Journal of Psychosomatic Research 77 (2014) 391400

Contents lists available at ScienceDirect

Journal of Psychosomatic Research

Personality traits modulate subcortical and cortical vestibular and

anxiety responses to sound-evoked otolithic receptor stimulation
Iole Indovina a,b,, Roberta Riccelli c, Jeffrey P. Staab d, Francesco Lacquaniti a,b,e, Luca Passamonti f
a

Laboratory of Neuromotor Physiology, IRCCS Santa Lucia Foundation, 00179, Rome, Italy
Centre of Space BioMedicine, University of Rome Tor Vergata, 00173, Rome, Italy
Department of Medical and Surgical Sciences, University Magna Graecia, Catanzaro, Italy
d
Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA
e
Department of Systems Medicine, Neuroscience Section, University of Rome Tor Vergata, 00133 Rome, Italy
f
Institute of Bioimaging and Molecular Physiology, National Research Council 88100, Catanzaro, Italy
b
c

a r t i c l e

i n f o

Article history:
Received 20 March 2014
Received in revised form 31 July 2014
Accepted 5 September 2014
Keywords:
Anxiety
Neuroticism
Introversion
Sound-evoked vestibular stimulation
fMRI
Chronic subjective dizziness

a b s t r a c t
Objective: Strong links between anxiety, space-motion perception, and vestibular symptoms have been recognized for decades. These connections may extend to anxiety-related personality traits. Psychophysical studies
showed that high trait anxiety affected postural control and visual scanning strategies under stress. Neuroticism
and introversion were identied as risk factors for chronic subjective dizziness (CSD), a common psychosomatic
syndrome. This study examined possible relationships between personality traits and activity in brain vestibular
networks for the rst time using functional magnetic resonance imaging (fMRI).
Methods: Twenty-six right-handed healthy individuals underwent fMRI during sound-evoked vestibular stimulation. Regional brain activity and functional connectivity measures were correlated with personality traits of
the Five Factor Model (neuroticism, extraversion-introversion, openness, agreeableness, consciousness).
Results: Neuroticism correlated positively with activity in the pons, vestibulo-cerebellum, and para-striate cortex,
and negatively with activity in the supra-marginal gyrus. Neuroticism also correlated positively with connectivity
between pons and amygdala, vestibulo-cerebellum and amygdala, inferior frontal gyrus and supra-marginal
gyrus, and inferior frontal gyrus and para-striate cortex. Introversion correlated positively with amygdala activity
and negatively with connectivity between amygdala and inferior frontal gyrus.
Conclusions: Neuroticism and introversion correlated with activity and connectivity in cortical and subcortical
vestibular, visual, and anxiety systems during vestibular stimulation. These personality-related changes in
brain activity may represent neural correlates of threat sensitivity in posture and gaze control mechanisms in
normal individuals. They also may reect risk factors for anxiety-related morbidity in patients with vestibular
disorders, including previously observed associations of neuroticism and introversion with CSD.
2014 Elsevier Inc. All rights reserved.

Introduction
Anxiety inuences postural control and locomotion in health and
disease, though neural mechanisms responsible for these effects are
incompletely understood. In the 1870s, publication of the original denition of agoraphobia (i.e., spatial disorientation and fear in busy town
squares) sparked debates about interactions among anxiety, spatial
orientation, and gait [1]. A century later, these interactions were investigated in clinical and laboratory studies [1,2]. Healthy people, when
positioned at height, were found to have a stiffer stance and experience
greater state anxiety, lower balance condence, and higher autonomic
arousal [39]. Individuals with high trait anxiety stiffened their stance
under modest stress that did not alter postural control of those with
Corresponding author at: Santa Lucia Foundation, Via Ardeatina 306, 00179 Rome
Italy.
E-mail address: i.indovina@hsantalucia.it (I. Indovina).

http://dx.doi.org/10.1016/j.jpsychores.2014.09.005
0022-3999/ 2014 Elsevier Inc. All rights reserved.

low trait anxiety [10]. Conversely, vestibular disorders were identied

as potent triggers of secondary anxiety disorders [1118] and elevated
state anxiety was associated with lower functional status [19] and
poorer treatment outcomes [19,20].
Animal studies provided evidence about important neural connections between subcortical anxiety and vestibular systems [2126]. Information about head motion is conveyed from vestibular labyrinths
to vestibular nuclei, and then to pathways that control oculomotor
and spinal reexes, modulated by loops through the cerebellum. This
information reaches systems that mediate affective responses via pathways from vestibular nuclei through the pontine nuclei to the amygdala
[2,2123]. In the cortex, vestibular, visual, proprioceptive, and somatosensory information about space and motion reach associative regions
via the thalamus. In monkeys, the core vestibular cortex is called the
parieto-insular vestibular cortex. The human homologue of this region
includes sylvian and peri-sylvian areas at the interface between the
posterior- and retro-insula, posterior superior temporal gyrus (STg)

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I. Indovina et al. / Journal of Psychosomatic Research 77 (2014) 391400

and parietal operculum. Neuroimaging studies showed that human

vestibular cortical network includes the inferior parietal lobule [supramarginal gyrus (SMg), temporo-parietal junction and ventral intraparietal area], parts of the prefrontal cortex [e.g., the inferior frontal
gyrus (IFg)], and the anterior cingulate cortex and hippocampus
[2733]. Vestibular and visual cortices interact in a reciprocally inhibitory manner. Vestibular stimuli activate vestibular cortex and suppress
visual cortical function, whereas visual motion stimuli do the opposite
[34,35]. Thus, the human vestibular cortex is a multimodal processor
that integrates vestibular, visual, proprioceptive, somatosensory, and
motor information [3638]. It also overlaps regions that process anxiety
and affective responses, particularly in the posterior parietal, insular,
hippocampal and prefrontal areas [25,3941]. This may provide the cortical substrate for anxiety to inuence vestibular information processing
and for vestibular data to affect emotional states.
Researchers have developed increasingly sophisticated models of
vestibularanxiety interactions at subcortical and cortical levels to
explain vestibular symptoms in patients with primary anxiety disorders,
and secondary anxiety disorders in patients with vestibular illnesses
[2,21,23]. These models may extend to other conditions with vestibularanxiety interactions, such as height phobia and phobic postural vertigo
[42,43] or chronic subjective dizziness (CSD) [2,44,45]. The latter two
are similar conditions that manifest with chronic non-vertiginous dizziness or unsteadiness exacerbated by upright posture, head motion, and
exposure to complex or moving visual stimuli, usually triggered by
acute vestibular or balance disorders. They occupy a place in clinical
neurotology akin to irritable bowel syndrome in gastroenterology
(i.e., independent psychosomatic conditions that occur with or without
medical or psychiatric comorbidity). A pre-existing anxiety diathesis
may increase the risk of developing CSD [18,46], add chronic psychiatric
comorbidity [18,46], and reduce treatment response [47]. Personality
traits of neuroticism and introversion were more closely associated
with CSD than with comorbid neurotologic disorders producing similar
levels of vestibular and psychological symptoms [48]. In contrast,
resilience, life satisfaction, and strong sense of coherence predicted
lower rates of persistent dizziness after acute vestibular illnesses [49].
Thus, personality traits associated with anxiety, specically neuroticism
and introversion may be important factors for anxiety-mediated vestibular conditions.
This untested hypothesis rests on the supposition that neurotic,
introverted people compared to non-neurotic, extraverted individuals
have: (1) central vestibular systems that are more reactive to vestibular
stimuli, (2) anxiety systems that are more reactive to vestibular stimuli,
or (3) central vestibular systems that react more strongly to inputs from
anxiety systems during vestibular stimulation. To investigate these
possible mechanisms, we examined correlations between personality
traits of the Five Factor Model (neuroticism, extraversionintroversion,
agreeableness, openness, and conscientiousness) measured by the
Revised NEO Personality Inventory (NEO-PI-R) [50] and brain activity
and connectivity within vestibular and anxiety networks using functional magnetic resonance imaging (fMRI) in healthy volunteers stimulated with short tone bursts (STB) at 100 dB SPL. The STB procedure is
known to activate primary afferents in sacculi of the labyrinths and
evoke robust responses in vestibular cortical areas [5153]. By using
healthy and drug-free volunteers imaged while in a comfortably relaxed
state, we focused on inherent relationships among personality traits
and brain activity during vestibular stimulation in subjects who were
free of potential confounds of high state anxiety, vestibular or anxiety
disorders, and medications.
We predicted that higher neuroticism and lower extraversion scores
(i.e., introversion) would correlate with increased reactivity to STB
stimuli in subcortical and cortical vestibular and anxiety regions and
greater vestibularanxiety system connectivity, thereby identifying
potential neural substrates for clinical vestibular conditions ranging
from comorbid anxiety in vestibular illnesses to CSD and phobias of
heights [2].

