CORTICAL SELF-ORGANIZATION AND PERCEPTUAL LEARNING
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
Freq
uenc
y
15 Word Speech Stream >1045 possibilities
Techniques used to study how complex sounds alter cortical processing
Environmental Nucleus Basalis Behavioral Enrichment Stimulation Training
20±10 vs. 75±20 μV 81±19 vs. 37±20 μV
0 50 100 150 200 250
Week 1
Am
plitu
de (m
V)
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
High-density Microelectrode
Mapping
• 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)
• Decrease in best rate by 1.1 Hz in enriched rats– 7.8 vs. 6.7 Hz (p< 0.001)
Enrichment effects persist under general anesthesia
n = 16 rats, 820 A1 sitesJournal of Neurophysiology, 2004
Enriched housing alters temporal processing
-100 0 100 200 300 400 500 600 700 800 900 -60
-40
-20
0
20
40
60
Time (milliseconds)
Vol
tage
(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
Pul
se R
atio
(2nd
/1st
)
Interstimulus Interval (milliseconds)
EnrichedStandard
Enrichment increases response strength and paired pulse depression
in awake and anesthetized rats
Nucleus basalis stimulation causes stimulus specific plasticity.
• NB stimulation paired with a sound 300 times per day for 25 days.
• Pairing occurred in awake unrestrained adult rats.
• Stimulation efficacy monitored with EEG.
• Stimulation evoked no behavioral response.
Nucleus basalis stimulation paired with sensory experience can alter:
• Cortical Topography
• Maximum Following Rate
• Receptive Field Size
• Response Strength
• Synchronization
• Spectrotemporal Selectivity
Best Frequency
Science, 1998
NB
Tone Frequency - kHz
Frequency-Specific Map Plasticity
N = 20 rats; 1,060 A1 sites
Naïve Control
1 Day Post
10 Day Post
20 Day Post
All Groups
40
30
20
10
0
Perc
ent o
f Cor
tex
Res
pond
ing
to
21
kHz
at 4
0 dB
* = p< 0.05** = p< 0.01
**
****
Tone Frequency (kHz)
• Reduced response to low frequency tones, p<0.001
• Decreased bandwidth of high frequency neurons – 2.8 vs. 3.8 octaves,
p<0.0001 (30 dB above threshold)
Plasticity in Posterior
Auditory Field
N = 12 rats; 396 PAF sites
How does experience alter temporal processing?
• Response of Neurons at a Single Site to Repeated Tones
• Group Average
Nature Neuroscience, 1998
N = 15 rats, 720 sites
2 4 6 8 10 12 14 16 18 200.2
0.4
0.6
0.8
1
1.2
Repetition Rate (pulses/second)
Nor
mal
ized
Spi
ke R
ate
Control15pps 9 kHz15pps Seven Carriers
Journal of Neurophysiology, 2001
N = 13 rats, 687 sites
Temporal Plasticity is Influenced by Carrier Frequency
Stimulus Paired with NB Activation Determines Degree and Direction of Receptive Field Plasticity
Frequency Bandwidth Plasticity N = 52 rats; 2,616 sites
Frequency Bandwidth is Shaped by Spatial and Temporal Stimulus Features
Modulation Rate (pps)0 5 10 15
Ton
e Pr
obab
ility
15%
50 %
10
0%
Journal of Neurophysiology, 2001
Spatial Variability
Leads toSmaller RF’s
Temporal Modulation
Leads toLarger RF’s
How do cortical networks learn to represent more complex sounds?
