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 Laboratory Department of Bioengineering Logo: http://www.mrutc.org/outreach/workshop/homelogo.jpg University of Illinois at Chicago Backdrop 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.
A disruption of blood flow in the brain that leads to long-term functional deficits due to the injury and death of neurons. Picture: http://jeffreyleow.files.wordpress.com/2007/10/emergency.jpg
Stroke Statistics leading cause of severe disability in the United States Stroke is the leading cause of severe disability 780,000 people suffer a stroke every year! 780,000 Associated yearly economic burden of $65.6 billion $65.6 billion 87% of strokes are ischemic strokes. 87%
Two types of stroke: Picture: http://www.beliefnet.com/healthandhealing/images/si55551195.jpg
What is so bad about 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 neurofunctional recovery Cerebrovasc Dis 2006; 21: 6-17.
Spatial view of stroke Not to scale Electrodes Picture: http://203.131.209.130/neurosurgery/cai/image/penum.gif
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
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Electrode array design PMMA Bottom Not to view scale Fiber optic Electrodes light and port
Electrode array Electrodes Fiber optic light Magnified
Two rat groups Control Group Experimental Group Subject to: Subject to: 1.Chronic 1.Chronic electrode electrode array implantation array 2.Photothrombotic Photothrombotic 2. implantation stroke stroke 2.Daily 3.Daily recordings recordings
Photothrombosis Fiber optic Electrode light Magnified
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 Test Measures upper forelimb function 2. Pasta Manipulation Test Measures 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 Implant Site Bregma 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…
SSPK_CH2 SSPK_CH1 SSPK_CH1 1200 1200 1200 Day 1 Day 0 Day 2 1000 1000 1000 800 800 Counts/bin Counts/bin Counts/bin 800 600 600 600 400 400 200 400 200 0 0.1 0.2 0.3 0.4 0.5 0 0.1 0.2 0.3 0.4 0.5 0 0.1 0.2 0.3 0.4 0.5 Time (sec) Time (sec) Time (sec) SSPK_CH1 SSPK_CH1 1200 1200 Day 5 Day 4 1000 1000 Control Subject 800 Control Subject 800 Counts/bin Counts/bin PSTHs 600 600 1 bin = 10 ms 400 400 200 0 0.1 0.2 0.3 0.4 0.5 0 0.1 0.2 0.3 0.4 0.5 Time (sec) Time (sec)
Control Subject Control Subject Time Elapsed between First and Second Local Maximums During Stimulus Presentation vs. Time ControlSubject 0.25 Time Elapsed (sec) 0.2 0.15 0.1 0.05 0 0 1 2 3 4 5 6 7 8 No. Days Post-Op
NoS timulusC h1 Log. (NoS timulusC h1) 100 90 y = ‐ 26.62Ln(x) + 70.283 Firing Frequency (Hz) 80 R 2 = 0.577 70 60 50 40 30 20 10 0 0 1 2 3 4 5 6 7 8 Control Subject Control Subject No. Days Post-Op Mean Firing Rate vs. Time S timulusC h1 Log. (S timulusC h1) 100 y = ‐ 28.158Ln(x) + 79.274 Firing Frequency (Hz) 90 R 2 = 0.6565 80 70 60 50 40 30 20 10 0 0 1 2 3 4 5 6 7 8 No. Days Post-Op
NoS timulusC h1 Log. (NoS timulusC h1) 100 90 Firing Frequency (Hz) 80 y = ‐ 33.912Ln(x) + 72.292 70 R 2 = 0.8954 60 50 40 30 20 10 Control Subject Control Subject 0 0 1 2 3 4 5 6 7 8 Mean Firing No. Days Post-Op Rate vs. Time (Day No. 5 Post- S timulusC h1 Log. (S timulusC h1) Op Excluded) 100 Firing Frequency (Hz) 90 y = ‐ 34.252Ln(x) + 80.953 80 R 2 = 0.8847 70 60 50 40 30 20 10 0 0 1 2 3 4 5 6 7 8 No. Days Post-Op
SSPK_CH2 SSPK_CH2 Day 0 1200 1200 Day 0 During Stroke 1000 1000 Before Stroke 800 800 Counts/bin Counts/bin 600 600 400 400 200 Experimental Experimental 200 0 0.1 0.2 0.3 0.4 0.5 0 0.1 0.2 0.3 0.4 0.5 Subject Time (sec) Subject Time (sec) SSPK_CH2 SSPK_CH3 1200 1200 Day 1 Day 4 PSTHs 1000 1000 1 bin = 10 ms 800 800 Counts/bin Counts/bin 600 600 400 400 200 200 0 0.1 0.2 0.3 0.4 0.5 0 0.1 0.2 0.3 0.4 0.5 Time (sec) Time (sec)
In the Motor Cortex…
Cylinder Test Data Cylinder Test Touches vs. Rat 20 18 Number of Touches 16 14 right forelimb 12 10 left forelimb 8 both forelimbs 6 4 2 0 1 2 3 4 Rat • All rats prefer using both forelimbs prior to stroke • All rats prefer their right forelimb
Cylinder Test Data A. B. Touches per Trial vs. Testing Day Right and Left Touches vs. Testing Day R1 right Number of Touches Number of Touches 50 16 R1 R1 left 40 12 R2 R2 right 30 8 R3 R2 left 20 4 R4 10 R3 right 0 0 R3 left 0 2 4 6 8 10 0 2 4 6 8 10 12 R4 right Testing Day Testing Day R4 left C. R1 (1 ‐ 5) R1 (6 ‐ 10) R2 (1 ‐ 5) R2 (6 ‐ 10) R4 (1 ‐ 5) R4 (6 ‐ 10) R/L Touches (stdev) 3.0 1.9 3.4 1.8 4.7 1.4 Total Touches (stedv) 8.8 5.1 14.2 3.6 5.3 4.7
Pasta Manipulation Test Data Time per Pasta Piece vs. Training Day 14 12 Tim e (sec) R1 10 R2 8 R4 6 4 0 2 4 6 8 10 Training Day R1 (1 ‐ 4) R1 (5 ‐ 9) R2 (1 ‐ 4) R2 (5 ‐ 9) R4 (1 ‐ 4) R4 (5 ‐ 7) time (stdev) 1.8 0.5 1.5 0.4 1.4 0.2
Pasta Manipulation Test Data Total Adjustments Per Pasta Piece vs. Training Day 10 Adjustments Number of 8 6 R1 4 R2 2 R4 0 0 2 4 6 8 10 Training Day
Stroke Behavioral Data Cylinder Test: Before and After Stroke A. Number of Touches 16 12 Pre-Stroke 8 Post-Stroke 4 0 right forelimb left forelimb both forelimbs Touch Type B. Pasta Test: Before and After Stroke 4 Adjustments Number of 3 Pre-Stroke 2 Post-Stroke 1 0 right left Adjustment
During Stroke Pre-Stroke Post-Stroke: Day 0 (Mean=146) (Mean=94) (Mean=4) Post-Stroke: Day 2 Post-Stroke: Day 1 (Mean=72) (Mean=83)
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
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