/home/precedings/apps/precedings/shared/storage/document/2008/1563/npre20081563-1

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Posterior parietal cortex controls spatial attention through modulation

of anticipatory alpha rhythms

Paolo Capotosto

, Claudio Babiloni

2,3,4

, Gian Luca Romani

and Maurizio Corbetta

1,5

1. Dip. di Scienze Cliniche e Bioimmagini and ITAB, Istituto di Tecnologie Avanzate

Biomediche Università "G. D'Annunzio", Chieti, Italy

2. Dip. Scienze Biomediche, Univ. di Foggia, Foggia-Italy;

3. Casa di Cura San Raffaele Cassino e IRCCS San Raffaele Pisana Roma, Italy

4. A.Fa.R. Dip Neuroscienze - Osp. FBF - Isola Tiberina, Roma, Italy;

5. Department of Neurology, Radiology, Anatomy & Neurobiology, Washington University

School of Medicine, St.Louis, USA

Running title: "Intraparietal cortex and spatial attention"

Corresponding author:

Claudio

Babiloni

PhD

Department of Biomedical Sciences

University of Foggia, Italy

e-mail:

claudio.babiloni@uniroma1.it

Maurizio Corbetta MD

Department of Neurology

Washington University, St.Louis

e-mail:

mau@npg.wustl.edu

Keywords: Visuospatial attention, frontal-parietal network, visual cortex, rTMS, EEG, Alpha

rhythms

Acknowledgement: This research was supported by a European Union 'Marie Curie Excellence
Chair' to M.C. (MEXC-CT-2004-006783). M.C was also supported by the J. S. McDonnell
Foundation, National Institute of Neurological Disorders and Stroke Grants F30 NS057926-01 and
R01 NS48013, National Institute of Mental Health Grant R01 MH71920-06. We thanks Vittorio
Pizzella for support, and Chris Lewis for editing.

Nature Precedings : hdl:10101/npre.2008.1563.1 : Posted 1 Feb 2008

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Abstract

A dorsal fronto-parietal network, including regions in intra-parietal sulcus (IPS) and

frontal eye field (FEF), has been hypothesized to control the allocation of spatial attention to

environmental stimuli. One putative mechanism of control is the de-synchronization of

electroencephalography (EEG) alpha rhythms (~8-12 Hz) in parieto-occipital cortex in

anticipation of a visual target. We show that brief interference by transcranial magnetic

stimulation (rTMS) with preparatory activity in right IPS or right FEF while subjects attend to

a spatial location impairs identification of target stimuli ~2 seconds later. Moreover, the visual

deficit relates to the disruption of anticipatory (pre-stimulus) alpha desynchronization and its

topography in parieto-occipital cortex. After right IPS stimulation, the degree to which alpha

desynchronization is suppressed predicts the speed of visual identification. These results

demonstrate the causal role of posterior parietal cortex in the control of visuo-spatial

attention exerted through the synchronization of visual neurons.

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Introduction

Observers develop expectations about visual scenes that can guide and enhance perception.

For example, we can voluntarily attend to a location in the visual field, and subsequent stimuli at

that location will be recognized more accurately and rapidly

1, 2

. Neuroimaging studies have

suggested that the influence of attention on perception involves an interaction between 'control'

regions in dorsal prefrontal and posterior parietal cortex that generate and maintain goal-driven

expectations, which in turn modulate sensory activity in occipital visual regions

3-6

. More directly,

recent studies have shown that electrical or magnetic stimulation of prefrontal or parietal regions

can induce signal changes in occipital cortex in the absence of visual stimulation

or modulate

stimulus-evoked activity in visual areas recorded from single neurons

8, 9

or blood oxygenation level

dependent (BOLD) signals

The neural mechanisms underlying the control of attention on visual representations are still

largely unknown. A leading hypothesis is that spatial attention controls visual cortex by

synchronization of inputs or modulation of the temporal coherence of ongoing oscillatory activity

