral motor cortices in

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between-hand and within-hand choices. In the latter case, the fingers of the non-involved

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hand were not possible response alternatives. While the 2-3cm spatial definition of the surface

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Laplacian (Babiloni, Cincotti, Carducci, Rossini, & Babiloni, 2001), allows one to

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differentiate the respective activities of the contralateral and ipsilateral motor cortex, it is

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insufficient to distinguish the activities generated by close motor cortical zones controlling

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fingers of the same hand. These methodological considerations led to the following

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predictions. If inhibition is due to interhemispheric connections, the positive wave should

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develop over the ipsilateral motor cortex, irrespective of the task condition. Alternatively, if

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inhibition is exerted among the responses defined as possible alternatives, it should be

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implemented within the contralateral motor cortex in the within-hand condition and no

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positive wave should develop over the ipsilateral hemisphere in this condition. In the within-

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hand condition, the activity recorded over the contralateral motor cortex should reflect both

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the activation and inhibition of the response alternatives and, providing that the sources

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corresponding to these respective activities do not cancel each other in the surface recordings,

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any negative or positive activity recorded over the contralateral hemisphere should be smaller

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in the within- than in the between-hand condition.

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Method Participants

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Twelve right-handed volunteers [7 females, aged 18-47 (M = 27 years; SD = 9)], with

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normal or corrected-to-normal vision, participated in the experiment. Informed written

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consent was obtained according to the Declaration of Helsinki.

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Apparatus

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Participants were seated in an armchair, the palm of their hands resting on a horizontal

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pull-out slide on which four response keys were fixed. A light contention tightened their arms

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to the chair. The two left-side response keys were respectively operated with the left little

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finger and thumb, while the two right-side keys were respectively operated with the right

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thumb and the little finger. The participants faced a horizontal black panel, 1.5 m distant at

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eye level. One bicolour light-emitting diode was positioned at the centre of the panel and

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displayed the stimuli (red or green).

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Design and Task

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Participants were to respond as quickly and accurately as possible to the colour stimuli

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by pressing one or another response key in six conditions: within-hand/left little finger-left

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thumb, within-hand/right thumb-right little finger, between-hand/thumbs, between-hand/little

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fingers, between-hand/left little finger-right thumb, between-hand/left thumb-right little

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finger. The stimuli were equiprobable, delivered according to a pseudo-random sequence and

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presented during 1 s maximum. The response turned off the stimulus, and 1 s after the

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response, the next stimulus was delivered. When participants failed to respond within 1 s, the

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stimulus was turned off and the next stimulus was delivered 1 s later. The stimulus-finger

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response mapping was counter-balanced across subjects and determined such as, irrespective

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of the condition, one colour was associated to the left response and the other colour to the

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right response. The order according to which the conditions were performed was counter

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balanced across subjects. Four blocks of 100 trials were to be completed in each condition.

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Electrophysiological recordings Electroencephalographic (EEG), Electro-oculographic and Electromyographic (EMG)

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activities were recorded with Ag/AgCl electrodes (BIOSEMI Active-Two electrodes,

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Amsterdam). The sampling rate was 1024 Hz (Filters: DC to 268 Hz, 3 dB/octave). For EEG,

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we used 64 channels (10-20 system positions). EOG was recorded bipolarly between

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electrodes situated above the right eye and its outer canthus. EMG was recorded bipolarly

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from the flexor pollicis brevis and from the abducbtor digiti minimi of the two hands, by

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surface Ag/AgCl electrodes (6 mm diameter), fixed 2 cm apart on the skin of the thenar and

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hypothenar eminences for the thumbs and little fingers, respectively. The EMG signal was

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continuously monitored by the experimenter in order to avoid as much as possible any

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background activity in order to facilitate the EMG onset detection. If the signal became noisy,

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the experimenter immediately asked the subject to relax his (her) muscles.

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Brain activities were recorded continuously during the experiment. Response-related

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activities were averaged time-locked to EMG onset. The EMG activities recorded during each

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trial were displayed on a computer screen aligned to the onset of the imperative stimulus and

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the onsets of the changes in activity were determined visually and marked with the computer

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mouse. This method was preferred to an automated one because it allows more precise

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detection (Staude, Flachenecker, Daumer, & Wolf, 2001).

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Artifact Rejection and signal processing

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Although the use of the surface Laplacian reduces blink and eye source

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contaminations (Law, Nuñez, & Wijesinghe, 1993), ocular artefacts were subtracted by the

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statistical method of Gratton, Coles, and Donchin (1983). Nevertheless when this subtraction

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was judged (by visual inspection) imperfect in a given trial, this trial was rejected because

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Laplacian transformation is sensitive to local artefacts. Laplacian transformation was then

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applied on each individual trace: First the signal was interpolated with the spherical spline

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interpolation procedure (Perrin, Pernier, Bertrand, & Echallier, 1989), and hence the second

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derivatives in the two dimensions of space were computed. We chose 3 as the degree of spline

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since this value minimizes errors (Perrin, Bertrand, & Pernier, 1987), and the interpolation

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was computed with a maximum of 15 degrees for the Legendre polynomial. The RT was

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measured between the onset of the imperative signal and the occurrence of the voluntary

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change in EMG activity.

