Neural Mechanisms in Eating Behaviors: A Pilot fMRI Study of Emotional Processing

Abstract

Objective:
Emotional processing dysfunction evident in eating disorders (ED) such as anorexia nervosa (AN) and bulimia nervosa (BN), is considered relevant to the development and maintenance of these disorders. The purpose of the current functional magnetic resonance imaging (fMRI) study was to pilot a comparison of the activity of the fronto-limbic and fronto-striatal brain areas during an emotion processing task in persons with ED.

Methods:
24 women patients with ED were scanned, while showing emotionally stimulating (pleasant, unpleasant) and neutral images from the International Affective Picture System (IAPS).

Results:
During the pleasant condition, significant differences in Dorsolateral Prefrontal Cortex (DLPFC) activations were found with AN participants presenting greater activation compared to BN and ED comorbid groups (EDc) and healthy controls also showing greater activation of this brain area compared to BN and EDc. Left putamen was less activated in EDc compared to both controls (C) and AN. During the unpleasant condition, AN participants showed hyperactivation of the Orbito-frontal Cortex (OFC) when compared to EDc.

Conclusion:
This study highlights the potential functional relevance of brain areas that have been associated with self-control. These findings should help advance understanding the neural substrate of ED, though they should be considered as preliminary and be cautiously interpreted.

Full text

Copyright
©
2020 Korean Neuropsychiatric Association 1
INTRODUCTION
Recent studies in eating disorders (ED) have found evi-
dence of emotional awareness and emotion processing altera-
tions in ED.1-5 However, the current literature is not sucient-
ly informative regarding the nature of emotional processing
in ED to develop a model on which to base therapeutic inter-
ventions. Emotional processes currently identied in ED im-
plicate amygdalo-cortical and cortico-striato-thalamo-cortical
re-entrant circuits6-10 in creating dysregulated appetitive be-
Print ISSN 1738-3684 / On-line ISSN 1976-3026
OPEN ACCESS
haviours (e.g., food restriction, vomiting) in ED.11
Based upon current studies of emotional processing in ED,
persons with anorexia nervosa (AN) may present with exag-
gerated cognitive control and seek to reduce negative emotions
and anxiety symptoms by restricting food; while those with
bulimia nervosa (BN) may have deficient cognitive control,
thus increasing the instability and erratic responding to appeti-
tive stimuli and obtaining a reduction of negative emotions
with binge eating and purging.12,13 Such impulsive eating be-
haviours are more frequently seen in EDs associated with bor-
derline personality traits.14-18 Based on this cognitive-control
model, extremes of eating behaviour would emerge from an
altered balance of reward and inhibitory processing.10 Conse-
quently this model for ED could be understood across an im-
pulsive-compulsive spectrum: from obsessive disorders, with a
greater tendency to harm avoidance and compulsive behav-
iours at the compulsive end (AN restrictive) in contrast to
those with high impulsivity, with a tendency towards harm
ORIGINAL ARTICLE
Objective Emotional processing dysfunction evident in eating disorders (ED) such as anorexia nervosa (AN) and bulimia nervosa
(BN), is considered relevant to the development and maintenance of these disorders. e purpose of the current functional magnetic
resonance imaging (fMRI) study was to pilot a comparison of the activity of the fronto-limbic and fronto-striatal brain areas during an
emotion processing task in persons with ED.
Methods 24 women patients with ED were scanned, while showing emotionally stimulating (pleasant, unpleasant) and neutral images
from the International Aective Picture System (IAPS).
Results During the pleasant condition, signicant dierences in Dorsolateral Prefrontal Cortex (DLPFC) activations were found with
AN participants presenting greater activation compared to BN and ED comorbid groups (EDc) and healthy controls also showing greater
activation of this brain area compared to BN and EDc. Le putamen was less activated in EDc compared to both controls (C) and AN.
During the unpleasant condition, AN participants showed hyperactivation of the Orbito-frontal Cortex (OFC) when compared to EDc.
Conclusion is study highlights the potential functional relevance of brain areas that have been associated with self-control. ese
ndings should help advance understanding the neural substrate of ED, though they should be considered as preliminary and be cau-
tiously interpreted. Psychiatry Investig
Key Words Functional magnetic resonance imaging, Eating disorders, Emotion processing, Prefrontal cortex, Striatum.
Received: April 4, 2019 Revised: June 22, 2019
Accepted: October 14, 2019

Correspondence: Rosa M. Molina-Ruiz
Psychiatry Department, Universitary Hospital ClÍnico San Carlos de Madrid,
Madrid, IddISC, Spain
Tel : +34-676106633, E-mail: rosamolina18@hotmail.com
cc is is an Open Access article distributed under the terms of the Creative Commons
Attribution Non-Commercial License (https://creativecommons.org/licenses/by-
nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduc-
tion in any medium, provided the original work is properly cited.
https://doi.org/10.30773/pi.2019.0038
Psychiatry Investig 2020 March 12 [Epub ahead of print]
Neural Mechanisms in Eating Behaviors: A Pilot fMRI
Study of Emotional Processing
Rosa M. Molina-Ruiz1 , T. García-Saiz2, Jeffrey C.L. Looi3, E. Via Virgili4, M. Rincón Zamorano2,
Laura de Anta Tejado1, Helena Trebbau López1, Jose Luis Carrasco Perera1, and Marina Díaz-Marsá1
1Psychiatry Department, Universitary Hospital Clinico San Carlos de Madrid, IddISC, Madrid, Spain
2Artificial Intelligence Department, UNED. E.T.S.I. Informatics, Madrid, Spain
3Academic Unit of Psychiatry and Addiction Medicine, Australian National University Medical School, Canberra Hospital, Canberra,
Australia 4Hospital Materno-Infantil Sant Joan de Déu, Barcelona, Spain

