fmri 를 이용한 대뇌기능평가 서울대학교 의과대학 신경과학교실 대학원...

fMRI 를 이용한 대뇌기능평가

서울대학교 의과대학 신경과학교실 대학원 인지과학 협동과정

이경민 , MD, PhD

주요 논의 내용

• fMRI 연구의 주요 관찰 결과 요약

• 대뇌기능평가의 실례 : 산술기능에 관여하는 대뇌피질의 기능적 분화 양상

BOLD 신호(blood-oxygenation level dependent)

• behavior neural activation increased cerebral blood flow decreased deoxyhemoglobin decreased perturbation of magnetic field

homogeneity increased T2* signal

fMRI 신호에 관한 세가지 관찰사실

• Local increases and decreases in brain activity are reliably accompanied by changes in blood flow.

• These blood flow changes exceed any accompanying change in the oxygen consumption.

• Blood flow changes are accompanied by changes in glucose metabolism of approximately equal magnitude and spatial extent.

Activity-circulation coupling in the brain

• 일반적인 해석 : oxydative metabolism of glucose

• 상반되는 관찰결과 : – CBF increase in excess of oxygen consumption– CBF decrease from baseline

산소소모량을 초과하는 국소 혈류 증가

• reactive hyperemia to localized oxygen depletion– transient decrease of oxygen level before increase– increased CBF in wider and greater extent due to nonlinear

coupling between oxydative metabolism of glucose and oxygen supply

– questions:• matching between glucose utilization and CBF• more tight spatial relationship in neurovascular coupling• no decrease in oxyHgb with increase in deoxyHgb: Capillary

recruitment ?• What happens with a negative BOLD signal ?

CBF decrease from baseline

• inhibitory activity ? but, energy-requiring process

• group reduction of activity ?– by diffuse projecting system from brainstem

as in cerebellar diaschisis

Characteristics of fMRI data

• Hemodynamic response to neural activity– 지연반응 :

• 2 ~ 3 초 후 신호변화시작• 4 ~ 6 초 후 최대 신호 변화

– Hemodynamic transfer function applied to instantaneous neural event

– Almost linear summation of signals

fMRI 와 기존의 대뇌피질 신경생리학 연구

• 기존 신경생리학적 지식의 확인

• 새로운 발견– Examples

• HERA model of memory encoding / retrieval

• Decrease of signal at retrosplenial / precuneus area & medial orbitofrontal cortex

뇌기능 분화에 대한 새로운 시각

• Holistic vs. localistic viewpoints– Brain “mass” vs. Brain “center”

• Network of cortical areas as a functional unit

fMRI 연구의 방향

• High SNR(signal-to-noise ratio)– 개인별 뇌활성화 연구– Parametric study design

cf) cognitive subtraction

• 뇌규준 지도 작성– 뇌기능의 정상적 변이– 뇌질환자에 대한 임상적 활용

fMRI 에 의한 대뇌피질 기능 평가

• 산술기능에 관여하는 대뇌피질의 기능적 분화 양상

Case 1

• 56 year-old woman with ICHat left temporoparietal area

• Mild attentional dysfunctionMild motor aphasiaGerstmann featuresIntact memory except initial recall dysfunction

KBJ

Subtraction

2nd

1st

1 2 3 4 5 6 7 8 9

1 X

2

3

4 X

5

6

7 X

8 X

9 X X

: Correct, X : Incorrect, : Correct magnitude without a minus sign,

1st, 2nd : The first and second operands of arithmetic.

Multiplication

2nd

1st

1 2 3 4 5 6 7 8 9

1

2 X X X X X

3 X X X X

4 X X X X

5 X X X

6 X X X X X X

7 X X X X

8 X X X X X X

9 X X X X X

: Correct, X : Incorrect,

1st, 2nd : The first and second operands of arithmetic.

Case 2

• 66 year-old man with general weakness, confusion, and urinary incontinence

• Impaired complex attentionCallosal disconnection syndrome

- impaired inter-manual transferDyscalculia:

worse with subtraction (RT ca. 5 sec) than with multiplication (RT ca. 2

sec).

JIS

Issues

• Cognitive components of calculation

• Neural substrates underlying such components

• Neural codes used in arithmetic operations

Impairments of calculation

• Attentional acalculia– Frontal dysfunction– metabolic encephalopathy etc.

• True acalculia– part of Gerstmann syndrome– isolated acalculia

Experiment 1

• Tasks: calculation vs. number reading

• Block design : (30 seconds for each task) X 10

• Subjects: 7 men, 4 women (25-35 y.o.)

• EPI gradient echo sequenceVoxel size: 3.75 x 3.75 x 5 mmSPM96

Calculation - Number reading (p < 0.001)

Reading numbers - Calculation (p < 0.001)

Experiment 2

• Tasks: subtraction vs. multiplicationof single digit numbers

• multiplication rote arithmetic factssubtraction quantitative numerical knowledge(Dehaene & Cohen, 1997)

• Block design : (30 seconds for each task) X 10

• Subjects: 6 men, 4 women (25-35 y.o.)

Figure 1 Lee

7 6 5 4 3 2 1 0

7 6 5 4 3 2 1 0

a

b

Subtraction - Multiplication (p < 0.001)

Multiplication - Subtraction (p < 0.001)

S M S M S M S M S M

1 10080604020

a

b

100.0

99.5

99.0

100.5

101.0

Scan number

MR

signa

l (%

)M

R sign

al

(%)

Figure 2 Lee

100.5

100.0

99.5

101.0

101.5

Areas with significant difference between subtraction and multiplication.

Talairach coordinates ClusterCortical area BA x mm y mm z mm z-score size

Multiplication > SubtractionLeft AG/SMG 39/40 -49.7 -54.5 31.0 7.22 147

Superior frontal gyrus 9/46 -23.3 33.2 44.2 6.61 142Right Lingual gyrus 18 11.1 -74.9 5.3 7.38 75

Precentral gyrus 4 51.3 -9.1 23.6 4.74 24Midline Anterior cingulate gyrus 30 2.15 49.5 15.7 6.95 82

Precuneus 7 -3.3 -44.5 49.1 6.79 59Subtraction > Multiplication

Left Intraparietal sulcus 7/40 -31.5 -52.1 49.9 8.44 330Superior frontal gyrus 6 -24.4 1.4 56.2 7.97 59Inferior frontal gyrus 44 -47.0 8.7 29.3 7.43 86Posterior ITG 37 -55.8 -58.0 -8.7 7.08 27

Right Intraparietal sulcus 7/40 28.7 -54.6 52.4 8.29 368Superior frontal gyrus 6 24.2 1.8 54.8 7.43 68Inferior frontal gyrus 44 42.5 10.8 30.8 7.82 130Posterior ITG 37 46.6 -57.3 -1.8 5.07 42

Only those clusters with maximum z-score higher than 3.09 (p < 0.001, corrected) andcluster size greater than 15 voxels are listed. Talairach and Tournoux coordinates (reference 12) of the z-score weighted centroid ofeach cluster.BA: Brodmann areaAG/SMG: the border area between angular gyrus and supramarginal gyrusITG : inferior temporal gyrus

KBJ

Z = 32 mm Z = 36 mm

Patient with more impaired multiplication than subtraction

Brain activation by fMRISubtraction > Multi. (Red)Multi. > Subtraction (Green)

4537.53022.5

44363224

a

b

Figure 3 Lee

JIS

Multiplication > Subtraction

Subtraction > Multiplication

Patient with more slowing of subtraction than multiplication

Conclusions

• Cases showing dissociation among arithmetic operations

• Differential brain activation by arithmetic operations

• Arithmetic operations in brain– Left fronto-parietal areas for multiplication

by rote number-fact memory– Bilateral parietal areas for subtraction by

quantitative manipulation

992.8 996.0

1169.5

993.0995.9

1271.2

800

1000

1200

1400

Multiplication Subtraction

Re

act

ion

tim

e (m

sec)

*

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Lee & Kang, Cognition (2002)