Cerebral blood flow predicts differential neurotransmitter activity

Dukart, Juergen; Holiga, Štefan; Chatham, Christopher H.; Hawkins, Peter Ct; Forsyth, Anna; McMillan, Rebecca; Myers, Jim; Lingford-Hughes, Anne; Nutt, David; Merlo‐Pich, Emilio; Risterucci, Céline; Boak, Lauren; Umbricht, Daniel; Schobel, Scott; Liu, Thomas T.; Mehta, Mitul A.; Zelaya, Fernando; Williams, Steven; Brown, Gregory G.; Paulus, Martin P.; Honey, Garry D.; Muthukumaraswamy, Suresh; Hipp, Joerg F.; Bertolino, Alessandro; Sambataro, Fabio

doi:10.1038/s41598-018-22444-0

Cited by 115 publications

(83 citation statements)

References 60 publications

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“…The correlation strength between ∆CBF and receptor density measured with PET varied between the different antipsychotics tested (Figure 4). One possible interpretation of this difference might be related to the differential affinities for these compounds to D 2 R (Dukart et al, 2018). Our data seems to be in line with this hypothesis.…”

Section: Differential Strength Of Association Between ∆Cbf and Receptsupporting

confidence: 89%

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Increased cerebral blood flow after single dose of antipsychotics in healthy volunteers depends on dopamine D2 receptor density profiles

et al. 2019

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Section: Differential Strength Of Association Between ∆Cbf and Receptsupporting

confidence: 89%

“…The use of multimodal approaches, e.g. combining MR measures with exvivo autoradiography (Dukart et al, 2018), have started to fill this gap of knowledge.…”

Section: Introductionmentioning

confidence: 99%

Increased cerebral blood flow after single dose of antipsychotics in healthy volunteers depends on dopamine D2 receptor density profiles

et al. 2019

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“…The integration between haemodynamic markers and molecular imaging data is still a challenge. Some studies investigated the spatial association between the main effects of different drugs on the CBF and the molecular information from gene-expression, PET or autoradiography data using simple ROI-to-ROI correlations (Dukart et al., 2018; Selvaggi et al., 2018). While this approach has proven its efficacy with ASL data sets, it would be over simplistic if applied to rs-fMRI data, since the temporal dynamics of the BOLD signal would be overlooked.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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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.

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“…Distinct relationships were found between drug-induced CBF changes and a range of associated underlying receptor densities. 70…”

Section: Pharmacological Pet/mrimentioning

confidence: 99%

Advances in simultaneous PET/MR for imaging neuroreceptor function

Sander

Hansen

Wey

2020

J Cereb Blood Flow Metab

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Hybrid imaging using PET/MRI has emerged as a platform for elucidating novel neurobiology, molecular and functional changes in disease, and responses to physiological or pharmacological interventions. For the central nervous system, PET/MRI has provided insights into biochemical processes, linking selective molecular targets and distributed brain function. This review highlights several examples that leverage the strengths of simultaneous PET/MRI, which includes measuring the perturbation of multi-modal imaging signals on dynamic timescales during pharmacological challenges, physiological interventions or behavioral tasks. We discuss important considerations for the experimental design of dynamic PET/MRI studies and data analysis approaches for comparing and quantifying simultaneous PET/MRI data. The primary focus of this review is on functional PET/MRI studies of neurotransmitter and receptor systems, with an emphasis on the dopamine, opioid, serotonin and glutamate systems as molecular neuromodulators. In this context, we provide an overview of studies that employ interventions to alter the activity of neuroreceptors or the release of neurotransmitters. Overall, we emphasize how the synergistic use of simultaneous PET/MRI with appropriate study design and interventions has the potential to expand our knowledge about the molecular and functional dynamics of the living human brain. Finally, we give an outlook on the future opportunities for simultaneous PET/MRI.

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Cerebral blood flow predicts differential neurotransmitter activity

Cited by 115 publications

References 60 publications

Increased cerebral blood flow after single dose of antipsychotics in healthy volunteers depends on dopamine D2 receptor density profiles

Increased cerebral blood flow after single dose of antipsychotics in healthy volunteers depends on dopamine D2 receptor density profiles

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

Advances in simultaneous PET/MR for imaging neuroreceptor function

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