Michael P. Kilgard

Healing the Human Brain:The Next Medical Revolution

University of Texas at Dallas

Axons

Dendrites

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

Alz

heim

er’s

Dis

ease

Affects 4 million Americans. 12 million predicted by 2040.

Hea

ring

Los

s

23 million Americans suffer irreversible hearing loss.

1 million are deaf.

Mig

rain

e an

d C

hron

ic P

ain

75 million Americans with chronic pain.

Sub

stan

ce A

buse

22 million Americans are drug or alcohol dependent.

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

Fantastic…

and Fragile

Mind vs. Brain• Meat • Mostly Fat• Boring• Ugly• Fragile

• Creative• Ever-Changing• Ever-Active• Beautiful• Enduring

Map

of t

he B

ody

Sur

face

Cortex

Midbrain

Medulla

Spinal Cord

Finger

Touch Cortex

Pat

h fr

om S

kin

to B

rain

Th

um

b

Ind

ex

Mid

dle

Rin

g

Lit

tleBrain Map

Causes the

Map to Reorganize

Th

um

b

Lit

tleBrain Map

Mid

dle

Amputation

Ind

ex

Rin

g

Can learning really change the brain?

Performance Improves with Practice

Days of Practice

0 5 10 15 20 25 30D

etec

tio

n T

hre

sho

ld

0

1

2

3 4

5

6

7

Learning Causes the Brain to Reorganize

Cortex

Midbrain

Medulla

Spinal Cord

Finger

Touch Cortex

Pat

h fr

om S

kin

to B

rain

Learning Causes the Brain to Reorganize

No Reorganization Without Attention

Fantastic…

and Fragile

Strain or Injury

Cortical Map Reorganization

Chronic Pain = Synchronous Spontaneous

Activity

Decreased attention span due to attention to pain

Stress/Anxiety

Problem:

TinnitusUncomfortable 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.

Tinnitus

Normal Map

Today most neurological and psychiatric disorders

are neither preventable nor curable.

Will this always be true?

+

= immunity

Polio coatproteins

Immunesystem irritant

How can we direct neural plasticity to heal the brain?

Nucleus Basalis

Electrical stimulation can be usedto direct neural plasticity.

Best Frequency

Science, 1998

NB

Nucleus basalis stimulation directs powerful and highly specific neural plasticity

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

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:

How to stimulate plasticity without deep brain stimulation?

Vagus Nerve Stimulation (VNS)

NB

NTS

Potential Tinnitus Therapy

Patient interface• Sound generator• Force transducer• Images & movies• EEG

Vagus Nerve Stimulator

Laptop

• Supervise Rehabilitation• Deliver physical stimuli• Collect data• Deliver nerve stimulation

Potential VNS-facilitated Therapies - Tinnitus- Chronic Pain- Motor Impairments- Cognitive Impairments- PTSD / Anxiety- Communication disorders

VNS + TonesVNS + TouchVNS + Skilled movement VNS + Cognitive therapyVNS + Desensitization therapy VNS + Speech therapy

Tinnitus Rehab Motor Rehab PTSD Rehab

VNS-facilitated Rehabilitation

Human recording video

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

UT Dallas

Michael Kilgard Tinnitus and motor deficits

Larry Cauller Wireless VNS and pain

Christa McIntyre PTSDMarco Atzori EpilepsyEmily Tobey Hearing lossJB Lee Device

constructionJin Liu Device designPhillip Loizou Signal

processingSandi Chapman TBIJohn Hart PTSDMichael Devous UTSW -

Imaging

MicroTransponder, Inc.

Today most neurological and psychiatric disorders

are neither preventable nor curable.

How will the world look when they are?

Thanks to: