Self-Regulated Complexity of Bio-Networks Activity Eshel Ben Jacob Eyal Hulata Itay Baruchi Ronen...
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![Page 1: Self-Regulated Complexity of Bio-Networks Activity Eshel Ben Jacob Eyal Hulata Itay Baruchi Ronen Segev Yoash Shapira Phys Rev Lett in press Complexity.](https://reader034.fdocuments.in/reader034/viewer/2022042615/56649d7e5503460f94a605b4/html5/thumbnails/1.jpg)
Self-Regulated Complexity of Bio-Networks Activity
Eshel Ben Jacob
Eyal Hulata
Itay Baruchi
Ronen Segev
Yoash Shapira
Phys Rev Lett in press
Complexity is still
a blurred intuitive notion
with no agreed upon definition
By looking for two quantified observables: Regularity and Complexity associated with the intuitive notion
Inspired by the recorded activity of cultured neural networks
We try to make sense out of the mess
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On the Agenda
Cultured networks and their activity
Hints about self-regulation
The requirements from the new observables
Looking at the time-frequency plane
The best tilling
The sequence regularity
The structure factor and structural complexity
Results
Looking ahead
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Our approach:Relative information in both time and frequency:
Tiling of the time-frequency plane
time
freq
uenc
y
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V. What do we expect from a measure of Structural
complexity?[Hubberman and Hogg, Physica D 86, Gellmann “The Quark and the Jaguar”]
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Comparison of the
Time-frequency domains
recorded shuffled
New clue
Local and global variations
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Neuronal cell cultures
• Dissociated cell culture from the cortex of one-day-old rats.
• 10,000 neurons/mm2.
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50µm
Multi Electrode Array
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Non-Invasive Recording of the Activity(Capacitive Coupling between neurons and electrodes)
……. Polymer
30micro
20 milliseconds
one action potential of one neuron
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Time
Formation of Bursting Events
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Tracking a WOOZLE
Information-bearing templates
in the
Temporal ordering
of the
Recorded spontaneous activity
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CONCISE HISTORICAL PERSPECTIVE
Neurons are binary elements
Localized information
storageDistributed information storage
RATE CODING vs. PULSE CODING
Currently: a Dynamic Networks picture
Guiding Questions
1. Is the spontaneous activity arbitrary or regulated ?
2. Can it provide clues about coding,
storage and retrieval of information ?
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Statistical scaling properties of the SBE sequences
I(i)
Interval distribution Increment distribution
DifI(i)
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Increment length (sec/τbin)
Pro
babl
ity
dens
ity
func
tion
(pd
f)
0 2 0
Lévy distribution
=2
1/1/ The sequence's plasticityThe sequence's plasticity
11// The sequence's regularityThe sequence's regularity
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Comparison between networks of various sizes
1. Similar most probable interval ~10 sec
2. DifI(i) can be approximated
with zero-means symmetric Levy distributions
Small medium large50 20,000 1000,000
(higher density)
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Experimental Model
100 sec 100 sec0.1 sec 0.1 sec
This feature can be simulated in modeled networks
if the neurons have two degrees of freedom
and the synapses are dynamical
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Interfacing Real and Modeled Networks
Volman et al., Phys Rev E
1.Feeding the modeled network from regulating neurons
2.Testing the effect of synaptic strengths
conclusion
To show the same rate of activity as the similar networks
the large networks have to be
composed of coupled sub-networks
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Hints about Self-Regulation
Controlled large variations vs. arbitrary large fluctuations
< [DifI(i)] >2
recorded
shuffled
model network
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another hint : hierarchical temporal ordering
Bursts of SBEs , bursts of bursts of SBEs …
x10
Time cascade
1ms 100ms 5-10sec 500-100sec
Spike width SBE width Inter-SBEs Inter bursts of SBEs
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510 210 [Hz]
Third hint :LONG-TIME CORRELATIONS
OVER a DAY !!!
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THE OBSERVATIONS IMPLY THAT
Both the PULSE CODING
and the RATE CODING
do not provide the proper template
A new picture is needed
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A DEDUCED CLUE
The recorded sequences
should be mapped
(via wavelet packet decomposition)
into time-frequency domains
time
freq
uen
cy
“energy”
time resolution
frequ
ency
resolution
Local and Global variations
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Structural complexity
What have we seen so far?
Local features in segments of time series.
Temporal ordering and local rates.
Variation among segments.
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Detour - Time-Frequency analysis
A. Wavelet Transform
0
2
0
d)(
C11
where
2ba,
ba,ba,
a
dadbtψ
aba,W
Ctf
a
b-tψtψdttψ
a
1f(t)ba,W
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Detour - Time-Frequency analysis
A. Wavelet Transform
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Time-Frequency Plane of the Wavelet Transform
Time bins
Time bins
Fre
quen
cy b
ands
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Detour - Time-Frequency analysis
B. Wavelet Packets Decomposition
Coifman & Wicherhauser, 1993
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How do we choose packets?
