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Arthur M. Jacobs
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Graf etal., 2005; Grady, 2007; Dehaene and Cohen, 2011; Beauregard,
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ORIGINAL RESEARCH
published: xx July 2015
doi: 10.3389/fnhum.2015.00423
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Many neighbors are not silent. fMRI

evidence for global lexical activity in
visual word recognition
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Neurocognition Lab, Centre for Cognitive Neuroscience, Universitt Salzburg, Salzburg, Austria, 2 Department of
Experimental and Neurocognitive Psychology, Freie Universitt Berlin, Berlin, Germany, 3 Center for Cognitive Neuroscience
Berlin, Berlin, Germany, 4 Dahlem Institute for Neuroimaging of Emotion, Berlin, Germany, 5 Christian Doppler Klinik,
Paracelsus Medical University, Salzburg, Austria
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Edited by:
Lynne E. Bernstein,
George Washington University, USA
Reviewed by:
Marcus Heldmann,
Department Neurology, Germany
Clara Scholl,
Georgetown University, USA
*Correspondence:
Mario Braun,
Neurocognition Lab, Centre
for Cognitive Neuroscience,
Universitt Salzburg, Hellbrunner
Strae 34, 5020 Salzburg, Austria
mario.braun@sbg.ac.at
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Mario Braun1,2* , Arthur M. Jacobs 2,3,4 , Fabio Richlan1 , Stefan Hawelka 1 , Florian Hutzler1
and Martin Kronbichler1,5
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Received: 28 April 2015

Accepted: 10 July 2015
Published: xx July 2015
Citation:
Braun M, Jacobs AM, Richlan F,
Hawelka S, Hutzler F
and Kronbichler M (2015) Many
neighbors are not silent. fMRI
evidence for global lexical activity
in visual word recognition.
Front. Hum. Neurosci. 9:423.
doi: 10.3389/fnhum.2015.00423
Many neurocognitive studies investigated the neural correlates of visual word

recognition, some of which manipulated the orthographic neighborhood density of
words and nonwords believed to influence the activation of orthographically similar
representations in a hypothetical mental lexicon. Previous neuroimaging research failed
to find evidence for such global lexical activity associated with neighborhood density.
Rather, effects were interpreted to reflect semantic or domain general processing. The
present fMRI study revealed effects of lexicality, orthographic neighborhood density and
a lexicality by orthographic neighborhood density interaction in a silent reading task.
For the first time we found greater activity for words and nonwords with a high number
of neighbors. We propose that this activity in the dorsomedial prefrontal cortex reflects
activation of orthographically similar codes in verbal working memory thus providing
evidence for global lexical activity as the basis of the neighborhood density effect. The
interaction of lexicality by neighborhood density in the ventromedial prefrontal cortex
showed lower activity in response to words with a high number compared to nonwords
with a high number of neighbors. In the light of these results the facilitatory effect for
words and inhibitory effect for nonwords with many neighbors observed in previous
studies can be understood as being due to the operation of a fast-guess mechanism
for words and a temporal deadline mechanism for nonwords as predicted by models
of visual word recognition. Furthermore, we propose that the lexicality effect with higher
activity for words compared to nonwords in inferior parietal and middle temporal cortex
reflects the operation of an identification mechanism based on local lexico-semantic
activity.
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Keywords: visual word recognition, neighborhood density effect, mental lexicon, orthographic similarity,
dorso- and ventromedial cortex, fast-guess mechanism, deadline mechanism, identification mechanism
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Introduction
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Successful visual word recognition involves the synchronized interplay of multiple sensorymotor, attentional and memory networks. Classical neurological models and current neuroimaging
results suggest a set of left hemispheric regions comprising the inferior temporal, inferior frontal,
supramarginal, and angular gyri to be strongly involved in this process (Geschwind, 1965;
Frontiers in Human Neuroscience | www.frontiersin.org
July 2015 | Volume 9 | Article 423
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Orthographic processing in silent reading
number of neighbors in lexical decision, as well as a greater N400

and N150/350 in a go/no-go semantic categorization task, but did
not directly relate these ndings to output from a computational
model. Later, Braun et al. (2006) did exactly this by using ERPs
to test the hypothesis of a global activation of representations of
orthographically similar words. Two mechanisms implemented
in the multiple read out model of visual word recognition
(MROM; Jacobs and Grainger, 1994; Grainger and Jacobs, 1996;
Jacobs et al., 1998) were proposed to be in eect in lexical
decisions to words and nonwords in their study: rst, an early
identication mechanism for stored representations of words
around 300 ms supposed to reect local, i.e., word specic,
lexical activity and to underly yes responses to words; second, a
temporal deadline mechanism around 500 ms assumed to reect
global, i.e., non-specic, lexical activity in a hypothetical mental
lexicon and to underly no responses to nonwords (see also
Barber and Kutas, 2007).
Neuroimaging research using neighborhood density as a
measure of orthographic similarity so far provided only little
evidence for higher activity in response to words or nonwords
with a high number of neighbors (Binder et al., 2003; Fiebach
et al., 2007). Rather, blood oxygen level dependent (BOLD)
responses were observed to be higher for stimuli with a low
number of neighbors. Binder et al. (2003) found higher activity
in response to words without neighbors in left prefrontal, angular
gyrus, and ventrolateral temporal areas which was interpreted to
reect the fact that accurate responses in lexical decisions depend
on the activation of semantic information. Thus, although not
being directly comparable, the results of Binder et al. (2003) are
somewhat at odds with the brain-electrical ndings of greater
lexico-semantic eects for items with a high number of neighbors
relative to those with a low number of neighbors (Holcomb et al.,
2002; Braun et al., 2006).
A second fMRI study (Fiebach et al., 2007) reported greater
activation for stimuli with a low number of neighbors in
the superior temporal sulcus and the angular gyrus (although
this main eect of neighborhood density did not exceed the
signicance threshold) thus replicating in part the results of
Binder et al. (2003). In addition, the analysis showed a lexicality
by neighborhood density interaction in the left mid-dorsolateral
prefrontal cortex, more specically in the posterior inferior
frontal sulcus and middle frontal gyrus, and in a region slightly
anterior to the pre-SMA in the medial superior frontal gyrus.
Activity in the mid-dorsolateral prefrontal cortex was strongest
in response to nonwords with a high number of neighbors. In
contrast, activity in the medial superior frontal gyrus was stronger
for words with a low number of neighbors. Fiebach et al. (2007)
interpreted this activity in frontal regions to reect domaingeneral processing at a late post-lexical level rather than reecting
activity associated with a hypothetical mental lexicon.
Although, the metaphor of a mental lexicon storing the
visual form of words which are co-activated when similar
items are presented is part and parcel of almost all current
computational models of word recognition (regardless of
whether they use localist or distributed units; cf. Jacobs and
Grainger, 1994), the neurocognitive literature dealing with
this notion is still inconclusive and the model-to-brain-data
Damasio and Geschwind, 1984; Bookheimer, 2002; Binder

