As stimulus size increases, motion direction of high-contrast patterns becomes increasingly harder to perceive. This counterintuitive
behavioral result, termed “spatial suppression,” is hypothesized to reflect center–surround antagonism—a receptive field property
these normally suppressed motion signals to reach perceptual awareness. Thus, our hypothesis was that a disruption of MT/V5 should
visual areas were also targeted as a control site. The results supported our hypotheses and showed that disruption of MT/V5 improved
motion discrimination of large, moving stimuli, presumably by weakening surround suppression strength. This effect was specific to
high-contrast stimuli involve MT/V5. Additionally, our findings mimic spatial suppression deficits that are observed in several patient
Center–surround antagonism is a simple, yet powerful recep-
tive field property that is found across sensory modalities,
ranging from vision to electroperception (Tadin and Lappin,
2005a). In vision, center–surround antagonism is typically
manifested as the reduction of a neuron’s firing when the
surround region. Consequently, such neurons respond poorly
to large, uniform stimuli. Theoretical and neurophysiological
work associates this basic mechanism with key neural pro-
cesses, including redundancy reduction, input normalization,
figure-ground segregation and computation of object motion
(Born et al., 2000; Vinje and Gallant, 2000; Schwartz and Si-
moncelli, 2001; Pack et al., 2005).
Despite their omnipresence at the neural level, we have rela-
subjects. In motion perception, it has been proposed that spatial
suppression—a counterintuitive elevation of direction discrimi-
nation thresholds with increasing stimulus size—is a direct per-
ceptual correlate of center–surround antagonism within cortical
area MT/V5 (Tadin et al., 2003). This linking hypothesis is sup-
ported by several studies offering largely correlational evidence.
For example, the dependency of spatial suppression on stimulus
size and eccentricity matches that of center–surround MT/V5
foreshadowed the discovery of contrast-dependent center–sur-
round antagonism in MT/V5 (Pack et al., 2005).
Our first aim was to investigate the hypothesized causal in-
volvement of human MT/V5 in spatial suppression of motion
signals. The assumption was that a disruption of neural mecha-
nisms critically involved in spatial suppression could allow these
normally suppressed motion signals to reach perceptual aware-
ing would reduce spatial suppression and improve motion
the intended effect of MT/V5 disruption would effectively be
the Harvard-Thorndike Clinical Research Center at Beth Israel Deaconess Medical Center [National Center for Re-
TheJournalofNeuroscience,Month??,2011 • 31(xx):xxx-xxx • 1
we used offline 1 Hz TMS—a technique that temporarily atten-
uates normal functioning of the stimulated cortex with an effect
that outlasts the period of stimulation (Boroojerdi et al., 2000;
Battelli et al., 2009). In addition to MT/V5, we targeted early
visual areas (EVA) because they also contain center–surround
neurons (Jones et al., 2001; Shushruth et al., 2009) and make
direct projections to MT/V5 (Born and Bradley, 2005). This ad-
ditional target site is a valuable active control of nonspecific and
indirect effects of TMS.
The feasibility of observing spatial suppression impairments
that are evident as better-than-normal perception of large mo-
populations, including the elderly (Betts et al., 2005, 2009), pa-
tients with schizophrenia (Tadin et al., 2006), and history of de-
comparable to spatial suppression abnormalities that are found
of observed deficits.
We studied six subjects (ages 22–32 years, 1 female) all of whom passed
TMS exclusion criteria (Rossi et al., 2009) and gave written informed
consent (approved by the Beth Israel Deaconess Medical Center’s Insti-
tutional Review Boards). No subject experienced any adverse effects.
attenuate TMS noise.
Selection of coil location for MT/V5 stimulation.For five subjects, we used
functional magnetic resonance imaging (fMRI) MT/V5 localization and
et al., 2006; Battelli et al., 2009) (supplemental Fig. 1, available at www.
jneurosci.org as supplemental material); for the remaining subject,
localized using standard neuroimaging procedures (described below).
