Deep brain stimulation for obesity: past, present, and future targets

Dupré, Derrick A.; Tomycz, Nestor D.; Oh, Michael; Whiting, Donald

doi:10.3171/2015.3.focus1542

Cited by 18 publications

(11 citation statements)

References 103 publications

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“…23,24,27,83,112 Neuroscience researchers have employed different techniques to reveal the minutiae of the functions of the hypothalamus, ranging from the tracing of fiber pathways to advanced molecular analysis. 48,50,99 The hypothalamus mainly exerts an integrative role; that is, it receives a range of afferent inputs and effectuates autonomic, endocrine, and behavioral responses to achieve homeostasis through allostasis.…”

Section: Implications For the Futurementioning

confidence: 99%

“…66 A larger follow-up report focusing on efficacy and metabolic results is expected. 24 Furthermore, sudden unexpected behavioral changes during implantation of DBS electrodes in the hypothalamus were reported in the literature (Table 3) This fortuitously evoked response paved the way for the rebirth of hypothalamic surgery for the treatment of aggressive behavior in mentally retarded patients. 27 Other effects of hypothalamic DBS may also provide insights to tackle other psychiatric symptoms.…”

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confidence: 96%

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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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Section: Implications For the Futurementioning

confidence: 99%

mentioning

confidence: 96%

The hypothalamus at the crossroads of psychopathology and neurosurgery

Barbosa

Oliveira‐Souza

Santo

et al. 2017

Neurosurgical Focus

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“…The nucleus accumbens (NAcc) has received much attention as a key target structure of the reward system in the treatment of obesity [ 19 – 21 ]. Therefore, NAcc-DBS could modulate the reward processes related to food intake and lead to weight reduction [ 7 , 20 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

Stimulating the nucleus accumbens in obesity: A positron emission tomography study after deep brain stimulation in a rodent model

et al. 2018

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PurposeThe nucleus accumbens (NAcc) has been suggested as a possible target for deep brain stimulation (DBS) in the treatment of obesity. Our hypothesis was that NAcc-DBS would modulate brain regions related to reward and food intake regulation, consequently reducing the food intake and, finally, the weight gain. Therefore, we examined changes in brain glucose metabolism, weight gain and food intake after NAcc-DBS in a rat model of obesity.ProceduresElectrodes were bilaterally implanted in 2 groups of obese Zucker rats targeting the NAcc. One group received stimulation one hour daily during 15 days, while the other remained as control. Weight and daily consumption of food and water were everyday registered the days of stimulation, and twice per week during the following month. Positron emission tomography (PET) studies with 2-deoxy-2-[18F]fluoro-D-glucose (FDG) were performed 1 day after the end of DBS. PET data was assessed by statistical parametric mapping (SPM12) software and region of interest (ROI) analyses.ResultsNAcc-DBS lead to increased metabolism in the cingulate-retrosplenial-parietal association cortices, and decreased metabolism in the NAcc, thalamic and pretectal nuclei. Furthermore, ROIs analyses confirmed these results by showing a significant striatal and thalamic hypometabolism, and a cortical hypermetabolic region. However, NAcc-DBS did not induce a decrease in either weight gain or food intake.ConclusionsNAcc-DBS led to changes in the metabolism of regions associated with cognitive and reward systems, whose impairment has been described in obesity.

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“…195 Interesting regional targets of the brain encompass the LHA, ventromedial hypothalamus (VMH) and the core and shell of the nucleus accumbens (NAc). 196 Recently, a study investigated the effects of bilateral DBS in the LHA in 3 morbidly obese patients. The authors did neither report any serious side effects nor effects on body weight gain with the DBS settings used for movement disorders.…”

Section: Surgical Treatment: Deep Brain Stimulationmentioning

confidence: 99%

“…204 Based on these studies, it is known that electrical stimulation of the NAc is safe and feasible in humans. 196 Direct stimulation of the NAc shell results in a modulation (either stimulation or inhibition) of food intake, 205,206 an effect likely involving GLP-1 signaling. 207,208 Treatment of the NAc shell and core with exendin-4 reduced food intake, especially of highly palatable food.…”

mentioning

confidence: 99%

Control of Food Intake by Gastrointestinal Peptides: Mechanisms of Action and Possible Modulation in the Treatment of Obesity

Prinz

Stengel

2017

J Neurogastroenterol Motil

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This review focuses on the control of appetite by food intake-regulatory peptides secreted from the gastrointestinal tract, namely cholecystokinin, glucagon-like peptide 1, peptide YY, ghrelin, and the recently discovered nesfatin-1 via the gut-brain axis. Additionally, we describe the impact of external factors such as intake of different nutrients or stress on the secretion of gastrointestinal peptides. Finally, we highlight possible conservative--physical activity and pharmacotherapy--treatment strategies for obesity as well as surgical techniques such as deep brain stimulation and bariatric surgery also altering these peptidergic pathways.

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Deep brain stimulation for obesity: past, present, and future targets

Cited by 18 publications

References 103 publications

The hypothalamus at the crossroads of psychopathology and neurosurgery

The hypothalamus at the crossroads of psychopathology and neurosurgery

Stimulating the nucleus accumbens in obesity: A positron emission tomography study after deep brain stimulation in a rodent model

Control of Food Intake by Gastrointestinal Peptides: Mechanisms of Action and Possible Modulation in the Treatment of Obesity

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