Hemispheric Asymmetry in the Remapping and - IA de Investigación especializada en el MIT

Asimetría hemisférica en la remapeo y
Maintenance of Visual Saliency Maps: A TMS Study

Martijn Gerbrand van Koningsbruggen1, Shai Gabay2, Ayelet Sapir1,
Avishai Henik2, and Robert D. Rafal1

Abstracto

■ Parietal cortex has been implicated in the updating, after eye
movimientos, of a salience map that is required for coherent visual
experience and for the control of visually guided behavior. El
current experiment investigated whether TMS over anterior intra-
parietal cortex (AIPCx), just after a saccade, would affect the ability
to update and maintain a salience map. In order to generate a
salience map, we employed a paradigm in which an uninforma-
tive cue was presented at one object in a display to generate in-
hibition of return (IOR)—an inhibitory tag that renders the cued
object less salient than others in the display, and that slows sub-
sequent responses to visual transients at its location. Following
the cue, participants made a saccade to either left or right, y
we then probed for updating of the location of IOR by measuring

manual reaction time to targets appearing at cued location of the
cued compared to an uncued object. Between the time of saccade
initiation and target appearance, dual-pulse TMS was targeted
over right (Experimento 1) or left AIPCx (Experimento 2), y un
vertex control side. Updating of the location of IOR was elimi-
nated by TMS over right, but not the left, AIPCx, suggesting that
right parietal cortex is involved in the remapping of IOR. Re-
mapping was eliminated by right AIPCx, independientemente de si
the saccade was made to the left (contralateral), or right (ipsi-
lateral) visual field, and regardless of which field the target ap-
peared in. We conclude that right AIPCx is the neural substrate
for maintaining a salience map across saccades, and not simply
for propagating an efference copy of saccade commands. ■

INTRODUCCIÓN

Although the retinal input changes dramatically with every
eye movement, our visual experience is coherent. Este
consistency is hypothesized to be achieved by a remapping
mechanism that uses corollary discharge as an “extra-retinal
signal” to compensate for each saccade (verano & Wurtz,
2008). This remapping mechanism integrates information
across successive fixations into a spatial consistent percept.
The current experiments investigated the role of human
parietal cortex in remapping visual saliency maps by apply-
ing TMS just after an eye movement.

Duhamel, Colby, and Goldberg (1992) reported the first
neurophysiological evidence of neurons in monkey lateral
intraparietal (LIP) cortex that remapped their receptive
fields either before or after eye movements. During a task
requiring continuous fixation, neurons in LIP only respond
to visual stimuli presented within their retinotopic recep-
tive field. Sin embargo, in an experiment that involved eye
movimientos, in which a stimulus was presented outside
a neuronʼs receptive field, and in which the monkey was
instructed to make a saccade which would bring the stimu-
lus into the receptive field, a subset of the LIP neurons
responded to stimuli at the location of the future receptive

1Bangor University, Reino Unido, 2Ben-Gurion University of the Negev,
Beer-Sheva, Israel

field before saccade initiation. Subsequent studies have
reported neurons with similar properties in monkey su-
perior colliculus (Caminante, Fitzgibbon, & Goldberg, 1995),
frontal eye field (FEF; Umeno & Goldberg, 1997, 2001),
striate, and extrastriate cortex (Nakamura & Colby, 2002).
More important to the current investigation, Duhamel,
Colby, et al. (1992) and Duhamel, Goldberg, Fitzgibbon,
Sirigu, and Grafman (1992) also observed LIP neurons
that responded to “remembered” targets. When a briefly
flashed stimulus was presented outside their receptive
fields before a saccade, the neurons responded after the
saccade brought this location into their receptive field, incluso
though this location no longer contained the stimulus.
Duhamel et al. concluded that visual memory has a retino-
topic representation, which is updated after every saccade.
More recently, it has been shown that LIP neurons do not
simply remap visual stimuli but, more specifically, remap
the saliency of the visual stimulus (Gottlieb, Kusunoki, &
Goldberg, 1998).

There is converging evidence implicating human parietal
cortex in saccade updating from neuropsychological, TMS,
and fMRI investigations. Patients with lesions in parietal
cortex are impaired when executing the second saccade
of a double-step saccade task. en esta tarea, two saccades
are made to sequentially flashed targets, each of which dis-
appears before the first eye movement. The first saccade can
be made on the basis of retinotopic coordinates. Sin embargo,

Revista de neurociencia cognitiva 22:8, páginas. 1730–1738

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an accurate second saccade requires updating of the loca-
tion of the second target based on the motor vector of the
first saccade. Failure to update the location faithfully results
in inaccurate saccades to the second target or, if no extra-
retinal signal is generated at all, the second saccade either
cannot be executed at all, or will be made to the retinal
location of the target. In a task in which the two targets
were presented in opposite visual fields, patients with
both left and right parietal lesions were impaired in the
second saccade when the first was directed contralesionally
(Heide, Blankenburg, Zimmermann, & Kompf, 1995). Re-
cent fMRI studies have confirmed and extended the involve-
ment of parietal cortex in spatial updating (Medendorp,
Goltz, & Vilis, 2005, 2006; Medendorp, Goltz, Vilis, &
Crawford, 2003; Merriam, Genovese, & Colby, 2003).

