Gender differences in the association between stop-signal reaction times, body mass indices and/or spontaneous food intake in pre-school children: an early model of compromised inhibitory control and obesity

Levitan, Robert D.; Rivera, Juan Carlos Aristizábal; Silveira, Patrícia Pelufo; Steiner, Meir; Gaudreau, Hélène; Hamilton, Jill; Kennedy, James L.; Davis, Caroline; Dubé, Laurette; Fellows, Lesley K.; Wazana, Ashley; Matthews, S; Meaney, Michael J.

doi:10.1038/ijo.2014.207

Cited by 54 publications

(34 citation statements)

References 25 publications

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“…the most appropriate test as per our a priori hypotheses), which can be used for future power calculations with higher doses and/or longer duration. The stop signal reaction time is a measure of inhibitory control, where a lower time indicates greater inhibitory control, which has been shown to be impaired with obesity [41]. This may indicate that with higher doses and/or more participants, liraglutide may increase inhibitory control, but this will need to be confirmed.…”

Section: Discussionmentioning

confidence: 99%

GLP-1 receptors exist in the parietal cortex, hypothalamus and medulla of human brains and the GLP-1 analogue liraglutide alters brain activity related to highly desirable food cues in individuals with diabetes: a crossover, randomised, placebo-controlled trial

et al. 2016

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Aims/hypothesis Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue that has been demonstrated to successfully treat diabetes and promote weight loss. The mechanisms by which liraglutide confers weight loss remain to be fully clarified. Thus, we investigated whether GLP-1 receptors are expressed in human brains and whether liraglutide administration affects neural responses to food cues in diabetic individuals (primary outcome). Methods In 22 consecutively studied human brains, expression of GLP-1 receptors in the hypothalamus, medulla oblongata and parietal cortex was examined using immunohistochemistry. In a randomised (assigned by the pharmacy using a randomisation enrollment table), placebo-controlled, double-blind, crossover trial, 21 individuals with type 2 diabetes (18 included in analysis due to lack or poor quality of data) were treated with placebo and liraglutide for a total of 17 days each (0.6 mg for 7 days, 1.2 mg for 7 days and 1.8 mg for 3 days). Participants were eligible if they had type 2 diabetes and were currently being treated with lifestyle changes or metformin. Participants, caregivers, people doing measurements and/or examinations, and people assessing the outcomes were blinded to the medication assignment. We studied metabolic changes as well as neurocognitive and neuroimaging (fMRI) of responses to food cues at the clinical research centre of Beth Israel Deaconess Medical Center. Results Immunohistochemical analysis revealed the presence of GLP-1 receptors on neurons in the human hypothalamus, medulla and parietal cortex. Liraglutide decreased activation of the parietal cortex in response to highly desirable (vs less desirable) food images (p < 0.001; effect size: placebo 0.53 ± 0.24, liraglutide −0.47 ± 0.18). No significant adverse effects were noted. In a secondary analysis, we observed decreased activation in the insula and putamen, areas involved in the reward system. Furthermore, we showed that increased ratings of hunger and appetite correlated with increased brain activation in response to highly desirable food cues while on liraglutide, while ratings of nausea correlated with decreased brain activation. Conclusions/interpretation For the first time, we demonstrate the presence of GLP-1 receptors in human brains. We also observe that liraglutide alters brain activity related to highly desirable food cues. Our data point to a central mechanism contributing to, or underlying, the effects of liraglutide on metabolism and weight loss. Future studies will be needed to confirm and extend these findings in larger samples of diabetic individuals and/or with the higher doses of liraglutide (3 mg) recently approved for obesity.

