Neuropsychologia 68 (2015) 5970

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Neuropsychologia
journal homepage: www.elsevier.com/locate/neuropsychologia

Spatial imagery relies on a sensory independent, though sensory

sensitive, functional organization within the parietal cortex: A fMRI study
of angle discrimination in sighted and congenitally blind individuals
Daniela Bonino a, Emiliano Ricciardi a,b,n, Giulio Bernardi a, Lorenzo Sani a, Claudio Gentili c,
Tomaso Vecchi d,e, Pietro Pietrini a,c
a
Laboratory of Clinical Biochemistry and Molecular Biology, Department of Surgery, Medical, Molecular Pathology, and Critical Care,
University of Pisa, Pisa, Italy
b
MRI Lab, Fondazione G. Monasterio Regione Toscana/C.N.R., Pisa, Italy
c
Clinical Psychology Branch, Department of Surgery, Medical, Molecular Pathology, and Critical Care, University of Pisa, Pisa, Italy
d
Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
e
Brain Connectivity Center, National Neurological Institute C. Mondino, Pavia, Italy

art ic l e i nf o a b s t r a c t

Article history: Although vision offers distinctive information to space representation, individuals who lack vision since
Received 23 August 2014 birth often show perceptual and representational skills comparable to those found in sighted individuals.
Received in revised form However, congenitally blind individuals may result in impaired spatial analysis, when engaging in visual
31 December 2014
spatial features (e.g., perspective or angle representation) or complex spatial mental abilities. In the
Accepted 5 January 2015
present study, we measured behavioral and brain responses using functional magnetic resonance ima-
Available online 6 January 2015
ging in sighted and congenitally blind individuals during spatial imagery based on a modied version of
Keywords: the mental clock task (e.g., angle discrimination) and a simple recognition control condition, as conveyed
Supramodality across distinct sensory modalities: visual (sighted individuals only), tactile and auditory. Blind in-
Spatial representation
dividuals were signicantly less accurate during the auditory task, but comparable-to-sighted during the
Blindness
tactile task. As expected, both groups showed common neural activations in intraparietal and superior
Parietal cortex
Sensory-deprivation parietal regions across visual and non-visual spatial perception and imagery conditions, indicating the
more abstract, sensory independent functional organization of these cortical areas, a property that we
named supramodality. At the same time, however, comparisons in brain responses and functional con-
nectivity patterns across experimental conditions demonstrated also a functional lateralization, in a way
that correlated with the distinct behavioral performance in blind and sighted individuals. Specically,
blind individuals relied more on right parietal regions, mainly in the tactile and less in the auditory
spatial processing. In sighted, spatial representation across modalities relied more on left parietal re-
gions. In conclusions, intraparietal and superior parietal regions subserve supramodal spatial re-
presentations in sighted and congenitally blind individuals. Differences in their recruitment across non-
visual spatial processing in sighted and blind individuals may be related to distinctive behavioral per-
formance and/or mental strategies adopted when they deal with the same spatial representation as
conveyed through different sensory modalities.
& 2015 Elsevier Ltd. All rights reserved.

1. Introduction vision in shaping and modulating these functions, as well as in

Since the pivotal studies by Kosslyn in the seventies (e.g.,
Kosslyn, 1973), there is ample evidence that chronometric prop-
erties of mental images are shared with visual percepts. The role of
n
Correspondence to: Laboratory of Clinical Biochemistry and Molecular Biology,
University of Pisa, Azienda Ospedaliero Universitaria Pisana, Santa Chiara, Via
Roma, 67 Bldg. 43, I-56127 Pisa, Italy. Fax: 39 050 993556.
E-mail address: emiliano.ricciardi@bioclinica.unipi.it (E. Ricciardi).
inuencing the development of the neural structures underlying
these abilities, however, remains still to be fully dened.
Although vision offers distinctive information for the re-
presentation of the surroundings, so that for a long time it has
been thought to be crucial for the development of spatial abilities,
a growing body of evidence suggests that the lack of visual
experience may have just limited effects on the perception
and mental representation of space (Cattaneo et al., 2008;
Ricciardi et al., 2010). As a matter of fact, individuals who are