Several TMS studies have investigated the role of parietal
cortex in remapping. Because the current study uses TMS,
these studies are discussed in more detail below. camioneta
Donkelaar and Muri (2002) found that right parietal TMS
150 mseg, but not earlier, after the onset of the first saccade
of a double-step paradigm impaired accuracy of the second
saccade. Right TMS only impaired performance if the first
saccade was to the left and the second saccade to the right.
morris, Chambers, and Mattingley (2007) used a more focal
figure-of-eight coil and found that a posterior part of the
intraparietal sulcus (IPS), close to the transverse occipital
sulcus, and not a more anterior part, was involved in updat-
ing in a variant of the double-step paradigm. Other studies
have found that TMS over parietal cortex also impairs the
detection of displacement of visual targets that moved
during a saccade (Chang & Ro, 2007) and transsaccadic
memory of visual feature (Prime, Vesia, & Crawford, 2008).
In an experiment motivating the current research, Sapir,
Hayes, Henik, Danziger, and Rafal (2004) demonstrated
that human parietal cortex is also involved in updating
visual saliency maps across eye movements. To generate
a salience map, the experiment employed an paradigm in
which an exogenous cue engendered an inhibitory tag
at the location of the cue, resulting in slower responses
to targets presented at the previously cued location (inhibi-
tion of return, IOR; posner, Rafal, Choate, & Vaughn, 1985).
IOR has been hypothesized to contribute to the elaboration
of a salience map that can guide efficient visual exploration
by favoring novel locations (Klein, 1988, 2000; Posner et al.,
1985). Sapir et al. (2004) exploited the fact that the location
of this inhibitory tag is updated after a saccade (Tipper,
Grison, & Kessler, 2003; Danziger, Fendrich, & Rafal, 1997;
Maylor & Hockey, 1985; posner & cohen, 1984).

In the IOR paradigm employed by Sapir et al. (2004), uno
of four boxes was briefly cued to generate an inhibitory tag
y, after a saccade was made to a new location, a target
requiring a manual detection response was presented at
either the retinal location of the cue, the environmental
location of the cue, or at corresponding uncued locations.
They tested five patients with a unilateral lesion involving
superior parietal cortex and healthy controls. Healthy con-
trol participants showed inhibitory tagging (IOR) at the re-

mapped, environmental location of the cue, as well as a
smaller inhibitory effect at the retinal location. The patientsʼ
results revealed no evidence of updating the location of the
inhibitory tag, eso es, IOR was observed only at the retinal
location of the cue.

In contrast to the results of double-step saccade para-
digms summarized above, the deficit in remapping was bi-
lateral; eso es, it occurred for targets in both the ipsilesional
and contralesional visual field, and after both ipsilesional
and contralesional saccades. Curiosamente, abolished re-
mapping of the inhibitory tag was found in the three pa-
tients with a right hemisphere lesion but not in the two
left hemisphere patients. Sin embargo, due to the small sam-
ple size, this was not statistically tested. Sapir et al. (2004)
interpreted their results to indicate that parietal cortex
was not simply the source of the corollary discharge that
provides the extra-retinal signal for saccade remapping,
but that it may also provide the neural substrate for main-
taining a salience map across saccades.

The patients studied by Sapir et al. (2004) all had chronic
lesiones. It is not clear whether the effects reported in those
patients reflect the normal function of parietal cortex, o
are the consequence of brain reorganization. Además,
Sapir et al. studied only two patients with left parietal
lesions and three with right parietal lesions, and therefore,
could not draw definitive conclusions about possible hemi-
spheric asymmetries for maintaining salience maps. Aquí
we employed dual-pulse TMS to transiently disrupt the
function of parietal cortex, and to compare the effects of
right and left parietal TMS in order to test for a hemispheric
asymmetry in two experiments: In Experiment 1, TMS was
applied over right parietal cortex, whereas TMS was given
over left parietal cortex in Experiment 2. The parietal stimu-
lation site, over superior parietal cortex, corresponded to
the area of lesion overlap in the patients studied by Sapir
et al. A TMS vertex control site was also stimulated in
each experiment. The timing of the TMS pulses, 150 y
250 msec after saccade onset, was based on the observa-
tions of van Donkelaar and Muri (2002).

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MÉTODOS

Participantes

Fourteen subjects (9 women) participated in Experiment 1
in which TMS was applied over either right parietal cortex,
or the vertex. A different group of 14 subjects (7 women;
mean age) participated in Experiment 2 in which TMS
was applied over either left parietal cortex, or the vertex. Six
subjects of (3 of whom had participated in Experiment 1,
the other 3 participated in Experiment 2) participó
also in a control experiment in which inhibitory tagging
without eye movement was tested. Written informed con-
sent was obtained from each participant. Además, sub-
jects filled in a safety screening questionnaire for TMS
(Keel, Herrero, & Wassermann, 2001). Ethics approval was

van Koningsbruggen et al.

