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

Laćan, Goran; Salles, Antonio A. F. De; Gorgulho, Alessandra; Krahl, Scott E.; Frighetto, Leonardo; Behnke, Eric; Melega, William P.

doi:10.3171/jns/2008/108/2/0336

Cited by 51 publications

(52 citation statements)

References 53 publications

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“…17,18 Several authors have showed modulation in BW in rats following lesion of lateral structures in the hypothalamus or ES in VMH. 19 --22 But the results in monkeys are limited and far from definite, 23 and only conflict reports have been published 24 in the sixties. The contradictory reports in monkeys possibly have a methodological reason.…”

Section: Bw and Bf Modulationmentioning

confidence: 99%

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Body fat and body weight reduction following hypothalamic deep brain stimulation in monkeys: an intraventricular approach

et al. 2012

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OBJECTIVE:The authors proposed an intraventricular 'floating' electrode inserted in the third ventricle (V3) adjacent to the ventromedian hypothalamus (VMH) in a freely moving Macaca fascicularis to modulate food intake (FI), body fat (BF), body weight (BW) and body mass index (BMI), as a potential treatment of obesity. METHODS: Five adult Macaca fascicularis monkeys were implanted stereotactically in the V3 contiguous to the VMH with one deep brain stimulation (DBS) electrode. The study was divided in two phases: (a) acute 24 h-fasting trials: different electrical stimulation parameters were applied to a fasting primate to determine the best combination in reducing FI; and (b) chronic 8-week stimulation trials: three cycles of intraventricular-VMH DBS lasting 8 --10 weeks were performed at 130 Hz, 80 Hz (most effective frequency reducing FI) and 30 Hz, respectively. BMI, BW, BF content, skinfolds and hormones were measured during baseline and at the end of each session of stimulation. RESULTS: Acute 24 h-fasting trials: there was a decrease in FI in all subjects at 80 Hz, (11 --19%, mean 15%). Chronic 8-week stimulation trials: a significant decrease in BW and BMI was observed in three out of four monkeys at 80 Hz (mean 8 ± 4.4%). Subcutaneous skinfolds were reduced in all four subjects at 80 Hz and slightly increased at 130 Hz. The sham monkey remained stable. No significant adverse effects were recorded. CONCLUSION: The stimulation of the VMH region through an intraventricular approach might acutely modulate FI and induce a sustained decrease in BW and fat mass in normal non-human primate. INTRODUCTIONObesity is a complex disorder that has reached epidemic proportions globally, with more than 1 billion adults overweight, according to WHO. It is associated with diminished quality of life 1 and reduces life expectancy. 2 Treatment includes non-pharmacological measures, drugs and surgical therapy. The use of pharmacological agents has demonstrated only discreet body weight (BW) reduction in controlled trials. For the surgery, some patients with morbid obesity still remain poor candidates for standard gastric bypass: complications occur in 15 --55% of bariatric patients, and the peri-surgical mortality rate is about 1.5% even in experienced centers. 3 Safer procedures, such as laparoscopic adjustable banded gastroplasty, are simpler but are not as effective. 4,5 Large room for effective and safer procedures still exists.Recently, modulation of brain circuits has emerged as a valuable clinical and research strategy in obesity. With the development of new hardware and electrophysiological techniques, deep brain stimulation (DBS) have been used for treating movement disorder, 6 pain, 7 obsessive compulsive disorders 8 --10 and clinical refractory epilepsy. 11,12 A recent report on the hypothalamic DBS applied in cases of chronic intractable cluster headaches 13 has revived the interest in the hypothalamic region, which is also wellknown to be involved in food intake (FI) and energy balance regulation. DBS is a reve...

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Section: Bw and Bf Modulationmentioning

confidence: 99%

“…Very short protocols 23 produced modulation in FI but failed to show BW loss. The present work used longer periods of stimulation, between 8 and 10 weeks with washout of 4 weeks.…”

Section: Bw and Bf Modulationmentioning

confidence: 99%

Body fat and body weight reduction following hypothalamic deep brain stimulation in monkeys: an intraventricular approach

et al. 2012

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“…33 These reports support the VMH as a region tightly related to sexual behavior, and this was confirmed by the observation of sexual behaviors in modern experimental primate work. 45 …”