et al., 2005; Price, 2012). On the stimulus side, a vast
number of sublexical and lexical variables have been shown to
inuence word recognition (e.g., bi- or trigram, syllable, and
word frequency) in a wide variety of tasks (e.g., perceptual
identication, lexical, or semantic decision, naming, silent
reading). Among the over 50 quantiable factors known to
aect word recognition performance (Graf et al., 2005), one
of the most prominent variables is orthographic neighborhood
density, i.e., the number of orthographic neighbors, which can
be generated by changing one letter of a given word (Coltheart
et al., 1977). When subjects make lexical decisions to words
and nonwords, a standard nding is that responses to words
with high neighborhood density are faster compared to words
with low neighborhood density (Andrews, 1989; Jacobs and
Grainger, 1992, 1994; Sears et al., 1995; Forster and Shen,
1996; Grainger and Jacobs, 1996; Carreiras et al., 1997; see
Hawelka et al., 2013 for eects in natural reading). On the
other hand, response times to nonwords show a reversed eect:
responses are slower for nonwords with high compared to
those with a low number of neighbors. The eect is of interest
because it is assumed to reect a direct topdown inuence
of memory representations on the perception of a letter string
which has played a signicant role in the development of
computational models of word recognition and reading (Jacobs
and Grainger, 1994). One explanation for the observed lexicality
by neighborhood interaction is that during the early stages of
visual word recognition a letter string activates orthographically
similar word representations in a hypothetical mental lexicon.
In the case of stimuli with a high number of neighbors this
is assumed to result in the activation of a larger number of
candidate representations compared to those with a low number
of neighbors. In interactive activation and hybrid dual-route
models of visual word recognition (McClelland and Rumelhart,
1981; Grainger and Jacobs, 1996; Coltheart et al., 2001; Hofmann
et al., 2011; Hofmann and Jacobs, 2014) this activation can
directly be computed on the basis of the summed activity over
all lexical units, i.e., the amount of global lexical activity for
both words and nonword stimuli thus providing a quantitative
predictor for both behavioral and neurocognitive studies of
word recognition. Jacobs and Carr (1995) speculated that levels
of neural activity in the left medial prestriate cortex vary
systematically with the levels of computational activity predicted
to occur in the orthographic lexicon of interactive activation
models. While this speculation was never directly tested, there is
some neurocognitive evidence indicating that Jacobs and Carrs
idea of a cross-fertilization between computational modelers
and mind mappers in the domain of reading was not too farfetched. Until now, however, neurocognitive evidence for the
organization and possibly distributed locations of such a neural
correlate of a hypothetical mental lexicon activated by words and
nonwords is still scarce.
Some evidence for global lexical activity as the basis of
neigbhorhood density eects was found in electrophysiological
research (Holcomb et al., 2002; Braun et al., 2006). Holcomb et al.
(2002) observed greater N400 eects for words and nonwords
with a high number of neighbors compared to those with a low
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for this nding was that visually presented words match

onto stored representations leading to less activity compared
to visually presented pseudowords which do not. Therefore,
Kronbichler et al. (2007) suggested that this region not only
computes letter string representations, but could be a region
which also stores word specic orthographic information (i.e.,
orthographic lexicon function). A third function of the ventral
occipitotemporal region in addition to the prelexical and lexical
ones was suggested by Devlin et al. (2006) who proposed that
the VWFA acts as a general interface area between bottom
up sensory information from dierent modalities and top
down higher order conceptual information. Word recognition
is assumed to involve reciprocal interactions between sensory
cortices and higher order processing regions via a hierarchy of
forward and backward connections with sensory areas sending
bottomup information and higher-order regions sending top
down predictions which are based on prior experience and serve
to resolve uncertainty about the sensory input (Dehaene and
Cohen, 2011; Price and Devlin, 2011; see also Schurz et al., 2014a).
The present study was designed to further investigate the
neural basis of the neighborhood density eect which provides
important information about the structure and functioning of
mental representations of words, i.e., the hypothetical mental
lexicon, as conceptualized in extant computational models of
word recognition (e.g., Grainger and Jacobs, 1996; Coltheart et al.,
2001; Perry et al., 2007; Hofmann and Jacobs, 2014).
Finding dierences in brain activity in response to words and
nonwords with high or low numbers of neighbors in ventral
occipitotemporal, inferior parietal, and/or middle temporal
cortex would support the orthographic similarity/global lexical
activity account as the basis of the neighborhood density eect
and thus strengthen the above computational models. In contrast,
activation in prefrontal cortex could suggest an extra-lexical locus
of the eect and would thus provide no neuroimaging evidence
for the existence and location of a mental lexicon as proposed by
the models (Fiebach et al., 2007).
We employed a silent reading paradigm in the scanner
to avoid potential confounds with executive task demands
like decision and response related processes. Previous studies
(Holcomb et al., 2002; Binder et al., 2003; Braun et al., 2006)
mostly used the lexical decision task to investigate activation
elicited by items with high and low number of neighbors which
makes it dicult to distinguish between extra-lexical and lexical
processes (Fiebach et al., 2007). Furthermore, we controlled the
words and nonwords on a number of sublexical and lexical
measures known to inuence visual word processing (see Table 1)
and used only short words (four letter in length) posing only low
demands on the reading process itself.
connection is still weak, despite some recent progress (e.g., Levy

