Modulation of food intake following deep brain stimulation of the ventromedial hypothalamus in the vervet monkey

Laboratory investigation

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Object

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.

Abbreviations used in this paper:ANS = autonomic nervous system; CRW = Cosman-Roberts-Wells; DBS = deep brain stimulation; GFAP = glial fibrillary acidic protein; IPG = internal pulse generator; MR = magnetic resonance; OD = outer diameter; PBS = phosphate-buffered saline; PD = Parkinson disease; STN = subthalamic nucleus; VMH = ventromedial hypothalamus.

Article Information

Address correspondence to: Antonio A. F. De Salles, M.D., Ph.D., 200 UCLA Medical Plaza, Suite 504, Los Angeles, California 90095. email: adesalles@mednet.ucla.edu.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    Images of brain sections showing the localization of VMH targets in the vervet monkey. Upper left: Ventro-medial hypothalamus targets (arrows) as viewed in a coronal section of a cryosectioned vervet brain. Upper right: Guide cannula tracks (arrows) in the precommissural brain block. Lower left: Nissl-stained coronal brain section showing the electrode placement in the left VMH of Vervet 9473 (arrow). Lower right: Coronal brain section stained for GFAP immunoreactivity, showing the electrode placement in the right VMH of Vervet 9473 (arrow). Bar = 5 mm.

  • View in gallery

    Bar graphs showing feeding results for the 2 vervet monkeys. Upper: Total biscuit consumption during DBS cycles. Lower: Biscuit consumption per day for the matching 11 days of DBS-off and DBS-on cycles. *p < 0.05. d = day; off = stimulation off; on = stimulation on; SEM = standard error of the mean.

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