1731

obtained from the School of Psychology at the Bangor
Universidad, Reino Unido. Participants received £10/hour for their
participación.

Apparatus

A limbus tracker (ASL 210, Bedford, MAMÁ) was used to
monitor horizontal eye position at a rate of 1000 Hz.
The eye movement recording device was calibrated by
a three-point calibration every 20 ensayos. A chin and cheek
rest was used to reduce head movements. The analogue
output of the eye tracker was processed on-line to deter-
mine the onset of saccades. When the velocity of saccades
reached 50°/sec, a TTL pulse was sent to stimulus PC which
recorded the saccadic latency and direction. Próximo, the stim-
ulus PC send out two TTL pulses to the TMS stimulator to
trigger the dual TMS pulse. On each trial, two TMS pulses
were given, 150 y 250 msec after the onset of the eye
movimiento. Presentation software (Neurobehavioral Sys-
tems, Albany, California) was used for stimulus presentation
and triggering of the TMS machine. Stimuli were presented
on an IIyama vision master pro 512 monitor (200 Hz). A
response device connected to the game port was used to
record manual reaction times (RTs).

Transcranial Magnetic Stimulation

A MagStim Super Rapid with a 70-mm figure-eight coil was
used for the TMS. The hand area of motor cortex was first
localized in the left hemisphere. The motor threshold then
was determined by finding the minimum amount of TMS
intensity that was required to elicit a visible hand twitch in
the relaxed right hand. Stimulation was set to 120% del
MONTE. All subjects participated in two sessions, separated by
al menos 1 week. In Experiment 1, subjects received TMS
over either the vertex (control site) or a right parietal loca-
tion that was 3 cm to the right and 4 cm posterior relative
to the vertex, with the order of TMS location counter-
balanced across subjects. In Experiment 2, subjects re-
ceived TMS over either the vertex, or a left parietal site
that was 3 cm to the left and 4 cm posterior relative to the
vertex. A similar criterion for parietal cortex stimulation
has been used in previous investigations (Chang & Ro,
2007; Kapoula, Cual, Coubard, Daunys, & Orssaud, 2004,
2005; van Donkelaar & Muri, 2002). All subjects were naive
to the purpose of the study and location of stimulation.
Vertex stimulation and parietal stimulation locations were
relatively close to each other, and only one location was
stimulated in each session, subjects did not report feeling
any differences between sessions.

Procedimiento

The experiment was conducted in a dimly lit room. The dis-
tance between the monitor and the subjects was 57 cm. El
stimulus display consisted of three small white fixation
puntos (0.1° × 0.1°) on a black background, one presented

in the center, and the other two presented 10° to the right
or left of the center. A white unfilled box (3° × 3°) was pre-
sented 5° above and below each fixation point. The six
boxes and the two peripheral fixation points were pre-
sented throughout the experiment. The stimulus display
and the trial structure are shown in Figure 1.

Each trial began with the onset of a central fixation
punto. If the subject did not fixate at the central fixation
point within 250 mseg, the trial was aborted and an error
sound was presented. Después 1000 mseg, a noninformative
cue was presented in one of the midline boxes, either
above or below the central fixation. The cue was a thicken-
ing of the line for 200 mseg. A right or left arrow (1°) era
presented at central fixation 300 msec after cue offset. El
arrow was presented for 200 mseg. Subjects were in-
structed to move their eyes as fast as possible in the direc-
tion of the arrow toward either the left or right peripheral
fixation point. If subjects made a saccade in the wrong
direction, or did not make a saccade within 500 mseg,
the trial was aborted and an error sound was presented.
Following the eye movement, subjects were required to
keep fixation at the indicated peripheral fixation point.
Después 700 o 900 mseg, a target was presented either above
or below the central fixation point (es decir., a SOA of either
700 o 900 mseg). The target was presented until the sub-
ject responded by pressing a button with their right index
finger, or for 1000 mseg (ver figura 1 for a graphical illus-
tration of the trial structure). Although both the cue and
targets were always presented in the box above, or below
initial central fixation, there were an additional four boxes.
The additional boxes were presented because pilot testing
revealed that this led to a reliable remapped IOR. Following
a training session of 20 ensayos, a total of 176 trials were pre-
enviado, con 10% catch trials. Catch trials were exactly the
same as the other trials (es decir., including TMS), except that no
target was presented.

All subjects participated in two sessions: one session
with either right parietal TMS (Experimento 1) or left parie-
tal TMS (Experimento 2), and one with TMS over the vertex.
Each session took around 60 mín., and the order of sessions
was counterbalanced across subjects. The intertrial interval
was set to 4000 mseg, in order to make sure that the time
between two successive TMS trains was never shorter than
5000 msec to conform with safety guidelines (Wassermann,
1998; Chen et al., 1997). Sapir et al. (2004) probed for IOR
at both retinal and environmental locations. Sin embargo,
because of the long intertrial interval required, in the cur-
rent study the TMS sessions were 60 min long, and it was
not practical to test for both retinal and environmental
IOR. Por lo tanto, we only tested environmental IOR in this
experimento.

