Signal Processing, modelling

and AI WP 5.1 - 5.4

Jari Hyttinen

HERMES CONSORTIUM MEETING

Dec 2-6th 2019

Funded by European Union’s Horizon 2020

FETPROACT-2018-2020 - GA n. 824164
WP 5
Task 5.1 Development and implementation of signal processing &
analysis methods [1-60]
Deliverable: core software architecture foreseen on M18
Task 5.2 Computer simulation framework for graft, host, NCS [1-12]
Deliverable: Computer simulation framework of dynamics
underlying graft/host/NCS
behavior to facilitate testing & optimization of the developed NCS
Task 5.3 Population of models Computer simulations to train & optimize
the AI agent, based on framework developed in T5.2 [4-36]
Task 5.4 AI agent [7-60]
Funded by European Union’s Horizon 2020
FETPROACT-2018-2020 - GA n. 824164
Overview
• Scales of neuronal systems in-vitro – in vivo and scales in Hermes
• Signal processing needs in neuronal analysis – Hermes
perspectives
• Modelling of neuronal system in scales – Hermes perspectives

Funded by European Union’s Horizon 2020

FETPROACT-2018-2020 - GA n. 824164
 Managing epilepsy by stimulus?

Control of
brain state

AI Driven
Memnistors,
neuromorphic chip Classification of the epilepitic
AI driven
events/system state
Stimulus to drive methods to do the classificaiton to
the organoid generate learning material ofr AI based
classification
Funded by European Union’s Horizon 2020
FETPROACT-2018-2020 - GA n. 824164
 Signal processing needs in HERMES
2D and 3D cultures and slices
on MEA: Spike and burst data
20Khz sampling 60- 4k
Channels

In-vitro organoids on 2D and 3DMEA

Spike and burst data + field
pontetials 10-20Khz sampling 60- 4k
Channels
Epileptic event?
Understand the
state of the
neuronal system
In-vivo animal EEG with epilepcy epochs for translation?
Field pontetials!
500hz sampling and few channels

Funded by European Union’s Horizon 2020

FETPROACT-2018-2020 - GA n. 824164
 Sinal processing in general : Measures – quantitative markers?
1. Activity IDENTIFICATION (including epilepcy):
• Events spikes, bursts, vaweforms…
• Frequency content, …
2. Connectivity & propagation measures?
• Network connections (functional and topological)
• Between electrodes… thus neuronal areas

3. Measuree State of the brainas dynamical

system?
Funded by European Union’s Horizon 2020
FETPROACT-2018-2020 - GA n. 824164
In Vitro Microelectrode Array (MEA) Basics

Funded by European Union’s Horizon 2020

FETPROACT-2018-2020 - GA n. 824164
Assessing in-vitro systems: spike/bursts
Spike and burst detection -> ”binarization”

amplitude (V)
0

1 2 3 4 5 6 7 8 9 10 11
time (s)

Funded by European Union’s Horizon 2020

FETPROACT-2018-2020 - GA n. 824164
D. Open-loop MEA2100 vs. Closed-loop
MEA2100
Fixed stimulation paradigms

PC & Software
Visual. during meas.
Minor online analysis
Offline data analysis

Base figure by Multi Channel Systems MCS GmbH, Reutlingen, Germany

Funded by European Union’s Horizon 2020
Modified for the presentation FETPROACT-2018-2020 - GA n. 824164
ID. Open-loop MEA2100 vs. Closed-loop
MEA2100
Adaptive stimulation paradigms

In the DSP: DSP output storage

Real-time analysis Data storage
Real-time feedback gen. Offline analysis

Base figure by Multi Channel Systems MCS GmbH, Reutlingen, Germany

Funded by European Union’s Horizon 2020
Modified for the presentation FETPROACT-2018-2020 - GA n. 824164
II. Close-loop Stimulation Experiment Example 2 Results

Activity pre-stimulation, during stimulation and post-stimulation at 20 DIV.

FS – Feedback stimulation; ES –Predetermined Stimulation
BA – Basal activity Funded by European Union’s Horizon 2020
FETPROACT-2018-2020 - GA n. 824164
II. Close-loop Stimulation Experiment Example 2 Results

Activity pre-stimulation, during stimulation and post-stimulation at 20 DIV.

