Localized transient waves of cortical spreading depression in migraine
-
Upload
mpi-dresden-hu-berlin -
Category
Health & Medicine
-
view
1.261 -
download
0
description
Transcript of Localized transient waves of cortical spreading depression in migraine
![Page 1: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/1.jpg)
Localized transient waves of cortical spreadingdepression in migraine
Markus A. Dahlem
Research group: Nonlinear Dynamics in Physiology and Medicine
nucleationcritical
23 min
21
19
17
17
15
1311
975
10°
1 cm
Visual hemifield Primary visual cortex
The Dynamics of Disease, Manchester August 23, 2012
Markus A. Dahlem, TU Berlin
![Page 2: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/2.jpg)
Outline
1 Introduction
2 Localized spots traveling in human cortex
3 Modeling migraine with aura
Markus A. Dahlem, TU Berlin
![Page 3: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/3.jpg)
Outline
1 Introduction
2 Localized spots traveling in human cortex
3 Modeling migraine with aura
Markus A. Dahlem, TU Berlin
![Page 4: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/4.jpg)
Long history in non-drug migraine treatment
Markus A. Dahlem, TU Berlin
![Page 5: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/5.jpg)
Long history in non-drug migraine treatment
Markus A. Dahlem, TU Berlin
![Page 6: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/6.jpg)
Berlin, Institute of Physiology
Markus A. Dahlem, TU Berlin
![Page 7: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/7.jpg)
Organic Physics – The Fab Four
Markus A. Dahlem, TU Berlin
![Page 8: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/8.jpg)
Organic Physics – The Fab Four
Markus A. Dahlem, TU Berlin
![Page 9: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/9.jpg)
Organic Physics – The Fab Four
Kymograph (Carl Ludwig)
Markus A. Dahlem, TU Berlin
![Page 10: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/10.jpg)
History of electrical stimuation (Don’t try this at home!)
Non-drug treatment for headaches.
P. J. Koehler and C. J. Boes, A history of non-drug treatment in headache,particularly migraine. Brain 133:2489-500. 2010
Markus A. Dahlem, TU Berlin
![Page 11: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/11.jpg)
History of electrical stimuation (Don’t try this at home!)
Non-drug treatment for headaches.
P. J. Koehler and C. J. Boes, A history of non-drug treatment in headache,particularly migraine. Brain 133:2489-500. 2010
Markus A. Dahlem, TU Berlin
![Page 12: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/12.jpg)
History of electrical stimuation (Don’t try this at home!)
Non-drug treatment for headaches.
P. J. Koehler and C. J. Boes, A history of non-drug treatment in headache,particularly migraine. Brain 133:2489-500. 2010
Markus A. Dahlem, TU Berlin
![Page 13: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/13.jpg)
History of electrical stimuation (Don’t try this at home!)
Non-drug treatment for headaches.
Markus A. Dahlem, TU Berlin
![Page 14: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/14.jpg)
Neuromodulation
”The headache future is bright for neuromodulation techniques ... if wemanage to understand how they work” (Jean Schoenen)
figure courtesy of Jean Schoenen
Markus A. Dahlem, TU Berlin
![Page 15: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/15.jpg)
Neuromodulation
”The headache future is bright for neuromodulation techniques ... if wemanage to understand how they work” (Jean Schoenen)
figure courtesy of Jean Schoenen
Markus A. Dahlem, TU Berlin
![Page 16: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/16.jpg)
Neuromodulation
”The headache future is bright for neuromodulation techniques ... if wemanage to understand how they work” (Jean Schoenen)
figure courtesy of Jean Schoenen
Markus A. Dahlem, TU Berlin
![Page 17: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/17.jpg)
Neuromodulation
”The headache future is bright for neuromodulation techniques ... if wemanage to understand how they work” (Jean Schoenen)
figure courtesy of Jean Schoenen
Markus A. Dahlem, TU Berlin
![Page 18: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/18.jpg)
Neuromodulation
”The headache future is bright for neuromodulation techniques ... if wemanage to understand how they work” (Jean Schoenen)
figure courtesy of Jean Schoenen
Markus A. Dahlem, TU Berlin
![Page 19: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/19.jpg)
Neuromodulation
”The headache future is bright for neuromodulation techniques ... if wemanage to understand how they work” (Jean Schoenen)
figure courtesy of Jean Schoenen
Markus A. Dahlem, TU Berlin
![Page 20: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/20.jpg)
Homo Neuromodulandus
”The headache future is bright for neuromodulation techniques ... if wemanage to understand how they work” (Jean Schoenen)
figure courtesy of Jean SchoenenMarkus A. Dahlem, TU Berlin
![Page 21: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/21.jpg)
Stimulating the brain
Markus A. Dahlem, TU Berlin
![Page 22: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/22.jpg)
Stimulating the brain
Markus A. Dahlem, TU Berlin
![Page 23: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/23.jpg)
Stimulating the brain
Markus A. Dahlem, TU Berlin
![Page 24: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/24.jpg)
Stimulating the brain
Markus A. Dahlem, TU Berlin
![Page 25: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/25.jpg)
Stimulating the brain
Markus A. Dahlem, TU Berlin
![Page 26: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/26.jpg)
Stimulating the brain
Neuralieve (California, USA) tests small, portable TMS device forpotentially treating migraine with aura ...
Markus A. Dahlem, TU Berlin
![Page 27: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/27.jpg)
IHS Classification ICHD-II – All Types
1.
1.1. 1.2. 1.4. 1.5. 1.6.1.3.
1.2.1. 1.3.1. 1.5.1. 1.6.1.
Sub
form
s
Migraine
Subtypes
2 symptom, 3 combinations: both or either of them
Markus A. Dahlem, TU Berlin
![Page 28: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/28.jpg)
IHS Classification ICHD-II – Major Types
with aura
without aura
typical aurawithout headache
1.
1.1. 1.2.
1.2.1.
Sub
form
s
Migraine
Subtypes
1.1.
1.2.1.
1.2.3.
