Spatiotemporal electrophysiology of cerebral ischemia observed - - PowerPoint PPT Presentation

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Spatiotemporal electrophysiology of cerebral ischemia observed - - PowerPoint PPT Presentation

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Spatiotemporal electrophysiology of cerebral ischemia observed using chronic electrode array Matthew T. Huberty and Madeline Midgett Peter Tek, Graduate Student Dr. Patrick J. Rousche, Principal Investigator Neural Engineering Applications

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Spatiotemporal electrophysiology

  • f cerebral ischemia observed

using chronic electrode array

Matthew T. Huberty and Madeline Midgett Peter Tek, Graduate Student

  • Dr. Patrick J. Rousche, Principal Investigator

Neural Engineering Applications Laboratory Department of Bioengineering University of Illinois at Chicago

Logo: http://www.mrutc.org/outreach/workshop/homelogo.jpg Backdrop used throughout: http://fweak.deviantart.com/art/neuron-2798115
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Overview

  • Purpose
  • Introduction
  • Methods
  • Results and Discussion
  • Conclusion
  • Acknowledgements
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A better understanding of brain tissue reorganization following stroke using electrophysiological recordings to help in developing stroke therapies and optimize recovery in the future.

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Picture: http://jeffreyleow.files.wordpress.com/2007/10/emergency.jpg

A disruption of blood flow in the brain that leads to long-term functional deficits due to the injury and death of neurons.

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Stroke Statistics

780,000 780,000 people suffer a stroke every year! 87% 87% of strokes are ischemic strokes.

Associated yearly economic burden of $65.6 billion $65.6 billion

Stroke is the leading cause of severe disability leading cause of severe disability in the United States

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Two types of stroke:

Picture: http://www.beliefnet.com/healthandhealing/images/si55551195.jpg

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What is so bad about cutting off blood supply to the brain?

Picture: http://images.jupiterimages.com/common/detail/10/60/23346010.jpg

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Temporal view of stroke

Picture: Kriesel SH et al: Pathophysiology of stroke rehabilitation: temporal aspects of neurofunctional recovery Cerebrovasc Dis 2006; 21: 6-17.

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Spatial view of stroke

Picture: http://203.131.209.130/neurosurgery/cai/image/penum.gif

Not to scale

Electrodes

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SLIDE 12
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In auditory cortex…

  • Did not use the Sprague-Dawley strain employed in

the proposed study

  • Created lesion in parietal, motor, or occipital

cortices

  • Made in vitro recordings in thin, post-mortem brain

slices (Domann et al. 1993 and Buchkremer- Ratzmann et al. 1996)

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In auditory cortex…

  • Concluded

recording after first 800 seconds following photothrombosis (Chiganos et al. 2006)

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In motor cortex…

Kleim J, Nudo R, Adkins D, Jones T:

Enhance motor recovery and plastic reorganization with rehabilitative training and electrical stimulation

Our Aim:

To record spatiotemporal dynamic changes

  • f electrophysiological and correlative behavioral

response before, during, and after stroke

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The following slides contain graphic material that may not be suitable for all

  • audiences. Viewer

discretion is advised.

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Electrode array design

Bottom view Not to scale Electrodes Fiber optic light and port PMMA

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Electrode array

Electrodes Fiber optic light Magnified

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Two rat groups

Control Group Subject to: 1.Chronic electrode array implantation 2.Daily recordings Experimental Group Subject to: 1.Chronic electrode array implantation 2. 2.Photothrombotic Photothrombotic stroke stroke 3.Daily recordings

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Photothrombosis

Magnified Fiber optic light Electrode

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In vivo recording setup

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Recording hardware

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A 100 dB click stimulus was played every 500 ms at a distance of 36 inches from subject’s ears for 5 minutes every morning

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Screenshot of: Tucker-Davis Technologies OpenEx software

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Motor Cortex Study Methods

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Behavioral Tests

  • 1. Cylinder Test

Measures upper forelimb function

  • 2. Pasta Manipulation Test

Measures forepaw function

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Cylinder Test (Behavioral)

  • Encourages upright exploratory movements
  • Characterizes neural damage with asymmetrical use
  • f forelimbs
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Cylinder Test

