interictal fast ripples recorded from a dense microelectrode array in human epileptic neocortex...
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Interictal Fast Ripples Recorded Interictal Fast Ripples Recorded from a Dense Microelectrode from a Dense Microelectrode
Array in Human Epileptic Array in Human Epileptic NeocortexNeocortex
Catherine Schevon, MD, PhD; Andrew Trevelyan, PhD; Robert Catherine Schevon, MD, PhD; Andrew Trevelyan, PhD; Robert Goodman, MD; Guy McKhann Jr, MD; Charles Schroeder, PhD; Goodman, MD; Guy McKhann Jr, MD; Charles Schroeder, PhD;
Ronald Emerson, MDRonald Emerson, MD
June, 2009June, 2009
Multielectrode Array (MEA)Multielectrode Array (MEA)NeuroPortNeuroPortTMTM, Cyberkinetics Neurotechnology Systems, Foxboro, MA, Cyberkinetics Neurotechnology Systems, Foxboro, MA(now Blackrock Microsystems, Salt Lake City, UT)(now Blackrock Microsystems, Salt Lake City, UT)
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
• Advantages:• Fine spatial/temporal resolution• Regular grid spacing
• Limitations:• Records from one small area• One cortical layer per site
II
III
IV
V
VI
WM
I
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
• Microelectrode recording downsampled and aligned with clinical EEG recording
• “Macrodischarges”
• Correlate with iEEG Correlate with iEEG epileptiform discharges epileptiform discharges
• Appear widespread in Appear widespread in µEEGµEEG
““µEEG”µEEG”iEEG
μEEG
““Microdischarges”Microdischarges”
200 µV
50 µV
30 µV
30 µV
200 µV
50 µV
30 µV
30 µV
µEEG
30 ms
1 second
HFO associated with a macrodischarge
HFO associated with a microdischarge
1 second
40 ms
µEEG
100-200 Hz
200-500 Hz
0.8 – 2 kHz
µEEG
µEEG
100-200 Hz
200-500 Hz
0.8 – 2 kHz
Correlation with interictal eventsCorrelation with interictal events
Detections/min during sleep and association with paroxysmal µEEG features
Percentage of macrodischarges and microdischarges with associated HFOs
Detections by array locationDetections by array location
85% of events were seen at a single channel
“HFO events” = time period during which one or more HFOs are detected
50 ms
40 µV
400 ms
40 µV
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
“HFO events” = time period during which one or more HFOs are detected
50 ms
200 µV
Site to site differences during a large scale event
50 ms
µEEG
100-200 Hz
200-500 Hz
0.8 – 2 kHz
µEEG
100-200 Hz
200-500 Hz
0.8 – 2 kHz
Conclusions and QuestionsConclusions and Questions
HFOs and microdischarges are distinct phenomenaHFOs and microdischarges are distinct phenomena– Evidence of different mechanisms underlying microdischarges Evidence of different mechanisms underlying microdischarges
and macrodischarges?and macrodischarges?
Large-scale HFOsLarge-scale HFOs– Arise from multiple simultaneous independent generatorsArise from multiple simultaneous independent generators– Specific markers of the epileptogenic zone?Specific markers of the epileptogenic zone?– Selectively detected by sparse sampling or large sensors?Selectively detected by sparse sampling or large sensors?– Evidence of an epileptic network?Evidence of an epileptic network?
Are fast ripples a primary event or a secondary local Are fast ripples a primary event or a secondary local response (eg excitability)?response (eg excitability)?
Co-authors and colleagues
Ron EmersonRobert GoodmanGuy McKhann, Jr.Charles SchroederAndrew TrevelyanAllen WaziriJulien BesleJoe IslerAnna IpataElana Zion-GolumbicSara InatiPeter LakatosDan FriedmanHelen ScharfmanMichael Goldberg
Are all HFOs created equal?Are all HFOs created equal?
Recording characteristics of Neuroport Recording characteristics of Neuroport microelectrodes vs microwires or depth microelectrodes vs microwires or depth electrodeselectrodes
Selective recording from cortical layers IV Selective recording from cortical layers IV and Vand V
Use of detection thresholds create the Use of detection thresholds create the impression of a binary processimpression 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
HFO ratesHFO rates
– Higher HFO rates Higher HFO rates (overall and max per (overall and max per channel) than seen with channel) than seen with microwires or microwires or macroelectrodes but avg macroelectrodes but avg per channel similarper channel similar
– HFOs more frequent in HFOs more frequent in epileptogenic zone (but epileptogenic zone (but N of 1 outside EZ…)N of 1 outside EZ…)
– Almost all HFOs had a Almost all HFOs had a fast ripple componentfast ripple component
0 5 10 15 20 25
Detections per minute
Average
Sleep
Wake
Sleep
Wake
Sleep
Wake
Sleep
Wake
Pat
ient
4P
atie
nt 3
Pat
ient
2P
atie
nt 1
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?)