Deep Brain Stimulation for Obesity

This chapter includes an accompanying lecture presentation that has been prepared by the authors: .

Key Concepts

  • Morbid obesity is a worldwide crisis with few successful treatment strategies.

  • Obesity is the result of a complex interplay among genetic, homeostatic, hedonic, and environmental factors, with several central nervous system pathways and mechanisms involved.

  • Several targets, including the lateral hypothalamus, ventromedial hypothalamus, and nucleus accumbens have been studied as potential targets for deep brain stimulation for obesity.

  • Case reports and one completed pilot study have shown promise with deep brain stimulation for the treatment of obesity.

  • Further studies are ongoing or planned; more information is needed to definitively determine if deep brain stimulation is a viable treatment strategy for obesity.

Obesity has become a worldwide epidemic, with prevalence increasing substantially in both developing and developed countries. The Centers for Disease Control and Prevention estimates that, in the United States, 16.9% of children 2 to 19 years of age and 34.9% of adults older than 19 years of age are obese, with 5.7% of the population considered morbidly obese. , Morbid obesity is linked with premature death, impaired quality of life, and multiple comorbidities, including type 2 diabetes, cardiovascular disease, musculoskeletal disease, and certain cancers. Annual obesity-related health care costs are estimated at nearly $190 billion in the United States alone.

Body mass index (BMI) is commonly used to assess fat composition of the body. It does not measure body fat directly, but studies have shown that it correlates to direct measures of body fat such as underwater weighing and dual-energy x-ray absorptiometry. , BMI is calculated by dividing weight in kilograms by the square of height in meters. A healthy weight is considered to be associated with a BMI from 18.5 to 24.5, while overweight is defined as a BMI of 25 to 29.9. Obesity is defined as a BMI greater than or equal to 30, and morbid obesity is regarded as a BMI greater than or equal to 40 or greater than 35 with comorbidities.

Obesity is most commonly approached as a problem of energy imbalance; however, more recent analyses have suggested that obesity should also be interpreted within the scope of psychiatric diseases. From an energy standpoint, obesity or weight gain is thought to result from a net positive energy balance, where energy intake (food consumption) exceeds energy expenditure (a combination of resting metabolic rate [RMR], physical activity, and the thermic effect of food). Theories for the burgeoning obesity epidemic are myriad, but the problem is multifactorial and is generally regarded as resulting from the perfect storm of more easily available food, higher-calorie foods, and more sedentary lifestyles than witnessed in previous centuries.

In addition to such environmental factors, genetic factors have been increasingly shown to play a role in obesity. The metabolic theory implies an imbalance of circulatory peptide hormones such as ghrelin, obestatin, nesfatin-1, leptin, and insulin interacting with genetic factors leading to obesity. Ghrelin, insulin, and leptin have been shown to act directly on the central nervous system to modulate both metabolism and food intake behaviors. The “incentive salience theory” of food reward recognizes a hedonic component as well as a reward-seeking, motivational component mediated by activation of the mesolimbic dopamine circuitry. Dysregulation of the mesolimbic dopamine system has been implicated in binge eating. , In support of the “incentive salience theory,” binge eating was included as a mental disorder in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5).

Whatever the cause, the population has been searching for an effective solution. The US market is overcrowded with weight-loss supplements, appetite suppressants, exercise plans, and dietary plans. Physicians have also been armed with weight-loss medications that act on both sides of the energy equation. The failure of medications to control obesity has been the impetus for surgical treatments such as gastric bypass, gastric banding (gastroplasty), and intragastric balloon placement. Although bariatric surgery has successfully facilitated weight loss in many patients refractory to other measures, there is a significant risk for morbidity and mortality associated with these procedures. Despite initial weight loss, some patients regain a significant amount of weight, even with technically successful surgery.

Deep brain stimulation (DBS) has become a well-established treatment option for movement disorders such as Parkinson disease, essential tremor, and dystonia. Because of its effectiveness in the treatment of these diseases, the low rates of complications, and the reversibility of the treatment modality, DBS is being investigated as a treatment option for medically refractory psychiatric conditions such as Tourette syndrome, obsessive-compulsive disorder, and depression. The growing recognition of the brain as the source of metabolism and appetite control has led to a resurgence of interest in treating obesity with a brain surgery strategy such as DBS. To understand the rationale behind different potential brain targets for DBS in the treatment of obesity, we provide a review of the neuroanatomy linked with body weight and discuss the various studies supporting DBS as a treatment option.


The hypothalamus is a structure composed of numerous nuclei, several of which have been implicated in feeding behavior as well as energy homeostasis. Feeding centers motivating food intake have been traditionally located to the lateral hypothalamus (LH), while the satiety center has been traditionally located to the ventromedial hypothalamus (VMH). The solution to obesity, though, may be more complicated than just inhibiting feeding behavior or stimulating the satiety center. The motivational reward center for food intake and other pleasurable human activities is mediated by the nucleus accumbens (NAcc) and also likely plays a role in the development of morbid obesity.

Lateral Hypothalamus

The LH has long been implicated in feeding behavior and energy expenditure. Lesioning of the LH has been shown to induce leanness and increased energy expenditure. , In humans, the LH measures approximately 6 × 5 × 3.5 mm in the largest dimensions laterally, anteroposteriorly, and dorsoventrally, respectively. Portions of the LH lie just inferior to the fornix and directly superior and posterior to the optic nerve and chiasm. The lateral preoptic nucleus is located rostrally, and the ventral tegmental area of the midbrain lies caudally. ,

Ventromedial Hypothalamus

The VMH has been dubbed the “satiety center” and regulates feeding behavior and energy expenditure. Lesions of the VMH induce weight gain in animals and lead to increased carcass lipid and hyperinsulinemia in rats, suggesting a metabolic bias toward obesity. , The VMH lies inferomedial to the LH and measures approximately 2 × 3 × 5 mm in the largest dimensions. The VMH is surrounded by the optic nerve anteriorly, the mammillary body posteriorly, and the anterior commissure superiorly. ,

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