11,

. A putative marker of the physiological interaction between fronto-parietal regions and occipital

visual areas is the modulation of the posterior alpha rhythms at about 8-12 Hz as recorded with

electroencephalography (EEG). In fact, alpha rhythms show high power over parietal and

occipital areas in the absence of visual stimulation

, which is then reduced in anticipation of visual

targets

. Moreover, when subjects expects a target at a specific location, the topography of alpha

rhythms also becomes spatially selective

15-18

and predicts trial-by-trial the locus of attention and

visual performance

. Similar gradients of anticipatory activity have been recorded with BOLD-

functional magnetic resonance imaging (fMRI) in visual occipital, posterior parietal and prefrontal

cortices

19-23

, and they have been also found to be predictive of the locus of attention and stimulus

perception

21, 24

Here, we test the hypothesis that dorsal prefrontal and parietal regions control spatial attention in

visual cortex through the anticipatory de-synchronization (or power modulation) of ongoing alpha

rhythms. We predict that disruption of neural activity in prefrontal and parietal cortices while

observers attend to a target location will interfere both with visual perception and the anticipatory

de-synchronization of alpha rhythms in parieto-occipital cortex. Moreover, if the rTMS-induced

disruption of alpha rhythms is behaviourally significant then the degree of disruption should

correlate with visual performance. To interfere with neural activity we employed repetititive

transcranial magnetic stimulation (rTMS), a method already successfully utilized for studying the

role of prefrontal and parietal cortices in target detection and reorienting of attention to sensory

stimuli

25-32

, while we monitored activity in visual cortex by simultaneous recordings of EEG

rhythms.

Results

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Behavior

Healthy subjects (N=16) performed a visual spatial discrimination task (Figure 1a). Each

trial began with the presentation of a foveal symbolic cue pointing to one of two target

locations in left and right visual field along the horizontal meridian. The cue correctly

indicated the target location on 80% of the trials. After a 2 s delay a target shape, either a T

or L, was briefly presented either at the cued or uncued location followed by a different

meaningless shape (or mask) to render the discrimination more difficult. The subject's task

was to identify the target by pressing one of two keys. The foveal cue provided information

about the target location but not the response (stimulus selection

To test the causal role of the dorsal attention network

in anticipatory spatial attention,

we applied short bursts of rTMS (150 ms, 20 Hz) time-locked to the onset of the cue in right

IPS or right FEF, the core regions of this network. As control conditions, we stimulated either

the right precentral gyrus (PrCe), a region near FEF (<10 mm vector distance, figure 1B) not

involved in anticipatory visuo-spatial attention, which is part of the ventral attention network

for stimulus-driven re-orienting

, or the vertex in Sham, i.e. no rTMS, mode of stimulation (see

Supplementary methods). The cortical regions were localized on the scalp with a neuro-

navigation system in a stereotactical atlas space

on the basis of their average location in a

recent meta-analysis of fMRI studies of spatial attention

(Figure 1B). The behavioral

interference caused by rTMS was measured on the accuracy and reaction times (RTs) of

target identification ~1.5 seconds later (Figure 1A).

The speed of response (F (3,45)=11.19; p<0.0001) and the accurate identification of target

stimuli (F (3,45)=10.88; p<0.0001) were differentially affected by the application of rTMS at

different cortical sites. Magnetic stimulation in right FEF (544 ms ± 31) and right IPS (560 ms ±

32) slowed down target responses as compared to Sham (524 ms ± 29; p<0.001 vs. FEF;

p<0.0001 vs. IPS) and right PrCe stimulation (502 ms ± 31; p<0.001 vs. FEF; p<0.0001 vs. IPS).

There was no significant difference between right PrCe and Sham stimulation (Figure 2A,

Table 1). Correct responses also occurred less frequently after rTMS in right FEF (86.3 % ±1.7)

and right IPS (85.9 % ± 1.9) than after Sham (91.1 % ± 1.1; p<0.0001 vs. FEF; p<0.0001 vs. IPS)

or right PrCe (88.7 % ± 1.9; p<0.01 vs. FEF; p<0.01 vs. IPS)(Figure 2B, Table 1). These deficits

were bilateral, i.e. for targets in both visual fields, and irrespective of whether targets

appeared at cued vs. uncued locations.

rTMS did not disrupt the observers' ability to direct spatial attention to the target location.

In fact there was an overall significant effect of target validity across conditions (RTs: valid, 503 ms

± 30; invalid, 552 ms ± 32; F (1,15)=14.84 p<0.002; accuracy: valid, 90.4% correct ± 1.5; invalid,

85.6% correct ± 2 F (1,15)=16.74 p<0.001). However, rTMS in right FEF and right IPS during

anticipatory attention more strongly impaired target detection at unattended locations (invalidly

cued)(Validity x rTMS Condition: F(3,45)=2.74 p=0.054) (Table 1, Supplementary Figure 1).

