[PPT] - Imaging Monoaminergic Systems and their Pharmacological Control PowerPoint Presentation

SLIDE 1

Context Technology Fingerprinting Psychopharmacology Meta Supplementary

Imaging Monoaminergic Systems and their Pharmacological Control

Horea-Ioan Ioan˘ as

,

[ chymera.eu ]

Institute for Biomedical Engineering, ETH and University of Zurich

August 14, 2019

Horea-Ioan Ioan˘ as

,

Institute for Biomedical Engineering, ETH and University of Zurich Imaging Monoaminergic Systems and their Pharmacological Control

SLIDE 2

Context Technology Fingerprinting Psychopharmacology Meta Supplementary Rationale, background, and aims

How can neuroscience change the world?

◮ Facilitate the betterment of the human mind. ◮ Establish natural scientific definitions of mental phenomena. ◮ Create reusable methods which empower other research.

Horea-Ioan Ioan˘ as

,

Institute for Biomedical Engineering, ETH and University of Zurich Imaging Monoaminergic Systems and their Pharmacological Control

SLIDE 3

Context Technology Fingerprinting Psychopharmacology Meta Supplementary Rationale, background, and aims

Monoaminergic Systems

◮ Widely implicated in emotional function ◮ Widely implicated in mental diseases ◮ High degree-centrality brain nodes

Ascending serotonergic (5HT) projections. Monoamine-centric representation of emotional states, from [1]

Horea-Ioan Ioan˘ as

,

Institute for Biomedical Engineering, ETH and University of Zurich Imaging Monoaminergic Systems and their Pharmacological Control

SLIDE 4

Context Technology Fingerprinting Psychopharmacology Meta Supplementary Rationale, background, and aims

Monoaminergic Pharmacology

◮ Popular targets of psychotropic drugs, including such as are:

◮ therapeutic ◮ neuroenhancing ◮ recreational ◮ addictive Notable molecular homology at monoaminergic synapses, from [2]

Horea-Ioan Ioan˘ as

,

Institute for Biomedical Engineering, ETH and University of Zurich Imaging Monoaminergic Systems and their Pharmacological Control

SLIDE 5

Context Technology Fingerprinting Psychopharmacology Meta Supplementary Rationale, background, and aims

Aims

◮ Develop technologies to automate and reproduce assays. ◮ Establish novel monoaminergic imaging assay — “endophenotype”. ◮ Determine psychopharmacological susceptibility of imaging assay.

Horea-Ioan Ioan˘ as

,

Institute for Biomedical Engineering, ETH and University of Zurich Imaging Monoaminergic Systems and their Pharmacological Control

SLIDE 6

Context Technology Fingerprinting Psychopharmacology Meta Supplementary Infrastructure for reusable neuroscientific methods

Software Management

◮ Gentoo Linux package management:

◮ comprehensive dependency resolution ◮ environment generation from source

◮ Added management instructions for

ver 60 neuroscientifically relevant

packages ◮ Implemented 1-step environment reproduction [3]

dev-python/imageio dev-python/setuptools dev-python/certifi dev-lang/python-exec app-arch/unzip dev-python/numpy media-libs/freeimage virtual/pkgconfig dev-util/pkgconfig-openbsd v i r t u a l / p e r l

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e t

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g p e r l

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g dev-lang/perl virtual/perl-Data-Dumper perl-core/Data-Dumper s y s

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i b s / z l i b app-admin/perl-cleaner sys-apps/portage sys-apps/sed app-misc/pax-utils a p p

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r c h / x z

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t i l s app-arch/tar sys-devel/patch s y s

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p p s / p a l u d i s a p p

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e x t / h t m l t i d y s y s

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sys-devel/autoconf sys-devel/m4 sys-devel/autoconf-wrapper s y s

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e v e l / a u t

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a k e sys-devel/automake-wrapper s y s

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p p s / h e l p 2 m a n sys-devel/gnuconfig d e v

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i b s / l i b l t d l app-eselect/eselect-package-manager a p p

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d m i n / e s e l e c t s y s

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p p s / c

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p p s / f i l e sys-freebsd/freebsd-bin sys-devel/flex virtual/pmake sys-freebsd/freebsd-mk-defs dev-libs/libedit sys-freebsd/freebsd-lib virtual/libiconv s y s

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r e e b s d / f r e e b s d

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r c e s dev-libs/expat sys-freebsd/freebsd-share sys-apps/miscfiles dev-util/dialog sys-apps/ed s y s

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p p s / t e x i n f

dev-perl/Text-Unidecode

virtual/perl-ExtUtils-MakeMaker p e r l

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a k e M a k e r virtual/perl-File-Spec virtual/perl-ExtUtils-Install v i r t u a l / p e r l