2 Psychiatry Investig
Emotional Processing in Eating Disorders
avoidance-AN binge-purging, BN and borderline personality
disorder (BPD)-.10,19-22 Regarding brain functioning, cortico-
striatal circuit dysfunction may be implicated in suppressing
or inhibiting inappropriate behaviours that underpin impul-
sive and compulsive symptomatology in obsessive-compul-
sive disorders22-24 and also in emotional processing and regu-
lation processes,25-27 and therefore they may be of interest in
the study of ED.
Neuroimaging techniques oer a window into the activity of
neuronal circuits involved in emotional processing in ED.28-30
ese functional MRI (fMRI) studies in ED have used body
images or food paradigms as aversive stimuli mainly.31-40 How-
ever, the paradigms and methodologies used in these studies
vary greatly, making it dicult to draw coherent conclusions.
Moreover, compared to these previous paradigms, the use of
general emotional stimuli may allow better understanding of
emotional processing in general in EDs, since emotional pro-
cessing is considered a core symptom related to eating behav-
iours (i.e., restricting, purging) and it might not be only a con-
sequence of food or body shape. From this point of view the
International Aective Picture System (IAPS),41 which consist
of a well-characterized collection of visual coloured images de-
signed to evoke either neutral, positive or negative emotional
states, seems a suitable tool. To our knowledge, although some
studies have used IAPS to test the emotional reactivity of ED
patients to social situations,42 no previous fMRI emotional
processing studies in ED have focused on general, as opposed
to disease-specic, emotional stimuli. fMRI studies in healthy
persons have identified brain networks involved in emotion
processing mechanisms, a number of them employing images
from the IAPS.41 In healthy individuals, viewing of emotional
pictures is associated with activation in prefrontal cortex areas
(dorsolateral, ventromedial and orbitofrontal),43-46 amygdala-
hippocampal regions44,45 and basal ganglia,44 among others.
e purpose of the present study was to explore the general
emotional processing in ED, through using a small subset of
complex visual scenes (depicting happiness, fear, anger, or
threat), derived from the IAPS as stimuli.41 Based on the above
previous studies, we hypothesized that AN patients may be
able to inhibit appetite and exert extraordinary self-control be-
cause of exaggerated cortico-amygdalar and cortico-striatal
circuit function (hyperactivation); whereas individuals with
BN may be more vulnerable to overeating because they have
less top down regulation, i.e., self-control, probably due to a
lower activation of cortico-amygdalar and cortico-striatal cir-
cuits (hypoactivation) when presented with emotional eliciting
cues (Figure 1). On the other hand, a high prevalence of bor-
derline personality disorder has been reported in BN and pur-
gative AN,16 which sometimes might complicate the dieren-
tial diagnosis and have BPD-associated hypofunction of
Figure 1. Diagram of impulsive-compulsive spectrum disorders. On the left: “compulsive end,” mainly represented by disorders where ob-
sessions and compulsions are prominent (AN, OCD, Tourette Sd: Tourette’s Syndrome). On the right: “impulsive end,” where impulsivity
plays a crucial role (e.g., BN, EDc, and BPD).20 Tourette Sd: Tourette’s Syndrome, OCD: Obsessive Compulsive Disorder, ANr: restrictive
Anorexia Nervosa, ANbp: binge purging type Anorexia Nervosa, BN: Bulimia Nervosa, EDc: Eating Disorder with comorbid with borderline
personality disorder.
Functional: prefrontal hyperactivity
Compulsivity
harm avoidance,
restriction, rigidity,
hypercontrol...
Predisposing factors: genetic,
neurobiologic, etc
Precipitating factors: trauma,
history, puberty, stress, etc
Tourette Sd OCD ANr ANbp BN EDc BPD
Impulsivity, novelty
seeking, decient
cognitive control,
mood instability...
Functional: prefrontal hypoactivity
Neuroplasticity
Maintenance factors: socio-cultural
factors, maintained malnutrition
Neuroplasticity

RM Molina-Ruiz et al.
www.psychiatryinvestigation.org 3
regions of prefrontal cortex.47 A subgroup study of ED with
BPD comorbidity was performed to differentiate from the
other pure ED groups.
METHODS
Subjects
Twenty-four female patients diagnosed with either AN
(n=8), BN (n=9), or eating disorder comorbid with border-
line personality disorder, ED+BPD (EDc) (n=7) were recruit-
ed. Patients with EDc had comorbid diagnoses of BPD and
BN. All of them were current outpatients at a major teaching
Hospital in Madrid (Spain), were stable (had not had any hos-
pitalization during the last year and were on regular ambula-
tory treatment), had similar sociodemographic characteristics
and were receiving regular ambulatory treatment (all of them
were receiving Cognitive Behavioural erapy, and might be
taking SSRI or benzodiazepines). None of them had been tak-
ing antipsychotics for the last 6 months.
Diagnoses were made by experienced psychiatrists (M.D.M;
R.M.M.R) according to DSM-IV-TR criteria;48 clinical diag-
nostic subtyping was made on the basis of current symptoms
at the time of the study.
A control group of healthy females, C (n=19), were recruit-
ed by advertisement at University Complutense of Madrid
and Hospital ClÍnico San Carlos, Madrid. ey were of the
same age range, education and socioeconomic level.
All patients and controls were interviewed by means of the
Structured Clinical Interview for DSM-IV (SCID-I and II)49
to evaluate Axis I and Axis II diagnosis, and to exclude co-
morbid Axis I mental disorders in the ED groups. Compre-
hensive assessments were undertaken to exclude any potential
major medical disease such as a history of head trauma, neu-
rological disease, substance use disorders or any other major
medical illnesses. We also ensured that controls had no histo-
ry of ED or any current of past Axis I or Axis II disorder.
Ethical approval for the study was obtained at Hospital ClÍni-
co San Carlos, Madrid Clinical Ethics Committee (E-07/121).
Written informed consent was provided by all participants.
Impulsivity and bulimic eating behaviors were assessed us-
ing both self-report questionnaire measures: 1) impulsivity
was assessed with the Barratt impulsiveness Scale (BIS)50,51 a
30-item questionnaire describing common impulsive or
non-impulsive (for reverse scored Ítems) behaviors and pref-
erences. Items are scored on a 4-point scale: rarely/never=1,
occasionally=2, oen=3, almost always/always=4. e BIS is
one of the most commonly administered self-report mea-
sures for the assessment of impulsiveness in both research
and clinical settings. For the behavioural assessment of im-
pulsivity, we focused on the general punctuation scale. 2)
Bulimic behaviors were assessed with a self-rating scale, the
Bulimic Investigatory Test, Edinburgh (BITE) for the detec-
tion and description of binge eating.52,53 BITE is a 33-item
self-report measure designed to identify individuals with
symptoms of bulimia or binge eating. It consists of two sub-
scales: the symptom scale (BITE-sas), which measures the
degree of symptoms present, and the severity scale (BITE-ss),
which provides an index of the severity of binging and purg-
ing behavior as dened by their frequency.
Procedures
Imaging acquisition
BOLD functional images were obtained for all participants
on a 1.5T General Electric Sigma MRI scanner (GE, Milwau-
kee, WI, USA) [repetition time (TR)/echo time (TE)=3,000/50
ms, field of view (FOV)=22×22 cm, 64×64 pixel matrix, 20
axial slices per scan, slice thickness=5 mm, gap=1.5 mm].
A total of 204 whole brain volumes were acquired for each
run. e rst two scans were discarded from analysis to allow
magnetic saturation eects. All scanning parameters were se-
lected to optimize the quality of the BOLD signal while main-
taining a sufficient number of slices to acquire whole-brain
data. Stimuli were presented via a back-projection system.
Experimental paradigm
The paradigm consisted of two sequences of alternating
blocks with experimental conditions that involved the presen-
tation of “emotionally stimulating’’ versus neutral images
from the IAPS (pleasant-neutral and unpleasant-neutral se-
quences). IAPS includes a standardized and well-character-
ized collection of visual coloured images designed to evoke
either neutral, positive or negative emotional states.54 Twenty
unpleasant pictures selected from the IAPS, consisted of neg-
ative-emotionally evocative images, e.g., injured people,
snakes or spiders; while other 20 pleasant pictures were se-
lected from IAPS and consisted of positive-emotion evoking
images, e.g., images of happy couples and family or nice land-
scapes. Finally 20 neutral-valenced pictures were selected to
show daily-life objects such as chairs, books or tables.
Each sequence consisted of a total of 7 blocks (3 stimulat-
ing blocks interleaved into 4 neutral control blocks). Each
experimental block consisted of 7 stimuli sequentially pre-
sented for 3 seconds. e order of the stimuli was counter-
balanced across participants. The paradigm was repeated
twice for each participant.
Subjects rested supine in the scanner while viewing the im-
ages and were instructed to keep their eyes open to watch all
images and to allow themselves to “feel whatever emotion the
slides produced.” During the rest condition, 30 seconds before

