Deep Brain Stimulation for Obesity

Allen L Ho, Eric S Sussman, Michael Zhang, Arjun V Pendharkar, Dan E Azagury, Cara Bohon, Casey H Halpern, Allen L Ho, Eric S Sussman, Michael Zhang, Arjun V Pendharkar, Dan E Azagury, Cara Bohon, Casey H Halpern

Abstract

Obesity is now the third leading cause of preventable death in the US, accounting for 216,000 deaths annually and nearly 100 billion dollars in health care costs. Despite advancements in bariatric surgery, substantial weight regain and recurrence of the associated metabolic syndrome still occurs in almost 20-35% of patients over the long-term, necessitating the development of novel therapies. Our continually expanding knowledge of the neuroanatomic and neuropsychiatric underpinnings of obesity has led to increased interest in neuromodulation as a new treatment for obesity refractory to current medical, behavioral, and surgical therapies. Recent clinical trials of deep brain stimulation (DBS) in chronic cluster headache, Alzheimer's disease, and depression and obsessive-compulsive disorder have demonstrated the safety and efficacy of targeting the hypothalamus and reward circuitry of the brain with electrical stimulation, and thus provide the basis for a neuromodulatory approach to treatment-refractory obesity. In this study, we review the literature implicating these targets for DBS in the neural circuitry of obesity. We will also briefly review ethical considerations for such an intervention, and discuss genetic secondary-obesity syndromes that may also benefit from DBS. In short, we hope to provide the scientific foundation to justify trials of DBS for the treatment of obesity targeting these specific regions of the brain.

Keywords: behavior; deep brain stimulation; food; hypothalamus; lateral hypothalamus; metabolism; neuromodulation; nucleus accumbens; obesity; reward pathway.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1. Schematic diagram depicting the deep…
Figure 1. Schematic diagram depicting the deep brain stimulation (DBS) targets for obesity and their role in homeostatic pathway of energy balance
The LH is responsible for providing anabolic feedback onto the autonomic nervous system effectors. The nucleus accumbens (NAc) is the center of the reward pathway in the brain integrating inputs from various high cortical brain areas and the limbic system to reinforce certain beneficial behaviors, such as feeding. Integration of the reward pathways with feeding behavior begins with dopamine release from the ventral tegmental area (VTA) neurons that project onto the nucleus accumbens (NAc). Within the NAc, there are neurons that projection onto the lateral hypothalamus (LH) which contain neurons that stimulate food intake. These nuclei also respond to various hormonal peptides, such as leptin, that are released by the the metabolic systems of the body that link food intake and energy metabolism to the reward pathways within the brain.

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