J Neurosurg 109:625–634,
109:000–000, 2008
Deep brain stimulation in the treatment of obesity
A review
Casey H. Halpern, M.D.,1 John A. Wolf, Ph.D., 3 Tracy L. Bale, Ph.D., 2
Albert J. Stunkard, M.D., 3,5 Shabbar F. Danish, M.D.,1 Murray Grossman, M.D., Ph.D.,4
Jurg L. Jaggi, Ph.D.,1 M. Sean Grady, M.D.,1 and Gordon H. Baltuch, M.D., Ph.D.1
Departments of 1Neurosurgery, 2Neuroscience, 3Psychiatry, and 4Neurology; and 5Center for Weight and
Eating Disorders, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
Obesity is a growing global health problem frequently intractable to current treatment options. Recent evidence
suggests that deep brain stimulation (DBS) may be effective and safe in the management of various, refractory neuropsychiatric disorders, including obesity. The authors review the literature implicating various neural regions in the
pathophysiology of obesity, as well as the evidence supporting these regions as targets for DBS, in order to explore
the therapeutic promise of DBS in obesity.
The lateral hypothalamus and ventromedial hypothalamus are the appetite and satiety centers in the brain, respectively. Substantial data support targeting these regions with DBS for the purpose of appetite suppression and weight
loss. However, reward sensation associated with highly caloric food has been implicated in overconsumption as well as
obesity, and may in part explain the failure rates of conservative management and bariatric surgery. Thus, regions of the
brain’s reward circuitry, such as the nucleus accumbens, are promising alternatives for DBS in obesity control.
The authors conclude that deep brain stimulation should be strongly considered as a promising therapeutic option for patients suffering from refractory obesity. (DOI: 10.3171/JNS/2008/109/10/0625)
Key Words • deep brain stimulation • hypothalamus • obesity • nucleus accumbens • reward
H
igh-frequency
deep brain stimulation is the treatment of choice for well-selected patients with
medically refractory PD. Deep brain stimulation
provides significant symptomatic improvement in parkinsonism in both animal and human studies,31,56 and at
high frequencies (130–160 Hz) mimics the clinical effects of tissue lesioning.6,9,11 In contrast to stereotactic
lesions, however, DBS provides the added benefit of reversibility and titratability,28 as well as a very low risk of
complications.27,118 Excessive or aberrant output from the
STN, currently the most favored target for DBS in PD, is
postulated to play a crucial role in the pathophysiology of
this disease.1 Given the remarkable improvement in parkinsonism, high-frequency STN DBS appears to induce
functional inhibition of this region.9 Indeed, some have
Abbreviations used in this paper: BMI = body mass index;
DBS = deep brain stimulation; GABA = γ-aminobutyric acid; LH =
lateral hypothalamus; MCH = melanin-concentrating hormone;
NAc = nucleus accumbens; OCD = obsessive-compulsive disorder;
PD = Parkinson disease; 6-OHDA = 6-hydroxydopamine; STN = sub­
thalamic nucleus; VMH = ventromedial hypothalamus; VP = ventral
pallidum.
J. Neurosurg. / Volume 109 / October 2008
shown that high-frequency STN DBS has an inhibitory
effect on STN single unit activity.111 There is evidence
that the primary effect of DBS is related to the frequency
of stimulation,58 but the precise mechanism of action remains unclear, whether it be excitatory59 or inhibitory in
nature.60,73,111
The success of DBS in relieving parkinsonism has
led to its application in multiple neurological diseases and
more recently to treatment-resistant psychiatric conditions.39 The purpose of this paper is to motivate the neurosurgical community to consider DBS for obesity control.
