Neural Plasticity:From Homeostasis to Speech

Mike KilgardAssociate ProfessorUniversity of Texas at Dallas

What is neural plasticity good for?

Turrigiano, 2004

Neural Plasticity as Homeostasis.

Turrigiano, 2004

Lidocaine Wash

Block Inhibition After Two Days

Strengthen Excitatory SynapsesWeaken Inhibitory Synapses

Weaken Excitatory SynapsesStrengthen Inhibitory Synapses

DECREASEACTIVITY

INCREASEACTIVITY

Turrigiano, 2004

Neural Plasticity as Electrician.

Hubel and Wiesel, 1970

Neural Plasticity as Electrician.

Hubel et al, Nature, 1982Visual Cortex

Schlaggar et al, Nature, 1993

After removal of C row whiskers

SomatosensoryCortex

P1

P2

P3

de Villers-Sidani, et al. J. Neurosci. 2007

AuditoryCortex

Is the young brain more plastic?- or -

Is plasticity just less tightly regulated in the young?

Best Frequency

Science, 1998

NB

Kilgard and Merzenich, Science. 1998

Recanzone and Merzenich, J. Neuroscience. 1993

Can unregulated plasticity putthe young brain at risk?

Control Age

16 days

19 days

22 days

80 days

NoiseReared

Zhang, et al.,PNAS, 2002

Naïve Noise Reared

Zhou and Merzenich, PNAS, 2008

Similar temporal processing and

cortical map disturbances

are caused by

- perinatal anoxia or

- perinatal environmental toxins - polychlorinated biphenyls (PCBs)

Strata, et al., PNAS, 2005Kenet, et al., PNAS, 2007

One in twenty children cannot effectively process the basic

elements of speech.

Primary Auditory Cortex Response to Speech Sounds

Engineer and Kilgard, Nature Neuroscience, 2008

BeforeSpeech Therapy

After Speech Therapy

Callan, et. al. Neuroimage, 2003

Conclusions1. The brain is highly plastic.

2. Modification of sensory experience and brain state is

sufficient to reorganize neural networks for good (or for ill).

PredictionIn 20 years, plasticity will be routinely manipulated for

the treatment of neurological and psychiatric illness.

Kraus et al., Science 1996

Brain Responses Da vs. Ga

Normal Learning Impaired

Processing Speech in Noise

Brain Responses to Speech in Noise

Infant brain responses may predict reading 8 years later.

Molfese, Brain &Language, 2000

TrainingImproves the Brain

Manner of Articulation

Stops Fricatives Affricatives Nasals Glides Liquids

Place o

f Articu

lation

Lip

sR

oo

fB

ack

0-600 ms0-30 kHz

Pad

Tad

Kad Gad Shad Had

Dad

Bad Fad Vad

Sad Zad

Mad Wad

Chad Jad Nad

Yad

Lad

Rad

Consonant Spectrograms

Inferior Colliculus Neurograms N=187 sites, 6 rats

Spatial Temporal

N=441 sites, 11 rats A1 Neurograms

N=441 sites, 11 rats A1 Neurograms

0 100 200 300 400 0 100 200 300 400

Sad Dad

High

Medium

Low

Time (milliseconds)

vs.

0 100 200 300 400 0 100 200 300 400

Dad

0 100 200 300 400 0 100 200 300 400

Sador

Speech Discrimination by Rats

Easy!

0 100 200 300 400 0 100 200 300 400

Rad Lad

High

Medium

Low

Time (milliseconds)

vs.

Impossible

0 100 200 300 400 0 100 200 300 400

Bad Dadvs.

High

Medium

Low

Impossibleusing mean rateor Easy using spike timing?

Rat Consonant Discrimination

m/n r/l sh/s sh/ch sh/h sh/j sh/f d/t d/g d/b d/s 0

20

40

60

80

100

Consonant Discrimination Task

Per

cen

t L

ever

Pre

ss

*********

N=11 rats

10000 15000 20000 25000

50

60

70

80

90

100

m/nr/l

sh/s

sh/chsh/h

sh/j

sh/f

d/td/g

d/bd/s

R2=0.66, P=0.002

Euclidean Distance Between Neurogram Pairs

Be

ha

vio

r P

erc

en

t C

orr

ec

t

50 60 70 80 90 100

50

60

70

80

90

100

m/nr/l

sh/s

sh/ch

sh/h sh/j

sh/fd/t

d/gd/b

d/s

R2=0.66, P=0.002

Classifier Percent Correct

Be

ha

vio

r P

erc

en

t C

orr

ec

tR= 0.81 P= 0.002

Neural Discrimination Predicts Behavioral Discrimination

Pediatric / Developmental Plasticity – Animal StudiesMovie of neurons connecting

What are they doing?Helping the brain survive, but how?

StabilityTurrigiano review

Vision - Hubel WeiselGive population sizetwo sides of the swordrecent studies demonstrating critical period may be reopenable

Auditory - Merzenich studiesGive population sizeenvironmenttoxinsrecoveryIs this limited to the young?No Recanzone, Kilgard, and

Relate to clinictwo key factors are knowing how to activate plasticity and how to direct plasticityspeech processing

Training benefits kids in many waysFFW plasticity trialsNeville attention

Pediatric / Developmental Plasticity – Animal StudiesOther speakers• Neural Plasticity in Animal Models• Brain Development and Plasticity• Limitations to Plasticity—Evidence From Epilepsy Studies• Limitations to Plasticity—Evidence From Neonatal Stroke StudiesThe developing brain is capable of a great dealof plasticity, with evidence for the ability to findalternate pathways of neural organization in the faceof structural, genetic and developmental disorders.In this symposium, we will discuss animal andhuman studies of neural plasticity in the developingbrain. We will then explore limitations to plasticityin pathological conditions, such as epilepsy andperinatal stroke. Finally, we will discuss potentialinterventions and neuroprotective therapies in thedeveloping brain.Target Audience: Developmental pediatricians,behavioral pediatricians, child neurologists,neonatologists, neuroscientists, developmentalbiologists, but this should have wide interest foranyone in pediatrics.

What is Neural Plasticity?

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

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