articles nature publishing group

Behavior and Psychology

Disinhibited Eating in Obese Adolescents

Is Associated With Orbitofrontal Volume
Reductions and Executive Dysfunction
Lawrence Maayan1,2, Claire Hoogendoorn3, Victoria Sweat3 and Antonio Convit2–4

In adults, obesity has been associated with disinhibited eating, decreased cortical gray matter (GM) volume, and
lower performance on cognitive assessments. Much less is known about these relationships in adolescence and
there are no studies assessing behavioral, cognitive, and neurostructural measures in the same group of study
participants. This study examined the relationship between obesity, executive function, disinhibition, and brain
volumes in relatively healthy youth. Participants included 54 obese and 37 lean adolescents. Participants received a
cognitive battery, questionnaires of eating behaviors, and magnetic resonance imaging (MRI). Neuropsychological
assessments included tasks targeting frontal lobe function. Eating behaviors were determined using the Three Factor
Eating Questionnaire (TFEQ), and structural MRIs were performed on a 1.5 T Siemens Avanto MRI System (Siemens,
Erlangen, Germany) to determine brain GM volumes. Lean and obese adolescents were matched on age, years of
education, gender, and socioeconomic status. Relative to lean adolescents, obese participants had significantly
higher ratings of disinhibition on the TFEQ, lower performance on the cognitive tests, and lower orbitofrontal cortex
(OFC) volume. Disinhibition significantly correlated with BMI, Stroop color-word score, and OFC volume. This is the
first report of these associations in adolescents and point to the importance of better understanding the associations
between neurostructural deficits and obesity.

Obesity (2011) 19, 1382–1387. doi:10.1038/oby.2011.15

Introduction key area in inhibition of behavior stretches back to the case of

The prevalence of child and adolescent obesity in the United Phineas Gage, the unfortunate 19th century rail worker who
States has more than tripled since 1970. Although recent evi- survived an accident likely damaging his OFC, which resulted
dence suggests that childhood obesity may have leveled off, the in personality changes and increased impulsivity (7).
present high rates predict an impending public health problem Neurostructural findings have also been correlated with BMI.
involving cardiovascular and endocrine illness (1). In a small study of women 55 years of age and older, which
Disinhibition in eating behavior, which is characterized in employed voxel-based morphometry, BMI was negatively cor-
part as the propensity to eat opportunistically in response to related with gray matter (GM) volumes in several frontal areas
environmental cues, has long been associated with obesity both including the left orbitofrontal, right inferior frontal, and right
in youth and adults (2). The related control failure in caloric precentral gyri in addition to other regions including the right
intake that leads to eventual obesity may occur at several lev- cerebellum as well as a large right posterior region encompass-
els in the brain including the hypothalamus (3) and, according ing the parahippocampal, fusiform, and lingual gyri (8). A
to more recent work, in cerebral cortex (4). A series of func- larger study of 1,428 adults found a negative correlation among
tional neuroimaging studies of lean and obese individuals in males between BMI and overall GM as well as specific brain
both hungry and fed states have shown several cortical regions regions such as bilateral medial temporal lobes, occipital lobes,
including the anterior cingulate, medial prefrontal (5), insula, frontal lobes, precuneus, midbrain and anterior lobe of the cer-
posterior cingulate, temporal, and orbitofrontal cortices (6) to ebellum (9). Another voxel-based morphometry study showed
be differentially activated depending on the level of satiety and that obese adults have lower GM density in areas such as fron-
BMI, suggesting their involvement in the regulation of caloric tal operculum, middle frontal gyrus, postcentral gyrus, as well
intake. The understanding of orbitofrontal cortex (OFC) as a as putamen (10). Our group has described neurostructural
The first two authors contributed equally to the work.
1
Department of Child Psychiatry, New York University School of Medicine, New York, New York, USA; 2Nathan Kline Institute for Psychiatric Research, Orangeburg,
New York, USA; 3Department of Psychiatry, New York University School of Medicine, New York, New York, USA; 4Department of Medicine, New York University School
of Medicine, New York, New York, USA. Correspondence: Antonio Convit (antonio.convit@med.nyu.edu)
Received 17 August 2010; accepted 8 January 2011; published online 24 February 2011. doi:10.1038/oby.2011.15