Obesity is a chronic disease with well-substantiated neuropsychiatric underpinnings. Appetite and satiety centers
in the brain have been well-documented93 and thus represent primary areas for investigation.21,97,98 Many studies
have indicated that the reward sensation associated with
food intake is also largely implicated in the pathophysiology of obesity.7,44,123 In support of this concept, it was recently proposed that obesity be included as a mental disorder
in the next (fifth) edition of the Diagnostic and Statistical
Manual of Mental Disorders (DSM-V).119 Below, we review
3 potential neural targets for DBS believed to be involved
in the excessive consumption of food in obesity.
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C. H. Halpern et al.
Background
Obesity, defined as a BMI > 30 kg/m , affects more
than 30% of adult Americans83 and over 300 million people worldwide.25 Annual health care costs are estimated
at nearly 100 billion dollars in the US alone.2 Obesity is
associated with diminished quality of life,92 high risk of
comorbidities,32,81 and the reduction of life expectancy by
up to 20 years.34 Pharmacological therapies and behavioral
techniques are rarely effective due to high relapse rates,51,63
explaining the more than 10-fold increase in bariatric surgeries performed over the past 8 years.107 Although mean
weight loss after bariatric surgery ranges from ~ 20 to ~
60%, with concomitant improvement in morbidity,65,70,121
complications occur in 15–55% of patients, and the perisurgical mortality rate is ~ 1.5% even in experienced centers.82,86 Furthermore, significant weight gain occurs after
the nadir weight is reached, approximately 2 years postoperatively.20 The failure rate due to noncompliant eating
patterns in patients followed up for 10 years is as high as
20% for obese and 40% for super-obese (BMI > 50 kg/m2)
patients.15,20 One follow-up study reported recurrent binge
eating in 46% of patients who had undergone bariatric surgery.52 Thus, consideration of the neuropsychiatric basis of
obesity may help explain these refractory eating habits and
the significant surgical failure rate.
2
Deep Brain Stimulation of the Hypothalamus:
Rationale
Overconsumption of calorically dense foods is a likely contributor to the rapidly progressing epidemic of obesity.16 Body weight results at least in part from a balance
between food intake and energy expenditure, and obesity
is due to an imbalance between energy input and output.
The hypothalamus has been shown to be integral in maintaining this energy homeostasis. Specifically, food intake
is at least in part controlled by a feeding center in the lateral hypothalamus and a satiety center in the ventromedial hypothalamus.93 We will discuss these regions below
as potential targets of DBS.
The Lateral Hypothalamus
The LH has long been implicated in feeding behavior
and energy expenditure.12 Its role in appetite regulation was
well described in early studies of LH lesioning, which induced leanness.3 This impact on appetite can be partially
explained by peptides expressed in the LH, such as MCH
and orexins (also known as hypocretins), as well as orexin
receptors.23,85,96 Indeed, MCH−/− mice have been shown to
be lean and hypophagic, and mice with overexpression of
MCH, obese and insulin-resistant.64 Chronic administration of an orally active MCH receptor antagonist decreased
food intake, body weight, and adiposity in rodent obesity
models.71 Injections of orexins into the LH increased feeding behavior and enhanced arousal. Indeed, upregulated
expression of the orexin gene has been demonstrated in
fasting rats.55 Other peptides shown to be critical regulators
of feeding behavior and body weight in­clude neuropeptide
Y68 and agouti-related protein,14 which densely project to
the LH.30,105
626
Anatomy of the LH. The LH is a fairly large region of
the hypothalamus, measuring approximately 6 × 5 × 3.5
mm in the largest dimensions laterally, anteroposteriorly,
and dorsoventrally, respectively.99 (See Fig. 1 for further
definition of this target structure.) Targeting the LH with
DBS has been associated with risk of the spread of stimulation to nearby hypothalamic nuclei. The hypothalamus comprises a large number of distinct nuclei, and thus
has many physiological functions not limited to appetite
control, including body temperature regulation, sexual activity, reproductive endocrinology, and the fight-or-flight
response.89 The effect of stimulating any adjacent hypothalamic region is thus associated with altering these physiological responses. Other neural structures located adjacent
