In this webinar sponsored by Data Sciences International, Dr. Marcio Furtado presents his research highlighting the importance of anomalous EEG detection to study experimental epilepsy and assess the efficacy of potential anticonvulsants and neuroprotectants. He also discusses why continuous EEG monitoring at a high sampling rate is critical to properly detect seizures and how to effectively deal with large telemetry data sets. Watch this webinar to learn: - Why neural hyper-synchronization (seizure activity) can result in permanent brain damage - Tips for organizing, standardizing, and batch processing large data sets - What features can be extracted from large EEG data sets - Why inadequate sampling rates can lead to signal aliasing and how to avoid it - How telemetry can be used to continuously monitor EEG and assess seizure activity in animal models of epilepsy

1. Marcio Furtado, PhD
CEO, BioSEaD, LLC.
Adjunct Assistant Professor,
Anatomy, Physiology and Genetics
Uniformed Services University of Health
and Sciences (USU).
EEG and Telemetry: Best Practices for
Managing Large Data Sets to Investigate
Key Aspects of Epilepsy in Rodent Models

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4. Marcio Furtado, PhD
EEG and Telemetry: Best Practices for
Managing Large Data Sets to Investigate
Key Aspects of Epilepsy in Rodent Models
Copyright 2019 M. Furtado and InsideScientific. All Rights Reserved.
CEO, BioSEaD, LLC.
Adjunct Assistant Professor,
Anatomy, Physiology and Genetics,
Uniformed Services University
of the Health Sciences

5. The Electroencephalogram (EEG)
• Brain Oscillations are essential for sensory
and cognitive process
• Synchronization is essential for information
processing in neural network
Epilepsy :
• Hypersynchronism
• Spontaneous and Recurrent Seizures
It is important to have continuous sampling over the
course of each study to properly detect seizures

6. Tethered EEG after Microinjection of Intra-Hippocampal Pilocarpine
Furtado, M. et al (2002).
Epilepsia, 43 Suppl 5(9),
37–9.
Figure adapted from
Furtado., 2003.
PhD dissertation.
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7. Brain damage and
rewiring after
microinjecton of intra-
hippocampal pilocarpine
Furtado, M. et al (2011).
Epilepsy & Behavior, 20(2),
257–66.

8. Animal Models
The susceptibility to seizures in animal models might be dependent on strain type and
endogenous factors might modulate seizure severity and latency
Wistar Audiogenic Rats are more susceptible to Pilocarpine
• Garcia-Cairasco, N., Rossetti, F., Oliveira, J. C., & Furtado, M. (2004). Epilepsy & Behavior :
E&B, 5(4), 455–63.
Wet dog shakes are inversely correlated with SE induced by pilocarpine injections
• Rodrigues MC, Rossetti F, Foresti ML, Arisi GM, Furtado MA, Dal-Cól ML, Bertti P,
Fernandes A, Santos FL, Del Vecchio F, Garcia-Cairasco N. (2005). Epilepsy Behav.: E&B,
6(3):328-36.

9. Telemetry
Transmitter
DSI Telemetry Data Array and Electrode Location
Furtado et al.
Presentation 302.03 / W1
Evaluation of an improved
telemetry transmitter (HD-
S02) in experimental
pharmacology studies to
assess seizure activity in rats.
Data digitized at 250 Hz (Data Sciences International - DSI, MN, 55112). 2-4 channels of
EEG data can be recorded in up to 16 rats simultaneously depending on the device type.

10. DSI Telemetry

11. Importance of Adequate Sampling Rate
Examples of spatial aliasing

12. Importance of
Adequate
Sampling Rate
By User: Simiprof, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=44402172
Furtado, M. et al (2011).
Epilepsy & Behavior, 20(2),
257–66.

13. Importance of
Adequate
Sampling Rate
Furtado, M. et al (2011).
Epilepsy & Behavior, 20(2),
257–66.
Actual signal
Aliased signal
Time (s)
Amplitude(mV)

14. Once parameters such as, sampling rate, filtering
and duration of recordings are determined, the
collection of data can be started.

15. time
(minutes)
0 1 40 (from SE onset) 60
GD
Exposure
Atropine+HI6
MDZ + VEH or
AED
13 min post-exposure 33 min post-exposure
Furtado, M., et al.
(2012).
Neurotoxicology, 33(6),
1476–90.
Status
Epilepticus
(SE)
Recurrent
Seizures
(RS)
Spontaneous
Recurrent
Seizures(SRS)
Seizures
induced by OP
compounds

16. Managing Large Data Sets
Organize data Standardize and
simplify file names
Hierarchize the
data according to
study groups

17. Managing Large Data Sets: What features can be extracted from an EEG signal?
Furtado, M. et al (2009). Journal of
Neuroscience Methods, 184(1), 176–83.
FFT
• Mean power/integrated power per frequency band
• Slope of robust fit (F vs Power)
• Slope of robust fit (log F vs log Power
• Frequency peaks
βαθδ γ
Signal Entropy
Cross-correlation
Wavelets
More….
Filtering of signal (for example: Butterworth filter;
passband of 0.5–125 Hz; notch filter of 60 Hz
Convert the data to another
format (such as EDF) depending
on the tool used for data analysis.
Preferentially use batch processing to
extract features from signals

