The brain – gut interaction: defining the role of the nutrient-induced human brain activation matrix

Due to the high prevalence of obesity in America (around 35%) and in Europe (above 20%) and its dramatic consequences on human health, research aiming to understand the basic mechanisms that regulate food intake, appetite and body weight is therefore needed. New evidences suggest that fuel sensing occurs in a number of peripheral cell types, which include specific taste receptors in the gut. These receptors produce a chemical cascade signaling the central nervous system (CNS) for energy balance regulation. At the same time in the CNS specific brain regions directly sense fuel status. An emerging new methodology investigates neural correlates of appetite and satiety, using functional neuroimaging techniques. In the present work we aim at investigating the brain-gut matrix. First, through a systematic review of the literature, previous studies assessing the effects of nutrients on brain functions were examined to identify a common research methodology and related results. Afterwards we extensively study the effects of sugars and amino acids on the food-reward system, focusing on brain resting state functional connectivity. Finally, we focus on glucose and fructose effects on cognitive functions, by investigating two of the most common dimensions of cognitive functions such as working memory and response inhibition

Comparative Effects of Methylphenidate, Modafinil, and MDMA on Response Inhibition Neural Networks in Healthy Subjects

Psychostimulants such as methylphenidate and modafinil are increasingly used by healthy people for cognitive enhancement purposes, whereas the acute effect of 3,4-methylenedioxymethamphetamine (ecstasy) on cognitive functioning in healthy subjects remains unclear. This study directly compared the acute effects of methylphenidate, modafinil, and 3,4-methylenedioxymethamphetamine on the neural mechanisms underlying response inhibition in healthy subjects.; Using a double-blind, within-subject, placebo-controlled, cross-over design, methylphenidate, modafinil, and 3,4-methylenedioxymethamphetamine were administrated to 21 healthy subjects while performing a go/no-go event-related functional magnetic resonance imaging task to assess brain activation during motor response inhibition.; Relative to placebo, methylphenidate and modafinil but not 3,4-methylenedioxymethamphetamine improved inhibitory performance. Methylphenidate significantly increased activation in the right middle frontal gyrus, middle/superior temporal gyrus, inferior parietal lobule, presupplementary motor area, and anterior cingulate cortex compared with placebo. Methylphenidate also induced significantly higher activation in the anterior cingulate cortex and presupplementary motor area and relative to modafinil. Relative to placebo, modafinil significantly increased activation in the right middle frontal gyrus and superior/inferior parietal lobule, while 3,4-methylenedioxymethamphetamine significantly increased activation in the right middle/inferior frontal gyrus and superior parietal lobule.; Direct comparison of methylphenidate, modafinil, and 3,4-methylenedioxymethamphetamine revealed broad recruitment of fronto-parietal regions but specific effects of methylphenidate on middle/superior temporal gyrus, anterior cingulate cortex, and presupplementary motor area activation, suggesting dissociable modulations of response inhibition networks and potentially the superiority of methylphenidate in the enhancement of cognitive performance in healthy subjects

Administering analgesia sublingually is a suitable option for children with acute abdominal pain in the emergency department

AIM: Acute abdominal pain is a frequent complaint in children attending emergency departments. The aim of this study was to investigate the pain score reductions when children with acute abdominal pain received medication sublingually. METHODS: We carried out a multicentre randomised controlled trial in three children's hospitals in Italy between March 2015 and June 2017. Children from four to 18 years of age with acute abdominal pain were recruited if their self-reported pain was at least six on a scale from 0-10. The children were randomised to receive ketorolac 0.5 mg/kg (n = 70) or tramadol 2 mg/kg (n = 70) sublingually or a melt in the mouth powder of 20 mg/kg paracetamol (n = 70). The main study outcome was the pain scores for the three drugs after two hours. RESULTS: The 210 children (58.6% girls) had a median age of 12 years with an interquartile range of 9-14.3. The median pain scores at two hours were not significantly different between ketorolac 2.0 (interquartile ranges, IQR 0.0-4.3) and tramadol 3.0 (IQR 1.0-5.0) vs paracetamol 3.0 (IQR 0.8-5.0). The median pain reductions were all 5.0 points. CONCLUSION: Delivering analgesia sublingually was a suitable option for pain relief in children with acute abdominal pain in the emergency department

Acute Effects of Methylphenidate, Modafinil, and MDMA on Negative Emotion Processing

Stimulants such as methylphenidate and modafinil are frequently used as cognitive enhancers in healthy people, whereas 3,4-methylenedioxymethamphetamine (ecstasy) is proposed to enhance mood and empathy in healthy subjects. However, comparative data on the effects of methylphenidate and modafinil on negative emotions in healthy subjects have been partially missing. The aim of this study was to compare the acute effects of methylphenidate and modafinil on the neural correlates of fearful face processing using 3,4-methylenedioxymethamphetamine as a positive control.; Using a double-blind, within-subject, placebo-controlled, cross-over design, 60 mg methylphenidate, 600 mg modafinil, and 125 mg 3,4-methylenedioxymethamphetamine were administrated to 22 healthy subjects while performing an event-related fMRI task to assess brain activation in response to fearful faces. Negative mood states were assessed with the State-Trait Anxiety Inventory and subjective ratings.; Relative to placebo, modafinil, but not methylphenidate or 3,4-methylenedioxymethamphetamine, increased brain activation within a limbic-cortical-striatal-pallidal-thalamic circuit during fearful face processing. Modafinil but not methylphenidate also increased amygdala responses to fearful faces compared with 3,4-methylenedioxymethamphetamine. Furthermore, activation in the middle and inferior frontal gyrus in response to fearful faces correlated positively with subjective feelings of fearfulness and depressiveness after modafinil administration.; Despite the cognitive enhancement effects of 600 mg modafinil in healthy people, potential adverse effects on emotion processing should be considered

Long-Term Nicotine Abstinence: Craving Regulation and Functional Connectivity Changes in Ex-Smokers

Background Although about one third of smokers tried to quit smoking within the last 12 months, only 3-5% remain abstinent at 6 months. This indicates the presence of long-term modifications in brain networks related to smoking. Using functional magnetic resonance imaging (fMRI), we compared ex-smokers to active and non-smokers to explore these modifications. Methods 18 non-smokers (29.51 ± 6.70 years, 11 females) 14 smokers (≥10 cigarettes a day > 2 years, 29.31 ± 6.04 years, 10 females) and 14 ex-smokers (>1 year of quitting 30.5 ± 5.70 years, 10 females) were recruited through local and Internet advertising. A block-design fMRI study was performed contrasting smoking cue videos versus control videos. Data analyses include task-related general linear model (GLM), seed based functional connectivity, voxel-based morphometry (VBM) of grey matter and tract based spatial statistics (TBSS) of white matter. Results Smoking cue videos versus control videos activated notably the right anterior insula for the contrast ex-smokers versus smokers, an effect correlating with the accumulated dose of nicotine. In addition, ex-smokers, compared to controls and similarly to smokers, showed a persistent decrease in the functional connectivity between anterior insula and anterior cingulate cortex (ACC)..