Major contributions to the understanding of human brain function have come from detailed clinical reports of responses evoked by electrical stimulation and specific brain regions during neurosurgical procedures in awake humans. In this study, microstimulation evoked responses and extracellular unit recordings were obtained intraoperatively in 3 awake patients undergoing bilateral implantation of deep brain stimulation electrodes in the lateral hypothalamus. The microstimulation evoked responses exhibited a clear anatomical distribution. Anxiety was most reliably evoked by stimulation directed ventromedially within or adjacent to the ventromedial nucleus of the hypothalamus, nausea was most reliably evoked by stimulation directed at the center of the lateral hypothalamus, and paresthesias were most reliably evoked by stimulation at the border of the lateral hypothalamus and basal nuclei. Regarding the unit recordings, the firing rates of individual neurons did not have an anatomical distribution, but a small subpopulation of neurons located at the border of the lateral hypothalamus and basal nuclei exhibited a fast rhythmically bursting behavior with an intraburst frequency of 200–400 Hz and an interburst frequency of 10–20 Hz. Based on animal studies, the lateral hypothalamic area and surrounding hypothalamic nuclei are putatively involved with a variety of physiological, behavioral, and sensory functions. The lateral hypothalamus is situated to play a dynamic and complex role in human behavior and this report further shows that to be true. In addition, this report should serve as a valuable resource for future intracranial work in which accurate targeting within this region is required.
W. Bryan Wilent, Michael Y. Oh, Catherine Buetefisch, Julian E. Bailes, Diane Cantella, Cindy Angle and Donald M. Whiting
W. Bryan Wilent, Michael Y. Oh, Cathrin M. Buetefisch, Julian E. Bailes, Diane Cantella, Cindy Angle and Donald M. Whiting
Panic attacks are sudden debilitating attacks of intense distress often accompanied by physical symptoms such as shortness of breath and heart palpitations. Numerous brain regions, hormones, and neurotransmitter systems are putatively involved, but the etiology and neurocircuitry of panic attacks is far from established. One particular brain region of interest is the ventromedial hypothalamus (VMH). In cats and rats, electrical stimulation delivered to the VMH has been shown to evoke an emotional “panic attack–like” escape behavior, and in humans, stimulation targeting nuclei just posterior or anterior to the VMH has reportedly induced panic attacks. The authors report findings obtained in an awake patient undergoing bilateral implantation of deep brain stimulation electrodes into the hypothalamus that strongly implicates the VMH as being critically involved in the genesis of panic attacks. First, as the stimulating electrode progressed deeper into the VMH, the intensity of stimulation required to evoke an attack systematically decreased; second, while stimulation of the VMH in either hemisphere evoked panic, stimulation that appeared to be in the center of the VMH was more potent. Thus, this evidence supports the role of the VMH in the induction of panic attacks purported by animal studies.
Donald M. Whiting, Nestor D. Tomycz, Julian Bailes, Lilian de Jonge, Virgile Lecoultre, Bryan Wilent, Dunbar Alcindor, E. Richard Prostko, Boyle C. Cheng, Cynthia Angle, Diane Cantella, Benjamin B. Whiting, J. Scott Mizes, Kirk W. Finnis, Eric Ravussin and Michael Y. Oh
Deep brain stimulation (DBS) of the lateral hypothalamic area (LHA) has been suggested as a potential treatment for intractable obesity. The authors present the 2-year safety results as well as early efficacy and metabolic effects in 3 patients undergoing bilateral LHA DBS in the first study of this approach in humans.
Three patients meeting strict criteria for intractable obesity, including failed bariatric surgery, underwent bilateral implantation of LHA DBS electrodes as part of an institutional review board– and FDA-approved pilot study. The primary focus of the study was safety; however, the authors also received approval to collect data on early efficacy including weight change and energy metabolism.
No serious adverse effects, including detrimental psychological consequences, were observed with continuous LHA DBS after a mean follow-up of 35 months (range 30–39 months). Three-dimensional nonlinear transformation of postoperative imaging superimposed onto brain atlas anatomy was used to confirm and study DBS contact proximity to the LHA. No significant weight loss trends were seen when DBS was programmed using standard settings derived from movement disorder DBS surgery. However, promising weight loss trends have been observed when monopolar DBS stimulation has been applied via specific contacts found to increase the resting metabolic rate measured in a respiratory chamber.
Deep brain stimulation of the LHA may be applied safely to humans with intractable obesity. Early evidence for some weight loss under metabolically optimized settings provides the first “proof of principle” for this novel antiobesity strategy. A larger follow-up study focused on efficacy along with a more rigorous metabolic analysis is planned to further explore the benefits and therapeutic mechanism behind this investigational therapy.