http://dx.doi.org/10.1016/j.neuropsychologia.2015.01.004
0028-3932/& 2015 Elsevier Ltd. All rights reserved.
60 D. Bonino et al. / Neuropsychologia 68 (2015) 5970
visually-deprived since birth show similar levels of performance to
sighted individuals in distinct spatial discrimination tasks, in-
cluding navigation, number processing or action planning (Aleman
et al., 2001; Cattaneo and Vecchi, 2011; Fleming et al., 2006;
Ricciardi et al., 2010; Vecchi, 1998).
Neuropsychological, lesion and functional brain studies in-
dicate that spatial perceptual abilities and spatial mental re-
presentations critically rely on posterior parietal regions (Ricciardi
et al., 2010; Sack et al., 2002a, 2002b; Trojano et al., 2002, 2000).
Interestingly, these cortical regions are activated during both
perceptual and imagery tasks, regardless of the sensory modality
through which such a spatial information has been acquired
(Cattaneo et al., 2008; Ptito et al., 2011; Ricciardi et al., 2014a,
2014b, 2010; Ricciardi and Pietrini, 2011). Furthermore, con-
genitally blind individuals recruit intraparietal and superior par-
ietal regions during non-visual spatial processing and localization
(Weeks et al., 2000), spatial imagery (Vanlierde et al., 2003), or-
ientation discrimination (Ptito, 2005), spatial attention and
memory (Bonino et al., 2008), and even numerical comparison
(Szucs and Csepe, 2005) tasks. Altogether, these observations
strongly suggest a more abstract, visual-independent sensory re-
presentation of spatial information in the human brain, that is, a
supramodal functional organization.
On the other hand, blind individuals do acquire a reduced
amount of sensorial information, in terms of both classical visual
spatial features (e.g., perspective or angle representation) and
their simultaneous and integrated perception, as compared to
sighted ones (Cattaneo and Vecchi, 2008). At a behavioral level,
these perceptual limitations result in impaired responses when
individuals perform spatial imagery tasks that rely on visually-
based representations, or that involve complex spatial mental
abilities (Cattaneo et al., 2008; Gori et al., 2014; Struiksma et al.,
2009). For instance, performance differed between congenitally
blind and sighted participants in a spatial-imagery task of angle
discrimination, but not in a visually-based or auditory-based
imagery tasks of object form (Noordzij et al., 2007). Similarly,
dealing with multiple or three-dimensional spatial mental re-
presentations may be rather problematic for congenitally blind
individuals (Vecchi, 1998; Vecchi et al., 1995). Indeed, blind in-
dividuals develop their cognitive mechanisms through touch and
hearing, which only allow for a sequential processing of informa-
tion. This may force people who lack vision since birth to rely, at a
higher cognitive level, on partially different non-visual spatial
processes (Noordzij et al., 2007; Vecchi, 1998).
At a neural level, brain responses across distinct perceptual
tasks in sighted and congenitally blind individuals show both si-
milar patterns of activation within wide portions of association
cortical areas (Ricciardi et al., 2014a) and a differential recruitment
of primary visual cortical areas (Vanlierde et al., 2003), due to
cross-modal plastic functional rearrangements in vision-related
cortical areas (Kupers et al., 2011a; Ricciardi and Pietrini, 2011).
Overall, these ndings indicate that in the brain supramodal and
cross-modal functional organizations coexist. As a matter of fact,
we can think of the two phenomena as of the two sides of the
same coin: supramodality is the functional architecture that takes
place despite the lack of visual input, whereas cross-modal plasti-
city is the functional rearrangement that occurs because of the lack
of sight (Ricciardi et al., 2014a, 2014b).
In the present study, we wished to examine to what extent (the
lack of) visual experience and the specic features of the distinct
sensory modalities may affect the brain functional architecture
that sustains spatial imagery. Specically, we measured brain re-
sponses in both sighted and congenitally blind individuals during
an angle discrimination task in which stimuli were presented
through the visual (sighted subjects only), tactile and auditory
pathways. Previous studies showed that in sighted individuals
angle size detection relies on a bilateral, though left-dominant,
recruitment of posterior parietal regions (Formisano et al., 2002;
Trojano et al., 2000). Further, at a behavioral level, congenitally
blind individuals showed signicantly lower degrees of perfor-
mance in a spatial-imagery task of angle discrimination as com-
pared to sighted ones (Noordzij et al., 2007).
Based on the observations discussed above, we predicted that
spatial imagery would be associated with a shared supramodal
functional response within the parietal cortical areas related to
spatial perception, that is, this area would be recruited in-
dependently from visual experience and from the sensory channel
used for angle spatial perception. At the same time, given the
distinctive features of mental processing, as well as previous
ndings from distinct studies on spatial perception in sighted and
congenitally blind individuals obtained in our own lab (Bonino
et al., 2008; Ricciardi et al., 2006, 2007), we also expected that
within this common supramodal functional architecture, patterns
of neural response would be shaped to some extent by visual ex-
perience and by the distinctive features of the specic sensory
modality utilized to acquire spatial information.
2. Materials and methods
2.1. Subjects
We measured neural activity in 10 sighted (7M/3F, mean
age7s.d. 29 73 years) and nine congenitally blind (5M/4F,
43716 years; age group comparison, t-test Bonferroni corrected,
p n.s.) right-handed healthy volunteers. Eight subjects were blind
from birth, and one became totally blind by the age of 18 months
(she lost the right eye vision at 10 months, and the left eye vision
at 18 months) and had no recollection of any visual memory. Only
individuals with a peripheral cause of congenital blindness were
admitted to the study. In order to avoid any possible bias due to
the familiarity with the task (e.g. Noordzij et al., 2007), we selected
only sighted and congenitally blind volunteers who had experi-
ence of analogical or traditional tactile Braille clocks, respectively.
Due to signicant head movement artifacts (greater than one voxel
sixe), three congenitally blind individuals had to be dismissed, so
that data from six congenitally blind (4M/2F, 39 716 years; age
group comparison, Bonferroni corrected p n.s.) volunteers en-
tered the behavioral and brain functional data analysis. Causes of
blindness for each of the six individuals are reported in Table 1.
All sighted and blind participants received a clinical examina-
tion, including routine blood tests and a brain structural MRI scan,
to exclude any disorder that could affect brain function or meta-
bolism, other than blindness in the blind group. No subject was
taking any psychotropic medication. All participants gave their
written informed consent after the study procedures and potential
risks had been explained. The study was conducted under a pro-
tocol approved by the Ethical Committee at the University of Pisa
Table 1
Characteristics of the congenitally blind volunteers enrolled in the study.
Gender Age Age of blindness onset Cause of blindness
(years) (months)
Male 31 0 Congenital glaucoma
Male 58 0 Congenital glaucoma
Male 53 0 Congenital optic atrophy of
unknown cause
Female 42 0 Retinopathy of prematurity
Female 20 18 Congenital glaucoma
Male 57 0 Congenital cataract
 D. Bonino et al. / Neuropsychologia 68 (2015) 5970
Fig. 1. Behavioral results. (A) fMRI design of the experimental tasks for the dif-
ferent sensory modality. ISI: inter-stimulus interval; ITI: inter-trial interval
(B) Accuracies in performance for the blind (red) and sighted (blue) groups during
the MCT conditions are shown in a graph bar plot. Signicant differences and in-
teractions in the group and post-hoc analyses are reported in black/thick lines and
gray/dotted lines for the repeated-measure ANOVAs between sighted and blind
groups and for within sighted participants, respectively. Chance level is shown at
50% as a bold white line. (For interpretation of the references to color in this gure
legend, the reader is referred to the web version of this article.)
Medical School. All participants retained the right to withdraw
from the study at any moment.
2.2. Experimental tasks and stimuli
2.2.1. Mental clock test
A revised version of Paivios Mental Clock Test (Paivio, 1978;
MCT) was used in our fMRI protocol (Fig. 1A). Participants were
asked to mentally compare the convex angles formed by the hands
of two analogical clocks, after they either perceived or imagined in
a sequential order a pair of clock faces prompted aurally, tactilely
or visually (only for the sighted individuals). Participants had to
decide in which clock the hands formed the wider convex angle
and answered by pressing foot pedals. The response correspon-
dence of right and left foot with the rst or second clock was
randomized across subjects, in order to control for any potential
effects of foot movements on brain activation. During the auditory
version of the MCT, volunteers sequentially listened to two clock
times for 2 s each, with a 1 s-long inter-stimulus period. During
the tactile version of the MCT, participants were asked to se-
quentially explore with both hands two wooden-made analogical
clocks (clock diameter: 20 cm, long hand: 8 cm, short hand: 5 cm)
for 4.5 s each, with a 1 s-long inter-stimulus period. During the
visual version of the MCT, sighted participants sequentially viewed
61
two analogical clocks for 2 s, with a 1 s-long inter-stimulus period.
Stimulation periods in the tactile and visual experimental tasks
were established by performing behavioral pre-test measures in
independent samples of individuals. Across all the three experi-
mental conditions, inter-trial interval (ITI) lasted 5 s, during which
the participants provided their responses. Within each fMRI ses-
sion, participants were presented with 18 trials.
2.2.2. Control conditions
Two control tasks for the tactile and auditory conditions were
administered to control for the sensorimotor and the semantic
components of the MCT.
For the tactile control task, non-sense scrambled wooden-
made clocks were used. The scrambled clocks were identical in
shape and dimension (clock diameter: 20 cm, long hand: 8 cm,
short hand: 5 cm) to the analogical clocks, but the two wooden-
made hands were positioned so that they did not form any angle.