et al., 2009; Taylor et al., 2012; Hofmann and Jacobs, 2014).
A likely candidate for a hypothetical mental lexicon is Wernickes
area in left posterior superior and middle temporal lobe since
this region was repeatedly found to be involved in language
comprehension (e.g., Howard et al., 1992; Beauregard, 1997).
Many studies report that the left middle temporal gyrus is
consistently more active during the processing of words than
during the processing of nonwords (e.g., Hagoort et al., 1999;
Fiebach et al., 2002; Binder et al., 2003). Activation in the middle
temporal gyrus is suggested to signal either semantic processing
(e.g., Price et al., 1997; Indefrey and Levelt, 2004; Gold et al.,
2005; Cao et al., 2006; Vigneau et al., 2006; Booth et al., 2007;
Richlan et al., 2009; Newman and Joanisse, 2011; Whitney, 2011;
Noonan et al., 2013), or phonological processing (e.g., Indefrey
and Levelt, 2004; Bitan et al., 2005; Brambati et al., 2009; Simos
et al., 2009; Newman and Joanisse, 2011; Graves et al., 2014), or
orthographic-phonological mapping (e.g., Graves et al., 2010).
Furthermore, neurological evidence from Wernicke aphasics
shows that these are unable to semantically categorize words (e.g.,
Zurif et al., 1974), or to explicitly judge words on the basis of
semantic information (Goodglass and Baker, 1976), leading to the
conclusion that controlled lexico-semantic processes are decient
in these patients (Milberg et al., 1987; see Friederici, 1998 for a
review). Thus, previous research suggests that the superior and
middle temporal gyri are likely regions for hosting a hypothetical
mental lexicon despite the lack of evidence for higher global
lexical activity for words or nonwords.
Another prominent brain region for being part of a
hypothetical mental lexicon is the ventral occipitotemporal
region, hosting the visual word form area (VWFA; Cohen
et al., 2000b). A great deal of research showed that the ventral
occipitotemporal region is involved in the identication of letters
and words (e.g., Cohen et al., 2000b, 2004, 2008; Vinckier et al.,
2007). Vinckier et al. (2007) observed a posterior to anterior
specialization within the ventral occipitotemporal cortex with the
anterior part showing the highest activity in response to words or
word like stimuli.
The VWFA is thought to be important for the prelexical
identication of letters and letter combinations. Research showed
that VWFA activity associated with the identication of letters
is independent of size, case, location or font (Dehaene et al.,
2005), suggesting the computation of perceptually higher-order
invariant orthographic units from the input. This information is
then thought to be transmitted to other regions involved in visual
word recognition, such as the temporal, parietal, and inferior
frontal regions (Cohen et al., 2004) which allow for further
phonological and semantic processing.
Beside this proposed prelexical function other ndings suggest
a possible role for the VWFA in lexical processing (e.g., Cohen
et al., 2004; Kronbichler et al., 2004, 2007; Bruno et al., 2008; Hauk
et al., 2008; Glezer et al., 2009; Schurz et al., 2010; Baeck et al.,
2015). For example, Kronbichler et al. (2007) reported activation
dierences in the VWFA by comparing words, pseudowords
and pseudohomophones in a visual phonological decision task.
Words elicited less activity compared to pseudohomophones and
pseudowords which did not dier in activity. Their explanation
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Materials and Methods
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Ethics
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The study was approved by the ethics committee of the University

of Salzburg (Ethikkommission der Universitt Salzburg) and
was in accordance with the principles expressed in the declaration
of Helsinki. Informed consent was obtained from all participants.
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was Presentation software from Neurobehavioral Systems1 (San

Francisco, CA, USA). On an irregular basis a four to seven letter
male or female name (10 in total) was presented. Subjects were
instructed to respond by pressing a button with the index nger
of their right hand of a MRI compatible button box whenever a
name was presented during testing. This test was administered to
ensure subjects attentive reading of all stimuli.
TABLE 1 | Means and (SD) for controlled variables for words and
nonwords.
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Words
Nonwords
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Low
High
Low
High
2(2)
6(2)
2(1)
6(2)
124(328)
97(164)
FN
1623(4628)
2423(6105)
894(1753)
2230(5119)
BiF
2247(4160)
3945(8085)
2655(5089)
4079(6660)
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Participants
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Twenty-two healthy participants (15 women) participated in the

fMRI experiment. All were right-handed native German speakers
and had no history of neurological disorders and normal or
corrected to normal vision. Age ranged from 18 to 44 years. Two
subjects were excluded from the analysis because of a problem
with stimulus presentation. Subjects were recruited by students
of the University of Salzburg, received course credit and were
oered a CD with their anatomical fMRI scans. Subjects were
tested individually at the Center for Cognitive Neuroscience at
the University of Salzburg.
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Experimental Materials and Procedure
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Brain activity responses to 100 monosyllabic words and 100

nonwords were collected in two sessions together with two other
experiments with 600 stimuli in total. The 200 stimuli were
all four letters in length. The nonwords were pronounceable
according to German pronunciation rules. The 200 stimuli were
split into four groups to investigate the neighborhood density
eect. Of the 100 words 50 had a low number of neighbors
(three or less than three) the other 50 had a high number of
neighbors (four or more). The same manipulation was applied to
the 100 nonwords. The stimuli were matched between conditions
for number of letters (let), word frequency (F), summed bigram
frequency (BiF), and summed frequency of the neighbors (FN; see
Table 1). Frequency counts were taken from the CELEX lexical
database (Baayen et al., 1993).
Subjects were asked to read the stimuli (words/nonwords)
silently while being in the scanner. To make sure the task was
clear, subjects performed a practice session with 20 items on
a laptop outside the scanner. The scanning session took about
50 min and the whole experiment took about 1 h and 30 min.
There were 5 min of anatomical scanning, followed by two
sessions of 21 min actual testing with a short break in between
to ensure that the subjects felt comfortable and could remain
concentrated. Stimuli were presented on a 1024 768 pixel
screen in white font on black surface projected on a mirror inside
the scanner. The font used was Arial with 50 pt size. Words
and nonwords were presented in random order for 700 ms, after
each stimulus a blank screen with a xation cross was presented.
Presentation times of the xation cross were jittered: 166 xation
crosses were presented for 2500 ms, 20 for 3200 ms, eight for
7500 ms, and six for 10500 ms. The experimental software used
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L, Number of letters, N, number of orthographic neighbors, F, word frequency per

million, FN, summed frequency of neighbors, BiF, summed bigram frequency count.
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Image Acquisition
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Functional and structural imaging was performed with a Siemens