4 Psychiatry Investig
Emotional Processing in Eating Disorders
the rst image block and between each positive and negative
image block, the patient was told to “relax” (Figure 2).
Image pre-processing and data analyses
We performed image processing and statistical analyses
fMRI data using the FMRIB Soware Library (F.S.L.) version
4.1.9 (FMRIB, Oxford, Oxfordshire, UK). Image pre-processing
included motion correction, slice timing correction, normaliza-
tion to the MNI 152 standard space, and spatial smoothing
with a 10 mm full width at half maximum (FWHM). Voxel size
aer the reconstruction was 2×2×2 mm3.
Statistics
We analyzed the data using SPSS 15.0 (SPSS Inc., Chicago,
IL, USA). Descriptive statistics were used to report the fre-
quencies for the categorical variables and the mean value
with the standard deviation (SD) for the continuous vari-
ables. Unpaired ANOVA and T-test were used to evaluate the
dierences among dierente groups. To analyse the images,
we performed planned three-stage statistical analyses:
1) In the first stage, we obtained the mean response for
each subject to the pleasant and unpleasant paradigms. In a
rst level analysis, correlations between the BOLD response
and emotional condition in each single session were exam-
ined at whole brain level. e emotional stimuli were mod-
elled by a square waveform convolved with a gamma func-
tion plus temporal and dispersion derivatives. e contrasts
of interest were pleasant versus neutral and unpleasant versus
neutral. In a second level of analysis, results were accumulat-
ed across sessions to obtain the mean response for each sub-
ject using a FWE-corrected cluster extent threshold (pFWE=
0.05) to correct for multiple comparisons.
2) The second stage involved planned within-group and
between-group analyses. Specically for between group anal-
yses we analysed all ED groups combined compared to con-
trols. We also analysed the subgroups as ED are recognised
as phenotypically heterogeneous comprising AN, BN and
comorbid with BPD groups.
• For each group, a t-test was dened in order to study the
mean group eect, that is, if the group activated on average.
• In order to nd signicant dierences between groups, C
group was compared with the whole eating disorder group (ED)
and each subgroup (AN, BN, EDc) and also subgroups were
compared between them. For each comparison, two t-tests
were dened to nd out, not only the existence of dierences
between groups, but also the direction of these dierences.
3) Finally, on the third stage of analysis, we analysed dier-
ent Regions of Interest (ROI). For each ROI, we report activa-
tions that surpass the uncorrected threshold (punc<0.001), and
at the same time surpass the FWE-corrected cluster extent
threshold (pFWE=0.05) to correct for multiple comparisons.
ROIs were dened using the “Harvard-Oxford Atlas”55 and
included the amygdala, striatum (caudate and putamen) and
parts of prefrontal cortex (PFC) such as the dorsolateral pre-
frontal cortex (DLPFC), orbitofrontal cortex (OFC), medial
prefrontal cortex (MPFC) and frontal pole (FP), areas in-
volved in emotion processing and regulation.6,9,25
RESULTS
Sociodemographic data are summarized in Table 1. ere
were no signicant dierences in mean age between the ED
as a group compared to controls. Controls were signicantly
younger on average compared to the AN and EDc groups
(C<AN, p=0.05). ese dierences (all patients and controls
ranged between 20 and 40 years) were not considered signi-
cant for functional analysis and given the small sample they
were not analysed as a covariate.
On average, body mass index in BN was higher compared
to all other three groups, though the greatest dierence was
found between AN and BN, as expected.
Education level was similar between eating disorder groups
but participants in the healthy control group showed greater
educational level compared to BN and EDc groups.
Figure 2. fMRI paradigms. Alternated blocks Neutral/Pleasant (N/
P), Neutral/Unpleasant (N/U). fMRI: functional magnetic reso-
nance imaging, IAPS: the International Affective Picture System.
Pleasant picture
Resting condition
Resting condition
30 secs
30 secs
3 secs
3 secs
3 secs
3 secs
Total: 147 seconds
Total: 147 seconds
Neutral
Neutral
Neutral
Unleasant
Neutral
Pleasant
Unpleasant IAPS picture
Neutral picture
Neutral picture

RM Molina-Ruiz et al.
www.psychiatryinvestigation.org 5
Pleasant paradigm, within group analysis
Group activation maps are shown in Table 2. All areas of
emotional processing and regulation measured, cortical and
subcortical (PFC, amygdala and striatum) were activated in
the control group. Similar results were obtained for AN and
BN groups excepting the regions: VMPFC and le putamen
in AN, le putamen and caudate in BN. EDc did not show
activation in the subcortical regions (amygdala, caudate and
putamen) except for le caudate, although all prefrontal ar-
eas were activated in this group.
Unpleasant paradigm, within group analysis
Group activation dierences are showed in Table 3.
When comparing unpleasant-neutral images between sub-
groups we found that: control group showed more activation
in all selected regions when exposed to unpleasant images
compared to neutral ones, except for VMPFC and le puta-
men. Patients with AN mainly activated DLPFC, FP and le
amygdala, while those with BN and EDc barely activated FP
and DLPFC respectively.
Pleasant paradigm, between group analysis
When comparing the activation between patients as a
whole group (all ED subtypes) and controls, no statistically
signicant dierences were found in any of the brain areas
selected in this study.
When doing the analysis by subgroups and by ROI, the
following dierences were found (Table 4 only showing those
contrasts that became statistically signicant):
- DLPFC was more activated in AN and C compared to
BN and EDc. ere was also a tendency towards greater acti-
vation of DLPFC in AN versus controls (x: 50.0, y: 34.0,
z:12.0; p: 0.0015).
- Le putamen was more activated in control group com-
pared to EDc and in AN compared to EDc.
- FP showed greater activation in AN compared to BN and
EDc, as well as in controls compared to AN (C>AN>BN> EDc).
Activation maps of more representative results are shown
below (Figures 3 and 4). Images from fMRI show brain acti-
vation (colored dots) overlaid on a transverse slice of the cor-
responding structural brain image (grayscale).
Unpleasant paradigm, between group analysis
During unpleasant paradigm, no statistically significant
dierences in activation (in any of the brain areas selected)
were found when comparing the ED group as a whole (in-
Table 1. Demographic variables
Variab le AN (N=8) BN (N=9) EDc (N=7) C (N=19) pComparison
Age, years, Mean (SD) 30.13 (9.25) 28.44 (11.21) 32 (10.47) 23.18 (2.404) 0.05 C<AN & EDc
BMI, kg/m2, Mean (SD) 16.92 (2.80) 25.90 (7.54) 19.69 (5.13) 19.79 (1.54) 0.002 BN> C,EDc, AN
Education (years) 15.14 (2.54) 14.67 (2.44) 13.20 (1.78) 16.33 (1.41) 0.16 C> EDc & BN
Barratt 35 (5.31) 52.78 (9.92) 63.43 (15.38) 33.94 (5.76) 0.001 EDc>BN, AN & C
BITE 13.38 (8.89) 26.78 (6.45) 21.71 (7.91) 3.47 (3.24) 0.001 BN>EDc, AN & C
Age, Body Mass Index (BMI), Education, BITE and Barratt scales according to diagnosis. p<0.05. AN: anorexia nervosa, BN: bulimia nervo-
sa, EDc: eating disorder comorbid with borderline personality disorder, C: control, BITE: Bulimic Investigatory Test, Edinburgh
Table 2. Pleasant paradigm
Pleasant-Neutral C (N=19)
p
AN (N=8)
p
BN (N=9)
p
EDc (N=7)
p
VMPFC 0.000052 0.0034 0.000094 0.000208
OFC 0.000025 0.000079 0.000023 0.000868
Frontal Pole 0.000015 0.000308 0.000019 0.000208
DLPFC 0.000019 0.0011 0.000021 0.000872
Le Amygdala 0.000208 0.00012 0.000830 0.007
Le Caudate 0.00026 0.00063 0.0023 0.00079
Le Putamen 0.00074 0.0015 0.0029 0.003
Right Amygdala 0.000066 0.000080 0.000303 0.006
Right Caudate 0.000053 0.000553 0.000775 0.010
Right Putamen 0.000211 0.0019 0.000480 0.019
Regions found signicantly activated by subgroups and by ROI. Activation=p<0.05. ROI: region of interest, MVPFC: ventro medial prefron-
tal cortex, OFC: orbitofrontal cortex, DLPFC: dorsolateral prefrontal cortex