The tactile control task followed the same presentation timing of
the tactile MCT. In a simple discrimination task, participants were
instructed to tactilely discriminate whether both the clocks of the
presented pair were analogical clocks or whether one of them was
a scrambled one. During each tactile control run, 28 scrambled
clocks and only four analogical clocks were administered.
Control auditory stimuli had the same characteristics of those
presented during the auditory MCT, but a time, rather than an
angle, discrimination task was performed. Participants sequen-
tially listened to two clock times for 2 s each, with a 1 s-long inter-
stimulus period, and had to decide which of the two clock times
was the earliest one in a chronological order. In both control tasks,
participants provided their responses via foot pedals. The response
correspondence of right and left foot was randomized across
subjects, in order to control for any potential foot movement la-
teralization effect on brain activation. Across the two control
conditions, ITI lasted 5 s, during which participants could provide
their responses. Within each fMRI session, participants were pre-
sented with 18 trials.
As previous MCT studies had shown that in sighted individuals
visual-based angle size detection relies on a bilateral, though left-
dominant, recruitment of posterior parietal regions, we chose not
to perform any visual control task in order to limit overall scan-
ning time (Sack et al., 2002b; Trojano et al., 2002, 2000). All the
verbal stimuli used during auditory experimental conditions were
administered by a MR-compatible pneumatic headphone system
(PureSound Audio System Wardray Premise Ltd. United Kingdom).
Visual stimuli were presented onto a rear projection screen viewed
by volunteers through the head coil prismatic mirror (visual eld:
25 wide and 20 high). Tactile stimuli were sequentially leaned by
an operator inside the MRI scanner on a magnetic compatible
small table placed over the participant abdomen, to be sure that
each volunteer could effectively touch the stimuli without any
head movement, as in similar tactile discrimination paradigms
adopted in previous experimental settings (Pietrini et al., 2004;
Ricciardi et al., 2007).
Prior to the fMRI scanning exam, all volunteers performed a
30 min long training session. Participants repeated the task across
all the three sensory modalities, and the two control tasks, until
they became familiar with the experimental paradigm. None of the
experimental stimulus pairs used during the training sessions was
employed in the subsequent fMRI experiment and no feedback
was provided to the subjects.
2.3. Image acquisition
fMRI images were acquired using a Gradient Echo echoplanar
(GRE-EPI) sequence with a GE Signa 1.5 T scanner (General Electric,
Milwaukee, WI). A scan cycle (repetition time (TR) 2500 ms) was
62 D. Bonino et al. / Neuropsychologia 68 (2015) 5970
composed of 21 contiguous axial slices (5 mm thickness, eld of
view (FOV) 24 cm, echo time (TE) 40 ms, ip angle 90, image
in plane resolution 64  64 pixels) and voxels dimensions were
3.75  3.75  5 mm3. We acquired 10 (congenitally blinds) and 13
(sighted subjects) runs for each participant. In both groups, ac-
cording to the specic experimental protocols, we recorded ve
sessions of 126 brain volumes (e.g., tactile MCT and control tasks,
overall acquisition time 315 s), and ve sessions with 90 brain
volumes (e.g., auditory MCT and control tasks, overall acquisition
time 230 s). Only sighted volunteers had three extra sessions with
90 brain volumes (e.g., visual MCT, overall acquisition time 230 s).
Each time series included 18 trial repetitions, began and ended
with 30 s and 20 s of no stimuli, respectively.
High-resolution T1-weighted spoiled gradient recall (SPGR-
TE 5.22 ms, TR 12.1 ms, FOV 240 mm with 256  256 acquisi-
tion matrix, 0.94  0.94 mm2 in-plane resolution, 120 axial slices
of 1.2 mm-thickness) images were obtained for each subject to
provide a detailed brain anatomy during structural image
acquisition.
2.4. Data analysis
2.4.1. Behavioral data
During the fMRI sessions, accuracy for each experimental
condition was recorded. Individual average accuracies for the
distinct experimental MCT conditions were used in a repeated-
measure, three-way ANOVA to evaluate differences in accuracy
within- and between-experimental groups (sighted and con-
genitally blind individuals) and sensory modalities (auditory and
tactile). Individual ages for the two groups were introduced as
covariate. Post-hoc T comparisons were assessed for signicant
(p o0.05) effects or interactions. In sighted individuals only, a re-
peated-measure, two-way ANOVA was used to assess differences
across sensory modalities for the MCT condition. Statistical ana-
lyses were performed by using IBMs SPSSs Statistics 21.
2.4.2. fMRI data
The AFNI and SUMA software package was used to analyze and
display functional imaging data (http://afni.nimh.nih.gov/afni,
(Cox, 1996)). Prior to standard preprocessing, the rst four vo-
lumes and the last volume acquired were discarded (resulting in a
total of 85 volumes for the visual and auditory sessions, and 121
for the tactile sessions) to allow the MR signal to remain at the
steady state. All raw volumes from the different runs were con-
catenated and coregistered (3dvolreg), temporally aligned
(3dTshift), and spatially smoothed (isotropic Gaussian lter,
FWHM 8 mm). Individual runs were normalized by calculating
the mean intensity baseline value for each voxel during the initial
(seven) and nal (three) resting volumes, and by dividing each
voxel value by its mean intensity to estimate the percent signal
change at each time point. Statistical analysis was performed using
a multiple regression to identify brain regions signicantly in-
volved in the auditory, tactile and visual MCT, and in the auditory
and tactile control conditions. The mean response to each stimulus
of each experimental condition was modeled with a separate re-
gressor, obtained by convolution of the task with a standard he-
modynamic response model (BLOCK basis function), to shape the
response to each of the 5 s (auditory and visual tasks) or 10 s
(tactile tasks) periods of stimulus presentation and processing,
followed by the 5 s response periods. By modeling each type of
stimulus presentation, this resulted in ve regressors of interest
for the sighted subjects (auditory, tactile and visual MCT and aural
and tactile control tasks) and in four regressors of interest for the
blind subjects (auditory and tactile MCT and aural and tactile
control tasks). Individual timepoints relative to uncorrected re-
sponses were censored, and thus not included in the multiple
regression analysis. The six movement parameters derived from
the volume registration and the polynomial regressors to account
for baseline shifts and linear/quadratic drifts in each scan series
were included in the multiple regression analysis as regressors of
no interest. Beta weights for the regressors that modeled the mean
responses to each experimental condition were used as estimates
of the strength of response relative to rest in each voxels. Beta
weights and T statistics for each experimental conditions were
transformed into the Talairach and Tournoux Atlas (Talairach and
Tournoux, 1988) coordinate system, and resampled into 1 mm3
voxels for group analyses. Activations were anatomically localized
on the sighted and congenitally blind group-averaged Talairach-
transformed T1-weighted images, and visualized using normalized
SUMA (SUrface MApping with AFNI) surface templates.
Group level analyses focused on, rst, identifying brain re-
sponses for each experimental condition in the two groups. Sec-
ond, overlapping, supramodal and MCT-specic responses in both
sighted and congenitally blind individuals were characterized. Fi-
nally, differential recruitments between sighted and congenitally
blind individuals were addressed, also through a comparison
among indices of functional connectivity strength from seed re-
gions showing supramodal responses.
2.4.2.1. Within-group and within-condition activations. A mixed-
effect meta-analysis (3dMEMA) identied patterns of activation
within experimental conditions for each group. Specically, a
within condition mixed-effects meta-analysis is equivalent to a
one-sample T-test. Compared to a conventional T-contrast, the
mixed-effects meta-analysis takes into account within-subject
variability of response in an activated brain region and assigns
each subject's contribution (from the individual T statistics of each
stimulus timeseries regression model) to the nal result based on
a weighted instead of an equal treatment (Chen et al., 2012). The
correction of these second-level analyses across task-activated
regions was made by using Monte-Carlo simulations, run via
3dClustSim with a voxelwise threshold of 0.01 that resulted in a
minimum cluster volume 4882 L, nearest-neighbor, for a cor-
rected p value o0.05 at cluster level.
2.4.2.2. Overlapping activations across conditions and across experi-
mental groups. To identify cortical areas responding within-single
subject to auditory and tactile MCT in congenitally blind in-
dividuals and to auditory, visual and tactile MCT in the sighted
group, a modied conjunction analysis also was used (as detailed
in Beauchamp et al., 2008). Briey, the T-statistic of the contrast
between stimulation vs. rest was calculated independently for
each experimental condition in each subject. Only signicant
voxels showing a positive BOLD response to each sensory modality
were selected (threshold for the unisensory response was set at
uncorrected po 0.05) and combined using a logical AND. All voxels
passing this test (signicant in Z7 sighted, or Z 5 early blind
individuals) were classied as common across conditions (Fig. 2A).
A conjunction analysis was also used to create the mixed-ef-
fects group map. A logical AND was performed with the mixed-
effect meta-analysis identied patterns of activation within ex-
perimental condition at a corrected p o0.05 cluster-level, as de-
tailed for the within-group and within-condition responses
(Fig. 2B). As supramodal areas, differentially from those cortical
regions showing a cross-modal plastic response, are present both
in sighted and blind individuals, a logical AND also was used to
overlap patterns of activation across experimental conditions be-
tween experimental groups (Fig. 2B).
2.4.2.3. Supramodal brain responses: correlation with behavioral
performances. According to the denition itself of supramodality,
cortical areas showing a supramodal response to spatial
 D. Bonino et al. / Neuropsychologia 68 (2015) 5970 63

