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