Tim Trio 3 Tesla using a 32-channel head coil (Siemens,
Erlangen, Germany). A gradient echo eld map (TR 488 ms,
TE 1 = 4.49 ms, TE 2 = 6.95 ms) and a high resolution
(1 mm 1 mm 1.2 mm) structural scan with a T1 weighted
MPRAGE sequence were acquired from each participant. The
structural images were followed by two runs with 510 volumes
each of functional images sensitive to BOLD contrast acquired
with a T2 weighted gradient echo EPI sequence (TR = 2520ms,
TE = 33 ms, ip angle = 77 , number of slices = 36, slice
thickness = 3 mm, 64 64 matrix, FOV = 192 mm). Six dummy
scans were acquired at the beginning of each functional run
before stimulus presentation. Low frequency noise was removed
with a high-pass lter (128 s).
For preprocessing and statistical analysis, SPM8 software2 ,
running in a MATLAB 7.6 environment (Mathworks Inc.,
Natick, MA, USA), was used. Functional images were realigned,
unwarped, corrected for geometric distortions using the eldmap
of each participant and slice time corrected. The high resolution
structural T1 weighted image of each participant was processed
and normalized with the VBM8 toolbox3 using default settings.
Each structural image was segmented into gray matter, white
matter and CSF and denoised and warped into MNI space
by registering it to the DARTEL template provided by the
VBM8 toolbox via the high-dimensional DARTEL (Ashburner,
2007) registration algorithm. Based on these steps, a skull
stripped version of each image in native space was created.
To normalize functional images into MNI space, the functional
images were co-registered to the skull stripped structural image
and the parameters from the DARTEL registration were used
to warp the functional images, which were resampled to
3 mm 3 mm 3 mm voxels and smoothed with a 8-mm
FWHM Gaussian kernel.
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fMRI Analysis
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Statistical analysis was performed with a GLM two staged mixed

eects approach. In the subject-specic rst level model, each
condition was modeled by convolving stick functions at its
onsets with SPM8s canonical hemodynamic response function
and no time derivatives. On the subject-specic rst level
model conditions of interest were contrasted against the xation
baseline. These subject-specic contrast images were used for
the 2nd level group analysis. Direct contrasts between words
and nonwords with a high and low number of neighbors were
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http://www.neurobs.com/
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http://www.l.ion.ucl.ac.uk/spm/
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http://dbm.neuro.uni-jena.de/vbm8
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calculated with 2 2 repeated measures ANOVAs and in case

of a signicant interaction with subsequent paired t-tests. For
all statistical comparisons an uncorrected cluster threshold of
p < 0.001 and a cluster extent of 25 was used. We decided
to use a lenient threshold which is not uncommon in reading
research (e.g., Martin et al., 2015, Table 1) to be able to nd
expected dierences in a silent reading task which is known to
elicit less brain activity compared to tasks which impose decision
and/or manual responses (e.g., Fiebach et al., 2007). By setting
the cluster extent to 25 we still allow for a correction of multiple
comparisons according to the theory of Gaussian random elds
(Kiebel et al., 1999). All stereotaxic coordinates for voxels with
maximal z-values within activation clusters are reported in the
MNI coordinate system.
cortex: words with a high number of neighbors showed lower

activity compared to words with a low number of neighbors.
The pattern of activity was reversed for the nonwords (see
Figures 1C,G; Table 2). The 2 2 repeated measures ANOVA
with lexicality (words, nonwords) and neighborhood density
(high, low) as within-subject factors with the beta estimates of the
peak values showed no main eect of lexicality [F(1,19) = 0.58,
p = 0.457] and no main eect of neighborhood density
[F(1,19) = 0.24, p = 0.63, but an interaction F(1,19) = 11.71,
p = 0.003]. Paired t-tests showed that both words: t = 2.26,
df = 19, p = 0.035, and nonwords: t = 3.25, df = 19,
p = 0.004, showed an eect of neighborhood density (see
Figure 1G).
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Results
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Imaging Results
Effect of Lexicality
The whole-brain analysis showed eects of lexicality and
neighborhood density as well as interactions between both
factors. The lexicality eect was evident at bilateral occipital poles,
the inferior parietal and middle temporal gyrus (Figures 1A,D;
Table 2) with higher activity for words compared to nonwords.
Furthermore, higher activity for nonwords compared to words
was obtained in the precentral gyrus and opercular cortex (see
Figures 1A,E; Table 2).
The separately performed 2 2 repeated measures ANOVAs
for these regions with either higher activity for words compared
to nonwords or vice versa with the beta estimates of the peak
values with lexicality (words, nonwords) and neighborhood
density (high, low) as within-subject factors showed main eects
of lexicality in left AG/MTG: F(1,19) = 23.44, p < 0.001 and left
precentral/opercular cortex: F(1,19) = 14.26, p = 0.001 and also
a main eect of neighborhood density in the opercular cortex
F(1,19) = 13.28, p = 0.002, and no interaction.
Effect of Neighborhood Density
496
The contrast of greater activity of high compared to low

neighborhood density revealed signicant dierences in
the dorsomedial prefrontal and left opercular cortex (see
Figures 1B,E,F; Table 2). The 2 2 repeated measures ANOVA
with lexicality (words, nonwords) and neighborhood density
(high, low) as within-subject factors with the beta estimates of
the peak values of high vs. low neighborhood density words and
nonwords showed no main eect of lexicality [F(1,19) = 0.21,
p = 0.655] and no interaction [F(1,19) = 0.19, p = 0.665,
but a main eect of neighborhood density F(1,19) = 21.24,
p < 0.001]. In contrast, no region showed greater activity
for low compared to high neighborhood density words and
nonwords at the chosen threshold (p < 0.001 uncorrected,
cluster extent 25).
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To further investigate the basis of the neighborhood density