Participants and methods

Participants
Twenty-six healthy volunteers (14 females, mean age = 32.4
7.3 years) gave written informed consent to participate in this study,
which was approved by the local Research Ethics Committee according
to the Helsinki declaration (http://www.wma.net/en/30publications/
10policies/b3/). Participants were systematically screened to exclude
migraine, chronic medical illnesses, pregnancy, medication use, smoking,
or history of head injury. The MINI International Neuropsychiatric
Inventory was used to exclude those with past or present psychiatric
disorders [54]. All participants were right-handed, as assessed via the
Edinburgh Handedness Inventory [55].
To measure personality traits of the Five Factor model, all participants completed a computerized version of the Italian translation of
the NEO-PI-R questionnaire [50]. Standardized T-scores for each personality factor were calculated via a script written in SPSS (Statistical
Package for Social Sciences, http://www.spss.it/) using combined
sex-norms reported in the NEO-PI-R manual.
fMRI task
Experimental stimuli were administered via piezo-electric MRI compatible headphones (NordicNeuroLab,http://www.nordicneurolab.
com/Products_and_Solutions/fMRI_Hardware/AudioSystem.aspx). Previous studies demonstrated that unilateral STB stimuli at 100 dB
sound pressure level (SPL) generate vestibular evoked motor potentials
(VEMPs) in sternocleidomastoid muscles ipsi- and contralateral to the
stimulated ear, a response used in clinical practice to assess saccular
function [51,53,5658]. STB 100 dB SPL also evoke robust responses in
vestibular cortical regions [51,53] (see also Supplementary Materials).
In contrast, the same STB stimuli delivered at 65 dB SPL do not evoke
VEMPs or activate the cortex [51,53]. Caloric and galvanic vestibular
stimuli have been used in other fMRI studies of vestibular brain activity [31], although their thermal and electrical sensations create undesirable effects that are more difcult to control than non-vestibular
responses to STBs. For example, caloric and galvanic stimuli are
more likely to elicit head movements that degrade fMRI data.
Hence, to investigate how personality traits inuenced reactivity of
the vestibular and anxiety systems, we compared responses to identical
STBs at 100 dB and 65 dB SPL. To control for non-specic reactions
to sound, we also obtained brain responses to white-noise stimuli at
100 dB SPL.
STBs had a frequency of 500 Hz, rise and fall times of 1 ms, plateau times of 8 ms, and were presented at repetition rates of 3 Hz,
as recommended in a number of previous studies [5961]. Whitenoise stimuli were sinusoidally modulated signals that reproduced
the time variability of STBs. In particular, white-noise had a loudness
that varied at a frequency of 3 Hz. This prevented habituation to
white-noise stimuli while obtaining data to control for startle and
other non-specic responses.
The experimental task included four stimuli: (1) STB100dB SPL;
(2) STB65dB SPL; (3) white noise 100dB SPL; and (4) rest periods
with no stimulus presentation. Forty-ve stimuli per type were grouped
in blocks lasting 15 sec each (rest blocks also lasted 15 sec). Four
sessions (2 for the left and 2 for the right ear) including 4 blocks per
type of stimuli were presented in about 16 minutes. The order of
sessions and side of rst stimulated ear were counterbalanced across
all participants. To attenuate interferences from MRI scanner noise, we
isolated the headphones with soundproof foam cushions and used
foam plugs in the non-stimulated ear. Participants were asked to xate
a central point, attend to auditory stimuli, and report how many types of
stimuli they heard. Following data acquisition, participants were asked
to report the unpleasantness of each type of stimulus on an annoyance
scale from 1 to 10 and any sensations of illusory body motion. All

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393

Table 1
Correlation between sound-evoked brain vestibular responses and personality traits
Positive

Negative
P

0.045

3.60

56

58

42

B. Extraversion
Amygdala R (ReS)

0.008

3.38

24

24

C. Openness
IFg (Triang) L (ReS)

0.014

3.97

52

34

12

A. Neuroticism
Cerebellar nuclei L (ReS)
Cerebellar nuclei R (ReS)
Pontine nuclei L (ReS)
Pontine nuclei R (ReS)
Visual cortex L (V2) (LeS)
SMg L (PFm) (LeS)

0.002
0.005
0.009
0.030
0.009

3.85
3.53
3.81
3.38
4.17

8
2
2
2
18

52
54
22
24
102

24
24
26
24
4

Correlation between sound-evoked brain vestibular responses (STB100dB vs. STB 65 dB excluding white noise vs. rest related activity) and personality traits at P b 0.05, small volume
correction. Activations in the visual area (V2) and SMg refer to the Left ear Stimulation (LeS) while activations in the cerebellum, amygdala and IFg (Triang) refer to the Right ear
Stimulation (ReS).
Z = Z-score, L = left hemisphere, R = right hemisphere. x,y,z = MNI coordinates in millimeters. SMg = supra marginal gyrus, IFg (triang) = inferior frontal gyrus pars triangularis.

volunteers conrmed that all stimuli were clearly distinguishable.

