Subject(s)
Bariatric Surgery/methods , Obesity, Morbid/pathology , Obesity, Morbid/surgery , Receptors, Opioid, mu/metabolism , Analgesics, Opioid/pharmacology , Brain/diagnostic imaging , Brain/drug effects , Brain/metabolism , Fentanyl/analogs & derivatives , Fentanyl/pharmacology , Humans , Positron-Emission Tomography , Receptors, Dopamine D2/metabolismABSTRACT
Positron emission tomography (PET) studies suggest opioidergic system dysfunction in morbid obesity, while evidence for the role of the dopaminergic system is less consistent. Whether opioid dysfunction represents a state or trait in obesity remains unresolved, but could be assessed in obese subjects undergoing weight loss. Here we measured brain µ-opioid receptor (MOR) and dopamine D2 receptor (D2R) availability in 16 morbidly obese women twice-before and 6 months after bariatric surgery-using PET with [(11)C]carfentanil and [(11)C]raclopride. Data were compared with those from 14 lean control subjects. Receptor-binding potentials (BPND) were compared between the groups and between the pre- and postoperative scans among the obese subjects. Brain MOR availability was initially lower among obese subjects, but weight loss (mean=26.1 kg, s.d.=7.6 kg) reversed this and resulted in ~23% higher MOR availability in the postoperative versus preoperative scan. Changes were observed in areas implicated in reward processing, including ventral striatum, insula, amygdala and thalamus (P's<0.005). Weight loss did not influence D2R availability in any brain region. Taken together, the endogenous opioid system plays an important role in the pathophysiology of human obesity. Because bariatric surgery and concomitant weight loss recover downregulated MOR availability, lowered MOR availability is associated with an obese phenotype and may mediate excessive energy uptake. Our results highlight that understanding the opioidergic contribution to overeating is critical for developing new treatments for obesity.
Subject(s)
Obesity, Morbid/metabolism , Receptors, Dopamine D2/metabolism , Receptors, Opioid, mu/metabolism , Adult , Bariatric Surgery , Brain/metabolism , Dopamine/metabolism , Female , Fentanyl/analogs & derivatives , Humans , Middle Aged , Positron-Emission Tomography/methods , Receptors, Dopamine D2/physiology , Receptors, Opioid/metabolism , Receptors, Opioid/physiology , Receptors, Opioid, mu/physiology , Weight LossABSTRACT
BACKGROUND: Movement accuracy is ensured by interaction between motor, somatosensory, and visual systems. In complex regional pain syndrome (CRPS), this interaction is disturbed. To explore CRPS patients' visual perception of actions, we investigated how these patients evaluate the applied force in observed hand actions of another person. METHODS: Nineteen patients suffering from unilateral upper-limb CRPS and 19 healthy control subjects viewed six different videos of left- and right-hand actions. They were asked to evaluate the applied force in each hand action, as well as their subjective sensations of unpleasantness and pain during the observation. RESULTS: The patients overestimated the force applied in the videos: the ratings were two times as large as in the control subjects for actions performed with the hand corresponding to the patients' affected hand, and 1.5 times as large for actions corresponding to their healthy hand. The control subjects considered the stimuli neutral and painless, whereas the patients rated them unpleasant. Moreover, the patients felt increased pain during viewing actions performed with the hand corresponding to their affected side. The overestimation of force was related to the elicited unpleasantness and pain, but not to the patients' muscle strength. CONCLUSIONS: We propose that the overestimation of force is explained both by the pain elicited by the observation and by the abnormal sensorimotor integration that is associated with perception of increased effort. This visually elicited unpleasantness and painfulness may promote avoidance of viewing own actions, further impairing the patients' motor performance.
Subject(s)
Complex Regional Pain Syndromes/physiopathology , Hand/physiopathology , Motor Activity/physiology , Pain Perception/physiology , Visual Perception/physiology , Adult , Female , Humans , Male , Middle Aged , Young AdultABSTRACT
Multifaceted and idiosyncratic aberrancies in social cognition characterize autism spectrum disorders (ASDs). To advance understanding of underlying neural mechanisms, we measured brain hemodynamic activity with functional magnetic resonance imaging (fMRI) in individuals with ASD and matched-pair neurotypical (NT) controls while they were viewing a feature film portraying social interactions. Pearson's correlation coefficient was used as a measure of voxelwise similarity of brain activity (InterSubject Correlations-ISCs). Individuals with ASD showed lower ISC than NT controls in brain regions implicated in processing social information including the insula, posterior and anterior cingulate cortex, caudate nucleus, precuneus, lateral occipital cortex, and supramarginal gyrus. Curiously, also within NT group, autism-quotient scores predicted ISC in overlapping areas, including, e.g., supramarginal gyrus and precuneus. In ASD participants, functional connectivity was decreased between the frontal pole and the superior frontal gyrus, angular gyrus, superior parietal lobule, precentral gyrus, precuneus, and anterior/posterior cingulate gyrus. Taken together these results suggest that ISC and functional connectivity measure distinct features of atypical brain function in high-functioning autistic individuals during free viewing of acted social interactions. Our ISC results suggest that the minds of ASD individuals do not 'tick together' with others while perceiving identical dynamic social interactions.