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We also found that targets presented in the right visual field were identified more accurately

and more rapidly than targets presented in the left visual field (left 507 msec ± 30.5; right 499 msec

± 30 F (1,15)=18.64 p<0.0005; accuracy: left, 90% correct ± 1.6; right, 91% correct ± 2 F

(1,15)=4.97 p<0.05) independently of rTMS condition (Supplementary Figure 2). The visual field

lateralization was somehow unexpected, but it may relate to the well-known superiority of the right

visual field (left hemisphere) for alphabetical material

. To insure that this effect did not depend

on magnetic stimulation, we ran a novel group of healthy volunteers (N=9) without rTMS. Once

again right visual field targets were detected faster and more accurately than left visual field targets

(RTs: left 663 msec ± 37.4; right 612 msec ± 40 F (1,8)=30.52 p<0.001; accuracy: left, 86% correct

± 2.75; right, 93% correct ± 1.8 F (1,8)=5.49 p<0.05).

Finally to verify that the behavioral deficits induced by rTMS did not reflect a cumulative

effect building up over trials, but that it actually reflected interference with trial-by-trial preparatory

processes, we checked whether the deficits differed in the first, second, third, and fourth quartile

of each block of trials, and found no difference. Although this null result does not rule out that a

cumulative effect occurred, it is more consistent with the notion that rTMS interfered

predominantly on the trial in which it was applied.

Overall these findings support the hypothesis that FEF and IPS contain preparatory signals

during anticipatory visuo-spatial attention whose disruption significantly alters subsequent visual

perception. Interestingly, visual perceptual deficits occurred in both visual fields which may be

counterintuitive given spatial cueing was lateralized. However, as later discussed both

spatial and non-spatial processes are likely to be prepared during an anticipatory delay, and

the latter tend to be more broadly represented in the pattern of cortical activation

3, 4, 24, 37

EEG

To assess the physiological impact of rTMS on anticipatory neural activity, we recorded

simultaneous EEG activity from the scalp in order to measure the effect of magnetic

stimulation in different cortical loci on the desynchronization of alpha rhythms in parieto-

occipital cortex, a reliable correlate of anticipatory spatial attention modulation

15-18

The EEG signals chosen for the analysis of alpha rhythms (+0.5 s to +1.5 s after cue onset)

were free of rTMS artifacts (see Supplementary methods). Supplementary figure 3a shows EEG

data at parietal and occipital electrodes of interest (P3, P4, O1, O2) from a single subject in the

four conditions (Sham, right FEF, right IPS, right PrCe). The rTMS artifact practically lasted the

stimulation period plus about 10 msec. Supplementary figure 3b shows EEG power spectra (3-40

Hz, 1 Hz resolution) for the 'baseline' (-1.5 s to -0.5 s before the cue stimulus onset) and the "cue

event" period (+0.5 s to 1.5 s). The alpha frequency peak is clearly recognizable at all electrodes of

interest, and the profile of the EEG spectra looks regular. Therefore, we computed the percentage

reduction (event-related desynchronization, ERD) or increment (event-related synchronization,

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ERS) of parieto-occipital alpha power in the `cue event' when referenced to the `baseline'

(see

Supplementary methods). This index reflects the relative synchronization or desynchronization of

cortical pyramidal neurons generating alpha rhythms.

Figure 3a illustrates the topography of parieto-occipital alpha ERD/ERS in the four

conditions (Sham, right FEF, right IPS, right PrCe), during the anticipation of the target. During

Sham we observed a robust bilateral ERD (desynchronization) at both low- and high-frequency

alpha sub-bands in parietal-occipital cortex. A slight anticipatory alpha ERD also occurred after

rTMS on right FEF and right PrCe. In contrast, the anticipatory alpha ERD was prevented by rTMS

in right IPS, and substituted by a bilateral increase of alpha power (ERS)(synchronization). This

qualitative impression was confirmed by statistical analysis. For the low-frequency alpha ERD/ERS

(Fig. 3b), an ANOVA showed a significant main effect of site of stimulation (F (3,45)=5.96;

p<0.002). This was accounted for by a greater anticipatory alpha power (ERS) for right IPS than

Sham (p<0.001), right PrCe (p<0.02), or right FEF stimulation (p<0.02) regardless of electrodes of

interest (occipital, parietal) or hemisphere (left, right)(Figure 5A). The same effect was observed for

the high-frequency alpha ERD/ERS (F (3,45)=6.10; p<0.002) with greater anticipatory alpha power

for right IPS than Sham (p<0.001), right PrCe (p<0.03), or right FEF (p<0.03) stimulation (Figure

3c). In summary, interference with right IPS preparatory activity during spatial attention abolished

the normal anticipatory desynchronization of alpha rhythms in parieto-occipital cortex.

