brain mapping of migraine aura
DESCRIPTION
Special Brain Mapping Center Seminar at UCLA, June 19, 2012TRANSCRIPT
Brain Mapping of Migraine Aura
Markus A. Dahlem
Research group: Nonlinear Dynamics in Physiology and Medicine
0
5
10
15
5min7min
9min
11min
15min
0 10 20 30 40 50mm
5min7min
9min11min
15min
23 min
21
19
17
17
15
1311
975
10°
1 cm
Visual hemifield Primary visual cortex
Special Brain Mapping Center Seminar June 19, 2012
Markus A. Dahlem, TU Berlin
Outline
1 Localized spots traveling in human cortex
2 Linking SD patterns to symptoms
3 Towards migraine therapy
Markus A. Dahlem, TU Berlin
Outline
1 Localized spots traveling in human cortex
2 Linking SD patterns to symptoms
3 Towards migraine therapy
Markus A. Dahlem, TU Berlin
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
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
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
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
”Migraine generator” in the brainstem
SD
aura
trigger
Markus A. Dahlem, TU Berlin
”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
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
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
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
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
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
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
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
Cerebral blood flow in migraine
Radionuclide xenon 133 method, 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
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
What is a migraine aura?
Markus A. Dahlem, TU Berlin
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
Tracking migraine aura symptoms
Vincent & Hadjikhani (2007) Cephalagia 27
Markus A. Dahlem, TU Berlin
Tracking migraine aura symptoms
Vincent & Hadjikhani (2007) Cephalagia 27
Markus A. Dahlem, TU Berlin
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
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
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
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
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
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
Clinical evidence
Markus A. Dahlem, TU Berlin
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
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
Cortical geometry
positive (fender)
negative (saddle)
gyral crowns
entrance to sulci
gyral crowns
entrance to sulci
Markus A. Dahlem, TU Berlin
The surface of the brain (cortex) is curved
Markus A. Dahlem, TU Berlin
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
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
Nucleation failure on torus
Markus A. Dahlem, TU Berlin
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
Simulation of an engulfing SD wave
Folds
Bumbs
In cooperation with Jens Dreier &
Denny Milakara, Charite
Markus A. Dahlem, TU Berlin
Migraine scotoma are well explained
Pattern matching
”Curved” retinotopic mapping
47
913
A B
C
Dahlem & Tusch, submitted to J. Math Neuroscie.
Markus A. Dahlem, TU Berlin
Migraine scotoma are well explained
Pattern matching ”Curved” retinotopic mapping
47
913
A B
C
A
C
BHM
10Æ10Æ
Dahlem & Tusch, submitted to J. Math Neuroscie.
Markus A. Dahlem, TU Berlin
Migraine scotoma are well explained
Pattern matching ”Curved” retinotopic mapping
47
913
A B
C
a d
b ce
m
m lv u10Ælingual gyrus uneus CS
Dahlem & Tusch, submitted to J. Math Neuroscie.
Markus A. Dahlem, TU Berlin
Migraine scotoma are well explained
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, submitted to J. Math Neuroscie.
Markus A. Dahlem, TU Berlin
Linking SD patterns to symptoms
Outline
1 Localized spots traveling in human cortex
2 Linking SD patterns to symptoms
3 Towards migraine therapy
Markus A. Dahlem, TU Berlin
Linking SD patterns to symptoms
Cortical homeostasis is stable
Hypothesis: Cortical susceptibility to SD depends on the size ofthe momentarily affected tissue.
Markus A. Dahlem, TU Berlin
Linking SD patterns to symptoms
Yet, too big a perturbation triggers SD
Hypothesis: Cortical susceptibility to SD depends on the size ofthe momentarily affected tissue.
Markus A. Dahlem, TU Berlin
Linking SD patterns to symptoms
Yet, too big a perturbation triggers SD
Hypothesis: Cortical susceptibility to SD depends on the size ofthe momentarily affected tissue.
nucleationcritical
Markus A. Dahlem, TU Berlin
Linking SD patterns to symptoms
But a global negative feedback keeps SD confined
Hypothesis: Cortical susceptibility to SD depends on the size ofthe momentarily affected tissue.
slow dynamicstransient and
Markus A. Dahlem, TU Berlin
Linking SD patterns to symptoms
Cellular models. What about cortex (continuum limit)?
ion
currents
ion gradient
ion
conductance
ion
pumps
activator−inhibitor dynamics
depolarization
firing rate
C∂V
∂t= −m∞(V )INa − n∞(V )IK − I
pumpK
(V )− IpumpNa
(V )
∂[ion]o
∂t=
IionA
FVolo+ Idiff
∂[ion]i
∂t=
IionA
FVoli
with
Iion = V αF Pion[ion]i − [ion]o e−αV
1− e−αV
Ipumpion (V ) = βion Imax
(1 +
KmK
[K ]o
)−2 (1 +
KmNa
[Na]i
)−3
M. A. Dahlem, Models of cortical SD, Scholarpedia (invited)
Markus A. Dahlem, TU Berlin
Linking SD patterns to symptoms
Cellular models. What about cortex (continuum limit)?
ion
currents
ion gradient
ion
conductance
ion
pumpsout in
diffu
sion
activator−inhibitor dynamics
depolarization
firing rate
neurovascular coupling
neural network activity
C∂V
∂t= −m∞(V )INa − n∞(V )IK − I
pumpK
(V )− IpumpNa
(V )
∂[ion]o
∂t=
IionA
FVolo+ Dion∇
2[ion]o
∂[ion]i
∂t=
IionA
FVoli
with
Iion = V αF Pion[ion]i − [ion]o e−αV
1− e−αV
Ipumpion (V ) = βion Imax
(1 +
KmK
[K ]o
)−2 (1 +
KmNa
[Na]i
)−3
F (S)
M. A. Dahlem, Models of cortical SD, Scholarpedia (invited)
Markus A. Dahlem, TU Berlin
Linking SD patterns to symptoms
Simulation of transient SD wave segment
gray = cortical surface; red = SD wave
Markus A. Dahlem, TU Berlin
Linking SD patterns to symptoms
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
Linking SD patterns to symptoms
Confined spatial patterns of spreading depression
neighboring points
collapse
?