RESULTADOS

TMS Location

Because the stimulation site was based on skull landmarks
(3 cm lateral and 4 cm posterior to the vertex, we acquired

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Revista de neurociencia cognitiva

Volumen 22, Número 8

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Cifra 1. Trial structure
and stimulation sequence
for a cued target with a saccade
to the right between the
cue and target presentation.
Note that the colors are
inverted for illustration
purposes.

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a T1-weighted anatomical MRI scan of six subjects (4 de
Experimento 1) to more precisely specify the anatomical
location target with TMS in a sample of our subjects. Irre-
spective of the experiment in which the subject had partic-
ipated, a marker (vitamin E capsule) was placed over both
the right and left parietal stimulation side prior to the MRI
scan. Brainsight Software was used to process the MRI
scans. Cifra 2 shows that the parietal TMS was over the
rostral superior parietal lobule, including the anterior part
of the IPS. This is in accordance with region of maximum
overlap in the Sapir et al. (2004) estudiar.

Results Experiment 1

Errores

There were two different types of errors subjects could
make: an eye movement error, or a manual keypress error.
A failure to keep fixation at the center, a blink, an eye move-
ment which was not in the right direction or was too slow
(>500 msec), or a failure to keep fixation at the peripheral
fixation point after a successful eye movement were
all classified as eye movement errors. We used such a strict
criterion as TMS was given relative to the saccade onset.
Subject made an average of 6.5% eye movement errors,
which did not differ between TMS conditions (right parietal,
or vertex), saccade direction ( left or right), or the inter-
action between these two (F < 1). All trials with a saccade error were aborted. Responses faster than 90 msec or slower than 750 msec were all classified as keypress errors, and omitted from the analyses. Subjects made a very small number of manual keypress errors (1.5%), and were there- fore not further analyzed. Catch trials were omitted from the analyses as well. Saccadic Reaction Times The overall mean saccadic RT was 306 msec (SD = 24 msec). Thus, on average, the two TMS pulses were given 456 msec and 556 msec after the onset of the arrow (i.e., 150 and 250 msec after the saccade onset). Mean saccade RTs were computed for each participant in each condition and were analyzed with a repeated measures analysis of variance (ANOVA) with TMS condition (right parietal or vertex) and saccade direction (left or right) as factors. TMS did not affect saccade latencies [F(1, 13) < 1]. The interaction between TMS condition and saccade direction was also not significant [F(1, 13) < 1]. However, the leftward directed saccades were significantly faster (302 msec) than rightward directed saccades (309 msec) [F(1, 13) = 7.48, p < .05, ηp 2 = .37]. Although the difference was statistically reliable, it was only 7 msec, that is, the TMS pulses were almost given at the same time for left and right saccades. Manual Reaction Times Anticipatory responses (faster than 90 msec) and slow re- sponses (slower than 750 msec) were excluded from the analysis. Note, that if subjects did not execute the saccade correctly, the trial would have been aborted. Mean RT for each subject in each condition was computed and analyzed in a repeated measures ANOVA with TMS condition (right parietal or vertex), saccade direction (left or right), cue (pre- viously cued or uncued box), and SOA (700 or 900 msec) van Koningsbruggen et al. 1733 as within-subject factors. There were only two significant effects. RTs were slower [F(1, 13) = 7.24, p < .05, ηp 2 = .36] for cued targets (296 msec) than for uncued targets (291 msec), that is, there was a significant IOR. As shown in Figure 3, the interaction between cue and TMS location was also significant [F(1, 13) = 24.72, p < .01, ηp 2 = .66], in- dicating that the site of TMS affected IOR. Two pairwise comparisons were performed to investi- gate the interaction between cue (previously cued or un- cued) and TMS location (vertex or right parietal). There was a significant effect of cue on RTs during vertex stimula- tion [t(13) = 5.64, p < .001], that is, there was a significant IOR of 11 msec. However, when TMS was administered over right parietal cortex, there was no significant differ- ence in RT for cued and uncued targets (t < 1). No other effects were significant, including the inter- action between TMS × Cue × Saccade direction (F < 1), indicating that the remapping impairment induced by right parietal stimulation was independent of the direction of the eye movement. Results Experiment 2 Errors Subject made an average of 6.7% eye movement errors, which did not differ between TMS condition, saccade direc- tion, or the interaction between these two (F < 1). Subjects made a very small number of manual keypress errors (1.9%), and were therefore not further analyzed. Saccadic Reaction Times Figure 2. The 3-D-rendered structural MRI scans of the six scanned subjects. On each scan, the two possible TMS locations are marked: 