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p l media-fonts/urw-fonts media-libs/jbig2dec app-text/poppler-data m e d i a

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t i l / g p e r f sci-libs/nipype dev-python/simplejson dev-python/future dev-python/pygraphviz sci-libs/nipy s c i

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a t a sci-libs/nipy-templates s c i

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a t h e m a t i c s / m d p sci-visualization/mricrogl dev-lang/lazarus net-misc/rsync sci-visualization/mricron sci-visualization/surf-ice

Monoamine-centric representation of emotional states, from

Horea-Ioan Ioan˘ as

,

Institute for Biomedical Engineering, ETH and University of Zurich Imaging Monoaminergic Systems and their Pharmacological Control

SLIDE 7

Context Technology Fingerprinting Psychopharmacology Meta Supplementary Infrastructure for reusable neuroscientific methods

Data Processing

Analysis System Acquisition System Share? Share? Share? Share! Analog Free Induction Decay Volumetric Reconstruction Raw Volumetric Metadata Preprocessing Volumetric Metadata Volumetric Statistic Metadata Plot or Summary Manual Metadata Metadata Manual Acquisition System Analysis System Share! Share! Share! Share! Analog Free Induction Decay Manual Metadata Volumetric Reconstruction Raw Volumetric +Metadata Preprocessed Volumetric +Metadata Volumetric Statistic +Metadata Plot or Summary Horea-Ioan Ioan˘ as

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Institute for Biomedical Engineering, ETH and University of Zurich Imaging Monoaminergic Systems and their Pharmacological Control

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Context Technology Fingerprinting Psychopharmacology Meta Supplementary Infrastructure for reusable neuroscientific methods

Data Format Standardization

Acquisition System (Bruker) Analysis System Sharing Sharing Sharing Sharing Sharing Analog Time Domain k-Space (raw) Volumetric Reconstruction (raw) 3D Format (raw) Preprocessed Data Statistic Summaries Plots

bru2bids

Horea-Ioan Ioan˘ as

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Institute for Biomedical Engineering, ETH and University of Zurich Imaging Monoaminergic Systems and their Pharmacological Control

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Context Technology Fingerprinting Psychopharmacology Meta Supplementary Infrastructure for reusable neuroscientific methods

Optimized Registration — Workflow and Template

p = 3.8 × 10−14, RMSEL/RMSEG ≃ 2.8 p = 9.9 × 10−22, RMSEL/RMSEG ≃ 2.9

Horea-Ioan Ioan˘ as

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Institute for Biomedical Engineering, ETH and University of Zurich Imaging Monoaminergic Systems and their Pharmacological Control

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Context Technology Fingerprinting Psychopharmacology Meta Supplementary Infrastructure for reusable neuroscientific methods

So what?

◮ Reproducible, hackable processing and analysis environments ◮ Shareable data representation ◮ Reusable and incrementally improvable processing workflows

Horea-Ioan Ioan˘ as

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Institute for Biomedical Engineering, ETH and University of Zurich Imaging Monoaminergic Systems and their Pharmacological Control

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Context Technology Fingerprinting Psychopharmacology Meta Supplementary An assay for Ventral Tegmental Area (VTA) dopaminergic signalling

pto-fMRI

◮ Optogenetics + functional Magnetic Resonance Imaging:

◮ Coherent site and cell-type specific stimulation ◮ Whole-brain reporting

Horea-Ioan Ioan˘ as

,

Institute for Biomedical Engineering, ETH and University of Zurich Imaging Monoaminergic Systems and their Pharmacological Control

SLIDE 12

Context Technology Fingerprinting Psychopharmacology Meta Supplementary An assay for Ventral Tegmental Area (VTA) dopaminergic signalling

Multivariate Assay Guide

Horea-Ioan Ioan˘ as

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Institute for Biomedical Engineering, ETH and University of Zurich Imaging Monoaminergic Systems and their Pharmacological Control

SLIDE 13

Context Technology Fingerprinting Psychopharmacology Meta Supplementary An assay for Ventral Tegmental Area (VTA) dopaminergic signalling

Whole-Brain Dopaminergic Fingerprint

◮ Incl: Midbrain, striatum ◮ Excl: Amygdala, cortex ◮ Lateralized (p=5.6×10−6)

Horea-Ioan Ioan˘ as

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Institute for Biomedical Engineering, ETH and University of Zurich Imaging Monoaminergic Systems and their Pharmacological Control

SLIDE 14

Context Technology Fingerprinting Psychopharmacology Meta Supplementary An assay for Ventral Tegmental Area (VTA) dopaminergic signalling

So what?

