Motivation

The motivation behind my neuroscience research is to combine modern molecular and functional brain imaging approaches in an innovative multimodal way that opens up novel possibilities of integrating findings from different levels of neuronal organization in order to build systems-level models with higher explanatory value than just using imaging modalities in an additive manner.

In general, the projects address fundamental questions of how information is processed by the brain, how different levels of emotional and cognitive information processing are linked to brain metabolism, and how brain function and subjective experience changes as a result of pharmacological intervention. Epistemically, an
ecological and cybernetic perspective serves as a theoretical framework to organize the empirical findings on the level of information processing and cerebral neuroenergetics according to the biological notion of homeostasis.

Insights from these basic research questions and methodological innovations are translated into
clinical applications in order to describe the changes in brain region-specific neurotransmission and metabolism that characterize affective disorders such as depression, the relationship between these changes and psychopathology, and the neural and psychological responses of patients to specific compounds with high therapeutic potential.


Exploring the Antidepressant Effects of Ketamine

There is growing evidence for imbalance with regard to glutamatergic neurotransmission in stress-related affective disorders. Further support for the hypothesis that dysfunctional glutamatergic signaling underlies major depressive disorder, and indeed that its reversal constitutes a potential efficacious mechanism of action, is provided by the evidence that pharmacological compounds active at the N-methyl-D-aspartate (NMDA) ionotropic glutamate receptor such as ketamine exert rapid antidepressant effects. As a tool compound ketamine enables the safe investigation of the brain region-specific effects of NMDA receptor antagonism in terms of glutamatergic neurotransmission, brain function and the association of these neural changes with emotional state, thereby allowing for increased understanding of the therapeutic mechanism of action.

Bildschirmfoto 2016-09-05 um 13.30.17


Insights from Multimodal Imaging

The possibility to simultaneously study brain perfusion (arterial spin labeling), functional brain activity (fMRI) and connectivity (resting state fMRI), neurometabolism (proton magnetic resonance spectroscopy) and metabotropic glutamate receptor densities (positron emission tomography) will unravel their functional interplay in the mechanisms underlying the regulation of mood and cognition. Combining those imaging modalities with treatment interventions in healthy subjects and clinical populations, this project aims at providing insight into the neuropharmacological effects of ketamine and its antidepressant properties.


Future Directions


Transformational Psychotherapy:

  • Integrative psychotherapy approach based on cognitive-behavioral, systemic and psychodynamic psychotherapy, including elements of mindfulness-based, transpersonal, and humanistic psychotherapy as well as existential philosophy
  • Development of psychotherapy protocols including pharmacologically induced altered states of consciousness (e.g. ayahuasca, 5-MeO-DMT, ketamine, psilocybin)
  • Facilitation of neurobehavioral transformation and integration in conjunction with mindfulness-based interventions

Psychedelics & Mindfulness

  • Neurobiology of expanded states of self and non-dual awareness (e.g. meditation, psychopharmacological challenge with psilocybin, 5-MeO-DMT)
  • Short- and long-term benefits of drug-induced mystical experiences in long-term meditation practitioners (in collaboration with Prof. Franz Vollenweider and Zen teacher Vanja Palmers, Stiftung Felsentor)

Psychedelic Frontiers: Targeting 5-MeO-DMT (Bufo alvarius toad medicine)

  • Neurobiology of non-dual states of consciousness (EEG/fMRT)
  • Development of adapted inhalation and infusion-protocols for clinical applications according to GCP standards
  • Clinical study: potential role in suicide prevention and to alleviate symptoms of depression, auto-aggression, addictive cravings and existential feelings of disconnection

Psychedelic Frontiers: Targeting Ayahuasca

  • Observational study of short vs. long-term benefits and potential risks factors in Swiss Ayahuasca users
  • Development of adapted botanical extraction procedures for clinical applications according to GCP standards
  • Clinical study: efficacy of ayahuasca-based transformational psychotherapy for stress-related affective disorders (e.g. burnout, depression)


Publications


Exploring the antidepressant effects of ketamine: Insights from multimodal neuroimaging
A thesis submitted to attain the degree of Dr. sc. ETH Zurich
Scheidegger M, DISS. ETH NO. 22922, 2015.