4 cm posterior and 3 cm to the right and left relative to the vertex. The overall mean saccadic RT was 335 msec (SD = 39 msec). Thus, on average, the two TMS pulses were given 485 and 585 msec after the onset of the arrow, that is, 150 D o w n l o a d e d l l / / / / j f / t t i t . : / / f r o m D h o t w t n p o : a / d / e m d i f t r o p m r c h . s p i l d v i e r e r c c t . h m a i r e . d u c o o m c / n j a o r c t i n c / e a - p r d t i 2 c 2 l 8 e - 1 p 7 d 3 f 0 / 1 2 9 2 3 / 9 8 4 / 8 1 9 7 o 3 c 0 n / 1 2 0 7 0 7 9 0 2 2 1 1 4 3 5 / 6 j o p c d n . b y 2 0 g 0 u 9 e . s t 2 o 1 n 3 5 0 6 7 . S p e d p f e m b y b e g r u 2 0 e 2 s 3 t / j . / f t . . o n 1 8 M a y 2 0 2 1 Figure 3. The mean manual RT for cued (gray) and uncued (black) targets for each TMS location. The data for Experiment 1 (right parietal and vertex TMS) are on the left. The data for Experiment 2 (left parietal and vertex TMS) are on the right. Error bars reflect within-subjects standard error of the mean (Loftus & Masson, 1994) calculated for each experiment separately. 1734 Journal of Cognitive Neuroscience Volume 22, Number 8 and 250 msec after the saccade onset. Mean saccade RT was computed for each subject in each condition and ana- lyzed with a repeated measures ANOVA with TMS (left pari- etal or vertex) and saccade direction (left or right) as within-subject factors. There were no significant effects (F < 1 in all cases). Manual Reaction Times Mean manual RTs for each subject in each condition were computed and analyzed in a repeated measures ANOVA, with TMS (left parietal or vertex), saccade direction (left or right), cue (previously cued or uncued box), and SOA (700 or 900 msec) as within-subject factors performed to study the effects of left parietal TMS. RTs were slower RTs for cued targets (305 msec) than for uncued targets (290 msec), indicating that there was a significant IOR of 15 msec [F(1, 13) = 19.45, p < .01, ηp 2 = .6]. IOR was larger at the short SOA (21 msec) than at the long SOA (9 msec) [F(1, 13) = 7.01, p < .05, ηp 2 = .35]. There was also a significant interaction between Sac- cade direction × TMS [F(1, 13) = 5.61, p < .05, ηp 2 = .30]. In order to study this interaction, four pairwise com- parisons were conducted. RTs were significantly faster after a saccade to the left (280 msec) than after a saccade to the right (289 msec) when left parietal TMS was admin- istered [t(13) = 5.96, p < .01]. There were no other sig- nificant effects. Most important, the interaction between TMS × Cue was not significant (F < 1), suggesting that TMS to the left parietal and TMS to the vertex have simi- lar effects. Figure 3 shows that there is a significant IOR after left parietal TMS, which is comparable to that ob- served after control stimulation at the vertex; that is, left parietal TMS does not influence the remapping of the inhibitory tag. Comparing the Results of Experiments 1 and 2 Two different ANOVAs were performed to compare the effects of right and left PPC TMS, with experiment as a between-subjects factor. One ANOVA compared the effect of vertex TMS for both experiments, whereas the other ANOVA compared the effect of parietal TMS for both ex- periments. The reason for comparing the vertex stimula- tion between experiments was to determine whether there is a baseline difference between the groups. The mixed effect repeated measures ANOVA with experiment (1 or 2) as a between-subjects factor, and saccade direction (left or right), cue (previously cued or uncued box), and SOA (700 or 900 msec) as within-subject factors revealed only a significant effect of cue [F(1, 26) = 20.91, p < .01, ηp 2 = .45], reflecting longer latencies for targets at cued (307 msec) than at uncued (294 msec) locations. There were no other significant effects, including no main effect of experiment, or interactions with the experiment factor. Thus, the groups in Experiments 1 and 2 did not differ from each other in the vertex condition. The same ANOVA was performed for parietal TMS. There was a significant effect of cue [F(1, 26) = 8.10, p < .01, ηp 2 = .24] and a significant Cue × Experiment inter- action [F(1, 26) = 9.70, p < .01, ηp 2 = .27]. The source of this interaction was examined by comparing the size of IOR for both experiments. As expected, the size of the IOR was significantly larger in Experiment 2 ( left parietal TMS; 16 msec) than in Experiment 1 (right TMS; −1 msec) [t(26) = 3.11, p < .01]. The effect of saccade direction was also significant [F(1, 26) = 5.05, p < .05, ηp 2 = .16], as was the interaction between saccade direction and ex- periment [F(1, 26) = 6.52, p < .05, ηp 2 = .20]. Follow-up t test found that there was no effect of saccade direction in Experiment 1 (right parietal TMS; RT was 297 msec inde- pendent of saccade direction). However, in Experiment 2 Figure 4. The mean size of IOR (thick black line) and individual subject data (thin gray lines). The data for Experiment 1 are on the left, and for Experiment 2 on the right. D o w n l o a d e d l l / / / / j t t f / i t . : / / f r o m D h o t w t n p o : a / d / e m d i f t r o p m r c h . s p i l d v i e r e r c c t . h m a i r e . d u c o o m c / n j a o r c t i n c / e a - p r d t i 2 