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

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. 정상 비정상 (ADHD, OCD, 약물중독 , 치매 ). Neuroanatomical mapping

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

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  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 정상 비정상(ADHD, OCD, 약물중독, 치매) Neuroanatomical mapping 15O-Water PET, FDG PET Tasks Neuropsychological tests Behavioral study Neurochemical mapping Dopamine Acetylcholine GABA 처치효과(methylphenidate, SSRI, detoxification) • 억제적 반응 통제의 신경해부학적 회로 규명 • 억제적 반응 통제의 신경화학적 기전 규명 • 인지신경기전의 신경화학적 해석 • 신개념의 억제적 반응 통제 인지모델 개발 • (신경해부학적-신경화학적 통합 인지모델) • 고차기능 응용시스템 개발을 위한 과학적 기반 구축

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

  4. Core clinical diagnostic features • 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

  5. Patients and Subjects MND SD PA AD FTD Controls No. 19 6 6 3 9 7 Age (yr) 5812 568 588 5614 704 576 Sex (M/F) 7/12 1/5 1/5 1/2 5/4 6/1 MMSE 189 136 167 86 178 All subjects were right-handed. Neuropsychological screening battery • Behavioral observation • MMSE • Frontal function: attention, frontal executive function, language • Temporal function: language, learning and memory • Parietal function: visuospatial function

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

  7. FTD < Healthy controls Z=-28 Z=-2 Z=16 Z=34 T value 6 4 2 o p < .001, k = 100 voxel

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

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

  10. MND < Healthy controls Z=-22 Z=-2 Z=14 Z=48 T value 6 4 2 o p < .001, k = 100 voxel

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

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

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

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

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

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

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

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

  20. Go/NoGo task Go/NoGo task

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

  22. (sec) 520 500 480 460 440 420 400 정상 대조군에서 각 조건별 반응 시간 * 501 sec 442 sec Go_Hit_RT NoGo_commission error_RT *p < 0.001

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

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

  25. OCD 환자에서 각 조건별 반응 시간 (sec) (sec) 600 520 504 sec 500 500 360 sec 400 480 300 460 440 200 420 100 400 0 Go_Hit_RT NoGo_commission error_RT 정상 대조군에서 각 조건별 반응 시간 * 501 sec 442 sec Go_Hit_RT 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

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