1. 1 1 2 2 2 2 2 1
Bellistri E , Gnatkovsky V , Sartori I , Pelliccia V , Gozzo F , Francione S , Cardinale F , de Curtis M
1
Fondazione I.R.C.C.S. Istituto Neurologico C. Besta, Epilettologia Clinica e Neurofisiologia Sperimentale, Milano, Italy,
2
Ospedale Niguarda Ca Granda, Centro per la Chirurgia dell'Epilessia 'C. Munari', Milano, Italy
P0154
Computer assisted analysis of response to high frequency stimulation during sEEG
H15
H4
N1
N16
O14
P11
R2
R8
X2
X6
X8
Z2
Z3
N15
P5
S9
X7
Y4
Z4
P1
Y6
H13
X5
Y5
O12
R5
R6
R7
Y1
S8
S7
X1
R9
S6
S4
S5
Y3
1
3
5
7
9
11
13 EZ contacts
EPZ contacts
NET contacts
n.ofconnections
electrode contacts
one HFS
0
0
200 400 600 800
-200
2
µV /Hz
200
400
2
µV /Hz
PSD Integral HFS
PSDIntegralHFS-preHFS
all HFSs
0.750 0.25 0.5
-0.2
0
0.2
0.4
0.6 EZ contacts
EPZ contacts
NET contacts
arbitrary units
(HFS)
arbitraryunits
(HFS-preHFS)
stimulated
contacts
pre-stim HFS post-stim2 mV
1s
a b
a (preHFS) b (HFS)
b - a
(HFS - preHFS)
2
µV /Hz2
µV /Hz
2
µV /Hz
1s 1s
Software
www.ni.com www.slicer.orgwww.cytoscape.org www.r-project.org
Accuracy Sensitivity Specificity
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
0
50
400
100
0
50
400
100
0 5
sec
0 5
sec
0 5
0
1000
0
1000
0 5
secsec
raw signal
artifact removal
filtered signal
[2-400Hz]
contact B1
raw signal
artifact removal
filtered signal
[2-400Hz]
contact A10
B1
A10
Electrode A Electrode B
0 5
A11
A12
A13
A14
A6
A7
A8
A9
A2
A3
A4
A5
B2
B3
B4
B5
B6
B7
B8
B9
B10
B11
B12
B13
B14
B15
80
70
60
50
80
70
60
50
HFS period HFS period
200
µV1 s
20 ms 20 ms
A subpopulation of patients suffering from pharmacoresistant focal
epilepsy candidate to epilepsy surgery are monitored using intracerebral
[1]
stereo-EEG electrodes to identify the epileptogenic zone (EZ) .
[2]
We propose a method to automatically define subsets of EZ contacts,
focusing on the features of brain signals in response to high frequency
(HF) 50Hz stimulation performed for diagnostic purposes during stereo-
EEG studies with intracranial electrodes. Our study presents a new
algorithm to evaluate signal parameters characterized by a fast activity
[3,4]
responses that are masked at visual inspection by the HF stimulation
artifacts.
Figure 2. Calculation of
c o n t a c t - s p e c i fi c h i g h
frequency PSD integral
evoked during 50 Hz HFS at
one single site.
3D reconstruction of the brain
with the implanted electrodes
and signals recorded in all
contacts considering a window
of 20 sec around the HFS period
(grey shading). For each
contact, the PSD integral is
calculated for 20 sec segments
pre-HFS (a), HFS (b) and post-
HFS.
The histograms represent the
integral of average PSD across
60-80 Hz in the segments (a)
and (b). The difference between
b and a (variation of PSD
integral) is shown in the right-
most panel. The magnification
clearly shows high frequency
activity in a subset of contacts
(later identified as EZ contacts).
Figure 3.
Semi-automatic clustering
On the top, two variables
calculated for each contact
(PSD integral and variation of
PSD integral) in response to
HFS of one single couple of
electrodes are represented in a
2 dimensional graph. K-mean
cluster algorithm identifies N
different clusters, defined in the
set-up parameters.
On the bottom, individual
scatterplots from all HFS
performed in a single patient
are merged in a single diagram.
Contacts identified by the
expert neurophysiologist as EZ
(epileptogenic zone) and EPZ
(epileptic propagation zone)
are represented by coloured
dots. Contacts from not
epileptogenic tissue (NET- grey
and open dots) cluster in the left
side of the graph. The contacts
characterized by increased
PSD integral response to HFS
form a virtual cluster (blue line)
that includes EZ and EPZ
contacts classified by expert
neurophysiologists.
Figure 4. Contacts selected
b y t h e a l g o r i t h m a r e
represented in a connection
diagram with a circular layout.
This representation clearly
highlights contacts that respond
only once during the entire
protocol, as they lay outside the
circle. The histogram below
represents the inbound degree
of the contacts. EZ and EPZ
contacts tend to have high
values of inbound degree.
Contacts with an inbound
degree of 1 are subsequently
discarded from the selected
contacts list.
Figure 5. ROC curve and algorithm performance.