These functional images were overlaid on structural brain scans and
coregistered to the subject’s head using Brainsight Frameless stereotaxy
studies demonstrating that left MT/V5 TMS is more effective at causing
appropriate coil location was confirmed by inducing moving phos-
phenes using short trains of 10 Hz stimulation. The TMS coil was held
at a 45° angle.
was localized functionally using phosphene induction (Fernandez et al.,
near the occipital pole targets these early visual areas (Kastner et al.,
left hemisphere 2 cm rostral and 2 cm lateral to the inion. The subjects
then viewed a circle (8° radius) at 9° eccentricity in the right visual field,
corresponding to the large stimulus used in the study (see below). The
experimenter then adjusted the coil location until a subject reported a
the target for TMS of EVA, henceforth “EVA TMS.” The TMS coil was
held in place with its handle facing upward.
TMS stimulation. TMS was administered with a Magstim 2T Rapid
delivering biphasic pulses. Stimulation intensity was 75% of maximal
described locations. Brainsight was used to continuously monitor coil
position and assure consistent targeting (Gugino et al., 2001).
Previous studies have shown that 1 Hz TMS temporarily reduces ex-
citability of the cortex within the stimulated area and that this effect
2004; Allen et al., 2007). The time required to perform the below-
described psychophysical task (?13–16 min) is within that for which 1
Hz TMS has been shown to have lasting effects in parietal regions as well
as in MT/V5 (Hilgetag et al., 2001; Silvanto et al., 2008; Battelli et al.,
we statistically examined trends across three trial blocks following each
TMS session. The rationale was that if the effect of TMS did not outlast
0.74, p ? 0.51).
Center for Biomedical Imaging). Standard procedures were used to lo-
calize MT/V5 (Tootell et al., 1995). Briefly, MT/V5 was localized as the
region on the ascending branch of the inferior occipital sulcus that ex-
hibited the stronger blood oxygenation level-dependent responses dur-
ing blocks of expanding and contracting concentric gratings compared
with the blocks of stationary concentric gratings (supplemental Fig. 1,
available at www.jneurosci.org as supplemental material).
1997) and were shown on a linearized monitor (wide-screen 24 inch
Sony GDM-FW900 CRT, 1024 ? 640 resolution, 120 Hz). Viewing was
and background illumination were 0.01 and 31 cd/m2.
Psychophysical thresholds were measured by adaptive QUEST staircases
uli were drifting gratings (horizontal orientation, 1 cycle/degree, 4°/s, 99%
cosine envelope, whose radius defined the stimulus size (Fig. 1A). For very
brief stimuli (? ? 15 ms), the temporal contrast envelope was Gaussian.
Longer temporal envelopes were trapezoid-like, where flanks were half-
Gaussians and the central portion was set to the maximum contrast. Fine
temporal Gaussians. Stimulus duration was defined as the width at half-
Four stimulus conditions were used (Fig. 1A): two sizes (small, 1.2°
radius, or large, 8° radius) at two stimulus locations (?9° horizontal
eccentricity). The small stimulus size was chosen based on pilot experi-
Lappin, 2005b). The large stimulus was selected to be large enough to
mone, 1987; Raiguel et al., 1995), but small enough not to cross the
location, with its size and location chosen pseudorandomly. Subjects
indicated the perceived direction (up or down) by a key press. Feedback
was provided. The next trial started 800 ms after subjects’ responses.
10 s break. Each block contained 8 interleaved staircases, yielding 2
thresholds estimates for each of 4 conditions. Over 3 blocks, this yielded
which ensured that all trials were completed while the effects of TMS
lasted (see above). Brief stimulus durations (?100 ms) and their unpre-
dictable peripheral location precluded both saccadic and pursuit eye
Each subject completed five sessions (Fig. 1B). The first session was
conducted a day before TMS, and was used as a practice session and to
generate staircase starting points for following sessions. The second ses-
sion was a pre-TMS baseline. The third and fourth sessions were con-
ducted immediately following MT/V5 and EVA TMS (order of
a post-TMS baseline. To prevent carryover effects, there was at least a 90
min break between sessions.