c 2 l 8 e - 1 p 7 d 3 f 0 / 1 2 9 2 3 / 9 8 4 / 8 1 9 7 o 3 c 0 n / 1 2 0 7 0 7 9 0 2 2 1 1 4 3 5 / 6 j o p c d n . b y 2 0 g 0 u 9 e . s t 2 o 1 n 3 5 0 6 7 . S p e d p f e m b y b e g r u 2 0 e 2 s 3 t / j . t / . . f o n 1 8 M a y 2 0 2 1 van Koningsbruggen et al. 1735 (left parietal TMS), RTs were faster after a saccade to the left (280 msec) than after a saccade to the right (289 msec) [t(13) = 5.96, p < .01]. No other effects were significant. The individual and mean sizes of IOR are displayed in Figure 4. Control Experiment The current result suggests that right parietal TMS impairs remapping of the inhibitory tag regardless of the direction of eye movements. However, the conditions in this study do not allow us to rule out the possibility that right parietal TMS abolishes IOR in general and not only the remapping of the inhibitory tag. Sapir et al. (2004) also presented tar- gets at retinal cued locations, for which no remapping was required. Like the healthy controls, the patientsʼ RTs were slower for the cued retinal location. This finding demon- strated that patients had a normal IOR, but that this IOR was lost when they were required to remap the inhibitory tag. Because there were no such targets presented at the retinal location of the cue in the current experiment (i.e., subjects were always required to remap the inhibitory tag), we performed a control experiment in a few partici- pants, in which no remapping was required. The procedure was identical, except that subjects were not required to make an eye movement. Instead of an arrow, an equal sign of the same size was presented, and subjects were instructed to maintain central fixation. The TMS pulses were given relative to their mean saccadic RTs of the previous experiment. We recruited six subjects who had participated in either Experiment (3 had participated in Experiment 1 and the other 3 in Experiment 2). They par- ticipated in one vertex and one right parietal TMS session. RTs were subject to a 2 (TMS) × 2 (cue) × 2 (SOA) re- peated measures ANOVA. The main effect of cue was signifi- cant [F(1, 5) = 16.43, p = .01, ηp 2 = .77], reflecting the slow RTs to valid than for invalid trials (i.e., IOR). There was no interaction between TMS site and cue, and a paired-samples t test confirmed that there was no significant difference in the size of IOR during vertex stimulation (11 msec) and parietal stimulation (10 msec) [t(5) = 0.16, p = .88]. This result confirms that right parietal TMS does not influence IOR when there is no need to update the saliency map. DISCUSSION The results of these experiments converge with those re- ported in neurological patients (Sapir et al., 2004), implicat- ing the rostral superior parietal lobule in updating saliency maps after eye movements. They also demonstrate a hemi- spheric asymmetry in representing salience maps. TMS over the right, but not the left, rostral superior parietal lobule prevented remapping of the inhibitory tag after either left or right saccades. This remapping deficit was regardless of whether the target appeared in the field ipsi- lateral or contralateral to the right parietal stimulation site. Our results also converge with another recent TMS study reporting that stimulation over the right, but not left, hemi- sphere, at a more dorsal site over the IPS than the one used here (i.e., at the P3 electrode site), disrupted transsaccadic working memory (Prime et al., 2008). As was the case in the case of the patients studied by Sapir et al. (2004), the absence of environmental IOR was a result of a slower detection RT at invalidly cued locations. There was no difference between right parietal cued, right parietal uncued, and vertex cued targets. One possible explanation for this effect is that the cued location has a reduced saliency, and that TMS impaired the updating of the whole saliency map, resulting in lower saliency and longer RTs for all possible target locations. Another possi- bility is that IOR occurs because the other target location becomes more salient, and that this benefit has been disrupted. Chang and Ro (2007) showed that TMS over right parie- tal cortex impaired perisaccadic displacement detection. Performance was only affected when the probe was pre- sented in the left visual field, subjects were required to make a contralateral saccade, and TMS was given just before the saccade. They hypothesized that the reason that TMS affects perception is that TMS introduces external noise into the PPC representation. In the current study, the absence of a remapped inhibitory tag might be caused by that TMS-introduced noise into the parietal representa- tion as Chang and Ro (2007) hypothesized. When subjects were not required to make eye movements (control experi- ment), or TMS was applied over left PPC, the inhibitory tag was remapped, making it less likely that TMS introduces just noise. To further investigate this issue, it would be in- teresting to study whether right PPC TMS affects retinal IOR. However, patients with a parietal lobe lesion show preserved retinal IOR. This further supports the idea that parietal lobe disruption interferes with remapping rather than just degrading location information. The TMS pulses were