Ch63. Context Effects and the Amygdala

(1)

Ch63. Context Effects and the

Amygdala

(2)

Responsible for learning about cues that predict biologically relevant outcomes

(3)

Using Facial Expressions to Study the Human Aymgdala

specific predictive cues

contextual information

amygdala response

(4)

(5)

(6)

(7)

fearful

vs

scared

(8)

The Facial Expression of Surprise

(9)

(10)

Davis & Whalen

• 놀란 표정 1(positive)~9(negative) rating

lateral ventral region of the amygdala가 valence에 따 라 다르게 activated

(11)

(12)

Modulating amygdala responses to surprised faces by modulating

the context in which they are presented

• 아미그달라의 반응이 context dependent 하다면, 놀란 표정이 보이는 동안의 맥락

정보가 아미그달라를 서로 다르게 affect할 것.

(13)

• 놀란 표정에 앞서서 맥락정보 제시

Kim et al. (2004)

(14)

• Ventral amygdala

Kim et al. (2004)

(15)

• Amygdala uses contextual information to resolve ambiguity in concert with

prefrontal cortex

(16)

Context Conditioning

• Context plays critical role in determining the meaning of conditioned “cue”

• ‘cue conditioning’에 amygdala가 관여

• Hippocampus—OFC—vmPFC와 함께 맥 락정보 처리

(17)

Grillion et al. (2008)

• Virtual reality 실험

• 여러 장소를 보여주고 어떤 맥락은

shock(CX+), 어떤 장소는 safety(CX-)를 predicted하게

• Grater activity during CX+ in amygdala, PFC, and hippocampus

• PFC와 hippo가 amygdala에게 조관화된 반응 이 특정맥락에 적합한지 알려줌

(18)

Milad et al. (2007)

• 불빛과 shock를 조건형성(context A)시킨 후 소거(context B)

• 소거 과정에서 amygdala와 vmPFC의 activity가 증가함을 발견

• 다음날 다시 context A나 B에 노출시켰더 니 B에서 vmPFC와 hippo의 activation이 greater

(19)

Face as Context

• Facial expression = predictive cue

• 우리는 자동적으로 이러한 cue를 위해 눈 과 입을 봄

• Amygdala damaged  fail to properly monitor eye region

 amygdala facilitate the search for predictive information

(20)

Ch64. Neurogenetics Studies of

Variability in Human Emotion

(21)

• Monoamine neurotransmission 사용해서 dopaminergic, norandrenergic,

serotonergic signaling이 조금이라도 alter 되면 정서, 성격, temperament를 관장하는 brain curcuitry의 functional response에

영향을 줌(bigos el al., 2008; 등등)

• 또한, multimodal 연구들이

monoaminergic signaling casca

(22)

Why Study Genes?

• Twin Study

• 인지, temperament, 성격의 variability의 40에서 70%까지 유전적 영향을 받음

(23)

Why Study Genes?

• Classic approach used in genetic

association analyses  candidate gene

(24)

Why Neuroimaging?

• Candidate gene을 사용해서 행동과

functional polymorphism을 바로 연결하 려는 연구들이 있었지만

• Weak and inconsistent

• 뇌와 관련된 genetic polymorphism의 기 능적인 impact를 explore하고 다양한 행동 이나 질병이 나타나는데 관련되어 있는 neural pathway를 identify

(25)

Basic principles of imaging genetics

1. Selection of candidate genes

2. Control for nongenotype factors 3. Task selection

(26)

Imaging genetics studies of

amygdala reactivity and human

emotion

(27)

Serotonin Transporter

• Abnormal 5-HT neurotransmission has been

implicated in the pathophysiology of mood and anxiety dirorders and has been a target of

pharmacological intervention(e.g.SSRI)

• 5-HTTLPR의 long (L) allel <-> short (S) allele  relatively increased 5-HT signaling과 연관

• Posession of one or two copies of S allele  increased level of temperamental anxiety,

conditioned fear response, and development of depression(particularly environmental stress)

(28)

• Threat-related reactivity of amygdala

– S allel carriers에서 L allel homozygote에 비 해 significantly increased

• 5-HTTLPR S allele –reduced GM

• Threat-related amygdala reactivity의 규모가 temperamental anxiety와 associated

 이 corticolimbic circuitry의 reactivity에 대 한 polymorphism 때문에 환경적 stressor에 취 약 5-HTTLPR

(29)

Monoamine Oxidase-A

• Corticolimbic의 5-HTTLPR variance와 emotion processing이 serotonin

mediated  serotonin function에 관여하 는 다른 gene들도 비슷한 effect를 보일 것

• 5-HT neurotransmission in also regulated through intracellular degradation via the metabolic enzyme monoamine oxidase- A(MAO-A)

(30)

• Common polymorphism in MAO-A gene resulting in relatively low-activity enzyme, has been associated with increased risk for violent or antisocial behavior as well as for depression and anxiety

• fMRI study  low-activity MAO-A 

exaggerated amygdala reactivity, diminished prefrontal regulation of amygdala

(31)

• Both 5-HTTLPR S and MAO-A low- activity  relatively increased 5-HT signaling and exaggerated amygdala reactivity

(32)

Tryptophan Hydroxylase-2 (TPH2)

• Rate-limiting enzyme in the synthesis of neuronal 5-HT  plays a key roles in

regulating 5-HT neurotransmission

• SNP in the regulatory region of human TPH2 gene affects amygdala function

• T allele associated with exaggerated amygdala reactivity

• SNP and another promoter SNP impact

transcriptional regulation of TPH2 that may

affect enzyme availability and 5-HT biosynthesis

(33)

Neuropeptide Y (NPY)

• 36-amino-acid peptide neurotransmitter

• Evolutionarily highly conserved molecular

component involved in the regulation^{of brain}

systems processing stress^andemotion

• Both cerebrospinal fluid and plasma NPY levels correlate with anxiety and stress levels

• Task-related hippocampal activation was predicted by NPY haplotype