Right Forelimb Only Left Forelimb Only Both Forelimbs

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Pasta Manipulation Test

  • measure of dexterous forepaw function
  • Rats given 7 cm lengths of uncooked pasta
  • Video recorded and eating patterns analyzed
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Eating Variables

  • 1. Number of adjustments made per

forepaw

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Eating Variables

  • 2. Time required to eat a whole strand
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Electrode Location

Bregma Implant Site 2-4 mm rostal and 2-4 mm lateral relative to Bregma

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Electrophysiological Recording

Figure taken from "Evaluation of the dynamic electrophysiological profile of the at cerebral cortex in response to focal infarction," Terry C. Chiganos, Jr., Preliminary Thesis Defense Summary, 2005.

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In the Auditory Cortex…

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SLIDE 40 0.1 0.2 0.3 0.4 0.5 Time (sec) 400 600 800 1000 1200 SSPK_CH2 Counts/bin 0.1 0.2 0.3 0.4 0.5 Time (sec) 200 400 600 800 1000 1200 SSPK_CH1 Counts/bin 0.1 0.2 0.3 0.4 0.5 Time (sec) 200 400 600 800 1000 1200 SSPK_CH1 Counts/bin 0.1 0.2 0.3 0.4 0.5 Time (sec) 200 400 600 800 1000 1200 SSPK_CH1 Counts/bin 0.1 0.2 0.3 0.4 0.5 Time (sec) 400 600 800 1000 1200 SSPK_CH1 Counts/bin

Control Subject Control Subject PSTHs 1 bin = 10 ms

Day 0 Day 1 Day 2 Day 4 Day 5

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SLIDE 41
  • No. Days Post-Op

Time Elapsed (sec)

Control Subject Control Subject Time Elapsed between First and Second Local Maximums During Stimulus Presentation vs. Time

0.05 0.1 0.15 0.2 0.25 1 2 3 4 5 6 7 8

ControlSubject

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SLIDE 42 y = ‐26.62Ln(x) + 70.283 R 2 = 0.577 10 20 30 40 50 60 70 80 90 100 1 2 3 4 5 6 7 8 NoS timulusC h1
  • Log. (NoS timulusC h1)
y = ‐28.158Ln(x) + 79.274 R 2 = 0.6565 10 20 30 40 50 60 70 80 90 100 1 2 3 4 5 6 7 8 S timulusC h1
  • Log. (S timulusC h1)
  • No. Days Post-Op

Firing Frequency (Hz)

  • No. Days Post-Op

Firing Frequency (Hz)

Control Subject Control Subject Mean Firing Rate

  • vs. Time
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SLIDE 43
  • No. Days Post-Op

Firing Frequency (Hz)

  • No. Days Post-Op

Firing Frequency (Hz)

Control Subject Control Subject Mean Firing Rate vs. Time (Day No. 5 Post- Op Excluded)

y = ‐33.912Ln(x) + 72.292 R 2 = 0.8954 10 20 30 40 50 60 70 80 90 100 1 2 3 4 5 6 7 8 NoS timulusC h1
  • Log. (NoS timulusC h1)
y = ‐34.252Ln(x) + 80.953 R 2 = 0.8847 10 20 30 40 50 60 70 80 90 100 1 2 3 4 5 6 7 8 S timulusC h1
  • Log. (S timulusC h1)
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SLIDE 44 0.1 0.2 0.3 0.4 0.5 Time (sec) 200 400 600 800 1000 1200 SSPK_CH2 Counts/bin 0.1 0.2 0.3 0.4 0.5 Time (sec) 200 400 600 800 1000 1200 SSPK_CH2 Counts/bin 0.1 0.2 0.3 0.4 0.5 Time (sec) 200 400 600 800 1000 1200 SSPK_CH2 Counts/bin 0.1 0.2 0.3 0.4 0.5 Time (sec) 200 400 600 800 1000 1200 SSPK_CH3 Counts/bin

Day 0

Before Stroke

Day 0

During Stroke

Day 1 Day 4

Experimental Experimental Subject Subject PSTHs 1 bin = 10 ms

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In the Motor Cortex…

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Cylinder Test Data

Cylinder Test Touches vs. Rat

2 4 6 8 10 12 14 16 18 20 1 2 3 4 Rat Number of Touches right forelimb left forelimb both forelimbs

