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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EThe neural control of food intake is a challenging area of research; it is not known how obesity and weight loss alter brain function. This article discusses updates in neuroimaging in patients who have undergone bariatric surgery, as well as off-label use of deep brain stimulation (DBS) in refractory obesity.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EObesity\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ENeuroimaging\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EInterventional Techniques \u0026amp; Devices\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EObesity\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ENeuroimaging\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EInterventional Techniques \u0026amp; Devices\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EThe neural control of food intake is a challenging area of research; it is not known how obesity and weight loss alter brain function. Christopher N. Ochner, PhD, Mount Sinai Hospital, New York, New York, USA, discussed what has been learned from neuroimaging in patients who have undergone bariatric surgery. Originally, studies focused on the hypothalamus to investigate the hypothesis that obese individuals have dysregulation of their homeostatic mechanisms. Subsequent hypotheses suggested that food intake was a balance between the desire to eat (involving activity of the ventral tegmental area, ventral striatum, dorsal striatum, amygdala, hippocampus, prefrontal cortex [PFC], and orbitofrontal cortex) and inhibition of eating (involving the dorsolateral PFC, inferior frontal gyrus, and cingulate cortex). Some studies appear to support the hypothesis that obese individuals receive more reward from food than normal-weight individuals; by contrast, other studies suggest that obese individuals receive less reward from food, causing them to overeat to make up for the reward deficit. The initial studies of neuroimaging in bariatric patients attempted to shed light on this seeming paradox.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EStudies looking at alterations of central dopamine type 2 (D2) receptors before and after gastric bypass surgery using positron emission tomography in small numbers of patients have shown conflicting results. More recently, a study using functional magnetic resonance imaging (fMRI) showed partial reversibility of hypothalamic dysfunction in 13 obese patients after massive weight loss compared with lean control patients (n = 8) [van de Sande-Lee S et al. \u003Cem\u003EDiabetes\u003C\/em\u003E. 2011]. Another study of 17 obese women showed increased cerebral metabolism, particularly in the posterior cingulate gyrus, which decreased to levels similar to those in lean women (n = 16) after weight loss after bariatric surgery [Marques EL et al. \u003Cem\u003EJ Clin Endocrinol Metab\u003C\/em\u003E. 2014]. Both of these studies were unusual for the size of the patient population and the inclusion of control patients. Gastric bypass surgery has also been shown to reduce neural responses to high-calorie foods in 10 obese women but not low-calorie foods measured by fMRI [Ochner CN et al. \u003Cem\u003EAnn Surg\u003C\/em\u003E. 2011]. Reductions in activation in key areas in the mesolimbic reward pathway mirrored a postsurgical reduction in the desire to eat high-calorie vs low-calorie foods.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EWhat is driving these postoperative changes in neural responsivity is not known. A comparison of functional brain changes in patients associated with surgical (n = 15) vs behavioral (n = 16) weight loss showed increased responses to food cues in the bilateral temporal cortex in surgical patients and in the medial PFC in dieters [Bruce AS et al. \u003Cem\u003EObesity (Silver Spring)\u003C\/em\u003E. 2014]. This suggests that the method of weight loss affects changes in brain function.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EAlthough more research is needed regarding the mechanisms behind pre- and postsurgical changes in neural responsivity to food cues, D2 receptor availability, and the role of the type of weight loss intervention, studies are being done to alter brain function to promote weight loss.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EDonald M. Whiting, MD, Allegheny Health Network, Pittsburgh, Pennsylvania, USA, discussed the off-label use of deep brain stimulation (DBS) in refractory obesity.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EThe use of DBS assumes that there is abnormally functioning circuitry in the brain that can be regulated. DBS has an established role in the treatment of movement disorders and obsessive-compulsive disorders. Target areas in the brain for obesity include the lateral and ventromedian hypothalamus (VMH) or \u201csatiety center,\u201d and more recently, the nucleus accumbens (NAc) or \u201creward center.\u201d\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EEarly animal studies in rats showed that lesions in the VMH were associated with increased levels of body fat and insulin, hyperphagia, and obesity [Penicaud L et al. \u003Cem\u003EAm J Physiol\u003C\/em\u003E. 1983; Cox JE, Powley TL. \u003Cem\u003EEndocrinology\u003C\/em\u003E. 1981]. Bilateral low-frequency stimulation (LFS) stopped feeding behavior in hungry rats [Krasne FB. \u003Cem\u003EScience\u003C\/em\u003E. 1962], whereas high-frequency stimulation (HFS) increased food consumption with no significant changes in weight [La\u0107an G et al. \u003Cem\u003EJ Neurosurg\u003C\/em\u003E. 2008]. However, stimulation of this region in humans was associated with a panic\/anxiety reaction.\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EThe lateral hypothalamic area (LHA) is a larger and therefore more desirable target with fewer physiologic effects, and has been implicated in feeding and energy expenditure. Early studies suggested that lesions in the LHA were associated with leanness and increased energy expenditure. In this region, LFS causes food seeking in animals in spite of satiety, whereas HFS resulted in weight loss in stimulated animals through food intake that was similar to that in the LFS group; HFS may raise the resting metabolic rate (RMR), leading to weight loss [Sani S et al. \u003Cem\u003EJ Neurosurg\u003C\/em\u003E. 2007].\u003C\/p\u003E\u003Cp id=\u0022p-10\u0022\u003EA pilot study of DBS was conducted in 3 individuals with refractory obesity for whom bariatric surgery had failed [Whiting DM et al. \u003Cem\u003EJ Neurosurg\u003C\/em\u003E. 2013]. The primary objective of this study was safety; body weight change and energy metabolism were also assessed. The LHA was stimulated bilaterally using settings established for mood disorders.\u003C\/p\u003E\u003Cp id=\u0022p-11\u0022\u003EAt 35 months of follow-up (range, 30 to 39 months), there were only mild adverse effects and no serious adverse events. There was 1 electrode fracture requiring revision. DBS may have reduced binge-eating episodes in 1 patient, with improvement in body shape and self-image feelings in 2 patients. DBS did not have a negative effect on quality of life. However, LFS at the setting used for mood disorders caused weight gain. Therefore, settings were altered to determine the effect on RMR. When settings were used that appeared to increase RMR in metabolic chamber experiments, DBS was associated with weight loss in 2 patients and stable weight in 1 patient.\u003C\/p\u003E\u003Cp id=\u0022p-12\u0022\u003EOnly a small area of the LHA is involved in RMR augmentation via DBS, and there may be a diminished effect over time. Other areas of the brain may provide additional targets, such as the NAc, which provides a larger target area.\u003C\/p\u003E\u003Cp id=\u0022p-13\u0022\u003EMany questions about the effect of bariatric surgery on neural responsivity remain to be answered, including whether weight loss is mediated by changes in receptor binding or in neural responsivity, and how long these changes last. Likewise, the role, if any, of DBS in refractory obesity needs to be determined by further definition of the appropriate target site and evaluation of efficacy and safety in a larger group of patients. The complex interaction between homeostatic and nonhomeostatic circuits suggests that a multitargeted approach to the treatment of obesity will be necessary.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2014 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/14\/47\/29.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzlx9p\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}