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Results

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Because of EEG artefacts (7%), tonic EMG activity (4%), 11% of the trials were

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discarded. We also took great care of further discarding multiple EMG activations occurring

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during the RT interval (29%), because such activations affect response-locked EEG activities.

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Since this study focuses on within- vs. between-hand comparisons, the data obtained in the

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two within-hand conditions and in the four between-hand conditions were grouped together,

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respectively. In what follows, the resulting conditions will be referred to as within and

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between-hand conditions.

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Behavioural data

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The arcsine transforms (Winer, 1970) of the error rate (4%) and the mean RT were

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submitted to one sample two-tailed Student’s t tests. Neither the error rate (between-hand:

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2.5% (thumb: 1.2%, little finger: 1.3%); within-hand: 1.5% (thumb: 0.6%, little finger: 0.9%),

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nor the mean RT (between-hand: 235 ms (thumb: 241 ms, little finger: 230 ms); within-hand:

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237 ms (thumb: 246 ms, finger: 229 ms), were affected by the condition: t(11) = -0.89, p =.39

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and t(11) = -0.30, p =.77, respectively. Errors trials were discarded from further analyses.

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Electrophysiological data

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Figure 1 shows Laplacians transforms, time-locked to EMG onset, over the

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contralateral and ipsilateral motor cortices in between-hand and within-hand conditions. In the

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two conditions, a negative wave developed over the contralateral motor cortex before EMG

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onset. A positive wave developed over the ipsilateral motor cortex in the between-hand

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condition but not in the within-hand condition. In order to assess the reliability of these waves

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and their dynamics, we analysed the slopes (estimated by computing linear regressions) and

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the amplitudes of the activity under interest in specific time windows.

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Figure 1 about here

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First, to test the reliability of the waves, for each subject we performed a backward

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analysis on the traces starting from EMG onset to 100 ms prior to EMG onset. For each

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condition, we measured the slope values during 25 ms consecutive sliding epochs by steps of

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5 ms (16 time epochs) by computing a linear regression for each epoch. Then, the slopes in

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each epoch were compared to 0 by the one sample two-tailed Student’s t test. The start of

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changes in activity was defined as the inferior boundary of the last epoch in which the slope

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value significantly differed from 0.

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The contralateral negative wave differed from 0 to 60 ms before EMG onset in the

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between-hand condition, t(11) = 3.61, p < .01 and from 0 to 55 ms before EMG onset in the

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within-hand condition, t(11) = 4.18, p < .01. The slope of the ipsilateral positive wave differed

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from zero from 0 to 70 ms before the EMG onset in the between-hand condition, t(11) = -

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2.84, p < .05, but none of the slopes in any time epochs differed from zero in the within-hand

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condition (all ps > .05).

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Second, based on the results of the above analysis, we tested the effect of condition on

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the activation component by comparing the negative slopes with the one sample one-tailed

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Student’s t test during the 55 ms preceding EMG onset (period for which both slopes differed

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from 0). The slope of this wave was steeper in the between- than in the within-hand condition,

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t(11) = 2.30, p < .05 (see Figure 1). We further compared the averaged amplitudes of the

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waves obtained in each condition in a time window starting 10 ms before EMG onset and

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finishing 10 ms after this event with the one tailed Student’s t test. For this analysis, the

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baseline was taken between -120 ms and -70 ms before the EMG onset. Our rationale was the

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following. As we sought for a measure free from any contamination by preceding events (for

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example upstream non-motor activities), we chose a baseline as close as possible to the waves

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of interest (activation/inhibition), in a period where we could demonstrate that these waves

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had not begun yet or, in other words, in a period where all the traces were “flat” over motor

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areas in all conditions. Since we showed that ipsilateral inhibition started 70 ms before EMG

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onset, we used, as a baseline, the first (flat) 50 ms time window preceding 70 ms, that is a -

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120 to -70 ms. The amplitude of the contralateral negativity was higher in the between- than

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in the within-hand condition, t(11) = 2.2, p < .05. No difference between the amplitude of the

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contralateral negativity and the ipsilateral positivity was observed in the between-hand

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condition, t(11) = -1.16, p = .47.