They reported that STB and white-noise stimuli at 100 dB were equally annoying (mean std = 4.7 2.7 and 5.2 2.9, respectively; paired
t-test p = 0.3), whereas STB stimuli at 65 dB were less bothersome

(mean std = 2.3 2.2; p b 0.001 paired t-test versus STB100dB

and white noise). Levels of annoyance did not correlate with NEOPI-R scores (p N 0.2). Participants did not report any illusory body
motion.

Fig. 1. Main effects of vestibular and acoustic stimulation. Statistical parametric maps (shown at P b 0.001 uncorrected for visualization purposes) for the STB100dB N rest comparison (A),
STB65dB N rest (B), modulated white noise 100 dB N rest (C), and STB100dB N STB65dB exclusively masked for white noise (D). Maps are separately reported for right and left ear
stimulation in normalized sterotactic space, overlaid on a high-resolution anatomical MR image (CH2, Montreal Neurological Institute), with the right side shown on the right. Sagittal,
coronal and axial slices are centered on the rst peak relative to each contrast reported on Supplementary Table S1.

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Image acquisition

Image pre-processing

fMRI was performed on a 3-T unit with an eight-channel head

coil. Head movements were minimized using foam pads around
participants' head. No participant had head movements N2 mm.
Whole-brain fMRI data were acquired with echo planar images sensitive to blood oxygenation level-dependent (BOLD) contrast (39
axial slices, 3-mm thickness each; repetition time = 2000 ms;
echo time = 30 ms; voxel size: 3 3 3 mm).

Data were pre-processed using SPM8 (http://www.l.ion.ucl.ac.uk/spm/).

Images were realigned to the rst scan by rigid body transformations
to correct for head movements. Realigned scans were normalized to
the standard template in the Montreal Neurological Institute space
using linear and nonlinear transformations, and nally images
were smoothed with a Gaussian kernel of full width at half maximum
of 8 mm.

Fig. 2. Effect of individual differences in neuroticism on brain activations during unilateral sound-evoked vestibular stimulation. Neuroticism scores were positively associated with the
activity in the cerebellar fastigial nuclei (A), and superior pons (B) during right saccular stimulation, and with parastriate visual cortex (V2) response during left saccular stimulation
(C). In contrast, neuroticism levels were negatively linked with the response in the supra-marginal gyrus (SMg) during left ear stimulation (D). The plots of the data are from the local
maxima in each region. The coordinates (X,Y,Z) are in the Montreal Neurological Institute space. Color bars represent T-statistics. Black lines represent the regression lines. Red lines
are the 95% condence interval. BOLD, blood oxygenation level dependent.

I. Indovina et al. / Journal of Psychosomatic Research 77 (2014) 391400

fMRI analysis of regional responses

For each participant, general linear models (GLMs) assessed regionally specic effects of task parameters on BOLD activations. First-level
GLMs included 4 experimental conditions (STB100dB, STB65dB, whitenoise 100dB, and rest) modeled as epochs of xed duration and convolved with the hemodynamic response function, and 6 realignment
parameters as effects of no interest to remove residual motion-related
variance. Low-frequency signal drift was eliminated using a high-pass
lter (cut-off, 128 sec). Autoregressive AR(1) models corrected for
voxels' autocorrelations.
Subjects' specic contrast images (i.e., STB100dB N rest, STB65dB N
rest, white-noise 100dB N rest, STB100dB N STB65dB) were generated
separately for right and left ears, averaging the two sessions of each
side, and entered into second-level GLMs investigating the main effect
of the task per each contrast (one sample t-tests). Because whitenoise stimuli were qualitatively different from STBs, they were not included in the comparison assessing brain activations associated with
vestibular stimulation (i.e., the STB100dB N STB65dB contrast). Instead,
white noise 100dB N rest contrast was used to exclusively mask the
STB100dB N STB65dB comparison. This way, we eliminated residual auditory activity that may have been present in the STB100dB N STB65dB
contrast as a result of differences in stimulus loudness. To create the
exclusive mask from the white noise 100dB N rest contrast, we used a
lenient threshold of P 0.05, uncorrected. This threshold was chosen

395

to exclude non-specic auditory voxels from the main STB100dB N

STB65dB comparison in a conservative way. The effects of Five Factor
personality traits on brain vestibular responses were evaluated via multiple regression GLMs assessing correlations between subject-specic
BOLD activity for the contrast STB100dB N STB65dB (exclusively masked
for the white-noise 100dB N rest comparison) with individual scores of
NEO-PI-R personality factors.
Second level maps were thresholded using two methods. First, we
reported regions that met a threshold of P0.05, Family Wise Error
(FWE), whole-brain correction for multiple comparisons. Second, we
employed a region of interest (ROI) approach using a threshold of
P 0.05, FWE, small volume correction (svc). This standard, commonly
employed procedure not only ensured robust protection against type I
errors but also prevented false negative results, particularly in ROIs for
which we had strong a priori hypotheses [62,63]. The vestibular nuclei,
cerebellar fastigial nuclei and parieto-insular vestibular cortex homologue were dened as ROIs given their key roles in processing vestibular
stimuli [2732]. Primary and secondary visual areas (i.e., V1 and
V2) were included as a ROI to test for the presence of reciprocal
inhibitory effects between visual and vestibular cortices found in
previous studies [34,35,64]. The amygdala was considered a ROI
given its role in emotional behaviors in healthy people [40]. Finally
SMg, IFg, anterior cingulum, and hippocampus were considered for
their roles in both anxiety and vestibular mechanisms [2931,33,
3941].
Each ROI was dened according to anatomical regions described in
the SPM Anatomy toolbox and automated anatomical labeling (aal)
atlas [6568]. The visual cortex ROI included primary and secondary
visual cortices (V1 plus V2), whereas the peri-sylvian ROI was constituted by the whole insula (as obtained from aal), parietal operculum, and
STg. This ROI also included retro-insula that was not incorporated into
the whole insula anatomical ROI. The SMg ROI included ve regions
dened by von Economo's nomenclature [69]. The IFg comprised pars
opercularis, triangularis, and orbitalis. The amygdala, anterior cingulum and hippocampal ROIs were taken from aal. As specic anatomical ROIs for cerebellar fastigial nuclei were not available, we used a
8-mm radius sphere ROI centered on coordinates reported in
Dimitrova et al. 2002 (i.e., X 4, Y 50, Z 28) [70]. Similarly, reliable coordinates for brainstem vestibular nuclei were not available,
so we dened a 15-mm radius ROI centered on the coordinates in
the brainstem obtained from a previous fMRI study using vestibular
stimulation [71]. Next, to localize more precisely pontine activations
that were found in correlation analyses, we employed the
Duvernoys atlas [72].
Task-dependent functional connectivity analyses

Fig. 3. Effect of individual differences in introversion on brain activations during right ear
vestibular stimulation. Introversion scores were positively associated with the activity in
the right amygdala during right saccular stimulation. The plot of the data is from the
local maxima in the amygdala. The coordinates (X,Y,Z) are in the Montreal Neurological
Institute space. The color bars represents T-statistics. Black line represents the regression
line. Red lines are the 95% condence interval. BOLD, blood oxygenation level dependent.