Section: The Hypothalamus As a Stereotactic Target Lessons From The Pmentioning

confidence: 99%

“…58,59 High-frequency stimulation of this zone leads to sexual arousal. 45 The posterior hypothalamus includes the posterior nucleus, the tuberomamillary nucleus, and the mammil- Sagittal T1-weighted MR image demonstrating the Fx as it dives into the hypothalamus (arrow), dividing it into medial and lateral regions, and ultimately reaching the Mb. Stimulation of electrodes in this location elicits a host of symptoms, such as sensation of heat, anxiety, tachycardia, blood pressure increase, recollections of autobiographic memories, and diaphoresis, which are related to the location of the contact stimulated from rostral to cranial, as well as to the parameters of stimulation.…”

Section: The Nuclear Zonementioning

confidence: 99%

The hypothalamus at the crossroads of psychopathology and neurosurgery

Barbosa

Oliveira‐Souza

Santo

et al. 2017

Neurosurgical Focus

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The neurosurgical endeavor to treat psychiatric patients may have been part of human history since its beginning. The modern era of psychosurgery can be traced to the heroic attempts of Gottlieb Burckhardt and Egas Moniz to alleviate mental symptoms through the ablation of restricted areas of the frontal lobes in patients with disabling psychiatric illnesses. Thanks to the adaptation of the stereotactic frame to human patients, the ablation of large volumes of brain tissue has been practically abandoned in favor of controlled interventions with discrete targets.Consonant with the role of the hypothalamus in the mediation of the most fundamental approach-avoidance behaviors, some hypothalamic nuclei and regions, in particular, have been selected as targets for the treatment of aggressiveness (posterior hypothalamus), pathological obesity (lateral or ventromedial nuclei), sexual deviations (ventromedial nucleus), and drug dependence (ventromedial nucleus). Some recent improvements in outcomes may have been due to the use of stereotactically guided deep brain stimulation and the change of therapeutic focus from categorical diagnoses (such as schizophrenia) to dimensional symptoms (such as aggressiveness), which are nonspecific in terms of formal diagnosis. However, agreement has never been reached on 2 related issues: 1) the choice of target, based on individual diagnoses; and 2) reliable prediction of outcomes related to individual targets. Despite the lingering controversies on such critical aspects, the experience of the past decades should pave the way for advances in the field. The current failure of pharmacological treatments in a considerable proportion of patients with chronic disabling mental disorders is reminiscent of the state of affairs that prevailed in the years before the early psychosurgical attempts.This article reviews the functional organization of the hypothalamus, the effects of ablation and stimulation of discrete hypothalamic regions, and the stereotactic targets that have most often been used in the treatment of psychopathological and behavioral symptoms; finally, the implications of current and past experience are presented from the perspective of how this fund of knowledge may usefully contribute to the future of hypothalamic psychosurgery.

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“…90 In a similar fashion, lesions to the VMH have led to weight gain, increased adipose tissue, and hyperinsulinemia in animal models, with similar effects observed with high-frequency DBS in both murine and primate models. 5,46 Low-frequency stimulation of this focus appeared to inhibit feeding behavior and increase weight loss in a wide variety of animal models, including in a recent study in primates in which Torres and colleagues proposed an intraventricular "floating" electrode inserted in the third ventricle contiguous to the VMH. Stimulation delivered to the VMH has been shown to evoke emotional panic attack-like behavior with autonomic disturbances in both animals and humans, which may preclude its suitability as a human DBS target for obesity.…”

Section: Deep Brain Stimulation Targets For Obesitymentioning

confidence: 99%

Deep brain stimulation for obesity: rationale and approach to trial design

Ho¹,

Sussman²,

Pendharkar³

et al. 2015

FOC

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Obesity is one of the most serious public health concerns in the US. While bariatric surgery has been shown to be successful for treatment of morbid obesity for those who have undergone unsuccessful behavioral modification, its associated risks and rates of relapse are not insignificant. There exists a neurological basis for the binge-like feeding behavior observed in morbid obesity that is believed to be due to dysregulation of the reward circuitry. The authors present a review of the evidence of the neuroanatomical basis for obesity, the potential neural targets for deep brain stimulation (DBS), as well as a rationale for DBS and future trial design. Identification of an appropriate patient population that would most likely benefit from this type of therapy is essential. There are also significant cost and ethical considerations for such a neuromodulatory intervention designed to alter maladaptive behavior. Finally, the authors present a consolidated set of inclusion criteria and study end points that should serve as the basis for any trial of DBS for obesity.

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

Cited by 51 publications

References 53 publications

Body fat and body weight reduction following hypothalamic deep brain stimulation in monkeys: an intraventricular approach

Body fat and body weight reduction following hypothalamic deep brain stimulation in monkeys: an intraventricular approach

The hypothalamus at the crossroads of psychopathology and neurosurgery

Deep brain stimulation for obesity: rationale and approach to trial design

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