1382 VOLUME 19 NUMBER 7 | july 2011 | www.obesityjournal.org


abnormalities among obese adolescents with type 2 diabetes
mellitus (T2DM) (11), but to our knowledge no such deficits
have been described among obese youth without T2DM.
In addition to structural findings, cognitive assessments have
demonstrated that executive functioning and response inhibi-
tion may be compromised in both adult and adolescent obese
individuals. One study employing positron emission tomogra-
phy and cognitive tests found obese adults to have decreased
baseline prefrontal glucose metabolism as well as diminished
performance on the Stroop task, a test of selective attention
and executive function (12). Other studies of executive func-
tion and response inhibition in adults have shown a negative
association of those variables with BMI (13–15). Furthermore,
extremely obese adolescents show decreased functioning on
executive tasks compared to normative data (16).
We hypothesized that consistent with previous findings
using the Three Factor Eating Questionnaire (TFEQ), obese
adolescents would have higher ratings of self-reported dis-
inhibition in eating behaviors. We further hypothesized
that obese adolescents would have lower scores on assess-
ments of executive function and reduced integrity in neu-
rostructural measures of frontal lobe (magnetic resonance
imaging (MRI)-based GM volumes as well as regional brain
volumes). In addition, we posited that disinhibition on the
TFEQ will be negatively associated with cognitive scores on
relevant domains as well as with MRI-based measurements
of brain areas involved in response inhibition and executive
control.
Methods and Procedures
Participants and procedures
Ninety-one youth (14–21 years old), thirty-seven lean (BMI <25 kg/m2
or waist to height ratio <0.5), and fifty-four obese (BMI ≥30 kg/m2 or
>95 percentile for BMI for age and gender) participated in the study.
Eighty-one of these (36 lean, 45 obese) received an MRI. Ten adoles-
cents did not receive an MRI for the following reasons: two did not
keep their appointments, one was pregnant and we chose to err on the
side of safety, one could not tolerate the MRI (claustrophobia), and six
had a BMI >50 kg/m2 and exceeded the body size that could be accom-
modated by the scanner.
Lean participants had a mean age of 17.3 ± 1.6 years and obese
17.5 ± 1.6 years. The two groups were also matched on years of educa-
tion, gender, and socioeconomic status and were all in the cognitively
normal range. Evidence of neurological, medical (other than dyslipi-
demia, insulin resistance short of T2DM, polycystic ovary disease, or
hypertension), or psychiatric (including depression and alcohol or
other substance abuse) illness excluded individuals from participa-
tion in the study. T2DM also excluded individuals from participation.
Participants and their parents gave written informed consent and were
compensated for their time and inconvenience. The study protocol was
approved by the New York University School of Medicine institutional
review board.
All study participants had a blood sample taken after a 10-h over-
night fast for the assessment of glucose, insulin, lipid, and inflammatory
marker (high-sensitivity C-reactive protein (CRP)) levels. Glucose was
measured using a glucose oxidase method (VITROS 950 AT; Ortho
Clinical Diagnostics, Amersham, England), insulin by chemilumines-
cence (Advia Centaur; Siemens), and CRP was measured in plasma
using an enzymatic immunoassay (Vitros CRP slide; Ortho Clinical
Diagnostics). Insulin sensitivity was estimated using the homeostasis
model assessment of insulin resistance.
obesity | VOLUME 19 NUMBER 7 | july 2011
articles
Behavior and Psychology
Assessments
Neuropsychological assessment. We conducted a broad evaluation
of neurocognitive functions, including intellectual achievement, recent
memory, working memory, attention, and executive function. We
hypothesized that there would be differences in frontal lobe functions
between lean and obese adolescents and therefore restricted our analy-
ses to neurocognitive tests that reflect frontal lobe integrity and intact
executive functions, namely the Controlled Oral Word Association
Test (COWAT), Trail Making Test parts A&B, Stroop Task, Attention/
Concentration Index of the Wide Range Assessment of Learning and
Memory (WRAML) and Working Memory Index of the WRAML.
With the exception of the WRAML and the Stroop, which provide age-
corrected standard scores, raw scores are reported. All tests adminis-
tered are standard neuropsychological instruments described in detail
elsewhere (17).
TFEQ. Characteristics of eating behavior were assessed by using the
TFEQ. The TFEQ is a 51-item instrument, composed of three subscales
measuring restraint (i.e., cognitive control of eating behavior; 21 items),
disinhibition (i.e., the susceptibility of eating in response to emotional
factors and sensory cues; 16 items), and hunger (i.e., the susceptibility
of eating in response to feelings of hunger; 14 items). The TFEQ was
administered ~1 h after subjects had lunch.
MRI acquisition and image analyses. All subjects were studied
on the same 1.5 T Siemens Avanto MRI System, which has a 65-inch
diameter bore and a table suitable for up to a 400 pound individual. We
acquired T1-weighted magnetization-prepared rapid acquisition gradi-
ent echo images (MPRAGE; repetition time 1300 ms; echo time 4.38 ms;
inversion time 800 ms; field of view 250 × 250; slice thickness 1.2 mm;
NEX 1; flip angle 15°; matrix size 256 × 256; 192 coronal slices).
WM/GM volumetric analysis. Spatial normalization and segmenta-
tion of MPRAGE images utilized automated procedures as described in
ref. (18) the statistical parametric mapping software (SPM5). MPRAGE
images were first corrected for signal non-uniformities and spatially
normalized to the standard T1 Montreal Neurological Institute tem-
plate. Using the tissue classification algorithm in SPM5, we segmented
the normalized MPRAGE images into their GM, white matter (WM),
and cerebrospinal fluid partitions, which are maps representing the
probability for each voxel being classified as GM, WM, or cerebrospi-
nal fluid. These segmented partitions were subsequently normalized to
their respective standard templates. In addition to performing whole
brain assessment, and given that during adolescence frontal lobe myeli-
nation is still ongoing, we utilized two different templates to derive the
regions of interest in the frontal lobe. These were the SPM automatic
anatomic labeling (19) template and our published reliable frontal lobe
parcelation method (20). The automatic anatomic labeling template
was used to derive a total frontal lobe, an anterior cingulate region,
and an orbitofrontal region. Our own parcelation method was used to
derive a prefrontal region (frontal lobe minus the supplementary motor
region). We quantified the proportions of WM, GM, cerebrospinal fluid
volumes in the whole brain and frontal regions at the case level by first
mapping the regions to each segmented partition and then averaging
the values across subjects for each of the two groups.
Statistical analyses
We conducted two-tailed independent samples t-tests examining group
differences in demographics, endocrine data, cognitive data, and brain
volumes as well as Pearson correlations between the TFEQ disinhibi-
tion score and BMI, Stroop color-word score, and OFC GM volume.
Data that were further than 2 s.d. from the mean of the group for that
variable were excluded. Given that there is individual variability in
regional brain volumes related to overall head size, we measured each
individual’s intracranial vault size and utilized the intracranial vault val-
ues to adjust the regional brain volumes. Therefore, to allow compara-
bility to other studies and give the reader a sense of the size of the brain
regions studied, the table describing regional brain volumes shows the
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Behavior and Psychology

