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?)