억제적 반응통제 기능의 신경해부학 연구 : 활성화 및 신경화학적 두뇌 기능 영상 PET 연구

Functional Neuroanatomical Study of Inhibitory Response-Control: Activation and Neurochemical PET Brain Imaging

연구책임자 : 김상은 ( 성균관대학교 의과대학 )

억제적 반응 통제 기능

• 신개념의 억제적 반응 통제 인지모델 개발( 신경해부학적 - 신경화학적 통합 인지모델 )

• 고차기능 응용시스템 개발을 위한 과학적 기반 구축

Neurochemical mappingDopamine

AcetylcholineGABA

Neuroanatomical mapping15O-Water PET, FDG PET

TasksNeuropsychological tests

Behavioral study

정상 비정상 (ADHD, OCD, 약물중독 , 치매 )

• 억제적 반응 통제의 신경해부학적 회로 규명 • 억제적 반응 통제의 신경화학적 기전 규명

• 인지신경기전의 신경화학적 해석

처치효과 (methylphenidate, SSRI, detoxification)

• Frontotemporal dementia (FTD)

• Frontotemporal dementia with motor neuron disease (MND)

• Semantic dementia (SD)

• Progressive nonfluent aphasia (PA)

Prototypic neurobehavioral syndromes

Frontotemporal lobar degeneration (FTLD)

• FTD: Impairment in social interpersonal conduct

• MND: Upper or lower motor neuron involvement

• SD: Fluent speech with impaired naming and comprehension

• PA: Nonfluent speech with agrammatism, anomia

Core clinical diagnostic features

All subjects were right-handed.

MMSE

6 6 3 919No.

Age (yr) 568 588 5614 7045812

MND SD PA ADFTD

Sex (M/F) 7/12 1/5 1/2 5/41/5

136 167 86 178189

7

576

Controls

6/1

Patients and Subjects

• Behavioral observation• MMSE• Frontal function: attention, frontal executive function, language• Temporal function: language, learning and memory• Parietal function: visuospatial function

Neuropsychological screening battery

Neuropsycological test

F S C V P

Fre

qu

ency

(%

)

0

50

100

SD

0

50

100

F S C V P

AD

Frontal

excutiveSpontaenous

speech

Comprehension

Visuospatial

Personality

change

FTD

Fre

qu

ency

(%

)

0

50

100

F S C V P

PA

0

50

100

Motor neuroninvolvment

F S C V P

MND

0

50

100

FTD < Healthy controls

p < .001, k = 100 voxel

Z=-28 Z=-2

Z=34Z=16 T value

6

4

2

o

FTD

Frontal

excutiveSpontaenous

speech

Comprehension

Visuospatial

Personality

change

Fre

qu

ency

(%

)

0

50

100

Neuropsycological test

Executive Function

Correlation analysis in FTD

Korean Boston Naming Test

Attention

p < .05, k = 100 voxel

MND < Healthy controls

p < .001, k = 100 voxel

Z=-22 Z=-2

Z=48Z=14 T value

6

4

2

o

MND

0

50

100

Fronta

l

excutiv

e

Spontae

nous

speech

Compre

hension

Motor n

euron

involvement

Personalit

y

change

Fre

qu

ency

(%

)

Visuospatial

Neuropsycological test

SD < Healthy controls

p < .001, k = 100 voxel

Z=-16 Z=-8

Z=14Z=2T value

10

8

6

4

2

o

SD

0

50

100

Frontal

excutiveSpontaenous

speech

Comprehension

Visuospatial

Personality

change

Fre

qu

ency

(%

)

Neuropsycological test

PA < Healthy controls

p < .001, k = 100 voxel

Z=-22 Z=-4

Z=6 Z=16T value

1

0

8

6

4

2

o

PA

0

50

100

Frontal

excutiveSpontaenous

speech

Comprehension

Visuospatial

Personality

change

Fre

qu

ency

(%

)

Neuropsycological test

AD > FTD

p < .001, k = 100 voxel

FTD > AD

ADFTD

0

50

100

Fronta

l

excuti

ve

Sponta

enou

s

spee

ch

Compre

hension

Visuo

spati

al

Personalit

y

change

Fre

qu

ency

(%

)

0

50

100

Fronta

l

excuti

ve

Sponta

enou

s

spee

ch

Compre

hension

Visuo

spati

al

Personalit

y

change

Neuropsycological test

Summary and Conclusion

• Different metabolic patterns between FTLD and AD

• Distinct metabolic patterns between clinical syndromes of FTLD

• Good correlation between metabolic patterns and clinicalsymptoms of FTLD

• Biochemical basis of clinical classification of FTLD

• Evaluation and classification of patients with FTLD at neurochemical levels

FTD Metabolic deficit in bilateral anterior cingulate gyrus and left inferior frontal cortex - Personality change and frontal dysfunction

MND Metabolic deficit in bilateral premotor areas - Frontal dysfunction with motor neuron involvement symptoms

SD Metabolic deficit in left posterior temporal cortex including Wernicke’s area - Impaired naming and comprehension

PA Metabolic deficit in bilateral prefrontal cortex and Broca’s area -Nonfluent aphasia

Clinico-Metabolic Correlation in FTLD(as revealed in this study)

Go/NoGo task

Go/NoGo task

정상 대조군에서 각 조건별 정반응률

98%

92%

Go_Hit NoGo_Hit

* p < 0.05

*

50

60

70

80

90

100(%)

8%

2%

0

2

4

6

8

10(%)

Go_miss NoGo_commissionerror

정상 대조군에서 각 조건별 오류율

*

501 sec

442 sec

Go_Hit_RT

정상 대조군에서 각 조건별 반응 시간

*

*p < 0.001

400

420

440

460

480

500

520

(sec)

NoGo_commission error_RT

73%Commission error

20%Miss error

7%Other errors

오류 분포율

92% 92% 8% 8%

0

2

4

6

8

10

OCD 환자에서 조건별 정반응률 OCD 환자에서 조건별 오류율

50

60

70

80

90

100(%) (%)

Go_Hit NoGo_Hit Go_miss NoGo_commissionerror

8%

2%

0

10

Go_miss NoGo_commissionerror

*(%)

98%92%

Go_Hit NoGo_Hit

*

50

100(%)

정상 대조군

504 sec

360 sec

0

100

200

300

400

500

600

Go_Hit_RT NoGo_commission error_RT

OCD 환자에서 각 조건별 반응 시간

(sec)

501 sec

442 sec

Go_Hit_RT

정상 대조군에서 각 조건별 반응 시간

*

400

420

440

460

480

500

520

(sec)

NoGo_commission error_RT

향후 연구계획

• 억제적 반응 통제의 신경해부학적 / 신경화학적 회로 구성

• 억제적 반응 통제 기능 이상 환자 (OCD, ADHD, 약물중독 ) 에서 치료 전후의 신경회로 변화 탐색

• 억제적 반응 통제 과제 (task) 개발