2 symptom, 3 combinations: both or either of them
Markus A. Dahlem, TU Berlin
![Page 29: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/29.jpg)
Mainly two neural theories of migraine
”Migraine generator”-theory
S1
PFCTh
PPC
PAG
Amyg Insula
SMA
ACC
”Spreading depression”-theory
Markus A. Dahlem, TU Berlin
![Page 30: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/30.jpg)
SD triggers trigeminal meningeal afferents, ie, headache
see e.g.: Bolay et al. Nature Medicine 8, 2002Review: Eikermann-Haerter & Moskowitz, Curr Opin Neurol. 21, 2008
Figure: Dodick & Gargus SciAm, August 2008
Markus A. Dahlem, TU Berlin
![Page 31: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/31.jpg)
”Migraine generator” in the brainstem
SD
aura
trigger
Markus A. Dahlem, TU Berlin
![Page 32: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/32.jpg)
”Migraine generator” in the brainstem
?
trigger A
SD
trigger B
?
trigger C
?
trigger D
postdromeprodrome aura headache
mysterious conductor
about 1 day about 1 day4−72h< 60 min
Markus A. Dahlem, TU Berlin
![Page 33: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/33.jpg)
A conductor of a neural orchestra playing migraine
?
trigger A
?
trigger C
?
trigger D
postdromeprodrome headache
mysterious conductor
trigger B
SD
aura
about 1 day about 1 day4−72h< 60 min
Markus A. Dahlem, TU Berlin
![Page 34: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/34.jpg)
A conductor of a neural orchestra playing migraine
?
trigger A
?
trigger D
postdromeprodrome
mysterious conductor
headache
trigger C
?SD
trigger B
aura
about 1 day about 1 day< 60 min 4−72h
Markus A. Dahlem, TU Berlin
![Page 35: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/35.jpg)
A conductor of a neural orchestra playing migraine
?
trigger A
SD
trigger B
?
trigger C
?
trigger D
postdromeprodrome aura headache
mysterious conductor
about 1 day about 1 day4−72h< 60 min
Markus A. Dahlem, TU Berlin
![Page 36: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/36.jpg)
SD is playing jazz – self-organizing dynamics
SD
postdromeaura headache
about 1 day about 1 day4−72h< 60 min
delaytime
trigger
prodrome
heightened susceptibility
cort
ical
hom
eost
asis
prodrome
Markus A. Dahlem, TU Berlin
![Page 37: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/37.jpg)
Pathway of upstream and downstream events
SD
headacheprodrome aura
trigger
heig
hten
edsusceptibility
delayed trigger
Only one upstream trigger?Silent aura?Delayed headache link?
Markus A. Dahlem, TU Berlin
![Page 38: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/38.jpg)
Outline
1 Introduction
2 Localized spots traveling in human cortex
3 Modeling migraine with aura
Markus A. Dahlem, TU Berlin
![Page 39: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/39.jpg)
Migraine full-scale attack is more confined
(a) (b)
(c)
LS
CS
(d)
affected areatemporarily
Dahlem et al. ”2D wave patterns ... ”. Physcia D 239 (2010) Special issue: Emerging Phenomena.
Markus A. Dahlem, TU Berlin
![Page 40: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/40.jpg)
SD wave in the cortex
-1
-2
-3
-4-7
-8
1 min
20 mV
log [cat] , M
(mM)
VeNa+
Na+
K+
Ve
K+
Ca++
Ca++
H+
0 10 20 30 s
150
6050
31.5
0.08
unitact.
Lauritzen (1994) Brain 117:199.
Markus A. Dahlem, TU Berlin
![Page 41: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/41.jpg)
Engulfing SD wave: current paradigm of full-scale attack
Xenon 133 method, radionuclide used to image brain’s blood flow.
Olesen, J. , Larsen, B. and Lauritzen, M., Focal hyperemia followed by spreading oligemia and impaired activation
of rCBF in classic migraine, Ann. Neurol. 9, 344 (1981)
Markus A. Dahlem, TU Berlin
![Page 42: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/42.jpg)
Engulfing SD wave: current paradigm of full-scale attack
M. Lauritzen (1987) Trends in Neurosciences 10:8.
Markus A. Dahlem, TU Berlin
![Page 43: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/43.jpg)
Engulfing SD wave: current paradigm of full-scale attack
M. Lauritzen (1987) Trends in Neurosciences 10:8.
Markus A. Dahlem, TU Berlin
![Page 44: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/44.jpg)
Migraine full-scale attack is more confined
(a) (b)
(c)
LS
CS
(d)
affected areatemporarily
Dahlem et al. ”2D wave patterns ... ”. Physcia D 239 (2010) Special issue: Emerging Phenomena.
Markus A. Dahlem, TU Berlin
![Page 45: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/45.jpg)
What is a migraine aura?
Markus A. Dahlem, TU Berlin
![Page 46: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/46.jpg)
Migraine visual field defects reported in 1941 by K. Lashley
visual field defect pattern on primary visual cortex
0
5
10
15
5min7min
9min
11min
15min
0 10 20 30 40 50mm
5min7min
9min11min
15min
Only about 2-10% but not 50% cortical surface area is affected!Dahlem & Hadjikhani (2009) PLoS ONE 4: e5007.
Markus A. Dahlem, TU Berlin
![Page 47: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/47.jpg)
Tracking migraine aura symptoms
Vincent & Hadjikhani (2007) Cephalagia 27
Markus A. Dahlem, TU Berlin
![Page 48: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/48.jpg)
Tracking migraine aura symptoms
Vincent & Hadjikhani (2007) Cephalagia 27
Markus A. Dahlem, TU Berlin
![Page 49: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/49.jpg)
Confined spatial patterns of spreading depression
Hadjikhani et al. (2001) PNAS
Dahlem & Hadjikhani (2009) PLoS ONEDahlem & Muller (1997) Exp. Brain Res.
Markus A. Dahlem, TU Berlin
![Page 50: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/50.jpg)
Confined spatial patterns of spreading depression
neighboring points
collapse
?
16 min
31 min
1 cm
nucleationrecordedslice not
Hadjikhani et al. (2001) PNAS
Dahlem & Hadjikhani (2009) PLoS ONEDahlem & Muller (1997) Exp. Brain Res.
Markus A. Dahlem, TU Berlin
![Page 51: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/51.jpg)
Confined spatial patterns of spreading depression
23 min18 min.
28 min.
Hadjikhani et al. (2001) PNAS
Dahlem & Hadjikhani (2009) PLoS ONEDahlem & Muller (1997) Exp. Brain Res.
Markus A. Dahlem, TU Berlin
![Page 52: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/52.jpg)
Confined spatial patterns of spreading depression
23 min18 min.
28 min.
Open wave fronts move along
a rather straight line
preventing a reentry of SD
Hadjikhani et al. (2001) PNAS
Dahlem & Hadjikhani (2009) PLoS ONEDahlem & Muller (1997) Exp. Brain Res.
Markus A. Dahlem, TU Berlin
![Page 53: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/53.jpg)
Confined spatial patterns of spreading depression
23 min18 min.
28 min.
Open wave fronts move along
a rather straight line
preventing a reentry of SD
Hadjikhani et al. (2001) PNASDahlem & Hadjikhani (2009) PLoS ONE
Dahlem & Muller (1997) Exp. Brain Res.
Markus A. Dahlem, TU Berlin
![Page 54: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/54.jpg)
Confined spatial patterns of spreading depression
18 min.
23 min
28 min.
33 min.
38 min.