The algorithm was tested on 22 patients. The % of number of contacts selected by the algorithm
that match with the EZ and the EPZ costitute the true positive (TP) rate of the results. The
amount of contacts discarded by the algorithm and labelled as healthy by neurophysiologists
constitute the true negative rate (TN).
In the histogram below the matching percentage with EZ is represented by red bars, the
matching with EPZ is represented by orange bars.
Figure 1. SEEG signal
processing.
In the upper traces the raw
signal are shown. In the middle
traces the HFS artifact was
subtracted. In the lower traces,
subtracted signals were band-
pass filtered at 2-400 Hz. In the
example A, the intensity of the
frequencies during the train did
not change compared to the
b a c k g r o u n d a c t i v i t y. A n
increase of the frequencies
between 60 and 80 Hz is
evident in the correspondence
of the HFS window in the traces
and in the frequency plot (lower
panel) in the example B. The
two different types of response
are analyzed with more detail to
define the response pattern to
HFS in the epileptogenic tissue
compared to healthy brain.
Histogram on the bottom shows
the integral across 60-80Hz
frequencies of average PSD
during the stimulation period, in
a representative subset of
contacts.
CONCLUSIONS
A contact classification based on the pattern of activity generated by HFS
could, in principle, be utilized to characterize the EZ and the boundaries of
the surgical excision. The dynamic of the responses to HFS could be
useful to define the epileptogenic networks and their functional properties.
BIBLIOGRAPHY
[1] F. Cardinale, M. Cossu, L. Castana, G. Casaceli, M. P. Schiariti,A. Miserocchi, D. Fuschillo,A. Moscato, C. Caborni, G.Arnulfo and G. Lo Russo,
Stereoelectroencephalography: Surgical methodology, safety, and stereotactic application accuracy in 500 procedures, Neurosurgery 72(3) (2013)
353–366.
[2] E. Bellistri, I. Sartori, V. Pelliccia, S. Francione, F. Cardinale, M. de Curtis and V. Gnatkovsky, Fast Activity Evoked by Intracranial 50 Hz Electrical
Stimulation as a Marker of the Epileptogenic Zone, Int J Neu Syst Vol. 25, No. 5 (2015) 1550022.
[3] S. Kalitzin, D. Velis, P. Suffczynski, J. Parra, F.L. da Silva. Electrical brain-stimulation paradigm for estimating the seizure onset site and the time to
ictal transition in temporal lobe epilepsy. Clin Neurophysiol. 2005 Mar;116(3):718-28.
[4] J. Jacobs, M. Zijlmans, R. Zelmann, A. Olivier, J. Hall, J. Gotman, F. Dubeau. Value of electrical stimulation and high frequency oscillations (80-
500 Hz) in identifying epileptogenic areas during intracranial EEG recordings. Epilepsia. 2010Apr;51(4):573-82.
iteration for each recording contact
semi-automatic clustering
artifact removal
& filtering
human intracranial
stereo-EEG
(up to 192 recording contacts)
5-sec intracerebral bipolar
50 Hz stimulations (HFS)
feature extraction
comparison with clinical identification
of EZ, EPZ and NET contacts
analysis and correction of
outlayer contacts
computer-assisted definition of
EZ, EPZ and NET contacts
and spatial distribution
on 3D MR brain reconstructions
iteration for each couple of HFS contacts
60-80 Hz
power integral
export 20-sec
HFS epochs
clinicalprotocol
comparisonw
clinicalevaluation
coreanalysis
study
output
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
1-6 sec
1 ms
20 ms (50Hz)
Twelve to sixteen intracerebral multichannel electrodes (Dixi Medical, France and ALCIS, France), each
exibiting 5–18 contacts (length, 2 mm, diameter, 0.8 mm; 1.5 mm apart) were implanted, for a total number of
105–162 recording sites per patient. SEEG recordings with 0.016–300 Hz band-pass filter were performed
using Neurofax EEG-1100 system (Nihon Kohden, Tokyo, Japan) at 1 kHz sampling rate and 16-bit resolution.
Intracerebral recording sites were identified on 3D MR reconstructions of the patient brain
Intracerebral HFS trains were performed as part of the routine clinical assessment to locate both the
epileptogenic and eloquent regions. A train of bipolar 4 ms pulses of variable intensity (in a range from 0.3
to 3 mA) were applied at 50 Hz to pairs of contiguous contacts on the same electrode shaft with a duration
variable between 3 and 6 seconds. HFS was performed in 15-40% of the leads available on implanted
electrodes. HF stimulation is not performed in a systematic way, but each patients could have a variable
number of contacts stimulated, belonging or not to the EZ and EZP.
CLINICAL PROTOCOL
To evaluate the algorithm performance, different parameters were evaluated.
ACCURACY is defined as (TP+TN)/P + N.
SENSITIVITY is defined as TP/P.
SPECIFICITY is defined as TN/N.
ROC curve (on the right) represents the relation between Sensitivity and Specificity. More
the area below the curve is close to 1, better is the performance of the algorithm.
P1 P2 P3 P4 P5 P6 P7 P8 P9 P10 P11 P12 P13 P14 P15 P16 P17 P18 P19 P20
100%
75%
50%
25%
P21 P22
0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.80
0.2
0.4
0.6
0.8
0
1
A B