• FM sweeps32
16
8
4
2
1
Freq
uenc
y
160msExperimental Brain Research, 2004
32
16
8
4
2
1
Freq
uenc
y
Time
NB
Stim
.FM Sweep paired with NB stimulation(8 to 4 kHz in 160 ms)
• No map expansion
• No preference for downward vs. upward FM sweeps
• Decreased threshold by 3 dB and latency by 2 ms,and increased RF size by 0.2 octaves only in the region of the frequency map activated by sweep (p<0.01)
32
16
8
4
2
1
Freq
uenc
y
Time
NB
Stim
.FM Sweeps paired with NB stimulationFive downward sweeps of one octave in 160 ms
• No significant plasticity
32
16
8
4
2
1
Freq
uenc
y
Time
NB
Stim
.Does acoustic context influence plasticity?Five downward sweeps of one octave in 160 ms plus unpaired upward (160 ms) and downward (40 or 640 ms) sweeps
• Decreased threshold by 5 dB and latency by 2 ms,and increased RF size by 0.2 octaves all across map (p<0.01)
• No preference for downward vs. upward FM sweeps
Spectrotemporal Sequence
100ms 20ms
High Tone(12 kHz)
Low Tone(5 kHz)
Noise Burst
Time
Freq
uenc
y
Paired w/ NB stimulation
100ms 20ms
High Tone(12 kHz)
Low Tone(5 kHz)
Noise Burst
Unpaired background
sounds}
Context-Dependent Facilitation
100ms 20ms
High Tone(12 kHz)
Low Tone(5 kHz)
Noise Burst
Num
ber o
f Spi
kes
0 100 200 300 400ms
+50%
• 58% of sites respond with more spikes to the noise when preceded by the high and low tones, compared to 35% in naïve animals. (p< 0.01)
Context-Dependent Facilitation
100ms 20ms
Low Tone(5 kHz) Noise Burst
Noise Burst
High Tone(12 kHz)
N = 13 rats, 261 sitesProceedings of the National Academy of Sciences, 2002
• 25% of sites respond with more spikes to the low tone when preceded by the high tone, compared to 5% of sites in naïve animals. (p< 0.005)
Context-Dependent Facilitation
Low Tone(5 kHz)
100ms 20ms
High Tone(12 kHz)
Low Tone(5 kHz) Noise Burst
N = 13 rats, 261 sitesProceedings of the National Academy of Sciences, 2002
• 10% of sites respond with more spikes to the high tone when preceded by the low tone, compared to 13% of sites in naïve animals.
Context-Dependent Facilitation
100ms 20ms
Noise Burst
High Tone(12 kHz)
High Tone(12 kHz)
N = 13 rats, 261 sitesProceedings of the National Academy of Sciences, 2002
Low Tone(5 kHz)
Time
Freq
uenc
y
How do cortical networks learn to represent speech sounds?
Sash
‘SASH’ Group - Spectrotemporal discharge patterns of A1 neurons to ‘sash’ vocalization (n= 5 rats)
kHz
Sash
16kHz @50dB:
35 % 1.9
55 % 5.3
(p<0.0005)
Tone Frequency (kHz)
Sensory experience can alter:• Cortical Topography
• Maximum Following Rate
• Receptive Field Size
• Response Strength
• Synchronization
• Spectrotemporal Selectivity
How does discrimination of complex sounds alter auditory cortex?
• Two months of training on one of six Go-No go tasks
• Anesthetized high density microelectrode mapping
100ms 20ms
High Tone(12 kHz)
Low Tone(5 kHz)
Noise Burst
CS+
CS-’s
CS-’s CS-’s
CS-’s
TaskSchematic
Experimental group#
Rats
# A1
SitesA) Naïve Controls 7 329
B) Sound Exposure Controls 4 263
C) Frequency Discrimination 8 444
D) HLN Detection Task 4 251
E) HLN vs. H L, or N Discrimination 4 253
F) HLN vs. HHH, LLL, NNN Discrimination 4 189
G) HLN vs. NNN, LLL, HHH Discrimination 7 433
H) HLN vs. NLH Reverse Discrimination 5 329
Totals 43 2,491
Summary of Operant Training Experiments
0 1 2 3 4 5 6 7-0.2
0.1
0.4
0.7
1.1
1.4
1.7
2
2.4
2.7
3
Task
Per
form
ance
: D-P
rime
DetectionFrequency DiscriminationHLN vs. HHH, LLL, NNNHLN vs. H, L, NHLN vs. NNN, LLL, HHHHLN vs. Rev
HLN
Detection
Frequency D
iscrimination
HLN
vs. H
HH
, LLL, NN
N
HLN
vs.H
, L, N
HLN
vs. N
NN
, LLL, HH
H
HLN
vs. R
everse
Group #
Possible results:
• Greater response to CS+
• Map expansion
• HLN order preference
• Temporal plasticity
• Receptive field plasticity
Possible results:
