Download µEEG

Interictal Fast Ripples Recorded
from a Dense Microelectrode
Array in Human Epileptic
Neocortex
Catherine Schevon, MD, PhD; Andrew Trevelyan, PhD; Robert
Goodman, MD; Guy McKhann Jr, MD; Charles Schroeder, PhD;
Ronald Emerson, MD
June, 2009
Multielectrode Array (MEA)
NeuroPortTM, Cyberkinetics Neurotechnology Systems, Foxboro, MA
(now Blackrock Microsystems, Salt Lake City, UT)
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Covers 4 x 4 mm area
96 contacts in a regular 10x10 grid
Depth 1 mm (Layer IV/V)
400 micron spacing
Active tips 35-75 μm long x 3-5 μm radius
30K samples/channel/sec
Implanted in epilepsy patients undergoing
chronic intracranial EEG recording, in neocortex
to be included in resection
I
II
III
IV
V
VI
WM
• Advantages:
• Fine spatial/temporal resolution
• Regular grid spacing
• Limitations:
• Records from one small area
• One cortical layer per site
Patient
MEA location
Epileptogenic Zone
Pathology
1 (41F)
R middle temporal
gyrus
R mesial temporal lobe
Nonspecific
2 (30M)
L lateral frontal
L lateral frontal and
temporal
N/A (MST only)
3 (39M)
L lateral frontal
L lateral frontal (3x3
cm area)
Nonspecific
4 (25F)
L inferior temporal
gyrus
L mesial/basal/lateral
temporal lobe
Mild MTS
“µEEG”
iEEG
Microelectrode recording
downsampled and aligned
with clinical EEG
recording
•
• “Macrodischarges”
μEEG
• Correlate with iEEG
epileptiform discharges
• Appear widespread in
µEEG
“Microdischarges”
µEEG
200 µV
µEEG
50 µV
100-200 Hz
200-500 Hz
30 µV
0.8 – 2 kHz
30 µV
HFO associated
with a
macrodischarge
1 second
30 ms
µEEG
200 µV
µEEG
100-200 Hz
50 µV
200-500 Hz
30 µV
HFO associated
with a
microdischarge
30 µV
0.8 – 2 kHz
1 second
40 ms
Correlation with interictal events
Macro
Micro
ND
Micro
Macro
Patient 1
Patient 2
Patient 2
Patient 3
Patient 3
Patient 4
Patient 4
0
5
10
15
20
25
0
Detections/min during sleep
and association with
paroxysmal µEEG features
10
20
30
40
50
Percentage of macrodischarges
and microdischarges with
associated HFOs
60
Detections by array location
“HFO events” = time period during which one or more HFOs are detected
85% of events were seen
at a single channel
40 µV
50 ms
“HFO events” = time period during which one or more HFOs are detected
11% of events occurred
on a large scale
Almost all were found
within the epileptogenic
zone (ie not in Patient 1)
80% of these occurred
with macrodischarges
40 µV
400 ms
µEEG
200 µV
Site to site
differences
during a large
scale event
100-200 Hz
200-500 Hz
0.8 – 2 kHz
50 ms
µEEG
100-200 Hz
200-500 Hz
0.8 – 2 kHz
50 ms
Conclusions and Questions
HFOs and microdischarges are distinct phenomena
– Evidence of different mechanisms underlying microdischarges
and macrodischarges?
Large-scale HFOs
–
–
–
–
Arise from multiple simultaneous independent generators
Specific markers of the epileptogenic zone?
Selectively detected by sparse sampling or large sensors?
Evidence of an epileptic network?
Are fast ripples a primary event or a secondary local
response (eg excitability)?
Co-authors and colleagues
Ron Emerson
Robert Goodman
Guy McKhann, Jr.
Charles Schroeder
Andrew Trevelyan
Allen Waziri
Julien Besle
Joe Isler
Anna Ipata
Elana Zion-Golumbic
Sara Inati
Peter Lakatos
Dan Friedman
Helen Scharfman
Michael Goldberg
Are all HFOs created equal?
Recording characteristics of Neuroport
microelectrodes vs microwires or depth
electrodes
Selective recording from cortical layers IV
and V
Use of detection thresholds create the
impression of a binary process
Patient
Implant Location
MEA location
Epileptogenic
Zone
Pathology
1 (41F)
Right lateral and
subtemporal regions
Right middle
temporal gyrus 4
cm from anterior
temporal pole
Right mesial temporal
lobe
Nonspecific, no
mesial
temporal
sclerosis
(MTS), no
dysplasia
2 (30M)
Left lateral frontal, mesial
frontal, and lateral
temporal lobes
Left lateral frontal,
minimum
distance 2 cm
superior to
Broca’s area and
on different
gyrus
Boundaries not
defined but
maximal area
identified in left
superior/lateral
frontal lobe
N/A (MST only)
3 (39M)
Left lateral and mesial
frontal lobe
Left lateral frontal,
minimum
distance 1.5 cm
superior to
Broca’s area and
on different
gyrus
Left frontal
operculum (3x3
cm cortical area),
superior to
Broca’s area
Nonspecific
4 (25F)
Left lateral and
subtemporal regions
Left inferior temporal
gyrus 2.5 cm
from anterior
temporal pole
Left mesial and
anterolateral
temporal lobe
Mild MTS
Patient 1
Patient 2
Patient 3
– Higher HFO rates
(overall and max per
channel) than seen with
microwires or
macroelectrodes but avg
per channel similar
– HFOs more frequent in
epileptogenic zone (but N
of 1 outside EZ…)
– Almost all HFOs had a
fast ripple component
Patient 4
HFO rates
Wake
Sleep
Wake
Sleep
Wake
Sleep
Wake
Sleep
Average
0
5
10
15
20
25
Detections per minute
LS-HFOEs
Avg per channel
Max per channel
HFOEs
FRs
HFOs
HFO duration
Filtered 100-500 Hz
activity in subset of
channels
Average of all channels
(what a macroelectrode
would see?)