)m,n(II k,jm,n packets choose we , if
2
nn
)t(f
ψf(t)q
: npacket of energy the is qn
)qlog(q)qlog(qI
(n,m)
mmnnm,n
:n)informatio Shannon by (inspired
packetsfor functioncost The
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Phase I:
Level 0 Level 1 Level 2
or ?Phase Ia: or ?Phase Ib: or ?Phase Ic: or ?Phase Id:
Phase II:
Level 0 Level 1
or ?Phase IIa:The best tiling:Thiele & Villemous, A.C.H.A., 1996
The Best Tiling Algorithm
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Back to Structural complexity…
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Physical Intuition - magnetization
tiles length of signal binbin NN
binbin
NarN
1;
Δt
Δωar :tile a of ratioaspect
1R1
Nlog
arlogR
n
bin2
2n
:tile a of resolution relative
![Page 35: Self-Regulated Complexity of Bio-Networks Activity Eshel Ben Jacob Eyal Hulata Itay Baruchi Ronen Segev Yoash Shapira Phys Rev Lett in press Complexity.](https://reader034.fdocuments.in/reader034/viewer/2022042615/56649d7e5503460f94a605b4/html5/thumbnails/35.jpg)
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binN
1nn
bin
RN
1RM :measure regularity
Regularity Measure
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Structure factor
energy) zero-non with tiles only (counting
neighbors tilingnearest :
:factor structure
n,m
RRSFn,m mn
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Structural complexity
jSF
)Nj1N
:word eachfor factor structure
( words into segmented is signal a
wN
1j
2
j SFSFN
1)SFvar(SC
:complexity structural
![Page 39: Self-Regulated Complexity of Bio-Networks Activity Eshel Ben Jacob Eyal Hulata Itay Baruchi Ronen Segev Yoash Shapira Phys Rev Lett in press Complexity.](https://reader034.fdocuments.in/reader034/viewer/2022042615/56649d7e5503460f94a605b4/html5/thumbnails/39.jpg)
Our results:
![Page 40: Self-Regulated Complexity of Bio-Networks Activity Eshel Ben Jacob Eyal Hulata Itay Baruchi Ronen Segev Yoash Shapira Phys Rev Lett in press Complexity.](https://reader034.fdocuments.in/reader034/viewer/2022042615/56649d7e5503460f94a605b4/html5/thumbnails/40.jpg)
Studied using artificial sequences with Levy distribution
The Regularity-Complexity Plane
![Page 41: Self-Regulated Complexity of Bio-Networks Activity Eshel Ben Jacob Eyal Hulata Itay Baruchi Ronen Segev Yoash Shapira Phys Rev Lett in press Complexity.](https://reader034.fdocuments.in/reader034/viewer/2022042615/56649d7e5503460f94a605b4/html5/thumbnails/41.jpg)
Applying to neuronal data:Neuronal time series of SBEs Shuffled Neuronal time series
freq
uenc
y
timefr
eque
ncy
time
![Page 42: Self-Regulated Complexity of Bio-Networks Activity Eshel Ben Jacob Eyal Hulata Itay Baruchi Ronen Segev Yoash Shapira Phys Rev Lett in press Complexity.](https://reader034.fdocuments.in/reader034/viewer/2022042615/56649d7e5503460f94a605b4/html5/thumbnails/42.jpg)
Zoom: shuffling of neuronal data
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Finding a characteristic time scale
x10
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Testing the Generality of Motives
Investigating cultured networks
made of neurons taken from
the frontal ganglion.
![Page 46: Self-Regulated Complexity of Bio-Networks Activity Eshel Ben Jacob Eyal Hulata Itay Baruchi Ronen Segev Yoash Shapira Phys Rev Lett in press Complexity.](https://reader034.fdocuments.in/reader034/viewer/2022042615/56649d7e5503460f94a605b4/html5/thumbnails/46.jpg)
In vivo
In vitro
frontalganglion
Ex vivo
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RATIONALE
This ganglion has a specificrole (feeding).
We will compare recordingsfrom the ganglion insidethe animal while feedingand while “thinking”, andwhen on the plate.
