Stimulating the Brain to Increase Weight Gain-and Loss

Two recent studies are showing how stimulating the brain may help patients with anorexia nervosa (AN) gain weight and, in an animal study, halt binge-eating and obesity.

A Brain ‘pacemaker’ for patients with AN

Deep brain stimulation (DBS) with a neurosurgical implant has produced positive results in a small group of patients with treatment-refractory anorexia nervosa (AN) (Lancet, March 7, 2013 [e-pub before publication]). DBS has been used successfully for patients with neurologic disorders such as chronic pain and Parkinson’s disease, and this is one of the few times the technology has been applied to patients with severe AN.

Drs. Nir Lipsman, Andres M. Lozano, a neurosurgeon at the Krembil Neuroscience Centre, and Blake Woodside, medical director of Canada’s largest eating disorders program at Toronto General Hospitals and the University of Toronto, collaborated on the phase I clinical trial. The 6 patients enrolled in their study had a mean age of 38 years and a mean duration of AN for 18 years. In addition to AN, all the patients had comorbidities such as major depressive disorder and obsessive-compulsive disease. The 6 patients also had long histories of hospitalizations for their illnesses (50 hospitalizations among the group), and all were at high risk due to the severity of their disorder and comorbidities.

Electrodes were implanted into the subcallosal cingulate gyrus, next to the corpus callosum, a thick bundle of nerve fibers that divides the left and right hemispheres of the brain. The corpus callosum transfers motor, sensory, and cognitive information between the brain hemispheres, and has been linked to human emotions. Once implanted, the electrodes were connected to an implanted pulse generator, very similar to a heart pacemaker, placed below the right clavicle.

After the pulse generator was implanted, patients were tested at 1-, 3-, and 6-month intervals. Nine months after the device was implanted, 3 of the 6 patients had gained weight, defined as reaching their highest-ever body mass index (BMI, or kg/m2). For these 3 patients, this was the longest period of sustained weight gain since their illness began. Four of the 6 patients experienced simultaneous changes in mood and anxiety levels. They also gained better control over their emotional responses; researchers reported lessening of urges to binge eat and purge and other AN-linked symptoms. For the first time in their illness, two patients were able to complete treatment in an inpatient eating disorders program.

Only a few adverse effects were reported

The devices also were associated with several adverse effects, including a seizure in one patient during programming of the device; this occurred about 2 weeks after surgery. Other related events were a panic attack during the implantation surgery, nausea, air embolus, and pain.
Drs. Woodside and Lozano and colleagues are planning a second trial that will determine the long-term effects of DBS in a larger number of AN patients.

Binge-eating in obese mice is halted by DBS

DBS to a precise region of the brain has reduced caloric intake and increased weight loss in obese mice, according to Dr. Casey Halpern and researchers at the University of Pennsylvania (J Neurosci. 2013; 118:487). DBS is currently used to reduce tremors in patients with Parkinson’s disease and is being investigated as a therapy for major depression and obsessive-compulsive disorder.  The NIH-funded study reinforced the theory that dopamine deficits are involved in increasing activities that result in obesity, such as binge-eating.

Noting that nearly half of obese persons binge-eat, the researchers targeted the nucleus accumbens, a small structure in the brain that is associated with pleasure, motivation, and addiction. Its activity is dependent on two neurotransmitters, dopamine and serotonin.
Mice that received DBS ate significantly less of a high-fat food compared to mice that did not have DBS. Dr. Halpern and colleagues also tested the long-term effects of DBS on obese mice that had been given unlimited access to high-fat food.  During 4 days of continuous stimulations, the obese mice ate fewer calories and their body weight dropped.  These mice also showed improved glucose sensitivity. Future clinical trials will clarify whether DBS can help curb binge eating in humans as well.