Human subthalamic nucleus activity during motor learning

1. Human subthalamic nucleus activity during motor learning Richard D. Penn,M.D. Matthew Cieslak Catherine L Ojakangas, Ph.D. Dept of Neurosurgery Rush Medical School And Section of Neurosurgery University of Chicago

2. STN Cell Activity During Motor Learning

3. Three Types of STN Neurons

4. Testing in the OR • Needed: Simple motor task with learning component • Adaptable within time constraints of OR • Preferably adaptation that could be performed many times in 15 – 20 minutes

5. Human intraoperative behavioral neurophysiology (20-30 minutes)

6. TASK: 2-direction radial task Hold (0.5 sec) time Instruction Cue ( 0.75-2s) Go Cue Movement Out

7. Gain change task Gain 1.0 Gain 2.0 Gain 0.5

8. Adaptation paradigm in OR15-20 minutes 1.LEARNING BLOCK: Gain Block (~50 trials, 3-4 gains in blocks of 10-15 trials each) 2. NON-LEARNING BLOCK : Gain Mix (3-4 gains randomly presented, 50 trials)

9. All units demonstrated stable peak to valley distance throughout experiment

10. Kinematic Measures TPV Peak Velocity Time of Correction start of correction SOM EOM Reaction Time Movement Duration GO Filtered derivative of velocity (acceleration)

11. DBS patients learned! Peak Velocity vs. Trial Numberin Learning Movement Duration vs. Trial Numberin Learning P< 0.05, R2=.162, ANOVA P<0.001, R2=.30

12. STN neurons

13. In the Non Learning Phase there were NO cells for any patient with significant firing rate change with gain In the Learning Phase significant cell firing rate changes were found after the start of the movement related to gain Results from STN recordings

14. Mathematical methods which avoid analysis biasPrincipal component analysis (PCA) involves a mathematical procedure that transforms a number of possibly correlated variables into a smaller number of uncorrelated variables called principal components. The first principal component accounts for as much of the variability in the data as possible, and each succeeding component accounts for as much of the remaining variability as possible. K-means clustering is a method of cluster analysis which aims to partition n observations into k clusters in which each observation belongs to the cluster with the nearest mean.

15. 2. Epochs identified trial-by-trial Trial Before Analysis49 cells • Categorized movement trials based on gain of previous trial < 1.0 1.0 > 1.0 106 47 36 <1.0 SOM to PV SOC to PC SOM to PV SOC to PC 49 64 13 1.0 19 82 32 > 1.0 “Go” to SOM PV to SOC PC to EOM Number of Trials per Previous Trial Code Red=Learning

16. K means- 3 groups- first 3 PCs

17. Patterns of Cell Firing Three groups found by sorting based PCA and K-mean clustering N=20 N=12 N=17

19. Interpretation

20. Firing Rate correlates with Peak Velocity and Correction Velocity Correlation: Firing rate with Peak velocity (Mean r +- SEM) Correlation: Firing rate with Correction velocity (Mean r +- SEM) 0.15 0 -0.15 p<0.05, t-test 1 2 3 1 2 3 Group

21. Conclusions The STN is involved in simple visuomotor learning. The STN cell population is not homogeneous, different functional classes. At least 3 distinct cell populations respond to different behavioral contexts

22. How do these results fit into a concept of the motor system?

23. Motor Learning Circuitry: An Idea thalamus Spinal Cord

24. FUTURE WORK Center of activated volume Figure 4- Ojakangas