Psycho-physiological interaction (PPI) in GLMs

To investigate how personality traits modulated functional connectivity within the vestibular and anxiety systems, we performed psychophysiological interaction (PPI) analyses. A PPI represents the change in
connectivity (i.e., correlation) between couples of regions (i.e., the
seed and the rest of the brain) that is induced by a specic task (here,
vestibular N non-vestibular stimulation) [73]. We sought to identify
brain target areas that had differential connectivity with a series of
seed regions (i.e., V1V2, SMg, cerebellum (fastigium), pons, amygdala
and IFg, Table 1) as functions of processing vestibular Nnon-vestibular
stimuli and personality factors (i.e., higher-order PPIs) [7476]. Seed
regions were those that showed signicant effects of personality traits
on regional brain responses (Table 1).
Time-series for participants' seeds were computed using rst
eigenvariates from all voxels' time series within a 8-mm sphere and
then deconvolved to estimate neuronal time series [77]. Separate PPIs
were carried out for the contrast STB100dB N STB65dB (exclusively
masked for the white-noise 100dB N rest comparison), using right
or left ear stimulation data and each previously described seed. PPI

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I. Indovina et al. / Journal of Psychosomatic Research 77 (2014) 391400

Fig. 4. Effect of individual differences in neuroticism on brain functional connectivity during sound-evoked vestibular stimulation. During right saccular stimulation, neuroticism scores
were positively associated with the functional connectivity between the left cerebellar fastigial nucleus seed region and the right amygdala (A), and with the functional connectivity
between the superior pons seed and the right amygdala (B). During left saccular stimulation, neuroticism levels were positively linked with the functional connectivity between the
left para-striate visual cortex (V2) seed and the left inferior frontal gyrus (IFg) pars triangularis (C) and with the connectivity between the left supra-marginal gyrus (SMg) seed
and the left IFg pars triangularis (D). The plots of the data are from the local maxima in each region. The coordinates (X,Y,Z) are in the Montreal Neurological Institute space. Color bars
represent T-statistics. Black lines represent the regression lines. Red lines are the 95% condence interval. BOLD, blood oxygenation level dependent.

regressors were calculated as element-by-element products of the

seed region neuronal time series and a vector coding main effect of
task (i.e., 1 for STB100dB, 1 for STB65dB). PPI regressors were entered in rst-level GLMs including the main effect of task and 6
movement parameters as effects of no interest. Subject-specic PPI
contrast images were entered into second-level GLMs that identied
brain areas for which changes in connectivity to seeds (for the contrast STB100dB NSTB65dB, exclusively masked by the white-noise

100dB N rest) were modulated by individual differences in personality scores.

Results
Personality traits
Means and ranges of NEO-PI-R T-scores were: Neuroticism (50.1, 31.571.6), Extraversion (53.7, 35.673.1), Openness (55.8, 34.071.6), Agreeableness (46.3, 28.959.3),

I. Indovina et al. / Journal of Psychosomatic Research 77 (2014) 391400

397

Table 2
Regional coupling during sound-evoked response as a function of personality
A. Coupling correlates with neuroticism.
Target:
Seed:

IFg (Triang) L
P

Cerebellar nuclei
L (ReS)
Pontine nuclei L
(ReS)
Visual cortex L
0.002 4.61 52 18
(V2) (LeS)
SMg L (LeS)
0.034 3.84 34 32

Amygdala R
z

0.006 3.54

18 2 16

0.044 2.83

18 2 16

22
18

B. Coupling correlates with extraversion.

Target:
Seed:
Amygdala R
(ReS)

IFg (Orb) R
P

0.003 4.51

IFg (Orb) L
y

36 24 22 0.034 3.86 20

14 20

Correlation of coupling (between SEED and target areas) and personality traits at P 0.05,
small volume correction. SEED areas are from Table 1, TARGET areas are those areas that
showed a signicant dependence of coupling on personality traits in the PPI analysis.
Z = Z-score, L = left hemisphere, R = right hemisphere. x,y,z = MNI coordinates
in millimeters. SMg = supra marginal gyrus, IFg (Orb) = inferior frontal gyrus pars
orbitalis.

and Conscientiousness (52.0, 33.568.1). Mean T-scores were within general population
norms (4555), except for minimally elevated openness. Individual T-scores covered the
full range from low (b45) to high (N55) for all ve traits.

Main effect of STB stimulation on regional brain activity

Main effects of experimental stimuli on regional brain activation patterns were examined and compared to published data. Regional effects for the contrasts STB100dB N rest,
STB65dB N rest, and white noise 100dB N rest are reported in Supplementary Table 1
and Fig. 1 (A,B,C, respectively). The contrast STB100dB N STB65dB (exclusively masked
by the white noise 100dB N rest comparison, separately for right and left ear) showed signicant activations in posterior insula, retro-insula and parietal operculum (one sample ttest, P b 0.05 FWE, whole-brain correction) (Supplementary Table 1D, and Fig. 1D). Activations of these cortical regions in the human homologue of the parieto-insular vestibular
cortex were fully consistent with previous results [2832]. In addition, activation of bilateral cerebellar nuclei including fastigial nuclei was observed at a small volume correction
level (Supplementary Table 1D).

Fig. 5. Effect of individual differences in introversion on brain functional connectivity.

Introversion scores were negatively associated with the functional connectivity between
the right amygdala seed and the bilateral inferior frontal gyrus (IFg) pars orbitalis during
right saccular stimulation. The plot of the data is from the local maxima in the right IFg.
The coordinates (X,Y,Z) are in the Montreal Neurological Institute space. The color bar
represents T-statistics. Black line represents the regression line. Red lines are the 95%
condence interval. BOLD, blood oxygenation level dependent.

Discussion
Effect of personality traits on vestibular and anxiety system activation
Neuroticism scores correlated (Table 1A): 1) positively with bilateral cerebellar
fastigial nuclei and pontine activity during right ear stimulation (Fig. 2A, B); 2) positively
with left V2 cortical activity during left ear stimulation (Fig. 2C); and 3) negatively with
the left SMg activity during left ear stimulation (Fig. 2D). Extraversion-introversion scores
did not correlate with stimulated activity in predominately vestibular regions. Openness
scores correlated negatively with left IFg activity during right ear stimulation (Table 1C).
Agreeableness and consciousness scores did not signicantly modulate activity in any
ROI during right or left vestibular stimulation (all analyses refer to STB100dB N STB65dB
contrast, exclusively masked for the white-noise 100dB N rest contrast) (P b 0.05, FWE,
svc).
Extraversion scores correlated negatively (i.e., introversion correlated positively)
with right amygdala activation during right ear stimulation (Fig. 3 and Table 1B).
Other traits did not correlate with stimulated activity in predominately anxiety
regions.