18. Managing Large Data Sets: Training Neural Networks
• Choose a platform
• Define the features that are relevant
to identify the signal of interest

19. Using Simulated Data
www.biosead.com
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20. Patterns of EEGraphic Seizures Post-GD Exposure (Recurrent Seizures)
Rossetti, F., Furtado, M., Pak, T., Bailey, K., Shields, M., Chanda,
S., … Yourick, D. L. (2012). Neurotoxicology, 33(3), 500–11.
0.8 and 1.4 Hz 1.4 and 3.7 Hz 4.8 and 5.4 Hz

21. Patterns of EEGraphic seizures post-GD exposure (Recurrent Seizures)
Rossetti, F., Furtado, M., Pak, T., Bailey, K., Shields, M., Chanda,
S., … Yourick, D. L. (2012). Neurotoxicology, 33(3), 500–11.
5.5 and 8.0 Hz 5.5 and 11 Hz 10.5 and 12 Hz

22. GD-induced status epilepticus can lead to the development of epilepsy
(spontaneous recurrent seizures) as a result of extensive brain damage and re-wiring.
EEGraphic seizures are often correlated with behavioral
seizures but there are exceptions
Furtado, M. et al (2010). Epilepsia, 51(8), 1503–10.

23. Exposure to nerve
agents: from status
epilepticus to
neuroinflammation,
brain damage,
neurogenesis and
epilepsy
Furtado, M. et al (2012).
Neurotoxicology, 33(6),
1476–90.

24. GD-induced status
epilepticus can
induce brain
damage
(silver staining)
Furtado, M. et al (2010).
Epilepsia, 51(8), 1503–10.
No seizure
Mild
seizure
Severe and
prolonged
seizure

25. VPA combined with DZP reduces the length of status epilepticus induced by GD.
VPA and SAHA in combination with DZP can protect against GD exposure
Rossetti, F., de Araujo Furtado, M., Pak, T., Bailey, K., Shields, M.,
Chanda, S., … Yourick, D. L. (2012). Neurotoxicology, 33(3), 500–11.

26. Caramiphen edisylate
combined with
diazepam attenuates
GD-induced seizures,
brain damage and
cognitive deficits
Schultz, M. et al (2014).
Neurotoxicology and
Teratology, 44, 89–104.

27. Caramiphen edisylate as
adjunct to standard
therapy attenuates
soman-induced seizures
and cognitive deficits in
rats
Animals treated with
standard therapy plus
caramiphen had greater
temperature reduction
compared to animals that
received only standard
therapy.
Schultz, M. et al (2014).
Neurotoxicology and
Teratology, 44, 89–104.
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28. Full protection against
soman-induced
seizures and brain
damage by LY293558
and caramiphen
combination treatment
in adult rats
Apland, J et al (2018). Neurotox
Res. 34(3):511-524.
Adjunct therapy of
LY293558 + CRM

29. Full protection against
soman-induced
seizures and brain
damage by LY293558
and caramiphen
combination treatment
in adult rats
Apland, J et al (2018). Neurotox
Res. 34(3):511-524.

30. Full protection against
soman-induced
seizures and brain
damage by LY293558
and caramiphen
combination treatment
in adult rats
Apland, J et al (2018). Neurotox
Res. 34(3):511-524.

31. Exploring a
Carboxylesterase
Knockout (ES1 -/-)
Model of Seizures
Through Telemetry

32. 10 min 20 min
30 min 60 min 2 h 4 h
16 h 24 h
5 min
8 h
Baseline
48 h
EEG traces from male carboxylesterase knockout (ES1 -/-) mice displaying seizure activity

33. Marrero-Rosado,
B. et al (2018).
Epilepsia, 59(12),
2206-2218.
Soman-induced status epilepticus, epileptogenesis, and neuropathology in
carboxylesterase knockout mice treated with midazolam
ES1 -/-
Mouse
Model

34. Marrero-Rosado, B. et al (2018).
Epilepsia, 59(12), 2206-2218.
Soman-induced status
epilepticus,
epileptogenesis, and
neuropathology in
carboxylesterase
knockout mice treated
with midazolam.

35. New
Directions

36. https://www.datasci.com/
Comparison Between Devices
HD-S02 presents more advantages:
Click Here to Learn More
About PhysioTel HD Implants

37. Telemetry
Implants for
Small Animals
https://www.datasci.com/

38. N3285.edf:
•Date:11/18/16
•Time: 22:34:41
•Temperature = 35.8°C
•Activity Counts: 0
•On time: 21.2 days
•Battery voltage 1.58 V
New Directions
Comparison between
data provided by an F40-
EET transmitter (top)
and an HD-S02 device
(bottom)
N3323.edf:
•Date:11/19/16
•Time: 19:41:10
•Temperature = 34.5 C
•Activity Counts: 7

39. Acknowledgments
USAMRICD
Lucille Lumley, PhD
Brenda Marrero-Rosado, PhD
Franco Rossetti, PhD
Maria Braga, PhD
Taiza Figueiredo, PhD

40. Marcio Furtado, PhD
marcio.furtado@usuhs.edu
support@biosead.com
CEO, BioSEaD, LLC.
Adjunct Assistant Professor,
Anatomy, Physiology and Genetics
Uniformed Services University of
Health and Sciences (USU)
Thank You
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