1 mm
Spiral waves (reentry) observed in retinal SDwith a rotation period of 2.45 min
Hadjikhani et al. (2001) PNASDahlem & Hadjikhani (2009) PLoS ONEDahlem & Muller (1997) Exp. Brain Res.
Markus A. Dahlem, TU Berlin
![Page 55: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/55.jpg)
Clinical evidence
Markus A. Dahlem, TU Berlin
![Page 56: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/56.jpg)
Mapped visual symptoms on cortex via fMRI retinotopy
1 cm
10°
1 357
15
1719
2123
25
27 min
Visual hemifield Primary visual cortex
Dahlem & Hadjikhani (2009) PLoS ONE 4: e5007.
Markus A. Dahlem, TU Berlin
![Page 57: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/57.jpg)
Mapped visual symptoms on cortex via fMRI retinotopy
23 min
21
19
17
17
15
1311
975
10°
1 cm
Visual hemifield Primary visual cortex
Dahlem & Hadjikhani (2009) PLoS ONE 4: e5007.
Markus A. Dahlem, TU Berlin
![Page 58: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/58.jpg)
Outline
1 Introduction
2 Localized spots traveling in human cortex
3 Modeling migraine with aura
Markus A. Dahlem, TU Berlin
![Page 59: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/59.jpg)
Mathematical models cells, circuits, and to tissue
I
II
III
IV
V
VI
Apic
al dendrite
Current distribution
Soma
Glia
Extra
cellu
lar
Osmotic force
Pump
INa,P
IK,DR
IK,A
INMDA
INa,T
K+
[K+]o
[Na+]i
Markus A. Dahlem, TU Berlin
![Page 60: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/60.jpg)
Local Dynamics during SDA
pic
al dendrite
Current distribution
Soma
Glia
Extra
cellu
lar
Osmotic force
Pump
INa,P
IK,DR
IK,A
INMDA
INa,T
K+
[K+]o
[Na+]i
C∂V
∂t= −INa − IK − ICl + I pump + Iapp
INa = −m3∞h(ENa − V )
IK = −n4(EK − V )
∂n
∂t= αn(1 − n) − βn,
∂h
∂t· · ·
∂[ion]o
∂t=
IionA
FVolo+ Idiff
∂[ion]i
∂t=
IionA
FVoli
I pumpion (V ) = βionImax
(1 +
KmK
[K ]o
)−2 (1 +
KmNa
[Na]i
)−3
Alternatively (GHK currents)
Iion = V αF Pion[ion]i − [ion]oe
−αV
1 − e−αV
M. A. Dahlem, Models of cortical SD, Scholarpedia
Markus A. Dahlem, TU Berlin
![Page 61: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/61.jpg)
Local Dynamics during SDA
pic
al dendrite
Current distribution
Soma
Glia
Extra
cellu
lar
Osmotic force
Pump
INa,P
IK,DR
IK,A
INMDA
INa,T
K+
[K+]o
[Na+]i
C∂V
∂t= −INa − IK − ICl + I pump + Iapp
INa = −m3∞h(ENa − V )
IK = −n4(EK − V )
∂n
∂t= αn(1 − n) − βn,
∂h
∂t· · ·
∂[ion]o
∂t=
IionA
FVolo+ Idiff
∂[ion]i
∂t=
IionA
FVoli
I pumpion (V ) = βionImax
(1 +
KmK
[K ]o
)−2 (1 +
KmNa
[Na]i
)−3
Alternatively (GHK currents)
Iion = V αF Pion[ion]i − [ion]oe
−αV
1 − e−αV
M. A. Dahlem, Models of cortical SD, Scholarpedia
Markus A. Dahlem, TU Berlin
![Page 62: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/62.jpg)
Local Dynamics during SDA
pic
al dendrite
Current distribution
Soma
Glia
Extra
cellu
lar
Osmotic force
Pump
INa,P
IK,DR
IK,A
INMDA
INa,T
K+
[K+]o
[Na+]i
C∂V
∂t= −INa − IK − ICl + I pump + Iapp
INa = −m3∞h(ENa − V )
IK = −n4(EK − V )
∂n
∂t= αn(1 − n) − βn,
∂h
∂t· · ·
∂[ion]o
∂t=
IionA
FVolo+ Idiff
∂[ion]i
∂t=
IionA
FVoli
I pumpion (V ) = βionImax
(1 +
KmK
[K ]o
)−2 (1 +
KmNa
[Na]i
)−3
Alternatively (GHK currents)
Iion = V αF Pion[ion]i − [ion]oe
−αV
1 − e−αV
M. A. Dahlem, Models of cortical SD, Scholarpedia
Markus A. Dahlem, TU Berlin
![Page 63: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/63.jpg)
Local Dynamics during SDA
pic
al dendrite
Current distribution
Soma
Glia
Extra
cellu
lar
Osmotic force
Pump
INa,P
IK,DR
IK,A
INMDA
INa,T
K+
[K+]o
[Na+]i
C∂V
∂t= −INa − IK − ICl + I pump + Iapp
INa = −m3∞h(ENa − V )
IK = −n4(EK − V )
∂n
∂t= αn(1 − n) − βn,
∂h
∂t· · ·
∂[ion]o
∂t=
IionA
FVolo+ Idiff
∂[ion]i
∂t=
IionA
FVoli
I pumpion (V ) = βionImax
(1 +
KmK
[K ]o
)−2 (1 +
KmNa
[Na]i
)−3
Alternatively (GHK currents)
Iion = V αF Pion[ion]i − [ion]oe
−αV
1 − e−αV
M. A. Dahlem, Models of cortical SD, Scholarpedia
Markus A. Dahlem, TU Berlin
![Page 64: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/64.jpg)
Local Dynamics during SDA
pic
al dendrite
Current distribution
Soma
Glia
Extra
cellu
lar
Osmotic force
Pump
INa,P
IK,DR
IK,A
INMDA
INa,T
K+
[K+]o
[Na+]i
C∂V
∂t= −INa − IK − ICl + I pump + Iapp
INa = −m3∞h(ENa − V )
IK = −n4(EK − V )
∂n
∂t= αn(1 − n) − βn,
∂h
∂t· · ·
∂[ion]o
∂t=
IionA
FVolo+ Idiff
∂[ion]i
∂t=
IionA
FVoli
I pumpion (V ) = βionImax
(1 +
KmK
[K ]o
)−2 (1 +
KmNa
[Na]i
)−3
Alternatively (GHK currents)
Iion = V αF Pion[ion]i − [ion]oe
−αV
1 − e−αV
M. A. Dahlem, Models of cortical SD, Scholarpedia
Markus A. Dahlem, TU Berlin
![Page 65: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/65.jpg)
Local Dynamics during SDA
pic
al dendrite
Current distribution
Soma
Glia
Extra
cellu
lar
Osmotic force
Pump
INa,P
IK,DR
IK,A
INMDA
INa,T
K+
[K+]o
[Na+]i
C∂V
∂t= −INa − IK − ICl + I pump + Iapp
INa = −m3∞h(ENa − V )
IK = −n4(EK − V )
∂n
∂t= αn(1 − n) − βn,
∂h
∂t· · ·
∂[ion]o
∂t=
IionA
FVolo+ Idiff
∂[ion]i
∂t=
IionA
FVoli
I pumpion (V ) = βionImax
(1 +
KmK
[K ]o
)−2 (1 +
KmNa
[Na]i
)−3
Alternatively (GHK currents)
Iion = V αF Pion[ion]i − [ion]oe
−αV
1 − e−αV
M. A. Dahlem, Models of cortical SD, Scholarpedia
Markus A. Dahlem, TU Berlin
![Page 66: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/66.jpg)
Tissue properties & engery state change time scales . . .
