translating plasticity research into clinical practice
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Sensory Experience Alters Response Strength, Selectivity
and Temporal Processingof Auditory Cortex Neurons
Mike KilgardUniversity of Texas at Dallas
• Pioneering experiments by Hubel and Wiesel, Merzenich, Weinberger, Greenough, and many others have shown that cortical circuits are highly adaptive.
• Neural plasticity is likely involved in perceptual learning, development, and recovery from brain injury.
Cochlea CortexTone Frequency
Act
ion
Pot
entia
ls
Time
Fre
quen
cy
15 Word Speech Stream >1045 possibilities
Techniques used to study how complex sounds alter cortical processing
Behavioral Nucleus Basalis Environmental Training Stimulation Enrichment
Environmental enrichment increases:• Brain weight
• Gene expression
• Cortical thickness
• Dendritic branching
• Acetylcholinesterase levels
• Oligodendrocyte to neuron ratio
• Number of synapses per neuron
What are the physiological consequences of these anatomical changes?
20±10 vs. 75±20 μV 81±19 vs. 37±20 μV
0 50 100 150 200 250
Week 1
Am
plit
ud
e (
mV
)
Time (ms)0 50 100 150 200 250
Week 2
Time (ms)0 50 100 150 200 250
Week 5
Time (ms)
0 50 100 150 200 250
Week 12
Time (ms)
.10
.05
0
-.05
-.10
Red Group Enriched Blue Enriched
22 rats total
Journal of Neurophysiology, 2004
Environmental Enrichment
• Rapid
• Dramatic
• Reversible
• No critical period
Environmental Enrichment
• State dependent?• Other response properties change?• Consequences for speech processing?• What aspects of enrichment are required?
– Exercise– Social– Sensory
• Cellular mechanisms?
High-density Microelectrode
Mapping
1 2 4 8 16 320
20
40
60
80
BW10
BW20
BW30
BW40
CF
Frequency (kHz)
Inte
nsi
ty (
dB
SP
L)
A.
1 2 4 8 16 320
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BW20
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CF
B.
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100C.
Time (ms)
Sp
ike
s/s
EnrichedStandard
First SpikeLatency
Peak Latency
End of Response
Enriched Housing
Standard Housing
Plasticity in Primary Auditory Cortex
• 40% increase in response strength– 1.4 vs. 1.0 spikes per noise burst (p< 0.00001)
• 10% decrease in frequency bandwidth– 2.0 vs. 2.2 octaves at 40dB above threshold
(p< 0.05)
• 3 dB decrease in threshold– 17.2 vs. 20 dB (p< 0.001)
Enrichment effects persist under general anesthesia
n = 16 rats, 820 A1 sitesJournal of Neurophysiology, 2004
Time
Fre
quen
cy
Consequences for speech processing?
-100 0 100 200 300 400 500 600 700 800 900
-60
-40
-20
0
20
40
60
Time (milliseconds)
Vo
ltag
e (
mic
rovo
lts)
200ms ISI
EnrichedStandard
200 ms Interstimulus Interval
Enrichment IncreasesPaired Pulse Depression
50ms 100ms 200ms 500ms0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
Pai
red
Pu
lse
Ra
tio (
2nd
/1st
)
Interstimulus Interval (milliseconds)
EnrichedStandard
• Response of Neurons at a Single Site to Repeated Tones
• Group Average
Enriched housing alters temporal processing
Decrease in best rate by 1.1 Hz in enriched rats7.8 vs. 6.7 Hz (p< 0.001)
Environmental Enrichment
• Rapid
• Dramatic
• Reversible
• No critical period
• Alters temporal processing
Why?
WA
TE
Ra
nd
Exercise can cause:• A persistent firing pattern in the rat hippocampus,
known as theta-rhythm• Increased release of brain-derived neurotrophic factor
and other growth factors• Changes in gene regulation • Increased cell proliferation and neurogenesis in the
adult mouse dentate gyrus
No ef
fect
on
evok
ed p
oten
tials
WA
TE
Ra
nd
No ef
fect
on
evok
ed p
oten
tials
Social Interactions can:• enhance some forms of learning• alter stress hormones• improve recovery from brain damage
Auditory Exposure Enriched Auditory Environment
Nucleus Basalis and Plasticity• Nucleus basalis neurons are activated by
any arousing stimuli.
• Cholinergic agonists and NB stimulation
increase plasticity.
• Cholinergic antagonists and NB lesions
prevent many forms of cortical
plasticity.No effect on
evoked potentials
Auditory Enrichment
• Rapid• Dramatic• Reversible• No critical period• Alters temporal processing• Not dependent on nucleus basalis• Not dependent on exercise or social interactions
Time
Fre
quen
cy
Enrichment Evoked Potentials - Cherie Percaccio
Enrichment A1 Experiments - Navzer Engineer
Acknowledgements:
For more information visit: www.utd.edu/~kilgard
Sash
Spectrotemporal discharge patterns of A1 neurons to ‘sash’(n= 12 rats, 445 cortical sites)
Time (msec)
Sit
e
Nu
mb
er
kH
z S
pik
es p
er s
econ
d
High
Low
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Spi
ke
Rat
e (H
z)
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ke
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e (H
z)
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Spi
ke
Rat
e (H
z)F
requ
ency
(kH
z)
5 102025
Fre
quen
cy (
kHz)
5 102025
Fre
quen
cy (
kHz)
5 102025
050
100150
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5 102025
5 102025
5 102025
A) 'back' E) 'back' - modified
B) 'pack' F) 'pack' - modified
C) 'sash' G) 'sash' - modified
50 100 150 200 250 300 350
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150
Time (ms)
Spi
ke
Rat
e (H
z)
pack
backa sh
D) Neural responses to normal speech
50 100 150 200 250 300 350
50
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Time (ms)
ba
p as a
ck
cksh
H) Neural responses to modified speech
0 100 200 300 400 500 600 700 800 900-150
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-50
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Time (milliseconds)
Vol
tage
(m
icro
volts
)
Individual Rat
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-50
-25
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75
Time (milliseconds)
Vol
tage
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icro
volts
)
Mean of Five Rats
BeforeDuringAfter
BeforeDuringAfter
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050
100150
Time (milliseconds)
Vol
tage
(m
icro
volts
)
Individual Rat
0 100 200 300 400 500 600 700 800 900-75-50-25
0255075
Time (milliseconds)
Vol
tage
(m
icro
volts
)
Mean of Five Rats
BeforeDuringAfter
BeforeDuringAfter
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