Fig. 2. Overlapping activations across experimental conditions. Statistical maps showing overlapping activations across conditions in sighted and congenitally blind in-
dividuals as a result of single subject (A) and group (B) conjunction maps. The spatially-normalized results are projected onto single-subject hemisphere templates in
Talairach space for the two experimental groups in a lateral view.

discrimination (i.e., angle representation) task should show pat-
terns of neural activity that overlap between the sighted and the
blind groups. Furthermore, these areas should show higher task-
specic neural responses across the MCTs as compared to the
control conditions, and neural activity should correlate with the
behavioral performances across sensory modalities.
First, as a repeated-measure two-way ANOVA-comparable to
behavioral outcomes-could not be performed on functional data
due to unbalanced samples (as reported in Section 2, data from
three blind subjects had to be discarded due to excessive head
motion artifacts), a mixed-effect meta-analysis was used to iden-
tify only those brain areas with a within-group stronger response
to both tactile and auditory MCT as compared to the control
conditions. In details, beta weights and T statistics of the differ-
ences between MCT and control conditions were considered for
the two sensory modalities (i.e., auditory and tactile) in a single
one-sample T contrast (Fig. 3A). To perform a small volume
correction (SVC), we created a binary mask across the four within
condition patterns of activation (at a whole brain corrected
po 0.05) for each group, used this volume as an inclusive mask
and calculated via 3dClustSim the minimum cluster size for the
sighted and blind groups for a SVC corrected po 0.05 with a voxel-
wise threshold of 0.025 (nearest-neighbor, minimum cluster size
of 844 L for sighted, and of 702 L for congenitally blind
subjects).
In order to characterize further the differential access to su-
pramodal areas between experimental conditions and groups, a
mixed-effect meta-analysis was used to identify parietal clusters
with a within-group stronger response to tactile or auditory MCT as
compared to the control conditions (one-sample T contrasts as
above, but separated for the auditory and tactile modalities; volumes
of interest limited to the mixed-effects group conjunction maps
across experimental conditions and groups; voxel-wise threshold of
0.05 and an arbitrary minimum cluster size of 200 L Fig. 3B).