Effect of personality traits on functional connectivity

Brain regions showing correlations with neuroticism, extraversion and openness
(Table 1A,B,C) were used as seeds for connectivity analyses exploring inuences of
personality traits on coupling between areas. Neuroticism was associated positively with
connectivity between: 1) left cerebellar/pontine nuclei and right amygdala, 2) left V2
and left IFg, and 3) left SMg and left IFg (Fig. 4AD, Table 2A). Extraversion was positively
associated (i.e., introversion correlated negatively) with connectivity between right amygdala and IFg (Fig. 5, Table 2B). No signicant effects were found for the remaining seed
regions.

The results, summarized in Fig. 6, support the latest models integrating vestibular and anxiety function in health and disease [2], and are
consistent with ndings regarding neuroticism and introversion as
risk factors for CSD [48]. They offer the rst evidence of possible neural
mechanisms linking personality traits to functional alterations in central
vestibular pathways and support the suppositions that: (1) central
vestibular systems may be more reactive to vestibular stimuli than
normal (in neurotic individuals), (2) anxiety systems may be more
reactive to vestibular stimuli than normal (in introverted individuals),
and (3) increased connectivity between subcortical vestibular and
anxiety systems may facilitate amplied vestibularanxiety reactions
to vestibular stimuli (in neurotic individuals).
Consistently with past studies [31], the posterior insula showed
robust activation to vestibular stimuli across all participants, but surprisingly, its response did not correlate with any personality trait. This
null result is in contrast to previous ndings showing that the insula
response during cognitive and emotional tasks may be modulated by
individual differences in anxiety-related traits [25,78,79]. It may be
that the sound-evoked vestibular stimulation was insufcient per se
to trigger altered insula responses in healthy individuals with variable
levels of neuroticism, while these effects may become evident in clinical
populations (e.g., CSD patients). Further studies are warranted to
explore these issues.

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I. Indovina et al. / Journal of Psychosomatic Research 77 (2014) 391400

Fig. 6. Summary of regional effects and functional connectivity results. Neuroticism was positively correlated with activity in cerebellar fastigial and superior pontine nuclei and with functional connectivity between these nuclei and the right amygdala during vestibular stimulation. These ndings reect potentiated processing of vestibular inputs in neurotic people that
may predispose them to enhanced viscero-motor and emotional responses to space-motion stimuli. Introversion was linked with increased amygdala response to vestibular stimuli
and reduced functional connectivity between the right amygdala and IFg pars orbitalis bilaterally. These results may be neural correlates of enhanced acquisition or decreased extinction
of fear conditioned responses to vestibular stimuli that are thought to play a role in development of specic phobias of falling and chronic subjective dizziness. Neuroticism levels were
positively associated with increased activity in the parastriate visual cortex (V2) and reduced response in the supra-marginal gyrus (SMg) during vestibular stimulation. Neuroticism
also modulated the connectivity between the IFg pars triangularis and both the V2 and SMg. The combination of SMg hypoactivity and V2 hyperactivity may reect a visual bias in the
reciprocally inhibitory connectivity of vestibular and visual cortices modulated by the IFg pars triangularis, a key region in attentional modulation. The lines connecting different brain
areas represent the positive (continuous lines) or negative (dotted lines) correlation of the inter-regional connectivity with the personality factor indicated within the black arrow.

Neuroticism and reactivity of vestibular systems to vestibular stimulation

Neuroticism scores were positively associated with activity in the
superior pons and cerebellar fastigial nuclei bilaterally. Feedback loops
through these regions modulate vestibulo-ocular and postural reexes.
In the cortex, neuroticism was positively linked with V2 response and
negatively with SMg activity. Although not tested explicitly in this
experiment as visual stimuli were not used, this result may reect visual
bias in the reciprocally inhibitory interactions of visual and vestibular
cortices thought to stabilize optic ow during self-motion [34,35,64],
a possible neural correlate of visual motion hypersensitivity in neurotic
individuals [80] and persistent visually induced dizziness, a core
symptom of CSD [45].

Introversion, openness and reactivity of anxiety systems to

vestibular stimulation
Introversion (low-extraversion) was associated with increased
amygdala activity during vestibular stimulation. In previous imaging
studies using resting-state measures in healthy volunteers, introversion
was not associated with amygdala activity [78]. However, during emotional learning tasks, increased amygdala activity and high introversion
were associated with enhanced fear conditioning and reward learning
[81]. The increased amygdala response to vestibular stimuli in introverted
subjects may thus support the hypothesis that conditioned hypersensitivity to vestibular stimuli plays a role in developing CSD [2].
Openness was also negatively associated with activation in the IFg.
Openness was previously linked to increased prefrontal cortical greymatter volume and activity during working-memory tasks and at rest
[8285]. For unknown reasons, this result was opposite the expected
direction. However, the nding of just one signicant correlation

between openness and brain activity and none with connectivity

suggests that openness may inuence vestibularanxiety interactions
less than neuroticism or introversion. This mirrors the personality trait
study of CSD, in which only one facet of openness differed between
CSD and comparison groups versus multiple facets of neuroticism and
extraversion [48]. Additional research is necessary to investigate
the role that openness may play in mediating anxiety responses in
vestibular disturbances and vice versa.
Neuroticism, introversion and anxietyvestibular system connectivity
High neuroticism correlated with vestibulo-cerebellum (i.e., fastigial
nuclei)-amygdala connectivity as well as with the pons-amygdala
connectivity. The superior part of the pons contains nuclei involved in
vestibular functions, although spatial resolution of fMRI cannot distinguish amongst these structures. These nuclei integrate vestibular inputs
with other interoceptive stimuli and send this information to the amygdala. The cross-talk with the amygdala is thought to orchestrate the
viscero-motor responses to emotional stimuli and postural perturbations [21,22,86,87]. Hence, enhanced pons-amygdala connectivity
could mediate amplied reexive responses of neurotic individuals to
vestibular stimuli, including exaggerated emotional reactivity. Less is
known about the cerebellar fastigial nuclei-amygdala link, but it may
be responsible for small gain increases in canal-ocular and otolith
ocular reexes observed in patients with panic disorder and agoraphobia [80].
Furthermore, neuroticism correlated with connectivity between
IFg and both visual cortex and SMg. The IFg has been implicated in
redirecting attention towards relevant stimuli [8890], including voluntary shifts of attention during visual search [91]. Hyper-vigilance to
potentially threatening visual stimuli was observed in highly neurotic
individuals with no vestibular symptoms [92]; hence, the nding of