eect and its relation to reading related areas we extracted three
regions of interests (ROIs) identied by the contrasts of words
vs. nonwords at the whole-brain level. Three ROIs were created
by drawing 4-mm spheres around the peak coordinates in the
opercular (51 3 13) and the inferior parietal/middle temporal
cortex (51 58 16) and in the inferior temporal gyrus near
the location of the VWFA (45 61 8). The 2 2 repeated
measures ANOVAs with lexicality (lex; words/nonwords) and
neighborhood density (n; high/low) as within subject factors for
the three ROIs revealed a main eect of lexicality for the inferior
parietal/middle temporal ROI [F(1,19) = 21.90, p < 0.001]
and main eects of lexicality and neighborhood density for the
opercular cortex [Flex(1,19) = 15.63, p = 0.002; Fn(1,19) = 12.86,
p = 0.002] and the VWFA [Flex(1,19) = 8.83, p = 0.005;
Fn(1,19) = 4.42, p = 0.029] ROIs and no interactions conrming
the results of the whole-brain analysis (see Figures 2AC).
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Discussion
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Computational models of visual word recognition predict that

words and nonwords with a high neighborhood density elicit
high values of global lexical activity by activating orthographically
similar entries in a hypothetical mental lexicon and that this
activity is the basis for the facilitatory eects for words with
many neighbors and the inhibitory eects for nonwords in lexical
decision (e.g., Grainger and Jacobs, 1996; Coltheart et al., 2001;
Braun et al., 2006). Simulations using these models show that
high levels of global lexical activity lead to word present signals
for both high-density words and nonwords, thus increasing both
hit and false alarm rates in data-limited lexical decision tasks
(Jacobs et al., 2003). In the case of words this allows for fast
responses in response-limited lexical decision tasks. In the case
of nonwords a temporal deadline mechanism was suggested to
prolong processing times to allow for deeper inspection of the
input resulting in longer response latencies for nonwords with
many neighbors (Grainger and Jacobs, 1996).
So far, however, evidence of higher brain-electrical or
hemodynamic activity for stimuli with many neighbors was
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Lexicality by Neighborhood Density Interaction
512
Furthermore, the whole-brain analysis revealed an interaction of

lexicality by neighborhood density in the ventromedial prefrontal
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ROI Analysis for Selected Regions Showing a

Lexicality Effect
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FIGURE 1 | (A) Effect of lexicality showing greater activation for words
compared to nonwords irrespective of neighborhood density in left
angular and middle temporal gyrus (AG/MTG) and bilateral occipital
poles. (B) Effect of neighborhood density with greater activation for
words and nonwords with high number of neighbors compared to
words and nonwords with low number of neighbors in dorsomedial
prefrontal cortex (dmPFC). (C) Interaction of lexicality and neighborhood
density with greater activity for words with low and nonwords with
high number of neighbors in ventromedial prefrontal cortex (vmPFC).
(DG) Signal change for words and nonwords with high and low
number of neighbors in AG/MTG, OP, dmPFC, vmPFC. AG, angular
gyrus, MTG, middle temporal gyrus, OP, opercular cortex, Occ.

Poles, occipital poles, dmPFC, dorsomedial prefrontal cortex, vmPFC,
ventromedial prefrontal cortex. High-N, high number of neighbors,
Low-N, low number of neighbors, SEM, Standard Error of the Mean.
The whole-brain analysis was thresholded at p < 0.001, voxel level
uncorrected and a cluster extent of 25. The displayed statistical
differences are based on a 2 2 repeated measures ANOVA with
Lexicality and Neighborhood density as within-subject factors for the
respective region. Differences between levels of conditions show the
results of paired t-tests with p < 0.05; p < 0.01, and
p < 0.005.
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Braun et al.
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TABLE 2 | Brain regions showing effects of lexicality and neighborhood density (voxel-level uncorrected, p < 0.001, cluster size >25).
Brain region
Brodmann Area
Hemisphere
51
58
688
Effect of lexicality (words >nonwords)
689
Angular gyrus, lateral occipital

cortex, superior division, middle
temporal gyrus,
temporooccipital part
21/37/39
Occipital Pole, lateral occipital

cortex, superior division
18
21
693
694
Occipital Pole
17
695
Effect of lexicality (nonwords > words)
696
697
Precentral gyrus, opercular

cortex, pars opercularis
698
Neighborhood density effect (high > low)
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700
Dorsomedial prefrontal cortex

(dmPFC), paracingulate gyrus
701
Lexicality neighborhood density interaction
702
Ventromedial prefrontal cortex,

paracingulate gyrus
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691
692
703
704
742
Cluster size
Zmax
16
77
4.26
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708
709
710
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712
713
714
715
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717
718
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720
721
722
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725
726
727
728
748
6/48
91
16
91
4.76
15
100
10
88
4.45
51
13
41
4.37
750
32
41
25
29
4.16
737
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740
741
756
757
11
758
L
44
11
34
4.26
759
760
x, y, z, peak coordinates according to MNI stereotactic space, cluster size in voxels; high, high number of neighbors, low, low number of neighbors.
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involved in higher order executive control processes like decision