2 • J.Neurosci.,Month??,2011 • 31(xx):xxx-xxxTadinetal.•CausalRoleofAreaMT/V5inSpatialSuppression
To measure spatial suppression strength, we used a simple task
where observers discriminated motion direction of brief stimuli.
Thresholds were measured for small (1.2° radius) and large (8°
radius) high-contrast stimuli that were moving either upward or
downward, and presented in either the right or the left visual
field (Fig. 1A). Typically, observers’ direction discrimination
thresholds are considerably higher for large than for small,
moving stimuli—a psychophysical finding described as spatial
suppression (Tadin et al., 2003). To quantify spatial suppres-
sion strength, we introduced the suppression index (SI), de-
fined as the difference of log10thresholds for large and small
stimuli (Tadin et al., 2003, 2006) with higher numbers indi-
cating stronger spatial suppression.
Results from pre-TMS baseline sessions demonstrated strong
spatial suppression (left field SI ? 0.41 ? 0.04, right field SI ?
0.46 ? 0.05), with motion discrimination thresholds for large
(20 ? 3 ms). These results are consistent with previous studies
(Tadin et al., 2003, 2006). As no SI differences were found be-
right field: t5? 0.60, p ? 0.58), these results were averaged to
this no TMS condition (the raw data are shown in the supple-
mental Fig. 2, available at www.jneurosci.org as supplemental
During TMS sessions, we applied 15 min of 1 Hz TMS to
either the scalp location corresponding to left MT/V5 (supple-
mental Fig. 1, available at www.jneurosci.org as supplemental
material) or the left occipital location where single-pulse TMS
was found to elicit peripheral phosphenes (EVA TMS). Our first
had an effect on spatial suppression strength. A repeated-
measures ANOVA, with stimulus location (contralateral and
ipsilateral to the stimulation) and TMS condition (no TMS,
MT/V5 TMS, EVA TMS) as main factors, revealed a significant
interaction (F(2,10)? 4.0, p ? 0.05). Planned pairwise compari-
sons showed that, for contralaterally presented stimuli, spatial
suppression strength was reduced following MT/V5 TMS (Fig.
2A; t5? 3.72, p ? 0.01) but not after EVA TMS (t5? 0.68, p ?
0.53). Demonstrating such specificity for the stimulated cortical
suggests that the measurable effects of TMS are largely confined
to the stimulated area. For ipsilaterally presented stimuli, no SI
changes were observed following MT/V5 TMS (t5? 0.32, p ?
0.76), demonstrating that the underlying mechanisms exhibit at
least a gross retinotopy.
The observed weakening of spatial suppression could be due
to (1) increased thresholds for discriminating small, moving
stimuli, (2) improved motion discriminations of large stimuli or
(3) a combination of both effects. Examination of post-TMS
threshold changes (Fig. 2B) showed that MT/V5 TMS had no
effect on direction discriminations of small grating stimuli (t5?
0.68, p ? 0.53) (see Discussion for more details). However, as
hypothesized, our results revealed improvements in motion dis-
criminations of large, moving stimuli presented contralateral to
stimulated MT/V5 (t5? 3.45, p ? 0.02). Specifically, the average
threshold for discriminating motion direction of large stimuli
decreased by 0.072 ? 0.02 log unit, which was, on average, a 10
ms threshold improvement. These paradoxical results mimic
Tadinetal.•CausalRoleofAreaMT/V5inSpatialSuppressionJ.Neurosci.,Month??,2011 • 31(xx):xxx-xxx • 3
depression who exhibit better-than-normal motion perception
of large patterns coupled with normal perception of small, mov-
ing stimuli (Golomb et al., 2009).
rect effects of TMS associated with reductions in effective stimu-
tial suppression, reduction of stimulus speed yields increasing
duration thresholds for all sizes (Lappin et al., 2009), while a
for small, moving stimuli (Tadin et al., 2003).
