Obesity is a growing health problem worldwide and is responsible for a significant proportion of health expenditures in developed nations. It is also notoriously difficult to treat. Prior attempts at pharmacological or neurological modulation, including deep brain stimulation, have primarily targeted homeostatic mechanisms of weight control centered in the hypothalamus. To date, these attempts have had limited success. Multiple lines of independent data suggest that dysregulated reward circuitry in the brain underlies behaviors leading to obesity. Here, we review the existing data and related neurocircuitry, as well as the scope of obesity and currently available treatments. Finally, we suggest a neuromodulation strategy geared toward regulating these dysfunctional circuits, primarily by alteration of frontolimbic circuits. ABBREVIATIONS: ACC, anterior cingulate cortex BMI, body mass index CSPT, Ccortico-striato-pallido-thalamo-cortical DBS, deep brain stimulation fMRI, functional magnetic resonance imaging NAcc, ccnucleus accumbens SCC, subgenual cingulate cortex VTA, ventral tegmental area
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