ab. Unilateral ac+va+on : Establishment of dominant ipsilateral connec6on. bc. Bilateral ac+va+on : Inability of weakened contralateral connec6on to reestablish its connec6on (synap6c compe66on) cd. Reverse ac+va+on : constraintinduced (CI) therapy. de. Bilateral ac+va+on : Reestablishment of normal contralateral connec6on by synap6c compe66on. Modeling activity-dependent constraint-induced therapy by spike-timing dependent plasticity (STDP) Won Joon Sohn 1 , Terence D. Sanger 1,2,3 1 Biomedical Engineering, 2 Biokinesiology and Physical Therapy, 3 Neurology University of Southern California, Los Angeles BCM theory • ratecoded 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 theory Introduction Results • Constraintinduced (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 ratebased 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 (Spike6ming dependent plas6city) has been proposed to solve fundamental issues of 100 0 0 time (ms) t post < t pre t post > t pre -100 100 -100 dW = P ∑ − D ∑ dI = ( I + W ) τ Excitatory Postsynaptic Current Pre Post P D 0 100 200 ms τ ≈15ms STDP implemented on FPGA All-to-all STDP STDP Curve (Froemke & Dan, Izhikevich neurons Neural structure • Four synapses • Four Izhikevich spiking neurons (Izhikevich, 2003) Technology: FPGA • High speed emula6on • Rapid prototyping • scalable This project is funded by NIH R01NS069214>02 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