6 Psychiatry Investig
Emotional Processing in Eating Disorders
Table 4. Pleasant paradigm
Standard space. montreal neurological institute
ROI Contrast x y z T Unc. p-value
DLPFC AN>EDc 50.0 38.0 12.0 4.208 0.0008
AN>BN 46.0 36.0 14.0 4.359 0.0005
C>BN -54 10 50 3.883 0.0009
C>EDc 40 -6 56 4.92 0.00009
Le Putamen C>EDc -26 -10 4 4.269 0.00043
AN>EDc -28 -10 4 4.59 0.0004
Frontal Pole C>AN -56 38 6 3.947 0.0009
AN>EDc 50 38 12 4.208 0.0008
AN>BN 46 36 14 4.359 0.0005
Group comparisons. Only signicant results are shown in this table. Unc. p-value: uncorrected p-value. AN: anorexia nervosa, BN: bulimia
nervosa, EDc: eating disorder with comorbid with borderline personality disorder, C: controls, ROI: region of interest, VMPFC: ventromedial
prefrontal cortex, OFC: orbitofrontal, Cortex; DLPFC: dorsolateral prefrontal cortex. Voxel size: 2×2×2 mm3
Table 3. Unpleasant paradigm
Unpleasant-Neutral C (N=19)
p
AN (N=8)
p
BN (N=9)
p
EDc (N=7)
p
VMPFC 0.012 0.013 0.002 0.02
OFC 0.000158 0.0012 0.002 0.003
Frontal Pole 0.000168 0.000496 0.000796 0.003
DLPFC 0.000294 0.000102 0.002 0.00022
Le Amygdala 0.000765 0.003 0.007 0.011
Le Caudate 0.000116 0,003 0.004 0.005
Le Putamen 0.002 0,002 0.011 0.006
Right Amygdala 0.0010 0.000705 0.016 0.049
Right Caudate 0.000083 0.002 0.003 0.056
Right Putamen 0.0010 0.001 0.01 0.081
Regions found signicantly activated by subgroups and by ROI. Activation=p<0.05. ROI: region of interest, MVPFC: ventro medial prefron-
tal cortex, OFC: orbitofrontal cortex, DLPFC: dorsolateral prefrontal cortex
cluding all ED subtypes) with controls.
On analysis the data by subgroups during the unpleasant
paradigm, the following significant differences were found
(Table 5): greater activation of FP when all patients as a group
were compared to controls; greater activation in AN group
when compared to EDc in Orbitofrontal cortex (OFC); greater
activation of FP in AN, BN and EDc when compared to con-
trols and BN when compared to AN.
Activation maps of more representative results are shown
below. Images from fMRI show brain activation (colored dots)
overlaid on a transverse slice of the corresponding structural
brain image (grayscale) (Figure 5).
DISCUSSION
e purpose of the present study was to explore the general
emotional processing response in ED, in order to develop hy-
potheses and directions for further research. We hypothesized
that an increased emotional reactivity more characteristic of
BN and EDc patients might be a consequence of their inability
to adequately engage a reective -executive system (prefrontal
areas) and thus rely heavily upon more automatic response
systems (amygdala and basal ganglia). We also hypothesized
decreased emotional reactivity and over-control of emotions
in AN would be a consequence of hyperactivation of prefron-
tal brain regions (dorsolateral and orbitofrontal), involved in
reective cortical processing and executive control.
To our knowledge, no previous functional neuroimaging
studies have used general emotional stimuli (e.g., IAPS) as a
paradigm for emotional processing in ED.56 Pictures in IAPS
identied as pleasant as well as unpleasant were experienced
by participants as stimulating compared to neutral pictures,

RM Molina-Ruiz et al.
www.psychiatryinvestigation.org 7
Figure 3. Pleasant stimuli. Dorsolateral Prefrontal Cortex (DLPFC), ROI-based analyses. AN and BN subgroups comparison (AN>BN).
Transverse slice. ROI: regions of interest, AN: anorexia; BN: bulimia nervosa.
Figure 4. Unpleasant stimuli. Dorsolateral Prefrontal Cortex (DLPFC), ROI-based analyses. C and EDc subgroups comparison (C>EDc).
Transverse slice. ROI: regions of interest, C: control, EDc: eating disorder comorbid.

8 Psychiatry Investig
Emotional Processing in Eating Disorders
Table 5. Unpleasant paradigm
Standard space. montreal neurological institute
ROI Contrast x y z T Unc. p-value
OFC AN>EDc 24.0 12.0 -20 4.126 0.001
Frontal Pole AN>C -42 64 2 4.063 0.0007
BN>C -44 52 -10 5.027 0.00009
EDc>C -40 48 -6 3.938 0.0009
BN>AN 22 40 14 4.192 0.0007
Group comparisons. Only signicant results are shown in this table. Unc. p-value=uncorrected p-value. AN: anorexia nervosa, BN: bulimia
nervosa, EDc: eating disorder with comorbid with borderline personality disorder, C: controls. ROI: region of interest; VMPFC: ventromedial
prefrontal cortex, OFC: orbitofrontal cortex, DLPFC: dorsolateral prefrontal cortex. Voxel size: 2×2×2 mm3
Figure 5. Unpleasant stimuli. Orbitofrontal cortex (OFC), ROI-based analyses. AN and EDc subgroups comparison (AN>EDc). Transverse
slice. AN: anorexia nervosa, EDc: eating disorder comorbid.
validating the emotional salience of our paradigm.
Within group analysis examined functional responses to
emotionally stimulating stimuli (pleasant or unpleasant ver-
sus neutral) for each group of participants. Controls showed
increased BOLD responses to both pleasant and unpleasant
stimuli compared to neutral ones, in all selected brain re-
gions that have been repeatedly shown to be relevant for
emotional processing and regulation: PFC, amygdala and
striatum.57-61 In contrast, ED subgroups failed to show this
default response in some of the selected brain areas (Table 2
and 3). e majority of patient groups showed activation at a
cortical level (PFC), lacking subcortical activation (amygdala
and striatum), especially during the unpleasant condition.
Preliminarily, these results might indicate a diculty in ade-
quately engaging brain circuits involved in emotional pro-
cessing in those with EDs.
ere may be a number of explanations for a lack of func-
tional activation of subcortical areas in ED groups in general
emotional processing:
1) A deficit in the first stage of emotional recognition.
However, this explanation contrasts with previous studies
that found greater activation in subcortical structures such as