given 150 and 250 msec after the onset of the eye movement. This time interval was chosen based on previous research indicating that this is the critical time of spatial updating in an ERP study (Bellebaum, Hoffmann, & Daum, 2005), in single-unit recordings (Gottlieb et al., 1998; Duhamel et al., 1992), and in previous studies using the double-step saccade paradigm (Morris et al., 2007; van Donkelaar & Muri, 2002). Although, no other time points were tested, it is interesting to note that there was no effect of SOA (700 or 900 msec) in right parietal TMS group. This indicates that once the representation of the inhibitory tag is affected by TMS, it cannot be regained. Further research is needed to definitively specify the critical time that TMS must be applied to disrupt remapping. Like the patient study of Sapir et al. (2004), but unlike previous patient (Heide & Kompf, 1998; Heide et al., 1995; Duhamel et al., 1992) and TMS (Morris et al., 2007; van Donkelaar & Muri, 2002) studies employing the double- step saccade paradigm, disruption of remapping occurred when saccades were directed toward the ipsilateral as well as contralateral fields. In double-step saccade studies, the deficit has been observed only when saccades were directed 1736 Journal of Cognitive Neuroscience Volume 22, Number 8 D o w n l o a d e d l l / / / / j t t f / i t . : / / f r o m D h o t w t n p o : a / d / e m d i f t r o p m r c h . s p i l d v i e r e r c c t . h m a i r e . d u c o o m c / n j a o r c t i n c / e a - p r d t i 2 c 2 l 8 e - 1 p 7 d 3 f 0 / 1 2 9 2 3 / 9 8 4 / 8 1 9 7 o 3 c 0 n / 1 2 0 7 0 7 9 0 2 2 1 1 4 3 5 / 6 j o p c d n . b y 2 0 g 0 u 9 e . s t 2 o 1 n 3 5 0 6 7 . S p e d p f e m b y b e g r u 2 0 e 2 s 3 t / j t / . f . . o n 1 8 M a y 2 0 2 1 contralateral to the disrupted cortex. The current results suggest that parietal cortex is not simply responsible for generating an extra-retinal signal necessary for updating a salience map of the visual field, but that right parietal cortex is critical for maintaining a durable, transsaccadic representa- tion of that map across the visual field. This interpretation of the current results is consistent with observations from neurophysiological recording in LIP of nonhuman primates, demonstrating that this area is con- cerned specifically with remapping of objects that are salient by virtue of either a recent appearance or because they are designated as targets of visual search (Gottlieb et al., 1998). Moreover, updating of the receptive fields of LIP neurons is independent of whether the saccade is directed ipsi- lateral or contralateral to the neuronʼs receptive field, and whether the object is updated within or between hemi- spheres (Heiser & Colby, 2006). It is possible that separate regions of the IPS may be responsible for generating the extra-retinal signal and for maintaining a remapped representation. A recent TMS study (Morris et al., 2007), using an adaptation of the double-step saccade paradigm, reported inaccurate second saccades after stimulation of a posterior area of right pa- rietal cortex, but not after TMS of a more rostral site that approximated the region stimulated in the current investi- gation. We might speculate that the more posterior part of parietal cortex is necessary for generating an extra-retinal signal, such that its inactivation only affects performance after contralateral saccades, whereas more anterior parts of right parietal cortex maintain durable representation of the remapped salience map after a saccade in either direc- tion. However, it is notable that the effect specific to PPC in the Morris et al. (2007) experiment was an increase in variability in the second saccade end point, suggestive perhaps of a degraded representation of the location of the second target. There was no evidence that TMS of this site resulted in saccades to the retinal location of the second target, as might be expected if TMS prevented the generation of a critical extra-retinal signal. Further TMS experiments, over the more posterior site examined by Morris et al., using the kind of paradigm used here, or the transsaccadic memory paradigm employed by Prime et al. (2008), may seek further evidence for a dissociation of function along parietal cortex that may contribute to up- dating and maintaining salience maps across saccades. A TMS study targeting FEF that examines the remapping of IOR may also be informative. Lesions of the FEF have been reported to not disrupt performance on double-step saccades (Heide et al., 1995). However, parietal cortex receives remapping signals from the colliculo-thalamic- FEF circuit elucidated by Sommer and Wurtz (2006), and these signals may be critical for the encoding of a durable salience map. All previous TMS studies using the double-step saccade paradigm have, to our knowledge, only stimulated the right parietal lobe (Morris et al., 2007; van Donkelaar & Muri, 2002), and further research is needed to clarify whether there may be hemispheric asymmetries in saccade re- mapping in this paradigm. The patient research using the double-step saccade paradigm, reported by Heide et al.’s (1995) lab, does suggest that the left parietal lobe participates in saccade