1. Restoring neural function through neural prosthetic “bypass” Ziv Williams, MD Associate Professor in Neurosurgery Faculty, Harvard-MIT Health Sciences and Technology Faculty, Harvard Medical School Program in Neuroscience Massachusetts General Hospital Harvard Medical School Boston, MA 02114

2. Re-growing disrupted CNS circuits

3. Brain-machine-interface No need to restore normal physiological continuity In principal, can be learned very rapidly (hours to days) Has the potential for recovering full motor function (across multiple degrees of freedom)

4. Williams, et al. Nature Neurosci. 2003 Williams et al. Exp Brain Res. 2005

6. Decoding neural activity based on native directional tuning V x position along the x-axis t time  time lag ay-intercept nneuronal firing rate wweight for each neuron  residual error Model training Model decoding

8. Functional cortical-to-spinal bypass Benefit of restoring one’s own paralyzed limb. In principal, can be used to functionally connect any proximal and distal neural site. Cortical to spinal Cortical to nerve Cortical to muscle

10. Shanechi M, et al. Nature Neurosci. 2012 Shanechi M, et al. Nature Comm. 2014 Brain - Neural recordings Spinal cord - Neural stimulation

13. Restoring other motor functions Premotor cortex – planned target of movement Primary motor cortex – ongoing trajectory Supplementary motor area – movement sequences

15. Shanechi M, et al. Nature Neurosci. 2012

16. Motor control based on native neural plasticity? In principal, any brain area. Williams Z, et al. Nature Neurosci. 2006 Haroush K & Williams Z. Cell 2015

18. Body-to-brain functional bypass (sensation)

19. Brain-to-brain information transmission

22. Thank you

23. Shanechi M, Hu R, Williams Z. A cortical-spinal neural prosthesis for targeted limb movement in paralyzed primate avatars. Nature Comm. 2014 Feb 18;5:3237. Haslinger R, Pipa G, Lewis LD, Nikolić D, Williams Z, Brown E. Encoding through patterns: regression tree-based neuronal population models. Neural Comput. 2013 Aug;25(8):1953-93. Shanechi MM, Hu RC, Powers M, Wornell GW, Brown EN, Williams Z. Neural population partitioning and a concurrent brain-machine interface for sequential motor function. Nature Neurosci. 2012 Dec;15(12):1715-22. Williams Z, Eskandar EN. Selective enhancement of associative learning by microstimulation of the anterior caudate. Nature Neurosci. 9: 562-8, 2006. NIH 1R01 HD059852 NIH 1R01 NS091390 NIH F32N S093769 PECASE Some references… Support