RM Molina-Ruiz et al.
www.psychiatryinvestigation.org 9
amygdala in ED patients,36,56 which had used specic aversive
stimuli (food or body silhouettes).
2) An excessive activation of PFC via “top-down”60,62 regu-
lation (cognitive control), that could lead to a relative deacti-
vation of the amygdala and striatum, as it has been shown in
previous studies where labelling a stimulus image (e.g., nam-
ing the expected aect), resulted in a reduction in amygdala
activity.63,64
3) Finally, a disconnection or desynchronization might ex-
ist between cortical structures (PFC) and subcortical regions,
as has been seen in BPD patients.65
e second phase of analysis included between group com-
parisons for each specic paradigm (pleasant-neutral and un-
pleasant-neutral). No dierences were found when comparing
all combined ED as a group versus controls whether during
pleasant or unpleasant paradigm. Since ED include both sub-
groups of AN and BN and EDc (polar opposite groups of what
we have hypothesized as the impulsive-compulsive continu-
um), we infer that it is possible the summation of hypo and
hyper-activity from respective ED groups which yields an
overall null dierence.
Analysis by subgroups during the pleasant paradigm showed
greater activation in AN in the DLPFC, frontal pole and left
putamen compared to EDc, and a tendency towards greater ac-
tivation of DLPFC in AN versus controls was also observed.
However, these are acknowledged as exploratory ndings due
to the small subgroup sample size.
The DLPFC is part of the cognitive control network and
has been associated with restriction of appetitive respons-
es.66-68 Dierences found in the DLPFC between AN and EDc
and BN and controls, may be tentatively interpreted in terms
of a greater tendency to restrict emotions in AN -through
“top-down” mechanisms of PFC inhibiting subcortical struc-
tures.12,69-71 In partial support of our ndings, in BN patients, a
deciency of activation of prefrontal brain regions during ap-
petitive stimuli has been demonstrated.6,28,72,73 However, a PET
study indicated that regional cerebral blood ow (rCBF) nor-
malized with long-term recovery in AN and BN. 74
Similar results were found in the Frontal Pole (FP) regions
(greater activation during the pleasant paradigm in AN com-
pared to BN and EDc but not compared to controls).
Taking into account that BN and EDc groups showed less
activation in the DLPFC when compared to controls, we can
therefore suggest there may be a gradient of activation in
PFC regions (AN>C>BN>EDc).
Moreover, the EDc group showed less activation in le pu-
tamen compared to controls and AN, however caudate or
amygdala dierences did not reach signicance compared to
other studies.75 The striatum (caudate and putamen) is in-
volved in the activation of motor programs (some innate) but
also in social-emotional expression, recognition,57,58,76-78 and
withdrawal behaviours.79 ose suering comorbid BD and
BPD have been characterized as showing a lack of emotional
control intrinsic to both disorders, in turn related to dysfunc-
tion of cortico-striatal circuits.80,81 Accordingly, the lower acti-
vation of putamen (as a component of corticostriatal circuit-
ry) in these patients might result in an increased anticipatory
response when facing emotional stimuli compared to other
ED subgroups as well as controls and therefore, a more dys-
regulated pattern of eating behaviours.
During the unpleasant paradigm the group dierences were
detected in OFC functional activity. OFC is involved in repre-
senting the aective value of reinforcers, decision-making pro-
cesses, expectation and processing of the negative valence of
emotional stimuli. Patients with AN may display excessive
control in the compulsive end of the impulsive-compulsive
spectrum, while those with BPD have shown frontal dysfunc-
tions, predisposing to lack of control, specically a disconnec-
tion between PFC and limbic areas and reduced frontal inhibi-
tory activity.65 erefore, the greater activation of OFC in AN
compared to EDc, suggests that patients with AN have greater
activity in the OFC as exertion of greater cognitive control
when facing emotional stimuli. Similar activation results were
found in previous studies in AN patients,31 however only dur-
ing presentation of specic disease aversive stimuli (food and
silhouettes) and not during general emotional stimuli82 as
found in this study. In another study using IAPS (emotional
perception test in ED), an AN restrictive group showed in-
creased fear when confronted with stimuli containing anger,
that was attributed to introversion and conflict avoidance of
patients with anorexia.56
Overall, our results suggest that there are dierential func-
tional patterns emotional processing (e.g., DLPFC) across
the groups in our study. Increased DLPFC activity for emo-
tional processing in AN patients might be the basis of exces-
sive top-down regulation: driving excessive emotional con-
trol, ruminations about weight, shape and an excessive ability
to restrain appetite. Conversely, decreased activation in DLP-
FC regions to emotional stimuli in BN and EDc might be the
basis of decreased control in eating behaviour and their emo-
tions (Figure 1).
ere appears to be dierential processing of general emo-
tional stimuli in subgroups of EDs on the basis of hyper or
hypo-activity in regions mediating cortical emotional control
(such as PFC). ese preliminary pilot ndings raise the pos-
sibility that, when processing emotional cues, persons with
AN rely more upon reective cortical processing and execu-
tive control compared to lesser involvement of such process-
ing in those with EDc, BN and controls. ese dierences in
emotional processing activity might thus influence eating