Here, we report seemingly paradoxical TMS-induced improve-
ment in motion discriminations of large, moving stimuli—a re-
sult specific to MT/V5 stimulation and the stimuli presented in
the contralateral visual field. The weakening of spatial suppres-
sion during a TMS-induced period of reduced excitability of
MT/V5 suggests that the critical neural constraints limiting mo-
MT/V5. These findings are consistent with our hypothesis that
behaviorally observed spatial suppression is a direct perceptual
correlate of center–surround antagonism in area MT. Support
to elucidate functional roles of center–surround antagonism in
suppression of large, background-like motions facilitates rapid
figure-ground segregation of moving objects by suppressing
background motion signals (Born et al., 2000; Tadin and Blake,
Why does the disruption of MT/V5 attenuate behaviorally
measured spatial suppression? Center–surround neurons are
et al., 1995; Born, 2000), indicating that surround inhibition in
MT/V5 is not inherited from feedforward inputs. This, in turn,
indicates that a selective disruption of MT/V5 processing should
interfere with the development of center–surround antagonism,
in turn affecting perceptual correlates of MT/V5 surround inhi-
suppressive surround of MT/V5 neurons (see Materials and
significant changes in MT/V5 surround inhibition. Although
surround inhibition also occurs in a number of earlier visual
areas [V1 (Jones et al., 2001); V2 (Shushruth et al., 2009)], these
center–surround interactions occur at a smaller spatial scale and
likely play a lesser role in suppressing neural responses to 16°
diameter stimuli used here.
on duration thresholds and, consequentially, briefly presented
stimuli (?100 ms), likely facilitated detection of changes in sur-
round inhibition for three specific reasons: First, considerable
prior work on spatial suppression has documented the utility of
this strategy (Tadin et al., 2003, 2005b, 2006; Betts et al., 2005,
et al., 2008). Specifically, information about motion direction of
brief stimuli (?100 ms) in area MT/V5 is primarily carried by
neurons with antagonistic surrounds, and not by MT/V5 neu-
rons that lack suppressive surround and actually prefer large,
background-like motions. Third, spatial suppression results ob-
tained using this approach cannot be explained by size-
dependent changes in contrast sensitivity (Glasser and Tadin,
2010) as might be the case for longer, counterphasing stimuli
(Aaen-Stockdale et al., 2009).
yields improvements in motion perception of large stimuli cou-
pled with unchanged motion discriminations of small gratings
with a history of depression). This finding suggests that while
MT/V5 is critical for suppression of large, background-like mo-
tions, it is not solely responsible for the processing of small, first-
order moving stimuli. A similar conclusion arises from lesion
work, which revealed relatively unimpaired motion discrimina-
and Pasternak, 1999). The observed robustness to MT/V5 injury
is likely due to widely distributed mechanisms underlying per-
ception of first-order motion (Plant and Nakayama, 1993; Su-
naert et al., 1999).
Finally, we note that our results mimic spatial suppression
patients with schizophrenia (Tadin et al., 2006) and a history of
depression (Golomb et al., 2009). Specifically, our results closely
mimic Golomb et al. (2009), who also reported a weakening of
spatial suppression that was due to better-than-normal percep-
tion of large, moving stimuli paired with normal perception of
small, moving stimuli. It should be noted, however, that the out-
TMS is presumed to cause a gross impairment of MT/V5 func-
tioning, special population deficits are likely more specific and
probably involve a decrease in the efficacy of inhibitory mecha-
nisms (Betts et al., 2005; Tadin et al., 2006; Golomb et al., 2009).
Indeed, old age, schizophrenia, and depression have all been
2003; Yoon et al., 2010). In schizophrenia, abnormal reductions
of GABA concentration in visual cortex strongly correlate with
abnormally weak surround suppression in the orientation do-
main (Yoon et al., 2010).