... otherwise robust!
0 1 2 3 4 5 6time (s)
100
50
0
50
volt
age
(mV
)
V
EK
ENa
Iapp
0 5 10 15 20 25 30 35
time (s)
100
50
0
50
volt
age
(mV
)
V
EK
ENa
Iapp
Parameters relevant for migraine aura–ischemic stroke continuum.
Markus A. Dahlem, TU Berlin
![Page 67: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/67.jpg)
Possible bifurcations involved in local dynamics of SD
0 1 2 3 4 5 6time (s)
100
50
0
50
volt
age (m
V)
V
EK
ENa
Iapp
−gate deactivation Hopf
−gatemembrane voltage
SNIC
Hopf
SNIC
Recovery
eletrogenic pump
FoldSeizure−like activity
in ischaemic stroke
hypoxic tissue
Spreading depression
(ceiling level)
n
nV
Ipump[K+]o
[K+]o = 10mM
Markus A. Dahlem, TU Berlin
![Page 68: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/68.jpg)
Feedback control of spreading depression
From bench to bedside
!
!"#$%&'$()'#"*(
+,-+,."(!"#$%&/*#(
0&1'2(3"'$#(
4#&5$1"(!"#$%&'$()'#"*( 6/&'7/2%1"(!"#$%&'$()'#"*(
Cooperation with Stephen Schiff & Bruce Gluckman Courtesy of Neuralieve
Markus A. Dahlem, TU Berlin
![Page 69: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/69.jpg)
Macroscopic RD with nonlocal transmission
ion
currents
ion gradient
ion
conductance
ion
pumpsout in
diffu
sion
activator−inhibitor dynamics
depolarization
firing rate
neurovascular coupling
neural network activity
Hodgkin-Huxley-Grafstein model
(1963) of SD
u =
(u − u3
3− v
)+ D∇2u
+ FHN inhibitor equations + ...
ε−1v = u + β − γv + KF [u]
global inhibitory control (mean field)
F [u] = Su(t)− S0
Su(t) =
∫H(u(r, t)− ue) dr,
Markus A. Dahlem, TU Berlin
![Page 70: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/70.jpg)
RD models on realistic cortical geometries
positive (fender)
negative (saddle)
gyral crowns
entrance to sulci
gyral crowns
entrance to sulci
Markus A. Dahlem, TU Berlin
![Page 71: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/71.jpg)
Traveling spots are unstable (w/o long-range inhibition)
Schenk, C. P. , Or-Guil, M. , Bode, M. and Purwins, H. -G. , Phys. Rev. Lett. 78, 3781 (1997)
Markus A. Dahlem, TU Berlin
![Page 72: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/72.jpg)
The surface of the brain (cortex) is curved
Markus A. Dahlem, TU Berlin
![Page 73: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/73.jpg)
Minimum threshold in a flat geometry
0
20
40
60
1.3 1.32 1.34 1.36 1.38 1.4
S
β
torus outside
flat
torus inside2
21
1
ring wave
1
2
∂P1D∂R∞
Markus A. Dahlem, TU Berlin
![Page 74: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/74.jpg)
Nucleation of visual aura clusters in the visual field
23 min
21
19
17
17
15
1311
975
10°
1 cm
Visual hemifield Primary visual cortex
Cooperation with Andrew Charles, UCLA.
Markus A. Dahlem, TU Berlin
![Page 75: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/75.jpg)
Nucleation of visual aura clusters in the visual field
1 cm
10°
1 357
15
1719
2123
25
27 min
Visual hemifield Primary visual cortex
Markus A. Dahlem, TU Berlin
![Page 76: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/76.jpg)
Nucleation of visual aura clusters in the visual field
1 cm
10°
1 357
15
1719
2123
25
27 min
Visual hemifield Primary visual cortex
Markus A. Dahlem, TU Berlin
![Page 77: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/77.jpg)
Nucleation failure on torus
Markus A. Dahlem, TU Berlin
![Page 78: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/78.jpg)
Transient times in flat and curved geometry
0
10
20
30
40
50
1.3 1.32 1.34 1.36 1.38
S
β
with controlwithout control
torus outside
flat
torus inside
ring wave
∂R∞
0
10
20
30
0 10 20 30 40 50 60 70 80
S
t
outside
inside
outside
inside
torus, without controltorus, with control
flat, without control
Markus A. Dahlem, TU Berlin
![Page 79: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/79.jpg)
Critical nucleation size varies with curvature
nucleationcritical
Markus A. Dahlem, TU Berlin
![Page 80: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/80.jpg)
Migraine full-scale attack is more confined
(a) (b)
(c)
LS
CS
(d)
affected areatemporarily
Dahlem et al. ”2D wave patterns ... ”. Physcia D 239 (2010) Special issue: Emerging Phenomena.
Markus A. Dahlem, TU Berlin
![Page 81: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/81.jpg)
Cortical homeostasis is excitable (bistabe)
Hypothesis: Cortical susceptibility to SD depends on the size ofthe momentarily affected tissue.
nucleationcritical
Markus A. Dahlem, TU Berlin
![Page 82: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/82.jpg)
Long transient: ghost behavior, inhib. global feedback
Hypothesis: Cortical susceptibility to SD depends on the size ofthe momentarily affected tissue.
slow dynamicstransient and
Markus A. Dahlem, TU Berlin
![Page 83: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/83.jpg)
Threshold surface separates attractor basins
supra
stim.
stim. su
b
traveling wave
homo. steady state
ui(x)
ui+1
(x)
ui+2
(x)
phase space
threshold
Excitable media.
Markus A. Dahlem, TU Berlin
![Page 84: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/84.jpg)
Solution on threshold surface
supra
stim.
stim. su
b
traveling wave
homo. steady state
ui(x)
ui+1
(x)
ui+2
(x)
phase space
threshold
Excitable media.