◮ Proof-of principle and guide for mouse dopaminergic opto-fMRI fingerprinting ◮ Reusable assay compatible with numerous model interventions ◮ Dopaminergic function reference endophenotype (non-diseased, drug-na¨ ıve)

Horea-Ioan Ioan˘ as

,

Institute for Biomedical Engineering, ETH and University of Zurich Imaging Monoaminergic Systems and their Pharmacological Control

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Context Technology Fingerprinting Psychopharmacology Meta Supplementary Imaging a longitudinal drug treatment — Selective Serotonin Reuptake Inhibition (SSRI)

pto-pharmaco-fMRI

◮ Optogenetics + pharmacology + functional Magnetic Resonance Imaging:

naïve acute chronic/2w chronic/4w post fMRI fMRI Fluoxetine i.v. fMRI Vehicle i.v. fMRI fMRI fMRI fMRI fMRI

Horea-Ioan Ioan˘ as

,

Institute for Biomedical Engineering, ETH and University of Zurich Imaging Monoaminergic Systems and their Pharmacological Control

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Context Technology Fingerprinting Psychopharmacology Meta Supplementary Imaging a longitudinal drug treatment — Selective Serotonin Reuptake Inhibition (SSRI)

The Pertinence of Monoaminergic Imaging

At the whole-brain level, even macroscopic resolution...

Horea-Ioan Ioan˘ as

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Institute for Biomedical Engineering, ETH and University of Zurich Imaging Monoaminergic Systems and their Pharmacological Control

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Context Technology Fingerprinting Psychopharmacology Meta Supplementary Imaging a longitudinal drug treatment — Selective Serotonin Reuptake Inhibition (SSRI)

The Pertinence of Monoaminergic Imaging

... maps onto cellular processes.

Horea-Ioan Ioan˘ as

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Institute for Biomedical Engineering, ETH and University of Zurich Imaging Monoaminergic Systems and their Pharmacological Control

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Context Technology Fingerprinting Psychopharmacology Meta Supplementary Imaging a longitudinal drug treatment — Selective Serotonin Reuptake Inhibition (SSRI)

Reference Map Reproduction

From [4] Drug-na¨ ıve session map

Horea-Ioan Ioan˘ as

,

Institute for Biomedical Engineering, ETH and University of Zurich Imaging Monoaminergic Systems and their Pharmacological Control

SLIDE 19

Context Technology Fingerprinting Psychopharmacology Meta Supplementary Imaging a longitudinal drug treatment — Selective Serotonin Reuptake Inhibition (SSRI)

Dorsal Raphe Trajectory

Session-treatment interaction: ◮ F9,92 =6.37, p=5.65×10−7 Post-hoc treatment contrasts: ◮ na¨ ıve: p=0.79 ◮ acute: p=0.15 ◮ chronic/2w: p=9×10−3 ◮ chronic/4w: p=4×10−3 ◮ post: p=0.77

Horea-Ioan Ioan˘ as

,

Institute for Biomedical Engineering, ETH and University of Zurich Imaging Monoaminergic Systems and their Pharmacological Control

SLIDE 20

Context Technology Fingerprinting Psychopharmacology Meta Supplementary Imaging a longitudinal drug treatment — Selective Serotonin Reuptake Inhibition (SSRI)

Trajectory Clustering

◮ Efference classification based on longitudinal trajectory via Gaussian Mixture Model.

Horea-Ioan Ioan˘ as

,

Institute for Biomedical Engineering, ETH and University of Zurich Imaging Monoaminergic Systems and their Pharmacological Control

SLIDE 21

Context Technology Fingerprinting Psychopharmacology Meta Supplementary Imaging a longitudinal drug treatment — Selective Serotonin Reuptake Inhibition (SSRI)

Brainstem Cluster Trajectory

Horea-Ioan Ioan˘ as

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Institute for Biomedical Engineering, ETH and University of Zurich Imaging Monoaminergic Systems and their Pharmacological Control

SLIDE 22

Context Technology Fingerprinting Psychopharmacology Meta Supplementary Imaging a longitudinal drug treatment — Selective Serotonin Reuptake Inhibition (SSRI)

Cortical Cluster Trajectory

Horea-Ioan Ioan˘ as

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Institute for Biomedical Engineering, ETH and University of Zurich Imaging Monoaminergic Systems and their Pharmacological Control

SLIDE 23

Context Technology Fingerprinting Psychopharmacology Meta Supplementary Imaging a longitudinal drug treatment — Selective Serotonin Reuptake Inhibition (SSRI)

So what?