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Section: Discussionmentioning

confidence: 99%

GLP-1 receptors exist in the parietal cortex, hypothalamus and medulla of human brains and the GLP-1 analogue liraglutide alters brain activity related to highly desirable food cues in individuals with diabetes: a crossover, randomised, placebo-controlled trial

et al. 2016

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“…Decades of research by developmental scientists demonstrates that positive parent-child relationships support children’s development of self-regulation [18, 19]. There is evidence that children who have lower levels of self-regulation have increased risk for obesity [20–26], but this is an emerging area of research [27], and what is meant by “self-regulation” in relation to children’s risk for obesity varies across studies.…”

Section: Introductionmentioning

confidence: 99%

Parent–Child Interaction, Self-Regulation, and Obesity Prevention in Early Childhood

2016

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This paper describes the epidemiologic evidence linking parent-child relationships, self-regulation, and weight status with a focus on early childhood. The emotional quality of parent-child interactions may influence children’s risk for obesity through multiple pathways. Prospective studies linking observer ratings of young children’s self-regulation, particularly inhibitory control, to future weight status are discussed. Although findings are preliminary, promoting positive relationships between parents/caregivers and young children holds promise as a component of efforts to prevent childhood obesity. Multi-disciplinary collaborations between researchers with training in developmental science and child health should be encouraged.

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“…For instance, the stop signal task or go/no-go task is often used to measure cognitive or inhibitory control [2-4] and can be combined with fMRI to study these complex mechanisms in the brain. Previous studies have found longer stop signal reaction times (SSRTs), which represent poorer inhibitory control, to correlate with future weight gain [5]. Intensive lifestyle changes decrease SSRTs, representing improved inhibitory control, in adolescents [6].…”

Section: Techniques To Study the Cns In Clinical Researchmentioning

confidence: 99%

“…The prefrontal cortex composes much of the cognitive control network, particularly the cingulate cortex, inferior frontal cortex, pre-supplementary motor area (pre-SMA) and dorsolateral prefrontal cortex (DLPFC) [184]. Several studies have demonstrated impaired inhibitory control in obese humans and a link of impaired control to future weight gain in normal weight individuals [4, 5, 179, 185-195]. Poorer inhibitory control, even on non-food-related tasks, has been observed to correlate with high calorie food intake [5] and a resistance to losing weight [195].…”

Section: Cognitive Control Systemsmentioning

confidence: 99%

“…Several studies have demonstrated impaired inhibitory control in obese humans and a link of impaired control to future weight gain in normal weight individuals [4, 5, 179, 185-195]. Poorer inhibitory control, even on non-food-related tasks, has been observed to correlate with high calorie food intake [5] and a resistance to losing weight [195]. In normal weight participants, the use of transcranial magnetic stimulation to deactivate the DLPFC has caused decreased valuation of food cues [196], suggesting that this area makes valuations about food choices.…”

Section: Cognitive Control Systemsmentioning

confidence: 99%

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Central nervous system regulation of eating: Insights from human brain imaging

2016

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Appetite and body weight regulation are controlled by the central nervous system (CNS) in a rather complicated manner. The human brain plays a central role in integrating internal and external inputs to modulate energy homeostasis. Although homeostatic control by the hypothalamus is currently considered to be primarily responsible for controlling appetite, most of the available evidence derives from experiments in rodents, and the role of this system in regulating appetite in states of hunger/starvation and in the pathogenesis of overeating/obesity remains to be fully elucidated in humans. Further, cognitive and affective processes have been implicated in the dysregulation of eating behavior in humans, but their exact relative contributions as well as the respective underlying mechanisms remain unclear. We briefly review each of these systems here and present the current state of research in an attempt to update clinicians and clinical researchers alike on the status and future directions of obesity research.

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Gender differences in the association between stop-signal reaction times, body mass indices and/or spontaneous food intake in pre-school children: an early model of compromised inhibitory control and obesity

Cited by 54 publications

References 25 publications

GLP-1 receptors exist in the parietal cortex, hypothalamus and medulla of human brains and the GLP-1 analogue liraglutide alters brain activity related to highly desirable food cues in individuals with diabetes: a crossover, randomised, placebo-controlled trial

GLP-1 receptors exist in the parietal cortex, hypothalamus and medulla of human brains and the GLP-1 analogue liraglutide alters brain activity related to highly desirable food cues in individuals with diabetes: a crossover, randomised, placebo-controlled trial

Parent–Child Interaction, Self-Regulation, and Obesity Prevention in Early Childhood

Central nervous system regulation of eating: Insights from human brain imaging

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