to the LH include the fornix and the optic nerve. Portions
of the LH are just inferior to the fornix and directly superior and posterior to the optic nerve and chiasm, further
complicating the targeting of this nucleus with DBS.99
Stereotaxy and Stimulation of the LH. Nevertheless,
targeting the hypothalamus with DBS has already been
shown to be safe and potentially effective in managing patients with intractable chronic cluster headache.61 Furthermore, stereotactic electrocoagulation of the LH in obese
hu­mans was performed safely more than 30 years ago, resulting in significant, although transient, appetite suppression and slight weight reduction in 3 patients.90 Given this
evidence, it was recently proposed that chronic bilateral
DBS of the LH at high frequencies would mimic the results of lesion studies, just as STN DBS for PD mirrors the
effect of subthalamotomy.98
To test this hypothesis, Sani et al.97 stereotactically
implanted electrodes bilaterally into the rat LH. Half of
the implanted animals underwent high-frequency stimulation (stimulation parameters: 2.0 V, pulse width 100 msec,
frequency 180–200 Hz), while the other half were left un­
stimulated. On postoperative Day 24, stimulation was associated with a mean loss of 2.3% of body weight, while
the unstimulated group had a mean weight gain of 13.8%
(p < 0.001). Interestingly, no difference in food intake was
found between groups. Thus, the authors concluded that
the stimulation-induced weight loss seen in the stimulated
group was secondary to metabolic change, although no
mea­surements of individual animals’ metabolic profiles
were made. In contrast to high frequency LH stimulation,
LH stimulation at lower frequencies (50–100 Hz) elicited
feeding in earlier studies.13,75,87,113 Hypothalamic stimulation
at 50 Hz resulted in immediate and sustained hoarding of
food in satiated rats.42 Similarly, unilateral LH stimulation
resulted in increased feeding in cats26,33 and induced rhythmic oral activity in rabbits.101 Other effects of LH stimulation included exploration, as well as escape and attack behaviors associated with autonomic changes with increases
in stimulation strength. These findings are consistent with
those observed in canine LH stimulation at 100 Hz, which
induced increases in coronary flow, blood pressure, heart
rate, and other sympathetic responses.35 Importantly, such
changes were also associated with cardiac arrhythmias.
Ventromedial Hypothalamus
Like the LH, the VMH has also been implicated in
J. Neurosurg. / Volume 109 / October 2008
Deep brain stimulation in the treatment of obesity
Fig. 1. A sagittal section depicting the lateral hypothalamus adjacent to the optic nerve. The fornix is not well visualized in this section. *lateral hypothalamus (L); #optic nerve (II); ^ nucleus accumbens (Fu.st). From Schaltenbrand
G, Warren W: Atlas for Stereotaxy of the Human Brain. Stuttgart: Thieme, 1977. Reprinted, with the addition of
*, #, and ^, by permission.
ap­petite regulation and the maintenance of energy homeostasis.43,54 Le­sions of the VMH have been shown to induce
weight gain in obese animals,18 and lesions resulted in substantially more carcass lipid and hyperinsulinemia in rats
even if pair-fed with sham-lesioned controls, suggesting a
metabolic bias toward obesity.22
Anatomy of the VMH. There are various challenges to
surgically targeting the VMH that need to be considered.
The VMH is a small bilobed target in the vertical axis
measuring approximately 2 × 3 × 5 mm in the largest dimensions (Fig. 2).99 Although found slightly inferior to the
anterior commissure in the anteroposterior plane, which
may facilitate accurate localization, an intraventricular
trajectory may be required given such a medial location
of the VMH. Furthermore, the VMH is bounded by the
optic nerve anteriorly and the mammillary body posteriorly. Deep brain stimulation of the mammillary bodies is
currently under in­vestigation as a potential target for seizure control.116 Due to their connections to the circuit of
Papez, and given substantial evidence pointing to an imJ. Neurosurg. / Volume 109 / October 2008
portant role of this circuitry in seizure propagation and expression, it is possible that the spread of stimulation from
this area may induce seizures.76 The VMH is located just
inferior and medial to the LH. The hypothalmic nuclei are
well-known to be largely interconnected,89 and thus it is
conceivable that stimulation spread to the LH may directly
antagonize the effect of low-frequency DBS of the VMH.