remapping. In a double-step saccade task, in which the first and second targets occurred in opposite visual fields, patients with left parietal lesions did show a deficit, although patients with right parietal lesions were more impaired. fMRI studies have not revealed hemispheric updating asymmetries (Medendorp et al., 2003; Merriam et al., 2003): Representations of stimuli presented to the right hemisphere are remapped to the left hemisphere after left saccades, and representations of stimuli pre- sented to the left hemisphere are remapped to the right hemisphere after right saccades. Although there is, then, evidence for a role of both hemi- spheres in saccade remapping, there is also evidence that their contributions may differ. Heide et al. (1995) also tested parietal lesioned patients on a within-hemifield double-step saccade task, in which both targets were pre- sented in the same visual field. In this task, in which no between-hemispheric spatial updating was necessary, an asymmetric effect of right and left parietal lesions was observed. In addition to impaired performance on the between-hemifield task, patients with right parietal lesions also had an impairment in the within-hemifield condi- tion in the left visual field. An ERP study by Bellebaum et al. (2005) also provided evidence for different contri- butions of left and right hemisphere in saccade remapping. Bellebaum et al. reported a larger slow positive wave when remapping was required, starting between 150 and 200 msec after first saccade onset. Source analysis showed that whereas the source was restricted to right PPC in trials with leftward first saccades, left and right PPC were both involved in rightward trials. Further research is needed to specify the circumstances under which left parietal cortex may be involved in up- dating salience maps. Future studies, using the paradigm employed here, will test for hemispheric asymmetries in salience updating when the stimuli to be updated are pre- sented to either the left or right visual field, when vertical saccades are made, and when stimuli must be remapped either within or between hemispheres. In conclusion, these observations converge with those made in neurological patients with chronic lesions of pari- etal cortex implicating this region as a neural substrate for maintaining the spatial constancy necessary for a coherent continuity of visual experience. They also suggest a special role for the right parietal lobe, at least under the condi- tions of the current experiments. The observation that re- mapping was disrupted when saccades were executed toward the field ipsilateral as well as contralateral to cortical disruption suggests that parietal cortex is not involved simply in generating the corollary discharge that provides the extra-retinal signal needed for remapping the visual scene. Rather, the results implicate parietal cortex as a van Koningsbruggen et al. 1737 D o w n l o a d e d l l / / / / j f / t t i t . : / / f r o m D h o t w t n p o : a / d / e m d i f t r o p m r c h . s p i l d v i e r e r c c t . h m a i r e . d u c o o m c / n j a o r c t i n c / e a - p r d t i 2 c 2 l 8 e - 1 p 7 d 3 f 0 / 1 2 9 2 3 / 9 8 4 / 8 1 9 7 o 3 c 0 n / 1 2 0 7 0 7 9 0 2 2 1 1 4 3 5 / 6 j o p c d n . b y 2 0 g 0 u 9 e . s t 2 o 1 n 3 5 0 6 7 . S p e d p f e m b y b e g r u 2 0 e 2 s 3 t / j f / . . t . o n 1 8 M a y 2 0 2 1 neural substrate that uses the extra-retinal signal to main- tain a continuous salience map across saccades. Acknowledgments This work was supported by the Wellcome Trust (grant 079886). Reprint requests should be sent to Martijn Gerbrand van Koningsbruggen, School of Psychology, Brigantia Building, Penrallt Road, Bangor, Gwynedd LL572AS, UK, or via e-mail: Martijn_van_ koningsbruggen@hotmail.com. REFERENCES Bellebaum, C., Hoffmann, K. P., & Daum, I. (2005). Post- saccadic updating of visual space in the posterior parietal cortex in humans. Behavioural Brain Research, 163, 194–203. Chang, E., & Ro, T. (2007). Maintenance of visual stability in the human posterior parietal cortex. Journal of Cognitive Neuroscience, 19, 266–274. Chen, R., Gerloff, C., Classen, J., Wassermann, E. M., Hallett, M., & Cohen, L. G. (1997). Safety of different inter-train intervals for repetitive transcranial magnetic stimulation and recommendations for safe ranges of stimulation parameters. Electroencephalography and Clinical Neurophysiology, 105, 415–421. Danziger, S., Fendrich, R., & Rafal, R. D. (1997). 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Electroencephalography and Clinical Neurophysiology, 108, 1–16. 1738 Journal of Cognitive Neuroscience Volume 22, Number 8 D o w n l o a d e d l l / / / / j f / t t i t . : / / f r o m D h o t w t n p o : a / d / e m d i f t r o p m r c h . s p i l d v i e r e r c c t . h m a i r e . d u c o o m c / n j a o r c t i n c / e a - p r d t i 2 c 2 l 8 e - 1 p 7 d 3 f 0 / 1 2 9 2 3 / 9 8 4 / 8 1 9 7 o 3 c 0 n / 1 2 0 7 0 7 9 0 2 2 1 1 4 3 5 / 6 j o p c d n . b y 2 0 g 0 u 9 e . s t 2 o 1 n 3 5 0 6 7 . S p e d p f e m b y b e g r u 2 0 e 2 s 3 t / j . . . f t / o n 1 8 M a y 2 0 2 1 Hemispheric Asymmetry in the Remapping and image

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