Looking for “function-follow-form” in action
![Page 48: Self-Regulated Complexity of Bio-Networks Activity Eshel Ben Jacob Eyal Hulata Itay Baruchi Ronen Segev Yoash Shapira Phys Rev Lett in press Complexity.](https://reader034.fdocuments.in/reader034/viewer/2022042615/56649d7e5503460f94a605b4/html5/thumbnails/48.jpg)
The Statistical Scaling Parameters of
In-vitroEx-vivo
In-vivoIn-situ
“thinking”digesting
3 different neurons
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regularity
0.8
0.75
0.7
0.65
0.6
0.55
0.5
0.45
0.4
1.61.8
1.4
2.12.0
6.0
In-vivo (f)
Ex-vivo
In-vivoCulture
Culture
gama alpha
com
ple
xit
y
Self-regulated complexity of neural activity
Hulata et al., PRLAyali et al., ?In vitro
In situ
In vivo (thinking)
Ex vivo
![Page 50: Self-Regulated Complexity of Bio-Networks Activity Eshel Ben Jacob Eyal Hulata Itay Baruchi Ronen Segev Yoash Shapira Phys Rev Lett in press Complexity.](https://reader034.fdocuments.in/reader034/viewer/2022042615/56649d7e5503460f94a605b4/html5/thumbnails/50.jpg)
10sec
Spikes ,
4 days
20sec
Alternation between active and non-active phases .
5-6 days
Looking at Networks Development
100sec
Burst organization9-10 days
100sec
Hierarchical structureBurst of bursts,
14 days
![Page 51: Self-Regulated Complexity of Bio-Networks Activity Eshel Ben Jacob Eyal Hulata Itay Baruchi Ronen Segev Yoash Shapira Phys Rev Lett in press Complexity.](https://reader034.fdocuments.in/reader034/viewer/2022042615/56649d7e5503460f94a605b4/html5/thumbnails/51.jpg)
100msec 10msec
Electrical activity Recorded from 14 days network
![Page 52: Self-Regulated Complexity of Bio-Networks Activity Eshel Ben Jacob Eyal Hulata Itay Baruchi Ronen Segev Yoash Shapira Phys Rev Lett in press Complexity.](https://reader034.fdocuments.in/reader034/viewer/2022042615/56649d7e5503460f94a605b4/html5/thumbnails/52.jpg)
Probability density function of increments distribution
APs time series
T1 … Tn-1 , Tn , Tn+1 …
Inter-spikes Intervals
ISIn= Tn-Tn-1
Increments of ISI
(ISI)n = ISIn- ISIn-1
4 days 5-6 days 9 days
104 106102100msec
100 102 104msec 104 106102100
msec
![Page 53: Self-Regulated Complexity of Bio-Networks Activity Eshel Ben Jacob Eyal Hulata Itay Baruchi Ronen Segev Yoash Shapira Phys Rev Lett in press Complexity.](https://reader034.fdocuments.in/reader034/viewer/2022042615/56649d7e5503460f94a605b4/html5/thumbnails/53.jpg)
log-log scale
linear scale
Inter burst intervals (IBI) distribution parameters
“young” networks “mature” networks
γ 2
5<δ<10
α1.6
“young” network Pdf parameters
γ 5
5<δ<10
α1.2
“mature” network Pdf parameters
Most probable interval
Decay slope
![Page 54: Self-Regulated Complexity of Bio-Networks Activity Eshel Ben Jacob Eyal Hulata Itay Baruchi Ronen Segev Yoash Shapira Phys Rev Lett in press Complexity.](https://reader034.fdocuments.in/reader034/viewer/2022042615/56649d7e5503460f94a605b4/html5/thumbnails/54.jpg)
t=0.002
Structural complexity of burst time series
complexity regularity
“young” networks
“mature” networks
“mature” networks
“young” networks
![Page 55: Self-Regulated Complexity of Bio-Networks Activity Eshel Ben Jacob Eyal Hulata Itay Baruchi Ronen Segev Yoash Shapira Phys Rev Lett in press Complexity.](https://reader034.fdocuments.in/reader034/viewer/2022042615/56649d7e5503460f94a605b4/html5/thumbnails/55.jpg)
Structural complexity of spike sequence during 4-6 days
0 9 183 6 12 15 0 9 183 6 12 15
time (hours) time (hours)
Complexity Regularity
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306 12 18 240
time (hours)
306 12 18 240time (hours)
ComplexityRegularity
Developments of the Bursts Regularity-Complexity
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γ 55<δ<10
α1.2
“mature” network Pdf parameters
γ 25<δ<10
α1.6
“young” network Pdf parameters
α 1/α;SC
γ 1/γ;RM
0=δ 20=δ
random periodic
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ConclusionsWe have defined a new set of structural measures: Regularity Measure, Structure Factor, Structural Complexity.The measures fulfill both intuitive and quantitative requirements.The measures reveal new features of the neuro-informatic template of in-vitro neural networks.Future work: 1. comparison of in-vitro vs. in-vivo networks.2. study the effects of chemical substances,
coupling between networks, stimulations etc.
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binN
1nn
bin
RN
1RM :measure regularity
Regularity Measure
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