Stereotaxy and Stimulation of the VMH. Electrical
stimulation of the VMH has been reported, and stimulation at low frequencies (60–100 Hz) inhibited feeding in
hungry rats, and eating resumed once the current was terminated.46,57 In goats, VMH stimulation at low frequencies
(for example, 50 Hz) inhibited feeding as well.5,127 Other
effects of stimulation included fear, aversion, restlessness,
and attempts at escape, which may have partially accounted for the decreased feeding behavior in these animals.46,57
These effects may be related to autonomic changes due to
VMH stimulation, which has been shown to increase metabolic rate.94 This increase in energy expenditure was associated with increased fat oxidation given a concomitant
627
C. H. Halpern et al.
Fig. 2. A sagittal section depicting the ventromedial hypothalamus bounded anteriorly by the optic nerve and posteriorly by the ipsilateral mammillary body. *ventromedial hypothalamus (Vm); #mammillary body (M.m); +optic
chiasm (Ch. II); ^anterior commissure (Cm.a). From Schaltenbrand G, Warren W: Atlas for Stereotaxy of the Hu­
man Brain. Stuttgart: Thieme, 1977. Reprinted, with the addition of *, #, +, and ^, by permission.
drop in the respiratory quotient. Thus, heightened metabolism induced by VMH stimulation was sustained by utilization of fat stores, most likely due to noradrenergic turnover.95,106 Recently, VMH DBS at 4 different frequencies
(25, 50, 75, and 100 Hz) in a rat was shown by means of indirect calorimetry to result in an increase in metabolism.21
There was a trend toward an indirect relationship between
energy expenditure and increasing frequencies, suggesting
that lower frequencies of stimulation drive VMH activity,
while higher frequencies may have lesioning effects (A. L.
Benabid, 2006, personal communication). These findings
are consistent with a frequency-dependent effect of stimulation.58
Deep Brain Stimulation of the Nucleus
Accumbens: Rationale
Physiological states associated with energy balance,
such as hunger and satiety, are strong determinants of feeding behavior. The above data support the idea that DBS
of the LH or VMH at various frequencies may be able to
modulate the neural regions associated with energy homeostasis. However, the assumption that feeding behavior
in obesity can be effectively modulated by inhibiting appetite sensation or driving satiety may not be correct. In
fact, there is a significant amount of evidence that feeding
behavior is strongly influenced by palatability, or the reinforcing value of food, irrespective of appetite. For example,
there is a 90% increase in food intake in mice fed a highfat diet compared with their consumption when fed normal
house chow.110 Such a palatable diet (45 kcal % fat) is pre628
ferred to standard house chow because of reinforcing properties believed to be mediated largely in the NAc.44,104,123
Anatomy of the NAc
The NAc is a ventral striatal region located immediately inferior to the anterior limb of the internal capsule.
As a DBS target, the NAc is very similar to the STN.
