Acute @entity2340 depletion alters the effective connectivity of emotional arousal circuitry during visceral stimuli in healthy XXXX .

@entity1 @entity1931 @entity75 @entity2340 @entity750 @entity158 @entity2195 @entity1142 @entity1744
OBJECTIVE: Alterations in @entity750 signalling within the brain-gut axis have been implicated in the pathophysiology of @entity1744 ( @entity2195 ) and is a treatment target. Acute @entity2340 depletion (ATD) decreases brain @entity750 ( @entity750 ; @entity750 ) levels, and increases visceral perception and negative emotional bias in @entity1 with @entity2195 . The aim of the present study was to determine the effect of ATD on brain activity and connectivity during visceral stimuli in healthy @entity1 , and to compare the ATD-induced brain connectivity of an arousal circuit in female @entity1 with @entity2195 without ATD. METHODS: 12 healthy females (19-25 years) were studied under placebo (PLA) conditions and ATD. Functional MRI measurements were performed during a rectal barostat protocol, consisting of random non-painful and maximal tolerable distensions. Partial least squares analyses and structural equation modelling were used to evaluate the effect of ATD on functional and effective brain connectivity during distension. Results in healthy controls under ATD were compared with the effective connectivity of brain responses to 45 mm   Hg rectal distension in 14 female @entity1 with @entity1142 -predominant @entity2195 ( @entity2195 ) (24-50 years). RESULTS: In healthy controls, ATD resulted in increased response of an extensive @entity75 , including the amygdala and nodes of emotional arousal and homeostatic afferent networks. The effect was greater during high inflation, suggesting greater engagement of the central serotonion system with more aversive visceral stimuli. Effective connectivity analysis revealed a profound effect of ATD on coupling between emotional arousal network nodes, resulting in loss of negative feedback inhibition of the amygdala. A near-identical pattern was identified in the @entity1 with @entity2195 . CONCLUSIONS: The findings are consistent with an ATD-induced disinhibition of and increased connectivity within an emotional arousal network during aversive stimulation. Together with the previous demonstration of ATD-induced @entity1931 in healthy controls, and the near-identical effective connectivity pattern observed in @entity1 with @entity2195 , these findings suggest that dysregulation of this brain network may play a role in central @entity158 and @entity2195 pathophysiology.