Markus A. Dahlem, TU Berlin
![Page 85: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/85.jpg)
Nonlinear delayed transitions: saddle-node ghosts
homo.
stead
y stat
e
fast
fast
slow
Markus A. Dahlem, TU Berlin
![Page 86: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/86.jpg)
Nonlinear delayed transitions: saddle-node ghosts
homo.
stead
y stat
e
fast
fast
slow
Markus A. Dahlem, TU Berlin
![Page 87: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/87.jpg)
Bottleneck due to saddle-node bifurcation
(a) (b)
(a)
(c)
(b)
(d)(c)
stable wave segment
homo.
stead
y stat
e
homo.
stead
y stat
e
homo.
stead
y stat
e
homo. steady state
supra
stim.
fast
fast
slow
trave
ling w
ave
stim. su
b
traveling wave
w
ave
size
S
threshold β
∂R
∂R
threshold
Markus A. Dahlem, TU Berlin
![Page 88: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/88.jpg)
Simulation of transient SD wave segment
gray = cortical surface; red = SD wave
Markus A. Dahlem, TU Berlin
![Page 89: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/89.jpg)
Typical trajectory: fast growth and collapse & bottleneck
0
5
10
15
20
25
0 5 10 15 20 25 30 35time
collapse
cort
ical
sur
face
are
a in
vade
d by
SD nucleation
CSD break−up
long transient propagation
model−based
stimulation strategiestherapeutic TMS
Markus A. Dahlem, TU Berlin
![Page 90: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/90.jpg)
Confined spatial patterns of spreading depression
neighboring points
collapse
?
16 min
31 min
1 cm
nucleationrecordedslice not
Markus A. Dahlem, TU Berlin
![Page 91: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/91.jpg)
Confined spatial patterns of spreading depression
neighboring points
0
4
8
12
16
20
32
28
24
time
16 min
31 min
1 cm
recordedslice not
Markus A. Dahlem, TU Berlin
![Page 92: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/92.jpg)
Confined spatial patterns of spreading depression
neighboring points 16 min
31 min
1 cm
recordedslice not
Markus A. Dahlem, TU Berlin
![Page 93: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/93.jpg)
Confined spatial patterns of spreading depression
neighboring points 16 min
31 min
1 cm
recordedslice not
Markus A. Dahlem, TU Berlin
![Page 94: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/94.jpg)
Confined spatial patterns of spreading depression
neighboring points 16 min
31 min
1 cm
recordedslice not
Markus A. Dahlem, TU Berlin
![Page 95: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/95.jpg)
Confined spatial patterns of spreading depression
5cm
00
0 0
32 16
6 24
time / m
in
Markus A. Dahlem, TU Berlin
![Page 96: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/96.jpg)
Varying contact to the ghost
0
50
100
150
200
250
300
350
400
450
tota
laff
ecte
dar
ea(T
AA
)
(1)
(2)
(3)
(4)
0 10 20 30 40 50 60
maximal instantaneous area (MIA)
0
50
100
150
200
250
300
exci
tati
on
du
rati
on(E
D)
(1)
(2)
(3)
(4)
0 50 100 150 200 250 300 350 400 450
total affected area (TAA)
(1)
(2)
(3)
(4)
0
80
160
240
#O
ccu
rren
ces
0 80 160240
0 80 160240# Occurrences
β0 = 1.32
(1)
(2) (3)
(4)
0 30 60 90 120150180210240270time
1
10
20
30
40
50
60
70
80
Markus A. Dahlem, TU Berlin
![Page 97: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/97.jpg)
Varying contact to the ghost
0
50
100
150
200
250
300
350
400
450
tota
laff
ecte
dar
ea(T
AA
)
(1)
(2)
(3)
(4)
0 10 20 30 40 50 60
maximal instantaneous area (MIA)
0
50
100
150
200
250
300
exci
tati
on
du
rati
on(E
D)
(1)
(2)
(3)
(4)
0 50 100 150 200 250 300 350 400 450
total affected area (TAA)
(1)
(2)
(3)
(4)
0
80
160
240
#O
ccu
rren
ces
0 100 200
0 100200300# Occurrences
β0 = 1.33
(1)
(2)
(3)
(4)
0 20 40 60 80 100120140160180time
1
10
20
30
40
50
60
70
80
90
Markus A. Dahlem, TU Berlin
![Page 98: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/98.jpg)
Varying contact to the ghost
0
50
100
150
200
250
300
350
400
450
tota
laff
ecte
dar
ea(T
AA
)
(1)
(2)
(3)
(4)
0 10 20 30 40 50 60
maximal instantaneous area (MIA)
0
50
100
150
200
250
300
exci
tati
on
du
rati
on(E
D)
(1)
(2)
(3)
(4)
0 50 100 150 200 250 300 350 400 450
total affected area (TAA)
(1)
(2)
(3)
(4)
0
80
160
240
#O
ccu
rren
ces
0 250 500
0 150 300# Occurrences
β0 = 1.34
(1)
(2)
(3)
(4)
0 10 20 30 40 50 60 70 80 90time
1102030405060708090100110120130
Markus A. Dahlem, TU Berlin
![Page 99: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/99.jpg)
IHS Classification ICHD-II – All Types
1.
1.1. 1.2. 1.4. 1.5. 1.6.1.3.
1.2.1. 1.3.1. 1.5.1. 1.6.1.
Sub
form
s
Migraine
Subtypes
2 symptom, 3 combinations: both or either of them
Markus A. Dahlem, TU Berlin
![Page 100: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/100.jpg)
IHS Classification ICHD-II – Major Types
with aura
without aura
typical aurawithout headache
1.
1.1. 1.2.
1.2.1.
Sub
form
s
Migraine
Subtypes
1.1.
1.2.1.
1.2.3.