Effects of serotonin 2A/1A receptor stimulation on social exclusion processing.
Preller KH, Pokorny T, Hock A, Kraehenmann R, Stämpfli P, Seifritz E, Scheidegger M, Vollenweider FX.
Proc Natl Acad Sci U S A. 2016 May 3;113(18):5119-24. doi: 10.1073/pnas.1524187113. Epub 2016 Apr 18.

Differential effects of rumination and distraction on ketamine induced modulation of resting state functional connectivity and reactivity of regions within the default-mode network.
Lehmann M, Seifritz E, Henning A, Walter M, Böker H, Scheidegger M*, Grimm S*.
Soc Cogn Affect Neurosci. 2016 Aug;11(8):1227-35. doi: 10.1093/scan/nsw034. Epub 2016 Apr 13.

Ketamine administration reduces amygdalo-hippocampal reactivity to emotional stimulation.
Scheidegger M, Henning A, Walter M, Lehmann M, Kraehenmann R, Boeker H, Seifritz E, Grimm S.
Hum Brain Mapp. 2016 May;37(5):1941-52. doi: 10.1002/hbm.23148. Epub 2016 Feb 25.

Effects of ketamine on cognition-emotion interaction in the brain.
Scheidegger M, Henning A, Walter M, Boeker H, Weigand A, Seifritz E, Grimm S.
Neuroimage. 2016 Jan 1;124(Pt A):8-15. doi: 10.1016/j.neuroimage.2015.08.070. Epub 2015 Sep 5.

Fast iterative pre-emphasis calibration method enabling third-order dynamic shim updated fMRI.
Fillmer A, Vannesjo SJ, Pavan M, Scheidegger M, Pruessmann KP, Henning A.
Magn Reson Med. 2016 Mar;75(3):1119-31. doi: 10.1002/mrm.25695. Epub 2015 May 7.

Glutamatergic and neurometabolic alterations in chronic cocaine users measured with (1) H-magnetic resonance spectroscopy.
Hulka LM, Scheidegger M, Vonmoos M, Preller KH, Baumgartner MR, Herdener M, Seifritz E, Henning A, Quednow BB.
Addict Biol. 2016 Jan;21(1):205-17. doi: 10.1111/adb.12217. Epub 2014 Dec 30.

Psilocybin-Induced Decrease in Amygdala Reactivity Correlates with Enhanced Positive Mood in Healthy Volunteers.
Kraehenmann R, Preller KH, Scheidegger M, Pokorny T, Bosch OG, Seifritz E, Vollenweider FX.
Biol Psychiatry. 2015 Oct 15;78(8):572-81. doi: 10.1016/j.biopsych.2014.04.010. Epub 2014 Apr 26.

Sleep deprivation increases dorsal nexus connectivity to the dorsolateral prefrontal cortex in humans.
Bosch OG, Rihm JS, Scheidegger M, Landolt HP, Stämpfli P, Brakowski J, Esposito F, Rasch B, Seifritz E.
Proc Natl Acad Sci U S A. 2013 Nov 26;110(48):19597-602. doi: 10.1073/pnas.1317010110. Epub 2013 Nov 11.

Smoking but not cocaine use is associated with lower cerebral metabotropic glutamate receptor 5 density in humans.
Hulka LM, Treyer V, Scheidegger M, Preller KH, Vonmoos M, Baumgartner MR, Johayem A, Ametamey SM, Buck A, Seifritz E, Quednow BB.
Mol Psychiatry. 2014 May;19(5):625-32. doi: 10.1038/mp.2013.51. Epub 2013 Apr 30.

Ketamine decreases resting state functional network connectivity in healthy subjects: implications for antidepressant drug action.
Scheidegger M*, Walter M*, Lehmann M, Metzger C, Grimm S, Boeker H, Boesiger P, Henning A, Seifritz E.
PLoS One. 2012;7(9):e44799. doi: 10.1371/journal.pone.0044799. Epub 2012 Sep 24.

Increased metabotropic glutamate receptor subtype 5 availability in human brain after one night without sleep.
Hefti K, Holst SC, Sovago J, Bachmann V, Buck A, Ametamey SM, Scheidegger M, Berthold T, Gomez-Mancilla B, Seifritz E, Landolt HP.
Biol Psychiatry. 2013 Jan 15;73(2):161-8. doi: 10.1016/j.biopsych.2012.07.030. Epub 2012 Sep 7.