Quantitative analysis ofelectroencephalographic (EEG) signals
www.epileptologie-bonn.de
Dept. of EpileptologyUniversity of Bonn
•Quantitative EEG-methods: why?
•Example: Wavelet-based event-related potential (ERP)-analysis
•Phase-locking analysis of mediotemporal lobe (MTL) depth ERPs
•Declarative memory formation: MTL connectivity
•Summary
Quantitative EEG analysis
Quantitative EEG methods: why?Example: sleep-EEG (qualitative)
Rechtschaffen and Kales, 1968
2 Hz
5 Hz
10 Hz
20 Hz
30 Hz
Time
Hypnogram
Quantitative EEG methods: why?Example: sleep-EEG (qualitative)
Quantitative EEG methods: why?Example: sleep-EEG (quantitative)
Electroencephalogr Clin Neurophysiol 1996; 98: 401-410
Quantitative EEG methods: why?EEG = superposition of oscillations
Visual analysis: only low-frequency oscillations perception, cognitive processes!
1/f amplitude- characteristic
Theta-gamma interaction within hippocampus
Chrobak u. Buzsáki, J. Neurosci. 1998
Interactions(hippocampus):
Theta (5Hz)
Gamma (>30Hz)
Quantitative EEG methods: why?
Quantitative EEG methods: why?Event-related EEG: averaging
Average
event-related
potential (ERP)
Reduction of background „noise“: 1/n
Quantitative EEG methods: why?
Averaged ERP-response ? ?
Amplitude-Changes Phase-Locking
Event-related EEG
evoked induced ( cognition)
Wavelet-based ERP analysisTraditional approach: Fourier-transform
Power density
P () = F () F* ()
Spectral Coherence
Cxy() = |Pxy()|2 Pxx() Pyy()
Fourier-transform
F () = f(t) eit dt
Discrete: Fast-Fourier-transform (FFT)
f = 1 / T !
Wavelet-based ERP analysisPhase-locking vs. amplitude-changes
Morlet-Wavelet: w(t,) = exp(-t2/22) * exp (it) Wavelet-Transform: W(t,) = f(t-) * w(,) d
Power (t,) = W(t,) 2 Phase (t,) = arctan (Im (t,) / Re (t,))
Wavelet-based ERP analysis
Original EEG
-150
-100
-50
0
50
100
150
Zeit [s]0 5 10
Wavelet-transform (real part)
-50
-30
-10
10
30
50
uV
* Amplitude/Power (t,)
Phase (t,)
Phase-locking vs. amplitude-changes
WT ERP-responses:
Wavelet-based ERP analysis
t,1Phases: t,2t,3 ...
Circular variance: | e i |
Shannon entropy: 1 + P log P
Histogram P():
-180 ° 0 ° 180 °
0°-180° 180°
Phase-locking vs. amplitude-changes
Variance?
Phase-locking index
e.g. Lachaux et al., Hum. Brain Mapp. 1999; Tass et al., Phys. Rev. Lett. 1998
Brain region A
Brain region B
t,1 ? t,2 ? t,3 ? t,4 ?
Phase-synchronisation
Variance of phase differences t Synchronisation index
Wavelet-based ERP analysis
Phase-locking analysis of MTL depth ERPsEpilepsy (prevalence 1%)
Seizures:
Unfamilar sensations
Unvoluntary body movements
Loss of consciousness
Parahippocampal cortex
Rhinal cortex
Amygdala
Hippocampus
Phase-locking analysis of MTL depth ERPsMTL depth-recordings in epilepsy patients
MTL-epilepsy: 45% pharmaco-resistant
Presurgical evaluation: seizure focus?