Fig. 3. Comparison between experimental conditions and performance/brain response correlation. Statistical maps showing brain regions with a signicantly different
response between MCT and control conditions across- (A) and within- (B) sensory modalities in sighted and congenitally blind individuals. (C) Clusters showing a signicant
correlation between supramodal responses and behavioral performance. The spatially-normalized results are projected onto single-subject hemisphere templates in Ta-
lairach space for the two experimental groups in a posterior view.
64 D. Bonino et al. / Neuropsychologia 68 (2015) 5970
Finally, to correlate supramodal brain responses with the be-
havioral performances across sensory modalities, the neural re-
sponses to MCT conditions for both the tactile and auditory
modalities of the two groups were considered in a single linear
trend analysis (run via 3dRegAna in AFNI) with the individual ac-
curacy for each experimental condition. Our volumes of interest
were limited for each group to brain regions showing a within-
group stronger response to both tactile and auditory MCT as
compared to the control conditions (uncorrected voxel-wise
threshold of 0.05), to limit any possible non-independence error
(Kriegeskorte et al., 2009; Vul et al., 2009). Results have been
graphically reported in Fig. 3C at a voxel-wise threshold of 0.05.
2.4.2.4. Differential brain response: between group comparisons. An
across groups mixed-effect meta-analysis (equivalent to an un-
paired T contrast) identied patterns of differential activation be-
tween sighted and congenitally blind groups for the tactile or the
auditory MCT condition. In order to perform a SVC, we limited our
volume of interest to brain regions activated during both auditory
and tactile MCT conditions (corrected po 0.05) across the sighted
and blind groups, with a voxel-wise threshold of 0.03 that resulted
in a minimum cluster volume 4 724 L, nearest-neighbor, for a
SVC corrected p value o 0.05 at cluster level.
2.4.2.5. Functional connectivity analysis. Each functional time-ser-
ies acquired during MCT execution was co-registered, temporally
aligned, spatially smoothed and normalized, as described above.
Then, data were resampled into 3 mm3 voxels, transformed into
Talairach space, and low-pass ltered (3dFourier) at 0.15 Hz to
remove high frequency physiological artifacts including cardiac
and respiratory pulsatility (Birn et al., 2006). The six movement
parameters estimated from the brain volume registration, and the
polynomial regressors that account for baseline shifts and linear/
quadratic/cubic drifts were mathematically removed from the
voxel timeseries (3dSynthesize) (Lund et al., 2006). To remove
potential residual artifacts and reduce the probability of nding
spurious functional correlations, white matter (WM) and cere-
brospinal uid (CSF) time-series were also regressed out (Ricciardi
et al., 2013). WM and CSF time courses were extracted from two
ROIs (1 voxel radius) located in the corpus callosum and lateral
ventricle, respectively, and identied on the common anatomical
template obtained by merging spatially normalized anatomical
images of all subjects included in the analyses. For each subject,
task-related scans obtained for tactile, auditory, and visual mod-
ality were concatenated separately. The seed ROIs were dened as
the overlapping clusters of response between sighted and blind
group conjunction maps obtained as logical AND with the patterns
of activation within experimental condition, as detailed above.
Whole brain functional connectivity was obtained by computing
the Pearsons correlation coefcient between the mean BOLD
time-course extracted from the seed ROI and the time-series of all
other voxels of the brain. Fisher's Z transformation was used to
convert correlation coefcients of each subject into Z scores. In
order to determine signicant differences in functional con-
nectivity between congenitally blind and sighted individuals,
nonparametric MannWhitney tests, equivalent to unpaired t-
tests, were performed for each ROI and modality. As before, our
volume of interest limited to brain regions activated during both
auditory and tactile MCT conditions (corrected po 0.05) across the
sighted and blind groups, with a SVC corrected p value o0.05 at
cluster level (voxelwise p o0.05, minimum volume of 1.053 L
voxels).
3. Results
3.1. Behavioral ndings
Accuracy (percent mean 7 st. dev) for both groups during the
MCT conditions were all signicantly above the chance level (50%;
po 0.001) sighted: auditory 82.3 7 6.9, tactile 78.5 75.4,
visual 90.5 77.8; Blind: auditory 72.3 7 10.9, tactile 81.2 79.4
(Fig. 1B). The repeated-measure, three-way ANOVA (age used as a
covariate) showed a signicant sensory modality  group interac-
tion (F(1,13) 10.5, p o0.006), but no signicant group (F(1,13) 0.2,
p4 0.6) or sensory modality (F(1,13) 3.5, p o0.08) effect. Post-hoc
comparisons showed a signicant within group effect in the au-
ditory MCT, and revealed a signicant (p o0.04, Bonferroni cor-
rected) higher accuracy in sighted as compared to blind in-
dividuals, while no group difference was found in the tactile MCT
(Fig. 1B).
The repeated-measure, two-way ANOVA in the sighted in-
dividuals revealed only a signicant modality effect (F(2,18) 10.35,
po 0.001), with a higher accuracy for the visual MCT as compared
to either the auditory (p o0.008, Bonferroni corrected) or tactile
(p o0.001, Bonferroni corrected) MCT conditions; no differences in
accuracy were found between the auditory and tactile MCT con-
ditions (Fig. 1B).
Behavioral data for each of the control task conditions showed
an accuracy greater than 95%. Due to this performance at a ceiling
level, no differences across sensory modalities or groups were
found.
3.2. Brain functional results
3.2.1. Neural response to auditory, visual and tactile MCT and control
conditions
In brief, both congenitally blind and sighted volunteers showed
a signicant (corrected p o0.05) recruitment of posterior parietal
cortical areas-including the intraparietal, the superior and inferior
parietal cortex-across auditory, visual and tactile MCT, as com-
pared to a resting baseline (Fig. S1). Additionally, in sighted vo-
lunteers, auditory, tactile and visual MCT conditions activated a
bilateral, though left prevalent, cortical pattern that included
dorsolateral and inferior frontal cortex, insula, ventral premotor,
and ventrotemporal regions. As expected, primary sensory cortical
areas were enrolled according to the specic sensory modalities
(see Supplementary materials, Fig. S1).
On the other hand, during the two control conditions, both
auditory and tactile tasks showed patterns of positive and negative
changes in brain activity as compared to the resting baseline si-
milar to those described for the respective MCT in both sighted
and blind individuals.
3.2.2. Overlapping activations across experimental conditions
The voxel-by-voxel analysis to obtain a single subject con-
junction map (Beauchamp et al., 2008) identied overlapping
clusters in bilateral posterior parietal and intraparietal regions in
both sighted and blind individuals (Table 2). Additionally, over-
lapping regions were found also in left middle frontal and pre-
motor areas in both groups, and in ventrotemporal, temporo-oc-
cipital and dorsal occipital regions in the blind group (Fig. 2A).
To determine the cortical regions that responded to all three
modalities, we also performed a conjunction analysis to create a
mixed-effects group map (Fig. 2B). The overlapping map showed
an active pattern of bilateral posterior parietal and intraparietal
regions recruited across all the three sensory conditions by both
sighted and congenitally blind individuals (Table 2). Additionally,
bilateral middle temporal, supplementary motor, bilateral middle
frontal and dorsal premotor areas were recruited in sighted
 D. Bonino et al. / Neuropsychologia 68 (2015) 5970 65

Table 2 Table 2 (continued )

Cortical regions with signicant clusters of neural activity as identied by the
different contrasts. Brain areas Hem Sighted Blind
Coordinatesa Coordinates
Brain areas Hem Sighted Blind
Coordinatesa Coordinates x y z x y z

x y z x y z Middle frontal L  46 2 33

Overlapping activations across experimental conditions single subject

conjunction map Comparison between groups-MCT tactile modality
Posterior parietal/ L  37  44 39  32  41 44 Superior parietal/ R 26  54 42
intraparietal intraparietal
R 40  39 43 27  52 43 Middle occipital R 28  80 6
Middle frontal/ L  51 0 33
precentral
Overlapping activations across experimental conditions mixed-effect group
map
Posterior parietal/ L  33  51 45  21  55 46 Comparison between groups-MCT auditory modality
intraparietal Middle occipital L  17  84 15
R 34  44 46 25  57 42 R 31  78 4
Middle temporal L  47  48 7  35  64  13 Ventro-temporal L  32  63  11
R 50  50 5 34  55  19 R 32  56  13
Supplementary L 0 6 53 Middle frontal/ L  51 2 35
motor precentral
Middle frontal L  47 1 31
a
R 48 6 30 39 1 48 For each region, x, y, and z coordinates of the peak overlap from Talairach and
Dorsal premotor L  27  10 53 Tournoux atlas (Talairach & Tournoux, 1988) are provided. x distance in milli-
areas meters to the right ( ) or the left () side of the midline, ydistance anterior ( )
R 29 7 56 or posterior () to the anterior commissure z distance superior ( ) or inferior ()
Ventral and dorsal L  21  87 9 to a horizontal plane through the anterior and posterior commissures.
b
occipital This coordinate value in italic has been reported at a uncorrected po 0.05, as
R 5  93 2 described in Section 3.
R 29  80 6