To test whether the interference with the physiological desynchronization of alpha rhythms

during the cue period impacted target processing, we ran a correlation analysis between the

parieto-occipital alpha ERD/ERS (at electrodes P3, P4, O1, O2) during the cue period and the RTs

to target stimuli. This analysis was carried out across subjects separately for the different rTMS

conditions (right IPS, right FEF, right PrCe). Only in the case of right IPS stimulation did we find a

positive correlation between low-frequency alpha ERD/ERS at the P3 electrode (left parietal region

contralateral to the rTMS stimulation) and RTs (r = 0.61 p< 0.01) (Figure 4A). Another positive

correlation was found between high-frequency alpha ERD/ERS at the O1 electrode (left occipital

region contralateral to the rTMS stimulation) and RTs (r=0.58 p< 0.02) (Figure 4b).

Finally, based on previous evidence

15, 17, 18, 39

, we expected anticipatory alpha ERD to be

higher in amplitude over the parieto-occipital areas contralateral to the spatial location of attention.

Consistent with previous work we observed that the anticipatory alpha ERD in high-frequency sub-

band was stronger over the hemisphere contralateral to the side of attention during Sham (F

(1,15)=13.60; p<0.003), but also during right PrCe rTMS (F (1,15)=6.37; p<0.03). Therefore, the

spatial topography of alpha power was spatially selective in the two control conditions. In contrast,

this inter-hemispheric asymmetry was disrupted when rTMS was applied to both right FEF and

right IPS (Figure 5), consistent with the hypothesis that these regions contribute to the normal

allocation of spatial attention and the asymmetrical decrement of alpha power over parieto-occipital

cortex.

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Discussion

Visual perception deficits after interference with spatial attention signals in right IPS and FEF

Several previous TMS studies

25-32

have shown the critical role of posterior parietal and FEF

cortices in selective visual processing and reorienting of attention to stimuli presented at

unattended locations, but this is the first study to find disruptive effects of rTMS over IPS and FEF

during the endogenous allocation of spatial attention in anticipation of a visual target. We applied

short burst of rTMS while subjects directed attention to a target location, and found that the

magnetic stimulation impaired the speed and accuracy of discrimination for targets presented >1.5

seconds later (Figure 2). This result is consistent with the hypothesis that right IPS and right FEF

play a causal role in the endogenous allocation of visual attention, and that a normal attentional

deployment is necessary for normal perception.

By applying rTMS simultaneously to spatial cueing, we insured that the behavioral deficits

reflected interference with endogenous signals for attention rather than secondary modulations of

target-evoked responses or response processes. Another recent study applied rTMS to FEF during

spatial cueing, but failed to find a significant disruption on target processing

. A potential

difference between the two studies is the relatively brief cue-target interval (400 msec) employed

by Taylor et al.'s, whereas in our study subjects maintained attention at the cued location for 2

seconds. It is possible that a shorter delay allowed for the recruitment of parallel reflexive

circuitries (e.g. superior colliculus) to direct covert attention, whereas a longer delay may have

enforced the utilization of a stronger endogenous set presumably more dependent on cortical

regions.

Target discrimination following right IPS or right FEF stimulation was disrupted in both visual

fields. These results can be related to the observation, in neuroimaging studies, that preparatory

activity for spatial attention is largely bilateral in prefrontal and parietal cortices (reviewed in

3, 4, 6

and that regions containing spatially selective responses are relatively small as compared to much

larger regions containing bilateral visual responses

. Finally, the selection of a target location

involves both spatial and non-spatial processes for featural and temporal selection

24, 40, 41

Therefore, we interpret the bilateral perceptual impairment to be related to the disruption of bi-

hemispheric non-spatial preparatory processes in dorsal parietal and frontal cortices. However,

there was also evidence of a spatially specific disruption as demonstrated by the breakdown of

spatially selective topography of alpha EEG power in occipital cortex after right FEF and right IPS

stimulation, as well as the stronger impairment for targets occurring at unexpected locations, which

involve a re-orienting of spatial attention to the novel target location.