In summary, our results show that disruption of MT/V5 pro-
cessing improves motion perception of large stimuli and, conse-
quently, reduces the strength of spatial suppression. While the
inhibitory processing within MT/V5 that normally impairs per-
ception of large background motions. In other words, normally
functioning MT/V5 is necessary for strong spatial suppression of
large moving stimuli. We speculate that this suppression of uni-
form background-like stimuli directly enhances saliency of
smaller moving objects—a hypothesis that is a topic of our cur-
Aaen-StockdaleCR,ThompsonB,HuangPC,HessRF (2009) Low-levelmech-
AlbrightTD,DesimoneR (1987) Localprecisionofvisuotopicorganizationin
Allen EA, Pasley BN, Duong T, Freeman RD (2007) Transcranial magnetic
Antal A, Nitsche MA, Paulus W (2003) Transcranial magnetic and direct
Battelli L, Alvarez GA, Carlson T, Pascual-Leone A (2009) The role of the
ulation. J Cogn Neurosci 21:1946–1955.
4 • J.Neurosci.,Month??,2011 • 31(xx):xxx-xxxTadinetal.•CausalRoleofAreaMT/V5inSpatialSuppression
balt6/zns-neusci/zns-neusci/zns99911/zns9428-11z xppwsS?112/16/10 11:26Art: 4121-10Input-JO
Betts LR, Taylor CP, Sekuler AB, Bennett PJ (2005) Aging reduces center-
surround antagonism in visual motion processing. Neuron 45:361–366.
Betts LR, Sekuler AB, Bennett PJ (2009) Spatial characteristics of center-
surround antagonism in younger and older adults. J Vis 9:25.1–25.15.
Born RT (2000) Center-surround interactions in the middle temporal vi-
sual area of the owl monkey. J Neurophysiol 84:2658–2669.
Born RT, Bradley DC (2005) Structure and function of visual area MT.
Annu Rev Neurosci 28:157–189.
BornRT,GrohJM,ZhaoR,LukasewyczSJ (2000) Segregationofobjectand
movements. Neuron 26:725–734.
Boroojerdi B, Prager A, Muellbacher W, Cohen LG (2000) Reduction of
lation. Neurology 54:1529–1531.
Brainard DH (1997) The Psychophysics Toolbox. Spat Vis 10:433–436.
Churan J, Khawaja FA, Tsui JM, Pack CC (2008) Brief motion stimuli pref-
erentially activate surround-suppressed neurons in macaque visual area
MT. Curr Biol 18:R1051–R1052.
Fernandez E, Alfaro A, Tormos JM, Climent R, Martínez M, Vilanova H,
Walsh V, Pascual-Leone A (2002) Mapping of the human visual cortex
using image-guided transcranial magnetic stimulation. Brain Res Brain
Res Protoc 10:115–124.
Glasser DM, Tadin D (2010) Low-level mechanisms do not explain para-
doxical motion percepts. J Vis 10:20.1–20.9.
Golomb JD, McDavitt JR, Ruf BM, Chen JI, Saricicek A, Maloney KH, Hu J,
Chun MM, Bhagwagar Z (2009) Enhanced visual motion perception in
major depressive disorder. J Neurosci 29:9072–9077.
Gugino LD, Romero JR, Aglio L, Titone D, Ramirez M, Pascual-Leone A,
Grimson E, Weisenfeld N, Kikinis R, Shenton ME (2001) Transcranial
magnetic stimulation coregistered with MRI: a comparison of a guided
versus blind stimulation technique and its effect on evoked compound
muscle action potentials. Clin Neurophysiol 112:1781–1792.
Hilgetag CC, The ´oret H, Pascual-Leone A (2001) Enhanced visual spatial
attention ipsilateral to rTMS-induced ‘virtual lesions’ of human parietal
cortex. Nat Neurosci 4:953–957.
Jones HE, Grieve KL, Wang W, Sillito AM (2001) Surround suppression in
primate V1. J Neurophysiol 86:2011–2028.
Kastner S, Demmer I, Ziemann U (1998) Transient visual field defects in-
duced by transcranial magnetic stimulation over human occipital pole.
Exp Brain Res 118:19–26.
LappinJS,TadinD,NyquistJB,CornAL (2009) Spatialandtemporallimits
of motion perception across variations in speed, eccentricity, and low
vision. J Vis 9:30.1–30.14.