raw (nonresidualized) volumes. However, statistical comparison and
the significance and effect size for all imaging presented utilized the
volumes adjusted (residualized) brain volumes.
Results
Demographics and endocrine data
Subject groups were matched for age, gender, school grade, and
Hollingshead socioeconomic status. Obese participants were,
by definition, higher in BMI, and as expected also had higher
systolic and diastolic blood pressure, fasting insulin, and glu-
cose levels (but all in the normoglycemic range) as well as the
homeostatic model assessment of insulin resistance, triglycer-
ides, low-density lipoprotein cholesterol, and high-sensitivity
CRP. Obese subjects also had significantly lower levels of high-
density lipoprotein (see Table 1).
TFEQ
Obese adolescents scored significantly higher than lean par-
ticipants on the disinhibition factor of the TFEQ (6.85 ± 3.55
vs. 3.91 ± 1.96, P < 0.000, Cohen’s d (d) = 1.07), as well as the
hunger factor (6.60 ± 3.37 vs. 4.68 ± 2.84, P = 0.008, d = 0.81)
and the cognitive restraint factor (9.19 ± 4.30 vs. 6.78 ± 4.11,
P = 0.012, d = 0.57). Please note that we repeated these analyses
for the subset of 81 participants with an MRI and the results
were essentially unchanged (data not shown).
Cognitive measures
Relative to lean adolescents, obese adolescents had worse cog-
nitive performance in every frontal lobe task, most pronounced
for the Stroop (a measure of inhibition), and the working
memory index of the WRAML, even when we controlled for
estimated IQ (Table 2).
Because 10 subjects did not receive an MRI evaluation (for
details please refer to the participants and procedures section
above), we repeated our analyses for the subgroup of 81 ado-
lescents who had an MRI and the direction and significance of
the cognitive results remained unchanged (data not shown).