making, conict monitoring, response conict, theory of mind,
and language comprehension (Bechara et al., 1998; Cohen et al.,
2000a; Ferstl and von Cramon, 2002; Ridderinkhof et al., 2004;
Rogers et al., 2004; Schurz et al., 2014b). Furthermore, there is
much evidence pointing to a prominent role of the dorsomedial
and ventrolateral prefrontal cortex in working memory (e.g., Rao
et al., 1997; Henson et al., 1999). The functions of a hypothetical
mental lexicon are rather associated with inferior parietal,
middle and inferior temporal regions (e.g., Howard et al., 1992;
Beauregard et al., 1997; Hagoort et al., 1999; Fiebach et al., 2002;
Binder et al., 2003, 2009; Kronbichler et al., 2004). The results
of the exploratory ROI analysis in the ventral occipitotemporal
cortex supports this hypothesis. The neighborhood density eect
near the coordinates of the VWFA (42 57 15) identied by
Cohen et al. (2002) for words and nonwords provides evidence
that orthographic similarity is also dierentially processed in this
region for our items.
Since subjects in the current study only silently read the
words and nonwords and no overt decisions had to be made, the
observed dorsomedial prefrontal activity in our study is not likely
to reect decision-related processes. Rather, it seems that words
and nonwords with many neighbors activate orthographically
similar representations which elicit higher activity for these
items in the dmPFC. We therefore suggest that this activation
reects the activation, maintenance, and monitoring of those
representations orthographically similar to the presented stimuli,
i.e., an implicit verbal working memory function.
Evidence for such a memory function in the dmPFC was
reported by Henson et al. (1999) who reported higher activity
for know-answers compared to remember-answers in an old-new
paradigm with ve-letter nouns in lexical decision. A remember
answer was given in the case of surely remembered items seen
before, a know-answer was given when subjects knew that
the items were presented during the study phase, but could
not recollect any contextual information about its previous
inconclusive providing less support for a direct model-tobrain-data connection. Only two ERP studies reported results
compatible with the idea of global lexical activity supporting
lexical decisions. The rst study found stronger N400s in
lexical and semantic decisions for stimuli with many neighbors
and interpreted this activity as reecting the sum of semantic
activation of the target word and its neighbors (Holcomb
et al., 2002). The second study found a parametric brainelectrical eect around 500 ms after stimulus presentation for
nonwords diering in model-generated global lexical activity
values that was interpreted to reect the temporal deadline
mechanism working dierentially on nonwords with varying
levels of orthographic similarity to the input (Braun et al., 2006).
In contrast neuroimaging research rather showed contradicting
evidence. One neuroimaging study showed a reversed eect of
neighborhood density (i.e., higher activity for stimuli with a
low number of neighbors) in language related areas such as the
middle temporal and angular gyri suggested to reect semantic
processing (Binder et al., 2003). The other study found prefrontal
activity in response to stimuli diering in number of neighbors
which was interpreted as reecting executive domain general
processes related to post-lexical rather than lexical processing
(Fiebach et al., 2007).
The current study revealed for the rst time a neighborhood

density eect with higher activity for stimuli with many
neighbors. Words and nonwords with many neighbors elicited
greater BOLD responses in the dorsomedial prefrontal cortex
(dmPFC) potentially signaling global lexical activity which is
in support of models suggesting orthographic similarity as the
basis of the neighborhood density eect. However, the results
of previous neuroimaging studies make it rather unlikely that
this dorsomedial prefrontal activity directly reects activation
of representations orthographically similar to the stimulus in
a hypothetical mental lexicon. The dmPFC is known to be
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FIGURE 2 | Regions chosen for the additional ROI analysis showing an

effect of lexicality in the whole-brain analysis. AG/MTG (A) and
opercular cortex (B) showed signficant effects at p < 0.001 (voxel level
uncorrected, cluster extent 25). Surface representations for visualizing the
ROIs in (D) were created using Caret software (Van Essen et al., 2001,
http://brainmap.wustl.edu/caret/). Activity in the VWFA (C) did not pass the
statistical cluster size criterion (25), which is not surprising because of the
known inter-subject variability in the location of the VWFA (e.g., Glezer and
Riesenhuber, 2013), but was chosen because of its suggested importance in
visual word recognition. AG, angular gyrus, MTG, middle temporal gyrus, OP,
opercular cortex; VWFA, visual word form area. High-N, high number of
neighbors, Low-N, low number of neighbors, SEM, Standard Error of the
Mean. The whole-brain analysis was thresholded at p < 0.001, voxel level
uncorrected and a cluster extent of 25. The displayed statistical differences
are based on a 2 2 repeated measures ANOVA with Lexicality and
Neighborhood density as within-subject factors for the respective ROI.
Differences between levels of conditions show the results of paired t-tests
with p < 0.05; p < 0.01, and p < 0.005.
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remembered items are likely to be identied in parietal/temporal

areas and that familiar items are processed in dmPFC (Miller and
Cohen, 2001).
occurrence. The higher activity for familiarity based judgments

compared to surely identied items was proposed to reect
stronger monitoring demands when memory judgments are
less certain. Furthermore, their results suggested a dissociation
between activity in parietal and prefrontal areas: in contrast
to the prefrontal activity in response to know answers surely
remembered items elicited higher activity in parietal/temporal
areas suggesting a dierential processing for remember/know
items. Henson et al. (1999) therefore proposed that surely
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Lexicality Effect
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The assumption of lexico-semantic processing in the parietotemporal region is in line with the obtained lexicality eect
revealed by the whole-brain analysis in this region with higher
activity for words irrespective of neighborhood density at the
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Such an interpretation is also supported by studies

investigating autobiographical, episodic, emotional, and
semantic memory processes (Gilboa, 2004; Kuchinke et al.,
2006; Burianova and Grady, 2007; Grady, 2007). Gilboa (2004)
reported greater activity in the left ventromedial prefrontal cortex
for autobiographical memory compared to episodic memory
and suggested that remembering of autobiographical memories
more strongly involves the monitoring of the accuracy and
cohesiveness of retrieved memories in relation to an activated
self-schema relying on a quick intuitive feeling of rightness
(Elliott et al., 2000; Moscovitch and Winocur, 2002).
Moscovitch and Winocur (2002) introduced the term felt
rightness to describe a possible role of the ventromedial
prefrontal cortex in working memory. Felt rightness should refer
to the ability to intuitively guess the correctness or accuracy of a
response in relation to the goals of a memory task. Furthermore,
these authors suggested that this kind of processing precedes an
elaborate cognitive verication of the truthfulness of the memory
and the context in which it is retrieved.
However, activity of the ventromedial prefrontal cortex is
not restricted to autobiographical memory, but is also found
in situations where responses are made by guessing under
conditions of uncertainty (Nathaniel-James et al., 1997; Elliott
et al., 2000). For example, Nathaniel-James et al. (1997) applied
the hayling test (Burgess and Shallice, 1997) and found greater
activation in the anterior ventromedial prefrontal cortex when
participants had to complete sentences that had many possible
correct completions compared to conditions with only a few
possible correct completions.
Elliott et al. (2000) emphasized the role of the medial
orbitofrontal cortex in monitoring and in holding things in
mind and that this function applies especially to aspects of
familiarity and rightness. They suggested that the ventromedial
prefrontal cortex is more active in a working memory matching
condition than in a non-matching condition which does not
involve any guessing. In two tasks subjects were initially shown
a complex, abstract visual stimulus, then after a delay interval,
were confronted with two stimuli, one of which was the sample
stimulus. In the delayed matching to sample, the subjects task
was to choose the familiar stimulus; in the delayed non-matching
task subjects had to choose the novel stimulus. When both
conditions were compared, greater activation in the medial
caudate and ventromedial orbitofrontal cortex was seen for the
matching condition.
However, according to Elliott et al. (2000) the medial
orbitofrontal activation in their matching task is unlikely to
reect working memory processes per se. They argued that in the
matching condition an association between a specic stimulus
and a forthcoming response can be formed and maintained
through the delay interval. For the non-matching condition a
sample stimulus does not specify a forthcoming response and
therefore no association is formed. Therefore, the dierential
orbitofrontal activation may reect the maintenance of stimulus
response mappings in the matching-to-sample task.
Since, in our silent reading study no stimulusresponse
mapping was required, the activity in the ventromedial prefrontal
cortex is thus not likely to be related to stimulusresponse
border of left angular, middle, and inferior temporal gyrus. We