2 symptom, 3 combinations: both or either of them
Markus A. Dahlem, TU Berlin
![Page 101: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/101.jpg)
Model-based hypothesis testing
1.1. 1.2.1
1.2.3Sub−threshold
Affe
cted
cor
tical
are
aSurvival time
SD in migraine attack
Markus A. Dahlem, TU Berlin
![Page 102: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/102.jpg)
Typical trajectory: fast growth and collapse & bottleneck
0
5
10
15
20
25
0 5 10 15 20 25 30 35time
collapse
cort
ical
sur
face
are
a in
vade
d by
SD nucleation
CSD break−up
long transient propagation
model−based
stimulation strategiestherapeutic TMS
Markus A. Dahlem, TU Berlin
![Page 103: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/103.jpg)
Typical trajectory: fast growth and collapse & bottleneck
0
5
10
15
20
25
0 5 10 15 20 25 30 35time
cort
ical
sur
face
are
a in
vade
d by
SD
sensory innervation
arachnoid
bone
blood
dura dural sinuses
cortex
pia
Markus A. Dahlem, TU Berlin
![Page 104: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/104.jpg)
Typical trajectory: fast growth and collapse & bottleneck
0
5
10
15
20
25
0 5 10 15 20 25 30 35time
cort
ical
sur
face
are
a in
vade
d by
SD
sensory innervation
arachnoid
bone
blood
dura
SD is pronociceptive
dural sinuses
cortex
pia
peak value
Markus A. Dahlem, TU Berlin
![Page 105: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/105.jpg)
Typical trajectory: fast growth and collapse & bottleneck
0
5
10
15
20
25
0 5 10 15 20 25 30 35time
cort
ical
sur
face
are
a in
vade
d by
SD
sensory innervation
arachnoid
bone
blood
dura
SD is pronociceptive
dural sinuses
cortex
pia
peak value
Markus A. Dahlem, TU Berlin
![Page 106: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/106.jpg)
Typical trajectory: fast growth and collapse & bottleneck
0
5
10
15
20
25
0 5 10 15 20 25 30 35time
collapse
cort
ical
sur
face
are
a in
vade
d by
SD nucleation
CSD break−up
long transient propagation
model−based
stimulation strategiestherapeutic TMS
Markus A. Dahlem, TU Berlin
![Page 107: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/107.jpg)
Typical trajectory: fast growth and collapse & bottleneck
0
5
10
15
20
25
0 5 10 15 20 25 30 35time
collapse
cort
ical
sur
face
are
a in
vade
d by
SD nucleation
CSD break−up
long transient propagation
noise!
model−based
stimulation strategiestherapeutic TMS
Markus A. Dahlem, TU Berlin
![Page 108: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/108.jpg)
Double pulse stimulation (current TMS strategy)
0
5
10
15
20
25
0 5 10 15 20 25 30 35
noise sample 1 k=0.010noise sample 1 k=0.100noise sample 1 k=0.300noise sample 2 k=0.010noise sample 2 k=0.100noise sample 2 k=0.300
without noise
time
noise on
wav
e si
ze
Markus A. Dahlem, TU Berlin
![Page 109: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/109.jpg)
Permanent noise stimulation
0
5
10
15
20
25
0 5 10 15 20 25 30 35
noise sample 1 k=0.030noise sample 1 k=0.040noise sample 1 k=0.050noise sample 2 k=0.030noise sample 2 k=0.040noise sample 2 k=0.050
without noise
time
noise on
wav
e si
ze
Markus A. Dahlem, TU Berlin
![Page 110: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/110.jpg)
Single pulse vs. constant noise stimulation
0 5 10 15 20 25 30 35survival time of unstable solitons
0.0
0.1
0.2
0.3
0.4
0.5
pro
babili
ty
Markus A. Dahlem, TU Berlin
![Page 111: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/111.jpg)
Single pulse vs. constant noise stimulation
0 5 10 15 20 25 30 35survival time
0.0
0.1
0.2
0.3
0.4
0.5
pro
babili
tyMigraine aura duration
without noiseon t=5, k = 0.050on t=5, k = 0.100noise 0.050pulse t=5, k = 0.100pulse t=5, k = 0.500
Markus A. Dahlem, TU Berlin
![Page 112: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/112.jpg)
Noise sensitivity of transient wave segments
0
5
10
15
20
25
0 5 10 15 20 25 30 35
without noisenoise k=0.010noise k=0.015noise k=0.020noise k=0.025noise k=0.030noise k=0.035noise k=0.040
wav
e si
ze
time
How to escape quicklyfrom the ”ghost” plateau?
Markus A. Dahlem, TU Berlin
![Page 113: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/113.jpg)
Simulation of an engulfing SD wave
In cooperation with Jens Dreier &
Denny Milakara, Charite
Folds
Bumbs
Markus A. Dahlem, TU Berlin
![Page 114: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/114.jpg)
Localized waves hitting a bump
(a) (b)
Markus A. Dahlem, TU Berlin
![Page 115: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/115.jpg)
Perturbed into boa of homogeneous steady state
(a) t=55 (b) t=80 (c) t=105
(d) t=130 (e) t=150 (f) t=165
(g) t=180 (h) t=200 (i) t=220
Markus A. Dahlem, TU Berlin
![Page 116: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/116.jpg)
Waves are scattered
(a) t=65 (b) t=100 (c) t=125
(d) t=145 (e) t=175 (f) t=220
Markus A. Dahlem, TU Berlin
![Page 117: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/117.jpg)
Scattering angle vs off set
Markus A. Dahlem, TU Berlin
![Page 118: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/118.jpg)
Another question: Why is the cortex intrinsically curved?
Markus A. Dahlem, TU Berlin
![Page 119: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/119.jpg)
Migraine scotoma reveal functional properties
Pattern matching
”Curved” retinotopic mapping
47
913
A B
C
Dahlem & Tusch, revision J. Math Neuroscie.
Markus A. Dahlem, TU Berlin
![Page 120: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/120.jpg)
Migraine scotoma reveal functional properties
Pattern matching ”Curved” retinotopic mapping
47
913
A B
C
A
C
BHM
10Æ10Æ
Dahlem & Tusch, revision J. Math Neuroscie.
Markus A. Dahlem, TU Berlin
![Page 121: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/121.jpg)
Migraine scotoma reveal functional properties
Pattern matching ”Curved” retinotopic mapping
47
913
A B
C
a d
b ce
m
m lv u10Ælingual gyrus uneus CS
Dahlem & Tusch, revision J. Math Neuroscie.
Markus A. Dahlem, TU Berlin
![Page 122: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/122.jpg)
Migraine scotoma reveal functional properties
Pattern matching ”Curved” retinotopic mapping
47
913
A B
C
2 4 6 8 10 12 14
0.1
0.2
0.3
2 4 6 8 10 12 14
20406080
100120140
2 4 6 8 10 12 14
0.2
0.4
0.6
0.8
1a 60Æ6Æ M=(a�1 )
HM�=(%)K=(mm2 ) �=(rad)a�2 00:20:40:60:8
b d
Dahlem & Tusch, revision J. Math Neuroscie.
Markus A. Dahlem, TU Berlin
![Page 123: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/123.jpg)
Conclusion
Conclusions
We need more non-invasive magingdata of the aura!
The predicted plateau (”ghost ofsaddle-node”) theory can be testedclinically with non-invasive imaging
Sef-organizing patterns provide aunifying concept including silent aura,migraine w or w/o headache/aura
Insights pattern formation may refineneuromodulation strategies:
Being close to a saddle-nodebifurcation (”ghost” plateau)Design (feedback) control tointelligently target certain propertiesof SD in migraine
1 cm
10°
1 357
15
1719
2123
25
27 min
Visual hemifield Primary visual cortex
Markus A. Dahlem, TU Berlin
![Page 124: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/124.jpg)
Conclusion
Conclusions
We need more non-invasive magingdata of the aura!