Table 1 Demographics and endocrine characteristics of lean and obese adolescent groups
Lean Obese
n = 37 n = 54
Mean ± s.d. t P d
Age (years) 17.32 ± 1.59 17.50 ± 1.59 0.538 0.592 0.08
Education (years) 11.77 ± 1.99 11.63 ± 1.71 0.322 0.748 0.10
Gender (% F) 56.8% 63.6%
Hollingshead SES 2.5 ± 1.59 2.1 ± 1.17 1.62 0.109 0.37
BMI (kg/m2) 21.67 ± 2.49 39.86 ± 9.46 −11.41 <0.01 2.45
Systolic BP (mm Hg) 101.0 ± 8.68 114.4 ± 12.46 −6.00 <0.01 1.29
Diastolic BP (mm Hg) 62.97 ± 7.72 69.51 ± 9.33 −3.73 <0.01 0.80
HOMAIR 1.03 ± 1.80 3.06 ± 3.70 −3.50 <0.01 0.73
Fasting insulin (U/ml) 6.95 ± 2.99 19.43 ± 11.82 −6.02 <0.01 1.59
Fasting glucose (mg/dl) 74.44 ± 7.02 77.90 ± 8.00 −2.11 0.038 0.48
Triglycerides (mg/dl) 66.20 ± 24.08 85.29 ± 35.58 −2.77 <0.01 0.61
HDL (mg/dl) 52.56 ± 9.55 43.50 ± 7.44 4.88 <0.01 1.09
LDL (mg/dl) 85.24 ± 22.17 98.29 ± 21.26 −2.73 <0.01 0.60
C-reactive protein (mg/dl) 0.53 ± 0.56 3.41 ± 2.19 −7.53 <0.01 1.73
BP, blood pressure; HDL, high-density lipoprotein; HOMAIR, homeostasis model assessment of insulin resistance; LDL, low-density lipoprotein.

Table 2 Cognitive differences between lean and obese adolescent groups

Lean Obese
Frontal lobe tasks Mean ± s.d. t P d
Stoop color-word score (no. correct/min.) (response inhibition) 46.3 ± 8.3 38.9 ± 7.6 4.30 <0.001 0.94
Trail making test part A (secs.) (attention) 22.6 ± 5.2 28.2 ± 8.1 −3.90 <0.001 0.88
Trail making test part B (secs.) (cognitive flexibility) 51.3 ± 16.3 68.1 ± 32.0 −2.71 0.008 0.62
COWAT—sum of F, A, S (verbal fluency) 39.3 ± 13.1 33.8 ± 7.9 2.21 0.032 0.50
WRAML working memory index 110.7 ± 13.3 99.4 ± 13.8 3.79 <0.001 0.83
WRAML attn./concent. index 108.6 ± 15.6 100.8 ± 12.4 2.58 0.012 0.56
Estimated full-scale IQ 108.6 ± 12.5 102.6 ± 10.9 2.37 0.020 0.51
COWAT, Controlled Oral Word Association Test; WRAML, Wide Range Assessment of Learning and Memory.