Illuminating for SSRI and monoaminergic research: ◮ Proof-of principle for longitudinal pharmacological sensitivity of fingerprint. ◮ Imaging-based support for “inhibition down-regulation” hypothesis ◮ Brainstem stimulation effect as possible candidate of action mechanism ◮ Homeostasis rebounding in healthy animals

Horea-Ioan Ioan˘ as

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Institute for Biomedical Engineering, ETH and University of Zurich Imaging Monoaminergic Systems and their Pharmacological Control

SLIDE 24

Context Technology Fingerprinting Psychopharmacology Meta Supplementary About this presentation

Outlook

◮ Dopaminergic reuptake inhibition challenge ◮ Noradrenergic fingerprinting ◮ Neuropeptidergic fingerprinting ◮ Concurrent application of multiple assays ◮ Fingerprint translation to human reference space

Horea-Ioan Ioan˘ as

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Institute for Biomedical Engineering, ETH and University of Zurich Imaging Monoaminergic Systems and their Pharmacological Control

SLIDE 25

Context Technology Fingerprinting Psychopharmacology Meta Supplementary About this presentation

Questions

Horea-Ioan Ioan˘ as

,

Institute for Biomedical Engineering, ETH and University of Zurich Imaging Monoaminergic Systems and their Pharmacological Control

SLIDE 26

Context Technology Fingerprinting Psychopharmacology Meta Supplementary About this presentation

External Materials

[1] H. L¨

vheim, “A new three-dimensional model for emotions and monoamine neurotransmitters.” Med Hypotheses,
vol. 78, no. 2, pp. 341–348, Feb 2012. [Online]. Available: http://dx.doi.org/10.1016/j.mehy.2011.11.016

[2] G. E. Torres, R. R. Gainetdinov, and M. G. Caron, “Plasma membrane monoamine transporters: structure, regulation and function,” Nature Reviews Neuroscience, vol. 4, no. 1, p. 13, 2003. [3] H.-I. Ioanas and M. Rudin, “Reproducible self-publishing for Python-based research.” EuroSciPy, Aug. 2018. [Online]. Available: https://figshare.com/articles/Reproducible Self-Publishing for Python-Based Research/7247339 [4] J. Grandjean, A. Corcoba, M. C. Kahn, A. L. Upton, E. S. Deneris, E. Seifritz, F. Helmchen, E. O. Mann, M. Rudin, and

B. J. Saab, “A brain-wide functional map of the serotonergic responses to acute stress and fluoxetine,” Nature

Communications, vol. 10, no. 1, Jan. 2019. [Online]. Available: https://doi.org/10.1038/s41467-018-08256-w

Horea-Ioan Ioan˘ as

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Institute for Biomedical Engineering, ETH and University of Zurich Imaging Monoaminergic Systems and their Pharmacological Control

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Context Technology Fingerprinting Psychopharmacology Meta Supplementary

Anatomical Parcellation

Horea-Ioan Ioan˘ as

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Institute for Biomedical Engineering, ETH and University of Zurich Imaging Monoaminergic Systems and their Pharmacological Control

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Context Technology Fingerprinting Psychopharmacology Meta Supplementary

Subcortical Cluster Trajectory

Horea-Ioan Ioan˘ as

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Institute for Biomedical Engineering, ETH and University of Zurich Imaging Monoaminergic Systems and their Pharmacological Control

SLIDE 29

Context Technology Fingerprinting Psychopharmacology Meta Supplementary

Unsupervised Classification Model Selection

◮ Reliability as a proxy for cross-validation ◮ Tentative indication of cluster correlation

Horea-Ioan Ioan˘ as

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Institute for Biomedical Engineering, ETH and University of Zurich Imaging Monoaminergic Systems and their Pharmacological Control

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Context Technology Fingerprinting Psychopharmacology Meta Supplementary

Seed-Based Connectivity — Concept

Brain Laser DR u1 Cingulate Cortex u2d Olfactory Bulb u2c Hippocampus u2b ... u2a

Horea-Ioan Ioan˘ as

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Institute for Biomedical Engineering, ETH and University of Zurich Imaging Monoaminergic Systems and their Pharmacological Control

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Context Technology Fingerprinting Psychopharmacology Meta Supplementary

Seed-Based Connectivity — Maps

Activation map (stimulation GLM) Transmission map (DR seed GLM)

Horea-Ioan Ioan˘ as

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Institute for Biomedical Engineering, ETH and University of Zurich Imaging Monoaminergic Systems and their Pharmacological Control

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Context Technology Fingerprinting Psychopharmacology Meta Supplementary

Seed-Based Connectivity — Timecourses

Activation timecourse in cortical cluster Transmission timecourse in cortical cluster

Horea-Ioan Ioan˘ as

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Institute for Biomedical Engineering, ETH and University of Zurich Imaging Monoaminergic Systems and their Pharmacological Control