I. Indovina et al. / Journal of Psychosomatic Research 77 (2014) 391400

reduced SMg activity and increased V2 response to STB100dB stimuli

raises the possibility of visual bias in multi-sensory integration of
space-motion stimuli in neurotic people.
Introversion was negatively associated (extraversion positively correlated) with amgydala-IFg (the orbitalis part) connectivity. Extensive
connections between amygdala and IFg are important for extinguishing
fear responses to conditioned stimuli [41,9396]. Imaging studies found
reduced connectivity between amygdala and frontal cortical areas in
social and generalized anxiety disorders [78,81], suggesting that reduced amygdala-prefrontal cortical connectivity may reect a general
proneness to anxiety-related disorders in introverts.
Although CSD was previously independently linked to neuroticism
and introversion, the two traits together separated CSD most strongly
from other neurotologic/anxiety disorders [48]. Therefore, the risk of
CSD may be conveyed by vestibular and anxiety systems that simultaneously express heightened reactivity to vestibular stimulation, mediated by neuroticism and introversion, respectively. Personality traits have
not been studied as explicitly in other anxiety-related vestibular
disorders, though the converse of neuroticism and introversion
(i.e., resilience and sense of coherence) predicted fewer psychosomatic
sequelae of acute vestibular syndromes [49].
This study provides the rst evidence that individual differences in
neuroticism, introversion, and possibly openness inuence activity
and functional connectivity within central vestibular and anxiety
systems in a pattern consistent with published models of vestibularanxiety interactions from brainstem to cortex [21,22,48]. Strengths of
this investigation included use of a previously well-developed experimental paradigm to evoke vestibular responses, and a study sample
with a full spectrum of personality traits compatible with population
norms, which provided valid data to test the personality modulation
hypotheses. The main limitation is that any correlates between brain
activation patterns and clinical phenotypes must be interpreted conservatively until they can be replicated and extended. For personality trait
modulation of vestibular responses that will require testing of additional visual and vestibular stimuli in larger cohorts of normal individuals
and patients with anxiety-related vestibular disorders (e.g., CSD).
Nevertheless, the concordance of these results with existing human
and animal data and recent neuroanatomical models is promising.
Financial support
Italian Ministry of University and Research (PRIN grant), National
Research Council.
Financial disclosures
None of the authors have conicts of interests.
Acknowledgments
We thank our volunteers for kindly participating in this study and
Dr. Martin Vestergaard for helping with auditory stimuli production.
Appendix A. Supplementary data
Supplementary data to this article can be found online at http://dx.
doi.org/10.1016/j.jpsychores.2014.09.005.
References
[1] Balaban CD, Jacob RG. Background and history of the interface between anxiety and
vertigo. J Anxiety Disord 2001;15:2751.
[2] Staab JP, Balaban CD, Furman JM. Threat assessment and locomotion: clinical applications of an integrated model of anxiety and postural control. Semin Neurol 2013;
33:297306.
[3] Carpenter MG, Frank JS, Silcher CP. Surface height effects on postural control: a
hypothesis for a stiffness strategy for stance. J Vestib Res 1999;9:27786.

399

[4] Adkin AL, Frank JS, Carpenter MG, Peysar GW. Postural control is scaled to level of
postural threat. Gait Posture 2000;12:8793.
[5] Brown LA, Frank JS. Postural compensations to the potential consequences of
instability: kinematics. Gait Posture 1997;6:8997.
[6] Davis JR, Campbell AD, Adkin AL, Carpenter MG. The relationship between fear of
falling and human postural control. Gait Posture 2009;29:2759.
[7] Davis JR, Horslen BC, Nishikawa K, Fukushima K, Chua R, Inglis JT, et al. Human
proprioceptive adaptations during states of height-induced fear and anxiety. J
Neurophysiol 2011;106:308290.
[8] Cleworth TW, Horslen BC, Carpenter MG. Inuence of real and virtual heights on
standing balance. Gait Posture 2012;36:1726.
[9] Adkin AL, Frank JS, Carpenter MG, Peysar GW. Fear of falling modies anticipatory
postural control. Exp Brain Res 2002;143:16070.
[10] Hainaut J-P, Caillet G, Lestienne FG, Bolmont B. The role of trait anxiety on static
balance performance in control and anxiogenic situations. Gait Posture 2011;
33:6048.
[11] Eckhardt A, Tettenborn B, Krauthauser H, Thomalske C, Hartmann O, Hoffmann SO,
et al. Vertigo and anxiety disorders results of interdisciplinary evaluation.
Laryngorhinootologie 1996;75:51722.
[12] Eckhardt-Henn A, Breuer P, Thomalske C, Hoffmann SO, Hopf HC. Anxiety disorders
and other psychiatric subgroups in patients complaining of dizziness. J Anxiety
Disord 2003;17:36988.
[13] Clark DB, Hirsch BE, Smith MG, Furman JM, Jacob RG. Panic in otolaryngology patients presenting with dizziness or hearing loss. Am J Psychiatry 1994;151:12235.
[14] Persoons P, Luyckx K, Desloovere C, Vandenberghe J, Fischler B. Anxiety and mood
disorders in otorhinolaryngology outpatients presenting with dizziness: validation
of the self-administered PRIME-MD Patient Health Questionnaire and epidemiology.
Gen Hosp Psychiatry 2003;25:31623.
[15] Eagger S, Luxon LM, Davies RA, Coelho A, Ron MA. Psychiatric morbidity in patients
with peripheral vestibular disorder: a clinical and neuro-otological study. J Neurol
Neurosurg Psychiatry 1992;55:3837.
[16] Kammerlind A-SC, Ledin TEA, Skargren EIB, Odkvist LM. Long-term follow-up after
acute unilateral vestibular loss and comparison between subjects with and without
remaining symptoms. Acta Otolaryngol (Stockh) 2005;125:94653.
[17] Celestino D, Rosini E, Carucci ML, Marconi PL, Vercillo E. Mnire's disease and
anxiety disorders. Acta Otorhinolaryngol Ital 2003;23:4217.
[18] Best C, Eckhardt-Henn A, Tschan R, Dieterich M. Psychiatric morbidity and comorbidity in different vestibular vertigo syndromes. Results of a prospective longitudinal
study over one year. J Neurol 2009;256:5865.
[19] Boleas-Aguirre MS, Snchez-Ferrandiz N, Guilln-Grima F, Perez N. Long-term disability of class A patients with Mnire's disease after treatment with intratympanic
gentamicin. Laryngoscope 2007;117:147481.
[20] Staab JP. Chronic dizziness: the interface between psychiatry and neuro-otology.
Curr Opin Neurol 2006;19:418.
[21] Balaban CD. Neural substrates linking balance control and anxiety. Physiol Behav
2002;77:46975.
[22] Balaban CD. Projections from the parabrachial nucleus to the vestibular nuclei: potential substrates for autonomic and limbic inuences on vestibular responses.
Brain Res 2004;996:12637.
[23] Balaban CD, Thayer JF. Neurological bases for balance-anxiety links. J Anxiety Disord
2001;15:5379.
[24] Gurvich C, Maller JJ, Lithgow B, Haghgooie S, Kulkarni J. Vestibular insights into
cognition and psychiatry. Brain Res 2013;1537:24459.
[25] Paulus MP, Stein MB. An insular view of anxiety. Biol Psychiatry 2006;60:3837.
[26] Viaud-Delmon I, Venault P, Chapouthier G. Behavioral models for anxiety and
multisensory integration in animals and humans. Prog Neuropsychopharmacol
Biol Psychiatry 2011;35:13919.
[27] Angelaki DE, Cullen KE. Vestibular system: the many facets of a multimodal sense.
Annu Rev Neurosci 2008;31:12550.
[28] Brandt T, Dieterich M. The vestibular cortex. Its locations, functions, and disorders.
Ann N Y Acad Sci 1999;871:293312.
[29] Zu Eulenburg P, Caspers S, Roski C, Eickhoff SB. Meta-analytical denition and
functional connectivity of the human vestibular cortex. Neuroimage 2012;60:1629.
[30] Indovina I, Maffei V, Bosco G, Zago M, Macaluso E, Lacquaniti F. Representation
of visual gravitational motion in the human vestibular cortex. Science 2005;308:
4169.
[31] Lopez C, Blanke O, Mast FW. The human vestibular cortex revealed by coordinatebased activation likelihood estimation meta-analysis. Neuroscience 2012;212:15979.
[32] Lopez C, Blanke O. The thalamocortical vestibular system in animals and humans.
Brain Res Rev 2011;67:11946.
[33] Hfner K, Strupp M, Smith P, Brandt T, Jahn K. Spatial separation of visual and
vestibular processing in the human hippocampal formation. Ann N Y Acad Sci
2011;1233:17786.
[34] Brandt T. Cortical visualvestibular interaction for spatial orientation and selfmotion perception. Curr Opin Neurol 1999;12:14.
[35] Brandt T, Bartenstein P, Janek A, Dieterich M. Reciprocal inhibitory visualvestibular
interaction. Visual motion stimulation deactivates the parieto-insular vestibular
cortex. Brain 1998;121:174958.
[36] Bremmer F, Schlack A, Shah NJ, Zaris O, Kubischik M, Hoffmann K, et al. Polymodal
motion processing in posterior parietal and premotor cortex: a human fMRI study
strongly implies equivalencies between humans and monkeys. Neuron 2001;29:
28796.
[37] Britten KH. Mechanisms of self-motion perception. Annu Rev Neurosci 2008;31:
389410.
[38] De Waele C, Baudonnire PM, Lepecq JC, Tran Ba Huy P, Vidal PP. Vestibular projections in the human cortex. Exp Brain Res 2001;141:54151.