Memory processes
Phase-locking analysis of MTL depth ERPs
(neue Wörter)„Oddball experiment“: X ... X ... X ... O ... X ... X ... O ... X ... X
Hippocampus sclerosis Non-pathological side
Target Target
Zeit (ms)
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Am
plit
ud
e (
µV
)
-120
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-60
-40
-20
0
20
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TargetNontarget
Zeit (ms)
-200 0 200 400 600 800 1000
Am
plit
ud
e (
µV
)
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0
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TargetNontarget
Neuroimage 2005; 24: 980-989
Hippocampal P3
Phase-locking analysis of MTL depth ERPs
Phase-locking
Power
Fre
qu
en
cy (
Hz)
5
10
15
20
25
30
-1 0 1 2 3 4 5
time(ms)
0 200 400 600 800
Hippocampus sclerosis Non-pathological side
time(ms)
0 200 400 600 800
Fre
qu
en
cy (
Hz)
5
10
15
20
25
30
-2 -1 0 1 2 3
Neuroimage 2005; 24: 980-989
Hippocampal P3: low-frequency range
Phase-locking analysis of MTL depth ERPs
Phase-locking
Power
Hippocampus sclerosis Non-pathological side
Neuroimage 2005; 24: 980-989
Hippocampal P3: gamma range
Fre
qu
en
cy (
Hz)
32
34
36
38
40
42
44
46
48
-1,0 -0,5 0,0 0,5 1,0 1,5 2,0 2,5
time (ms)0 200 400 600 800 1000
Fre
qu
en
cy (
Hz)
32
34
36
38
40
42
44
46
48
-1,0 -0,5 0,0 0,5 1,0 1,5
0 200 400 600 800 1000time (ms)
(neue Wörter)„Continuous recognition experiment“:
Haus ... Schiff ... Pferd ... Schiff ... Baum ... Haus ... Tisch ...
Old
time (ms)
-200 0 200 400 600 800 1000
am
plitu
de (
µV
) -60
-40
-20
0
20
Correct rejections (new)Hits (old)
OldNewNewNew New New
J. Cogn. Neurosci. 2004; 16:1595-1604
Phase-locking analysis of MTL depth ERPsAnterior mediotemporal lobe (AMTL)-N4
J. Cogn. Neurosci. 2004; 16:1595-1604
Phase-locking
Power
( fMRI)
ERPs
(neue Wörter)(old words) (new words)
Phase-locking analysis of MTL depth ERPsAMTL-N4
Declarative memory formation: MTL connectivityMTL depth electrodes
Interaction?
Declarative long-term memory: Consciously accessible information,
e.g. events and facts
Rhinal Cortex
Convergence of sensory data,semantic preprocessing Hippocampus
Synaptic plasticity, long term potentiation (LTP)
•9 TLE patients with unilateral focus
•“Dm-effect” (difference due to memory):
remembered vs. forgotten words
Subsequent memory paradigm
Sahne
„Uhr“„Appetit“
„Sahne“„Ende“„Leistung“
„Mutter“
87
LearningLearning DistractionDistraction
?
Free recallFree recall
„84“„81“
„78“„75“
„72“. . .
Declarative memory formation MTL connectivity
I I I I I I I I I II2000
µV– 20
400 1600120080020
ms
Rhinal cortex
Hippocampus
remembered
forgotten
Fernández et al., Science 1999
MTL-ERPs: “difference due to memory”
Dm-effects correlated (r = 0.92) rhinal-hippocampal interaction
Direct evidence?
-sync. coupling of assemblies
Declarative memory formation: MTL connectivity
time [s]
Fre
quen
cy [
Hz]
0.0 0.5 1.0 1.532
34
36
38
40
42
44
46
48
- 30 - 20 - 10 0 + 10 + 20 + 30
Change [%]: remembered - forgotten
Desynchronisation Synchronisation
Nat. Neurosci. 2001; 4: 1259-1264
Rhinal-hippocampal gamma synchronisationDeclarative memory formation: MTL connectivity
-180 ° 0 180 °
0°-180° 180°
Phase-synch. index:
remembered - forgotten
Nat. Neurosci. 2001; 4: 1259-1264
Changes of gamma power
Rhinal cortex
-10
0
10
20
Changes of gamma power compared to baseline
Hippocampus
-10
0
10
20
time [s]
remembered forgotten
0.0 0.5 1.0 1.5
Declarative memory formation: MTL connectivity
Interpretation
• Rhinal-hippocampal phase coupling initiates information transfer ( 100 ms poststim.)
• Information transfer after onset of rhinal dm-effect (ERPs, 300 ms poststim.)