FS – Feedback stimulation; ES –Predetermined Stimulation
BA – Basal activity Funded by European Union’s Horizon 2020
FETPROACT-2018-2020 - GA n. 824164
Combined spike and burst analysis for analyzing
networks

F. E. Kapucu, et al ,“Joint analysis of extracellular action

potentials and neuronal network events for in vitro
neurotoxicology,” submitted to NeuroToxicology

Spike activity curves for the

GABA tests

Funded by European Union’s Horizon 2020

FETPROACT-2018-2020 - GA n. 824164
Assessing in-vitro systems: spike/bursts
Event detection and classification

Angel Alonso

Funded by European Union’s Horizon 2020

FETPROACT-2018-2020 - GA n. 824164
Ahtiainen 2019
Funded by European Union’s Horizon 2020
FETPROACT-2018-2020 - GA n. 824164
Network connectivity and propagation

The development of a functional

neuronal network in a mouse cortical
cell culture unraveled by SE

Funded by European Union’s Horizon 2020

FETPROACT-2018-2020 - GA n. 824164
Neuronal dynamics in various scales
Wu et al 2016 Front. Neuroanat., 03 March 2016 |
https://doi.org/10.3389/fnana.2016.00018

https://www.alamy.com/stock-photo-coronal-
view-of-rat-brain-connectivity-top-view-images-
reconstructed-87046775.html

Application of the entropy on experimental in

vivo (rat hippocampal)and in-vitro rat cortical
cell connectivity (Kapucu et al. 2016) Funded by European Union’s Horizon 2020
FETPROACT-2018-2020 - GA n. 824164
Human brain…. Morphological and
functional connectoivity

Funded by European Union’s Horizon 2020

FETPROACT-2018-2020 - GA n. 824164
 GFAP, DAPI beta 3-tubuilin

Organoid?
• Signaling Morphology

• ??? Ahtiainen 2019

Funded by European Union’s Horizon 2020

FETPROACT-2018-2020 - GA n. 824164
Brain and neuronal network as dynamical system…
assessment of the state

path length

transitivity dimension

assortativity

Funded by European Union’s Horizon 2020

FETPROACT-2018-2020 - GA n. 824164
 Electrodes vs signals and stimulus
Tanskanen et al 2010
1. Electrode size Halonen et al 2019
2. Electrode material g ! ! !
s s in
r oc e
3. Electrode location
na lp
(reference electrode o sig
location!!!) n s t
ati o
p lic
4. ”biomaterial” surrounding = im
electrode n a ls
o sig
VS: on t .
licati ing …
5. NeuronalIm p d e
cells propertiesll
m o
nd
near the electode
A Alarautalahti et al 2019
Biran, et al Experimental neurology 195.1 (2005):
6. Neuronal netowork sychrony 115-126.

Funded by European Union’s Horizon 2020

FETPROACT-2018-2020 - GA n. 824164
 Signal processing and modelling need SIGNALS

Where, size, distances,

materials? Paldanius et al 2019
- Measurement
electrodes?
- Simulus electrodes ?
- ”organoid” ?

- We can also SIMULATE

these!

https://www.sciencedirect.com/science Funded by European Union’s Horizon 2020

/article/pii/S2212877815001428 FETPROACT-2018-2020 - GA n. 824164
 Modelling ? In-silico simulation

Control of
brain state

To test the HERMES hypotheis

Test the software and hardware
components and systems
To provide learning material for Ai
and neuromophic systems

AI Driven
Memnistors,
neuromorphic chip AI basedClassification of the
AI driven epilepitic events/system state
Stimulus to drive methods to do the classificaiton to
the organoid generate learning material and
measures for classification
Funded by European Union’s Horizon 2020
FETPROACT-2018-2020 - GA n. 824164
Astrocyte
communication with Tripartite
neurons and Synapse
pericytes/endothelia
1. Energy (lactate)
2. Ion Balance
3. Gliotransmission
4. Astrocyte Ca excitability intra and
ibtercellular Ca signals
De Pitta and Hugues
(eds): Computational
Ca-signaling Clioscience 2019 Funded by European Union’s Horizon 2020
FETPROACT-2018-2020 - GA n. 824164
|
 Electrophysiological models…

• Ion channel models

• Hodgin-Huxley type models of neurons
• Local neuronal networks (+astrocytes ?)
• Integrated and fire, Poisson neurons…
• Neuron connectome based network models
• Neural mass models (phenomenological)
• Connectome of neuronal mass (brain connectivity)

Funded by European Union’s Horizon 2020

FETPROACT-2018-2020 - GA n. 824164
 Modelling ?

Control of
Organoid
brain state

Stimulus to Classification of the epilepitic

drive the Memnistors,
neuromorphic system, events/system state?
organoid AI ?

Funded by European Union’s Horizon 2020

FETPROACT-2018-2020 - GA n. 824164
VI. Questions & Discussion

Funded by European Union’s Horizon 2020

FETPROACT-2018-2020 - GA n. 824164