CNS, GM talks

Things I did this summer

Gustavo Patow
ViRVIG-Udg, CNS-UPF

gustavo.patow@udg.edu
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 Watched
TV &
Cinema
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 Went to the
beach…

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Had fun!

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And more fun! ;-)

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And of course, work a little
bit! ;-)
But not too much! :-)))

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Alzheimer’s Disease: Overview

• Most common
type of dementia
• 60% - 80% of
cases

• Progressive –
symptoms
gradually worsen
over number of
years The New York Times:
https://www.nytimes.com/2016/11/23/health/eli-lillys-experimental-alzheimers-drug-failed-in-large-trial.html

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What does it do?

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Stages of Alzheimer’s
Disease
• Average lifespan 4-8 years after
diagnosis; as long as 20 years
• Progresses slowly in 3 stages:
o Mild (early-stage)
o Moderate (middle-stage)
o Severe (late-stage)

Alzheimer’s Association. Stages of Alzheimer’s. Accessed June 8, 2015 from

website: http://www.alz.org/alzheimers_disease_stages_of_alzheimers.asp 10
Pathophysiology: Abeta (Aβ)

Alzheimer's disease. Nat Rev Dis

Primers 1, 15059 (2015)
https://doi.org/10.1038/nrdp.2015.59 11
Pathophysiology: Tau

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The story so far…
• Wrote my first AD paper (Project #1)
• Desk-rejected several times (once just “rejected”)
• Now (seriously) being considered for a good AD journal

• Desember 2022: Read Anira’s thesis… Wow!

• January 2023: what if… ;-)
• Learn…
• Fast!
• Rely on Anira ;-)

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The past…
Project #1: Aβ&Tau
Under review…

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Model: BEI Pretty standard…

Standard,
but not that
much!

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Specific Model

As simple as it can get!

s for scalings
b for bias

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Are all parameters equally important (AD)?

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Status of now…
• Only 15 days to do a series of minor-not-so-minor changes
• AT(N) classification
• Changing plots
• Rewritting…

• Bah! The usual stuff! ;-)

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Project #2
Codename: Project AD-Meta
Before summer, but writing during summer…
With Anira’s help…

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Ignition Framework
• [Deco & Kringelbach 2017]
• Purpose: measure and understand the intrinsic dynamics and
communication principles of brain activity across all levels of
networks
• Characterize the way that information propagates from a local node
through the network
• The underlying fluctuations and their functional network consequences
• Intrinsic ignition refers to the capability of a given local node in
space to propagate feedforward and recurrent neuronal activity to
other nodes in the network as measured by the whole-brain
integration elicited

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Metastability
• Local metastability:
• the variability of a state that falls outside the natural
equilibrium state of the system but persists for an extended
period
• different levels of temporal diversity in each node can be
thought of as a measure of local functional variability and thus
describe the versatility of a given network node

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Intrinsic Ignition Framework
[Deco and Kringelbach 2017]

22
Spectrum of Possible Dynamical Processing
Hierarchies

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 Hierarchy Disruption Factor (HDF)
Meta & Whole-Brain

24
Meta & RSNs

Nice, lots of stars!!! ;-) 25

Aβ & Tau levels

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Mixed effects models
• Set out to study the relation between Metastability and Aβ and tau
at
• Whole Brain
• RSNs (Yeo’s 7 RSNs)

• Mixed what?

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Learn!

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Mixed effects models
• Metastability and Aβ and tau in
• Whole Brain
• RSNs (Yeo’s 7 RSNs)
W
ilk
• Automatic formulae analysis in s
(Python statsmodels → Matlab Engine) No on-R
tat og
ion er
s
Meta ~ ABeta*Tau + (1|ID) + (ABeta|ID) + (Tau|ID)

Abeta + Tau + Abeta:Tau

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Results (Whole Brain)

Meta ~ ABeta*Tau + (1|ID) + (ABeta|ID) + (Tau|ID)

(Intercept) 0.06363808576954283 0.1075

ABeta -0.0019687474922957574 0.9349

Tau 0.03294103969714491 0.0197

ABeta:Tau -0.011958699927983879 0.1352

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RSN_Meta ~ ABeta*Tau + (1|ID) + (ABeta|ID) + (Tau|ID)

RSN_SalVentAttn (Intercept) 0.3054838670918788 0.0

ABeta -0.08764630114774977 0.0159
Tau -0.08372209810718427 0.0001
ABeta:Tau 0.03781606134444512 0.002

RSN_SomMot (Intercept) 0.1117300217281923 0.0002

ABeta -0.034032563301507966 0.0453
Tau -0.011263288780150926 0.228
ABeta:Tau 0.01096638234663435 0.0478

RSN_Vis (Intercept) 0.10921097280779922 0.0553

ABeta -0.029322491503064506 0.3975
Tau 0.07066723469379906 0.0008
ABeta:Tau -0.019128379656994435 0.0959

What about DMN? → more work! 31

DMN and Abeta & tau
• Abundant literature about DMN
• Other RSN barely touched
• Consistent findings of inhomogeneous affectation across
subareas…

• Do it! ;-)

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Project #3
Codename: Project AD-LEiDA
My real summer project! ;-)
With Anira’s help…

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Leading Eignevector Dynamics Analysis

State1 Probabilistic StateN Probabilistic

Metastable Substate Metastable Substate

Let’s see each stage in more detail…

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Computations (I)
• BOLD phase synchronisation
• Compute BOLD phase
• Hilbert: xa = a(t)ei𝜙(t)

35
Computations (II)
• Phase dFC and Leading Eigenvectors
• Calculate phase synchrony: dFCn,p(t) = cos(𝜙n(t) - 𝜙p(t))

36
Computations (III)
• Clustering and probabilistic metastable substate (PMS)

State1 Probabilistic StateN Probabilistic

Metastable Substate Metastable Substate

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Our (current) implementation
• Run clustering for k between 2 and 20
• Run for 100 different rnd seeds:
• because internally clustering uses rnd configurations
• Used Dunns clustering criterion…

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EVect!

39
Transitions…

40
Probs and lifetimes…

No stars, no paper… yet! ;-)

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(Current) Future Work
• What can the problem be?
• Alzheimer itself!

• Change criterion
• Many many options
• Silhouette?
• Maximize PMS discrimination?
• Other?

• Of course, if *’s, Write! ;-)

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(Real) Future Work

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Project #4
Codename: Project AD-Awakening
Put on hold for now… (see next)
With Anira and… Jakub? ;-)

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Burden propagation (Starting: October/2023)
Project #5

(a)Clinical
observation

(b) continuum
model

(c) Network
spreading
model
[Fornari et al. 2019]
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Better model? (secret project #6)
• Why?
• OK, it is the simplest model… but really, WHY?

With insights from Sebi… ;-)

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Secondary current project #7
Codename: AD-FDT
• With Juan Monti, on my (scarce) free time

• Do a model-free implementation of the FDT framework

• Key: formulate as Langevin process
• Needs a gaussian noise…
• If x(t) is BOLD… who’s 𝜂 ?
• A gaussian noise! ;-)

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Future Work (Someday) [Noori et al. 2020]

Bidirectional Myelin Remodeling as a compensation

mechanism…

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Thanks!
For Projects #2 and #3, co-authors:
• Gus D. and Petra R.
• Anira E.

For Project #7:

• Juan M.

And those who helped:

• Paulina D.
• Daniela A-V.
• Joana C. for the online code
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CNS, GM talks

Things I did this summer

Thanks!
Questions?

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