• Phase decoupling terminates information transfer ( 1000 ms poststim.)
• Reduced gamma power: specific assembly activation, suppression of gamma “noise”
Declarative memory formation: MTL connectivity
Memory-related theta-gamma cooperation
Sp
ectr
al co
he
ren
ce
[%
] b
etw
ee
nrh
ina
l co
rte
x a
nd
hip
po
ca
mp
us
0
5
10
15
20
25
30
forgotten words
remembered words
delta1-4Hz
theta4-7Hz
alpha17-10Hz
alpha210-13Hz
beta113-16Hz
beta216-19Hz
Eur. J. Neurosci. 2003; 17: 1082-1088
"dm"-effect: Gamma-synchronization
-0,2 0,0 0,2 0,4 0,6 0,8 1,0 1,2 1,4
"dm
"-ef
fect
: The
ta-c
oher
ence
0,0
0,2
0,4
0,6
0,8
1,0
r = 0.80, p = 0.018
Non-specific increase of theta-coherence
Specific theta-gamma
interaction
Declarative memory formation: MTL connectivity
Gamma activity: interactions with theta and action potentials
Chrobak u. Buzsáki, J. Neurosci. 1998
Interactions(hippocampus):
Theta (5Hz)
Gamma (>30Hz)
Spikes
Declarative memory formation: MTL connectivity
Hebbian assembly formation
Correlated firing of pre- and postsynaptic neuron Increase of synaptic efficacy (1949)
Experimental validation:
• Long-term potentiation and depression (LTP, LDP)• Spike timing dependent synaptic plasticity (STDP)
Synchronized gamma activity: precise spike timing (t < 10 ms)
(z.B. Engel u. Singer, Trends Cogn. Sci. 2001; Fries et al., Nat. Neurosci. 2001)
Abbott u. Nelson, Nat.. Neurosci. 2000
Declarative memory formation: MTL connectivity
Rhinal-hippocampal coupling during sleep
• Dreams are difficult to remember
• Unrecognized scene shifts
• Duration severely misestimated
Memory formation during (REM-) sleep reduced
(e.g. Hobson et al., Behav. Brain Sci. 2000)
Sleep recordings in 8 unilateral MTLE patients
(Indirect) electrophysiological correlate?
Declarative memory formation: MTL connectivity
Rhinal-hippocampal coupling during sleep
Eur. J. Neurosci. 2003; 18: 1711-1716
Declarative memory formation: MTL connectivity
0
10
20
30
40
WachStadium 1Stadium 2SWS = 3, 4REM
1-4
4-8
8-12
12-16
16-20
20-28
28-36
36-44 Hz
Rhinal-hippocampal 40 Hz coherence
Awake
Stage 1
REM
Stage 2
SWS
0.5
0.
Time (hours)0 2 4 6
Eur. J. Neurosci. 2003; 18: 1711-1716
Declarative memory formation: MTL connectivity
Memory formation during sleep
Direct correlate?
Awakenings from REM sleep: dream recall in 6 patients (good, 79.2%) vs. 6 patients (poor, 6.7%)
• No group differences in daytime memory performance
• Sleep: “spontaneous memory formation”, attention, volition, semantic processing
Core factor of declarative memory formation
Declarative memory formation: MTL connectivity
EEG power within hippocampusDeclarative memory formation: MTL connectivity
Rhinal-hippocampal EEG coherenceDeclarative memory formation: MTL connectivity
Rhinal-hippocampal connectivity
= core factor of
declarative memory formation
Declarative memory formation: MTL connectivityConclusion
Summary
Quantitative EEG-analysis
•EEG = superposition of functionally specific oscillations
•Averaged ERPs = phase locking + amplitude changes
•Connectivity may be more relevant than amplitudes of local activations
Guillén Fernández
Peter Klaver
Christoph Helmstädter
Thomas Dietl
Rüdiger Köhling
Edgar Kockelmann
Martin Lutz
Wieland Burr
Hakim Elfadil
Mario Städtgen
Carlo Schaller
Christian E. Elger
Kontakt: [email protected]
Dept. of EpileptologyUniversity of Bonn
www.epileptologie-bonn.de
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