16 min
31 min
1 cm
nucleationrecordedslice not
Markus A. Dahlem, TU Berlin
Linking SD patterns to symptoms
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
Linking SD patterns to symptoms
Confined spatial patterns of spreading depression
neighboring points 16 min
31 min
1 cm
recordedslice not
Markus A. Dahlem, TU Berlin
Linking SD patterns to symptoms
Confined spatial patterns of spreading depression
neighboring points 16 min
31 min
1 cm
recordedslice not
Markus A. Dahlem, TU Berlin
Linking SD patterns to symptoms
Confined spatial patterns of spreading depression
neighboring points 16 min
31 min
1 cm
recordedslice not
Markus A. Dahlem, TU Berlin
Linking SD patterns to symptoms
Confined spatial patterns of spreading depression
5cm
00
0 0
32 16
6 24
time / m
in
Markus A. Dahlem, TU Berlin
Linking SD patterns to symptoms
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
Linking SD patterns to symptoms
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
Linking SD patterns to symptoms
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
Linking SD patterns to symptoms
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
Linking SD patterns to symptoms
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
Linking SD patterns to symptoms
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
Linking SD patterns to symptoms
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
Linking SD patterns to symptoms
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
Linking SD patterns to symptoms
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
Towards migraine therapy
Outline
1 Localized spots traveling in human cortex
2 Linking SD patterns to symptoms
3 Towards migraine therapy
Markus A. Dahlem, TU Berlin
Towards migraine therapy
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
Towards migraine therapy
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
Towards migraine therapy
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
Towards migraine therapy
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
Towards migraine therapy
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
Towards migraine therapy
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
Towards migraine therapy
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
Towards migraine therapy
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
Towards migraine therapy
From bifurcation bench to bedside
Markus A. Dahlem, TU Berlin
Towards migraine therapy
From bifurcation bench to bedside
Markus A. Dahlem, TU Berlin
Towards migraine therapy
From bifurcation bench to bedside
Markus A. Dahlem, TU Berlin
Towards migraine therapy
From bifurcation bench to bedside
Markus A. Dahlem, TU Berlin
Towards migraine therapy
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
Towards migraine therapy
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
Towards migraine therapy
Single-pulse transcranial magnetic stimulation
Lipton et al. Lancet Neurology 9,373, 2010
Markus A. Dahlem, TU Berlin
Towards migraine therapy
Single-pulse transcranial magnetic stimulation
Markus A. Dahlem, TU Berlin
Towards migraine therapy
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
Towards migraine therapy
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
Towards migraine therapy
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
Towards migraine therapy
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
Towards migraine therapy
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
Conclusion
(i) Persistent migraine w/o infarction, (ii) Migrainousinfarction, (iii) ischemia-induced migraine
Dahlem et al. Physica D 239, 889 (2010)
Markus A. Dahlem, TU Berlin
Conclusion
Clinical evidence for localized SD
Cortical perfusion measurement by indocyanine-green videoangiography inpatients undergoing hemicraniectomy for malignant stroke
cf. Woitzik J et al., Stroke 37,1549 (2006)
Markus A. Dahlem, TU Berlin
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
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
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
Conclusion ¡
Cooperation & Funding
Nouchine Hadjikhani(EPFL & Martinos Center for Biomedical Imaging, MGH)
Paul Van Valkenburgh
Jens Dreier(Department of Neurology, Charite; University Medicine, Berlin)
Steve Schiff(Penn State Center for Neural Engineering)
Klaus Podoll(University Hospital Aachen)
Thomas Isele
berlin
Migraine Aura Foundation
Markus A. Dahlem, TU Berlin
Conclusion ¡
2 symptoms, 3 combinations: both or either of them
SD ?
aura headache
trigger trigger
Markus A. Dahlem, TU Berlin
Conclusion ¡
A conductor of a neural orchestra playing migraine
SD ?
aura headache
mysterious conductor
trigger trigger
Markus A. Dahlem, TU Berlin
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
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
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
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
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
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
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
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
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
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
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
Conclusion ¡
Localized stimulation: sampling of phase space
Orientation selective
−π/2
0
π/2
Markus A. Dahlem, TU Berlin
Conclusion ¡
Localized stimulation: sampling of phase space
Orientation selective
−π/2
0
π/2
Markus A. Dahlem, TU Berlin
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
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
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
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
Conclusion Open wave segments - fMRI evidence & retinal SD
Tracking migraine aura symptoms
Vincent & Hadjikhani (2007) Cephalagia 27
Markus A. Dahlem, TU Berlin
Conclusion Open wave segments - fMRI evidence & retinal SD
Tracking migraine aura symptoms
Vincent & Hadjikhani (2007) Cephalagia 27
Markus A. Dahlem, TU Berlin
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
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
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
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
Conclusion Open wave segments - fMRI evidence & retinal SD
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
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
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
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
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
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
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
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
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
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
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
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
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
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