The predicted plateau (”ghost ofsaddle-node”) theory can be testedclinically with non-invasive imaging
Sef-organizing patterns provide aunifying concept including silent aura,migraine w or w/o headache/aura
Insights pattern formation may refineneuromodulation strategies:
Being close to a saddle-nodebifurcation (”ghost” plateau)Design (feedback) control tointelligently target certain propertiesof SD in migraine
SD
headacheprodrome aura
trigger
heig
hten
ed
susceptibility
delayed trigger
Markus A. Dahlem, TU Berlin
![Page 125: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/125.jpg)
Conclusion
Conclusions
We need more non-invasive magingdata of the aura!
The predicted plateau (”ghost ofsaddle-node”) theory can be testedclinically with non-invasive imaging
Sef-organizing patterns provide aunifying concept including silent aura,migraine w or w/o headache/aura
Insights pattern formation may refineneuromodulation strategies:
Being close to a saddle-nodebifurcation (”ghost” plateau)Design (feedback) control tointelligently target certain propertiesof SD in migraine
0
50
100
150
200
250
300
350
400
450
tota
laff
ecte
dare
a(T
AA
)
(1)
(2)
(3)
(4)
0 10 20 30 40 50 60
maximal instantaneous area (MIA)
0
50
100
150
200
250
300
exci
tati
ond
ura
tion
(ED
)
(1)
(2)
(3)
(4)
0 50 100 150 200 250 300 350 400 450
total affected area (TAA)
(1)
(2)
(3)
(4)
0
80
160
240
#O
ccu
rren
ces
0 250 500
0 150 300# Occurrences
β0 = 1.34
(1)
(2)
(3)
(4)
0 10 20 30 40 50 60 70 80 90time
1102030405060708090100110120130
Markus A. Dahlem, TU Berlin
![Page 126: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/126.jpg)
Conclusion ¡
Cooperation & Funding
Frederike KneerSebstian BoieNiklas HubelThomas Isele
Paul Van Valkenburgh
Nouchine Hadjikhani(EPFL & Martinos Center for Biomedical Imaging, MGH)
Andrew Charles(Headache Research and Treatment Program, UCLA School of
Medicine)
Steven Schiff(Penn State Center for Neural Engineering)
Jens Dreier(Department of Neurology, Charite; University Medicine, Berlin)
Klaus Podoll(University Hospital Aachen)
berlin
Migraine Aura Foundation
Markus A. Dahlem, TU Berlin
![Page 127: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/127.jpg)
Conclusion ¡
2 symptoms, 3 combinations: both or either of them
SD ?
aura headache
trigger trigger
Markus A. Dahlem, TU Berlin
![Page 128: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/128.jpg)
Conclusion ¡
A conductor of a neural orchestra playing migraine
SD ?
aura headache
mysterious conductor
trigger trigger
Markus A. Dahlem, TU Berlin
![Page 129: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/129.jpg)
Conclusion ¡
A conductor of a neural orchestra playing migraine
?
trigger A
SD
trigger B
?
trigger C
?
trigger D
postdromeprodrome aura headache
mysterious conductor
about 1 day about 1 day4−72h< 60 min
Markus A. Dahlem, TU Berlin
![Page 130: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/130.jpg)
Conclusion ¡
A conductor of a neural orchestra playing migraine
?
trigger A
?
trigger C
?
trigger D
postdromeprodrome headache
mysterious conductor
trigger B
SD
aura
about 1 day about 1 day4−72h< 60 min
Markus A. Dahlem, TU Berlin
![Page 131: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/131.jpg)
Conclusion ¡
A conductor of a neural orchestra playing migraine
?
trigger A
?
trigger D
postdromeprodrome
mysterious conductor
headache
trigger C
?SD
trigger B
aura
about 1 day about 1 day< 60 min 4−72h
Markus A. Dahlem, TU Berlin
![Page 132: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/132.jpg)
Conclusion ¡
SD is playing jazz – self-organizing dynamics
SD
postdromeaura headache
about 1 day about 1 day4−72h< 60 min
delaytime
trigger
prodrome
heightened susceptibility
cort
ical
hom
eost
asis
prodrome
Markus A. Dahlem, TU Berlin
![Page 133: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/133.jpg)
Conclusion ¡
SD is playing jazz – self-organizing dynamics
SD
postdromeprodrome aura headache
trigger
delayed trigger
about 1 day about 1 day4−72h< 60 min
heig
hten
ed
susceptibility
Markus A. Dahlem, TU Berlin
![Page 134: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/134.jpg)
Conclusion ¡
SD is playing jazz – self-organizing dynamics
SD
postdromeprodrome aura headache
trigger
delayed trigger
about 1 day about 1 day4−72h< 60 min
heig
hten
ed
susceptibility
Markus A. Dahlem, TU Berlin
![Page 135: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/135.jpg)
Conclusion ¡
SD is playing jazz – self-organizing dynamics
postdromeprodrome aura headache
trigger
delayed triggerSD
about 1 day about 1 day4−72h< 60 min
heig
hten
ed
susceptibility
Markus A. Dahlem, TU Berlin
![Page 136: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/136.jpg)
Conclusion ¡
SD is playing jazz – self-organizing dynamics
postdromeprodrome aura headache
trigger
SD
?
delayed trigger
about 1 day about 1 day4−72h< 60 min
heig
hten
ed
susceptibility
Markus A. Dahlem, TU Berlin
![Page 137: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/137.jpg)
Conclusion ¡
Orchestrated vs self-organizing dynamics
postdromeprodrome headache
?
delayed trigger
about 1 day about 1 day4−72h
trigger
SD
< 60 min
aura
heig
hten
ed
susceptibility
Markus A. Dahlem, TU Berlin
![Page 138: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/138.jpg)
Conclusion ¡
Orchestrated vs self-organizing dynamics
SD
postdromeaura headache
about 1 day about 1 day4−72h< 60 min
delaytime
trigger
prodrome
heightened susceptibility
cort
ical
hom
eost
asis
prodrome
Markus A. Dahlem, TU Berlin
![Page 139: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/139.jpg)
Conclusion ¡
Localized stimulation: sampling of phase space
Retinotopic”A”-”Z”,”0”-”9” (36 patterns), 4 sizes, 10 stimulation strengths =33 420 stimulation patterns (elevation of activator concentration u)
12.56.25
Markus A. Dahlem, TU Berlin
![Page 140: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/140.jpg)
Conclusion ¡
Localized stimulation: sampling of phase space
Orientation selective
−π/2
0
π/2
Markus A. Dahlem, TU Berlin
![Page 141: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/141.jpg)
Conclusion ¡
Localized stimulation: sampling of phase space
Orientation selective
−π/2
0
π/2
Markus A. Dahlem, TU Berlin
![Page 142: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/142.jpg)
Conclusion ¡
Localized stimulation: sampling of phase space
Orientation selective
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
Markus A. Dahlem, TU Berlin
![Page 143: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/143.jpg)
Conclusion ¡
Localized stimulation: sampling of phase space
Orientation selective
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
Markus A. Dahlem, TU Berlin
![Page 144: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/144.jpg)
Conclusion ¡
Localized stimulation: sampling of phase space
Orientation selective
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
Markus A. Dahlem, TU Berlin
![Page 145: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/145.jpg)
Conclusion ¡
Visual migraine aura model
b
a
c
e
d
Dahlem et al. (2000) Eur. J. Neurosci. 12:767.