It measures approximately 8 × 6 × 6 mm in the largest
dimensions, thus making it only slightly larger than the
STN, which is approximately 8 × 4 × 4 mm.99 (See Figs. 1
and 3 for further delineation of the NAc.) The NAc has a
well-circumscribed, ellipsoid shape with relatively clearcut boundaries on myelin-stained sections, with the most
superior edge directed medially.99 The center of the NAc
is located just about 3 mm anterior to the anterior commissure and approximately 6 mm lateral from the mid­
line. To target the NAc, a trajectory can be taken just lat­
eral to the ventricle and through the caudate nucleus; this
approach has been well tolerated in reports of DBS for
OCD and depression37,100 as well as DBS of the globus
pal­lidus in PD.4 Certainly some cognitive deficits such as
mem­ory impairment are possible due to microtrauma to
the caudate, but patients without preoperative dementia
are less at risk.19 Some of the other nearby structures that
may compromise safe targeting of the NAc include the
an­terior cerebral artery located just inferiorly, as well as
the optic nerve found inferomedially.99
The NAc is divided into 2 subregions, core and shell,
based on cytoarchitectonic and neurotransmitter characteristics, as well as differences in the afferent and efferent
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Deep brain stimulation in the treatment of obesity
Fig. 3. A coronal section depicting the nucleus accumbens located in the ventral striatum just inferior to the caudate nucleus and inferolateral to the lateral ventricle. *nucleus accumbens (Fu.st); #caudate nucleus (Cd); + putamen
(Put). From Schaltenbrand G, Warren W: Atlas for Stereotaxy of the Human Brain. Stuttgart: Thieme, 1977. Re­
printed, with the addition of *, #, and ^, by permission.
connections.128 Anatomical tracing studies have shown
that the core region connects extensively to extrapyramidal motor structures, such as the VP, the STN, and the
substantia nigra.29 The shell region is believed to be confined to the ventromedial margins of the NAc41 and is embedded in a complex mesocorticolimbic circuit providing
control of reward sensitivity. The NAc shell receives dopaminergic input from the ventral tegmental area, as well
as afferents from the amygdala, hippocampus, prefrontal cortex, and thalamus.29,38,130 Efferent output projects
mainly to the VP, as well as the thalamus and cingulate
cortex.24,129 Recent work has implicated simultaneous involvement of the NAc shell and the VP in favorable reactions to taste in rodents (“liking”), such as tongue protrusions, whereas the NAc shell exerted independent control
of food intake (“wanting”).104 Thus, output from the NAc
shell may in part bypass the VP and project directly to the
J. Neurosurg. / Volume 109 / October 2008
LH,129 suggesting that communication exists between the
reward processing and feeding centers in the brain. Sig­
nif­icant debate exists as to whether electrical stimulation
of the LH alone induces rewarding sensations.13,45
The NAc and Food Reward
The NAc is integral to the modulation of reward sensation shown to be associated with palatability of foods.
Results from single-unit recordings from the NAc demonstrated that in a subset of neurons, firing rates varied significantly as a function of sucrose concentration.109 Furthermore, palatable food such as chow with high fat content (45
kcal % fat) was preferred to standard house chow because
of reinforcing properties believed to be mediated in part by
dopamine neurotransmission in the NAc.44,123 Indeed, NAc
injections of dopamine antagonists suppressed feeding.10
629
C. H. Halpern et al.
Furthermore, the levels of dopamine release were proportional to the amount ingested,69 and there is a significantly
greater amount of dopamine released in the NAc of obese
rats relative to lean rats in response to food stimuli.74,123
Sensitivity to reward can vary from one person to
another, but those individuals with more frequent and intense food cravings are more likely to be obese.8 Mice
withdrawn from a highly palatable diet will endure an
aversive environment to obtain preferred foods, and show
a significant increase in expression of corticotropin-releasing factor associated with a stress state.110 Thus, we
support the recent suggestion that at least some forms of
obesity may be driven by an excessive motivational drive
for food intake that overrides the hypothalamic circuitry
normally involved in regulating food consumption.77 In
fact, in addition to projections from the NAc to the LH,129
there are projections from the LH to the NAc,85 suggesting that signals of internal homeostasis may be relevant
in modulating food reward.67 Studies in animal models
of obesity, however, have demonstrated altered expression of many of the peptides involved in feeding behavior
at the level of the LH, resulting in increased hunger for
highly palatable food.47,48,125 Thus, hypothalamic control
of intake may be impaired in obesity.47,125 It is conceivable
that significant relapse and failure rates may be at least in
part a result of a dysregulated reward system, leading to
our experience to date with conservative measures and
bariatric surgery.
