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Multi disciplinary approach to understanding face processing mechanism
G A01Research Group A01fMRI and NIRS (Iidaka)
ResearchSupport Team
Group A02
Group A06Engineering and Group A02
MEG and EEG (Kakigi)Engineering and
computation (Akamatsu)
Group A05Monkey neurophysiology
Group A03ASD and Face (Inagaki)Monkey neurophysiology
(Eifuku)ASD and Face (Inagaki)
G A04Group A04Psychology and Cognitive Sciences (Yamaguchi)
Face perception Face perception d itid iti
human fMRI
and recognitionand recognition
Iidaka MEG/EEG
M ltidi i li
Eifuku
MultidisciplinaryEvolutionary
Anthropological
Kakigimonkey infant culture
Yamaguchi Chiao
Face vs. House: fMRI and ERP in normal subject4100msec 400msec 500msec
++ +** ++ + or
P
LFace? or House?
ER
P
*
fMR
I**
amygdala
N170**
FFA
2-way ANOVA (electrode x condition), F=45.6, p<0.01 T 1 4 02 k>20 R d F Bl H
**y ( ), , p
Post-hoc t-test, * p<0.05, ** p<0.01T=1 - 4.02, k>20, Red: Face Blue: House
Iidaka et al., Brain and Cognition, 2006
Amygdala activation differed with differentAmygdala activation differed with different facial expressions of others
ControlPositiveNeutral Negative
Large SmallF MF M M F Large SmallF M M F
Task: gender discrimination (Male vs. Female)
L
n=12, REMp=0.001(unc.)
t l
Neutral Positive Negative
Lvs. control
Iidaka et al. 2001, J Cogn. Neurosci.
Amygdala and facial expressionAmygdala and facial expression
• Negative vs. Neutral expression→ Left amygdala (x, y, z= -26, 4, -14)
Lt amygdala0.1
Rt amygdala0.1
0.06
0.08po
nse
0.06
0.08
onse
0 02
0.04
uste
d r
esp
0 02
0.04
uste
d r
espo
Iid k t l 20010
0.02
Adju
Neg
Pos
Neu0
0.02
Adju
NegPosNeu
Iidaka et al., 2001J Cogn Neurosci
-0.02
0 16 32
Time (s)
-0.02
0 16 32
Time (s)
Signal extracted from VOI (r 8mm) in the bilateral amygdaloid region (n 12)Signal extracted from VOI (r=8mm) in the bilateral amygdaloid region (n=12)
Implicit processing of facial expression in p p g pamygdala
P dProcedure
Prime stimuli (35ms) Target stimuli (500ms)Condition
or or
Prime stimuli (35ms) Target stimuli (500ms)
or or
Ambiguous expressionAnger Neutral Blank
Nomura et al., Neuroimage, 2004(Task: anger, neutral, or
happy)Anger Neutral Blank
Right amygdala and angry prime faceg yg g y p
Angry primeAngry primevs.
Neutral primevs.
Blank
P=0.005 k=10P=0 005 k=10P 0.005 k 10
Rt amygdala (r=.74, p<0.05)○ Rt Inf. Frontal gyrus▲Rt Fusiform gyrusBrain behavior
Nomura et al 2004
▲Rt Fusiform gyrusBrain-behavior correlation Angry prime face condition
Nomura et al., 2004,Neuroimage
Schizophrenia and facial expression recognitionp p gSchizophrenia
(n=12) Patients characteristics: M/F = 6/6, mean age = 26.0 (4.5),
Amygdala
Duration of illness = 3.8 (3,5) yrs, Medication On/Off = 10/2, Mean CPZ dose 322 (264) mg/day, mean BPRS score = 31.9 (8.1), mean PANS score = 56.3 (14.4), positive score = 11.3
Amygdala(-18, -4, -10)(20, -6, -10)
Schizophrenia > Control
(4.6), negative score = 16.3 (4.5), general score = 28.8 (7.3)
Control( 12)
RSchizophrenia > Control
(n=12)
0.3
rt AMG
Amygdala(-22, -6, -8)(22, 0, -16)
0.2
sted s
ign
al
R Rt. amygdala
R0
0.1
Adju
Schizo Control
Kosaka et al., Schizo. Res., 2002(22, -6, -12)
Amygdala and normal aging--Negative facial expression--
Left amygdalax,y,z = -16,-6,-20 Signal change in AMG
Negative vs. ControlGroup n (M/F) Mean age
Young 12 (6/6) 25 years
4
5
nse
Old 12 (6/6) 65 years
Negative
2
3
juste
d r
esponNegative
p=0.001uncorrectedY > Old
0
1
Adj
Young OldM F
Young > Old Young Old
A meta-analysis indicated that elderly L
Iid k l 2002 Hi
people had difficulty in recognizing negative expression as compared with young subjects. (Ruffman, 2008)
L
Iidaka et al., 2002, Hippocampuswith young subjects. (Ruffman, 2008)
Serotonin type 3 receptor gene(HTR3A HTR3B) and the polymorphism(HTR3A・HTR3B) and the polymorphism
SNP in promoter i C178THTR3A B Yamada et al., Biol Psychiatry 2006region; C178T
HTR3 distributed in the limbic system including amygdala.
