Spatiotemporal electrophysiology of cerebral ischemia observed using chronic electrode array

Matthew T. Huberty and Madeline MidgettPeter Tek, Graduate Student

Dr. Patrick J. Rousche, Principal InvestigatorNeural Engineering Applications Laboratory

Department of BioengineeringUniversity of Illinois at Chicago

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

Overview• Purpose• Introduction• Methods

• Results and Discussion• Conclusion• Acknowledgements

A better understanding of brain tissue reorganization

following stroke using electrophysiological recordings

to help in developing stroke therapies and optimize recovery

in the future.

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.

Stroke Statistics

780,000780,000 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 disabilityleading cause of severe disability in the United States

Two types of stroke:

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

What is so badabout cutting off blood supply to

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

Temporal view of stroke

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

Spatial view of stroke

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

Not to scale

Electrodes

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)

In auditory cortex…•Concluded

recording after first 800 seconds

following photothrombosis

(Chiganos et al. 2006)

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

of electrophysiological and correlative behavioral response before, during, and after stroke

The following slides contain graphic

material that may not be suitable for all

audiences. Viewer discretion is advised.

Electrode array design

Bottom view

Not to scale

ElectrodesFiber optic light and port

PMMA

Electrode arrayElectrodesFiber optic

light

Magnified

Two rat groupsControl Group

Subject to:

1.Chronic electrode array implantation

2.Daily recordings

Experimental Group

Subject to:

1.Chronic electrode array implantation

2.2.PhotothromboticPhotothromboticstrokestroke

3.Daily recordings

Photothrombosis

Magnified

Fiber optic light

Electrode

In vivo recording setup

Recording hardware

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

Screenshot of: Tucker-Davis Technologies OpenEx software

Motor Cortex Study Methods

Behavioral Tests

1. Cylinder TestMeasures upper forelimb function

2. Pasta Manipulation TestMeasures forepaw function

Cylinder Test (Behavioral)

• Encourages upright exploratory movements

• Characterizes neural damage with asymmetrical use of forelimbs

Cylinder Test

Right Forelimb Only Left Forelimb Only Both Forelimbs

Pasta Manipulation Test

• measure of dexterous forepaw function

• Rats given 7 cm lengths of uncooked pasta

• Video recorded and eating patterns analyzed

Eating Variables

1. Number of adjustments made per forepaw

Eating Variables

2. Time required to eat a whole strand

Electrode Location

Bregma

Implant Site

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

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.

In the Auditory Cortex…

0 0.1 0.2 0.3 0.4 0.5Time (sec)

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SSPK_CH1C

ount

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Control SubjectControl Subject

PSTHs

1 bin = 10 ms

Day 0 Day 1 Day 2

Day 4 Day 5

No. Days Post-Op

Tim

e El

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d (s

ec)

Control SubjectControl Subject

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

0

0.05

0.1

0.15

0.2

0.25

0 1 2 3 4 5 6 7 8

ControlSubject

y  =   ‐26.62Ln(x) +  70.283

R 2 =  0.577

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0 1 2 3 4 5 6 7 8

NoS timulus C h1 Log. (NoS timulus C h1)

y  =   ‐28.158Ln(x) +  79.274

R 2 =  0.6565

0102030405060708090

100

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S timulus C h1 Log. (S timulus C h1)

No. Days Post-Op

Firin

g Fr

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ncy

(Hz)

No. Days Post-Op

Firin

g Fr

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Control SubjectControl Subject

Mean Firing Rate vs. Time

No. Days Post-Op

Firin

g Fr

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(Hz)

No. Days Post-Op

Firin

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(Hz)

Control SubjectControl Subject

Mean Firing Rate vs. Time

(Day No. 5 Post-Op Excluded)

y  =   ‐33.912Ln(x) +  72.292

R 2 =  0.8954

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0 1 2 3 4 5 6 7 8

NoS timulus C h1 Log. (NoS timulus C h1)

y  =   ‐34.252Ln(x) +  80.953

R 2 =  0.8847

0102030405060708090

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0 1 2 3 4 5 6 7 8

S timulus C h1 Log. (S timulus C h1)

0 0.1 0.2 0.3 0.4 0.5Time (sec)

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SSPK_CH2

Cou

nts/

bin

0 0.1 0.2 0.3 0.4 0.5Time (sec)

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Day 0 Before Stroke

Day 0 During Stroke

Day 1 Day 4

Experimental Experimental SubjectSubject

PSTHs

1 bin = 10 ms

In the Motor Cortex…

Cylinder Test Data Cylinder Test Touches vs. Rat

02468

101214161820

1 2 3 4

Rat

Num

ber

of T

ouch

es

right forelimbleft forelimbboth forelimbs

• All rats prefer using both forelimbs prior to stroke

• All rats prefer their right forelimb

Cylinder Test Data

Right and Left Touches vs. Testing Day

0

4

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0 2 4 6 8 10Testing Day

Num

ber o

f Tou

ches R1 right

R1 left

R2 right

R2 left

R3 right

R3 left

R4 right

R4 left

4.75.33.614.25.18.8Total Touches (stedv)

1.44.71.83.41.93.0R/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

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Testing Day

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R2

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Pasta Manipulation Test Data

Time per Pasta Piece vs. Training Day

468

101214

0 2 4 6 8 10

Training Day

Tim

e (s

ec) R1

R2

R4

0.21.40.41.50.51.8time (stdev)

R4 (5‐7)R4 (1‐4)R2 (5‐9)R2 (1‐4)R1 (5‐9)R1 (1‐4)

Pasta Manipulation Test Data

Total Adjustments Per Pasta Piece vs. Training Day

02468

10

0 2 4 6 8 10

Training Day

Num

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f A

djus

tmen

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R2

R4

Stroke Behavioral DataCylinder Test: Before and After Stroke

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right forelimb left forelimb both forelimbs

Touch Type

Num

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Pre-Stroke

Post-Stroke

Pasta Test: Before and After Stroke

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Adjustment

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Pre-Stroke

Post-Stroke

A.

B.

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)

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

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

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.   

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

References[1] American Heart Association 2008 Heart Disease and StrokeStatistics—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.