Modulation of food intake following deep brain stimulation of the ventromedial hypothalamus in the vervet monkey. Laboratory investigation.
OBJECTIVE
Deep brain stimulation (DBS) has become an effective therapy for an increasing number of brain disorders. Recently demonstrated DBS of the posterior hypothalamus as a safe treatment for chronic intractable cluster headaches has drawn attention to this target, which is involved in the regulation of diverse autonomic functions and feeding behavior through complex integrative mechanisms. In this study, the authors assessed the feasibility of ventromedial hypothalamus (VMH) DBS in freely moving vervet monkeys to modulate food intake as a model for the potential treatment of eating disorders.


METHODS
Deep brain stimulation electrodes were bilaterally implanted into the VMH of 2 adult male vervet monkeys by using the stereotactic techniques utilized in DBS in humans. Stimulators were implanted subcutaneously on the upper back, allowing ready access to program stimulation parameters while the animal remained conscious and freely moving. In anesthetized animals, intraoperatively and 6-10 weeks postsurgery, VMH DBS parameters were selected according to minimal cardiovascular and autonomic nervous system responses. Thereafter, conscious animals were subjected to 2 cycles of VMH DBS for periods of 8 and 3 days, and food intake and behavior were monitored. Animals were then killed for histological verification of probe placement.


RESULTS
During VMH DBS, total food consumption increased. The 3-month bilateral implant of electrodes and subsequent periods of high-frequency VMH stimulation did not result in significant adverse behavioral effects.


CONCLUSIONS
This is the first study in which techniques of hypothalamic DBS in humans have been applied in freely moving nonhuman primates. Future studies can now be conducted to determine whether VMH DBS can change hypothalamic responsivity to endocrine signals associated with adiposity for long-term modulation of food intake.
Laćan
Goran
G
Division of Neurosurgery, Department of Surgery, David Geffen School of Medicine at UCLA, 3 VA Greater Los Angeles Healthcare System, Los Angeles, California 90095, USA.
De Salles
Antonio A F
AA
Gorgulho
Alessandra A
AA
Krahl
Scott E
SE
Frighetto
Leonardo
L
Behnke
Eric J
EJ
Melega
William P
WP
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002522:Chlorocebus aethiops; D046690:Deep Brain Stimulation / Q000295:instrumentation / Q000379:methods*; D004435:Eating / Q000502:physiology*; D004567:Electrodes, Implanted; D005240:Feasibility Studies; D005247:Feeding Behavior / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006339:Heart Rate / Q000502:physiology; D007033:Hypothalamus, Middle / Q000502:physiology*; D008297:Male; D023421:Models, Animal; D013238:Stereotaxic Techniques; D014697:Ventromedial Hypothalamic Nucleus / Q000502:physiology
D005904:Glial Fibrillary Acidic Protein