Dahlem and Chronicle (2004) Prog. Neurobiol. 74:351.
Markus A. Dahlem, TU Berlin
![Page 146: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/146.jpg)
Conclusion Open wave segments - fMRI evidence & retinal SD
Tracking migraine aura symptoms
Vincent & Hadjikhani (2007) Cephalagia 27
Markus A. Dahlem, TU Berlin
![Page 147: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/147.jpg)
Conclusion Open wave segments - fMRI evidence & retinal SD
Tracking migraine aura symptoms
Vincent & Hadjikhani (2007) Cephalagia 27
Markus A. Dahlem, TU Berlin
![Page 148: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/148.jpg)
Conclusion Open wave segments - fMRI evidence & retinal SD
2D patterns with laser speckle-contrast imaging
SG
EG
KCLMG
(a)
(b) 5 min 37s (c) 9 min 07s
Dahlem et al. 239, 889 (2009) Physica D
Markus A. Dahlem, TU Berlin
![Page 149: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/149.jpg)
Conclusion Open wave segments - fMRI evidence & retinal SD
Re-entrant SD waves with anatomical block
Reshodko, L. V. and Bures, J Biol. Cybern. 18,181 (1975)
Markus A. Dahlem, TU Berlin
![Page 150: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/150.jpg)
Conclusion Open wave segments - fMRI evidence & retinal SD
Drugs adjust excitability:retracting & collapsing waves
a b c
d e f
g h i
j k l
Dahlem et al. 2D wave patterns ... . (2010) Physcia D
Markus A. Dahlem, TU Berlin
![Page 151: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/151.jpg)
Conclusion Open wave segments - fMRI evidence & retinal SD
Drugs adjust excitability:retracting & collapsing waves
What happens if SD wave fragments with open ende occur inhuman pathophysiology during migraine?
Do they form spirals?
Do fragments quickly retract?
Or: can wave fragments propagte some distance?
Markus A. Dahlem, TU Berlin
![Page 152: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/152.jpg)
Conclusion Open wave segments - fMRI evidence & retinal SD
Parameter space of excitability
Classifications of excitabile elements and excitability in activemedia.
Schneider, Scholl & Dahlem, Chaos 19 015110, (2009)
Markus A. Dahlem, TU Berlin
![Page 153: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/153.jpg)
Conclusion Open wave segments - fMRI evidence & retinal SD
Parameter space of excitability
Classifications of excitabile elements and excitability in activemedia.
Schneider, Scholl & Dahlem, Chaos 19 015110, (2009)
Markus A. Dahlem, TU Berlin
![Page 154: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/154.jpg)
Conclusion Open wave segments - fMRI evidence & retinal SD
Characteristic time scale due to bottleneck
Three spatiotempral SD patterns:2 short lasting patterns: large and low amplitude (∼90%)long lasting wave with characteristic shape (∼10%)
0 10 20 30 40 50 600
10
20
30
40
50
600.00.20.40.60.81.01.21.4
0.00.20.40.60.81.01.21.4
Markus A. Dahlem, TU Berlin
![Page 155: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/155.jpg)
Conclusion Open wave segments - fMRI evidence & retinal SD
Noise sensitivity of transient wave segments
0
5
10
15
20
25
0 5 10 15 20 25 30 35
without noisenoise k=0.010noise k=0.015noise k=0.020noise k=0.025noise k=0.030noise k=0.035noise k=0.040
wav
e si
ze
time
How to escape quicklyfrom the ”ghost” plateau?
Markus A. Dahlem, TU Berlin
![Page 156: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/156.jpg)
Conclusion Open wave segments - fMRI evidence & retinal SD
Localized stimulation: sampling of phase space
Retinotopic”A”-”Z”,”0”-”9” (36 patterns), 4 sizes, 10 stimulation strengths =33 420 stimulation patterns (elevation of activator concentration u)
12.56.25
Markus A. Dahlem, TU Berlin
![Page 157: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/157.jpg)
Conclusion Open wave segments - fMRI evidence & retinal SD
Localized stimulation: sampling of phase space
Orientation selective
−π/2
0
π/2
Markus A. Dahlem, TU Berlin
![Page 158: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/158.jpg)
Conclusion Open wave segments - fMRI evidence & retinal SD
Localized stimulation: sampling of phase space
Orientation selective
−π/2
0
π/2
Markus A. Dahlem, TU Berlin
![Page 159: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/159.jpg)
Conclusion Open wave segments - fMRI evidence & retinal SD
Localized stimulation: sampling of phase space
Orientation selective
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
Markus A. Dahlem, TU Berlin
![Page 160: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/160.jpg)
Conclusion Open wave segments - fMRI evidence & retinal SD
Localized stimulation: sampling of phase space
Orientation selective
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
Markus A. Dahlem, TU Berlin
![Page 161: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/161.jpg)
Conclusion Open wave segments - fMRI evidence & retinal SD
Localized stimulation: sampling of phase space
Orientation selective
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
Markus A. Dahlem, TU Berlin
![Page 162: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/162.jpg)
Conclusion Open wave segments - fMRI evidence & retinal SD
fMRI patterns is more diffuse than SD patterns
reference (min 0)
start (min 20)
end (min 30)
What if the the blood flow provides along-range or global negative feedback?
modified from Hadjikhani et al. (2001) PNAS 98
Markus A. Dahlem, TU Berlin
![Page 163: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/163.jpg)
Conclusion Open wave segments - fMRI evidence & retinal SD
fMRI patterns is more diffuse than SD patterns
reference (min 0)
start (min 20)
end (min 30)
What if the the blood flow provides along-range or global negative feedback?modified from Hadjikhani et al. (2001) PNAS 98
Markus A. Dahlem, TU Berlin
![Page 164: Localized transient waves of cortical spreading depression in migraine](https://reader033.fdocuments.in/reader033/viewer/2022052600/558438e7d8b42abf1e8b4a52/html5/thumbnails/164.jpg)
Conclusion Open wave segments - fMRI evidence & retinal SD
Localized stimulation: sampling of phase space
”A”-”Z”,”0”-”9” (36 patterns), 4 sizes, 10 stimulation strengths =1440 stimulation patterns (elevation of activator concentration u)
12.56.25
Markus A. Dahlem, TU Berlin