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60 for obese youth in OFC (32.3 ± 3.68 vs. 33.3 ± 3.99; residual-
ized 0.00781 ± 0.024944 vs. −0.01227 ± 0.018947, P = 0.005,
50 d = 0.66). The OFC volume group differences were unchanged
after controlling for systolic blood pressure or homeostasis
40
model assessment of insulin resistance. Other brain regions
assessed, including prefrontal cortex and anterior cingulate
BMI

30
cortex were not significantly different between obese and lean
participants. Covarying for age did not change any of these
20 Lean
relationships.
Obese
10 R 2 = 0.165
Associations
We found significant associations between the TFEQ and
0
−1 1 3 5 7 9 11 13 15 cognitive, BMI, and MRI volume measures. Specifically, the
Three factor eating questionnaire—disinhibition disinhibition factor score on the TFEQ showed a significant
correlation with BMI (r(81) = 0.406, P < 0.001), Stroop color-
Figure 1 Association between BMI and Three Factor Eating word score (r(77) = −0.272, P = 0.017; Figure 1), and OFC
Questionnaire (TFEQ) disinhibition score. The association between BMI
GM volume (r(71) = −0.273, P = 0.021). In order to further
(in kg/m2) and TFEQ disinhibition factor score have been shown. Obese
individuals are noted by filled pyramids and lean individuals by filled understand the relationship between OFC volume and dis-
circles. inhibition we explored the association separately for the two
groups (Figure 2). We found that there was no association
a 0.08
Lean and obese
between disinhibition and OFC volume for obese individuals
0.06
R 2 = 0.075
(r(40) = −0.028, P = 0.864), whereas there was a strong associa-
Residualized gray matter

0.04 tion for the lean group (r(31) = −0.460, P = 0.009). The associa-
volume—OFC

0.02
tions between the disinhibition factor score and the BMI and
0
−0.02
stroop remained significant for the subset of individuals with
−0.04
MRI (data not shown).
−0.06
−1 3 7 11 15
Three factor eating
Discussion
questionnaire—disinhibition
Obese adolescents had significantly higher ratings of disinhibi-
b 0.08 Lean
c 0.08
Obese tion, hunger, and cognitive restraint on the TFEQ. Although
0.06 R 2 = 0.213 R 2 = 0.001
higher levels of cognitive restraint among obese adolescents
Residualized gray matter