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Third, because in a preceding study, we showed that a negative wave (N-40)

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developed at FCz prior to the activities observed over the motor cortices (Vidal et al., 2003),

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we checked whether this component was present in the present data set. To this end, we used

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the same method as described above for the negative component obtained over the

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controlateral motor cortex in a time window lasting from –200 ms to EMG onset. None of the

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slopes in any time epoch differed from 0 in any condition (all ps > .05).

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Discussion Before the contraction of the response agonist, a positive wave developed over the

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ipsilateral motor cortex in the between-hand condition but not in the within-hand condition. A

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negative wave developed over the contralateral motor cortex in all task conditions. The slope

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and amplitude of this negative wave at EMG onset were smaller in the within- than in the

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between-hand condition. In the between-hand condition, the onset of the positive wave

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preceded that of the negative wave.

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We shall first briefly evoke previous findings so as to facilitate the discussion of the

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present original findings. We shall then examine the modulations of the positive and negative

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waves in this study and draw possible implications of these findings.

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The data obtained in the between-hand condition replicate the findings of previous

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studies showing that a contralateral negativity/ipsilateral positivity pattern develops over the

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motor cortex prior to the contraction of the response agonists (Vidal et al., 2003, see also

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Praamstra & Seiss, 2005). Transcranial magnetic stimulation and monosynaptic reflex

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investigations indicate that the negative component reflects the activation of the contralateral

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motor cortex while the positive component reflects the inhibition of the ipsilateral motor

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cortex (see Burle et al., 2004). In the within-hand condition, no positive wave developed over the ipsilateral motor

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cortex, indicating that there was no active interhemispheric inhibition when the responses

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were to be chosen among fingers of the same hand. Active inhibition seems therefore to be

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implemented through interhemispheric connections in between-hand but not in within-hand-

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tasks, a conclusion discarding the possibility that the inhibition observed in previous studies

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was a passive by-product of connections to the ipsilateral cortex. This outcome shows that

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inhibition is task-dependent, as conjectured in our earlier study (Vidal et al., 2003).

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A negative wave was observed over the contralateral motor cortex in the within-hand

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condition, which suggests that the Laplacian picked up preferentially the negative source

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compared to the positive one. The slope and amplitude of this component were smaller than in

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the between-hand condition. This can be due to an intra-hemispheric positive activity related

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to the inhibition of the alternative response. This outcome is compatible with formal models

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of choice RT according to which inhibition is implemented between the responses defined as

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possible alternatives by the task instructions, irrespective of the between or within-hand

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condition in which the task is completed (see e.g. Bogacz, Brown, Moehlis, Holmes, &

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Cohen, 2006). Now, in the between-hand condition, the positive wave developed prior to the

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negative wave. The anteriority of the positive wave discards lateral inhibition as a viable

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formal alternative. Indeed, with such a scheme, inhibition develops as a consequence of

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response activation and cannot precede this event. The present pattern is therefore necessarily

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generated through feed-forward inhibition and possibly from structures located upstream from

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the motor cortex, like the anterior cingulate cortex (Gemba & Sasaki, 1990) or the

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supplementary motor area (Babiloni et al. 2003; Goldberg, 1985; Tanji & Kurata, 1985).

8

In Vidal et al. (2003), we have reported a trace of such an upstream feed-forward

9

process at FCz, that is over these structures. This wave was called N-40 and we proposed that

10

it reflected response selection and/or motor programming operations. No such component was

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measurable in the present data set, which may seem odd. It may be noted, however, that in the

12

present study, the stimulus-response mapping was very simple and quickly learned by the

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subjects while in Vidal et al. (2003), the stimulus-response mapping was more complex as the

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task was a variant of the Stroop task (Stroop, 1935). Although this interpretation is

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speculative, it is possible that in the present study, selection operations were so easily

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performed that they did not sufficiently recruit the SMAs to evoke a measurable N-40 at scalp

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level.

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References

2

Babiloni, C., Babiloni, F., Carducci, F., Cincotti, F., Del Percio, C., Hallett, M., Kelso,

3

A.J.S., Moretti, D.V., Liepert, J., & Rossini, P.M. (2003). Shall I Move My Right or My Left

4

Hand?: An EEG Study in Frequency and Time Domains. Journal of Psychophysiology, 17,

5

69-86.

6

Babiloni, F., Cincotti, F., Carducci, F., Rossini, P. M., & Babiloni, C. (2001). Spatial

7

enhancement of EEG data by surface Laplacian estimation: The use of magnetic resonance

8

imaging-based head models. Clinical Neurophysiology, 112, 724-727.

9

Bogacz, R., Brown, E., Moehlis, J., Holmes, P., & Cohen, J. D. (2006). The physics of

10

optimal decision making: A formal analysis of models of performance in two-alternative

11

forced-choice tasks. Psychological Review, 113, 700-765.