10 Psychiatry Investig
Emotional Processing in Eating Disorders
behaviours. Since these results are regarded as exploratory
this should be conrmed in future longitudinal studies.
Our functional emotional processing ndings are poten-
tially consistent with the compulsivity to impulsivity contin-
uum model of ED, corresponding to compulsivity of control
in AN and impulsivity of decreased control in BN and EDc.83
is model of ED also allows a conceptualisation for a bipo-
lar spectrum of emotional processing of ED symptoms over
the course of illness (Figure 1) and may potentially have im-
portant implications in their classification, treatment and
prognosis.
Methodological limitations of this study, which limit gen-
eralizability, include: 1) small sample size which limits the
power of the study to derive definitive findings, hence our
the ndings should be regarded as preliminary and explor-
atory pilot data to help inform future studies; 2) lack of lon-
gitudinal follow up in this cross-sectional study; 3) concep-
tual and methodological limitations when trying to study the
dierent components of emotional processing and emotional
responsiveness variability;77 4) methodological limitations
due to fMRI characteristics (e.g., 1.5 tesla MRI against more
frequently used 3 tesla MRI); 5) lack of data on severity of
psychopathology and pharmacological treatment.
Against these limitations, the strengths of our study must
be balanced: the exploratory conceptual advancement of
studying general emotional responsiveness developing a hy-
pothetical impulsivity-compulsivity continuum model of
ED; distinction of an independent subgroup of EDc allowing
a better control of the presence of borderline personality
traits in the sample; a priori hypothesis-based stepwise fMRI
analysis; and matching of healthy controls on relevant so-
ciodemographic parameters.
In conclusion, dierences in functional brain activity in pre-
frontal areas may help in the phenotypic dierentiation of ED
subtypes. Our ndings provide preliminary exploratory sup-
port of a hypothesized pathophysiologic cognitive-control
model of ED.
AN patients showed greater activation of areas involved in
emotional control (DLPFC) compared to the rest of the
groups. ese results might be related to a tendency of those
with AN to over-control emotions. e control group showed
greater activation of DLPFC compared to BN, potentially
consistent with the hypothesis of diametrically opposed
mechanisms of emotional control among AN and BN groups
(AN-over-control and BN-decient control).
In comparison to other diagnostic subgroups, the ED co-
morbid group (EDc=ED+BPD) showed less activation in
DLPFC and this might be related to lesser activation of reec-
tive cortical processing areas mediated by the presence of bor-
derline traits.
Overall, dierences in activation of PFC areas in ED may
potentially represent key functional bases in the general emo-
tional responsiveness of these disorders with implications for
their pathophysiologic phenomenology. However, we ac-
knowledge this is a small exploratory pilot study, which will
need replication in a larger sample size with investigation of
additional regions of interest to see if the ndings hold true.
Acknowledgments
JCLL self-funded travel costs as co-director for RMM-R’s PhD (Com-
plutense University) thesis on which this research is based. Ms. Via is sup-
ported by an Endeavour Research Fellowship, provided by Australian gov-
ernment, the Department of Education (I.D. 3993_2014). The authors
would like to thank all patients and volunteers for their participation in the
study and sta at the Psychiatry and Radiology Department of Hospital
ClÍnico San Carlos for their dedicated support.
Conflicts of Interest
e authors have no potential conicts of interest to disclose.
Author Contributions
Conceptualization: Rosa M. Molina Ruiz, Marina Díaz-Marsá, Laura de
Anta Tejado, Jose Luis Carrasco Perera. Data curation: Rosa M. Molina
Ruiz, Marina Díaz-Marsá, Laura de Anta Tejado, Helena Trebbau López.
Formal analysis: T. García-Saíz, M. Rincón Zamorano. Investigation: Rosa
M. Molina Ruiz, Marina Díaz-Marsá, Laura de Anta Tejado, Jose Luis
Carrasco Perera. Methodology: Rosa M. Molina Ruiz, Marina Díaz-Marsá,
Laura de Anta Tejado, Jose Luis Carrasco Perera. Project administration:
Rosa M. Molina Ruiz, Marina Díaz-Marsá, Laura de Anta Tejado, Jose Luis
Carrasco Perera. Resources: Rosa M. Molina Ruiz, Marina Díaz-Marsá,
Laura de Anta Tejado, Jose Luis Carrasco Perera. Soware: T. García-Saíz,
M. Rincón Zamorano. Supervision: E. Via Virgili, Marina Díaz-Marsá,
Jose Luis Carrasco Perera, Jerey C.L. Looi. Validation: E. Via Virgili, Ma-
rina Díaz-Marsá, Jose Luis Carrasco Perera, Jerey C.L. Looi. Visualiza-
tion: E. Via Virgili, Marina Díaz-Marsá, Jose Luis Carrasco Perera, Jerey
C.L. Looi. Writing—original dra: Rosa M. Molina Ruiz. Writing—review
& editing: Rosa M. Molina Ruiz, Helena Trebbua López, E. Via Virgili, Ma-
rina Díaz-Marsá, Jose Luis Carrasco Perera, Jerey C.L. Looi.
ORCID iDs
Rosa M. Molina-Ruiz https://orcid.org/0000-0003-1551-2802
T. García-Saiz https://orcid.org/0000-0002-8321-6274
Jerey C.L. Looi https://orcid.org/0000-0003-3351-6911
E. Via Virgili https://orcid.org/0000-0002-2331-3232
M. Rincón Zamorano https://orcid.org/0000-0002-0138-4662
Laura de Anta Tejado https://orcid.org/0000-0001-6127-2788
Helena Trebbau López https://orcid.org/0000-0001-8249-8954
Jose Luis Carrasco Perera https://orcid.org/0000-0003-1481-3574
Marina Díaz-Marsá https://orcid.org/0000-0003-1364-3163
REFERENCES
1. Brewer R, Cook R, Cardi V, Treasure J, Bird G. Emotion recognition
decits in eating disorders are explained by co-occurring alexithymia.
R Soc open Sci 2015;2:140382.
2. Oldershaw A, Hambrook D, Stahl D, Tchanturia K, Treasure J, Schmidt U.
e socio-emotional processing stream in Anorexia Nervosa. Neurosci
Biobehav Rev 2011;35:970-988.
3. Harrison A, Sullivan S, Tchanturia K, Treasure J. Emotional function-
ing in eating disorders: attentional bias, emotion recognition and emo-
tion regulation. Psychol Med 2010;40:1887-1897.
4. Espina Eizaguirre A, Ortego Saenz de Cabezón A, Ochoa de Alda I, Joar-

