KTH ROYAL INSTITUTE

OF TECHNOLOGY

Introduction to Neuroinformatics
Importance of Modelling and Simulations

Pawel Herman
Department of Computational Science and Technology,
School of Computer Science and Communication
KTH Royal Institute of Technology, Sweden

Neuroscience course, May 17

 Why is it important to study brains?

• Quest for knowledge

• Computational inspiration

• Brain disorders and diseases

http://www.modernmedicalguide.com/alzheimers-disease/ Marja-Leena Line, INCF

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 Where are we today?

• collecting more data, building more advanced models,

performing more complex analyses

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 Where are we today?

• collecting more data, building more advanced models,

performing more complex analyses
• BUT:
– studying individual components of neural systems with
little integration/generalisation effort
– focused on a limited set of spatio-temporal scales
– working on disconnected data sets using different tools,
procedures, protocols
– disappointing reproducibility of experimental work (much
improved for simulations)
– poor understanding of neural mechanisms (computational
primitives) at any level of the organisation -> richer
computational mindset needed

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 Where are we today?

Progress is not satisfactory and the needs

are immense, so are the implications of
the advancement of brain science

What could we do to advance the brain science?

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 Where are we today?

Progress is not satisfactory and the needs

are immense, so are the implications of
the advancement of brain science

What could we do to advance the brain science?

Combine efforts, collaborate
interdisciplinarily, organise and share
data, integrate biological evidence,
build multi-scale models etc.

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 What is neuroinformatics?

NEUROSCIENCE

NEUROINFORMATICS COMPUTER SCIENCE

INFORMATION
NEUROMEDICINE TECHNOLOGY (IT)

Neuroinformatics is the mean to connect neuroscience, medical

science, information technology and computer science.

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 What is neuroinformatics?

NEUROSCIENCE eSCIENCE

NEUROSCIENCE

NEUROINFORMATICS COMPUTER SCIENCE

INFORMATION
NEUROMEDICINE TECHNOLOGY (IT)

Neuroinformatics is the mean to connect neuroscience, medical

science, information technology and computer science.

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 Fundamental goals of neuroinformatics
ICT-based brain research – aims and implications

• organise and integrate neuroscience data

• accelerate our quest for understanding the brain

• support neuromedicine, understanding brain diseases

• develop brain-inspired future computing technologies,

brain-like intelligent systems

• promote education, deliver multi-disciplinary training.

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 Fundamental goals of neuroinformatics

ICT-based brain research – fundamental goals

• organise and integrate neuroscience data

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 Fundamental goals of neuroinformatics

ICT-based brain research – fundamental goals

• organise and integrate neuroscience data

“Data tsunami”

“We are drowning in information but starved for knowledge”

John Naisbitt

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 Data Age ̶ Multiomic Neuroscience Data

From sub-cellular resolution to whole brain resolution Sean Hill, INCF

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 Fundamental goals of neuroinformatics

ICT-based brain research – fundamental goals

• organise and integrate multi-level data

gather
existing data
across scales
and levels,
identify
missing data
Sean Hill, INCF

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 Fundamental goals of neuroinformatics

ICT-based brain research – fundamental goals

• organise and integrate multi-level data

gather
existing data
across scales
and levels,
identify
missing data
from genes to behaviour

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 Integrative and data-oriented
neuroinformatics

NEUROINFORMATICS

Sean Hill, INCF

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 Focus for neuroinformatics – data, theory

organise and integrate multi-level data

gather existing data at develop tools for build models, simulate,

multiple levels, storing, visualising develop theories
identify missing data and sharing
information
build databases,
devise new
brain atlases
approaches to
data analysis

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 Focus for neuroinformatics – data, theory

organise and integrate multi-level data

gather existing data at develop tools for build models, simulate,

multiple levels, storing, visualising develop theories
identify missing data and sharing
information
build databases,
devise new
brain atlases
approaches to
data analysis

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Computational neuroscience and
neuroinformatics

Marja-Leena Linne, INCF

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 Modelling – towards integrative neuroscience

What is the purpose of computational modelling?

adapted by
A Kumar

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 Modelling – towards integrative neuroscience

What is the purpose of computational modelling?

