1. Neural Plasticity: From Homeostasis to Speech Mike Kilgard Associate Professor University of Texas at Dallas

3. What is neural plasticity good for?

4. Turrigiano, 2004 Neural Plasticity as Homeostasis.

5. Turrigiano, 2004 LidocaineWash Block InhibitionAfter Two Days

6. Strengthen Excitatory Synapses Weaken Inhibitory Synapses Weaken Excitatory Synapses Strengthen Inhibitory Synapses DECREASE ACTIVITY INCREASE ACTIVITY Turrigiano, 2004

7. Neural Plasticity as Electrician.

8. Hubel and Wiesel, 1970 Neural Plasticity as Electrician.

9. Hubel et al, Nature, 1982 Visual Cortex

10. Schlaggar et al, Nature, 1993 After removal of C row whiskers Somatosensory Cortex P1 P2 P3

11. de Villers-Sidani, et al. J. Neurosci. 2007 Auditory Cortex

12. Is the young brain more plastic? - or - Is plasticity just less tightly regulated in the young?

13. Best Frequency Science, 1998 NB Kilgard and Merzenich, Science. 1998 Recanzone and Merzenich, J. Neuroscience. 1993

14. Can unregulated plasticity put the young brain at risk?

15. Control Age 16 days 19 days 22 days 80 days Noise Reared Zhang, et al., PNAS, 2002

16. Naïve Noise Reared Zhou and Merzenich, PNAS, 2008

17. Similar temporal processing and cortical map disturbances are caused by - perinatal anoxia or - perinatal environmental toxins - polychlorinated biphenyls (PCBs) Strata, et al., PNAS, 2005 Kenet, et al., PNAS, 2007

18. One in twenty children cannot effectively process the basic elements of speech.

19. Primary Auditory Cortex Response to Speech Sounds Engineer and Kilgard, Nature Neuroscience, 2008

20. Before Speech Therapy After Speech Therapy Callan, et. al. Neuroimage, 2003

21. Conclusions 1. The brain is highly plastic. 2. Modification of sensory experience and brain state is sufficient to reorganize neural networks for good (or for ill). Prediction In 20 years, plasticity will be routinely manipulated for the treatment of neurological and psychiatric illness.

22. Kraus et al., Science 1996 Brain Responses Da vs. Ga Normal Learning Impaired

23. Processing Speech in Noise

24. Brain Responses to Speech in Noise

25. Infant brain responses may predict reading 8 years later. Molfese, Brain & Language, 2000

26. Training Improves the Brain

27. Manner of Articulation StopsFricativesAffricativesNasalsGlidesLiquids Place of Articulation Lips Roof Back 0-600 ms 0-30 kHz Pad Tad KadGadShadHad Dad BadFadVad SadZad MadWad ChadJadNad Yad Lad Rad Consonant Spectrograms

28. Inferior Colliculus Neurograms N=187 sites, 6 rats

29. Spatial Temporal N=441 sites, 11 rats A1 Neurograms

30. N=441 sites, 11 rats A1 Neurograms

31. SadDad High Medium Low Time (milliseconds) vs.

32. DadSador Speech Discrimination by Rats Easy!

33. RadLad High Medium Low Time (milliseconds) vs. Impossible

34. BadDadvs. High Medium Low Impossible using mean rate or Easy using spike timing?

35. Rat Consonant Discrimination N=11 rats

36. R= 0.81 P= 0.002 Neural Discrimination Predicts Behavioral Discrimination

37. Pediatric / Developmental Plasticity – Animal Studies Movie of neurons connecting What are they doing? Helping the brain survive, but how? Stability Turrigiano review Vision - Hubel Weisel Give population size two sides of the sword recent studies demonstrating critical period may be reopenable Auditory - Merzenich studies Give population size environment toxins recovery Is this limited to the young? No Recanzone, Kilgard, and Relate to clinic two key factors are knowing how to activate plasticity and how to direct plasticity speech processing Training benefits kids in many ways FFW plasticity trials Neville attention

38. Pediatric / Developmental Plasticity – Animal Studies Other speakers Neural Plasticity in Animal Models Brain Development and Plasticity Limitations to Plasticity—Evidence From Epilepsy Studies Limitations to Plasticity—Evidence From Neonatal Stroke Studies The developing brain is capable of a great deal of plasticity, with evidence for the ability to find alternate pathways of neural organization in the face of structural, genetic and developmental disorders. In this symposium, we will discuss animal and human studies of neural plasticity in the developing brain. We will then explore limitations to plasticity in pathological conditions, such as epilepsy and perinatal stroke. Finally, we will discuss potential interventions and neuroprotective therapies in the developing brain. Target Audience: Developmental pediatricians, behavioral pediatricians, child neurologists, neonatologists, neuroscientists, developmental biologists, but this should have wide interest for anyone in pediatrics.

39. What is Neural Plasticity?

42. Plasticity makes the young more resilient and more at risk / fragile.

43. Stimulating NB paired with different sounds alters: Frequency Maps - primary auditory cortex – Science, 1998 - non-primary auditory cortex – J. Neurophys, 2007 - subcortical structures – Suga, 2003 Selectivity – Science, 1998 Sensitivity – J. Neurophys, 2001 Temporal Processing – Nature Neuroscience, 1998 Sequence Selectivity, and – PNAS, 2001 Synchrony – Hearing Research, 2007 for more than a month. – unpublished