Transcript Interaction?

Quantitative analysis of
electroencephalographic (EEG) signals
Dept. of Epileptology
University of Bonn
www.epileptologie-bonn.de
Quantitative EEG analysis
• 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 methods: why?
Example: sleep-EEG (qualitative)
d  2 Hz
q  5 Hz
a  10 Hz
b  20 Hz
g > 30 Hz
Rechtschaffen and Kales, 1968
Quantitative EEG methods: why?
Example: sleep-EEG (qualitative)
Hypnogram
Time
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
b/g  perception, cognitive processes!
1/f amplitudecharacteristic

Quantitative EEG methods: why?
Theta-gamma interaction within hippocampus
Interactions
(hippocampus):
Theta (5Hz)


Gamma (>30Hz)
Chrobak u. Buzsáki, J. Neurosci. 1998
Quantitative EEG methods: why?
Event-related EEG: averaging
Average
event-related
potential (ERP)
Reduction of background „noise“: 1/n
Quantitative EEG methods: why?
Event-related EEG
Averaged ERP-response
?
?
Amplitude-Changes
evoked
Phase-Locking
induced ( cognition)
Wavelet-based ERP analysis
Traditional approach: Fourier-transform
Fourier-transform
Power density
F () =  f(t)  eit dt
P () = F ()  F* ()
Discrete: Fast-Fouriertransform (FFT)
Spectral Coherence
f=1/T!
Cxy() = |Pxy()|2 / Pxx()  Pyy()
Wavelet-based ERP analysis
Phase-locking vs. amplitude-changes
Morlet-Wavelet:
w(t,) = exp(-t2/22) * exp (it)
Wavelet-Transform:
W(t,) =  f(t-) * w(,) d
Power (t,) = W(t,) 2
Phase (t,) = arctan (Im (t,) / Re (t,))
Wavelet-based ERP analysis
Phase-locking vs. amplitude-changes
*
Amplitude/Power (t,)
Phase (t,)


Wavelet-transform (real part)
50
uV
30
10
-10
-30
-50
Wavelet-based ERP analysis
Phase-locking vs. amplitude-changes
WT ERPresponses:
Phases:
Histogram P():
t,3 ...
t,2
t,1

Variance?
-180 °
-180°
Circular variance:
|  e i |
Shannon entropy:
1 +  P log P
0°
0°
180°
180 °
Phase-locking
index
e.g. Lachaux et al., Hum. Brain Mapp. 1999; Tass et al., Phys. Rev. Lett. 1998
Wavelet-based ERP analysis
Phase-synchronisation
Brain region A
t,1 ?
t,2 ?
t,3 ?
t,4 ?
Brain region B
Variance of phase differences t  Synchronisation index
Phase-locking analysis of MTL depth ERPs
Epilepsy (prevalence  1%)
Seizures:
 Unfamilar
sensations
 Unvoluntary
body movements
 Loss of
consciousness
Phase-locking analysis of MTL depth ERPs
MTL depth-recordings in epilepsy patients
MTL-epilepsy:  45% pharmaco-resistant
Presurgical evaluation: seizure focus?
Hippocampus
Amygdala
Parahippocampal cortex
Rhinal cortex
Memory processes
Phase-locking analysis of MTL depth ERPs
Hippocampal P3
(neue Wörter)
„Oddball experiment“: X ... X ... X ... O ... X ... X ... O ... X ... X
Target
Hippocampus sclerosis
Non-pathological side
-120
-100
-120
Target
Nontarget
-100
Target
Nontarget
-80
Amplitude (µV)
Amplitude (µV)
-80
-60
-40
-20
0
-60
-40
-20
0
20
20
40
40
60
-200
Target
60
0
200
400
Zeit (ms)
600
800
1000
-200
0
200
400
600
800
1000
Zeit (ms)
Neuroimage 2005; 24: 980-989
Phase-locking analysis of MTL depth ERPs
Hippocampal P3: low-frequency range
Hippocampus sclerosis
Non-pathological side
Phase-locking
Frequency (Hz)
30
25
20
15
10
-1
0
1
2
3
4
5
5
Power
Frequency (Hz)
30
25
20
15
10
-2
-1
0
1
2
3
5
0
200
400
600
800 time
(ms)
0
200
400
600
800 time
(ms)
Neuroimage 2005; 24: 980-989
Phase-locking analysis of MTL depth ERPs
Hippocampal P3: gamma range
Hippocampus sclerosis
Non-pathological side
Phase-locking
Frequency (Hz)
48
-1,0
-0,5
0,0
0,5
1,0
1,5
2,0
2,5
46
44
42
40
38
36
34
32
48
Power
Frequency (Hz)
46
44
42
40
38
36
-1,0
-0,5
0,0
0,5
1,0
1,5
34
32
0
200
400
600
800
1000
time (ms)
0
200
400
600
800
1000
time (ms)
Neuroimage 2005; 24: 980-989
Phase-locking analysis of MTL depth ERPs
Anterior mediotemporal lobe (AMTL)-N4
„Continuous recognition experiment“:
(neue Wörter)
Haus ... Schiff ... Pferd ... Schiff ... Baum ... Haus ... Tisch ...
New
New
-60
amplitude (µV)
New
New
Old
Old
New
Correct rejections (new)
Hits (old)
-40
-20
0
20
-200
0
200
400
600
800
1000
time (ms)
J. Cogn. Neurosci. 2004; 16:1595-1604
Phase-locking analysis of MTL depth ERPs
AMTL-N4
(old words)
(new words)
(neue
Wörter)
ERPs
Phase-locking
Power
( fMRI)
J. Cogn. Neurosci. 2004; 16:1595-1604
Declarative memory formation: MTL connectivity
MTL depth electrodes
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)
Interaction?
Declarative memory formation MTL connectivity
Subsequent memory paradigm
...
„72“
„75“
„78“
„81“
„84“
Sahne
?
87
Learning
„Mutter“
„Leistung“
„Ende“
„Sahne“
„Appetit“
„Uhr“
Distraction
Free recall
• 9 TLE patients with unilateral focus
• “Dm-effect” (difference due to memory):
remembered vs. forgotten words
Declarative memory formation: MTL connectivity
MTL-ERPs: “difference due to memory”
remembered
forgotten
Rhinal cortex
Dm-effects correlated (r = 0.92)
 rhinal-hippocampal interaction
Direct evidence?
g-sync.  coupling of assemblies
Hippocampus
– 20 µV
I
20
ms
I I I I I I I I I I
400 800 1200 1600 2000
Fernández et al., Science 1999
Declarative memory formation: MTL connectivity
Rhinal-hippocampal gamma synchronisation
48
48
46
46
44
44
[Hz]
Frequency
frequency [Hz]
Phase-synch.
index:
remembered forgotten
42
42
40
40
38
38
36
36
34
34
32
32

0.0
0.0
0.5
0.5
desynchronization
Desynchronisation
time [s]
1.0
1.0
synchronization
Synchronisation
1.5
1.5
time [s]
- 30
- 20
- 10
0
+ 10 + 20 + 30
percentage
change
relative
to
prestimulus
baseline
- 20 - 10 0 + 10 + 20
+
- 30
30
Change [%]: remembered - forgotten
-180°
-180 °
0
0°
180 °
180°
Nat. Neurosci. 2001; 4: 1259-1264
Declarative memory formation: MTL connectivity
Changes of gamma power
Rhinal cortex
Changes of gamma power compared to baseline
20
10
0
-10
Hippocampus
20
10
0
-10
0.0
0.5
1.0
1.5
time [s]
remembered
forgotten
Nat. Neurosci. 2001; 4: 1259-1264
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

Spectral coherence [%] between
rhinal cortex and hippocampus
30
25
"dm"-effect: Theta-coherence
Non-specific increase
of theta-coherence
1,0
0,8
0,6
0,4
0,2
r = 0.80, p = 0.018
0,0
20
-0,2
0,0
0,2
0,4
0,6
0,8
1,0
1,2
1,4
"dm"-effect: Gamma-synchronization
15
10

5
0
delta
1-4Hz
theta
4-7Hz
alpha1
7-10Hz
forgotten words
alpha2
10-13Hz
beta1
beta2
13-16Hz 16-19Hz
Specific theta-gamma
interaction
remembered words
Eur. J. Neurosci. 2003; 17: 1082-1088
Declarative memory formation: MTL connectivity
Gamma activity: interactions with theta and action potentials
Interactions
(hippocampus):
Theta (5Hz)


Gamma (>30Hz)


Spikes
Chrobak u. Buzsáki, J. Neurosci. 1998
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
Wach
Stadium 1
Stadium 2
SWS = 3, 4
REM
40
30
20
10
0
d
q
1-4
4-8
a
b
b
g
g
g
8-12 12-16 16-20 20-28 28-3636-44 Hz
Eur. J. Neurosci. 2003; 18: 1711-1716
Declarative memory formation: MTL connectivity
Rhinal-hippocampal 40 Hz coherence
0.5
0.
Awake
Stage 1
REM
Stage 2
SWS
0
2
4
6
Time (hours)
Eur. J. Neurosci. 2003; 18: 1711-1716
Declarative memory formation: MTL connectivity
Memory formation during sleep
Direct correlate?
•  Awakenings from REM sleep:
recall in 6 patients (good, 79.2%)
patients (poor, 6.7%)
dream
vs. 6
• 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 hippocampus
Declarative memory formation: MTL connectivity
Rhinal-hippocampal EEG coherence
Declarative memory formation: MTL connectivity
Conclusion
Rhinal-hippocampal connectivity
= core factor of
declarative memory formation
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
Dept. of Epileptology
University of Bonn
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]
www.epileptologie-bonn.de