1. Michael P. Kilgard Healing the Human Brain: The Next Medical Revolution University of Texas at Dallas

3. Axons Dendrites

8. We hold these truths to be self-evident...

12. Alzheimer’s Disease Affects 4 million Americans. 12 million predicted by 2040.

13. Hearing Loss 23 million Americans suffer irreversible hearing loss. 1 million are deaf.

14. Migraine and Chronic Pain 75 million Americans with chronic pain.

15. Substance Abuse 22 million Americans are drug or alcohol dependent.

16. Anxiety Disorders 25,000,000 Depression 19,000,000 Epilepsy 2,500,000 Schizophrenia 2,000,000 Traumatic Brain Injury 750,000 / year Stroke 700,000 / year Autism 500,000 Multiple Sclerosis 400,000

17. Fantastic … and Fragile

18. Mind vs. Brain Meat Mostly Fat Boring Ugly Fragile Creative Ever-Changing Ever-Active Beautiful Enduring

19. Map of the Body Surface

20. Cortex Midbrain Medulla Spinal Cord Finger Touch Cortex Path from Skin to Brain

21. Thumb IndexMiddle Ring Little Brain Map

22. Causes the Map to Reorganize Thumb Little Brain Map Middle Amputation Index Ring

23. Can learning really change the brain?

24. Performance Improves with Practice Days of Practice 0 5 10 15 20 25 30 Detection Threshold 0 1 2 3 4 5 6 7

25. Learning Causes the Brain to Reorganize

26. Cortex Midbrain Medulla Spinal Cord Finger Touch Cortex Path from Skin to Brain

28. Learning Causes the Brain to Reorganize

29. No Reorganization Without Attention

30. Fantastic … and Fragile

31. Strain or Injury Cortical Map Reorganization Chronic Pain = Synchronous Spontaneous Activity Decreased attention span due to attention to pain Stress/Anxiety Problem:

33. Tinnitus  Uncomfortable sensation of ringing in the ears in the absence of external sound.  14 million Americans have tinnitus.  Interferes with daily activity in 1 million.  No effective treatment to eliminate tinnitus.  Associated with hearing impairment due to aging, noise exposure or ototoxic drugs.  The dominant theory is that pathological plasticity plays a critical role.  Tinnitus severity is correlated with extent of map expansion.

34. Tinnitus Normal Map

35. Today most neurological and psychiatric disorders are neither preventable nor curable. Will this always be true?

37. + = immunity Polio coat proteins Immune system irritant

38. How can we direct neural plasticity to heal the brain?

39. Nucleus Basalis Electrical stimulation can be used to direct neural plasticity.

40. Best Frequency Science, 1998 NB Nucleus basalis stimulation directs powerful and highly specific neural plasticity

41. Stimulating NB paired with different sounds alters: Frequency Maps - in primary auditory cortex - Science, 1998 - in non-primary auditory cortex – J. Neurophys, 2007 - in 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 and improves discrimination. – unpublished

42. Auditory cortex Map Plasticity LC Cochlea Nucleus Basalis ACh + NTS Hearing Loss or Noise Exposure Auditory Cortex Map Reorganization Tinnitus = Synchronous Spontaneous Activity Decreased attention span due to attention to ringing Stress/Anxiety Vagal Nerve Stimulation Problem:Solution:

44. How to stimulate plasticity without deep brain stimulation?

45. Vagus Nerve Stimulation (VNS) NB NTS

46. Potential Tinnitus Therapy

47. Patient interface Sound generator Force transducer Images & movies EEG Vagus Nerve Stimulator Laptop Supervise Rehabilitation Deliver physical stimuli Collect data Deliver nerve stimulation

48. Potential VNS-facilitated Therapies - Tinnitus - Chronic Pain - Motor Impairments - Cognitive Impairments - PTSD / Anxiety - Communication disorders VNS + Tones VNS + Touch VNS + Skilled movement VNS + Cognitive therapy VNS + Desensitization therapy VNS + Speech therapy

49. Tinnitus RehabMotor RehabPTSD Rehab VNS-facilitated Rehabilitation

50. Human recording video

51. Blast-induced Brain Injury - Tinnitus (26%) - Hearing loss (48%) - Chronic Pain (83%) - Motor Impairments (62%) - Cognitive Impairments (88%) - Communication (50%) - PTSD / Anxiety (42%) - Depression (37%) - Epilepsy (?) Stats from Sayer, 2008

52. UT Dallas Michael Kilgard Tinnitus and motor deficits Larry Cauller Wireless VNS and pain Christa McIntyre PTSD Marco Atzori Epilepsy Emily Tobey Hearing loss JB Lee Device construction Jin Liu Device design Phillip Loizou Signal processing Sandi ChapmanTBI John HartPTSD Michael Devous UTSW - Imaging MicroTransponder, Inc.

54. Today most neurological and psychiatric disorders are neither preventable nor curable. How will the world look when they are?

55. Thanks to: