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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

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Page 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

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

Page 2: Matt Mehne, USC Brain Project 1 USC Brain Project Matt Mehne – Progress Update – May 15, 2007 Modeling Action Selection in the Parkinsonian Basal Ganglia

Matt Mehne, USC Brain Project 2

The old model

Project 4 paper

A computational model of visually assisted A computational model of visually assisted motor control in Parkinson’s diseasemotor 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 movementinability or difficutly initiating movement

Deficiencies include:

-Shortened gait

- Difficulty initiating movement w/o attentional cue

Page 3: Matt Mehne, USC Brain Project 1 USC Brain Project Matt Mehne – Progress Update – May 15, 2007 Modeling Action Selection in the Parkinsonian Basal Ganglia

Matt Mehne, USC Brain Project 3

Parkinson’s Disease

Page 4: Matt Mehne, USC Brain Project 1 USC Brain Project Matt Mehne – Progress Update – May 15, 2007 Modeling Action Selection in the Parkinsonian Basal Ganglia

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.

Page 5: Matt Mehne, USC Brain Project 1 USC Brain Project Matt Mehne – Progress Update – May 15, 2007 Modeling Action Selection in the Parkinsonian Basal Ganglia

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…

Page 6: Matt Mehne, USC Brain Project 1 USC Brain Project Matt Mehne – Progress Update – May 15, 2007 Modeling Action Selection in the Parkinsonian Basal Ganglia

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)

Page 7: Matt Mehne, USC Brain Project 1 USC Brain Project Matt Mehne – Progress Update – May 15, 2007 Modeling Action Selection in the Parkinsonian Basal Ganglia

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?

Page 8: Matt Mehne, USC Brain Project 1 USC Brain Project Matt Mehne – Progress Update – May 15, 2007 Modeling Action Selection in the Parkinsonian Basal Ganglia

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

Page 9: Matt Mehne, USC Brain Project 1 USC Brain Project Matt Mehne – Progress Update – May 15, 2007 Modeling Action Selection in the Parkinsonian Basal Ganglia

Matt Mehne, USC Brain Project 9

Expanded TRN Role

Ch1 Ch2

Cortex Cortex

STNSTN

StriatumStriatum

GPiGPi

TRNTRN

VLVL

Low DA levels

Hyper-direct pathway

Page 10: Matt Mehne, USC Brain Project 1 USC Brain Project Matt Mehne – Progress Update – May 15, 2007 Modeling Action Selection in the Parkinsonian Basal Ganglia

Matt Mehne, USC Brain Project 10

Expanded TRN Role

Cortex Cortex

STNSTN

StriatumStriatum

GPiGPi

TRNTRN

VLVL

Low DA

- Burst mode vs. Spike mode

- Integrating visual cortex

Page 11: Matt Mehne, USC Brain Project 1 USC Brain Project Matt Mehne – Progress Update – May 15, 2007 Modeling Action Selection in the Parkinsonian Basal Ganglia

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