0.06
Residualized gray matter

0.04 0.04 would on first inspection appear counterintuitive, it conforms

volume—OFC

volume—OFC

0.02 0.02 to the described model of “rigid restraint” in which an indi-

0 0
vidual with disinhibited eating and cognitive restraint may
−0.02 −0.02

−0.04
−0.06
−1 3 7
Three factor eating
questionnaire—disinhibition
Figure 2 Association between BMI and orbitofrontal cortex (OFC)
volume. The association between BMI and intracranial vault (ICV)-
residualized orbitofrontal cortex volume have been shown. (a) All study
participants, (b) the significant association for lean youth, and (c) the
lack of association for obese adolescents.
Brain imaging
Frontal lobe grey matter volume (in cm3) trended smaller,
although not at a level of statistical significance, among
obese adolescents (265.3 ± 29.5 vs. 269.6 ± 26.7; residual-
ized 0.00369 ± 0.018312 vs. −0.00609 ± 0.014076, P = 0.139,
d = 0.35). Please note that although the absolute differences
between these volumes was small, the analyses were conducted
after residualizing to the intracranial vault and significance
values and effect sizes reflect these analyses. Furthermore in
order to control for the possible developmental effects of age
on frontal and cerebral volumes we re-ran our analyses covary-
ing for age. We found significantly lower grey matter volumes
−0.04
tend to restrict food in some situations but grossly overeat in
−0.06
others (21).
11 15 −1 3 7 11 15 Our novel neurostructural results among obese adolescents
Three factor eating
questionnaire—disinhibition are consistent with findings in the adult literature (8,9) dem-
onstrating GM volume reductions. In our adolescent sample
these decreases were most marked for the OFC, a brain region
important in impulse control, but also showed a weak trend
for whole frontal lobe. We speculate that the more subtle vol-
ume reductions that exist in other brain regions among obese
adolescents may actually reach statistical significance in an
expanded sample.
Importantly for this report, we found the group with excess
weight to not only have higher disinhibition scores on the
TFEQ, but lower performance on cognitive tests reflecting
brain functions thought to be central to behavioral inhibition,
even when controlling for IQ. Out of the frontal lobe regions
and functions we measured, we were particularly interested in
ascertaining the relationship between the disinhibition factor
of the TFEQ and the OFC, a brain region that is very impor-
tant for behavioral inhibition (impulse control). We selected
the Stroop because it is the only one of our frontal lobe tasks
(including those that tap executive functions) that specifically