12

Burle, B., Bonnet, M., Vidal, F., Possamaï, C. A., & Hasbroucq, T. (2002). A

13

transcranial magnetic stimulation study of information processing in the motor cortex:

14

Relationship between the silent period and the reaction time delay. Psychophysiology, 39,

15

207-217.

16 17 18

Burle, B., Vidal, F., Tandonnet, C., & Hasbroucq, T. (2004). Physiological evidence for response inhibition in choice reaction time tasks. Brain and Cognition, 56, 153-164. Ferbert, A., Priori, A., Rothwell, J.C, Day, B.L., Colebatch, J.G., & Marsden, C.D.

19

(1992). Interhemispheric inhibition of the human motor cortex. Journal of Physiology, 453,

20

525-546.

21

Gemba, H., & Sasaki, K. (1990). Potential related to no-go reaction in go/no-go hand

22

movement with discrimination between tone stimuli of different frequencies in the monkey.

23

Brain Research, 537, 340-344.

24 25

Goldberg, G. (1985). Supplementary motor area structure and function: review and hypothesis. Behavioral and Brain Sciences, 8, 567-616.

Psychophysiology

Page 13 of 17

Psychophysiology

Neural inhibition 13 1

Gratton, G., Coles, M. G., & Donchin, E. (1983). A new method for off-line removal

2

of ocular artifact. Electroencephalography and Clinical Neurophysiology, 55, 468-484.

3

Law, S.K., Nunez, P. L., & Wijesinghe, R.S. (1993). High-resolution EEG using

4

spline generated surface Laplacians on spherical and ellipsoidal surfaces. IEEE Transactions

5

on Biomedical Engineering, 40, 145-153.

6

Perrin, F., Bertrand, O., & Pernier, J. (1987). Scalp current density mapping: Value

7

and estimation from potential data. IEEE Transaction on Biomedical Engineering, 34, 283-

8

288.

9

Perrin, F., Pernier, J., Bertrand, O., & Echallier, J. (1989). Spherical splines for scalp

10

potential and current density mapping. Electroencephalography and Clinical

11

Neurophysiology, 72, 184-187.

12

Praamstra, P., & Seiss, E. (2005). The neurophysiology of response competition:

13

Motor cortex activation and inhibition following subliminal response priming. Journal of

14

Cognitive Neuroscience, 17, 483-494.

15

Staude, G., Flachenecker, C., Daumer, M., & Wolf, W. (2001). Onset detection in

16

surface electromyographic signals: A systematic comparison of methods. European Journal

17

on Applied Signal Processing, 2, 67-81.

18 19 20

Stroop, J.R. (1935). Studies of interference in verbal reactions. Journal of Experimental Psychology, 18, 643-662. Tanji, J., & Kurata, K. (1985). Contrasting neuronal activity in supplementary and

21

precentral motor cortex of monkeys. I. Responses to instructions determining motor responses

22

to forthcoming signals of different modalities. Journal of Neurophysiology, 53, 129-141.

23

Vidal, F., Grapperon, J., Bonnet, M., & Hasbroucq, T. (2003). The nature of unilateral

24

motor commands in between-hand choice tasks as revealed by surface Laplacian estimation.

25

Psychophysiology, 40, 796-805.

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Winer, B. J. (1970). Statistical principles in experimental design. London: McGrawHill.

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Author Note

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We are grateful to Remy Pernaud and Dany Palleresompoulle for their technical contribution.

3

We also thank Karen Davranche for helpful discussions and to Hartmut Leuthold an an

4

anonymous reviewer for valuable comments on a preliminary version of this paper. The first

5

author was supported by a grant of the Ministry of Education and Research. Address reprint

6

requests to: Thierry Hasbroucq, CNRS & Université de Provence, Laboratoire de

7

Neurobiologie de la Cognition, UMR 6155 Case C, 3 Place Victor Hugo, 13331 Marseille

8

Cedex 3, France. E-Mail: [email protected]

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Figure caption

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Figure 1. Laplacian maps (top) and Laplacian grand average (bottom) computed by spherical

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spline interpolation. Maps show a view of the head, (nose up) at three times before the EMG

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onset (-50 ms, -25 ms and 0 ms before the EMG onset) for between-hand (top) and within

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hand (bottom) conditions. Black circles symbolize the electrodes locations and the black dots

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represent C3 and C4. The traces represent the amplitude of the surface Laplacian (microvolts

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per square centimetre, ordinate) as a function of time (milliseconds, abscissa), over the motor

8

cortex contralateral to the responding hand (blue lines), and the motor cortex ipsilateral to the

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responding hand (red lines) in between-hand (thick lines) and within-hand (thin lines)

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conditions. The zero of time corresponds to EMG onset of the responding finger and the

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period baseline was ranged from -120 ms to -70 ms. BH and WH abbreviations correspond to

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Between-hand and Within-hand, respectively.

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216x183mm (96 x 96 DPI)

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