Overlapping clusters in the conjunction analyses across experimental con-

individuals, while congenitally blind individuals showed addi-
ditions and between experimental groups
Posterior parietal/ L  27  57 45  27  57 45 tional bilateral ventral and dorsal occipital, middle temporal and
intraparietal right middle frontal clusters (Table 2).
R 30  53 44 30  53 44 Overlapping clusters in the conjunction analyses across ex-
perimental conditions and between experimental groups were
Comparison between experimental conditions: MCT4control tasks-auditor- found in bilateral posterior parietal and intraparietal regions
y tactile modalities (green clusters in Fig. 2B; Table 2).
Superior parietal/ L  22  71 46  25  49 40b
intraparietal
R 23  65 49 26  56 39 3.2.3. Comparison between experimental conditions: MCT vs. control
Middle frontal L  50 0 33 tasks
R 53 8 31 The within-group MCT vs. control comparisons identied brain
Precentral R 56  17 39 areas with a stronger response to both tactile and auditory MCT as
Supplementary R 3  20 68
motor
compared to the control conditions (Fig. 3A). Interestingly, even if
Anterior middle L  57  27 6 both groups relied on common superior parietal and intraparietal
temporal regions bilaterally, the within-group MCT vs. control condition
Fusiform and in- L  34  72  20  20  69  18 comparisons identied a distinct lateralization of the recruitment
ferior occipital
R 28  66  14
across this spatial processing network in the tactile and auditory
conditions.
In sighted individuals (Fig. 3A, left side and Table 2), bilateral
Comparison between experimental conditions: MCT4control tasks-auditory
modality superior parietal and intraparietal cortex, bilateral middle frontal
Superior parietal/ L  17  70 51 and right precentral clusters showed a signicantly stronger (SVC
intraparietal po 0.05) response to both auditory and tactile MCT as compared
R 26  55 39
to the control conditions. Vice versa, supplementary motor area
and paracentral cortex, and left anterior middle temporal, bilateral
Comparison between experimental conditions: MCT4control tasks-tactile fusiform and inferior occipital clusters showed a higher response
modality
to both auditory and tactile control conditions.
Superior parietal/ L  21  70 48
intraparietal In blind individuals (Fig. 3A, right side), brain areas with a
R 26 64 49 25  54 41 within-group signicantly stronger (SVC po0.05) response to both
auditory and tactile MCT as compared to the control conditions
Correlation between supramodal responses and behavioral performances were identied in the right superior parietal and intraparietal re-
Superior parietal/ L  14  71 51  31  44 34 gion and left middle occipital and lingual gyri. At an uncorrected
intraparietal threshold, a left superior parietal and intraparietal cluster also
L  37  43 35
showed a stronger response to MCT task as compared to the control
R 35  44 40 39  46 42
Inferior/middle L  49  60 6 conditions in blind individuals. A signicantly higher response in
temporal the right inferior/middle temporal cortex was found in the blind
R 55 58  13 group for the control conditions as compared to the MCT tasks.
66 D. Bonino et al. / Neuropsychologia 68 (2015) 5970

As an experimental group  condition interaction could not be
directly assessed at a functional level due to the unbalanced
sample sizes, within-group MCT vs. control comparisons were also
performed separately for the tactile and auditory modalities. In
particular, we characterized the extent of those parietal clusters
with a stronger response to MCT as compared to the control task,
as an indirect evaluation of the group-specic access to supra-
modal spatial processing regions for the two sensory modalities
(Fig. 3B).
Sighted individuals showed a signicantly greater supramodal
response in a left superior/intraparietal cluster for both tactile and
auditory conditions (Fig. 3B, Table 2). A right superior parietal
cluster also showed a stronger response in sighted participants
during the tactile modality.
On the contrary, blind individuals showed signicantly greater
intraparietal clusters located on the right hemisphere for both
tactile and auditory conditions (Fig. 3B, Table 2).
3.2.4. Correlations between supramodal responses and behavioral
performance
As described in the Methods, a linear trend analysis was per-
formed to correlate the supramodal response specic to the MCTs
with the experimental behavioral outcomes. Specically, as com-
pared to multisensory regions, a supramodal response should be
expected to be higher across the MCTs as compared to the control
conditions, and even to correlate with the behavioral performance
measures. The linear trend showed that bilateral, though prevalent
in the left hemisphere, superior parietal and intraparietal clusters
in both groups showed a neural response across the MCTs that
correlated to the individual accuracy levels (Fig. 3C and Table 2). In
sighted individuals, also left inferior/middle temporal and middle
frontal clusters showed a signicant correlation between neural
responses and performance levels.
3.2.5. Differential brain responses: between group comparisons of
functional activation and connectivity strength patterns
Brain responses during experimental tasks in the two groups
were compared by using an across groups mixed-effect meta-
analysis to determine patterns of differential activation between
sighted and congenitally blind groups for the tactile or the audi-
tory MCT condition (Fig. 4A). During the tactile MCT task, sig-
nicant (SVC cluster po 0.05; voxel-wise po 0.01) differences
were found between the two groups, with a greater activation in
the right superior parietal and intraparietal region and in right
middle-dorsal occipital clusters in blind individuals, while sighted
individuals showed a signicantly higher response in left middle
frontal/precentral cortex. During the auditory MCT, a similar dif-
ferential pattern was found, but no differences in parietal regions
were found. Blind individuals resulted in a signicantly higher
activation of bilateral middle occipital and ventro-temporal cortex
(Table 2), while sighted individuals relied more on the recruitment
of the left middle frontal/precentral cortex.
For the functional connectivity comparison, the conjunction
map (Fig. 2B) obtained by combining task-related group activation
maps for all the investigated sensory modalities revealed two
clusters located symmetrically in left and right superior parietal
cortex (Talairach x, y, and z coordinates:  24,  57, 45; 30,
 53, 44). These supramodal clusters were used as seed ROIs for
whole brain functional connectivity computation for each group
and experimental condition. When using both the left and right
parietal clusters as seed ROIs, blind individuals showed a sig-
nicantly higher connectivity strength from the parietal seeds to
left superior parietal/intraparietal regions and ventral and dorsal
occipital clusters, while sighted individuals to left middle frontal/
precentral regions (Fig. 4B).
4. Discussion
Individuals who lack vision since birth often show perceptual
and representational skills comparable to sighted individuals.
However, in tasks that involve complex spatial mental abilities,
congenitally blind individuals may reveal an impaired spatial
analysis. In order to dissect the differential effects of the lack of
visual experience on the behavioral and neural correlates of spatial
imagery sustained by distinct sensory modalities, in the present

