PMID- 30953835
OWN - NLM
STAT- MEDLINE
DCOM- 20191220
LR  - 20210109
IS  - 1095-9572 (Electronic)
IS  - 1053-8119 (Print)
IS  - 1053-8119 (Linking)
VI  - 195
DP  - 2019 Jul 15
TI  - Receptor-Enriched Analysis of functional connectivity by targets (REACT): 
      A novel, multimodal analytical approach informed by PET to study the 
      pharmacodynamic response of the brain under MDMA.
PG  - 252-260
LID - S1053-8119(19)30293-9 [pii]
LID - 10.1016/j.neuroimage.2019.04.007 [doi]
AB  - One of the main limitations of pharmacological fMRI is its inability to provide a 
      molecular insight into the main effect of compounds, leaving an open question 
      about the relationship between drug effects and haemodynamic response. The aim of 
      this study is to investigate the acute effects of 
      3,4-methylenedioxymethamphetamine (MDMA) on functional connectivity (FC) using a 
      novel multimodal method (Receptor-Enriched Analysis of functional Connectivity by 
      Targets - REACT). This approach enriches the resting state (rs-)fMRI analysis 
      with the molecular information about the distribution density of serotonin 
      receptors in the brain, given the serotonergic action of MDMA. Twenty healthy 
      subjects participated in this double-blind, placebo-controlled, crossover study. 
      A high-resolution in vivo atlas of four serotonin receptors (5-HT(1A), 5-HT(1B), 
      5-HT(2A), and 5-HT(4)) and its transporter (5-HTT) was used as a template in a 
      two-step multivariate regression analysis to estimate the spatial maps reflecting 
      the whole-brain connectivity behaviour related to each target under placebo and 
      MDMA. Results showed that the networks exhibiting significant changes after MDMA 
      administration are the ones informed by the 5-HTT and 5-HT(1A) distribution 
      density maps, which are the main targets of this compound. Changes in the 
      5-HT(1A)-enriched functional maps were also associated with the pharmacokinetic 
      levels of MDMA and MDMA-induced FC changes in the 5-HT(2A)-enriched maps 
      correlated with the spiritual experience subscale of the Altered States of 
      Consciousness Questionnaire. By enriching the rs-fMRI analysis with molecular 
      data of voxel-wise distribution of the serotonin receptors across the brain, we 
      showed that MDMA effects on FC can be understood through the distribution of its 
      main targets. This result supports the ability of this method to characterise the 
      specificity of the functional response of the brain to MDMA binding to 
      serotonergic receptors, paving the way to the definition of a new fingerprint in 
      the characterization of new compounds and potentially to a further understanding 
      to the response to treatment.
CI  - Copyright (c) 2019 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Dipasquale, Ottavia
AU  - Dipasquale O
AD  - Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, 
      King's College London, London, United Kingdom. Electronic address: 
      ottavia.dipasquale@kcl.ac.uk.
FAU - Selvaggi, Pierluigi
AU  - Selvaggi P
AD  - Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, 
      King's College London, London, United Kingdom.
FAU - Veronese, Mattia
AU  - Veronese M
AD  - Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, 
      King's College London, London, United Kingdom.
FAU - Gabay, Anthony S
AU  - Gabay AS
AD  - Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, 
      King's College London, London, United Kingdom.
FAU - Turkheimer, Federico
AU  - Turkheimer F
AD  - Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, 
      King's College London, London, United Kingdom.
FAU - Mehta, Mitul A
AU  - Mehta MA
AD  - Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, 
      King's College London, London, United Kingdom.
LA  - eng
GR  - MR/N026063/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20190404
PL  - United States
TA  - Neuroimage
JT  - NeuroImage
JID - 9215515
RN  - 0 (Serotonin Agents)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Adult
MH  - Brain/*drug effects
MH  - Cross-Over Studies
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Neuroimaging/*methods
MH  - Positron-Emission Tomography/*methods
MH  - Serotonin Agents/*pharmacology
MH  - Young Adult
PMC - PMC6547164
OTO - NOTNLM
OT  - Functional connectivity
OT  - MDMA
OT  - Pharmacodynamic response
OT  - Pharmacological neuroimaging
OT  - Resting state fMRI
OT  - Serotonin
EDAT- 2019/04/07 06:00
MHDA- 2019/12/21 06:00
PMCR- 2019/07/15
CRDT- 2019/04/07 06:00
PHST- 2018/11/21 00:00 [received]
PHST- 2019/03/11 00:00 [revised]
PHST- 2019/04/02 00:00 [accepted]
PHST- 2019/04/07 06:00 [pubmed]
PHST- 2019/12/21 06:00 [medline]
PHST- 2019/04/07 06:00 [entrez]
PHST- 2019/07/15 00:00 [pmc-release]
AID - S1053-8119(19)30293-9 [pii]
AID - 10.1016/j.neuroimage.2019.04.007 [doi]
PST - ppublish
SO  - Neuroimage. 2019 Jul 15;195:252-260. doi: 10.1016/j.neuroimage.2019.04.007. Epub 
      2019 Apr 4.