• to integrate available data and build theories
• to describe & understand the underlying mechanisms
• to reveal causal relationships
• to generate insights and predictions for experimental
neuroscience, etc.

adapted by
A Kumar

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 Modelling in neuroscience
• What is a model?
Mathematical model is a description of a system using
mathematical concepts - rules, mainly in terms of formulae, e.g.

du
τm = −u (t ) + R I (t )
dt subthreshold activity in the
integrate-and-fire (IF) model

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 An example of a single neuron model – HH
formalism

• Various levels of mathematical description –

• zooming in (on details) vs. zooming out (abstraction)

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 An example of a single neuron model – rate
unit

• Various levels of mathematical description –

• zooming in (on details) vs. zooming out (abstraction)

y = φ(Σ wi xi)
y
φ

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 An example of a single neuron model – rate
unit

• Various levels of mathematical description –

• zooming in (on details) vs. zooming out (abstraction)

y = φ(Σ wi xi)
y
φ

time time

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 Modelling strategy – bridging levels
EMERGING PHENOMENA,
”top-down” HIGHER-LEVEL FUNCTION /
THEORY, GLOBAL / DYNAMICS
FUNCTIONAL PRINCIPLES

NEURAL DETAIL, WEALTH OF

NEURAL IMPLEMENTATION BIOLOGICAL DATA
(DYNAMICS, ARCHITECTURE)
Gerstner et al., Science 2012 ”bottom-up”

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 Modelling strategy – bridging levels
EMERGING PHENOMENA,
”top-down” HIGHER-LEVEL FUNCTION /
THEORY, GLOBAL / DYNAMICS
FUNCTIONAL PRINCIPLES

Synthetic LFP
60
50

Frequency (Hz)
40

NEURAL DETAIL, WEALTH OF

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20
10

NEURAL IMPLEMENTATION BIOLOGICAL DATA

(DYNAMICS, ARCHITECTURE)
2 3 4 5
Time (seconds)
6 7 8
”bottom-up”

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 Modelling strategy – bridging levels
EMERGING PHENOMENA,
”top-down” HIGHER-LEVEL FUNCTION /
THEORY, GLOBAL / DYNAMICS
FUNCTIONAL PRINCIPLES

RESEARCH QUESTION SUITABLE STRATEGY

(DATA, CONSTRAINTS) AND LEVEL OF DETAIL

NEURAL DETAIL, WEALTH OF

NEURAL IMPLEMENTATION BIOLOGICAL DATA
(DYNAMICS, ARCHITECTURE)
”bottom-up”

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 Computational modelling approaches

How can we go about modelling? David Marr’s theoretical approach

Phenomenological models – Statistical models –

mathematical description of description of a system in
phenomena without handling terms of random variables
constituent parts and their distributions (they
Mechanistic models – can be mechanistic or
description of a system in phenomenological)
terms of its constituent parts

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 Computational mindset of David Marr
Three levels of description:

1. Computational level – what does the system do?

• What logic defines the nature of resulting mental 1945-1980
representations of incoming stimuli?

2. Algorithmic level – how does the system do it?

• What processes are involved in building mental
representations? How is input translate to output?

3. Implementation level – how is the system physically

realised – implemented?
• What is the neural hardware – substrate?

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 Typical modelling workflow
1. Defining the model: the research question and the research hypothesis
determine the type of model, the model components, and the approach to
solving the model.
2. Parameter fitting: complex high-dimensional models (biophysical) often have a
huge parameter space that cannot be fully explored, instead parameters are
fitted from the data, available data influences construction of the model.
3. Simulation: model is implemented in the suitable simulator(s), the obtained
simulation results are analyzed and visualized.
4. Validation: the model is confronted with more experimental data, the model
behaviour should correspond to the modelled biological system (at least
qualitatively).
5. Prediction: good models have predictive power, when additionally perturbed
they can show the behaviour of the system under the new conditions.