Finally, the differential effect of rTMS during spatial cueing at different cortical locations is

consistent with a division of labor and functional segregation between a dorsal attention network,

including right IPS and right FEF specialized in directing spatial attention, and a ventral attention

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network, including right PrCe, which is not recruited during anticipatory attention, but is activated in

conjunction with the dorsal network during target processing and stimulus-driven reorienting

. This

separation was originally proposed on the basis of fMRI task activation studies, but it has been

more recently strengthened by fMRI functional connectivity studies

, fMRI studies of stroke

patients with spatial neglect

43, 44

, and now inactivation studies with rTMS.

Right IPS controls spatial attention through alpha de-synchronization of occipital cortex

Application of rTMS on prefrontal and parietal cortices during spatial cueing induced not only

changes in visual performance for subsequent targets, but also modulated the ongoing pattern of

oscillatory neural activity. In fact interference with right IPS during the cue period blocked the

normal alpha de-synchronization of occipito-parietal cortex, one of the neural mechanisms through

which visual attention modulates visual cortex

15-18

. The suppression of alpha desynchronization

was positively correlated across subjects with the speed of target discrimination, i.e. subjects with

lower alpha desynchronization (or paradoxical synchronization) detected visual targets more

slowly. Finally, both right IPS and right FEF rTMS disrupted the normal topography of anticipatory

alpha desynchronization in occipito-parietal cortex. In fact anticipatory alpha desynchronization is

stronger on the hemisphere contralateral to the attended visual field

17, 18

, and the difference of

anticipatory activity between attended and unattended hemisphere predicts trial-by-trial locus of

attention and speed of response to subsequent visual targets

. After rTMS to right IPS and right

FEF this asymmetrical hemisphere gradient was disrupted. These findings indicate that alpha

desynchronization is one of the mechanisms by which dorsal fronto-parietal regions (IPS, FEF)

control, in a top-down manner, visual cortex, and that interference with this mechanism has a

negative effect on visual selection.

These findings cannot be explained with artifacts (see Supplemental materials), but rather,

they demonstrate that dorsal fronto-parietal regions control the degree (IPS) and topography (IPS,

FEF) of alpha desynchronization in parieto-occipital cortex during anticipatory spatial attention, and

that interference with this mechanism has a negative effect on perception. These results support

more directly the hypothesis that the dorsal attention network controls visual cortex partly through

the modulation of ongoing alpha rhythms, consistent with previous correlation studies which

demonstrate that the topography of anticipatory alpha desynchronization is modulated by the

direction of spatial attention

17, 18

, and that it predicts trial-by-trial the locus of attention and the

speed of visual perception of subsequent stimuli

What is, then, the relationship between ongoing anticipatory alpha rhythms and top-down

control of visual attention? It is well known that (i) the power of alpha rhythms is dominant over

the parieto-occipital cortex; (ii) alpha rhythms are predominantly generated by cortico-cortical

interactions; (iii) are tightly modulated in power by attentional processes

13, 14, 38

; (iv) are

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topographically specific

15-18

; and, (v) their hemispheric lateralization correlates with the locus of

attention, and visual performance

An important issue is whether the modulation of alpha power reflects modulation of activity in

visual cortex. Recent magnetoencephalography (MEG) studies have provided maps of attention-

related changes of alpha and beta power. Although these changes were distributed over the dorsal

visual system the most robust changes occurred in occipital and occipito-parietal cortices

45, 46

, in

agreement with much lower resolution EEG power maps (Figure 3). A recent study showed a link

between spontaneous oscillation of alpha power and excitability of occipital cortex to visual stimuli

. Interestingly, anticipatory BOLD fMRI changes related to the allocation of spatial attention also

show an asymmetrical distribution in visual cortex, which predicts trial-by-trial the locus of spatial

attention and visual performance

similarly to what has been reported for anticipatory modulation

of alpha power

. Finally, several recent fMRI/EEG studies have linked changes of alpha and beta

power to spontaneous fluctuation of the BOLD signal in dorsal fronto-parietal and occipital areas

recruited during spatial attention

48, 49

. Therefore, there is fairly good evidence that at the large-

scale level of cortical areas alpha rhythm fluctuations occur both in occipital cortex and fronto-

parietal regions, and that these fluctuations are modulated by spatial attention.

