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dc.contributor.author
Zimmermann, Josua
dc.contributor.supervisor
Polania, Rafael
dc.contributor.supervisor
Quednow, Boris B.
dc.contributor.supervisor
Tobler, Philippe
dc.date.accessioned
2022-10-26T14:01:51Z
dc.date.available
2022-10-26T12:31:20Z
dc.date.available
2022-10-26T14:01:51Z
dc.date.issued
2022
dc.identifier.uri
http://hdl.handle.net/20.500.11850/577920
dc.identifier.doi
10.3929/ethz-b-000577920
dc.description.abstract
Serotonin (5-hydoxytryptamine [5-HT]) is an important neuromodulatory agent in the brain. Serotonergic projection fibers originate in the raphe nuclei and influence signal transmission throughout the brain. This thesis applied magnetic resonance techniques in humans to evaluate the effects of acute and chronic 5 HT modulation on functional connectivity, white matter integrity, and major neurotransmitter levels. Numerous pathological conditions are associated with disturbances in the 5-HT system. However, non invasive evaluation of 5-HT system alterations in humans is challenging. The first study therefore assessed two human models of 5-HT modulation. Short-term 5-HT stimulation was investigated with an acute drug challenge using lysergic acid diethylamide (LSD), a selective 5 HT1A/5 HT2A receptor agonist. In addition, chronic 3,4 Methylenedioxymethamphetamine (MDMA, “Ecstasy”) consumption was used to examine long-term changes in the 5-HT system. MDMA is a potent 5-HT-releasing agent and repeated use in humans has been associated with long-term 5-HT depletion as well as altered 5-HT transporter and receptor levels. Functional magnetic resonance imaging (fMRI) results indicated that measuring the resting-state network of the raphe nuclei (i.e., dorsal and median raphe) facilitates the non invasive assessment of both short- and long-term changes in the human 5-HT system. In animals, long-term alterations in the 5-HT system in response to chronic MDMA exposure include degradation of axons and nerve terminals. To test whether this also occurs in human MDMA users, diffusion tensor imaging (DTI) and neurofilament light chain levels in blood (a biomarker for axonal pathology) were evaluated in the second study. However, results provided no evidence for MDMA induced axonal injury in humans. To examine whether chronic changes in the 5-HT system of regular MDMA users also affect glutamate and γ-aminobutyric acid (GABA) levels, proton magnetic resonance spectroscopy (MRS) was applied in the third study. Glutamate levels in the left striatum were elevated in MDMA users, but GABA concentrations were not altered. This thesis provides evidence that raphe nuclei functional connectivity facilitates non-invasive assessment of 5-HT system alterations in humans, relevant for the future examination of 5-HT disturbances in neurological or psychiatric patients. Moreover, the consequences of long-term 5-HT alterations in MDMA users were assessed to improve understanding of neurophysiological mechanisms underpinning cognitive deficits commonly observed in chronic MDMA users.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
ETH Zurich
en_US
dc.subject
neuroscience
en_US
dc.subject
Neuroimaging
en_US
dc.subject
Serotonin
en_US
dc.subject
MDMA
en_US
dc.subject
LSD
en_US
dc.subject
fMRI
en_US
dc.subject
DTI
en_US
dc.subject
MR spectroscopy
en_US
dc.title
The effects of short- and long-term neuroplastic adaptations in the human serotonin system assessed via neuroimaging
en_US
dc.type
Doctoral Thesis
dc.date.published
2022-10-26
ethz.size
174 p.
en_US
ethz.code.ddc
DDC - DDC::5 - Science::500 - Natural sciences
en_US
ethz.code.ddc
DDC - DDC::5 - Science::570 - Life sciences
en_US
ethz.identifier.diss
28547
en_US
ethz.publication.place
Zurich
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02535 - Institut für Bewegungswiss. und Sport / Institut of Human Movement Sc. and Sport::09630 - Polania Jimenez, Rafael (ehemalig) / Polania Jimenez, Rafael (former)
en_US
ethz.date.deposited
2022-10-26T12:31:21Z
ethz.source
FORM
ethz.eth
yes
en_US
ethz.availability
Embargoed
en_US
ethz.date.embargoend
2024-10-26
ethz.rosetta.installDate
2022-10-26T14:01:52Z
ethz.rosetta.lastUpdated
2024-02-02T18:48:45Z
ethz.rosetta.versionExported
true
ethz.COinS
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