The idea that dopamine plays a dominant role in modulating palatability has been recently called into question.
Multiple neurotransmitters have been implicated in accumbal reward processes, some with potent effects on intake of high-fat diets. Injections of opioid receptor agonists
into the NAc induced hyperphagia and a preference for
fat consumption that was independent of dopamine neurotransmission and was blocked by cotreatment with naltrexone.79,122,131 The majority of corticolimbic inputs to the
NAc use an excitatory amino acid as their neurotransmitter.
Indeed, blockade of α-amino-hydroxy-5-methylisoxazole4-propionic acid (AMPA) receptors in the shell subregion
of the NAc resulted in pronounced feeding.67 However, the
majority of the cells in the NAc are GABAergic and therefore inhibitory, both locally and at their projection targets.
In addition, there is also significant cholinergic neuromodulation of these cells. Thus, within the NAc is an extensive
network of multiple neurotransmitter systems, some or all
of which may be intimately involved in food reward sensation. Further study, including detailed computational modeling of the modulation of this network, will be necessary
to determine the effect of DBS on specific components of
this network.78,124
Evidence From Lesion Studies
Destruction of the dopaminergic neuron terminals
projecting to the NAc with a stereotactic injection of
the neurotoxin 6-OHDA results in dopamine depletion
in this region. The 6-OHDA lesions of NAc resulted in
significant attenuation of food hoarding and weight loss
in rats,53 and administration of levodopa restored normal
hoarding behavior. While lesioning effects of DBS at high
frequencies are well documented, it is difficult to predict
630
whether DBS could mimic the effects of 6-OHDA lesions
given the variety of neurotransmitter systems involved in
the NAc and the differentiated anatomical projections of
the accumbal subregions. N-methyl-d-aspartate lesions
of the NAc core induced weight loss in rats, whereas the
shell-lesion group gained weight.66 The authors of the
study argued that the loss of weight in the core group was
due to changes in motor function given the core’s connections to the extrapyramidal system.29 It is conceivable
that the core and shell have opposing effects on ingestive behavior, explaining the lack of any change in weight
with large, nonspecific excitotoxic lesions encompassing
both regions of the NAc. Given the functional dissociation within the NAc, further investigation is necessary to
determine if modulation of reward sensation is possible
with DBS, what region of the NAc is most appropriate to
target, and what frequencies are necessary to obtain the
desired effects. Furthermore, given the proximity of the
NAc to various structures, including the globus pallidus,
anterior limb of the internal capsule, VP, and caudate, rigorous stereotactic methods are necessary to ensure precise placement of the permanent electrode.
Evidence From Neurofunctional Imaging
Functional MR imaging studies have demonstrated
activation of striatal reward areas during exposure to a
high-fat stimulus, particularly in those patients with enhanced reward sensitivity.8 A hyperfunctioning region is
known to be susceptible to the effects of DBS given the
lesioning effect of high frequency stimulation of the overactive STN in PD. Positron emission tomography and autoradiographic studies have shown reductions in striatal
D2 receptors, as well as elevated levels of the dopamine
transporter.49,120 It follows that lower extracellular levels
of dopamine have been found in the NAc of obese mice
relative to the levels found in obesity-resistant mice, a differnce that may be due to enhanced clearance.49,102 While
heightened reward is evident in obesity associated with
increased levels of accumbal dopamine release following exposure to a food stimulus, this sensation may be
short-lived due to a decreased sensitivity of dopaminergic
reward circuits. Thus, a need to compensate with food reinforcers in conjunction with an increased stress response
to palatable food restriction may be the underlying causes
for the reported high rates of recurrent binge eating and
surgical failures in bariatric patients.
