1. 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

2. 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 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
Note that array is the size of a subdural electrode II
III IV V VI WM I
Advantages:
Fine spatial/temporal resolution
Regular grid spacing
Limitations:
Records from one small area
One cortical layer per site 2

3. 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 (3x3 cm area)
4 (25F)
L inferior temporal gyrus
L mesial/basal/lateral temporal lobe
Mild MTS

4. “µEEG” “Macrodischarges” Appear widespread in µEEG
iEEG
Microelectrode recording downsampled and aligned with clinical EEG recording
“Macrodischarges”
Correlate with iEEG epileptiform discharges
Appear widespread in µEEG
μEEG

5. “Microdischarges”
Are they epileptiform? Are they related to interictal discharges and seizures?

6. HFO associated with a macrodischarge
µEEG
µEEG
200 µV
50 µV Hz
HFO associated with a macrodischarge Hz
30 µV
0.8 – 2 kHz
30 µV
1 second
30 ms
µEEG
200 µV
µEEG
HFOs with macrodischarges: common, almost all fast ripples (selective recording of Layers iv/v?), FR with MUA, at or trailing discharge peak
HFOs with micros: ripple range, rare, preceded peak, no discernable MUA increase Hz
50 µV
HFO associated with a microdischarge Hz
30 µV
0.8 – 2 kHz
30 µV
1 second
40 ms

7. Correlation with interictal events
HFO rates high compared to previous studies; greater in epileptogenic zone
Commonly seen with macrodischarges, but rarely detected with microdischarges
Detections/min during sleep and association with paroxysmal µEEG features
Percentage of macrodischarges and microdischarges with associated HFOs

8. Detections by array location
Point out: 1) poisson-like distribution 2) larger area and higher rate within ez, 3) not co-located with microdcs

9. “HFO events” = time period during which one or more HFOs are detected
85% of events were seen at a single channel
Simultaneous hfo detections have been reported before; introduce term “hfo events”
Single channel event = limited to a single cortical microdomain (400 sq microns)
50 ms
40 µV

10. “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
Large scale = evidence of simultaneous activity in multiple cortical domains
HF activity is increased in many channels outside of detections
Differences between channels suggest that multiple independent generators are responsible
400 ms
40 µV

11. Site to site differences during a large scale event
µEEG
200 µV
Site to site differences during a large scale event Hz Hz
0.8 – 2 kHz
50 ms
µEEG Hz Hz
0.8 – 2 kHz
50 ms

12. 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)?

13. 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

14. 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
2-3 um recording tips; compare to microwires (40 um diameter disks) and depth macroelectrodes (2mm cylindrical)

15. 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

16. 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

17. HFO duration
Filtered Hz activity in subset of channels
Average of all channels (what a macroelectrode would see?)