Fig. 4. Between group comparisons of functional activation and connectivity strength patterns. Statistical maps showing signicantly different brain responses of functional
activation (A) and connectivity strength (B top: right parietal seed; bottom: left parietal seed) patterns between sighted and congenitally blind individuals for the two
sensory modalities. The spatially-normalized results are projected onto single-subject hemisphere templates in Talairach space for the two experimental groups. The ROI
spheres used as functional connectivity seeds are shown in light green. SP/IPS: superior parietal and intraparietal regions; MF/PM: middle frontal and premotor regions.
(For interpretation of the references to color in this gure legend, the reader is referred to the web version of this article.)
 D. Bonino et al. / Neuropsychologia 68 (2015) 5970
study sighted and congenitally blind subjects were asked to per-
form the same spatial angle discrimination task under distinct
sensory conditions, using visual, tactile and auditory stimuli,
respectively.
Our ndings showed both common and differential behavioral
and functional responses between congenitally blind and sighted
subjects. Specically, from a behavioral point of view, we found
that in the tactile based angle discrimination task, performance
did not differ between the two groups, while performance was
signicantly impaired in the blind group when using the auditory
modality, in line with previous reports (Noordzij et al., 2007).
Then, we investigated the neural counterparts for these com-
mon and distinct behavioral effects in spatial imagery across
sensory modalities and groups.
First, we tested the hypothesis that the neural mechanisms that
subserve angle spatial perception and imagery are supramodal in
nature. In addition, we predicted that these parietal cortical areas
would be recruited in the mental representation of spatial in-
formation acquired through non-visual sensory modalities both in
sighted and in congenitally blind subjects, in a way related to their
distinct performance levels. Consequently, differences in the pat-
terns of neural response in blind individuals between the tactile
and auditory MCTs could be interpreted as functional correlates of
specic levels of performance, or mental strategies, when subjects
deal with the same spatial representation as conveyed through
different sensory modalities.
4.1. Overlapping activations across sensory conditions and groups
reect supramodal responses in the parietal cortex
Superior parietal and intraparietal regions have been strongly
involved in the perception, representation and processing of spa-
tially-coded information, independently from the sensory mod-
ality through which this information is conveyed to the brain (e.g.
Bonino et al., 2008; Cattaneo et al., 2008; Ptito, 2005; Ricciardi
et al., 2006, 2007; Vanlierde et al., 2003; Weeks et al., 2000). Here,
we expanded this scheme of a common and more abstract re-
presentation of spatial information to geometric in-plane re-
presentations. Specically, this experimental paradigm showed
both that common clusters in superior parietal and intraparietal
cortex process perceptual features and sustain mental re-
presentation of spatial information as prompted by the three dif-
ferent sensory modalities (i.e., tactile, auditory and visual stimu-
lation) in sighted individuals, and that overlapping parietal re-
sponses occur in individuals who lack sight since birth as well.
These observations in both sighted and congenitally blind in-
dividuals indicate that visual experience is not a necessary pre-
requisite for the development of a functional neural architecture
within the parietal cortex, which indeed plays a more general role
in processing spatial information. In addition, these shared acti-
vations in areas within the posterior parietal cortex provide sup-
port to a common neural basis for the analysis of space in per-
ception and imagery (Trojano et al., 2000).
Overall, the superior parietal and intraparietal cortical areas
appear to play a more general role in spatial representation. As a
matter of fact, the mental representation of several cognitive
functions, including the domains of number processing and
mathematics, music, language, or learning, is spatial in format
(Hubbard et al., 2005; Ricciardi et al., 2014b; Beecham et al., 2009).
Moreover, spatial localization and representation are necessarily
integrated in motion discrimination, motor planning and control,
or action understanding (Grefkes and Fink, 2005; Johnson et al.,
1996). Additionally, the ability to navigate in the surrounding
space relates to individual spatial map processing (Cattaneo and
Vecchi, 2011; Ricciardi et al., 2010). Altogether, these spatial-re-
lated abilities critically rely on the mental representation of the
67
space itself, and on the processing of sensorimotor information
within specic frames of reference. Interestingly, our observation
of a supramodal parietal role supports our perspective that, al-
though vision offers distinctive information for spatial processing,
individuals who are visually-deprived since birth show spatial
representation that are for the most part comparable to those in
sighted individuals, even for those cognitive domains that im-
plicitly rely on mental spatial representations, such as number
processing or action planning (Cattaneo et al., 2010; Eger et al.,
2003; Ricciardi et al., 2009, 2010; Zacks, 2008).
In order to precisely dene the parietal areas involved in the
geometric in-plane representation tasks, different univariate
comparisons were conducted to isolate specic supramodal re-
sponses (Ricciardi et al., 2014a; Ricciardi and Pietrini, 2011). As the
current experimental design does not allow to assess whether the
neural content of spatial information was truly shared across
sensory modalities-for instance, as by performing a multivariate
analysis (a depth discussion abouth this topic may be found in
Ricciardi and Pietrini, 2011; Ricciardi et al., 2014a, 2014b) , in the
current protocol we expected that supramodal responses should
reasonably fulll the following three functional conditions.
First, by denition, supramodal recruitment should be shared,
that is, should overlap, across sensory modalities-visual, tactile
and auditory-in both sighted and congenitally blind (auditory and
tactile modalities only) individuals. Indeed, the bilateral superior
parietal and intraparietal clusters reported here were commonly
recruited by both experimental groups.
Second, supramodal clusters should show a content specic
response (i.e., signicantly higher responses during the MCTs as
compared to the control conditions) and also correlate with the
behavioral performance levels across sensory modalities. This
second characteristic should differentiate supramodal from multi-
sensory responses: indeed, neural responses in multisensory areas
equally overlap across modalities but in an independent way from
the specic content of sensory information (Beauchamp et al.,
2008; Ricciardi and Pietrini, 2011). In the present study, as com-
pared to control conditions, bilateral superior parietal and in-
traparietal clusters demonstrated signicantly higher responses
for angle representation across sensory modalities.
Finally, the linear trend analysis indicated that neural responses
across the MCTs of bilateral superior parietal and intraparietal
clusters in both groups correlated to the individual accuracy le-
vels.. Therefore, superior parietal and intraparietal cortex t all the
three functional criteria required for a brain region to be dened as
supramodal.
The supramodal parietal responses reported here closely
overlap with the clusters of activation in precuneus, superior
parietal and intraparietal cortex found during tactile (Bonino et al.,
2008) or auditory (Gougoux et al., 2009; Voss et al., 2008) pro-
cessing of spatial information, or spatial imagery (Vanlierde et al.,
2003) in congenitally/early blind individuals.
Our two groups also showed additional areas of shared brain
responses. Both the conjunction maps at individual and group
levels showed in congenitally blind individuals an overlapping
cross-modal recruitment in ventrotemporal, temporo-occipital and
dorsal occipital regions across sensory modalities, as shown for a
wide gamut of non-visual perceptual and cognitive tasks (re-
viewed, among others, in Cattaneo and Vecchi, 2011; Cattaneo
et al., 2008; Kupers et al., 2011b; Merabet and Pascual-Leone,
2010; Noppeney, 2007; Pietrini et al., 2009; Ricciardi and Pietrini,
2011; Collignon et al., 2011).
In sighted individuals, a common response was also found in a
middle frontal and precentral cluster, consistent with previous
fMRI studies using the MCT to examine visuospatial imagery
(Formisano et al., 2002; Sack et al., 2002b; Trojano et al., 2000).
This prefrontal area has been associated consistently with
68 D. Bonino et al. / Neuropsychologia 68 (2015) 5970
attentional and working memory processes with visual and non-
visual stimuli in both sighted and blind individuals (Bonino et al.,
2008; Ricciardi et al., 2006). While blind individuals in our non-
visual MCTs also recruited this cluster, in the sighted group the
midfrontal/precentral areas showed both a signicantly greater
activation and a stronger connectivity with supramodal parietal
regions, maybe related to a more prominent role of these pre-
frontal areas in the integration of sensory inputs coming from
different modalities. In turn, the absence of vision may determine
a modication in the involvement of central functions and, more
specically, of connections with parietal and intraparietal areas
(Leo et al., 2012).