At the local level, of individual areas or groups of neurons, attention has a powerful effect on

synchronization at higher frequencies. Several studies have reported spike-triggered increases in

gamma coherence during object selection and spatial attention

50-52

. Gamma coherence

modulations can also occur prior to visual stimulation and be predictive of performance

Interestingly, recent evidence indicates that attention-induced modulation of gamma coherence

can be observed across multiple visual areas (V1, V2, V4) and that they occur predominantly in the

superficial layers of cortex. Conversely parallel changes at lower frequencies (alpha and beta

bands) have been recorded from deeper layers of cortex (Robert Desimone, personal

communication), and they may correspond to the modulations recorded by EEG.

Our findings add a critical piece of information by showing that anticipatory alpha rhythms in

parieto-occipital cortex are controlled by signals from IPS and FEF, and that their disruption leads

to a sub-optimal state of neural synchronization in visual cortex that delays target processing.

Interference with spatial attention signals in dorsal regions leads not only to abnormal

ongoing oscillations in visual cortex, but also abnormal stimulus-evoked activity as recently

demonstrated in two elegant studies. Both studies analyzed the impact on stimulus-evoked

potentials in occipital cortex of rTMS applied to either posterior parietal cortex during a visual

search task

, or over FEF during a spatial orienting task

. Both studies reported significant

changes in visually evoked activity consistent with top-down interference from parietal and

prefrontal cortex on target processing in visual cortex. Interestingly, neither study reported a

positive correlation between modulation of stimulus-evoked activity and performance, in contrast to

Thut et al.' and the current study in which anticipatory alpha rhythms were found to predict the

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speed of subsequent visual discrimination. Therefore, these EEG studies, along with similar fMRI

work on anticipatory attention signals

24, 54

, challenge the commonly held view of a direct

relationship between the quality of sensory representations and perception; rather, they suggest a

more complex link between variability at the distinct levels of behavior, ongoing neuronal activity

and stimulus-evoked responses.

Conclusions

To our knowledge, this is the first experiment that directly links the control of spatial

attention by frontal and parietal cortex with anticipatory alpha rhythms in occipital cortex. This

study underscores the importance of ongoing oscillatory neural activity in large-scale cognitive

functions

11, 12

, such as spatial attention, which involve a dynamic interaction between cognitive

systems specialized in control and sensory areas specialized in data analysis

Materials and Methods

Full details of the methodology are reported in the Supplementary methods. The

experiments were performed on 16 right-handed (Edinburgh Inventory) healthy adult volunteers

with normal or corrected-to-normal vision. Informed consent was obtained. The task began with the

presentation of a foveal spatial cue (200 ms) that indicated (80% validity) the location of a target

(70 ms) in the left or right visual field 2 seconds later; the target was followed by a mask stimulus

(130 ms). Subjects pressed a key with the right or left hand to identify either a letter 'T' or 'L' (either

in the canonical upright orientation, 50%, or rotated 180 degrees along the vertical axis, 50%). The

spatial cue indicated the position of the stimulus, but did not provide any information relevant to the

response. This is important to insure that preparatory processes are indeed visuo-spatial and not

motor in origin. Reaction times and the accuracy of the response indexed behavioral performance.

The rTMS was delivered at the onset of the cue stimulus based on the following parameters:

150 ms duration, 20-Hz frequency, and intensity set at 100% of the individual motor threshold

(single-pulse TMS over the hand region of right primary motor cortex). These parameters are

consistent with published safety guidelines for TMS stimulation

55-57

. The experimental design

included four conditions of rTMS, pseudo-randomized across subjects: 1) SHAM, in which the

stimulation was given at the vertex with the coil in reversed position; 2) FEF, 3) IPS, and 4) PrCe

regions of the right hemisphere with the coil in proper position. The locations of right FEF, IPS, and

PrCe were automatically identified on the subject's scalp within a stereotaxic MRI atlas brain

using the SofTaxic neuronavigator system (E.M.S. Italy,

www.emsmedical.net

). The reference

coordinates for the rTMS were those reported in a recent meta-analysis of fMRI studies on spatial

attention

In the same session of rTMS, EEG data were recorded (BrianAmp; bandpass, 0.05-100Hz,

sampling rate, 256 Hz) from 27 EEG electrodes placed according to an augmented 10-20 system

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(EEG cap resistant

to magnetic pulses). The artifact of magnetic

stimulation on the EEG activity

lasted about 10 ms after the rTMS period (Supplementary figure 3a). The EEG single trials

contaminated by eye movement, blinking, or involuntary motor acts were rejected off-line. To

remove the effects of the electric reference, EEG single trials were re-referenced to common

average reference. On average, the artifact-free EEG segments for each condition were 92 (± 11) .

