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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