  • All rats prefer using both forelimbs prior to stroke
  • All rats prefer their right forelimb
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Cylinder Test Data

Right and Left Touches vs. Testing Day

4 8 12 16 2 4 6 8 10 Testing Day Number of Touches R1 right R1 left R2 right R2 left R3 right R3 left R4 right R4 left

4.7 5.3 3.6 14.2 5.1 8.8 Total Touches (stedv) 1.4 4.7 1.8 3.4 1.9 3.0 R/L Touches (stdev) R4 (6‐10) R4 (1‐5) R2 (6‐10) R2 (1‐5) R1 (6‐10) R1 (1‐5)

A. B. C.

Touches per Trial vs. Testing Day

10 20 30 40 50 2 4 6 8 10 12 Testing Day Number of Touches R1 R2 R3 R4
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Pasta Manipulation Test Data

Time per Pasta Piece vs. Training Day

4 6 8 10 12 14 2 4 6 8 10 Training Day Tim e (sec) R1 R2 R4

0.2 1.4 0.4 1.5 0.5 1.8 time (stdev) R4 (5‐7) R4 (1‐4) R2 (5‐9) R2 (1‐4) R1 (5‐9) R1 (1‐4)

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Pasta Manipulation Test Data

Total Adjustments Per Pasta Piece vs. Training Day

2 4 6 8 10 2 4 6 8 10 Training Day Number of Adjustments R1 R2 R4

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Stroke Behavioral Data

Cylinder Test: Before and After Stroke

4 8 12 16 right forelimb left forelimb both forelimbs Touch Type Number of Touches Pre-Stroke Post-Stroke

Pasta Test: Before and After Stroke

1 2 3 4 right left Adjustment Number of Adjustments Pre-Stroke Post-Stroke

A. B.

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Pre-Stroke

(Mean=94)

During Stroke

(Mean=146)

Post-Stroke: Day 0

(Mean=4)

Post-Stroke: Day 1

(Mean=83)

Post-Stroke: Day 2

(Mean=72)

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Implant Trauma and Viability

1.Suggests that the penetrating trauma associated with electrode implantation possibly led to altered primary auditory cortex neuronal firing activity 2.Suggests that the formation of scar tissue around the electrode possibly led to a decrease in electrode viability

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Future Directions

1.Carry out more surgeries to increase sample size and continue recording for broadened temporal “picture” 2.Develop a logarithmic mathematical model of the erosion of electrode viability 3.Employ multi-channel electrodes to generate spatial data 4.Perform studies that will characterize and explain the physiological phenomenon responsible for the findings of the proposed study

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Motor Cortex

  • Regular behavioral training is necessary to accurately

assess motor cortex function after stroke.

  • Trauma associated with electrode implant and recovery

does not affect behavioral performance.

  • Both the cylinder and the pasta manipulation tests show

deficits in forepaw function after stroke in the stroke animal.

  • The changing mean firing rates of neural activity shows

evidence of a stroke and neural recovery.

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Acknowledgements

  • Dr. C. G. Takoudis, REU Director
  • Dr. G. Jursich, REU Co-Director
  • Dr. Patrick J. Rousche, Principal Investigator
  • Peter Tek, MS Student
  • UIC Animal Care Committee
  • National Science Foundation EEC-0755115

REU Grant

  • Department of Defense ASSURE Grant
  • National Science Foundation Career Award

#0348145

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References

[1] American Heart Association 2008 Heart Disease and Stroke Statistics—2008 Update [2] W. Jensen, P.J. Rousche, T.C. Chiganos, “A method for monitoring intra‐ cortical motor cortex responses in an animal model of ischemic stroke,” IEEE EMBS Annual International Conference New York City, USA, Aug 30‐ Sept 3, 2006. [3] T.C. Chiganos,W. Jensen, P.J. Rousche: J. Neural Eng. 3, 2006, L15–L22. [4] R.P. Allred, T.A. Jones: Experimental Neurology 210, 2008, 172–181. [5] R. P. Allred, D.L. Adkins: J. Neuroscience Methods 170, 2008, 229–244. [6] W. Jensen, P. J. Rousche, “Encoding of Self‐Paced, Repetitive Forelimb Movements in Rat Primary Motor Cortex,” IEEE 2004.