• Greater response to CS+
• Map expansion
• HLN order preference
• Temporal plasticity
• Receptive field plasticity
A. B.
C. D.
A. B.
C. D.
Naï
ve C
ontr
olEx
posu
re C
ontr
olD
etec
tion
Freq
uenc
yTr
iple
t (hi
gh fi
rst)
Sequ
ence
Ele
men
tTr
iple
t (no
ise
first
)R
ever
se o
rder
Naï
ve C
ontr
olEx
posu
re C
ontr
olD
etec
tion
Freq
uenc
yTr
iple
t (hi
gh fi
rst)
Sequ
ence
Ele
men
tTr
iple
t (no
ise
first
)R
ever
se o
rder
Peak
Lat
ency
(mse
c)
Ban
dwid
th a
t 40d
B a
bove
th
resh
old
(oct
aves
)
Ons
et L
aten
cy to
sec
ond
nois
e
Su
ppre
ssio
n In
dex
Task difficulty (d prime)
Impr
ovem
ent i
ndex
y = - 0.28x2+0.76x+0.21
Task difficulty (d prime)
Impr
ovem
ent i
ndex
y = - 0.28x2+0.76x+0.21
F (2, 32) =14.2, MSE = 0.01, p < 0.0001Exposure ControlDetectionFrequencyTriplet (high first)Sequence ElementTriplet (noise first)Reverse order
Nucleus Basalis Stimulation
versus
Natural Learning
Behavioral Relevance
Neural Activity
- Internal Representation
External World-Sensory Input
Neural Plasticity- Learning and
Memory
CONCLUSIONS1) Response strength, topography, receptive field size, maximum following rate, and spectrotemporal sensitivity are influenced by acoustic experience associated with neuromodulator release.
2) Map plasticity can endure at least 20 days.
3) Both primary and non-primary fields are plastic, but do not necessarily express the same changes.
4) Background (CS-) sounds powerfully shape the expression of cortical plasticity.
CONCLUSIONS, continued 5) Plastic changes induced using simple sounds are also evoked by exposure to complex sounds.
6) Operant training does not induce the same cortical plasticity as NB stimulation.
7) Cortical refinement is an inverted U-shaped function of task difficulty.
8) Plasticity is shaped by sensory experience, attention, and neuromodulator release.
Enrichment A1 Experiments - Navzer Engineer
Enrichment Evoked Potentials - Cherie Percaccio
FM Experiments - Raluca Moucha
Speech Experiments - Pritesh Pandya
PAF Experiments - Amanda Puckett
Time Course Experiments - Rafael Carrasco
Operant Training Experiments - Navzer Engineer
Crystal Novitski
Acknowledgements:
and
Behavioral Relevance
Neural Activity
- Internal Representation
External World-Sensory Input
Neural Plasticity- Learning and
Memory
Behavioral Relevance
Neural Activity
- Internal Representation
External World-Sensory Input
Neural Plasticity- Learning and
Memory
Plasticity Rules- Educated Guess
BehavioralChange
Neuron 1
Inputs to Neuron A
Neuron 2
Receptive Field Overlap
Neuron A Neuron B
Inputs to Neuron B
Spike synchronization and RF overlap are correlated.
