1. Matt Mehne, USC Brain Project 1 USC Brain Project Matt Mehne – Progress Update – May 15, 2007 Modeling Action Selection in the Parkinsonian Basal Ganglia A Focus on Compensation Mechanisms

2. Matt Mehne, USC Brain Project 2 The old model Project 4 paper A computational model of visually assisted motor control in Parkinson’s disease An attempt to explain, via BG action selection model, the dynamics of PD movement disorders, specifically: inability or difficutly initiating movement Deficiencies include: -Shortened gait - Difficulty initiating movement w/o attentional cue

3. Matt Mehne, USC Brain Project 3 Parkinson’s Disease

4. Matt Mehne, USC Brain Project 4 Modeling Parkinson’s Disease Behavioral studies suggest that trouble with movement is not due to loss of movement pattern but, instead, due to problems with attentional modulation required in executing the movement. Numerous lab experiments show a very clear correlation between PD symptoms and dopamine deficiency, particularly in the basal ganglia.

5. Matt Mehne, USC Brain Project 5 Modeling PD compensation mechanisms Causing existing BG models to fail under PD effects and respond like real life BG has been done, but how about causing them to correct erroneous behavior in correlation with studies? There is more related to attention than intrinsic basal ganglia architecture…

6. Matt Mehne, USC Brain Project 6 Thalamic Reticular Nucleus The overarching finding is that stride length can be regulated in Parkinson's disease using stationary visual cues without increased central processing capacity or perceived effort. (Lewis et al. 2000) “ ” Crick spot-light hypothesis The TRN plays a central role in shifting attention TRN is involved in visual attention. Receives much input from visual cortex. “Their axons, which project to the thalamus, give off rather extensive collaterals that ramify, sometimes for long distances, within the sheet of the reticular complex” (Crick, 1984)

7. Matt Mehne, USC Brain Project 7 TRN Role in PD Example: Movement Disorder in PD It is known that visual cues can help overcome movement disorders Effects of Long-Term Gait Training Using Visual Cues in an Individual With Parkinson Disease. Sidaway B, Anderson J, Danielson G, Martin L, Smith G (2006) PHYS THER 86:186-194. Stride length regulation in Parkinson's disease: the use of extrinsic, visual cues. Lewis GN, Byblow WD, Walt SE (2000) Brain 123:2077-2090. Influence of visual cues on gait in Parkinson's disease: Contribution to attention or sensory dependence? Azulay J-P, Mesure S, Blin O (2006) Journal of the Neurological Sciences 248:192-195. The question is how do the visual cues translate to enhanced motor performance?

8. Matt Mehne, USC Brain Project 8 TRN Role in PD Possible problem areas: -Motor planning -Sensory feedback -Attention Evidence points to TRN/Crick Hypothesis… TRN known to enhance signal selection although not directly affected by dopamine depletion

9. Matt Mehne, USC Brain Project 9 Expanded TRN Role Ch1Ch2 Cortex STNStriatum GPi TRN VL Low DA levels Hyper-direct pathway

10. Matt Mehne, USC Brain Project 10 Expanded TRN Role Cortex STNStriatum GPi TRN VL Low DA - Burst mode vs. Spike mode - Integrating visual cortex

11. Matt Mehne, USC Brain Project 11 Project Plans - Simulate burst mode/spike mode interaction between TRN and thalamus relay circuit - Develop a rudimentary model for simulating Crick’s ‘Malsburg Synapses’ - Simulate visual cue following behavior