Objective:The significant weight loss observed with combination naltrexone-sustained release (SR) 32 mg and bupropion SR 360 mg (NB32) therapy is thought to be due, in part, to bupropion stimulation of hypothalamic pro-opiomelanocortin (POMC) neurons, and naltrexone blockade of opioid receptor-mediated POMC autoinhibition, but the neurobiological mechanisms are not fully understood. We assessed changes in brain reactivity to food cues before and after NB32 treatment.Methods:Forty women (31.1±8.1 years; body mass index: 32.5±3.9) received 4 weeks of NB32 or placebo, and were instructed to maintain their dietary and exercise habits. Functional magnetic resonance imaging responses (analyzed using SPM2 and clusters (>100 pixels)) to a 5-min food video (preparation of the subject's favorite food) and a 5-min neutral video (manipulation of neutral objects) under conditions of mild food deprivation (∼14 h) were assessed before and after treatment.Results:The food cues video induced positive brain activation in visual and prefrontal cortices, insula and subcortical brain regions. The group-by-treatment interaction on regional brain activation was significant and showed that whereas NB32 attenuated the activation in the hypothalamus in response to food cues (P<0.01), it enhanced activation in regions involved in inhibitory control (anterior cingulate), internal awareness (superior frontal, insula, superior parietal) and memory (hippocampal) regions (whole-brain analysis; P<0.05).Conclusions:Blunting the hypothalamic reactivity to food cues while enhancing the activation of regions involved with self-control and internal awareness by NB32 might underlie its therapeutic benefits in obesity.

Phosphene sensation is commonly used to measure cortical excitability during transcranial magnetic stimulation (TMS) of the occipital cortex. However, some individuals lack this perception, and the reason for it is still unknown. In this work, we used functional magnetic resonance imaging (fMRI) to detect brain activation during local TMS of the occipital cortex in twelve healthy subjects. We found that TMS modulated brain activity in areas connected to the stimulation site, even in people unable to see phosphene. However, we observed a trend for a lower blood-oxygenation-level dependent (BOLD) signal, and smaller brain-activation clusters near the stimulated site than in the interconnected brain areas, suggesting that TMS pulse is more effective downstream than at its application site. Furthermore, we noted prominent differences in brain activation/deactivation patterns between subjects who perceived phosphene and those who did not, implying a functional distinction in their neuronal networks that might explain the origin of differences in phosphene generation.

1 Hz repetitive Transcranial Magnetic Stimulation (rTMS) is considered to have an inhibitory effect in healthy people because it suppresses the excitability of the motor or visual cortex that is expressed as an increase in the motor or the phosphene threshold (PT), respectively. However, the underlying mechanisms and the brain structures involved in the action of rTMS are still unknown. In this study we used two sessions of simultaneous TMS-functional magnetic resonance imaging (fMRI), one before and one after, 15 minutes of 1Hz rTMS to map changes in brain function associated with the reduction in cortical excitability of the primary visual cortex induced by 1 Hz rTMS, when TMS was applied on the occipital area of healthy volunteers. Two groups were evaluated, one group composed of people that can see phosphenes, and another of those lacking this perception. The inhibitory effect, induced by the 1 Hz rTMS, was observed through the increase of the PT, in the first group, but did not lead to a global reduction in brain activation, instead, showed change in the activation pattern before and after rTMS. Conversely, for the second group, changes in brain activation were observed just in few brain areas, suggesting that the effect of 1 Hz rTMS might not be inhibitory for everyone and that the concept of inhibitory/excitatory effect of rTMS may need to be revised.