Leventhal AG, Wang Y, Pu M, Zhou Y, Ma Y (2003) GABA and its agonists
improved visual cortical function in senescent monkeys. Science
Merabet L, Thut G, Murray B, Andrews J, Hsiao S, Pascual-Leone A (2004)
Feeling by sight or seeing by touch? Neuron 42:173–179.
Pack CC, Hunter JN, Born RT (2005) Contrast dependence of suppressive
influences in cortical area MT of alert macaque. J Neurophysiol 93:
Plant GT, Nakayama K (1993) The characteristics of residual motion per-
ception in the hemifield contralateral to lateral occipital lesions in hu-
mans. Brain 116:1337–1353.
Raiguel S, Van Hulle MM, Xiao DK, Marcar VL, Orban GA (1995) Shape
and spatial distribution of receptive fields and antagonistic motion sur-
rounds in the middle temporal area (V5) of the macaque. Eur J Neurosci
Rossi S, Hallett M, Rossini PM, Pascual-Leone A, Safety of TMS Consensus
Group (2009) Safety, ethical considerations, and application guidelines
for the use of transcranial magnetic stimulation in clinical practice and
research. Clin Neurophysiol 120:2008–2039.
RudolphK,PasternakT (1999) Transientandpermanentdeficitsinmotion
perception after lesions of cortical areas MT and MST in the macaque
monkey. Cereb Cortex 9:90–100.
Sack AT, Kohler A, Linden DE, Goebel R, Muckli L (2006) The temporal
characteristics of motion processing in hMT/V5?: combining fMRI and
neuronavigated TMS. Neuroimage 29:1326–1335.
Schwartz O, Simoncelli EP (2001) Natural signal statistics and sensory gain
control. Nat Neurosci 4:819–825.
ShushruthS,IchidaJM,LevittJB,AngelucciA (2009) Comparisonofspatial
Silvanto J, Cattaneo Z, Battelli L, Pascual-Leone A (2008) Baseline cortical
excitability determines whether TMS disrupts or facilitates behavior.
J Neurophysiol 99:2725–2730.
Stewart L, Battelli L, Walsh V, Cowey A (1999) Motion perception and per-
ceptual learning studied by magnetic stimulation. Electroencephalogr
Clin Neurophysiol Suppl 51:334–350.
Sunaert S, Van Hecke P, Marchal G, Orban GA (1999) Motion-responsive
regions of the human brain. Exp Brain Res 127:355–370.
TadinD,BlakeR (2005) Motionperceptiongettingbetterwithage?Neuron
Tadin D, Lappin JS (2005a) Linking psychophysics and physiology of
Tadin D, Lappin JS (2005b) Optimal size for perceiving motion decreases
with contrast. Vision Res 45:2059–2064.
Tadin D, Lappin JS, Gilroy LA, Blake R (2003) Perceptual consequences of
centre-surround antagonism in visual motion processing. Nature 424:
Tadin D, Kim J, Doop ML, Gibson C, Lappin JS, Blake R, Park S (2006)
Weakened center-surround interactions in visual motion processing in
schizophrenia. J Neurosci 26:11403–11412.
Tootell RB, Reppas JB, Kwong KK, Malach R, Born RT, Brady TJ, Rosen BR,
Belliveau JW (1995) Functional analysis of human MT and related vi-
sual cortical areas using magnetic resonance imaging. J Neurosci 15:
Vinje WE, Gallant JL (2000) Sparse coding and decorrelation in primary
visual cortex during natural vision. Science 287:1273–1276.
Wassef A, Baker J, Kochan LD (2003) GABA and schizophrenia: a review of
basic science and clinical studies. J Clin Psychopharmacol 23:601–640.
Yoon JH, Maddock RJ, Rokem A, Silver MA, Minzenberg MJ, Ragland JD,
Carter CS (2010) GABA concentration is reduced in visual cortex in
sion. J Neurosci 30:3777–3781.
Tadinetal.•CausalRoleofAreaMT/V5inSpatialSuppressionJ.Neurosci.,Month??,2011 • 31(xx):xxx-xxx • 5
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