Interictal Fast Ripples Recorded from a Dense Microelectrode Array in Human Epileptic Neocortex

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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

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Multielectrode Array (MEA) NeuroPortTM,
Cyberkinetics Neurotechnology Systems, Foxboro,
MA (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

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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
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µEEG
iEEG

• Microelectrode recording downsampled and
  aligned with clinical EEG recording
• Macrodischarges
• Correlate with iEEG epileptiform discharges
• Appear widespread in µEEG

µEEG
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Microdischarges
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µEEG
µEEG
100-200 Hz
HFO associated with a macrodischarge
200-500 Hz
0.8 2 kHz
µEEG
µEEG
100-200 Hz
HFO associated with a microdischarge
200-500 Hz
0.8 2 kHz
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Correlation with interictal events
Detections/min during sleep and association with
paroxysmal µEEG features
Percentage of macrodischarges and microdischarges
with associated HFOs
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Detections by array location
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HFO events time period during which one or
more HFOs are detected
85 of events were seen at a single channel
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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
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Site to site differences during a large scale
event
µEEG
100-200 Hz
200-500 Hz
0.8 2 kHz
µEEG
100-200 Hz
200-500 Hz
0.8 2 kHz
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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)?

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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
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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

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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 Brocas 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 Brocas area and on different gyrus Left frontal operculum (3x3 cm cortical area), superior to Brocas 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
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HFO rates

• 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

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HFO duration
Filtered 100-500 Hz activity in subset of channels
Average of all channels (what a macroelectrode
would see?)