1. 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 )

2. 억제적 반응 통제 기능 신개념의 억제적 반응 통제 인지모델 개발 ( 신경해부학적 - 신경화학적 통합 인지모델 ) 고차기능 응용시스템 개발을 위한 과학적 기반 구축 Neurochemical mapping Dopamine Acetylcholine GABA Neuroanatomical mapping 15 O-Water PET, FDG PET Tasks Neuropsychological 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)

3. Frontotemporal dementia (FTD) Frontotemporal dementia with motor neuron disease (MND) Semantic dementia (SD) Progressive nonfluent aphasia (PA) Prototypic neurobehavioral syndromes Frontotemporal lobar degeneration (FTLD)

4. 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

5. All subjects were right-handed. MMSE 663919 No. Age (yr) 56  858  856  1470  458  12 MNDSDPAAD FTD Sex (M/F) 7/121/51/25/41/5 13  616  7868617  8 18  9 7 57  6 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

6. Neuropsycological test F S C V P Frequency (%) 0 50 100 SD 0 50 100 F S C V P AD Frontal excutive Spontaenous speech Comprehension Visuospatial Personality change FTD Frequency (%) 0 50 100 F S C V P PA 0 50 100 Motor neuron involvment F S C V P MND 0 50 100

7. FTD < Healthy controls p <.001, k = 100 voxel Z=-28Z=-2 Z=34Z=16 T value 642o642o

8. FTD Frontal excutive Spontaenous speech Comprehension Visuospatial Personality change Frequency (%) 0 50 100 Neuropsycological test

9. Executive Function Correlation analysis in FTD Korean Boston Naming Test Attention p <.05, k = 100 voxel

10. MND < Healthy controls p <.001, k = 100 voxel Z=-22Z=-2 Z=48Z=14 T value 642o642o

11. MND 0 50 100 Frontal excutive Spontaenous speech Comprehension Motor neuron involvement Personality change Frequency (%) Visuospatial Neuropsycological test

12. SD < Healthy controls p <.001, k = 100 voxel Z=-16Z=-8 Z=14Z=2 T value 10 8 6 4 2 o

13. SD 0 50 100 Frontal excutive Spontaenous speech Comprehension Visuospatial Personality change Frequency (%) Neuropsycological test

14. PA < Healthy controls p <.001, k = 100 voxel Z=-22Z=-4 Z=6Z=16 T value 10 8 6 4 2 o

15. PA 0 50 100 Frontal excutive Spontaenous speech Comprehension Visuospatial Personality change Frequency (%) Neuropsycological test

16. AD > FTD p <.001, k = 100 voxel FTD > AD

17. ADFTD 0 50 100 Frontal excutive Spontaenous speech Comprehension Visuospatial Personality change Frequency (%) 0 50 100 Frontal excutive Spontaenous speech Comprehension Visuospatial Personality change Neuropsycological test

18. Summary and Conclusion Different metabolic patterns between FTLD and AD Distinct metabolic patterns between clinical syndromes of FTLD Good correlation between metabolic patterns and clinical symptoms of FTLD Biochemical basis of clinical classification of FTLD Evaluation and classification of patients with FTLD at neurochemical levels

19. 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)

20. Go/NoGo task

21. 정상 대조군에서 각 조건별 정반응률 98% 92% Go_HitNoGo_Hit * p < 0.05 * 50 60 70 80 90 100 (%) 8% 2% 0 2 4 6 8 10 (%) Go_miss NoGo_commission error 정상 대조군에서 각 조건별 오류율 *

22. 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

23. 73% Commission error 20% Miss error 7% Other errors 오류 분포율

24. 92% 8% 0 2 4 6 8 10 OCD 환자에서 조건별 정반응률 OCD 환자에서 조건별 오류율 50 60 70 80 90 100 (%) Go_HitNoGo_Hit Go_miss NoGo_commission error 8% 2% 0 10 Go_miss NoGo_commission error * (%) 98% 92% Go_HitNoGo_Hit * 50 100 (%) 정상 대조군

25. 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

26. 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