HTR3A・B
T allele was associated with depression (Niesler, 2001) and harm avoidancetemperament (Melke, 2003)in Caucasian. Although there was no association between T allele and depression in Japanese (Yamada, 2006), the patients with T allele were poor-responder to antidepressant treatment (Kato, 2006).
HTR3A C178T polymorphism d d l ti tiand amygdala activation
C178T genotype C/C C/TRight AMG
Number of subjects 15 11
Sex(M/F) 6/9 7/4
Mean age 23 21
Right AMG
0.4
0.5
es
Education years 15 15
5-HTTLPR genotype s/s:10, s/l:5 s/s:4, s/l:5, l/l:2
Beck Depression Inventory 3.9 4.00.2
0 .3
0 .4
r esti
mate
p y
TCI Novelty seeking 9.8 9.9
Harm avoidance 12.0 11.1
Reward dependence 9 5 9 9-0.1
0
0.1
Para
mete
Reward dependence 9.5 9.9
Persistence 2.4 2.6-0.2
C/C C/T
X,Y,Z=22,-4,-30p=0 001 uncorrectedp=0.001, uncorrectedFace vs. house comparison
Iidaka et al., J Neurosci, 2005
Behavioral data genotype and brain activityBehavioral data, genotype, and brain activity
R ti ti
600
Reaction timep<0.05
500
s)R ight AMG
Right FG
300
400
RT
(m
0 .3
0 .4
0 .5
tim
ate
s
BOLDRight FG
0.2
0.4
mate
s
BOLD
200
300
-0.1
0
0.1
0 .2
Para
mete
r est
-0 .4
-0.2
0
Para
mete
r esti
Face vs. houseAmygdala pathway Fusiform pathway
C/C C/T-0.2
C/C C/T
P
-0.6
C/C C/T
P
Face vs. house judgment task
Amygdala pathway↓
Faster response
Fusiform pathway↓
Slower response
Iidaka et al., J Neurosci, 2005
Amygdala, medial PFC, and thalamus
HormonalDorsal mPFC GABA?GABA?
Hypot
Ventral mPFC GABAGABA Autonomic
thalamus
T allele5-HTR3↑ Radley et al., 2006
HIP
actio
n
Sensory inputvision, audition, etcLAIn
tera
PFC:prefrontal cortexLA: lateral nucleus
LA
Ce LA: lateral nucleusBA: basal nucleusCe: central nucleusBA
CeITC:intercalated regionHIP: hippocampusG
BAFight or Flight
AmygdalaGlu:glutamate
Quirk et al., 2003 revised
Neural circuit for emotional and stress responses
dPFCdecision, intension
Conditioning and human fMRIPhelps et al., 2004anxiety
depression
hyper-cortisolautonomic reaction
dPFC
PVHmPFC
AMG Stupid!EcologicalAMG
Aversive XXX
USStupid!g
Validity
conditioning
CS
CR
Real-life situation
Aversive conditioning paradigm i f d iusing face and voice
HabHab.Run 1
(w/o voice)CS+ 10 events
Acq
CS+CS-
Stupid! Stupid!
10 events
Hemodynamic responsesAcq.Run 2-6
(w/ voice)
Stupid! Stupid!