Brosch and Schreiner, 1999
-50 -40 -30 -20 -10 0 10 20 30 40 500
200
400
600
800
1000
1200N
umbe
r of
Syn
chro
nous
Eve
nts
Interval (msec)
Cross-correlation: TC 025C1.MAT x TC025C2.MAT
Cross-correlationShift PredictorCorrelation strength
= correlation peak in normalized cross-correlation
histogram
Correlation width = width at half height
of correlation peak
250 um separation
After RF increase and Map Expansion: ~85% shared inputs
After Sharper Frequency Tuning: ~25% shared inputs
Predicted effects of cortical plasticity on spike synchronization
Before plasticity: ~50% shared inputsBefore Plasticity: ~50% shared inputs
Increased Correlation
Decreased Correlation
Experience-Dependent Changes in Cortical Synchronization
• Map expansion increased synchronization– 15pps 9kHz tone trains
50% increase in cross-correlation height (p<0.0001)
17% decrease in cross-correlation width (p<0.01)
• Bandwidth narrowing reduced synchronization– Two different tone frequencies
50% decrease in cross-correlation height (p<0.0001)
22% increase in cross-correlation width (p<0.001)
• Intermediate stimuli caused no change in synchronization– 15pps tone trains with several different carrier frequencies
No change in cross-correlation height or width
N = 34 rats; 1,395 sites; 556 pairs
Experience-Dependent Changes in Cortical Synchronization (con’t)
• Enrichment also sharpened synchronization 25% increase in cross-correlation height (p<0.01)
20% decrease in cross-correlation width (p<0.01)
N = 8 rats; 397 sites; 159 pairs
Time
Freq
uenc
y
Example Speech Stream
050
100150
Spi
ke
Rat
e (H
z)
050
100150
Spi
ke
Rat
e (H
z)
050
100150
Spi
ke
Rat
e (H
z)Fr
eque
ncy
(kH
z)
5 102025
Freq
uenc
y (k
Hz)
5 102025
Freq
uenc
y (k
Hz)
5 102025
050
100150
050
100150
050
100150
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
50
100
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
100
150
Time (ms)
ba
p as a
ck
cksh
H) Neural responses to modified speech
2 4 8 16 320
0.1
0.2
0.3
0.4
0.5
0.6
0.7
Frequency Bin (kHz)
Prop
ortio
n of
A1
Site
s19kHz paired with NB stimulationNaive Controls
**
* = p< 0.05
** = p< 0.01
*** = p< 0.001
**
** ***
* ***
**
***
Percent of Cortical Field Responding to 60 dB Tones
Tone Frequency
2 kHz 4 kHz 8 kHz 16 kHz
PAF
Control 87 ± 3 91 ± 2 81 ± 6 66 ± 7
19k w/NB 52 ± 6
70 ± 3
86 ± 2 74 ± 6
A1
Control 42 ± 4 38 ± 3 43 ± 3 40 ± 3
19k w/NB 32 ± 6 35 ± 2 48 ± 5 54 ± 5
Decrease in Response significant to p<0.001
Increase in Response significant to p<0.01
-100 0 100 200 300 400 500 600 700 800 900 -60
-40
-20
0
20
40
60
Time (milliseconds)
Vol
tage
(mic
rovo
lts)
500ms ISI
EnrichedStandard
-100 0 100 200 300 400 500 600 700 800 900 -60
-40
-20
0
20
40
60
Time (milliseconds)
Vol
tage
(mic
rovo
lts)
200ms ISI
EnrichedStandard
-100 0 100 200 300 400 500 600 700 800 900 -60
-40
-20
0
20
40
60
Time (milliseconds)
Vol
tage
(mic
rovo
lts)
100ms ISI
EnrichedStandard
-100 0 100 200 300 400 500 600 700 800 900 -60
-40
-20
0
20
40
60
Time (milliseconds)
Vol
tage
(mic
rovo
lts)
50ms ISI
EnrichedStandard
50 100 150 200 250
-50
-40
-30
-20
-10
0
10
20
30
40
50
Time (milliseconds)
Vol
tage
(mic
rovo
lts)
Enriched Housing
50 100 150 200 250-50
-40
-30
-20
-10
0
10
20
30
40
50
Time (milliseconds)
Vol
tage
(mic
rovo
lts)
Standard Housing
First Tone500ms ISI200ms ISI100ms ISI 50ms ISI
First Tone500ms ISI200ms ISI100ms ISI 50ms ISI
Enriched Housing Standard Housing
0 1 2 3 4 5 6 7 8 9 10-0.8
-0.6
-0.4
-0.2
0
0.2
0.4
0.6
0.8
1
1.2ar 10:100
SocialAuditoryExerciseAP Deprived Early Enr AdultsAP Enriched Early Std AdultsSham StandardDeprived LesionEnriched LesionSham Enriched
12 rats per group
Pla
stic
ity In
dex
1X
2X
Enr
iche
d
Sta
ndar
d
NB
Les
ion
Enr
iche
d
NB
Les
ion
Sta
ndar
d
Sha
mE
nric
hed
Sha
mS
tand
ard
Exe
rcis
e
Soc
ial
Aud
itory
Exp
osur
e
METHODS
Stimulating Electrode Location from Bregma: 3.3 mm Lateral 2.3 mm Posterior 7.0 mm Ventral