propose that this reects lexico-semantic processing (Binder
et al., 2003, 2009; Gold et al., 2005; Lau et al., 2008) based on local
lexical activity as proposed by the MROM or the DRC (Jacobs
and Grainger, 1994; Grainger and Jacobs, 1996; Coltheart et al.,
2001). In the case of words this results in successful activation
of a stored lexico-semantic representation whereas in the case
of nonwords no such representation can be found resulting in
greater deactivation of this region. This interpretation is also
supported by the additional ROI analysis which revealed a main
eect of lexicality but no main eect of neighborhood density
and no interaction in the angular and middle temporal gyrus.
We therefore suggest that the results of Henson et al. (1999) and
the present lexicality eect in the inferior parietal and middle
temporal cortex reect the activation and retrieval of wordspecic lexico-semantic information leading to higher activity
for words compared to nonwords (cf. Binder et al., 2003). The
obtained lexicality eect in the precentral and opercular cortex
with higher activity for nonwords compared to words is probably
related to the stronger demands on orthographic-phonological
mapping during reading of nonwords (e.g., Bitan et al., 2007;
Braun et al., 2009, 2015).
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Lexicality by Neighborhood Density Interaction
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Furthermore, the current study revealed an interaction of

lexicality by neighborhood density in left ventromedial prefrontal
cortex. Nonwords with a high number of neighbors showed
higher activity than words with a high number of neighbors in
this region. This activity mirrors the BOLD response pattern
obtained in lexical decision from Fiebach et al. (2007) in the
medial superior frontal gyrus who suggested that it reects
extra-lexical processing in the form of a domain-general neural
mechanism of executive control due to the processing demands of
speeded lexical decisions. Fiebach et al. (2007) further suggested
that the lower activity for words and the higher activity for
nonwords with a high number of neighbors reect executive
control processes suppressing the global lexical activation elicited
by the many neighbors of the target nonword. While this seems
plausible for lexical decisions, it is rather unlikely for silent
reading. Therefore, we would like to propose that the lexicality
by neighborhood interaction is not due to response suppression
or inhibition but rather to memory related processing in the
ventromedial prefrontal cortex.
Recently, Harand et al. (2012) reported a number of
prefrontal regions to be active during the remember/know task
that are relevant to our interpretation of the neighborhood
density eect in the prefrontal cortex. In particular, it was
suggested that frontal nodes in this network subserves topdown
attentional processes, involving inhibition, monitoring, and
working memory operative in memory retrieval. Analogously,
assuming that silent reading imposes only low demands
on executive control processes the present activity in the
ventromedial prefrontal cortex for words and nonwords with
a high numbers of neighbors may reect processes of working
memory including maintenance, monitoring, and the verication
of activated memory representations associated with presented
targets.
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activity in the models but appear to elicit low hemodynamic

activity. One possible explanation for this discrepancy is that
the longer a stimulus is processed the higher the BOLD
response (Buxton et al., 2004), an eect that was implemented
in the ACT-R, for example (Anderson et al., 2004). Words
and nonwords with a high number of neighbors may initially
elicit a higher BOLD response because the orthography of
these stimuli and their neighbors is more familiar and better
represented and thus easier accessed. This leads to a faster
identication and earlier termination of processing. In contrast,
words and nonwords with a low number of neighbors activate
fewer similar mental codes which probably also have a reduced
or noisier orthographic representation and thus an initially
lower BOLD response. This would make identication of
these items more dicult and eortful as proposed by Taylor
et al. (2012) in their engagement and eort model-to-braindata connection hypothesis. The result would be prolonged
processing and, in turn, by summation of activity over time,
a higher BOLD response for words or nonwords with few
neighbors. This explanation ts with simulations of the DRC,
predicting that words with many neighbors need less processing
cycles to reach an identication threshold, at least for low
frequency words in lexical decision (Coltheart et al., 2001),
compared to those with few neighbors (see Hofmann and
Jacobs, 2014 for a similar explanation of word frequency
eects).
mappings. We rather suggest that the lexicality by neighborhood

