Cortical Stimulation Improves Skilled Forelimb Use Following a Focal Ischemic Infarct in the Rat

1. Cortical Stimulation Improves Skilled Forelimb Use Following a Focal Ischemic Infarct in the Rat Campbell Teskey et al, 2003

2. Background • Brain plasticity may explain recovery of impaired function • Rehabilitative training has shown clear benefits for functional recovery • Electrical stimulation: • In humans there is anecdotal evidence that motor cortex stimulation improves motor performance • In nonhumans it has shown to be effective at potentiating and depressing synaptic strength in the neocortex • In nonhumans it also alters movement representations that have shifted due to focal ischemic lesions • Pulsed electrical stimulation has been shown to facilitate peripheral neuronal growth

3. Purpose • To determine ifa combination of rehabilitative training with cortical electrical stimulation will augment brain plasticity, therefore improving functional recovery

4. Methods • 75 male, Long-Evans • Behavioral Training: Pasta Matrix Task • Surgery: Rats underwent a craniotomy and received a cortical stimulation electrode • Evoked Potential • Cortical Surface Stimulation • Histology • Statistical Analysis

5. Results • Figure A: • 100Hz displayed significantly greater reaching success than no stimulation on all test days • 250 Hz • no stimulation group displayed significantly reduced performance on all 10 assessment days • Figure B: • Performance on pasta matrix task

6. Results • Figure A1 and B1: • Rats switched back and forth between preferred and non-preferred to retrieve more distal pieces during pre-infarct training • Figure A2 and B2: • A2: 0 Hz rat on first test day • B2: 50 Hz rat on first test day • Figure A3 and B3: • A3: 0 Hz rat on 10th test day • B3: 50 Hz rat on 10th test day

7. Results • Figure A: • Rats receiving no electrical stimulation • Figure B: • Rats receiving 50 Hz stimulation

8. Results • Polysynaptic Potentiation • Figure A: • Neocortical evoked response • Shows synapses are taking longer to stop firing…so more synapses recruited • Figure B: • 10 days of cortical stimulation • Animals with 50 Hz or greater had larger polysynaptic potentiation

9. Results • Movement Thresholds: • After 10 days of cortical stimulation the movement threshold of rats that received cortical stimulation was significantly reduced • Time and frequency are important

10. Kleim et al Findings Examined the behavioral and physiological effects of cortical stimulation in combination with motor rehabilitation NS= no stimulation BCS= Bipolar Cathodal Stimulation MCS= Monopolar Cathodal Stimulation MAS= Monopolar Anodal Stimulation

11. Conclusions • Shows that 20 minutes of continuous cortical stimulation concurrent with skilled forelimb usage results in superior reaching performance • In the pasta reaching task the animals that received no cortical stimulation had use of both forelimbs drastically decreased • Rats with stimulation also shifted to their non-preferred limb and showed same amount of persistence and energy as they did with their previous preferred limb • Movement thresholds were significantly reduced in rats that received 25-500 Hz stimulation

12. Look at the relationship between frequency of cortical stimulation, neocortical polysynaptic potentiation and a long-term superior skilled performance Optimize the electrical parameters of the cortical stimulation Look at the cortical stimulation phenomenon in other brain regions Examine the persistence of recovery Future Directions