Granger causality reveals a dominant role of memory circuit in chronic opioid dependence.

Resting-state magnetic resonance imaging has uncovered abnormal functional connectivity in heroin-dependent individuals (HDIs). However, it remains unclear how brain regions implicated in addictions are related in baseline state without conditioned cues in heroin dependent individuals during opioid maintenance treatment (HDIs-OMT). Previous connectivity analysis assessed the strength of correlated activity between brain regions but lacked the ability to infer directional neural interactions. In the current study, we employed Granger causality analysis to investigate directional causal influences among the brain circuits in HDIs-OMT and non-opioid users. The results revealed a weaker effective connectivity between the caudate nucleus implicated in mediating the reward circuit and other brain regions and also a weaker connectivity between the anterior cingulate cortex and medial prefrontal cortex implicated in mediating inhibitory control. Conversely, HDIs-OMT exhibited stronger effective connectivity between the hippocampus and amygdala implicated in mediating learning-memory, and the anterior cingulate cortex involved in mediating inhibitory control while the putamen mediated learned habits, suggesting that the hippocampus and amygdala may propel the memory circuit to override the control circuit and drive the learned habit in HDIs-OMT. Alterations in learning-memory and inhibitory control may contribute jointly and form a basis for relapse risk even after a period of heroin abstinence. Sustained neural effect of opioid dependence on methadone maintenance including hyperactivation in the memory circuit and impairment in the control circuit support the role of the memory circuitry in relapse and may help redefine targets for treatment.

The neurobiological drive for overeating implicated in Prader-Willi syndrome.

Prader-Willi syndrome (PWS) is a genetic imprinting disorder characterized mainly by hyperphagia and early childhood obesity. Previous fMRI studies examined the activation of eating-related neural circuits in PWS patients with or without exposures to food cues and found an excessive eating motivation and a reduced inhibitory control of cognitive processing of food. However, the effective connectivity between various brain areas or neural circuitry critically implicated in both the biological and behavioral control of overeating in PWS is largely unexplored. The current study combined resting-state fMRI and Granger causality analysis (GCA) techniques to investigate interactive causal influences among key neural pathways underlying overeating in PWS. We first defined the regions of interest (ROIs) that demonstrated significant alterations of the baseline brain activity levels in children with PWS (n = 21) as compared to that of their normal siblings controls (n = 18), and then carried out GCA to characterize the region-to-region interactions among these ROIs. Our data revealed significantly enhanced causal influences from the amygdala to the hypothalamus and from both the medial prefrontal cortex and anterior cingulate cortex to the amygdala in patients with PWS (P < 0.001). These alterations offer new explanations for hypothalamic regulation of homeostatic energy intake and impairment in inhibitory control circuit. The deficits in these dual aspects may jointly contribute to the extreme hyperphagia in PWS. This study provides both a new methodological and a neurobiological perspective to aid in a better understanding of neural mechanisms underlying obesity in the general public. This article is part of a Special Issue entitled 1618.

Obesity: pathophysiology and intervention.

Obesity presents a major health hazard of the 21st century. It promotes co-morbid diseases such as heart disease, type 2 diabetes, obstructive sleep apnea, certain types of cancer, and osteoarthritis. Excessive energy intake, physical inactivity, and genetic susceptibility are main causal factors for obesity, while gene mutations, endocrine disorders, medication, or psychiatric illnesses may be underlying causes in some cases. The development and maintenance of obesity may involve central pathophysiological mechanisms such as impaired brain circuit regulation and neuroendocrine hormone dysfunction. Dieting and physical exercise offer the mainstays of obesity treatment, and anti-obesity drugs may be taken in conjunction to reduce appetite or fat absorption. Bariatric surgeries may be performed in overtly obese patients to lessen stomach volume and nutrient absorption, and induce faster satiety. This review provides a summary of literature on the pathophysiological studies of obesity and discusses relevant therapeutic strategies for managing obesity.