Deep brain stimulation trial in treatment-resistant obesity links weight loss trend to metabolism increase programmed in metabolic chamber

Animal and lesioning studies suggested the LHA may be a promising neurostimulation target to augment weight-loss efforts for morbidly obese patients, patients whose weight exceeds 50 percent of normal, and who had failed other weight-loss attempts. In the FDA-approved study focused on safety and early efficacy findings, three patients who had failed to keep weight off after gastric bypass surgery received deep brain stimulation implants in 2009-2010.

Deep brain stimulation (DBS) is routinely used to control motor symptoms in patients with Parkinson's disease and dystonia, and the same movement-disorder stimulation program was initially used in these obesity trial patients. Deep brain stimulation involves implanting slender leads tipped by a row of electrical contacts designed to non-destructively deliver mild electric pulses to a specific location. The leads are connected to a compact, battery-operated pulse generator in a fashion similar to a heart pacemaker. Electrical brain stimulation is intended to rebalance neural circuits, influencing a symphony of nerve firing and neurotransmitter release, and offers the advantage of being programmable and reversible.

With collaborators at Pennington Metabolic Center in Baton Rouge, LA, Oh and colleagues arranged for the patients to undergo detailed metabolic studies over the course of three days. Based on results of individually testing stimulation with a different electrical contact on the DBS leads each day, the researchers chose a stimulation regime that showed the greatest effect in raising resting metabolic rate. The rate was measured while the patients rested comfortably in an enclosed metabolic chamber where their respiration (consumption of oxygen and release of carbon dioxide) and related factors were analyzed.

Patients were encouraged but not required to lie down during testing, and were also allowed to read, surf the Internet, or watch television. Infrared sensors and videotape footage let researchers track activity. During periods of relative inactivity, the rate of energy expended (or calories "burned") was captured. A baseline score was measured when the device was turned off, with multiple "off" readings averaged over the time in the chamber and then repeated with the stimulation "on." Rates of change were considered indeterminate if a patient's spontaneous movement made it difficult to tell if it was caused by stimulation or motion.

In addition, the patients' lipid profiles and psychological factors were screened. No negative effects on psychological or cognitive function were found.

After nine months, one patient who had experienced a 9 percent increase in resting metabolic rate reduced his weight by 16.4 percent. Another patient, whose metabolic chamber metabolic rate change was indeterminate due to motion during the selected stimulation approach, lost 12.3 percent of her weight after 11 months at the optimal setting. The final patient had a 0.9 percent decrease after 16 months at optimal settings, but also commented that this was the first time in her life that she did not have to fight constant hunger, and her binge eating score reduced from severe to within normal range.

The metabolic studies proved useful to guide optimal settings, Oh said. The team believes expanded research studies might show that optimal settings would reduce appetite and food cravings, as well. With the existing patients, the team will continue to monitor effects of hypothalamic deep brain stimulation and examine persistence of the impact on metabolic rate. In order for survival during lean times, humans have evolved to automatically lower metabolic rate when food intake goes down -- an innate "set point" that can add challenge to weight-loss efforts. This work by Oh and colleagues suggests that the "set point" can be adjusted like a thermostat.