Location of reference points used to record EEG activity prior, during and after each stimulation. This information was used to confirm the efficacy of NB activation
NUCLEUS BASALIS ACTIVATIONEEG Desynchronization Caused by
NB Stimulation
EEG
V
OLT
AG
E (m
V)
TIME (msec)
The stimulation currents levels (70-150 μAmps) were individually established to be the minimum necessary to briefly desyncronize the EEG during slow wave sleep. The stimulation consisted of a train of twenty biphasic pulses (100 Hz, 0.1 msec pulse width)
19 kHz tone @ 50dB
250 msec duration
Behavioral Relevance
Neural Activity
- Internal Representation
External World-Sensory Input
Neural Plasticity- Learning and
Memory
Plasticity Rules- Educated Guess
BehavioralChange
Target stimulus(CS+)
Add firstdistractor (CS-1)
Add second distractor
(CS-2)
Add third distractor
(CS-3)
Task
A) Sequence detection
B) Frequency discrimination
C) Triplet distractor-High first
D) Sequence elementdiscrimination
E) Triplet distractor-Noise first
F) Reverse Order
Freq
uenc
y (k
Hz)
Time (ms)
H L N
H L N
L L L H H H
H H H
H H H
L L L
L L L
N N N
N N N
NL
N L H
H
H L N
H L N
H L N
None
None
None None
None
None None
Time (weeks)
Target stimulus(CS+)
Add firstdistractor (CS-1)
Add second distractor
(CS-2)
Add third distractor
(CS-3)
Task
A) Sequence detection
B) Frequency discrimination
C) Triplet distractor-High first
D) Sequence elementdiscrimination
E) Triplet distractor-Noise first
F) Reverse Order
Freq
uenc
y (k
Hz)
Time (ms)
H L N
H L N
L L L H H H
H H H
H H H
L L L
L L L
N N N
N N N
NL
N L H
H
H L N
H L N
H L N
None
None
None None
None
None None
Time (weeks)
Amphetamine, haloperidol, and experience interact to affect rate of recovery after motor cortex injuryFeeney, Gonzalez, Law, Science. 1982 Aug 27;217(4562):855-7.
Beam Scoring7 = traversed normally with <2 slips6 = traversed using affected limbs to aid >50% of the steps5 = traversed using affected limbs to aid <50% of the steps4 = traversed and placed affected hind paw on horizontal surface at least once3 = traversed dragging affected hind limb2 = unable to traverse but placed hind limb on horizontal surface at least once1 = unable to traverse and unable to place hind limb on horizontal surface
Amphetamine paired with physical therapy accelerates motor recovery after stroke. Walker-Batson D, Smith P, Curtis S, Unwin H, Greenlee R Stroke. 1995 Dec;26(12):2254-9.
• 25% of sites respond with more spikes to the low tone when preceded by the high tone, compared to 5% of sites in naïve animals. (p< 0.005)
• 10% of sites respond with more spikes to the high tone when preceded by the low tone, compared to 13% of sites in naïve animals.
• 58% of sites respond with more spikes to the noise when preceded by the high and low tones, compared to 35% in naïve animals. (p< 0.01)
Context-Dependent Facilitation - Group Data
N = 13 rats, 261 sitesProceedings of the National Academy of Sciences, 2002
100ms 20ms
High Tone(12 kHz)
Low Tone(5 kHz)
Noise Burst
• Simple to Complex Sounds• Primary Auditory Cortex is strongly influenced by acoustic experience
– Enrichment – LTP & PPD– NB map plasticity
• Frequency specificity• Time course• PAF vs. A1
– Temporal plasticity• Faster or slower
– Complex sounds and CS- (or distractors)• FM and twitter• Combination sensitivity• Speech
– Summary • What about natural learning?
– Edeline, Weinberger, Recanzone, Wang, Merzenich, Fritz, Shamma, and others…– Neurons respond better (more strongly and/or synchronously) to CS+ vs. CS-
• 2 exceptions visual cortex and frequency discrimination in cats• Need to test with more tasks and more subjects
– We expected forms of plasticity seen in above summary – Despite clear learning, we see no evidence of selective response to CS+ over CS-.– Instead we see inverted-U function relating task difficulty and plasticity
• Neuromodulators and experience RULE• Extra xcorr
Hopkins 2005 Outline
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