RM Molina-Ruiz et al.
www.psychiatryinvestigation.org 11
isti Olariaga L, Juaniz M. Alexithymia and its relationships with anxiety
and depression in eating disorders. Pers Individ Dif 2004;36:321-331.
5. Gilboa-schechtman E, Avnon ÃL, Zubery E, Jeczmien P. Emotional
processing in eating disorders: specic impairment or general distress
related deciency? Depress Anxiety 2006;23:331-339.
6. Marsh R, Steinglass JE, Gerber AJ, Graziano O’Le ar y K, Wang Z, Murphy
D, et al. Decient activity in the neural systems that mediate self-regula-
tory control in bulimia nervosa. Arch Gen Psychiatry 2009;66:51-63.
7. Kelley AE. Ventral striatal control of appetitive motivation: role in in-
gestive behavior and reward-related learning. Neurosci Biobehav Rev
2004;27:765-776.
8. Kaye WH, Wierenga CE, Bailer UF, Simmons AN, Bischo-Grethe A.
Nothing tastes as good as skinny feels: the neurobiology of anorexia
nervosa. Trends Neurosci 2013;36:110-120.
9. Frank GK, Shott ME, Hagman JO, Mittal VA. Alterations in brain
structures related to taste reward circuitry in ill and recovered anorexia
nervosa and in bulimia nervosa. Am J Psychiatry 2013;170:1152-1160.
10. Wierenga CE, Ely A, Bischoff-Grethe A, Bailer UF, Simmons AN,
Kaye WH. Are extremes of consumption in eating disorders related to
an altered balance between reward and inhibition? Front Behav Neu-
rosci 2014;8:410.
11. Meyer C, Waller G, Waters A. Emotional States and Bulimic Psychopa-
thology. In: Hoek H, Treasure J, Katzman M, Editors. Neurobiology in
the Treatment of Eating Disorders. Chichester: Wiley, 1998, p.271-289.
12. Kaye WH, Fudge JL, Paulus M. New insights into symptoms and neuro-
circuit function of anorexia nervosa. Nat Rev Neurosci 2009;10:573-584.
13. Waters A, Hill A, Waller G. Bulimics’ responses to food cravings: is
binge-eating a product of hunger or emotional state? Behav Res er
2001;39:877-886.
14. Selby EA, Doyle P, Crosby RD, Wonderlich SA, Engel SG, Mitchell JD,
et al. Momentary emotion surrounding bulimic behaviors in women
with bulimia nervosa and borderline personality disorder. J Psychiatr
Res 2012;46:1492-1500.
15. Lacey JH, Evans CD. e Impulsivist: a multi-impulsive personality
disorder. Addiction 1986;81:641-649.
16. Herzog DB, Keller MB, Lavori PW, Kenny GM, Sacks NR. e preva-
lence of personality disorders in 210 women with eating disorders. J
Clin Psychiatry 1992;53:147-152.
17. Skodol AE, Oldham JM, Hyler SE, Kellman HD, Doidge N, Davies M.
Comorbidity of DSM-III-R eating disorders and personality disorders.
Int J Eat Disord 1993;14:403-416.
18. Koepp W, Schildbach S, Schmager C, Rohner R. Borderline diagnosis
and substance abuse in female patients with eating disorders. Int J Eat
Disord 1993;14:107-110.
19. Van Velzen LS, Vriend C, de Wit SJ, van den Heuvel OA. Response in-
hibition and interference control in obsessive-compulsive spectrum
disorders. Front Hum Neurosci 2014;8:419.
20. Hollander E, Evers M. Review of obsessive-compulsive spectrum dis-
orders: what do we know? where are we going? Clin Neuropsychiatry J
Treat Eval 2004;1:32-51.
21. Skodol AE, Oldham JM. Phenomenology, Differential Diagnosis and
Comorbidity of the Impulsive-Compulsive Spectrum Disorders. In:
Oldham JM, Hollander E, Editors. Impulsivity and Compulsivity. Wash-
ington DC, London: American Psychiatric Press, Inc, 1996, p.1-26.
22. Fineberg NA, Potenza MN, Chamberlain SR, Berlin HA, Menzies L,
Bechara A, et al. Probing compulsive and impulsive behaviors, from
animal models to endophenotypes: a narrative review. Neuropsycho-
pharmacology 2010;35:591-604.
23. Chamberlain SR, Blackwell AD, Fineberg NA, Robbins TW, Sahakian
BJ. e neuropsychology of obsessive compulsive disorder: the impor-
tance of failures in cognitive and behavioural inhibition as candidate
endophenotypic markers. Neurosci Biobehav Rev 2005;29:399-419.
24. Stein DJ, Lochner C. Obsessive-compulsive spectrum disorders: a mul-
tidimensional approach. Psychiatr Clin North Am 2006;29:343-351.
25. Whalen PJ, Rauch SL, Etco NL, McInerney SC, Lee MB, Jenike MA.
Masked presentations of emotional facial expressions modulate amyg-
dala activity without explicit knowledge. J Neurosci 1998;18:411-418.
26. Baxter LR. Neuroimaging studies of obsessive compulsive disorder.
Psychiatr Clin North Am 1992;15:871-884.
27. Baxter L, Saxena S, Brody A, Ackermann R, Colgan M, Schwartz J, et
al. Brain mediation of obsessive-compulsive disorder symptoms: evi-
dence from functional brain imaging studies in the human and non-
human primate. Semin Clin Neuropsychiatry 1996;1:32-47.
28. Frank GK, Bailer UF, Henry S, Wagner A, Kaye WH. Neuroimaging
studies in eating disorders. CNS Spectr 2004;9:539-548.
29. Jáuregui-Lobera I. Neuroimaging in eating disorders. Neuropsychiatr
Dis Treat 2011;7:577-584.
30. Ellison ZR, Foong J. Neuroimaging in eating disorders. In: Hoek HW,
Treasure J, Melanie A, Editors. Neurobiology in the Treatment of Eat-
ing Disorders. West Sussex; John Wiley & Sons Ltd, 1998, p.255.
31. Wagner A, Matthias R, Dieter B, Schmidt M. Neuronal activity changes
and body image distortion in anorexia nervosa. Neuroreport 2003;14:
2193-2197.
32. Uher R, Murphy T, Friederich HC, Dalgleish T, Brammer MJ, Giampi-
etro V, et al. Functional neuroanatomy of body shape perception in
healthy and eating-disordered women. Biol Psychiatry 2005;58:990-997.
33. Fladung AK, Grön G, Grammer K, Herrnberger B, Schilly E, Grasteit
S, et al. A neural signature of anorexia nervosa in the ventral striatal
reward system. Am J Psychiatry 2010;167:206-212.
34. Miyake Y, Okamoto Y, Onoda K, Shirao N, Okamoto Y, Otagaki Y, et al.
Neural processing of negative word stimuli concerning body image in
patients with eating disorders: an fMRI study. Neuroimage 2010;50:
1333-1339.
35. Vocks S, Busch M, Grönemeyer D, Schulte D, Herpertz S, Suchan B.
Neural correlates of viewing photographs of one’s own body and an-
other woman’s body in anorexia and bulimia nervosa: an fMRI study. J
Psychiatry Neurosci 2010;35:163-176.
36. Seeger G, Braus DF, Ruf M, Goldberger U, Schmidt MH. Body image
distortion reveals amygdala activation in patients with anorexia nervo-
sa -a functional magnetic resonance imaging study. Neurosci Lett
2002;326:25-28.
37. Sachdev P, Mondraty N, Wen W, Gulliford K. Brains of anorexia ner-
vosa patients process self-images dierently from non-self-images: an
fMRI study. Neuropsychologia 2008;46:2161-2168.
38. Gizewski E, Rosenberger C, de Grei A, Moll A, Senf W, Wanke I, et
al. Inuence of satiety and subjective valence rating on cerebral activa-
tion patterns in response to visual stimulation with high-calorie stim-
uli among restrictive anorectic and control women. Neuropsychobiol-
ogy 2010;62:182-192.
39. Esposito R, Cieri F, di Giannantonio M, Tartaro A. e role of body
image and self-perception in anorexia nervosa: the neuroimaging per-
spective. J Neuropsychol 2018;12:41-52.
40. Spangler DL, Allen MD. An fMRI investigation of emotional process-
ing of body shape in bulimia nervosa. Int J Eat Disord 2012;45:17-25.
41. Lang PJ, Bradley MM, Cuthbert BN. International Aective Pictures
System (IAPS): Technical Manual and Aective Ratings. Gainesville,
FL: NIMH Cent Study Emot Attention, University of Florida; 2001.
42. Tapajóz P, de Sampaio F, Soneira S, Aulicino A, Harris P, Allegri R.
Emotional reactivity to social stimuli in patients with eating disorders.
Psychiatry Res 2015;229:887-894.
43. Northo G, Richter A, Gessner M, Schlagenhauf F, Fell J, Baumgart F,
et al. Functional dissociation between medial and lateral prefrontal
cortical spatiotemporal activation in negative and positive emotions: a
combined fMRI/MEG study. Cereb Cortex 2000;10:93-107.
44. Takahashi H, Koeda M, Oda K, Matsuda T, Matsushima E, Matsuura
M, et al. An fMRI study of dierential neural response to aective pic-
tures in schizophrenia. Neuroimage 2004;22:1247-1254.
45. Britton JC, Phan KL, Taylor SF, Welsh RC, Berridge KC, Liberzon I.
Neural correlates of social and nonsocial emotions: An fMRI study.
Neuroimage 2006;31:397-409.