400

I. Indovina et al. / Journal of Psychosomatic Research 77 (2014) 391400

[39] Sylvester CM, Corbetta M, Raichle ME, Rodebaugh TL, Schlaggar BL, Sheline YI, et al.
Functional network dysfunction in anxiety and anxiety disorders. Trends Neurosci
2012;35:52735.
[40] Bishop SJ. Neurocognitive mechanisms of anxiety: an integrative account. Trends
Cogn Sci 2007;11:30716.
[41] Indovina I, Robbins TW, Nez-Elizalde AO, Dunn BD, Bishop SJ. Fear-conditioning
mechanisms associated with trait vulnerability to anxiety in humans. Neuron
2011;69:56371.
[42] Brandt T. Phobic postural vertigo. Neurology 1996;46:15159.
[43] Brandt T, Dieterich M. Phobischer Attacken-Schwank-schwindel, ein neues
Syndrom? Munch Med Wochenschr 1986;28:24750.
[44] Staab JP, Ruckenstein MJ. Expanding the differential diagnosis of chronic dizziness.
Arch Otolaryngol Head Neck Surg 2007;133:1706.
[45] Staab JP. Chronic subjective dizziness. Continuum (Minneap Minn) 2012;18:111841.
[46] Staab JP, Ruckenstein MJ. Which comes rst? Psychogenic dizziness versus otogenic
anxiety. Laryngoscope 2003;113:17148.
[47] Staab JP, Ruckenstein MJ. Chronic dizziness and anxiety: effect of course of illness on
treatment outcome. Arch Otolaryngol Head Neck Surg 2005;131:6759.
[48] Staab JP, Rohe DE, Eggers SDZ, Shepard NT. Anxious, introverted personality traits in
patients with chronic subjective dizziness. J Psychosom Res 2014;76:803.
[49] Tschan R, Best C, Beutel ME, Knebel A, Wiltink J, Dieterich M, et al. Patients' psychological well-being and resilient coping protect from secondary somatoform vertigo
and dizziness (SVD) 1 year after vestibular disease. J Neurol 2011;258:10412.
[50] Costa Jr PT, McCrae RR. Stability and change in personality assessment: the revised
NEO Personality Inventory in the year 2000. J Pers Assess 1997;68:8694.
[51] Janzen J, Schlindwein P, Bense S, Bauermann T, Vucurevic G, Stoeter P, et al. Neural
correlates of hemispheric dominance and ipsilaterality within the vestibular system.
Neuroimage 2008;42:150818.
[52] Miyamoto T, Fukushima K, Takada T, de Waele C, Vidal P-P. Saccular stimulation of
the human cortex: a functional magnetic resonance imaging study. Neurosci Lett
2007;423:6872.
[53] Schlindwein P, Mueller M, Bauermann T, Brandt T, Stoeter P, Dieterich M. Cortical
representation of saccular vestibular stimulation: VEMPs in fMRI. Neuroimage
2008;39:1931.
[54] Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, et al. The MiniInternational Neuropsychiatric Interview (M.I.N.I.): the development and validation
of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 1998;59:2233 [quiz 3457].
[55] Oldeld RC. The assessment and analysis of handedness: the Edinburgh inventory.
Neuropsychologia 1971;9:97113.
[56] Brantberg K. Vestibular evoked myogenic potentials (VEMPs): usefulness in clinical
neurotology. Semin Neurol 2009;29:5417.
[57] Colebatch JG, Halmagyi GM, Skuse NF. Myogenic potentials generated by a clickevoked vestibulocollic reex. J Neurol Neurosurg Psychiatry 1994;57:1907.
[58] Isaradisaikul S, Navacharoen N, Hanprasertpong C, Kangsanarak J. Cervical
vestibular-evoked myogenic potentials: norms and protocols. Int J Otolaryngol
2012;2012:913515.
[59] Akin FW, Murnane OD, Proftt TM. The effects of click and tone-burst stimulus
parameters on the vestibular evoked myogenic potential (VEMP). J Am Acad Audiol
2003;14:5009 [quiz 534535].
[60] Cheng PW, Murofushi T. The effect of rise/fall time on vestibular-evoked myogenic
potential triggered by short tone bursts. Acta Otolaryngol (Stockh) 2001;121:6969.
[61] Cheng PW, Murofushi T. The effects of plateau time on vestibular-evoked myogenic
potentials triggered by tone bursts. Acta Otolaryngol (Stockh) 2001;121:9358.
[62] Friston KJ. Testing for anatomically specied regional effects. Hum Brain Mapp 1997;
5:1336.
[63] Worsley KJ, Marrett S, Neelin P, Vandal AC, Friston KJ, Evans AC. A unied statistical
approach for determining signicant signals in images of cerebral activation. Hum
Brain Mapp 1996;4:5873.
[64] Bense S, Stephan T, Yousry TA, Brandt T, Dieterich M. Multisensory cortical signal
increases and decreases during vestibular galvanic stimulation (fMRI). J Neurophysiol
2001;85:88699.
[65] Tzourio-Mazoyer N, Landeau B, Papathanassiou D, Crivello F, Etard O, Delcroix N,
et al. Automated anatomical labeling of activations in SPM using a macroscopic
anatomical parcellation of the MNI MRI single-subject brain. Neuroimage 2002;15:
27389.
[66] Eickhoff SB, Stephan KE, Mohlberg H, Grefkes C, Fink GR, Amunts K, et al. A new SPM
toolbox for combining probabilistic cytoarchitectonic maps and functional imaging
data. Neuroimage 2005;25:132535.
[67] Eickhoff SB, Heim S, Zilles K, Amunts K. Testing anatomically specied hypotheses in
functional imaging using cytoarchitectonic maps. Neuroimage 2006;32:57082.
[68] Eickhoff SB, Paus T, Caspers S, Grosbras M-H, Evans AC, Zilles K, et al. Assignment of
functional activations to probabilistic cytoarchitectonic areas revisited. Neuroimage
2007;36:51121.