obesity | VOLUME 19 NUMBER 7 | july 2011 1385

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Behavior and Psychology
tests the ability to inhibit automated responses. This is the
direct cognitive parallel of the behavioral (disinhibition factor
of the TFEQ) and brain region (OFC) also involved in inhibi-
tion of automatic responses. Our interest was to ascertain the
functional (Stroop vs. other frontal tasks that do not measure
response inhibition) and anatomic (OFC) specificity of our
findings and their association to the disinhibition factor of the
TFEQ.
We also found significant associations between disinhibi-
tion factor scores and both BMI and OFC volume. When
the relationship between disinhibition and OFC volume was
examined separately in lean and obese participants, we found
a strong negative association only for the lean group. It is pos-
sible that obese individuals have already experienced a critical
level of disinhibition (which as we demonstrated is associated
with BMI), whereby additional disinhibition is not as clearly
reflected in further changes in OFC, but perhaps in different
brain regions or networks not assessed as part of this study.
Another possibility for these different findings for each of the
two weight groups is that given that the obese groups has higher
degree of item endorsement, they may be more susceptible to
issues of social desirability and therefore they may be less likely
to fully report the extent of their behavioral disinhibition in
eating, dampening the association in this group. Lastly, it is
also possible that range restriction, namely the phenomena
of correlations decreasing when the variance is decreased as
occurs when we divide our sample in two could be affecting
our results.
Although our study finds that disinhibition in feeding behav-
ior is associated with reductions in executive functioning and
frontal GM volumes, the cross-sectional nature of our design
does not allow us to address the issue of directionality or cau-
sation. With that being said, there are several plausible theories
regarding the direction of these associations.
One possibility is that primary structural or functional brain
deficits lead to disinhibited eating and reductions in neurocog-
nitive function. This line of reasoning is partially supported
by work showing disinhibtion in eating behavior to presage
increased caloric intake (22) and obesity (23). It is also con-
sistent with functional imaging work demonstrating that indi-
viduals, who in response to visualized intake of palatable foods
show weaker activation of brain reward circuits, are at elevated
risk for future weight gain (24); perhaps they need a larger
stimulus (more food) to derive the same reward response.
Another possible explanation is that brain structural deficits
like those demonstrated in this study result from obesity and
its associated insulin resistance. This possibility is supported
by a 24-year longitudinal study showing increased BMI begin-
ning in middle age correlated with decreased temporal lobe
volume in later life (25). Also supporting this effect order is
our own work in adults where we find that hippocampal vol-
umes were associated with impairments in glucose tolerance
(26) as well as that in adolescents with T2DM, where we find
cognitive impairments and reductions in frontal lobe volumes
and in WM microstructural integrity (11). We posit that the
obesity-associated insulin resistance exhibited by our group
1386
of adolescents with excess weight may contribute to decreased
executive function and structural deficits. We have described
a possible model for these effects (27) in which we hypoth-
esize that insulin resistance is associated with decreased
brain vascular reactivity related to endothelial dysfunction.
We know that during brain activation, such as occurs when
performing a cognitive task, there is an increase in synaptic
activity in the brain region involved. In the normal brain this
results in regional vasodilation and thus an increase in glucose
availability to that region to support the increased cognitive
demand (28). Therefore, vascular reactivity, which is integral
to well-regulated cerebral blood flow, is key for maintaining
an optimal neuronal environment during brain activation (29).
Research showing endothelial dysfunction in obese children,
even before the development of diabetes (30), further supports
this premise. In addition, the inflammatory marker CRP was
elevated in our obese adolescents. In studies examining large
cohorts of adults, investigators have found increased levels
of inflammatory cytokines as putative mediators of cognitive
decline among individuals with metabolic syndrome (31–34).
A possible mechanism for these cognitive effects is provided by
animal data demonstrating that excess inflammatory cytokines
can decrease long-term potentiation, a process understood as
essential in consolidation of memory in the hippocampus.
Inflammatory cytokines may also cause impairment in neuro-
genesis and neuroplasticity, processes vital to the formation of
memories and the maintenance of structural neural integrity.
A third possibility is that these effects are bidirectional
whereby behavioral disinhibition predisposes to obesity, which
may negatively impact brain areas responsible for executive
function and inhibition of caloric intake, thus causing a vicious
cycle of dysfunction. This third possibility could help explain
why it so difficult for individuals to lose weight once it has been
gained.
We are encouraged by the fact that among the few brain
regions that we evaluated, the OFC, a brain region that has
been demonstrated as important in behavioral inhibition in
both animal and human studies, had the most significant vol-
ume reduction among obese adolescents. Our findings, includ-
ing lower performance on cognitive tests thought to require
intact OFC, coupled with volume reductions in this area asso-
ciated to behavioral disinhibition point to its likely importance
in weight gain.
This study has some clear limitations. First, it is a cross-
sectional view that does not allow us to comment on clear
causality. Second, given our relatively modest sample size we
restricted our measurements to brain regions that in previous
studies had either been found to have been associated to obes-
ity or disinhibition, or those that we had good theoretical rea-
sons to believe could be involved. Therefore, it is possible that
there are other brain areas, which we did not evaluate, that may
also be involved. A third limitation of our study is that we only
have participants’ current weight and we cannot comment on
duration of obesity; the sample that we studied is likely to have
considerable variability in duration of obesity and its associ-
ated insulin resistance. Nevertheless, our study has significant
VOLUME 19 NUMBER 7 | july 2011 | www.obesityjournal.org

strengths, including the careful matching between groups, the
multidimensional evaluations conducted, and the unbiased
MRI methods utilized in the analyses of the MRI data.
To better understand the issues described here, future work
should evaluate subjects longitudinally, tracking the develop-
ment of obesity across time while concomitantly measuring cog-
nitive, behavioral, and neurostructural changes. Alternatively,
our understanding could also be improved through a study
designed to examine the consequences of a successful obesity
treatment (e.g., bariatric surgery), and thus ascertain whether
some of these deficits are reversible. Furthermore, future work
should evaluate other possible associated factors such as pro-
and anti-inflammatory cytokines as well as utilize more sensi-
tive MRI techniques such as diffusion tensor imaging.
Acknowledgments
The authors wish to acknowledge the children and families who participated
in this research as well as Po Lai Yau and Valentin Polyakov in the collection
and processing of the data and the assistance of Allison Larr in the
preparation of this manuscript. The study was supported by grants from
the National Institutes of Health R21 DK070985 and RO1 DK083537 and,
supported in part by grant 1UL1RR029893 from the National Center for
Research Resources.
Disclosure
The authors declared no conflict of interest.
© 2011 The Obesity Society
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