12 Psychiatry Investig
Emotional Processing in Eating Disorders
46. Grimm S, Schmidt CF, Bermpohl F, Heinzel A, Dahlem Y, Wyss M, et
al. Segregated neural representation of distinct emotion dimensions in
the prefrontal cortex-an fMRI study. Neuroimage 2006;30:325-340.
47. Berlin HA, Rolls ET, Iversen SD. Borderline personality disorder, impul-
sivity, and the orbitofrontal cortex. Am J Psychiatry 2005;162:2360-2373.
48. American Psychiatric Association. Diagnostic and Statistical Manual
of Mental Disorders (DSM-IV). 4th Ed. Washington, DC.: American
Psychiatry Press; 2000.
49. Spitzer RL, Williams JB, Gibbon M, First MB. e Structured Clinical
Interview for DSM-III-R (SCID). I: History, rationale, and description.
Arch Gen Psychiatry 1992;49:624-629.
50. Patton JH, Stanford MS, Barratt ES. Factor structure of the Barratt im-
pulsiveness scale. J Clin Psychol 1995;51:768-774.
51. Orozco-Cabal L, RodrÍguez M, Herin DV, Gempeler J, Uribe M. Va-
lidity and Reliability of the Abbreviated Barratt Impulsiveness Scale in
Spanish (BIS-15S). Rev Colomb Psiquiatr 2010;39:93-109.
52. Henderson M, Freeman CP. A self-rating scale for bulimia: e “BITE.”
Br J Psychiatry 1987;150:18-24.
53. Rivas T, Bersabé R, Jiménez M. Reliability and validity of Bulimic In-
vestigatory Test, Edinburgh (BITE)-Behavioral Psychology / PsicologÍa
Conductual. Behav Psychol 2004;12:447-461.
54. Jayaro C, de la Vega I, DÍaz-Marsá M, Montes A, Carrasco JL. e use of
the International Aective Picture System for the study of aective dys-
regulation in mental disorders. Actas españolas Psiquiatr 2008;36:177-
182.
55. Desikan RS, Ségonne F, Fischl B, Quinn BT, Dickerson BC, Blacker D,
et al. An automated labeling system for subdividing the human cere-
bral cortex on MRI scans into gyral based regions of interest. Neuro-
image 2006;31:968-980.
56. Joos AA, Saum B, van Elst LT, Perlov E, Glauche V, Hartmann A, et al.
Amygdala hyperreactivity in restrictive anorexia nervosa. Psychiatry
Res 2011;191:189-195.
57. Adolphs R. Neural systems for recognizing emotion. Curr Opin Neu-
robiol 2002;12:169-177.
58. Cancelliere AE, Kertesz A. Lesion localization in acquired decits of
emotional expression and comprehension. Brain Cogn 1990;13:133-
147.
59. Davidson R, Irwin W. e functional neuroanatomy of emotion and
aective style. Trends Cogn Sci 1999;3:11-21.
60. Ochsner KN, Gross JJ. e cognitive control of emotion. Trends Cogn
Sci 2005;9:242-249.
61. Vuilleumier P. How brains beware: neural mechanisms of emotional
attention. Trends Cogn Sci 2005;9:585-594.
62. Banks SJ, Eddy KT, Angstadt M, Nathan PJ, Phan KL. Amygdala-fron-
tal connectivity during emotion regulation. Soc Cogn Aect Neurosci
2007;2:303-312.
63. Hariri AR, Bookheimer SY, Mazziotta JC. Modulating emotional re-
sponses: eects of a neocortical network on the limbic system. Neuro-
report 2000;11:43-48.
64. Lieberman MD, Eisenberger NI, Crockett MJ, Tom SM, Pfeifer JH,
Way BM. Putting feelings into words: aect labeling disrupts amygdala
activity in response to aective stimuli. Psychol Sci 2007;18:421-428.
65. New AS, Hazlett EA, Buchsbaum MS, Goodman M, Mitelman SA,
Newmark R, et al. Amygdala-prefrontal disconnection in borderline
personality disorder. Neuropsychopharmacology 2007;32:1629-1640.
66. Val-Laillet D, Aarts E, Weber B, Ferrari M, Quaresima V, Stoeckel LE,
et al. Neuroimaging and neuromodulation approaches to study eating
behavior and prevent and treat eating disorders and obesity. NeuroIm-
age Clin 2015;8:1-31.
67. Geller J, Cockell SJ, Hewitt PL, Goldner EM, Flett GL. Inhibited ex-
pression of negative emotions and interpersonal orientation in an-
orexia nervosa. Int J Eat Disord 2000;28:8-19.
68. Schlösser RGM, Wagner G, Schachtzabel C, Peikert G, Koch K,
Reichenbach JR, et al. Fronto-cingulate eective connectivity in obses-
sive compulsive disorder: a study with fMRI and dynamic causal mod-
eling. Hum Brain Mapp 2010;31:1834-1850.
69. Van Kuyck K, Gérard N, Van Laere K, Casteels C, Pieters G, Gabriëls L,
et al. Towards a neurocircuitry in anorexia nervosa: evidence from
functional neuroimaging studies. J Psychiatr Res 2009;43:1133-1145.
70. Zastrow A, Kaiser S, Stippich C, Walther S, Herzog W, Tchanturia K, et
al. Neural correlates of impaired cognitive-behavioral exibility in an-
orexia nervosa. Am J Psychiatry 2009;166:608-616.
71. Adan W, Kaye WH. Behavioral Neurobiology of Eating Disorders.
Berlin: Springer; 2011.
72. Klump KL, Strober M, Bulik CM, ornton L, Johnson C, Devlin B, et
al. Personality characteristics of women before and aer recovery from
an eating disorder. Psychol Med 2004;34:1407-1418.
73. Uher R, Murphy T, Brammer MJ, Dalgleish T, Phillips ML, Ng VW, et
al. Medial prefrontal cortex activity associated with symptom provoca-
tion in eating disorders. Am J Psychiatry 2004;161:1238-1246.
74. Guido KWF, Bailer UF, Meltzer CC, Price JC, Mathis CA, Wagner A,
et al. Regional cerebral blood ow aer recovery from anorexia or bu-
limia nervosa. Int J Eat Disord 2007;40:488-492.
75. Koenigsberg HW, Siever LJ, Lee H, Pizzarello S, New AS, Goodman M,
et al. Neural correlates of emotion processing in borderline personality
disorder. Psychiatry Res 2009;172:192-199.
76. Calder AJ, Keane J, Manes F, Antoun N, Young AW. Impaired recogni-
tion and experience of disgust following brain injury. Nat Neurosci
2000;3:1077-1078.
77. Canli T, Zhao Z, Desmond JE, Kang E, Gross J. An fMRI study of per-
sonality. Behav Neurosci 2001;115:33-42.
78. Pell MD, Leonard CL. Processing emotional tone from speech in Par-
kinson’s disease: a role for the basal ganglia. Cogn Aect Behav Neuro-
sci 2003;3:275-288.
79. Grillner S, Hellgren J, Ménard A, Saitoh K, Wikström MA. Mecha-
nisms for selection of basic motor programs--roles for the striatum
and pallidum. Trends Neurosci 2005;28:364-370.
80. Bohon C, Stice E. Reward abnormalities among women with full and
subthreshold bulimia nervosa: a functional magnetic resonance imag-
ing study. Int J Eat Disord 2011;44:585-595.
81. Wagner A, Aizenstein H, Venkatraman VK, Bischo-Grethe A, Fudge
J, May JC, et al. Altered striatal response to reward in bulimia nervosa
aer recovery. Int J Eat Disord 2010;43:289-294.
82. Uher R, Brammer MJ, Murphy T, Campbell IC, Ng VW, Williams
SCR, et al. Recovery and chronicity in anorexia nervosa: brain activity
associated with differential outcomes. Biol Psychiatry 2003;54:934-
942.
83. Allen A, King A, Hollander E. Obsessive-compulsive spectrum disor-
ders. Dialogues Clin Neurosci 2003;5:259-271.