( )
CS+ pairedCS+ unpaired
5 events5 events
Ext.Run 7 8
CS+ unpairedCS- 10 events
Hemodynamic responsesRun 7-8
(w/o voice)CS+ 25 eventsCSCS- 25 events
Hemodynamic responses
Hippocampus/Amygdala activity andHippocampus/Amygdala activity and conditioning: CS+ vs. CS-
Hab. phase (w/o voice) Ext. phase (w/o voice)
AcqAcq.
p = 0 005 uncorrectedp = 0.05, uncorrected
CS+ = CS-
p = 0.005, uncorrectedSVC, p = 0.05 at lt AMG
CS+ > CS-18 healthy male subjects (mean age = 21 years)
Time modulation of amygdala activationAcq: CS+up (w/o voice) vs. CS- (w/o voice)
F ti l ti it l iFunctional connectivity analysisSeed voxel at amygdala
RMPFC
x=-4
p 0 001 uncorrected
• Amygdala–MPFC signal coupling
p = 0.001, uncorrected
• Amygdala shows transientp = 0.001, uncorrected
• Amygdala: transient activation in run2 • Fusiform gyrus: gradual decrease across runs
• Amygdala shows transient activity in early acquisition.
• Functional connectivity between amygdala and
p 0 00 , u co ected
Fusiform gyrus: gradual decrease across runs between amygdala and MPFC.
Amygdala-auditory coupling during acquisitionAmygdala auditory coupling during acquisitionCS+p vs. CS+up
Psychophysiological Interaction (PPI)
Auditory pathwayCochlea→Sup. Olive
Interaction (PPI)
SVC p < 0 05→Inf. collic. → MGB →Auditory cortex
SVC, p < 0.05
P i dit t
AMG
Primary auditory cortex and
Medial geniculate bodyMGB
Si l li fSignal coupling of AMG and MGB was larger when
i i d Seed ROI at MGBCS+p vs. CS+up
voice was paired with face.
Structural Equation ModelingStructural Equation Modeling Possible time course Structural Equation ModelingStructural Equation ModelingAcqAcq ((RunRun1)1) Input of aversive
of aversive conditioning
Acq Acq ((RunRun1)1)
CS+CS+ppMGB activity had
amygdalaInput of aversive
face/voice
Ea
positive influence on AMG activityAMG Signal coupling
of MGB and AMG
arly acq
.08 .34*.34*-.01 -.07 Phasic activation
uisition
-.08
of AMG
nLat
PAC MGB.73
?? Prefrontal inhibition on AMG
te acqu
AMOS5, Standardized path coefficient, * p < 0.05
primary auditory cortex medial geniculate body
Aversive memory of face/voice
isition
of face/voice
Iidaka et al., J Cog Neurosci, 2010
5-HTTLPR and aversive conditioning• These regions showed tonic
and continuous activation th h t th 5 d i
5-HTTLPR genotype s/s s/l + l/l
Number 12 12 (9+3)throughout the 5 runs during Acq. phase.
s-group (s/s)
Sex (M/F) 12/0 12/0
Handedness (R/L) 12/0 11/1
Mean age (SD) 21.5 (2.8) 25.4 (8.1) s-group (s/s)•Activities in right PFC and STS are predominant.
g ( ) ( ) ( )
Education years (SD) 15.3 (2.0) 16.3 (2.9)
BDI (SD) 3.5 (4.1) 2.0 (2.1)
TCI (SD) N lt ki 9 4 (5 1) 10 5 (3 8)l-group (s/l + l/l)
•PFC activation is dominant
TCI (SD) Novelty seeking 9.4 (5.1) 10.5 (3.8)
Harm avoidance 9.8 (5.1) 9.5 (5.0)
Reward dependence 7.9 (2.8) 8.8 (2.2)in the left hemisphere.Persistence 2.4 (1.8) 2.6 (1.5)
R s-group R l-group
Acq: CS+up vs. CS-, p = 0.001, uncorrected
s-group and l-group comparison 2-sample t-test
Superior Frontal Gyrusp
Acq: CS+up vs. CS-
l/lR s-group > l-group, p<0.001
Inferior Frontal Gyrusy
l/ll/l
Rl-group > s-group, p<0.001
• No significant group difference in amygdala activity
Neural circuit involved in social, affective, and cultural behavior in humancultural behavior in human
Bodily responseempathy
Externally oriented
HPA axis
autonomic
hyper-cortisol
sweat/palpitationoutput
empathydecision
mirror neuron
Environment
sweat/palpitationIntera polymorphism
stressHypo-thalamus
ction
p y p
AMG
stress
stress
thalamusinputself
emotiondefault mode
subcorticalInteraction
AMG stressdefault modeInternally oriented
C b l EnvPsychological Cerebraldomain
Env.domain
Psychologicaldomain
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