4.2. Access to supramodal spatial representation is modulated by
sensory experience and behavioral performance
During spatial perception and imagery, supramodal superior
parietal and intraparietal regions were activated bilaterally.
Nonetheless, the within-group MCT vs. control task condition
comparisons identied parietal clusters with a signicantly higher
response to tactile and auditory MCT in the left hemisphere in
sighted individuals, and in the right hemisphere in the con-
genitally blind sample (Fig. 3A and B). Additionally, in a group
comparison, congenitally blind individuals showed a greater re-
sponse in the right superior parietal and intraparietal region
during the tactile, but not during the auditory, MCT as compared to
sighted individuals. Finally, although spatial representation in
congenitally blind individuals appeared to rely more on the right
parietal regions, supramodal parietal seeds resulted in a higher
connectivity strength with left superior parietal/intraparietal re-
gions and occipito-temporo visual areas both during the tactile
and auditory MCT tasks, as compared to sighted individuals.
Altogether, these results delineate a bilateral spatial re-
presentation, which is left-dominant in sighted and right-domi-
nant in congenitally blind individuals, respectively. In particular,
both group activations and functional connectivity maps suggest
that blind individuals make a greater use of the right parietal
regions when an effective spatial representation occurs, as mir-
rored by the behavioral differences between auditory and tactile
MCTs. In fact, as blind individuals had an impaired performance
during the auditory, but not the tactile, spatial imagery task, the
right superior and intraparietal clusters showed signicantly
higher responses in blind as compared to sighted individuals only
during the tactile, but not the auditory, MCT condition.
Is this asymmetric response in parietal regions related to a
distinct spatial mental representation (and strategy) in con-
genitally blind individuals, or to an additional recruitment that
compensates for the lack of visual inputs?
Specic hemispheric differences in brain response during vi-
suospatial processes have been reported already in sighted in-
dividuals. Of interest, Sack et al. (2002a, 2002b) showed that,
while a visual MCT activated bilaterally the superior parietal and
intraparietal regions, only the subgroup of sighted individuals who
received repetitive transcranial magnetic stimulation (rTMS) to the
right parietal lobe resulted in an impaired visuospatial perfor-
mance. No signicant differences were reported in the sham and
in the left hemisphere stimulation groups. This observation sug-
gests an hemispheric asymmetry in the functional relevance of
parietal regions in spatial performance with the right parietal
cluster being able to compensate for the suppression of the left
one, and showing a high lateralized cortical representation of
some visuospatial functions (Sack et al., 2002b).
Furthermore, additional pieces of evidence indicate that the
recruitment of parietal (and prefrontal) regions during spatial
processing of mental images show a pattern of relative later-
alization according to the specic cognitive computation used by
participants, with the left hemisphere being mainly activated
during the categorical encoding and the right in the coordinate
(metric) task (Baciu et al., 1999; Trojano et al., 2002). The func-
tional observations in sighted individuals on the lateralization of
visuospatial representations suggest that blind individuals may
employ compensatory cognitive mechanisms to overcome the
limitations due to sight loss. In our protocol, a greater recruitment
of right parietal regions occurred in blind individuals, in particular
when their performance was analogous to the sighted sample, i.e.,
during the tactile-based spatial processing task. This additional
recruitment may be consistent with the hypothesis of a functional
compensation of the right parietal cluster when the contribution
of the left parietal regions to spatial processing is insufcient, or
(sensory) impaired (Sack et al., 2002b). In our case, the MCT es-
sentially involves a size comparison. Typically, during the auditory
task condition, most of the sighted participants would compare
digital times by rst generating visual images of the two clocks
from the numerical/verbal cues, and then by mentally contrasting
the angles formed by their hands. For blind individuals, though,
while the tactile condition of the mental clock task mainly requires
a simpler perceptual comparison, the auditory mental clock task
condition relies on a more complex translation of the digital in-
formation into a symbolic representation of spatial differences. As
a matter of fact, the observed impaired behavioral performance in
the blinds during the auditory task is consistent with the fact that
perceptual limitations related to the lack of visual inputs impair
behavioral performance when dealing with multiple spatial
mental representations (Vecchi, 1998; Vecchi et al., 1995) and
likely force blind individuals to rely, at a higher cognitive level, on
partially different non-visual spatial processes (Noordzij et al.,
2007; Vecchi, 1998), as we also conrmed at a functional level.
On the other hand, it cannot be excluded that this lateralization
may be more directly related to specic spatial representations in
conditions of sensory-deprivation. Categorical-based, left-dominant
spatial representation relies on a more global reconstruction of
mental images, which could be more typically related to vision. Co-
ordinate evaluation is based on a metric spatially-organized assem-
bling of multi-part mental images, is lateralized to the right parietal
cortex and could be more related to tactile (and maybe auditory)
processing in blind individuals (Kosslyn, 1994). Consistently with this
hypothesis, blind individuals have been recently shown to be speci-
cally impaired in the ability, that requires a metric representation of
auditory space, to judge the relative position of a sound source in a
sequence of three spatially separated stimuli (Gori et al., 2014). The
specic impairment in a task requiring a well-calibrated auditory
spatial representation (auditory space bisection) is consistent with
the behavioral and functional observations of our protocol.
4.3. Limitations of the study
In the present experimental protocol, behavioral and functional
data were acquired from relatively small samples of sighted and
congenitally blind subjects as compared to those frequently found
nowadays in fMRI studies.
However, it should be kept in mind that individuals with con-
genital blindness due to a peripheral cause represent an ex-
ceptionally rare sample, and even more so when strict selection
criteria from a medical (e.g., healthy, drug-free) and demographic
(e.g., independent living conditions, socially integrated) perspec-
tive are adopted. Moreover, all our congenitally blind volunteers
had to be familiar with the use of traditional tactile Braille clocks.
Also, the different task conditions that comprised the experi-
mental paradigms were overall relatively demanding, and this
likely led to the loss of fMRI data from three-out of the original
group of nine-congenitally blind individuals due to excessive head
movement during scanning.
 D. Bonino et al. / Neuropsychologia 68 (2015) 5970
Furthermore, some methodological issues in data analysis were
taken into consideration to comply with the characteristics of
these experimental samples. Specically, within-condition mixed-
effects meta-analysis available in AFNI were employed. As com-
pared to conventional T-contrasts, this approach takes into ac-
count within-subject variability of response in an activated brain
region and it is useful for comparisons with limited samples (Chen
et al., 2012). In addition, in our statistical evaluations, we always
selected statistical thresholds corrected for multiple comparisons,
even when analyses were limited to selected task-specic brain
areas, thus minimizing type II error risks.
In conclusion, in spite of the limitations discussed above, that
certainly warrant that this study be replicated in larger in-
dependent groups, our ndings indicate that spatial representa-
tion relies on a distributed parietal cortical network that develops
and functions independently from visual experience and is able to
process non-visual spatial information. Our results are in line with
and expand data from previous studies supporting the supramodal
nature of this functional cortical organization. Our data also show
that within this supramodal cortical organization both visual ex-
perience and the distinct sensory modalities do play a modulatory
effect, again in line with ndings from separate studies, including
those from our own lab (Ricciardi et al., 2014a, 2014b, 2007).
From a more general perspective, along with a number of
functional brain studies conducted in congenitally blind in-
dividuals over the last decade (see Ricciardi and Pietrini, 2011;
Ricciardi et al., 2014a, 2014b for reviews), these ndings corro-
borate the hypothesis that the brain ne morphological and
functional architecture is to a large extent pre-programmed to
occur independently from (the lack of) visual experience and,
likely, other sensory modalities as well. This may contribute to
explain how individuals who are born deprived of sight may re-
present a world that they have never seen and interact efciently
with others.
Appendix A. Supplementary material
Supplementary data associated with this article can be found in
the online version at http://dx.doi.org/10.1016/j.neuropsychologia.
2015.01.004.
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