Evidence From NAc Stimulation Studies
Electrical stimulation of the NAc has been performed
in rats.53,72,88 Multiple effects of NAc stimulation have been
reported in rats, including increased sniffing, excitement,
and even aggression, which were all observed at a stimulation frequency of 60 Hz.40 These findings have been
replicated in cats,36 although no such effects were noted
in rhesus monkeys.126 No consistent documentation of the
response of feeding behavior to NAc DBS has been report­
ed,80,117 but none of these studies included overweight or
obese animals. Some evidence for the potential of NAc
DBS in obesity control can be derived from its success in
re­lieving symptoms of OCD.37
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Deep brain stimulation in the treatment of obesity
Reward Circuitry DBS in Other Treatment-Resistant
Conditions
Bilateral NAc stimulation in a rat model of OCD has
shown promise for the use of this modality in humans.
Electrodes were implanted bilaterally using stereotactic
coordinates similar to those previously documented.53 Although further investigation is required, high-frequency
stimulation appeared to diminish OCD symptoms in various rat models of OCD.50,114,115 One explanation for these
findings, as well as for the success of NAc DBS in patients
with OCD, comes from a recent study in which high-frequency NAc stimulation at 130 Hz reduced the firing rate
of orbitofrontal cortex neurons in rats.72 Indeed, metabolic
hyperactivity in this region has been consistently associated with OCD symptoms.17
A trial of DBS of the ventral capsule/ventral striatum
site, a region that encompasses the NAc, in 10 OCD patients
with long-term follow-up demonstrated a 36% decrease in
disease severity and nearly a 50% improvement in global
functioning.37 This region has been consistently implicated
in OCD given its central position between the amygdala,
basal ganglia, thalamus, and prefrontal cortex, all regions
known to be involved in this disorder.91,103 Furthermore, the
ventral striatum, and particularly the NAc, has been shown
to respond abnormally to pleasurable stimuli in patients
suffering from severe depression.112 Deep brain stimulation of the NAc provided a 42% improvement in depression severity in one study.100 These reports not only provide
encouraging evidence for the therapeutic effect and safety
of DBS, but also for its promise in modulating neural regions implicated in reward sensation associated with the
pathophysiology of obesity.
Conclusions
Appetite modulation in conjunction with enhancement
of the metabolic rate by means of hypothalamic lesions
has been widely documented in animal models and even
in humans. It appears that these effects can be reproduced
by DBS, and the titratability and reversibility of this procedure, in addition to its well-established safety profile,
make hypothalamic DBS an appealing option for obesity
treatment. Given that palatability significantly increases
food intake, however, suppressing appetite and increasing
energy expenditure may prove to be inadequate, especially
over the long term. Indeed, electrocoagulation of the LH in
humans only transiently suppressed appetite and provided
minimal weight loss.90 Chronic NAc DBS may allow us
to modulate reward sensation and dietary preferences by
interacting with the systems known to be implicated in the
reinforcing properties of food. Inhibition of food reward
may provide significant weight reduction over time and effectively lessen relapse rates associated with conservative
and surgical treatments. Moreover, stimulation frequency
may be titratable to adequate inhibition of food preference
and overconsumption. Deep brain stimulation of the NAc
region has already been established as safe in the treatment
of patients with refractory OCD and depression.84,108 Thus,
we need to consider the potential role of DBS in attenuating the reinforcing properties of highly palatable foods
J. Neurosurg. / Volume 109 / October 2008
that have clearly contributed to the worldwide epidemic of
obesity. Furthermore, established animal models of obesity
exist62 and should be used in studies measuring the effects
of DBS on weight loss.
Disclaimer
The authors do not report any conflict of interest concerning
the materials or methods used in this study or the findings specified
in this paper.
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Manuscript submitted August 27, 2007.
Accepted February 21, 2008.
Address correspondence to: Casey H. Halpern, M.D., Department
of Neurosurgery, 3 Silverstein, Hospital of the University of Penn­
sylvania, 3400 Spruce Street, Philadelphia, Pennsylvania 19104.
email: [email protected].
J. Neurosurg. / Volume 109 / October 2008