[69] von Economo C, Koskinas GN. Atlas of cytoarchitectonics of the adult human
cerebral cortex. In: Triarhou LC, editor. Basel: Karger; 2008 [trans, rev].
[70] Dimitrova A, Weber J, Redies C, Kindsvater K, Maschke M, Kolb FP, et al. MRI atlas of
the human cerebellar nuclei. Neuroimage 2002;17:24055.
[71] Stephan T, Deutschlnder A, Nolte A, Schneider E, Wiesmann M, Brandt T, et al.
Functional MRI of galvanic vestibular stimulation with alternating currents at different frequencies. Neuroimage 2005;26:72132.
[72] Naidich TP, Duvernoy HM, Delman BN, Sorensen AG, Kollias SS, Haacke EM.
Duvernoy's Atlas of the Human Brain Stem and Cerebellum. Springer; 2009.
[73] Friston KJ, Buechel C, Fink GR, Morris J, Rolls E, Dolan RJ. Psychophysiological and
modulatory interactions in neuroimaging. Neuroimage 1997;6:21829.
[74] Passamonti L, Rowe JB, Ewbank M, Hampshire A, Keane J, Calder AJ. Connectivity
from the ventral anterior cingulate to the amygdala is modulated by appetitive
motivation in response to facial signals of aggression. Neuroimage 2008;43:56270.
[75] Passamonti L, Rowe JB, Schwarzbauer C, Ewbank MP, von dem Hagen E, Calder AJ.
Personality predicts the brain's response to viewing appetizing foods: the neural
basis of a risk factor for overeating. J Neurosci 2009;29:4351.
[76] Passamonti L, Crockett MJ, Apergis-Schoute AM, Clark L, Rowe JB, Calder AJ, et al.
Effects of Acute Tryptophan Depletion on Prefrontal-Amygdala Connectivity While
Viewing Facial Signals of Aggression. Biol Psychiatry 2012;71:3643.
[77] Gitelman DR, Penny WD, Ashburner J, Friston KJ. Modeling regional and psychophysiologic interactions in fMRI: the importance of hemodynamic deconvolution.
Neuroimage 2003;19:2007.
[78] Deckersbach T, Miller KK, Klibanski A, Fischman A, Dougherty DD, Blais MA, et al.
Regional cerebral brain metabolism correlates of neuroticism and extraversion.
Depress Anxiety 2006;23:1338.
[79] Paulus MP, Rogalsky C, Simmons A, Feinstein JS, Stein MB. Increased activation in the
right insula during risk-taking decision making is related to harm avoidance and
neuroticism. Neuroimage 2003;19:143948.
[80] Jacob RG, Redfern MS, Furman JM. Space and motion discomfort and abnormal
balance control in patients with anxiety disorders. J Neurol Neurosurg Psychiatry
2009;80:748.
[81] Hooker CI, Verosky SC, Miyakawa A, Knight RT, D'Esposito M. The inuence of
personality on neural mechanisms of observational fear and reward learning.
Neuropsychologia 2008;46:270924.
[82] Sutin AR, Beason-Held LL, Resnick SM, Costa PT. Sex differences in resting-state
neural correlates of openness to experience among older adults. Cereb Cortex
2009;19:2797802.
[83] DeYoung CG, Shamosh NA, Green AE, Braver TS, Gray JR. Intellect as distinct from
Openness: differences revealed by fMRI of working memory. J Pers Soc Psychol
2009;97:88392.
[84] Kapogiannis D, Sutin A, Davatzikos C, Costa Jr P, Resnick S. The ve factors of personality and regional cortical variability in the Baltimore longitudinal study of aging.
Hum Brain Mapp 2013;34:282940.
[85] Hu X, Erb M, Ackermann H, Martin JA, Grodd W, Reiterer SM. Voxel-based
morphometry studies of personality: issue of statistical model specicationeffect
of nuisance covariates. Neuroimage 2011;54:19942005.
[86] Halberstadt AL, Balaban CD. Anterograde tracing of projections from the dorsal
raphe nucleus to the vestibular nuclei. Neuroscience 2006;143:64154.
[87] Halberstadt AL, Balaban CD. Selective anterograde tracing of the individual serotonergic and nonserotonergic components of the dorsal raphe nucleus projection to
the vestibular nuclei. Neuroscience 2007;147:20723.
[88] Corbetta M, Patel G, Shulman GL. The reorienting system of the human brain: from
environment to theory of mind. Neuron 2008;58:30624.
[89] Indovina I, Macaluso E. Occipital-parietal interactions during shifts of exogenous
visuospatial attention: trial-dependent changes of effective connectivity. Magn
Reson Imaging 2004;22:147786.
[90] Indovina I, Macaluso E. Dissociation of stimulus relevance and saliency factors
during shifts of visuospatial attention. Cereb Cortex 2007;17:170111.
[91] Fairhall SL, Indovina I, Driver J, Macaluso E. The brain network underlying serial
visual search: comparing overt and covert spatial orienting, for activations and for
effective connectivity. Cereb Cortex 2009;19:294658.
[92] Staab JP. The inuence of anxiety on ocular motor control and gaze. Curr Opin
Neurol 2014;27:11824.
[93] Delgado MR, Nearing KI, Ledoux JE, Phelps EA. Neural circuitry underlying the regulation of conditioned fear and its relation to extinction. Neuron 2008;59:82938.
[94] Hartley CA, Phelps EA. Changing fear: the neurocircuitry of emotion regulation.
Neuropsychopharmacology 2010;35:13646.
[95] Milad MR, Wright CI, Orr SP, Pitman RK, Quirk GJ, Rauch SL. Recall of fear extinction
in humans activates the ventromedial prefrontal cortex and hippocampus in
concert. Biol Psychiatry 2007;62:44654.
[96] Ochsner KN, Gross JJ. The cognitive control of emotion. Trends Cogn Sci 2005;9:
2429.