!

a-‐b.  Unilateral  ac+va+on  :  Establishment  of  dominant  ipsilateral  connec6on.  

b-‐c.  Bilateral  ac+va+on  :  Inability  of  weakened  contralateral  connec6on  to  re-‐establish  its  connec6on  (synap6c  compe66on)  

c-‐d.  Reverse  ac+va+on  :    constraint-‐induced  (CI)  therapy.  d-‐e.  Bilateral  ac+va+on  :  Re-‐establishment  of  normal  contralateral  connec6on  by  synap6c  compe66on.  

Modeling activity-dependent constraint-induced therapy by spike-timing dependent plasticity (STDP) Won Joon Sohn1, Terence D. Sanger1,2,3

1Biomedical Engineering, 2Biokinesiology and Physical Therapy, 3Neurology University of Southern California, Los Angeles

BCM theory

•rate-‐coded  hebbian  learning  (sliding  threshold)    

•explaines  how  vision  can  recover  from  the  deleterious  efects  of  monocular  depriva6on  (MD)

Question What did we find?

http://www.sangerlab.net

SangerLab

Is STDP sufficient to explain constraint-induced therapy?

• Constraint-induced therapy can be explained by mechanism of synaptic competition in STDP with realistic spiking neuron model.

• STDP captures some phenomena previously explained by BCM theoryIntroduction Results

•Constraint-‐induced  (CI)  movement  therapy  has  been  demonstrated  to  be  an  effec6ve  interven6on  for  some  individuals  with  hemiplegia  aEer  stroke  to  increase  strength  of  weaker  upper  extremi6es.  

•In  feline  cerebral  palsy  (CP)  model,  CI  therapy  repaired  the  abnormal  cor6cospinal  tract  (CST)  and  restored  normal  skilled  movement  control.(Mar6n,  1999,  2005);  

•Amblyopia  (poor  image  forma6on  in  one  eye  during  early  childhood)  can  be  thought  as  equivalent  to  hemiplegic  CP  in  visual  system.    

•Previously,  the  CI  therapy  was  explained  only  in  the  framework  of  rate-‐based  BCM  theory.  

Reference [*] L.N. Cooper, and M.F. Bear, The BCM theory of synapse modification at 30: interaction of theory with experiment. Nature reviews. Neuroscience 13 (2012) 798-810. [*] J.H. Martin, S. Chakrabarty, and K.M. Friel, Harnessing activity-dependent plasticity to repair the damaged corticospinal tract in an animal model of cerebral palsy. Developmental medicine and

child neurology 53 Suppl 4 (2011) 9-13. [*] R.C. Froemke, and Y. Dan, Spike-timing-dependent synaptic modification induced by natural spike trains. Nature 416 (2002) 433-8.

Ipad  Video:  19  days  of  plas6city  

simula6on  

STDP

•STDP  (Spike-‐6ming  dependent  plas6city)  has  been  proposed  to  solve  fundamental  issues  of  

100

0

0time (ms)

tpost < tpre tpost > tpre

-100 100

-100

dW = P∑ − D∑

dI =(I +W )τ

Excitatory Postsynaptic Current

Pre

PostP

D

0 100 200 ms

τ ≈15ms

STDP implemented on FPGA

All-to-all STDPSTDP Curve

(Froemke & Dan,

Izhikevich neurons

Neural  structure  •Four  synapses  •Four  Izhikevich  

spiking  neurons(Izhikevich, 2003)

Technology:  FPGA  •High  speed  emula6on  •Rapid  prototyping  •scalable

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Amblyopia•  Only    aEer  3  days  of  

monocular  depriva6on(MD)    there  are  clear  structural  changes  in  thalamocor6cal  synapse.

(Martin, 2011)

CST termination in cats and the role of activity-dependent process

M1

Change in CST termination upon therapy

Hemiplegic CP

* ipsilateral connection has higher decay rate than contralateral. side.

BCM Simulation of

ocular competition

Expressed by

STDP (simulation)

(Cooper & Bear, 2012)

http://www.sangerlab.net