density interaction observed in the ventromedial prefrontal
cortex is mainly associated with the comparison/matching of
the stimuli to stored representations orthographically similar to
them.
We further propose that the obtained interaction in the
ventromedial prefrontal cortex for words and nonwords with
a high number of neighbors is not independent of the activity
in the ventral occipitotemporal cortex (e.g., Cavada et al., 2000;
Uylings et al., 2003; Bar, 2003) and to reect the operation of
dierent memory related processes. Words with a high number
of neighbors elicited lower activity in the ventromedial prefrontal
cortex compared to nonwords with a high number of neighbors.
It is likely that words with many neighbors are fast and easily
identied based on the processing in the VWFA eliciting a
quick intuitive feeling of rightness which allows for a true fastguess response in lexical decisions. In contrast, nonwords with a
high number of neighbors elicited higher activity in the ventral
occipitotemporal and ventromedial prefrontal cortex compared
to words. This probably reects more dicult matching processes
in the VWFA and probably eliciting only a lower degree of felt
rightness in the ventromedial prefrontal cortex which could lead
to prolonged processing by extending a response deadline in
lexical decisions for these stimuli.
The exploratory ROI analysis in the ventral occipitotemporal
cortex with the main eects of lexicality and neighborhood
density with lower activity for words compared to nonwords
and lower activity for words and nonwords with many neighbors
compared to those with few neighbors could support this view.
The VWFA seems to be involved in the coding of the lexical status
as well as the orthographic similarity of presented letter strings
(Glezer et al., 2009; Baeck et al., 2015). The observed pattern of
activity could reect easier access to words analogously to the
interpretation of lower activity in response to high frequency
words compared to low frequency words in the VWFA by
Kronbichler et al. (2004). Kronbichler et al. (2004) suggested
that high frequency words and orthographically familiar forms
allow for a fast assimilation of the letter input by readily available
orthographic representations of specic words in the VWFA. It
seems that the VWFA responds with lower activity to targets
which are similar to known and already stored items compared
to those which are less known or new (Kronbichler et al., 2004).
This is also consistent with the nding of Glezer et al. (2015)
who showed that word learning selectively increases neuronal
specicity for new words in the VWFA which could point to
the sensitivity of the VWFAs in the processing of letter strings
dependent on experience. In the light of these and our ndings,
we propose that words and nonwords with many neighbors
are identied based on their orthographic similarity to wholeword representations in the VWFA which is further evidence
for making this region a likely candidate for being part of an
orthographic lexicon.
Concerning the model-to-brain-data connection it seems that
there is no simple mapping between model activation and
the hemodynamic activity in the VWFA or the ventromedial
prefrontal cortex, as speculated by Jacobs and Carr (1995).
Words with many neighbors produce high values of global lexical
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Conclusion
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In sum, the present study sheds light on the neural bases

of orthographic processing by investigating the neighborhood
density eect in relation to the predictions of computational
models of visual word recognition. We interpret the obtained
activity in the dmPFC to mainly reect processes of verbal
working memory. This activity is modulated by the orthographic
similarity of the presented words and nonwords to stored
representations. We further suggest that the observed pattern of
brain activity could reect the operation of three mechanisms
proposed by the above-mentioned models: (i) a fast-guess
mechanism (Jacobs et al., 2003) based on the fast and easy visual
identication of stimuli in the VWFA and on a spontaneous
intuitive feeling of rightness of words with a high number of
neighbors in the ventromedial prefrontal cortex; (ii) a deadline
mechanism in the ventromedial prefrontal cortex which is
supposed to prolong processing time for words with few and
nonwords with many neighbors eliciting only lower levels of
felt rightness. Thus, similar to the suggestion of Moscovitch
and Winocur (2002) we think that the ventromedial prefrontal
cortex may be involved in criterion setting for accepting
or rejecting a memory trace. Both proposed mechanisms
probably are at work during this process. In the case of
words the fast-guess mechanism sets a positive criterion
leading to fast identication and subsequent termination of
processing. In the case of nonwords the temporal deadline
mechanism sets a negative criterion which prolongs processing
time for accepting or rejecting an item. In lexical decision
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propose that this activity reects the identication of single items

and their meaning based on local lexico-semantic activity.
the operation of both mechanisms results in shorter response

latencies for words and longer response latencies for nonwords
which probably is the basis of the dissociation of the
neighborhood density eects previously found for words and
nonwords with many neighbors. Finally, we propose the
operation of an identication mechanism indicated by the
lexicality eect in the inferior parietal and middle temporal
cortex with higher activity for words compared to nonwords and
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Acknowledgment
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We thank Sarah Schuster and Matthias Tholen for assistance in

preparing the gures of this manuscript.
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Conflict of Interest Statement: The authors declare that the research was
conducted in the absence of any commercial or nancial relationships that could
be construed as a potential conict of interest.
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Many neighbors are not silent. fMRI

Received: 28 April 2015

Many neurocognitive studies investigated the neural correlates of visual word

Frontiers in Human Neuroscience | www.frontiersin.org

July 2015 | Volume 9 | Article 423

Orthographic processing in silent reading

number of neighbors in lexical decision, as well as a greater N400

Damasio and Geschwind, 1984; Bookheimer, 2002; Binder

Frontiers in Human Neuroscience | www.frontiersin.org

July 2015 | Volume 9 | Article 423

Orthographic processing in silent reading

for this nding was that visually presented words match

connection is still weak, despite some recent progress (e.g., Levy

Frontiers in Human Neuroscience | www.frontiersin.org

Materials and Methods

The study was approved by the ethics committee of the University

July 2015 | Volume 9 | Article 423

Orthographic processing in silent reading

was Presentation software from Neurobehavioral Systems1 (San

Twenty-two healthy participants (15 women) participated in the

Experimental Materials and Procedure

Brain activity responses to 100 monosyllabic words and 100

Frontiers in Human Neuroscience | www.frontiersin.org

L, Number of letters, N, number of orthographic neighbors, F, word frequency per

Functional and structural imaging was performed with a Siemens

Statistical analysis was performed with a GLM two staged mixed

July 2015 | Volume 9 | Article 423

Orthographic processing in silent reading

calculated with 2 2 repeated measures ANOVAs and in case

cortex: words with a high number of neighbors showed lower

Effect of Neighborhood Density

The contrast of greater activity of high compared to low

To further investigate the basis of the neighborhood density

Computational models of visual word recognition predict that

Lexicality by Neighborhood Density Interaction

Furthermore, the whole-brain analysis revealed an interaction of

ROI Analysis for Selected Regions Showing a

Frontiers in Human Neuroscience | www.frontiersin.org

July 2015 | Volume 9 | Article 423

Orthographic processing in silent reading

gyrus, MTG, middle temporal gyrus, OP, opercular cortex, Occ.

Frontiers in Human Neuroscience | www.frontiersin.org

July 2015 | Volume 9 | Article 423

Orthographic processing in silent reading

Effect of lexicality (words >nonwords)

Angular gyrus, lateral occipital

Occipital Pole, lateral occipital

Effect of lexicality (nonwords > words)

Precentral gyrus, opercular