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 My general modelling philosophy

abstract and conceptual

functional models

Model/simulate
functional aspects cognitive
phenomena,
behavioural
Develop or build effects
on a theory constrain translate

Implement neural anatomy,

signal
substrate
recordings
detailed models with
neural dynamics

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 My general modelling philosophy

Model/simulate
functional aspects Recurrent
associative memory
Develop or build (Hopfield, 1982)
on a theory

Implement neural
substrate

Cortical attractor networks

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 Cortical attractor memory model example
Cortical column
Hopfield network

Cortical
attractor
model

Local
RSNP

Distant
pyramidal

Local
basket cell

Local

Hypercolumn with columns

pyramidal

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 From abstract to biologically detailed
implementation
• individual neurons
• neural populations
• cortical columns
mapping
(Mountcastle et al., 1955)
to biology

Hopfield recurrent neural network

(the concept of a cell assembly, (horizontal connections in the cortical

Hebb’s association) layer 2/3 implementing recurrency)

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 Biologically detailed cortical models

HYPERCOLUMN

MINICOLUMN

Modular structure with hypercolumns consisting

of minicolumnar units (distributed patterns)

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 Biologically detailed cortical models

Attractor networks
HYPERCOLUMN

MINICOLUMN ~1.5 mm

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 Cortical attractor memory model

Hopfield network

Cortical
mapping attractor
model
to biology

Cortical patch

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 Cortical memory function

completion

0 1 2 3 4 5 6 7
seconds

bistability, competition
Lundqvist, Herman et al. (2011) J Cogn Neurosci Herman, Lundqvist et al. (2013) Brain Research

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Oscillatory dynamics in the model

Mesoscopic scales

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Oscillatory phenomena

Synthetic LFP
60
50
Frequency (Hz)

40
30
20
10

2 3 4 5 6 7 8
Time (seconds)

Herman, Lundqvist et al. (2013) Brain Research

Lundqvist, Herman et al. (2011) J Cogn Neurosci

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Large-scale simulations
Hodgkin-Huxley

TOOLS

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 A holistic computational model of
mammalian olfactory system

receptors and olfactory receptor cells

Buck and Axel, 1991

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 A holistic computational model of
mammalian olfactory system

olfactory
bulb

Benjaminsson, Herman et al.(2012)

Buck and Axel, 1991

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 A holistic computational model of
mammalian olfactory system
olfactory cortex

Benjaminsson, Herman et al.(2012)

Buck and Axel, 1991

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 Abstract model vs spiking detailed model

Benjaminsson, Herman et al.(2012) Kaplan et al., 2014

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 Abstract model of mammalian olfaction

A wide spectrum of results

Benjaminsson, Herman et al.(2012)

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 How do computational models help?

• Integrate (and fit) experimental data

• Describe neural systems – provide
mechanistic understanding of the neural
system
• Make predictions about the system behavior
in new conditions
• Provide new ways to study brain diseases Marja-Leena

• Provide principles to develop new technology

(brain-like computing, neuromorphic systems,
control for robots)

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 Future challenges for computational
neuroscience

• Design of biologically realistic models that span over

many levels of spatial organization and a wide range of
temporal scales
• The need for development of multi-scale interoperable
simulation tools (e.g. MUSIC)
• Further advancement of simulation technology allowing
for interactive control with visualisation capabilities
• Enforcing tighter links with biology – interactive and
iterative process that deeply involves experimental work

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Trends and future outlook – what do we need
for that?

• more theory and simulations

• tighter connections with experimentalists

(from genes to behaviour)

• computational power for large-scale massively

parallel simulations

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Trends and future outlook – what do we need
for that?

• more theory and simulations

• tighter connections with experimentalists

(from genes to behaviour)

• computational power for large-scale massively

parallel simulations

• tools for simulations, analysis and visualisation

MOOSE

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Thank you for attention

QUESTIONS ?

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