For the EEG spectral analysis, the frequency bands of interest were low- and high-frequency

alpha (Supplementary figure 3b). The low-frequency alpha was defined as the frequencies from the

peak of individual alpha frequency (IAF Klimesch, 1998) to IAF-2 Hz; the high-frequency alpha was

defined as the frequencies from IAF to IAF+2 Hz. For both frequency bands, the alpha ERD/ERS

(%) was computed as follows:

ERD/ERS = (E R)/R x 100,

where E indicates the power density at the "event" period (from 0.5 to 1.5 s after the cue stimulus),

and R indicates the power density at the "rest" period (from -1.5 to -0.5 s before the cue stimulus).

For the analysis of both behavioral data and anticipatory alpha ERD/ERS, ANOVAs for

repeated measures were used. Mauchley's test evaluated the sphericity assumption of the

ANOVA. Green-house-Geisser procedure served for the correction of the degrees of freedom.

Duncan test was used for post-hoc comparisons (alpha, p<0.05). To test the relationship between

anticipatory alpha ERD/ERS and behavioral indexes (RT, accuracy), correlation analysis was

performed (Pearson test, p<0.05).

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Table legend

Table 1. Mean and standard error of reaction time (ms) and accuracy (%) in the four rTMS

conditions for valid and invalid trials and target location.

Figure legends

Figure 1. (a): Sequence of events during a trial. (b): Magnetic resonance imaging (MRI)-

constructed stereotaxic template showing the sagittal (a), coronal (b), and axial (c) projections of

the three rTMS sites on the right hemisphere.

Figure 2. (a): Group means (± standard error, SE) of the reaction time (ms) for the valid and invalid

trials. Duncan post-hoc tests: one (p<0.001) or two asterisks (p<0.0001). (b): Group means (±

standard error, SE) of the accuracy (%) for the valid and invalid trials.

Figure 3. (a): Topographic maps of anticipatory low and high alpha ERD/ERS during the cue period

(+500-2000 msec after the onset of the cue). (b): Group means (± standard error, SE) of the low

alpha ERD/ERS. Duncan post-hoc tests: one (p<0.05) or two asterisks (p<0.001). (c): Group

means (± standard error, SE) of the high alpha ERD/ERS.

Figure 4. (a): Scatterplot showing the (positive) linear correlation between anticipatory low alpha

ERD/ERS at P3 electrode and reaction time, for right "IPS" condition normalized with Sham

condition. (b): Scatterplot showing the (positive) linear correlation between anticipatory high alpha

ERD/ERS at O1 electrode and reaction time, for right "IPS" condition normalized with Sham

condition.

Figure 5. Group means (± standard error, SE) of the high alpha ERD/ERS for the four Conditions

(Sham, Right PrCe, Right FEF, Right IPS) divided by Hemisphere (contra or ipsi to cue stimulus).

Nature Precedings : hdl:10101/npre.2008.1563.1 : Posted 1 Feb 2008

1/31/08 12:10 PM

Tab. 1.

VALID TRIALS

RIGHT TARGET

LEFT TARGET

Sham

Right PrCe

Right FEF

Right IPS

Sham

Right PrCe

Right FEF

Right IPS

Reaction time (ms)

mean

478.8 474.8 511.9 531.7 485.7 478.0 525.4 538.6

S.E.

29.4 29.2 30.2 31.5 29.7 28.2 31.6 30.7

Accuracy (%)

mean

92.8 92.7 89.3 88.5 91.6 90.3 89.6 88.0

S.E.

1.2 1.4 1.2 1.9 1.2 1.9 1.6 1.7

INVALID TRIALS

RIGHT TARGET

LEFT TARGET

Sham

Right PrCe

Right FEF

Right IPS

Sham

Right PrCe

Right FEF

Right IPS

Reaction time (ms)

mean

514.5 515.2 553.1 566.5 535.0 538.4 596.1 599.6

S.E.

31.5 33.9 32.0 29.4 27.7 29.1 37.8 35.0

Accuracy (%)

mean

91.3 87.2 83.9 85.0 88.6 85.6 81.0 82.9

S.E.

1.8 2.4 1.9 1.8 1.9 1.9 1.7 2.4

Nature Precedings : hdl:10101/npre.2008.1563.1 : Posted 1 Feb 2008

1/31/08 12:10 PM

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